id category name description provided_by synonym deprecated end_coordinate position type http://omim.org/entry/100050 biolink:NamedThing|biolink:Disease Aarskog Syndrome, Autosomal Dominant omim.nt AARSKOG SYNDROME, AUTOSOMAL DOMINANT owl:Class MONARCH:.well-known/genid/OMIM100050ref3 biolink:NamedThing Elucidation of a 'new' pleiotropic connective tissue disorder. omim.nt IAO:0000310 PMID:6344635 biolink:NamedThing omim.nt IAO:0000013 PMID:6652957 biolink:NamedThing omim.nt IAO:0000013 UMLS:C3149220 biolink:NamedThing omim.nt owl:Class ORPHA:915 biolink:NamedThing|biolink:Disease omim.nt owl:Class http://omim.org/entry/100070 biolink:NamedThing|biolink:Disease Aortic Aneurysm, Familial Abdominal, 1 Aortic Aneurysm, Familial Abdominal, 1 omim.nt AORTIC ANEURYSM, FAMILIAL ABDOMINAL, 1; AAA1|Abdominal Aortic Aneurysm|Aneurysm, Abdominal Aortic owl:Class MONARCH:.well-known/genid/OMIM100070ref10 biolink:NamedThing Personal Communication. omim.nt IAO:0000310 PMID:10558909 biolink:NamedThing omim.nt IAO:0000013 PMID:10805895 biolink:NamedThing omim.nt IAO:0000013 PMID:12563204 biolink:NamedThing omim.nt IAO:0000013 PMID:12799723 biolink:NamedThing omim.nt IAO:0000013 PMID:15096456 biolink:NamedThing omim.nt IAO:0000013 PMID:15156361 biolink:NamedThing omim.nt IAO:0000013 PMID:15944607 biolink:NamedThing omim.nt IAO:0000013 PMID:16311603 biolink:NamedThing omim.nt IAO:0000013 PMID:1642543 biolink:NamedThing omim.nt IAO:0000013 PMID:19497516 biolink:NamedThing omim.nt IAO:0000013 PMID:19672284 biolink:NamedThing omim.nt IAO:0000013 PMID:1985458 biolink:NamedThing omim.nt IAO:0000013 PMID:2787414 biolink:NamedThing omim.nt IAO:0000013 PMID:2900988 biolink:NamedThing omim.nt IAO:0000013 PMID:3047388 biolink:NamedThing omim.nt IAO:0000013 PMID:3418662 biolink:NamedThing omim.nt IAO:0000013 PMID:3761500 biolink:NamedThing omim.nt IAO:0000013 PMID:3855680 biolink:NamedThing omim.nt IAO:0000013 PMID:4038055 biolink:NamedThing omim.nt IAO:0000013 PMID:588966 biolink:NamedThing omim.nt IAO:0000013 PMID:6538765 biolink:NamedThing omim.nt IAO:0000013 PMID:6729702 biolink:NamedThing omim.nt IAO:0000013 PMID:6845177 biolink:NamedThing omim.nt IAO:0000013 PMID:7563401 biolink:NamedThing omim.nt IAO:0000013 PMID:7613891 biolink:NamedThing omim.nt IAO:0000013 PMID:7651004 biolink:NamedThing omim.nt IAO:0000013 PMID:7707569 biolink:NamedThing omim.nt IAO:0000013 PMID:7956205 biolink:NamedThing omim.nt IAO:0000013 PMID:8048013 biolink:NamedThing omim.nt IAO:0000013 PMID:8093508 biolink:NamedThing omim.nt IAO:0000013 PMID:8455684 biolink:NamedThing omim.nt IAO:0000013 PMID:9786252 biolink:NamedThing omim.nt IAO:0000013 UMLS:C0162871 biolink:NamedThing omim.nt owl:Class UMLS:C1853365 biolink:NamedThing omim.nt owl:Class ORPHA:86 biolink:NamedThing|biolink:Disease omim.nt owl:Class http://www.omim.org/phenotypicSeries/PS100070 biolink:NamedThing|biolink:Disease Aortic aneurysm, familial abdominal omim.nt owl:Class http://omim.org/entry/100100 biolink:NamedThing|biolink:Disease Prune Belly Syndrome Prune Belly Syndrome omim.nt PRUNE BELLY SYNDROME; PBS|Abdominal Muscles, Absence Of, With Urinary Tract Abnormality and Cryptorchidism|Eagle-Barrett Syndrome owl:Class MONARCH:.well-known/genid/OMIM100100ref10 biolink:NamedThing Prune belly syndrome: possible genetic implications. omim.nt IAO:0000310 MONARCH:.well-known/genid/OMIM100100ref16 biolink:NamedThing Congenital absence of the abdominal muscles with distended and hypertrophied urinary bladder. omim.nt IAO:0000310 MONARCH:.well-known/genid/OMIM100100ref8 biolink:NamedThing Der Mangel der Muskeln, insbesondere der Seitenbauchmuskeln. omim.nt IAO:0000310 PMID:13328166 biolink:NamedThing omim.nt IAO:0000013 PMID:144797 biolink:NamedThing omim.nt IAO:0000013 PMID:14797335 biolink:NamedThing omim.nt IAO:0000013 PMID:156252 biolink:NamedThing omim.nt IAO:0000013 PMID:156413 biolink:NamedThing omim.nt IAO:0000013 PMID:15912376 biolink:NamedThing omim.nt IAO:0000013 PMID:15922438 biolink:NamedThing omim.nt IAO:0000013 PMID:16145 biolink:NamedThing omim.nt IAO:0000013 PMID:18388787 biolink:NamedThing omim.nt IAO:0000013 PMID:22077972 biolink:NamedThing omim.nt IAO:0000013 PMID:27602 biolink:NamedThing omim.nt IAO:0000013 PMID:3047433 biolink:NamedThing omim.nt IAO:0000013 PMID:31441039 biolink:NamedThing omim.nt IAO:0000013 PMID:4150949 biolink:NamedThing omim.nt IAO:0000013 PMID:4231058 biolink:NamedThing omim.nt IAO:0000013 PMID:4239017 biolink:NamedThing omim.nt IAO:0000013 PMID:4382958 biolink:NamedThing omim.nt IAO:0000013 PMID:4400845 biolink:NamedThing omim.nt IAO:0000013 PMID:4402425 biolink:NamedThing omim.nt IAO:0000013 PMID:6128960 biolink:NamedThing omim.nt IAO:0000013 PMID:6231862 biolink:NamedThing omim.nt IAO:0000013 PMID:6454342 biolink:NamedThing omim.nt IAO:0000013 PMID:7070906 biolink:NamedThing omim.nt IAO:0000013 PMID:7118560 biolink:NamedThing omim.nt IAO:0000013 UMLS:C0033770 biolink:NamedThing omim.nt owl:Class ORPHA:2970 biolink:NamedThing|biolink:Disease omim.nt owl:Class http://omim.org/entry/100200 biolink:NamedThing Abducens Palsy omim.nt ABDUCENS PALSY owl:Class MONARCH:.well-known/genid/OMIM100200ref1 biolink:NamedThing The ocular palsies. omim.nt IAO:0000310 MONARCH:.well-known/genid/OMIM100200ref2 biolink:NamedThing Heredity in Ophthalmology. omim.nt IAO:0000310 MONARCH:.well-known/genid/OMIM100200ref3 biolink:NamedThing Congenital bilateral palsy of abducens. omim.nt IAO:0000310 UMLS:C4551519 biolink:NamedThing omim.nt owl:Class http://omim.org/entry/100300 biolink:NamedThing|biolink:Disease Adams-Oliver Syndrome 1 Adams-Oliver Syndrome 1 omim.nt ADAMS-OLIVER SYNDROME 1; AOS1|Absence Defect of Limbs, Scalp, and Skull|Aos|Aplasia Cutis Congenita, Congenital Heart Defect, and Frontonasal Cysts|Aplasia Cutis Congenita With Terminal Transverse Limb Defects|Congenital Scalp Defects With Distal Limb Reduction Anomalies owl:Class MONARCH:.well-known/genid/OMIM100300ref1 biolink:NamedThing Hereditary deformities in man due to arrested development. omim.nt IAO:0000310 PMID:1018305 biolink:NamedThing omim.nt IAO:0000013 PMID:10440823 biolink:NamedThing omim.nt IAO:0000013 PMID:10546102 biolink:NamedThing omim.nt IAO:0000013 PMID:10982487 biolink:NamedThing omim.nt IAO:0000013 PMID:1173820 biolink:NamedThing omim.nt IAO:0000013 PMID:1424238 biolink:NamedThing omim.nt IAO:0000013 PMID:1481809 biolink:NamedThing omim.nt IAO:0000013 PMID:15326631 biolink:NamedThing omim.nt IAO:0000013 PMID:1536190 biolink:NamedThing omim.nt IAO:0000013 PMID:15948197 biolink:NamedThing omim.nt IAO:0000013 PMID:1642283 biolink:NamedThing omim.nt IAO:0000013 PMID:16451141 biolink:NamedThing omim.nt IAO:0000013 PMID:17539905 biolink:NamedThing omim.nt IAO:0000013 PMID:18792979 biolink:NamedThing omim.nt IAO:0000013 PMID:1887843 biolink:NamedThing omim.nt IAO:0000013 PMID:18924173 biolink:NamedThing omim.nt IAO:0000013 PMID:1951437 biolink:NamedThing omim.nt IAO:0000013 PMID:19610107 biolink:NamedThing omim.nt IAO:0000013 PMID:2012136 biolink:NamedThing omim.nt IAO:0000013 PMID:21565291 biolink:NamedThing omim.nt IAO:0000013 PMID:2161342 biolink:NamedThing omim.nt IAO:0000013 PMID:25132448 biolink:NamedThing omim.nt IAO:0000013 PMID:2519562 biolink:NamedThing omim.nt IAO:0000013 PMID:2929669 biolink:NamedThing omim.nt IAO:0000013 PMID:3066221 biolink:NamedThing omim.nt IAO:0000013 PMID:3354598 biolink:NamedThing omim.nt IAO:0000013 PMID:3514708 biolink:NamedThing omim.nt IAO:0000013 PMID:3656372 biolink:NamedThing omim.nt IAO:0000013 PMID:3839451 biolink:NamedThing omim.nt IAO:0000013 PMID:3906608 biolink:NamedThing omim.nt IAO:0000013 PMID:474617 biolink:NamedThing omim.nt IAO:0000013 PMID:5536130 biolink:NamedThing omim.nt IAO:0000013 PMID:752066 biolink:NamedThing omim.nt IAO:0000013 PMID:7606848 biolink:NamedThing omim.nt IAO:0000013 PMID:8160731 biolink:NamedThing omim.nt IAO:0000013 PMID:8291551 biolink:NamedThing omim.nt IAO:0000013 PMID:862297 biolink:NamedThing omim.nt IAO:0000013 PMID:9385961 biolink:NamedThing omim.nt IAO:0000013 PMID:9823488 biolink:NamedThing omim.nt IAO:0000013 PMID:9916843 biolink:NamedThing omim.nt IAO:0000013 UMLS:C1970140 biolink:NamedThing omim.nt owl:Class UMLS:C4551482 biolink:NamedThing omim.nt owl:Class ORPHA:974 biolink:NamedThing|biolink:Disease omim.nt owl:Class http://www.omim.org/phenotypicSeries/PS100300 biolink:NamedThing|biolink:Disease Adams-Oliver syndrome omim.nt owl:Class http://omim.org/entry/100500 biolink:NamedThing omim.nt True owl:Class http://omim.org/entry/200150 biolink:NamedThing|biolink:Disease Choreoacanthocytosis Choreoacanthocytosis omim.nt CHOREOACANTHOCYTOSIS; CHAC|Acanthocytosis With Neurologic Disorder|Chorea-Acanthocytosis|Levine-Critchley Syndrome|Neuroacanthocytosis owl:Class http://omim.org/entry/100600 biolink:NamedThing|biolink:Disease Acanthosis Nigricans Acanthosis Nigricans omim.nt ACANTHOSIS NIGRICANS owl:Class MONARCH:.well-known/genid/OMIM100600ref3 biolink:NamedThing Genetic studies on acanthosis nigricans. omim.nt IAO:0000310 MONARCH:.well-known/genid/OMIM100600ref6 biolink:NamedThing Acanthosis nigricans, telangiectasia and diabetes mellitus. omim.nt IAO:0000310 PMID:10914675 biolink:NamedThing omim.nt IAO:0000013 PMID:1282780 biolink:NamedThing omim.nt IAO:0000013 PMID:13312473 biolink:NamedThing omim.nt IAO:0000013 PMID:5826935 biolink:NamedThing omim.nt IAO:0000013 PMID:6486848 biolink:NamedThing omim.nt IAO:0000013 PMID:7669619 biolink:NamedThing omim.nt IAO:0000013 UMLS:C0000889 biolink:NamedThing omim.nt owl:Class http://omim.org/entry/100640 biolink:NamedThing|biolink:Gene ALDH1A1 Aldehyde Dehydrogenase 1 Family, Member A1 omim.nt ALDEHYDE DEHYDROGENASE 1 FAMILY, MEMBER A1; ALDH1A1|Acetaldehyde Dehydrogenase 1|Aldehyde Dehydrogenase 1|Aldh, Liver Cytosolic|Retinal Dehydrogenase 1 owl:Class MONARCH:.well-known/genid/b833ef899960fe30f4ed biolink:NamedThing GRCh38chr9-72900670-72953052-Region omim.nt MONARCH:.well-known/genid/b4f1b27faa5bf451ae66 faldo:Region PMID:17529981 biolink:NamedThing omim.nt IAO:0000013 PMID:224930 biolink:NamedThing omim.nt IAO:0000013 PMID:2591967 biolink:NamedThing omim.nt IAO:0000013 PMID:26430123 biolink:NamedThing omim.nt IAO:0000013 PMID:2729894 biolink:NamedThing omim.nt IAO:0000013 PMID:2987944 biolink:NamedThing omim.nt IAO:0000013 PMID:3013004 biolink:NamedThing omim.nt IAO:0000013 PMID:3943866 biolink:NamedThing omim.nt IAO:0000013 PMID:6127541 biolink:NamedThing omim.nt IAO:0000013 PMID:6723659 biolink:NamedThing omim.nt IAO:0000013 OBO:CHR_9606chr9q21 biolink:NamedThing omim.nt owl:Class UMLS:C1412333 biolink:NamedThing omim.nt owl:Class SO:0000704 biolink:NamedThing omim.nt https://www.ncbi.nlm.nih.gov/gene/216 biolink:NamedThing omim.nt http://omim.org/entry/100650.0001 biolink:NamedThing ALDH2, GLU504LYS ({dbSNP rs671}) The designation for the ALDH2*2 polymorphism has been changed from GLU487LYS to GLU504LYS. The numbering change includes the N-terminal mitochondrial leader peptide of 17 amino acids ({31:Li et al., 2006}). The ALDH2*2-encoded protein was first reported to have a change from glutamic acid (glutamate) to lysine at residue 487 ({55:Yoshida et al., 1984}). {22:Hempel et al. (1985)} and {25:Hsu et al. (1985)} also showed that the catalytic deficiency in mitochondrial ALDH in East Asians that manifests as acute alcohol sensitivity ({610251}) can be traced to a structural point mutation at amino acid position 487 of the polypeptide. The substitution of lysine for glutamic acid results from a G-A transition. Alcohol Sensitivity and Protection Against Alcohol Dependence About 50% of East Asians are missing the ALDH2 isozyme. {27:Impraim et al. (1982)} found that the livers of East Asians lacking the ALDH2 isozyme show an enzymatically inactive but immunologically cross-reactive material (CRM) corresponding to the ALDH2 isozyme. To study the mechanism by which the ALDH2*2 allele exerts its dominant effect in decreasing ALDH2 activity in liver extracts and producing cutaneous flushing when the subject drinks alcohol, {52:Xiao et al. (1995)} cloned ALDH2*1 cDNA and generated the ALDH2*2 allele by site-directed mutagenesis. These cDNAs were transduced using retroviral vectors into HeLa and CV1 cells, which do not express ALDH2. The normal allele directed synthesis of immunoreactive ALDH2 protein with the expected isoelectric point and increased aldehyde dehydrogenase activity. The ALDH2*2 allele directed synthesis of mRNA and immunoreactive protein, but the protein lacked enzymatic activity. When ALDH2*1-expressing cells were transduced with ALDH2*2 vectors, both mRNAs were expressed and immunoreactive proteins with isoelectric points ranging between those of the 2 gene products were present, indicating that the subunits formed heteromers. ALDH2 activity in these cells was reduced below that of the parental ALDH2*1-expressing cells. Thus, the authors concluded that ALDH2*2 allele is sufficient to cause ALDH2 deficiency in vitro. {51:Xiao et al. (1996)} referred to the ALDH2 enzyme encoded by the ALDH2*1 allele (the wildtype form) as ALDH2E and the enzyme subunit encoded by ALDH2*2 as ALDH2K. They found that the ALDH2E enzyme was very stable, with a half-life of at least 22 hours. ALDH2K, on the other hand, had an enzyme half-life of only 14 hours. In cells expressing both subunits, most of the subunits assemble as heterotetramers, and these enzymes had a half-life of 13 hours. Thus, the effect of ALDH2K on enzyme turnover is dominant. Their studies indicated that ALDH2*2 exerts its dominant effect both by interfering with the catalytic activity of the enzyme and by increasing its turnover. Because genetic epidemiologic studies have suggested a mechanism by which homozygosity for the ALDH2*2 allele inhibits the development of alcoholism ({103780}) in Asians, {40:Peng et al. (1999)} recruited 18 adult Han Chinese men, matched by age, body-mass index, nutritional state, and homozygosity at the ALDH2 gene loci from a population of 273 men. Six individuals were chosen for each of the 3 ALDH2 allotypes, i.e., 2 homozygotes and 1 heterozygote. Following a low dose of ethanol, homozygous ALDH2*2 individuals were found to be strikingly responsive with pronounced cardiovascular hemodynamic effects as well as subjective perception of general discomfort for as long as 2 hours following ingestion. Among 71 Japanese nondrinkers and 268 drinkers of alcohol, {32:Liu et al. (2005)} found that drinkers had a significantly higher frequency of the 504glu allele. Individuals with the 504lys allele had an increased risk of alcohol-induced flushing (odds ratio of 33.0). In a study of 32 adult Han Chinese male students with no personal or family history of alcoholism, {39:Peng et al. (2007)} found that heterozygosity for the ALDH2*2 allele resulted in higher acetaldehyde levels after alcohol ingestion compared to wildtype homozygotes. After ingestion, heterozygotes also had faster heart rates, faster blood flow in the facial and carotid arteries, and more subjective discomfort compared to wildtype homozygotes. Overall, the findings indicated that acetaldehyde, rather than ethanol or acetate, are responsible for observed alcohol sensitivity reactions. {39:Peng et al. (2007)} postulated that ALDH2*2 heterozygotes have decreased aversion to the adverse effects of alcohol, and thus increased risk of drinking, compared to those who are homozygous for ALDH2*2. Among 1,032 Korean individuals, {29:Kim et al. (2008)} found that the combination of the ADH1B his48 allele ({dbSNP rs1229984}; {103720.0001}) and the ALDH2 lys504 allele offered protection against alcoholism. Individuals who carried both susceptibility alleles (arg48 and glu504, respectively) had a significantly increased risk for alcoholism (OR, 91.43; p = 1.4 x 10(-32)). Individuals with 1 protective and 1 susceptibility allele had a lesser increased risk for alcoholism (OR, 11.40; p = 3.5 x 10(-15)) compared to those with both protective alleles. {29:Kim et al. (2008)} calculated that alcoholism in the Korean population is 86.5% attributable to the detrimental effect of the ADH1B arg48 and the ALDH2 glu504 alleles. Susceptibility to Severe Hangover In a study of 140 men and women of Chinese, Japanese, and Korean heritage, {49:Wall et al. (2000)} found that those with ALDH2*2 alleles experienced more severe hangovers (see {610251}) and suggested that this may contribute, in part, to protection against the development of excessive or problematic drinking in Asian Americans. {54:Yokoyama et al. (2005)} found that inactive heterozygous ALDH2, alcohol flushing, and increased mean corpuscular volume (MCV) were positively associated with hangover susceptibility in Japanese workers, suggesting that acetaldehyde is etiologically linked to the development of hangover. Susceptibility to Alcohol-Related Esophageal Cancer In a case-control study with 221 Chinese patients with esophageal cancer and 191 controls, {11:Ding et al. (2010)} found that alcohol drinkers with the ALDH2 A allele showed a significantly increased risk of esophageal cancer compared to drinkers with the ALDH2 G/G genotype (OR, 3.08) or compared to nondrinkers with any genotype (OR, 3.05). There was a significantly higher risk of esophageal cancer in those with higher alcohol consumption (OR, 11.93), and a dose-dependent positive effect was observed. Drinkers with high cumulative lifetime consumption (greater than 2.5 kg*year calculated as grams of alcohol consumed per day multiplied by number of years of consumption) carrying both the ALHD2 A allele and the G allele of ADH1B (his48 allele) had an even higher risk of esophageal cancer (OR, 53.15) compared to individuals with the ALDH2 G/G and ADH1B A/A genotypes. {11:Ding et al. (2010)} hypothesized that increased acetaldehyde in drinkers with these susceptibility alleles has a carcinogenic effect. Susceptibility to Poor Response to Sublingual Nitroglycerin In 80 Han Chinese patients with arteriography-confirmed coronary artery disease who used only sublingual nitroglycerin, or glyceryl trinitrate (GTN) for angina relief, {31:Li et al. (2006)} found that the ALDH2*2 allele was associated with lack of efficacy of sublingual GTN. Enzyme kinetic analysis revealed that the catalytic efficiency of GTN metabolism of the glu504 protein is approximately 10-fold higher than that of the lys504 enzyme. {31:Li et al. (2006)} concluded that the presence of the ALDH2*2 allele contributes, in large part, to the lack of an efficacious clinical response to GTN and recommended that this genetic factor be considered when administering GTN, particularly to Asian patients, 30 to 50% of whom possess the inactive ALDH2*2 mutant allele. AMED Syndrome, Digenic In 10 patients from 8 unrelated Japanese families with AMED syndrome (AMEDS; {619151}), {37:Oka et al. (2020)} identified homozygous or compound heterozygous mutations in the ADH5 gene ({103710.0001}-{103710.0003}) as well as a homozygous (3 cases) or heterozygous (7 cases) E504K variant in the ALDH2 gene. The mutations, which were found by whole-exome sequencing (ADH5) or direct sequencing (ALDH2), segregated with the disorder in the families from whom parental DNA was available. Patient cells showed increased sensitivity to formaldehyde treatment compared to controls. In vitro functional expression studies in U2OS cells showed that while loss of either ADH5 or ALDH2 attenuated cell cycle progression, loss of both genes led to significant inhibition of DNA replication after formaldehyde treatment. Patient-derived AMEDS cells showed significant DNA damage after formaldehyde exposure, which could be completely rescued by ectopic expression of either wildtype ADH5 or ALDH2, suggesting that both genes are involved in formaldehyde detoxification. CD34+ hematopoietic progenitor stem cells with loss of ADH5 combined with the ALDH2 variant had impaired proliferation and differentiation capacity, suggesting that formaldehyde detoxification deficiency can cause a wide range of hematopoietic abnormalities. Loss of Adh5 function in combination with reduced Aldh2 activity recapitulated the phenotype of AMEDS in mice. {37:Oka et al. (2020)} emphasized that AMEDS is a true digenic disorder, since variations in 2 distinct genes (ADH5 and ALDH2) are necessary and sufficient to cause the disease. Although the ALDH2 variant influences the severity of the disease, it is still essential for disease development. The findings suggested a mechanism in which defects in the enzymatic detoxification processes of highly reactive genotoxic chemicals, such as formaldehyde, results in the accumulation of DNA damage that overburdens DNA repair pathways, thus causing multisystemic effects. omim.nt GENO:0000002 http://omim.org/entry/100650 biolink:NamedThing|biolink:Gene ALDH2 Aldehyde Dehydrogenase 2 Family omim.nt ALDEHYDE DEHYDROGENASE 2 FAMILY; ALDH2|Acetaldehyde Dehydrogenase 2|Aldehyde Dehydrogenase 2|Aldh2/Hmgic Fusion Gene|Aldh, Liver Mitochondrial|Esophageal Cancer, Alcohol-Related, Susceptibility to|Sublingual Nitroglycerin, Susceptibility to Poor Response to owl:Class ClinVar:RCV000020058 biolink:NamedThing omim.nt ClinVar:RCV000020059 biolink:NamedThing omim.nt ClinVar:RCV000020060 biolink:NamedThing omim.nt ClinVar:RCV000020061 biolink:NamedThing omim.nt ClinVar:RCV000020062 biolink:NamedThing omim.nt ClinVar:RCV001290000 biolink:NamedThing omim.nt dbSNP:rs671 biolink:NamedThing omim.nt owl:NamedIndividual http://omim.org/entry/100650#0001 biolink:NamedThing omim.nt MONARCH:.well-known/genid/b3eb6e29add79bdd009d biolink:NamedThing GRCh38chr12-111766932-111817531-Region omim.nt MONARCH:.well-known/genid/b07fdb363620d07436fa faldo:Region MONARCH:.well-known/genid/OMIM100650ref2 biolink:NamedThing Mechanism of biological sensitivity to alcohol: inherited deficiency of aldehyde dehydrogenase isoenzyme I in Mongoloids. (Abstract) omim.nt IAO:0000310 MONARCH:.well-known/genid/OMIM100650ref20 biolink:NamedThing Aldehyde metabolism and polymorphism of aldehyde dehydrogenase in Japanese. (Abstract) omim.nt IAO:0000310 MONARCH:.well-known/genid/OMIM100650ref26 biolink:NamedThing Chromosomal assignment of the genes for human aldehyde dehydrogenase 1 (ALDH1) and aldehyde dehydrogenase 2 (ALDH2). (Abstract) omim.nt IAO:0000310 MONARCH:.well-known/genid/OMIM100650ref42 biolink:NamedThing Human Polymorphic Genes: World Distribution. omim.nt IAO:0000310 MONARCH:.well-known/genid/OMIM100650ref44 biolink:NamedThing Genotypes of alcohol metabolizing enzymes in Japanese with alcoholic liver diseases: a strong association of the usual Caucasian type aldehyde dehydrogenase allele (ALDH2) with the disease. (Abstract) omim.nt IAO:0000310 MONARCH:.well-known/genid/OMIM100650ref47 biolink:NamedThing Personal Communication. omim.nt IAO:0000310 MONARCH:.well-known/genid/OMIM100650ref50 biolink:NamedThing Personal Communication. omim.nt IAO:0000310 PMID:10441588 biolink:NamedThing omim.nt IAO:0000013 PMID:10627091 biolink:NamedThing omim.nt IAO:0000013 PMID:10780266 biolink:NamedThing omim.nt IAO:0000013 PMID:11535626 biolink:NamedThing omim.nt IAO:0000013 PMID:1244489 biolink:NamedThing omim.nt IAO:0000013 PMID:15008789 biolink:NamedThing omim.nt IAO:0000013 PMID:15654505 biolink:NamedThing omim.nt IAO:0000013 PMID:15863807 biolink:NamedThing omim.nt IAO:0000013 PMID:16046871 biolink:NamedThing omim.nt IAO:0000013 PMID:16103363 biolink:NamedThing omim.nt IAO:0000013 PMID:16440063 biolink:NamedThing omim.nt IAO:0000013 PMID:16685648 biolink:NamedThing omim.nt IAO:0000013 PMID:1733836 biolink:NamedThing omim.nt IAO:0000013 PMID:17885622 biolink:NamedThing omim.nt IAO:0000013 PMID:18056758 biolink:NamedThing omim.nt IAO:0000013 PMID:18787169 biolink:NamedThing omim.nt IAO:0000013 PMID:20010786 biolink:NamedThing omim.nt IAO:0000013 PMID:2014795 biolink:NamedThing omim.nt IAO:0000013 PMID:20729865 biolink:NamedThing omim.nt IAO:0000013 PMID:21734703 biolink:NamedThing omim.nt IAO:0000013 PMID:22922648 biolink:NamedThing omim.nt IAO:0000013 PMID:2298906 biolink:NamedThing omim.nt IAO:0000013 PMID:2562960 biolink:NamedThing omim.nt IAO:0000013 PMID:2777251 biolink:NamedThing omim.nt IAO:0000013 PMID:2838413 biolink:NamedThing omim.nt IAO:0000013 PMID:3017845 biolink:NamedThing omim.nt IAO:0000013 PMID:3189337 biolink:NamedThing omim.nt IAO:0000013 PMID:33355142 biolink:NamedThing omim.nt IAO:0000013 PMID:3687946 biolink:NamedThing omim.nt IAO:0000013 PMID:3953578 biolink:NamedThing omim.nt IAO:0000013 PMID:4065146 biolink:NamedThing omim.nt IAO:0000013 PMID:511165 biolink:NamedThing omim.nt IAO:0000013 PMID:6117742 biolink:NamedThing omim.nt IAO:0000013 PMID:6543304 biolink:NamedThing omim.nt IAO:0000013 PMID:6582480 biolink:NamedThing omim.nt IAO:0000013 PMID:6650498 biolink:NamedThing omim.nt IAO:0000013 PMID:6724582 biolink:NamedThing omim.nt IAO:0000013 PMID:6881146 biolink:NamedThing omim.nt IAO:0000013 PMID:6987864 biolink:NamedThing omim.nt IAO:0000013 PMID:7013538 biolink:NamedThing omim.nt IAO:0000013 PMID:7126112 biolink:NamedThing omim.nt IAO:0000013 PMID:7180842 biolink:NamedThing omim.nt IAO:0000013 PMID:730161 biolink:NamedThing omim.nt IAO:0000013 PMID:7593603 biolink:NamedThing omim.nt IAO:0000013 PMID:7635462 biolink:NamedThing omim.nt IAO:0000013 PMID:8521389 biolink:NamedThing omim.nt IAO:0000013 PMID:870762 biolink:NamedThing omim.nt IAO:0000013 PMID:8903321 biolink:NamedThing omim.nt IAO:0000013 PMID:8929946 biolink:NamedThing omim.nt IAO:0000013 http://omim.org/entry/610251 biolink:NamedThing|biolink:Disease Alcohol Sensitivity, Acute Alcohol Sensitivity, Acute omim.nt ALCOHOL SENSITIVITY, ACUTE|Hangover, Susceptibility to owl:Class OBO:CHR_9606chr12q24.2 biolink:NamedThing omim.nt owl:Class UMLS:C1412335 biolink:NamedThing omim.nt owl:Class UMLS:C1863487 biolink:NamedThing omim.nt owl:Class UMLS:C2676227 biolink:NamedThing omim.nt owl:Class UMLS:C3149226 biolink:NamedThing omim.nt owl:Class https://www.ncbi.nlm.nih.gov/gene/217 biolink:NamedThing omim.nt http://omim.org/entry/100660 biolink:NamedThing|biolink:Gene ALDH3A1 Aldehyde Dehydrogenase, Family 3, Subfamily A, Member 1 omim.nt ALDEHYDE DEHYDROGENASE, FAMILY 3, SUBFAMILY A, MEMBER 1; ALDH3A1|Acetaldehyde Dehydrogenase 3|Aldehyde Dehydrogenase 3|Aldh, Stomach Type owl:Class MONARCH:.well-known/genid/b594a0ef8a58c2321f05 biolink:NamedThing GRCh38chr17-19737983-19748389-Region omim.nt MONARCH:.well-known/genid/bf8560408f92b35c2d0b faldo:Region MONARCH:.well-known/genid/OMIM100660ref5 biolink:NamedThing Human Polymorphic Genes: World Distribution. omim.nt IAO:0000310 PMID:10780262 biolink:NamedThing omim.nt IAO:0000013 PMID:1737758 biolink:NamedThing omim.nt IAO:0000013 PMID:4073832 biolink:NamedThing omim.nt IAO:0000013 PMID:7228061 biolink:NamedThing omim.nt IAO:0000013 PMID:7774944 biolink:NamedThing omim.nt IAO:0000013 PMID:9027499 biolink:NamedThing omim.nt IAO:0000013 PMID:9391071 biolink:NamedThing omim.nt IAO:0000013 OBO:CHR_9606chr17p11.2 biolink:NamedThing omim.nt owl:Class UMLS:C1412336 biolink:NamedThing omim.nt owl:Class https://www.ncbi.nlm.nih.gov/gene/218 biolink:NamedThing omim.nt http://omim.org/entry/100670 biolink:NamedThing|biolink:Gene ALDH1B1 Aldehyde Dehydrogenase 1 Family, Member B1 omim.nt ALDEHYDE DEHYDROGENASE 1 FAMILY, MEMBER B1; ALDH1B1|Acetaldehyde Dehydrogenase 5|Aldehyde Dehydrogenase 5 owl:Class MONARCH:.well-known/genid/b37cbbe2aca32fcd9fa9 biolink:NamedThing GRCh38chr9-38392701-38398664-Region omim.nt MONARCH:.well-known/genid/b328cf34273e6fd5e02a faldo:Region MONARCH:.well-known/genid/OMIM100670ref3 biolink:NamedThing Cloning of a new human aldehyde dehydrogenase gene and comparison with liver cytosolic ALDH1 and mitochondrial ALDH2 genes. (Abstract) omim.nt IAO:0000310 PMID:2061311 biolink:NamedThing omim.nt IAO:0000013 PMID:6985464 biolink:NamedThing omim.nt IAO:0000013 OBO:CHR_9606chr9p13 biolink:NamedThing omim.nt owl:Class UMLS:C1412338 biolink:NamedThing omim.nt owl:Class https://www.ncbi.nlm.nih.gov/gene/219 biolink:NamedThing omim.nt http://omim.org/entry/100675 biolink:NamedThing Acetaminophen Metabolism omim.nt ACETAMINOPHEN METABOLISM owl:Class MONARCH:.well-known/genid/OMIM100675ref1 biolink:NamedThing Decreased glucuronidation and increased bioactivation of acetaminophen in Gilbert's disease. (Abstract) omim.nt IAO:0000310 PMID:1302042 biolink:NamedThing omim.nt IAO:0000013 PMID:3829578 biolink:NamedThing omim.nt IAO:0000013 UMLS:C1863486 biolink:NamedThing omim.nt owl:Class http://omim.org/entry/100678 biolink:NamedThing|biolink:Gene ACAT2 Acetyl-Coa Acetyltransferase 2|encoded on strand opposite TCP1 omim.nt ACETYL-CoA ACETYLTRANSFERASE 2; ACAT2|Acetoacetyl-Coa Thiolase, Cytosolic|Acetocoenzyme a Acetyltransferase 2 owl:Class MONARCH:.well-known/genid/b4e90ce129adc0ee6e58 biolink:NamedThing GRCh38chr6-159762044-159779111-Region omim.nt MONARCH:.well-known/genid/b27fa30a4242ee3073c2 faldo:Region PMID:1850510 biolink:NamedThing omim.nt IAO:0000013 PMID:20597 biolink:NamedThing omim.nt IAO:0000013 PMID:2475872 biolink:NamedThing omim.nt IAO:0000013 PMID:3653076 biolink:NamedThing omim.nt IAO:0000013 PMID:7904580 biolink:NamedThing omim.nt IAO:0000013 PMID:7911016 biolink:NamedThing omim.nt IAO:0000013 PMID:8812443 biolink:NamedThing omim.nt IAO:0000013 http://omim.org/entry/614055 biolink:NamedThing Acetyl-Coa Acetyltransferase-2 Deficiency omim.nt ACETYL-CoA ACETYLTRANSFERASE-2 DEFICIENCY; ACAT2D|Acat2 Deficiency owl:Class OBO:CHR_9606chr6q25.3 biolink:NamedThing omim.nt owl:Class UMLS:C1412112 biolink:NamedThing omim.nt owl:Class https://www.ncbi.nlm.nih.gov/gene/39 biolink:NamedThing omim.nt http://omim.org/entry/100680 biolink:NamedThing omim.nt True owl:Class http://omim.org/entry/100740 biolink:NamedThing|biolink:Gene ACHE Acetylcholinesterase|blood group YT (112100) = epitope of ACHE omim.nt ACETYLCHOLINESTERASE; ACHE|Acetylcholine Acetylhydrolase|Yt owl:Class http://omim.org/entry/100690.0001 biolink:NamedThing CHRNA1, ASN217LYS In a 30-year-old woman with slow-channel congenital myasthenic syndrome-1A (CMS1A; {601462}), {8:Engel et al. (1996)} identified a heterozygous 651C-G transversion in exon 6 of the CHRNA1 gene, resulting in an asn217-to-lys (N217K) substitution at a conserved residue in the M1 transmembrane domain. The mutation cosegregated with the disease through 3 generations. Functional expression studies showed that the N217K mutation slowed the rate of AChR channel closure, increased the apparent affinity for ACh, and enhanced desensitization. Cationic overload of the postsynaptic region caused an endplate myopathy. omim.nt GENO:0000002 http://omim.org/entry/100690 biolink:NamedThing|biolink:Gene CHRNA1 Cholinergic Receptor, Nicotinic, Alpha Polypeptide 1 omim.nt CHOLINERGIC RECEPTOR, NICOTINIC, ALPHA POLYPEPTIDE 1; CHRNA1|Acetylcholine Receptor, Muscle, Alpha Subunit|Chrna owl:Class ClinVar:RCV000020044 biolink:NamedThing omim.nt dbSNP:rs137852798 biolink:NamedThing omim.nt owl:NamedIndividual http://omim.org/entry/100690#0001 biolink:NamedThing omim.nt http://omim.org/entry/100690.0002 biolink:NamedThing CHRNA1, VAL156MET In a 34-year-old man with slow-channel congenital myasthenic syndrome-1A (CMS1A; {601462}), {5:Croxen et al. (1997)} identified a heterozygous 466G-A transition in the CHRNA1 gene, resulting in a val156-to-met (V156M) substitution in a putative ACh-binding region of the protein. Functional studies suggested that the V156M mutation stabilizes the open state of the AChR channel. omim.nt GENO:0000002 ClinVar:RCV000020045 biolink:NamedThing omim.nt ClinVar:RCV001237075 biolink:NamedThing omim.nt dbSNP:rs137852799 biolink:NamedThing omim.nt owl:NamedIndividual http://omim.org/entry/100690#0002 biolink:NamedThing omim.nt http://omim.org/entry/100690.0003 biolink:NamedThing CHRNA1, THR254ILE In a 60-year-old woman with slow-channel congenital myasthenic syndrome-1A (CMS1A; {601462}), {5:Croxen et al. (1997)} identified a heterozygous 761C-T transition in the CHRNA1 gene, resulting in a thr254-to-ile (T254I) substitution in the M2 transmembrane domain, which lines the AChR channel pore. The patient, who first developed symptoms at age 16 years, was previously reported by {4:Chauplannaz and Bady (1994)}. Functional expression studies suggested that the T254I mutation stabilized the open state of the AChR channel. omim.nt GENO:0000002 ClinVar:RCV000020046 biolink:NamedThing omim.nt dbSNP:rs137852800 biolink:NamedThing omim.nt owl:NamedIndividual http://omim.org/entry/100690#0003 biolink:NamedThing omim.nt http://omim.org/entry/100690.0004 biolink:NamedThing CHRNA1, GLY153SER In 5 members of a family and another unrelated person with slow-channel congenital myasthenic syndrome-1A (CMS1A; {601462}), {25:Sine et al. (1995)} identified a heterozygous 457G-A transition in the CHRNA1 gene, resulting in a gly153-to-ser (G153S) substitution in the extracellular domain of the subunit. Electrophysiologic analysis of endplates revealed prolonged decay of miniature endplate currents (MEPCs) and prolonged activation episodes of single AChR channels. Single-channel kinetic analysis of engineered alpha-G153S AChR showed a markedly decreased rate of acetylcholine dissociation, indicating an increased affinity for ACh, causing the mutant AChR to open repeatedly during ACh occupancy. In addition, ACh-binding measurements combined with the kinetic analysis indicated increased desensitization of the mutant AChR. {25:Sine et al. (1995)} concluded that ACh-binding affinity can dictate the time course of the synaptic response. The patients had previously been reported by {7:Engel et al. (1982)}. {5:Croxen et al. (1997)} identified the G153S mutation in a 41-year-old woman with CMS1 and her affected mother. The proband had previously been reported by {4:Chauplannaz and Bady (1994)}. The G153S substitution resides in the putative ACh-binding domain of the protein, and functional expression studies suggested that the G153S mutation impedes dissociation of ACh from the AChR. omim.nt GENO:0000002 ClinVar:RCV000020047 biolink:NamedThing omim.nt ClinVar:RCV000556947 biolink:NamedThing omim.nt dbSNP:rs137852801 biolink:NamedThing omim.nt owl:NamedIndividual http://omim.org/entry/100690#0004 biolink:NamedThing omim.nt http://omim.org/entry/100690.0005 biolink:NamedThing CHRNA1, SER269ILE In a 28-year-old woman with slow-channel congenital myasthenic syndrome-1A (CMS1A; {601462}) with onset in the eighth month of her first pregnancy ({21:Oosterhuis et al., 1987}), {5:Croxen et al. (1997)} identified an 806G-T transversion in the CHRNA1 gene, resulting in a ser269-to-ile (S269I) substitution. The mutation lies within the short extracellular sequence between the M2 and M3 transmembrane domains of the protein. omim.nt GENO:0000002 ClinVar:RCV000020048 biolink:NamedThing omim.nt dbSNP:rs137852802 biolink:NamedThing omim.nt owl:NamedIndividual http://omim.org/entry/100690#0005 biolink:NamedThing omim.nt http://omim.org/entry/100690.0006 biolink:NamedThing CHRNA1, VAL249PHE In a patient with a severe form of slow-channel congenital myasthenic syndrome-1A (CMS1A; {601462}), {17:Milone et al. (1997)} identified a heterozygous 745G-T transversion in exon 7 of the CHRNA1 gene, resulting in a val249-to-phe (V249F) substitution in the M2 transmembrane domain of the protein that does not face the channel lumen. The patient's unaffected father was a mosaic for the mutation. Functional expression studies showed that the V249F mutation causes increased channel opening in the absence of ACh, prolonged opening in the presence of ACh, increased affinity for ACh, and enhanced desensitization. The findings indicated that the structure of the M2 domain is essential for correct stabilization of functional channel states and that mutation in this region results in multiple functional defects. omim.nt GENO:0000002 ClinVar:RCV000020049 biolink:NamedThing omim.nt ClinVar:RCV000623150 biolink:NamedThing omim.nt dbSNP:rs137852803 biolink:NamedThing omim.nt owl:NamedIndividual http://omim.org/entry/100690#0006 biolink:NamedThing omim.nt http://omim.org/entry/100690.0007 biolink:NamedThing CHRNA1, VAL285ILE In 2 sibs with fast-channel congenital myasthenic syndrome-1B (CMS1B; {608930}), {28:Wang et al. (1999)} identified compound heterozygosity for 2 mutations in the CHRNA1 gene. The functional mutation was an 853G-A transition in exon 7, resulting in a val285-to-ile (V285I) substitution in the upper third of the M3 transmembrane domain. The other mutation was a c.697T-G transversion in exon 6, resulting in a phe233-to-val substitution (F233V; {100690.0008}) in the M1 transmembrane domain, causing markedly reduced protein expression; this was essentially a null mutation. Functional expression studies showed that the V285I mutation reduced the amplitude of the miniature endplate current (MEPC), accelerated the decay of the MEPC, and reduced total current flow through the AChR channel. Kinetic analysis showed abnormally slow channel opening and rapid closing, resulting in an abnormally brief current. omim.nt GENO:0000002 ClinVar:RCV000020050 biolink:NamedThing omim.nt dbSNP:rs137852804 biolink:NamedThing omim.nt owl:NamedIndividual http://omim.org/entry/100690#0007 biolink:NamedThing omim.nt http://omim.org/entry/100690.0008 biolink:NamedThing CHRNA1, PHE233VAL For discussion of the phe233-to-val (F233V) mutation in the CHRNA1 gene that was found in compound heterozygous state in a patient with fast-channel congenital myasthenic syndrome-1B (CMS1B; {608930}) by {28:Wang et al. (1999)}, see {100690.0007}. omim.nt GENO:0000002 ClinVar:RCV000020051 biolink:NamedThing omim.nt dbSNP:rs137852805 biolink:NamedThing omim.nt owl:NamedIndividual http://omim.org/entry/100690#0008 biolink:NamedThing omim.nt http://omim.org/entry/100690.0009 biolink:NamedThing CHRNA1, PHE256LEU In a patient with fast-channel congenital myasthenic syndrome-1B (CMS1B; {608930}), originally reported by {27:Vincent et al. (1981)}, {29:Webster et al. (2004)} identified a heterozygous 766T-C transition in exon 7 of the CHRNA1 gene, resulting in a phe256-to-leu (F256L) substitution in the M2 transmembrane domain of the protein. Functional expression studies showed that the F256L mutation results in fewer and shorter ion channel activations, with a decreased channel- opening rate and an increased channel-closing rate. The patient's mildly affected father also had the F256L mutation. {29:Webster et al. (2004)} noted that autosomal dominant inheritance of fast-channel CMS is rare. omim.nt GENO:0000002 ClinVar:RCV000020052 biolink:NamedThing omim.nt dbSNP:rs137852806 biolink:NamedThing omim.nt owl:NamedIndividual http://omim.org/entry/100690#0009 biolink:NamedThing omim.nt http://omim.org/entry/100690.0010 biolink:NamedThing CHRNA1, VAL132LEU In a girl with severe fast-channel congenital myasthenic syndrome-1B (CMS1B; {608930}), {24:Shen et al. (2003)} identified compound heterozygosity for 2 mutations in the CHRNA1 gene: a frameshifting null mutation (381delC; {100690.0011}), and a 394G-C transversion, resulting in a val132-to-leu (V132L) substitution, in a highly conserved cys-loop at the junction between the extracellular ligand-binding and transmembrane domains of the protein. Functional kinetic expression studies showed that channels with the V132L mutation had an increased dissociation constant for ACh, shorter burst duration, and resistance to desensitization, culminating in a reduced probability of channel opening over a range of ACh concentrations. The mutant channel showed an approximately 30-fold decrease of ACh-binding affinity for the second of 2 closed-state binding sites, but only a 2-fold decrease in gating efficiency. Mutations corresponding to the val132 residue in other AChR subunits showed different effects, indicating functional asymmetry between cys-loops of the different subunits. omim.nt GENO:0000002 ClinVar:RCV000020053 biolink:NamedThing omim.nt dbSNP:rs137852807 biolink:NamedThing omim.nt owl:NamedIndividual http://omim.org/entry/100690#0010 biolink:NamedThing omim.nt http://omim.org/entry/100690.0011 biolink:NamedThing CHRNA1, 1-BP DEL, 381C For discussion of the 381delC mutation in the CHRNA1 gene that was found in compound heterozygous state in a patient with fast-channel congenital myasthenic syndrome-1B (CMS1B; {608930}) by {24:Shen et al. (2003)}, see {100690.0010}. omim.nt GENO:0000002 ClinVar:RCV000020054 biolink:NamedThing omim.nt http://omim.org/entry/100690#0011 biolink:NamedThing omim.nt http://omim.org/entry/100690.0012 biolink:NamedThing CHRNA1, CYS418TRP In a 24-year-old man with congenital slow-channel congenital myasthenic syndrome-1A (CMS1A; {601462}) and mild symptoms since birth, {23:Shen et al. (2006)} identified a de novo heterozygous 1362C-G transversion in the CHRNA1 gene, resulting in a cys418-to-trp (C418W) substitution in the M4 domain of the protein. This residue is highly conserved across AChR-alpha subunits of different species but not across individual subunits. Functional kinetic expression studies in HEK cells showed that the AChR with the mutant alpha subunit increased the channel-opening equilibrium as well as the mean duration of open durations and bursts characteristic of a slow-channel mutation. The C418W mutant subunit increased the rate of channel opening and slowed the rate of channel closing, but had no effect on agonist binding. {23:Shen et al. (2006)} used a check plasmid as a screening tool to identify a specific siRNA that suppressed the mutant, but not the wildtype allele, at the mRNA, protein, and functional levels in vitro. omim.nt GENO:0000002 ClinVar:RCV000020055 biolink:NamedThing omim.nt dbSNP:rs137852808 biolink:NamedThing omim.nt owl:NamedIndividual http://omim.org/entry/100690#0012 biolink:NamedThing omim.nt http://omim.org/entry/100690.0013 biolink:NamedThing CHRNA1, ARG254LEU In a consanguineous Pakistani family, {16:Michalk et al. (2008)} demonstrated that multiple pterygium syndrome ({253290}) was caused by homozygosity for a G-to-T transversion at nucleotide 761 in exon 6 of the CHRNA1 gene that resulted in an arg234-to-leu (R234L) substitution in the mature protein (R254L in the precursor). omim.nt GENO:0000002 ClinVar:RCV000020056 biolink:NamedThing omim.nt dbSNP:rs137852809 biolink:NamedThing omim.nt owl:NamedIndividual http://omim.org/entry/100690#0013 biolink:NamedThing omim.nt http://omim.org/entry/100690.0014 biolink:NamedThing CHRNA1, 17-BP DUP, NT117 In a nonconsanguineous African family, {16:Michalk et al. (2008)} found that multiple pterygium syndrome ({253290}) was caused by homozygous duplication of 17 basepairs in exon 2 of the CHRNA1 gene, 117_133dup17, that resulted in frameshift and subsequent premature protein termination (H24RfsX19; H45RfsX19 in the precursor). omim.nt GENO:0000002 ClinVar:RCV000020057 biolink:NamedThing omim.nt http://omim.org/entry/100690#0014 biolink:NamedThing omim.nt http://omim.org/entry/100690.0015 biolink:NamedThing CHRNA1, IVS3AS, G-A, -8 In a woman with autosomal recessive inheritance of fast-channel congenital myasthenic syndrome-1B (CMS1B; {608930}), {15:Masuda et al. (2008)} identified compound heterozygosity for 2 mutations in the CHRNA1 gene: a G-to-A transition in intron 3 (IVS3-8G-A) and a 937C-T transition in exon 7, resulting in an arg313-to-trp (R313W; {100690.0016}) substitution in a highly conserved residue. Neither mutation was found in 200 control alleles. Functional expression studies in HEK cells showed decreased expression of the R313W mutant, which showed mild fast-channel properties. The -8G-A transition occurred just before exon P3A, and disrupted an intronic splicing silencer (ISS) sequence, resulting in the inclusion of exon P3A and yielding a nonfunctional protein. omim.nt GENO:0000002 ClinVar:RCV000022417 biolink:NamedThing omim.nt http://omim.org/entry/100690#0015 biolink:NamedThing omim.nt http://omim.org/entry/100690.0016 biolink:NamedThing CHRNA1, ARG313TRP For discussion of the arg313-to-trp (R313W) mutation in the CHRNA1 gene that was found in compound heterozygous state in a patient with fast-channel congenital myasthenic syndrome-1B (CMS1B; {608930}) by {15:Masuda et al. (2008)}, see {100690.0015}. omim.nt GENO:0000002 ClinVar:RCV000022418 biolink:NamedThing omim.nt ClinVar:RCV000803477 biolink:NamedThing omim.nt dbSNP:rs374391312 biolink:NamedThing omim.nt owl:NamedIndividual http://omim.org/entry/100690#0016 biolink:NamedThing omim.nt MONARCH:.well-known/genid/be18e7bb5aedfd747bfd biolink:NamedThing GRCh38chr2-174747591-174764471-Region omim.nt MONARCH:.well-known/genid/b5fec86933e3384d5297 faldo:Region MONARCH:.well-known/genid/OMIM100690ref1 biolink:NamedThing Assignment of the human acetylcholine receptor beta subunit gene to chromosome 17 and the alpha and delta subunit genes to chromosome 2. (Abstract) omim.nt IAO:0000310 PMID:10195214 biolink:NamedThing omim.nt IAO:0000013 PMID:12454998 biolink:NamedThing omim.nt IAO:0000013 PMID:12588888 biolink:NamedThing omim.nt IAO:0000013 PMID:12827192 biolink:NamedThing omim.nt IAO:0000013 PMID:15079006 biolink:NamedThing omim.nt IAO:0000013 PMID:16685696 biolink:NamedThing omim.nt IAO:0000013 PMID:1694127 biolink:NamedThing omim.nt IAO:0000013 PMID:17687331 biolink:NamedThing omim.nt IAO:0000013 PMID:18252226 biolink:NamedThing omim.nt IAO:0000013 PMID:18633353 biolink:NamedThing omim.nt IAO:0000013 PMID:18806275 biolink:NamedThing omim.nt IAO:0000013 PMID:2221824 biolink:NamedThing omim.nt IAO:0000013 PMID:2423878 biolink:NamedThing omim.nt IAO:0000013 PMID:2558853 biolink:NamedThing omim.nt IAO:0000013 PMID:27626380 biolink:NamedThing omim.nt IAO:0000013 PMID:3022377 biolink:NamedThing omim.nt IAO:0000013 PMID:3338555 biolink:NamedThing omim.nt IAO:0000013 PMID:3651795 biolink:NamedThing omim.nt IAO:0000013 PMID:6287911 biolink:NamedThing omim.nt IAO:0000013 PMID:6688857 biolink:NamedThing omim.nt IAO:0000013 PMID:7254233 biolink:NamedThing omim.nt IAO:0000013 PMID:7619526 biolink:NamedThing omim.nt IAO:0000013 PMID:7863154 biolink:NamedThing omim.nt IAO:0000013 PMID:7902325 biolink:NamedThing omim.nt IAO:0000013 PMID:7910962 biolink:NamedThing omim.nt IAO:0000013 PMID:8872460 biolink:NamedThing omim.nt IAO:0000013 PMID:9158151 biolink:NamedThing omim.nt IAO:0000013 PMID:9221765 biolink:NamedThing omim.nt IAO:0000013 OBO:CHR_9606chr2q24 biolink:NamedThing omim.nt owl:Class http://omim.org/entry/253290 biolink:NamedThing|biolink:Disease Multiple Pterygium Syndrome, Lethal Type Multiple Pterygium Syndrome, Lethal Type omim.nt MULTIPLE PTERYGIUM SYNDROME, LETHAL TYPE; LMPS|Pterygium Syndrome, Multiple, Lethal Type owl:Class http://omim.org/entry/601462 biolink:NamedThing|biolink:Disease Myasthenic Syndrome, Congenital, 1A, Slow-Channel Myasthenic Syndrome, Congenital, 1A, Slow-Channel omim.nt MYASTHENIC SYNDROME, CONGENITAL, 1A, SLOW-CHANNEL; CMS1A|Cms Iia, Formerly|Myasthenic Syndrome, Congenital, Type Iia, Formerly owl:Class http://omim.org/entry/608930 biolink:NamedThing|biolink:Disease Myasthenic Syndrome, Congenital, 1B, Fast-Channel Myasthenic Syndrome, Congenital, 1B, Fast-Channel omim.nt MYASTHENIC SYNDROME, CONGENITAL, 1B, FAST-CHANNEL; CMS1B owl:Class http://www.omim.org/phenotypicSeries/PS601462 biolink:NamedThing|biolink:Disease Myasthenic syndrome, congenital omim.nt owl:Class UMLS:C1413401 biolink:NamedThing omim.nt owl:Class https://www.ncbi.nlm.nih.gov/gene/1134 biolink:NamedThing omim.nt http://omim.org/entry/100700 biolink:NamedThing Achard Syndrome omim.nt ACHARD SYNDROME owl:Class MONARCH:.well-known/genid/OMIM100700ref1 biolink:NamedThing Arachnodactylie. omim.nt IAO:0000310 MONARCH:.well-known/genid/OMIM100700ref4 biolink:NamedThing Arachnodactyly. omim.nt IAO:0000310 PMID:14430455 biolink:NamedThing omim.nt IAO:0000013 PMID:6082898 biolink:NamedThing omim.nt IAO:0000013 UMLS:C1332135 biolink:NamedThing omim.nt owl:Class http://omim.org/entry/100710.0001 biolink:NamedThing CHRNB1, VAL266MET In a 19-year-old female with slow-channel congenital myasthenic syndrome-2A (CMS2A; {616313}), {4:Engel et al. (1996)} identified a heterozygous 796G-A transition in exon 8 of the CHRNB1 gene, resulting in a val266-to-met (V266M) substitution in a conserved residue in the M2 transmembrane domain of the AChR-beta subunit. Functional expression studies showed that the V266M mutation slowed the rate of AChR channel closure and increased the apparent affinity for ACh. The mutation also caused pathologic channel openings even in the absence of ACh, resulting in a leaky channel. Cationic overload of the postsynaptic region caused an endplate myopathy. omim.nt GENO:0000002 http://omim.org/entry/100710 biolink:NamedThing|biolink:Gene CHRNB1 Cholinergic Receptor, Nicotinic, Beta Polypeptide 1|mutation identified in 1 CMS2C family omim.nt CHOLINERGIC RECEPTOR, NICOTINIC, BETA POLYPEPTIDE 1; CHRNB1|Acetylcholine Receptor, Muscle, Beta Subunit|Chrnb owl:Class ClinVar:RCV000020040 biolink:NamedThing omim.nt ClinVar:RCV000726984 biolink:NamedThing omim.nt dbSNP:rs137852810 biolink:NamedThing omim.nt owl:NamedIndividual http://omim.org/entry/100710#0001 biolink:NamedThing omim.nt http://omim.org/entry/100710.0002 biolink:NamedThing CHRNB1, LEU263MET In a 32-year-old male with slow-channel congenital myasthenic syndrome-2A (CMS2A; {616313}), {5:Gomez et al. (1996)} identified a heterozygous C-to-A transversion in the CHRNB1 gene, resulting in a leu263-to-met (L263M) substitution. Functional expression studies showed that the L263M mutation interrupted the leucine ring of the AChR channel gate, causing an 8-fold increase in channel open time and resulting in severe endplate myopathy as well as extensive remodeling of the postsynaptic membrane. The pronounced abnormalities in neuromuscular synaptic architecture and function and the muscle fiber damage and weakness resulting from a single point mutation were a dramatic example of a mutation having a dominant gain of function and of hereditary excitotoxicity. omim.nt GENO:0000002 ClinVar:RCV000020041 biolink:NamedThing omim.nt dbSNP:rs137852811 biolink:NamedThing omim.nt owl:NamedIndividual http://omim.org/entry/100710#0002 biolink:NamedThing omim.nt http://omim.org/entry/100710.0003 biolink:NamedThing CHRNB1, 9-BP DEL, NT1276 In 3 sibs with congenital myasthenic syndrome-2C associated with acetylcholine receptor deficiency (CMS2C; {616314}), {9:Quiram et al. (1999)} identified compound heterozygosity for 2 mutations in the CHRNB1 gene. One mutation was a 9-bp deletion (1276del9) in exon 10, resulting in a deletion of 3 codons (426-428) in the long cytoplasmic loop between the M3 and M4 domains of the protein. The second mutation was a skipping of exon 8 ({100710.0004}), truncating the beta subunit before its M1 transmembrane domain and abolishing surface expression of pentameric AChR. By coexpressing the 3-codon deleted subunit with combinations of wildtype subunits in HEK293 cells, {9:Quiram et al. (1999)} demonstrated that the mutation impairs AChR assembly by disrupting a specific interaction between the beta and delta ({100720}) subunits. Studies with related deletion and missense mutations indicated that secondary structure in this region of the beta subunit is crucial for interaction with the delta subunit. The findings implied that the mutated residues are positioned at the interface between beta and delta subunits and demonstrated contribution of this local region of the long cytoplasmic loop to AChR assembly. omim.nt GENO:0000002 ClinVar:RCV000020042 biolink:NamedThing omim.nt http://omim.org/entry/100710#0003 biolink:NamedThing omim.nt http://omim.org/entry/100710.0004 biolink:NamedThing CHRNB1, EX8DEL For discussion of the mutation that caused skipping of exon 8 in the CHRNB1 gene that was found in compound heterozygous state in patients with congenital myasthenic syndrome-2C associated with acetylcholine receptor deficiency (CMS2C; {616314}) by {9:Quiram et al. (1999)}, see {100710.0003}. omim.nt GENO:0000002 ClinVar:RCV000020043 biolink:NamedThing omim.nt http://omim.org/entry/100710#0004 biolink:NamedThing omim.nt MONARCH:.well-known/genid/bf6c5a32c915da95457d biolink:NamedThing GRCh38chr17-7445060-7457709-Region omim.nt MONARCH:.well-known/genid/ba8375505a8907623663 faldo:Region MONARCH:.well-known/genid/OMIM100710ref2 biolink:NamedThing Assignment of the human acetylcholine receptor beta subunit gene to chromosome 17 and the alpha and delta subunit genes to chromosome 2. (Abstract) omim.nt IAO:0000310 PMID:10562302 biolink:NamedThing omim.nt IAO:0000013 PMID:2740233 biolink:NamedThing omim.nt IAO:0000013 PMID:8651643 biolink:NamedThing omim.nt IAO:0000013 http://omim.org/entry/616314 biolink:NamedThing|biolink:Disease Myasthenic Syndrome, Congenital, 2C, Associated With Acetylcholine Receptor Deficiency Myasthenic Syndrome, Congenital, 2C, Associated With Acetylcholine Receptor Deficiency omim.nt MYASTHENIC SYNDROME, CONGENITAL, 2C, ASSOCIATED WITH ACETYLCHOLINE RECEPTOR DEFICIENCY; CMS2C owl:Class OBO:CHR_9606chr17p12 biolink:NamedThing omim.nt owl:Class http://omim.org/entry/616313 biolink:NamedThing|biolink:Disease Myasthenic Syndrome, Congenital, 2A, Slow-Channel Myasthenic Syndrome, Congenital, 2A, Slow-Channel omim.nt MYASTHENIC SYNDROME, CONGENITAL, 2A, SLOW-CHANNEL; CMS2A owl:Class UMLS:C1413407 biolink:NamedThing omim.nt owl:Class https://www.ncbi.nlm.nih.gov/gene/1140 biolink:NamedThing omim.nt http://omim.org/entry/100720.0001 biolink:NamedThing CHRND, SER268PHE In a patient with slow-channel congenital myasthenic syndrome-3A (CMS3A; {616321}), {4:Gomez et al. (2002)} identified a de novo heterozygous C-T transition in exon 8 of the CHRND gene, resulting in a ser268-to-phe (S268F) substitution in the twelfth residue of the delta subunit M2 domain. The mutation was not present in either parent or in 100 normal controls. Functional expression studies showed that the mutation caused delayed closure of AChR ion channels, increasing the propensity for open-channel block, as well as a reduced rate of channel opening. {4:Gomez et al. (2002)} suggested that the observations were consistent with steric hindrance on the channel, introduced by the large mutant phenylalanine residue in place of the wildtype serine. omim.nt GENO:0000002 http://omim.org/entry/100720 biolink:NamedThing|biolink:Gene CHRND Cholinergic Receptor, Nicotinic, Delta Polypeptide|mutation identified in 1 CMS3A patient and 1 CMS3C family omim.nt CHOLINERGIC RECEPTOR, NICOTINIC, DELTA POLYPEPTIDE; CHRND|Acetylcholine Receptor, Muscle, Delta Subunit owl:Class ClinVar:RCV000020031 biolink:NamedThing omim.nt ClinVar:RCV001218475 biolink:NamedThing omim.nt dbSNP:rs121909502 biolink:NamedThing omim.nt owl:NamedIndividual http://omim.org/entry/100720#0001 biolink:NamedThing omim.nt http://omim.org/entry/100720.0002 biolink:NamedThing CHRND, PRO250GLN In 3 Saudi Arabian patients with fast-channel congenital myasthenic syndrome-3B (CMS3B; {616322}), {12:Shen et al. (2002)} identified a homozygous c.749C-A transversion in exon 7 of the CHRND gene, resulting in a pro250-to-gln (P250Q) substitution at the penultimate C-terminal residue of the M1 transmembrane domain. All 3 patients were born to consanguineous parents, and 2 of the patients were first cousins. Functional expression studies showed that the P250Q mutation caused a decreased amplitude of the miniature endplate potential (MEPP) and current (MEPC) to approximately 26 to 35% of normal. The opening burst duration was decreased and disassociation of ACh was increased, resulting in brief channel-opening episodes. In addition, the mutant CHRND protein showed abnormal association with the alpha (CHRNA1; {100690}) subunit, resulting in a decreased number of fully assembled AChRs. omim.nt GENO:0000002 ClinVar:RCV000020032 biolink:NamedThing omim.nt dbSNP:rs121909503 biolink:NamedThing omim.nt owl:NamedIndividual http://omim.org/entry/100720#0002 biolink:NamedThing omim.nt http://omim.org/entry/100720.0003 biolink:NamedThing CHRND, GLU59LYS In a girl with fast-channel congenital myasthenic syndrome-3B (CMS3B; {616322}) who was born with contractures of both hands, {2:Brownlow et al. (2001)} identified compound heterozygosity for 2 mutations in the CHRND gene: a 175G-A transition in exon 3, resulting in a glu59-to-lys (E59K) substitution in a conserved extracellular region of the protein, and a 2-bp deletion (756delAG; {100720.0004}) in the exon 7/intron 7 boundary, resulting in a null allele. The E59K allele was inherited from the mother and the 2-bp deletion was inherited from the father. Functional expression studies showed reduced adult and fetal AChR expression and a reduced probability of both adult and fetal AChR being in the open state, consistent with a fast-syndrome phenotype. omim.nt GENO:0000002 ClinVar:RCV000020034 biolink:NamedThing omim.nt dbSNP:rs121909504 biolink:NamedThing omim.nt owl:NamedIndividual http://omim.org/entry/100720#0003 biolink:NamedThing omim.nt http://omim.org/entry/100720.0004 biolink:NamedThing CHRND, 2-BP DEL, 756AG For discussion of the 756delAG mutation in the CHRND gene that was found in compound heterozygous state in a patient with fast-channel congenital myasthenic syndrome-3B (CMS3B; {616322}) by {2:Brownlow et al. (2001)}, see {100720.0003}. (The abstract of the article by {2:Brownlow et al. (2001)} described this mutation as 756insAG, whereas the text described it as 756delAG.) omim.nt GENO:0000002 ClinVar:RCV000020035 biolink:NamedThing omim.nt dbSNP:rs879255564 biolink:NamedThing omim.nt owl:NamedIndividual http://omim.org/entry/100720#0004 biolink:NamedThing omim.nt http://omim.org/entry/100720.0005 biolink:NamedThing CHRND, TRP57TER In a consanguineous Turkish family, {7:Michalk et al. (2008)} found that lethal multiple pterygium syndrome ({253290}) in 2 male sibs was caused by homozygosity for a G-to-A transition in exon 3 of the CHRND gene that resulted in a trp57-to-ter amino acid substitution (W57X; W78X in the precursor). omim.nt GENO:0000002 ClinVar:RCV000020036 biolink:NamedThing omim.nt ClinVar:RCV001093255 biolink:NamedThing omim.nt dbSNP:rs121909505 biolink:NamedThing omim.nt owl:NamedIndividual http://omim.org/entry/100720#0005 biolink:NamedThing omim.nt http://omim.org/entry/100720.0006 biolink:NamedThing CHRND, PHE74LEU {7:Michalk et al. (2008)} found that lethal multiple pterygium syndrome ({253290}) in multiple sibs in a German family was caused by compound heterozygosity for mutation in the CHRND gene: a T-to-C transition in exon 4 (283T-C), resulting in a phe74-to-leu substitution in the mature protein (F74L; F95L in the precursor), and a nonsense mutation The other allele carried a nonsense mutation (R443X; {100720.0007}). omim.nt GENO:0000002 ClinVar:RCV000020037 biolink:NamedThing omim.nt dbSNP:rs121909506 biolink:NamedThing omim.nt owl:NamedIndividual http://omim.org/entry/100720#0006 biolink:NamedThing omim.nt http://omim.org/entry/100720.0007 biolink:NamedThing CHRND, ARG443TER {7:Michalk et al. (2008)} found that lethal multiple pterygium syndrome ({253290}) in multiple sibs in a German family was caused by compound heterozygosity for mutation in the CHRND gene: a 1390C-T transition in exon 12 resulting in an arg443-to-ter (R443X) substitution in the mature protein (R464X in the precursor) on one allele, and on the other a missense mutation (F74L; {100720.0006}). omim.nt GENO:0000002 ClinVar:RCV000020038 biolink:NamedThing omim.nt dbSNP:rs121909507 biolink:NamedThing omim.nt owl:NamedIndividual http://omim.org/entry/100720#0007 biolink:NamedThing omim.nt http://omim.org/entry/100720.0008 biolink:NamedThing CHRND, LEU42PRO In a 20-year-old woman with fast-channel congenital myasthenic syndrome-3B (CMS3B; {616322}) since birth, {11:Shen et al. (2008)} identified compound heterozygosity for 2 mutations in the CHRND gene: leu42-to-pro (L42P) and ile58-to-lys (I58K; {100720.0009}). In vitro functional expression studies showed that the I58K substitution prevented expression of the delta subunit and was a null mutation. The L42P substitution resulted in reduced gating efficiency, slower opening of the channel, and decreased probability that the channel would open in response to ACh. Further studies showed that the L42P-mutant protein altered the intersubunit linkage of the adjacent delta subunit N41 with the juxtaposed alpha subunit (CHRNA1; {100690}) residue Y127. omim.nt GENO:0000002 ClinVar:RCV000020039 biolink:NamedThing omim.nt dbSNP:rs121909508 biolink:NamedThing omim.nt owl:NamedIndividual http://omim.org/entry/100720#0008 biolink:NamedThing omim.nt http://omim.org/entry/100720.0009 biolink:NamedThing CHRND, ILE58LYS For discussion of the ile58-to-lys (I58K) mutation in the CHRND gene that was found in compound heterozygous state in a patient with fast-channel congenital myasthenic syndrome-3B (CMS3B; {616322}) by {11:Shen et al. (2008)}, see {100720.0008}. omim.nt GENO:0000002 ClinVar:RCV000020033 biolink:NamedThing omim.nt dbSNP:rs121909509 biolink:NamedThing omim.nt owl:NamedIndividual http://omim.org/entry/100720#0009 biolink:NamedThing omim.nt http://omim.org/entry/100720.0010 biolink:NamedThing CHRND, GLU381LYS In a German boy with congenital myasthenic syndrome-3C associated with acetylcholine receptor deficiency (CMS3C; {616323}), {9:Muller et al. (2006)} identified compound heterozygosity for a c.1141G-A transition in exon 10 of the CHRND gene, resulting in a glu381-to-lys (E381K) substitution, and a 2.2-kb deletion ({100720.0011}) resulting in the loss of half of exon 8 and the entire exon 9. The E381K mutation, which occurred at a highly conserved residue in the cytoplasmic loop, was not found in 200 control alleles. The mutations segregated with the disorder in the family. In vitro functional expression studies in HEK293 cells showed that the E381K mutation resulted in decreased expression of the AChR at the cell surface (about 70% of wildtype). The mutant protein impaired normal clustering of the AChR channel with rapsyn (RAPSN; {601592}), which stabilizes the AChR at the cell surface. Muscle biopsy from the patient was not available. omim.nt GENO:0000002 ClinVar:RCV000170317 biolink:NamedThing omim.nt dbSNP:rs145955590 biolink:NamedThing omim.nt owl:NamedIndividual http://omim.org/entry/100720#0010 biolink:NamedThing omim.nt http://omim.org/entry/100720.0011 biolink:NamedThing CHRND, 2.2-KB DEL For discussion of 2.2-kb deletion in the CHRND gene that was found in compound heterozygous state in a patient with congenital myasthenic syndrome-3C associated with acetylcholine receptor deficiency (CMS3C; {616323}) by {9:Muller et al. (2006)}, see {100720.0010}. omim.nt GENO:0000002 ClinVar:RCV000170318 biolink:NamedThing omim.nt http://omim.org/entry/100720#0011 biolink:NamedThing omim.nt MONARCH:.well-known/genid/b6240aa3dea4c1af7bde biolink:NamedThing GRCh38chr2-232526159-232537906-Region omim.nt MONARCH:.well-known/genid/b66cd3a60b72587f27d6 faldo:Region PMID:11435464 biolink:NamedThing omim.nt IAO:0000013 PMID:11782989 biolink:NamedThing omim.nt IAO:0000013 PMID:12499478 biolink:NamedThing omim.nt IAO:0000013 PMID:16916845 biolink:NamedThing omim.nt IAO:0000013 PMID:18398509 biolink:NamedThing omim.nt IAO:0000013 PMID:2564730 biolink:NamedThing omim.nt IAO:0000013 PMID:8103404 biolink:NamedThing omim.nt IAO:0000013 http://omim.org/entry/616321 biolink:NamedThing|biolink:Disease Myasthenic Syndrome, Congenital, 3A, Slow-Channel Myasthenic Syndrome, Congenital, 3A, Slow-Channel omim.nt MYASTHENIC SYNDROME, CONGENITAL, 3A, SLOW-CHANNEL; CMS3A owl:Class http://omim.org/entry/616323 biolink:NamedThing|biolink:Disease Myasthenic Syndrome, Congenital, 3C, Associated With Acetylcholine Receptor Deficiency Myasthenic Syndrome, Congenital, 3C, Associated With Acetylcholine Receptor Deficiency omim.nt MYASTHENIC SYNDROME, CONGENITAL, 3C, ASSOCIATED WITH ACETYLCHOLINE RECEPTOR DEFICIENCY; CMS3C owl:Class OBO:CHR_9606chr2q33 biolink:NamedThing omim.nt owl:Class http://omim.org/entry/616322 biolink:NamedThing|biolink:Disease Myasthenic Syndrome, Congenital, 3B, Fast-Channel Myasthenic Syndrome, Congenital, 3B, Fast-Channel omim.nt MYASTHENIC SYNDROME, CONGENITAL, 3B, FAST-CHANNEL; CMS3B owl:Class UMLS:C1413411 biolink:NamedThing omim.nt owl:Class https://www.ncbi.nlm.nih.gov/gene/1144 biolink:NamedThing omim.nt http://omim.org/entry/100725.0001 biolink:NamedThing CHRNE, THR264PRO In a 20-year-old woman with slow-channel congenital myasthenic syndrome-4A (CMS4A; {605809}), {23:Ohno et al. (1995)} identified a heterozygous c.790A-C transversion at nucleotide 790 in exon 8 of the CHRNE gene, resulting in a thr264-to-pro (T264P) substitution at a highly conserved residue in the M2 transmembrane domain lining the channel pore. Genetically engineered mutant T264P AChR expressed in a human embryonic kidney fibroblast cell line showed markedly prolonged channel openings in the presence of agonist, as well as opening in the absence of agonist. omim.nt GENO:0000002 http://omim.org/entry/100725 biolink:NamedThing|biolink:Gene CHRNE Cholinergic Receptor, Nicotinic, Epsilon Polypeptide omim.nt CHOLINERGIC RECEPTOR, NICOTINIC, EPSILON POLYPEPTIDE; CHRNE|Acetylcholine Receptor, Muscle, Epsilon Subunit owl:Class ClinVar:RCV000020011 biolink:NamedThing omim.nt ClinVar:RCV001093141 biolink:NamedThing omim.nt dbSNP:rs121909510 biolink:NamedThing omim.nt owl:NamedIndividual http://omim.org/entry/100725#0001 biolink:NamedThing omim.nt http://omim.org/entry/100725.0002 biolink:NamedThing CHRNE, LEU269PHE In 3 affected members of a family with slow-channel congenital myasthenic syndrome-4A (CMS4A; {605809}), {12:Gomez and Gammack (1995)} identified heterozygosity for a C-to-T transition in the CHRNE gene, resulting in a leu269-to-phe (L269F) substitution within the M2 transmembrane domain of the protein. In a 16-year-old male with CMS4A, {11:Engel et al. (1996)} identified a heterozygous c.805C-T transition in exon 8 of the CHRNE gene, resulting in the L269F substitution at a conserved residue in the M2 transmembrane domain that lines that AChR channel pore. Functional expression studies showed that the L269F mutation slowed the rate of AChR channel closure and increased the apparent affinity for ACh. The mutation also caused pathologic channel openings even in the absence of ACh, resulting in a leaky channel. Cationic overload of the postsynaptic region caused an endplate myopathy. omim.nt GENO:0000002 ClinVar:RCV000020012 biolink:NamedThing omim.nt dbSNP:rs121909511 biolink:NamedThing omim.nt owl:NamedIndividual http://omim.org/entry/100725#0002 biolink:NamedThing omim.nt http://omim.org/entry/100725.0003 biolink:NamedThing CHRNE, PRO121LEU In 2 unrelated patients with fast-channel congenital myasthenic syndrome-4B (CMS4B; {616324}), 1 of whom had been reported by {32:Uchitel et al. (1993)}, {25:Ohno et al. (1996)} identified compound heterozygosity for 2 mutations in the CHRNE gene. Both patients shared a heterozygous c.362C-T transition in exon 5, resulting in a pro121-to-leu (P121L) substitution at a conserved residue in the extracellular domain of the subunit. Functional expression studies showed that the P121L mutation caused a marked decrease in the rate of AChR channel opening (nearly 500-fold slower compared to controls), a reduction in the frequency of the open channel state, and resistance to desensitization by ACh. One patient also had a heterozygous c.-24G-A transition ({100725.0017}), resulting in a gly(-8)-to-arg (G-8R) substitution in the signal peptide region; the other patient had a heterozygous c.428C-T transition in exon 5 of the CHRNE gene, resulting in a ser143-to-leu (S143L; {100725.0018}) substitution in a conserved N-glycosylation consensus sequence of the protein. Both of these mutations were determined to be null mutations, with the clinical phenotype defined by the P121L mutation. omim.nt GENO:0000002 ClinVar:RCV000020014 biolink:NamedThing omim.nt ClinVar:RCV000691820 biolink:NamedThing omim.nt dbSNP:rs121909512 biolink:NamedThing omim.nt owl:NamedIndividual http://omim.org/entry/100725#0003 biolink:NamedThing omim.nt http://omim.org/entry/100725.0004 biolink:NamedThing CHRNE, ARG64TER In a patient with congenital myasthenic syndrome-4C associated with AChR deficiency (CMS4C; {608931}), {24:Ohno et al. (1997)} identified compound heterozygosity for 2 mutations in the CHRNE gene: a c.190C-T transition that converted an arginine codon to a TGA stop codon at position 64 (R64X), and a c.440G-T transversion predicted to result in an arg147-to-leu (R147L; {100725.0005}) substitution. An affected brother had both mutations; the asymptomatic mother had the R64X allele and the asymptomatic father and brother had the R147L allele. The mutated arginine (R64X) is conserved across epsilon subunits of other species, but not in other subunits. R64X predicted truncation of the epsilon subunit in its extracellular domain, and expression studies in human embryonic kidney fibroblasts (HEK cells) indicated that it was a null mutation. The R147L mutation significantly reduced AChR expression. omim.nt GENO:0000002 ClinVar:RCV000020015 biolink:NamedThing omim.nt ClinVar:RCV000687026 biolink:NamedThing omim.nt dbSNP:rs121909513 biolink:NamedThing omim.nt owl:NamedIndividual http://omim.org/entry/100725#0004 biolink:NamedThing omim.nt http://omim.org/entry/100725.0005 biolink:NamedThing CHRNE, ARG147LEU For discussion of the arg147-to-leu (R147L) mutation in the CHRNE gene that was found in compound heterozygous state in a patient with congenital myasthenic syndrome-4C associated with acetylcholine receptor deficiency (CMS4C; {608931}) by {24:Ohno et al. (1997)}, see {100725.0004}. omim.nt GENO:0000002 ClinVar:RCV000020013 biolink:NamedThing omim.nt ClinVar:RCV000801881 biolink:NamedThing omim.nt dbSNP:rs121909514 biolink:NamedThing omim.nt owl:NamedIndividual http://omim.org/entry/100725#0005 biolink:NamedThing omim.nt http://omim.org/entry/100725.0006 biolink:NamedThing CHRNE, 1-BP DEL, 911T {30:Sieb et al. (2000)} found that a brother and sister with congenital myasthenic syndrome-4C associated with AChR deficiency (CMS4C; {608931}) were compound heterozygotes for a 1-bp deletion (c.911delT) and a splice site mutation (IVS4+1G-A; {100725.0007}) in the CHRNE gene. Both mutations resulted in truncation of the protein. The family had previously been reported by {29:Sieb et al. (1998)}. In a patient with a mild form of postsynaptic congenital myasthenic syndrome, {21:Muller et al. (2005)} identified compound heterozygosity for 2 mutations in the CHRNE gene: c.911delT and a splice site mutation ({100725.0020}). omim.nt GENO:0000002 ClinVar:RCV000020016 biolink:NamedThing omim.nt ClinVar:RCV000326857 biolink:NamedThing omim.nt ClinVar:RCV000641735 biolink:NamedThing omim.nt ClinVar:RCV001271737 biolink:NamedThing omim.nt dbSNP:rs879255562 biolink:NamedThing omim.nt owl:NamedIndividual http://omim.org/entry/100725#0006 biolink:NamedThing omim.nt http://omim.org/entry/100725.0007 biolink:NamedThing CHRNE, IVS4DS, G-A, +1 For discussion of the IVS4+1G-A mutation in the CHRNE gene that was found in compound heterozygous state in a patient with congenital myasthenic syndrome-4C associated with AChR deficiency (CMS4C; {608931}) by {30:Sieb et al. (2000)}, see {616146.0006}. omim.nt GENO:0000002 ClinVar:RCV000020017 biolink:NamedThing omim.nt dbSNP:rs879253722 biolink:NamedThing omim.nt owl:NamedIndividual http://omim.org/entry/100725#0007 biolink:NamedThing omim.nt http://omim.org/entry/100725.0008 biolink:NamedThing CHRNE, 1-BP DEL, 1030C In a 30-year-old woman with congenital myasthenic syndrome-4C associated with AChR deficiency (CMS4C; {608931}), {30:Sieb et al. (2000)} found compound heterozygosity for a novel c.1030delC mutation and the previously described R64X mutation ({100725.0004}). omim.nt GENO:0000002 ClinVar:RCV000020018 biolink:NamedThing omim.nt dbSNP:rs879253723 biolink:NamedThing omim.nt owl:NamedIndividual http://omim.org/entry/100725#0008 biolink:NamedThing omim.nt http://omim.org/entry/100725.0009 biolink:NamedThing|biolink:SequenceVariant omim.nt True owl:NamedIndividual http://omim.org/entry/100725.0022 biolink:NamedThing CHRNE, SER278DEL {6:Croxen et al. (2002)} reported a rare example of a patient with recessively inherited slow-channel congenital myasthenic syndrome-4A (CMS4A; {605809}), born of consanguineous Bangladeshi parents, who presented with failure to breathe after administration of an anesthetic. She had bilateral ptosis and weakness of facial, neck, shoulder, hip, and small muscles of the hand. Molecular analysis revealed compound heterozygosity for 2 mutations in the CHRNE gene: ser278del on 1 allele and an arg217-to-leu substitution (R217L; {100725.0023}) on the other. (In the original publication, {6:Croxen et al. (2002)} erroneously stated that this patient had a homozygous c.233T-C transition in the CHRNE gene, resulting in a leu78-to-pro (L78P) substitution in an extracellular region of the AChRE subunit.) omim.nt GENO:0000002 http://omim.org/entry/100725.0010 biolink:NamedThing CHRNE, LEU221PHE In 2 unrelated families with a mild form of slow-channel congenital myasthenic syndrome-4A (CMS4A; {605809}), {6:Croxen et al. (2002)} identified a heterozygous c.661C-T transition in the CHRNE gene, resulting in a leu221-to-phe (L221F) substitution located near the extracellular end of the M1 domain of the AChRE subunit. The authors hypothesized that the mutation may enhance the affinity of the AChRE subunit for ACh. The 2 pedigrees showed different inheritance patterns: in 1 family, all members with the mutation were affected, whereas in the other family, 2 members with the mutation were clinically unaffected, thus illustrating incomplete penetrance. The patients had previously been reported by {26:Oosterhuis et al. (1987)} and {3:Chauplannaz and Bady (1994)}. omim.nt GENO:0000002 ClinVar:RCV000020020 biolink:NamedThing omim.nt dbSNP:rs28999110 biolink:NamedThing omim.nt owl:NamedIndividual http://omim.org/entry/100725#0010 biolink:NamedThing omim.nt http://omim.org/entry/100725.0011 biolink:NamedThing CHRNE, 156C-T In 2 sibs, born of consanguineous parents, with congenital myasthenic syndrome-4C associated with AChR deficiency (CMS4C; {608931}), {22:Nichols et al. (1999)} identified a homozygous c.156C-T transition in the CHRNE promoter region (termed the N-box). Both parents were heterozygous for the mutation. Intercostal muscle biopsy from 1 patient showed loss of expression of the AChR-epsilon mRNA. {22:Nichols et al. (1999)} stated that this was the first evidence in humans that an N-box mutation can lead to disruption of epsilon subunit transcription. omim.nt GENO:0000002 ClinVar:RCV000020021 biolink:NamedThing omim.nt dbSNP:rs748144899 biolink:NamedThing omim.nt owl:NamedIndividual http://omim.org/entry/100725#0011 biolink:NamedThing omim.nt http://omim.org/entry/100725.0012 biolink:NamedThing CHRNE, 1-BP DEL, 1267G In 13 patients from 11 Gypsy families with congenital myasthenic syndrome-4C associated with AChR deficiency (CMS4C; {608931}), {1:Abicht et al. (1999)} identified a homozygous 1-bp deletion in exon 12 of the CHRNE gene (c.1267delG). All families were of Gypsy or southeastern European origin. Genotype analysis indicated that they derived from a common ancestor. In patients from India and Pakistan with CMS and AChR deficiency, {7:Croxen et al. (1999)} identified the 1267delG mutation in exon 12 of the CHRNE gene. {18:Middleton et al. (1999)} identified a homozygous c.1267delG mutation in affected members of 5 families with CMS4C previously reported by {4:Christodoulou et al. (1997)}. Four of the families were of Gypsy descent. {20:Morar et al. (2004)} used the 1267delG mutation and 4 other private mutations among the Roma (Gypsies) to infer some of the missing parameters relevant to the comprehensive characterization of the population history of the Gypsies. Sharing of mutations and high carrier rates supported a strong founder effect. The identity of the congenital myasthenia 1267delG mutation in Gypsy and Indian/Pakistani chromosomes provided strong evidence for the Indian origins of the Gypsies. {14:Hantai et al. (2004)} reported a carrier rate of 3.74% for the 1267delG mutation in these ethnic groups. omim.nt GENO:0000002 ClinVar:RCV000020022 biolink:NamedThing omim.nt ClinVar:RCV000235026 biolink:NamedThing omim.nt ClinVar:RCV000516854 biolink:NamedThing omim.nt ClinVar:RCV000556621 biolink:NamedThing omim.nt ClinVar:RCV001169937 biolink:NamedThing omim.nt dbSNP:rs763258280 biolink:NamedThing omim.nt owl:NamedIndividual http://omim.org/entry/100725#0012 biolink:NamedThing omim.nt http://omim.org/entry/100725.0013 biolink:NamedThing CHRNE, 1-BP INS, 1101T In a patient with congenital myasthenic syndrome-4C associated with AChR deficiency (CMS4C; {608931}), {10:Engel et al. (1996)} identified compound heterozygosity for two 1-bp insertions in the CHRNE gene: c.1101insT and c.1293insG ({100725.0014}). Both mutations predict premature termination of the protein between the third (M3) and fourth (M4) transmembrane domains. The patient's asymptomatic son carried the 1293insG mutation. Functional expression studies of both mutations showed a marked reduction of AChR expression. {10:Engel et al. (1996)} found that the patient expressed the fetal AChR gamma subunit (CHRNG; {100730}), which likely served as a means of phenotypic rescue. omim.nt GENO:0000002 ClinVar:RCV000020023 biolink:NamedThing omim.nt dbSNP:rs886037628 biolink:NamedThing omim.nt owl:NamedIndividual http://omim.org/entry/100725#0013 biolink:NamedThing omim.nt http://omim.org/entry/100725.0014 biolink:NamedThing CHRNE, 1-BP INS, 1293G {27:Richard et al. (2008)} identified a homozygous 1-bp insertion (c.1293insG) in the CHRNE gene in 14 (60%) of 23 North African families with congenital myasthenic syndrome-4C associated with AChR deficiency (CMS4C; {608931}). All 14 families were consanguineous; 9 originated from Algeria, 3 from Tunisia, and 1 each from Morocco and Libya. Haplotype analysis indicated a founder effect that occurred about 700 years ago. The phenotype was relatively homogeneous without fetal involvement and with moderate hypotonia and oculobulbar involvement, mild and stable disease course, and good response to cholinesterase inhibitors. For discussion of the 1293insG mutation in the CHRNE gene that was found in compound heterozygous state in a patient with CMS4C by {10:Engel et al. (1996)}, see {100725.0013}. omim.nt GENO:0000002 ClinVar:RCV000020024 biolink:NamedThing omim.nt ClinVar:RCV000235035 biolink:NamedThing omim.nt ClinVar:RCV000479377 biolink:NamedThing omim.nt ClinVar:RCV000804085 biolink:NamedThing omim.nt dbSNP:rs773526895 biolink:NamedThing omim.nt owl:NamedIndividual http://omim.org/entry/100725#0014 biolink:NamedThing omim.nt http://omim.org/entry/100725.0015 biolink:NamedThing CHRNE, 7-BP DEL, 553 In a patient with congenital myasthenic syndrome-4C associated with AChR deficiency (CMS4C; {608931}), {24:Ohno et al. (1997)} identified compound heterozygosity for 2 mutations in the CHRNE gene: a 7-bp deletion (c.553del7), resulting in a truncated protein, and a c.931C-T transition in exon 9, resulting in an arg311-to-trp (R311W; {100725.0016}) substitution. One of these 2 mutations was found in heterozygous state in several asymptomatic family members. Functional expression studies showed that the R311W mutation had a mild fast-channel kinetic effect on the AChR by shortening the long burst and increasing the decay of the endplate current. omim.nt GENO:0000002 ClinVar:RCV000020025 biolink:NamedThing omim.nt ClinVar:RCV000551845 biolink:NamedThing omim.nt ClinVar:RCV000598584 biolink:NamedThing omim.nt ClinVar:RCV000853364 biolink:NamedThing omim.nt ClinVar:RCV001271739 biolink:NamedThing omim.nt dbSNP:rs753828284 biolink:NamedThing omim.nt owl:NamedIndividual http://omim.org/entry/100725#0015 biolink:NamedThing omim.nt http://omim.org/entry/100725.0016 biolink:NamedThing CHRNE, ARG311TRP For discussion of the arg311-to-trp (R311W) mutation in the CHRNE gene that was found in compound heterozygous state in a patient with congenital myasthenic syndrome-4C associated with AChR deficiency (CMS4C; {608931}) by {25:Ohno et al. (1996)}, see {100725.0015}. omim.nt GENO:0000002 ClinVar:RCV000020026 biolink:NamedThing omim.nt ClinVar:RCV000711205 biolink:NamedThing omim.nt dbSNP:rs121909515 biolink:NamedThing omim.nt owl:NamedIndividual http://omim.org/entry/100725#0016 biolink:NamedThing omim.nt http://omim.org/entry/100725.0017 biolink:NamedThing CHRNE, GLY-8ARG For discussion of the gly(-8)-to-arg (G-8R) mutation in the CHRNE gene that was found in compound heterozygous state in a patient with fast-channel congenital myasthenic syndrome-4B (CMS4B; {616324}) by {25:Ohno et al. (1996)}, see {100725.0003}. Functional expression studies showed that the G-8R mutant CHRNE shows impaired association with the alpha (CHRNA1; {100690}) subunit of the AChR. omim.nt GENO:0000002 ClinVar:RCV000020027 biolink:NamedThing omim.nt ClinVar:RCV000559012 biolink:NamedThing omim.nt ClinVar:RCV001004610 biolink:NamedThing omim.nt dbSNP:rs372635387 biolink:NamedThing omim.nt owl:NamedIndividual http://omim.org/entry/100725#0017 biolink:NamedThing omim.nt http://omim.org/entry/100725.0018 biolink:NamedThing CHRNE, SER143LEU For discussion of the ser143-to-leu (S143L) mutation in the CHRNE gene that was found in compound heterozygous state in a patient with fast-channel congenital myasthenic syndrome-4B (CMS4B; {616324}) by {25:Ohno et al. (1996)}, see {100725.0003}. Functional expression studies showed that the S143L mutant CHRNE fails to assemble with the alpha (CHRNA1; {100690}) subunit of the AChR. omim.nt GENO:0000002 ClinVar:RCV000020028 biolink:NamedThing omim.nt ClinVar:RCV000356252 biolink:NamedThing omim.nt ClinVar:RCV000429916 biolink:NamedThing omim.nt ClinVar:RCV000707387 biolink:NamedThing omim.nt ClinVar:RCV001004608 biolink:NamedThing omim.nt dbSNP:rs121909516 biolink:NamedThing omim.nt owl:NamedIndividual http://omim.org/entry/100725#0018 biolink:NamedThing omim.nt http://omim.org/entry/100725.0019 biolink:NamedThing CHRNE, ALA411PRO In 4 affected patients from 3 unrelated families with fast-channel congenital myasthenic syndrome-4B (CMS4B; {616324}) {33:Wang et al. (2000)} identified a c.1231G-C transversion in the CHRNE gene, resulting in an ala411-to-pro (A411P) substitution in the cytoplasmic domain known as the amphipathic helix, which spans the M3 and M4 transmembrane domains. Two patients were homozygous for the mutation, and 2 patients were compound heterozygous with another null mutation in CHRNE. Functional expression studies showed that the A411P mutation caused an increase in the distributions of rates for channel opening and closing, increasing the range of activation kinetics. Using structural modeling, {33:Wang et al. (2000)} concluded that the energy landscape of the AChR is shaped like a funnel, with corrugations running perpendicular to the long axis of the funnel. omim.nt GENO:0000002 ClinVar:RCV000020029 biolink:NamedThing omim.nt dbSNP:rs121909517 biolink:NamedThing omim.nt owl:NamedIndividual http://omim.org/entry/100725#0019 biolink:NamedThing omim.nt http://omim.org/entry/100725.0020 biolink:NamedThing CHRNE, IVS5AS, G-A, -16 In a patient with a mild form of congenital myasthenic syndrome-4C associated with AChR deficiency (CMS4C; {608931}), {21:Muller et al. (2005)} identified compound heterozygosity for 2 mutations in the CHRNE gene: a G-to-A transition in intron 5, resulting in a premature termination codon after 19 amino acids in the extracellular part of the protein, and a 1-bp deletion ({100725.0006}). However, detailed RNA analysis showed that the patient had 4 CHRNE mRNA transcripts differing at the exon 5/exon 6 boundary, 2 of which were generated by use of a cryptic donor site in exon 5. omim.nt GENO:0000002 ClinVar:RCV000020030 biolink:NamedThing omim.nt dbSNP:rs879255563 biolink:NamedThing omim.nt owl:NamedIndividual http://omim.org/entry/100725#0020 biolink:NamedThing omim.nt http://omim.org/entry/100725.0021 biolink:NamedThing CHRNE, TRP55ARG In an 8-year-old boy, born of consanguineous parents, with fast-channel congenital myasthenic syndrome-4B (CMS4B; {616324}), {28:Shen et al. (2012)} identified a homozygous c.163T-C transition in the CHRNE gene, resulting in a trp55-to-arg (W55R) substitution at a highly conserved residue at the alpha/epsilon ACh-binding site interface. The patient had severe myasthenic symptoms since birth and was wheelchair-bound. Three similarly affected sibs died in infancy, and he had 1 similarly affected brother. In vitro functional expression in HEK293 cells showed that the mutant protein was expressed, but patch-clamp recordings indicated 30-fold reduced ACh affinity and 75-fold reduced apparent gating efficiency. The mutation hindered isomerization of the receptor from the closed to the open state, slowed the apparent opening rate, accelerated the apparent closing rate, and reduced open channel probability. These altered channel kinetics predicted a short duration and low amplitude of the endplate potential with an inability to activate postsynaptic sodium channels. There was also a low opening probability of the mutant receptor over a range of ACh concentrations, which explained the limited clinical response to pyridostigmine that was observed in this patient. omim.nt GENO:0000002 ClinVar:RCV000033219 biolink:NamedThing omim.nt dbSNP:rs193919341 biolink:NamedThing omim.nt owl:NamedIndividual http://omim.org/entry/100725#0021 biolink:NamedThing omim.nt ClinVar:RCV000033234 biolink:NamedThing omim.nt dbSNP:rs398122830 biolink:NamedThing omim.nt owl:NamedIndividual http://omim.org/entry/100725#0022 biolink:NamedThing omim.nt http://omim.org/entry/100725.0023 biolink:NamedThing CHRNE, ARG217LEU For discussion of the arg217-to-leu (R217L) mutation in the CHRNE gene that was found in compound heterozygous state in a patient with autosomal recessive slow-channel congenital myasthenic syndrome-4A (CMS4A; {605809}) by {6:Croxen et al. (2002)}, see {100725.0022}. omim.nt GENO:0000002 ClinVar:RCV000033235 biolink:NamedThing omim.nt ClinVar:RCV000876183 biolink:NamedThing omim.nt ClinVar:RCV001128140 biolink:NamedThing omim.nt dbSNP:rs201434993 biolink:NamedThing omim.nt owl:NamedIndividual http://omim.org/entry/100725#0023 biolink:NamedThing omim.nt MONARCH:.well-known/genid/b88b3952bbbd33ba6293 biolink:NamedThing GRCh38chr17-4897770-4905018-Region omim.nt MONARCH:.well-known/genid/bf581e9ab8872e4c7d7b faldo:Region PMID:10211467 biolink:NamedThing omim.nt IAO:0000013 PMID:10496269 biolink:NamedThing omim.nt IAO:0000013 PMID:10514102 biolink:NamedThing omim.nt IAO:0000013 PMID:10534268 biolink:NamedThing omim.nt IAO:0000013 PMID:10962020 biolink:NamedThing omim.nt IAO:0000013 PMID:11030414 biolink:NamedThing omim.nt IAO:0000013 PMID:12087176 biolink:NamedThing omim.nt IAO:0000013 PMID:12141316 biolink:NamedThing omim.nt IAO:0000013 PMID:12417530 biolink:NamedThing omim.nt IAO:0000013 PMID:12481987 biolink:NamedThing omim.nt IAO:0000013 PMID:15322984 biolink:NamedThing omim.nt IAO:0000013 PMID:15367858 biolink:NamedThing omim.nt IAO:0000013 PMID:15471888 biolink:NamedThing omim.nt IAO:0000013 PMID:16087917 biolink:NamedThing omim.nt IAO:0000013 PMID:17853947 biolink:NamedThing omim.nt IAO:0000013 PMID:1881908 biolink:NamedThing omim.nt IAO:0000013 PMID:19064877 biolink:NamedThing omim.nt IAO:0000013 PMID:22592360 biolink:NamedThing omim.nt IAO:0000013 PMID:7531341 biolink:NamedThing omim.nt IAO:0000013 PMID:7538206 biolink:NamedThing omim.nt IAO:0000013 PMID:7688301 biolink:NamedThing omim.nt IAO:0000013 PMID:8232384 biolink:NamedThing omim.nt IAO:0000013 PMID:8755487 biolink:NamedThing omim.nt IAO:0000013 PMID:8917583 biolink:NamedThing omim.nt IAO:0000013 PMID:8957026 biolink:NamedThing omim.nt IAO:0000013 PMID:9097970 biolink:NamedThing omim.nt IAO:0000013 PMID:9158150 biolink:NamedThing omim.nt IAO:0000013 PMID:9443457 biolink:NamedThing omim.nt IAO:0000013 PMID:9839364 biolink:NamedThing omim.nt IAO:0000013 OBO:CHR_9606chr17p13 biolink:NamedThing omim.nt owl:Class http://omim.org/entry/605809 biolink:NamedThing|biolink:Disease Myasthenic Syndrome, Congenital, 4A, Slow-Channel Myasthenic Syndrome, Congenital, 4A, Slow-Channel omim.nt MYASTHENIC SYNDROME, CONGENITAL, 4A, SLOW-CHANNEL; CMS4A|Cms Ia1, Formerly|Congenital Myasthenic Syndrome Type Ia1, Formerly owl:Class http://omim.org/entry/608931 biolink:NamedThing|biolink:Disease Myasthenic Syndrome, Congenital, 4C, Associated With Acetylcholine Receptor Deficiency Myasthenic Syndrome, Congenital, 4C, Associated With Acetylcholine Receptor Deficiency omim.nt MYASTHENIC SYNDROME, CONGENITAL, 4C, ASSOCIATED WITH ACETYLCHOLINE RECEPTOR DEFICIENCY; CMS4C|Cms Id, Formerly|Myasthenia, Familial Infantile, 1, Formerly|Myasthenic Syndrome, Congenital, Type Id owl:Class http://omim.org/entry/616324 biolink:NamedThing|biolink:Disease Myasthenic Syndrome, Congenital, 4B, Fast-Channel Myasthenic Syndrome, Congenital, 4B, Fast-Channel omim.nt MYASTHENIC SYNDROME, CONGENITAL, 4B, FAST-CHANNEL; CMS4B owl:Class UMLS:C1413412 biolink:NamedThing omim.nt owl:Class https://www.ncbi.nlm.nih.gov/gene/1145 biolink:NamedThing omim.nt http://omim.org/entry/100730.0001 biolink:NamedThing CHRNG, GLN18TER In affected members of a family with Escobar syndrome (EVMPS; {265000}) reported by {6:Rajab et al. (2005)}, {2:Hoffmann et al. (2006)} detected a C-to-T transition at nucleotide 13 in exon 1 of the CHRNG gene that caused a gln-to-ter substitution at codon 18 (Q18X) of the gamma AChR subunit. omim.nt GENO:0000002 http://omim.org/entry/100730 biolink:NamedThing|biolink:Gene CHRNG Cholinergic Receptor, Nicotinic, Gamma Polypeptide|tightly linked to CHRND by RE omim.nt CHOLINERGIC RECEPTOR, NICOTINIC, GAMMA POLYPEPTIDE; CHRNG|Acetylcholine Receptor, Muscle, Gamma Subunit owl:Class ClinVar:RCV000020002 biolink:NamedThing omim.nt ClinVar:RCV001257365 biolink:NamedThing omim.nt dbSNP:rs267606725 biolink:NamedThing omim.nt owl:NamedIndividual http://omim.org/entry/100730#0001 biolink:NamedThing omim.nt http://omim.org/entry/100730.0002 biolink:NamedThing CHRNG, ARG217CYS In affected members of 2 unrelated consanguineous families from Lebanon and Turkey, respectively, with Escobar syndrome (EVMPS; {265000}) and the lethal form of multiple pterygium syndrome (LMPS; {253290}), {2:Hoffmann et al. (2006)} found homozygosity for a 715C-T transition in exon 7 of the CHRNG gene that resulted in an arg217-to-cys (R217C) amino acid substitution. In the Lebanese family 1 affected individual died at age 13 days, whereas the other was alive at 7 years of age; the affected individual from the Turkish family was stillborn. There was a family history of abortions in each family. omim.nt GENO:0000002 ClinVar:RCV000020003 biolink:NamedThing omim.nt ClinVar:RCV000020004 biolink:NamedThing omim.nt dbSNP:rs121912670 biolink:NamedThing omim.nt owl:NamedIndividual http://omim.org/entry/100730#0002 biolink:NamedThing omim.nt http://omim.org/entry/100730.0003 biolink:NamedThing CHRNG, 9-BP DUP In 2 affected sibs in a nonconsanguineous family from Germany segregating Escobar syndrome (EVMPS; {265000}), {2:Hoffmann et al. (2006)} identified compound heterozygosity for mutations in the CHRNG gene: a 9-bp duplication (300dup9) in exon 4, resulting in duplication of 3 amino acids (78dup3), and a 1408C-T transition, resulting in an arg448-to-ter (R448X; {100730.0004}) substitution. omim.nt GENO:0000002 ClinVar:RCV000020005 biolink:NamedThing omim.nt dbSNP:rs863223313 biolink:NamedThing omim.nt owl:NamedIndividual http://omim.org/entry/100730#0003 biolink:NamedThing omim.nt http://omim.org/entry/100730.0004 biolink:NamedThing CHRNG, ARG448TER For discussion of the arg448-to-ter (R448X) mutation in the CHRNG gene that was found in compound heterozygous state in 2 sibs with Escobar syndrome ({265000}) by {2:Hoffmann et al. (2006)}, see {100730.0003}. omim.nt GENO:0000002 ClinVar:RCV000020006 biolink:NamedThing omim.nt dbSNP:rs121912671 biolink:NamedThing omim.nt owl:NamedIndividual http://omim.org/entry/100730#0004 biolink:NamedThing omim.nt http://omim.org/entry/100730.0005 biolink:NamedThing CHRNG, 320T-G, VAL107GLY In a large consanguineous Arab family with both Escobar syndrome (EVMPS; {265000}) and the lethal variant of multiple pterygium syndrome (LMPS; {253290}), {5:Morgan et al. (2006)} detected a homozygous missense mutation, 320T-G (val107 to gly, V107G) in the CHRNG gene. The val107 residue is conserved in the CHRNG proteins of 6 other species. omim.nt GENO:0000002 ClinVar:RCV000020007 biolink:NamedThing omim.nt ClinVar:RCV000020008 biolink:NamedThing omim.nt dbSNP:rs267606726 biolink:NamedThing omim.nt owl:NamedIndividual http://omim.org/entry/100730#0005 biolink:NamedThing omim.nt http://omim.org/entry/100730.0006 biolink:NamedThing CHRNG, ARG46TER In a consanguineous Pakistani family in which 2 sisters had the Escobar variant of multiple pterygium syndrome (EVMPS; {265000}), {5:Morgan et al. (2006)} found a homozygous 136C-T transition in the CHRNG gene, resulting in an arg46-to-ter (R46X) substitution. omim.nt GENO:0000002 ClinVar:RCV000020009 biolink:NamedThing omim.nt dbSNP:rs121912672 biolink:NamedThing omim.nt owl:NamedIndividual http://omim.org/entry/100730#0006 biolink:NamedThing omim.nt http://omim.org/entry/100730.0007 biolink:NamedThing CHRNG, 2-BP DEL, 753CT In a Turkish family with parental consanguinity, {5:Morgan et al. (2006)} demonstrated that the lethal form of multiple pterygium syndrome (LMPS; {253290}) was caused by a deletion mutation in exon 7 of the CHRNG gene, 753_754delCT (Pro251ProfsTer46). For discussion of the 2-bp deletion in the CHRNG gene that was found in compound heterozygous state in patients with Escobar syndrome (EVMPS; {265000}) by {8:Seo et al. (2015)}, see {100730.0009}. omim.nt GENO:0000002 ClinVar:RCV000020010 biolink:NamedThing omim.nt ClinVar:RCV000201795 biolink:NamedThing omim.nt ClinVar:RCV000282633 biolink:NamedThing omim.nt ClinVar:RCV000622703 biolink:NamedThing omim.nt ClinVar:RCV000778602 biolink:NamedThing omim.nt dbSNP:rs767503038 biolink:NamedThing omim.nt owl:NamedIndividual http://omim.org/entry/100730#0007 biolink:NamedThing omim.nt http://omim.org/entry/100730.0008 biolink:NamedThing CHRNG, 1-BP DUP, 459A {12:Vogt et al. (2012)} identified a 1-bp duplication (459dupA) in exon 5 of the CHRNG gene in affected members of 3 unrelated kindreds with lethal multiple pterygium syndrome (LMPS; {253290}) and in 3 unrelated kindreds with nonlethal Escobar syndrome (EVMPS; {265000}). Four families were homozygous for the mutation, whereas 2 carried it in compound heterozygosity with another pathogenic CHRNG mutation. Haplotype analysis of 3 families did not show a common haplotype, suggesting that this is a mutation hotspot. omim.nt GENO:0000002 ClinVar:RCV000022419 biolink:NamedThing omim.nt ClinVar:RCV000022420 biolink:NamedThing omim.nt http://omim.org/entry/100730#0008 biolink:NamedThing omim.nt http://omim.org/entry/100730.0009 biolink:NamedThing CHRNG, PRO143ARG In 3 patients from 2 unrelated Korean families with Escobar syndrome (EVMPS; {265000}), {8:Seo et al. (2015)} identified compound heterozygous mutations in the CHRNG gene: a C-to-G transversion, resulting in a pro143-to-arg (P143R) substitution at a highly conserved residue in the extracellular domain, and a 2-bp deletion, resulting in a frameshift and premature termination (Pro251fsTer45; {100730.0007}) after the second transmembrane domain. The mutations, which were found by whole-exome sequencing and confirmed by Sanger sequencing, segregated with the disorder in 1 of the families from whom DNA was available, and were not found in the 1000 Genomes Project or Exome Variant Server databases. The P143R variant was found at an allele frequency of 0.1% (1 in 1,142 alleles) among Korean controls. Functional studies of the variants were not performed. omim.nt GENO:0000002 ClinVar:RCV000201797 biolink:NamedThing omim.nt dbSNP:rs765746795 biolink:NamedThing omim.nt owl:NamedIndividual http://omim.org/entry/100730#0009 biolink:NamedThing omim.nt MONARCH:.well-known/genid/b94318b309f52b36c2c2 biolink:NamedThing GRCh38chr2-232539691-232548114-Region omim.nt MONARCH:.well-known/genid/b7426c9ebc7e122b43e1 faldo:Region PMID:12101101 biolink:NamedThing omim.nt IAO:0000013 PMID:15704180 biolink:NamedThing omim.nt IAO:0000013 PMID:15905852 biolink:NamedThing omim.nt IAO:0000013 PMID:16826520 biolink:NamedThing omim.nt IAO:0000013 PMID:16826531 biolink:NamedThing omim.nt IAO:0000013 PMID:1981051 biolink:NamedThing omim.nt IAO:0000013 PMID:22167768 biolink:NamedThing omim.nt IAO:0000013 PMID:25608830 biolink:NamedThing omim.nt IAO:0000013 PMID:2630182 biolink:NamedThing omim.nt IAO:0000013 PMID:3967651 biolink:NamedThing omim.nt IAO:0000013 PMID:8040310 biolink:NamedThing omim.nt IAO:0000013 http://omim.org/entry/265000 biolink:NamedThing|biolink:Disease Multiple Pterygium Syndrome, Escobar Variant Multiple Pterygium Syndrome, Escobar Variant omim.nt MULTIPLE PTERYGIUM SYNDROME, ESCOBAR VARIANT; EVMPS|Escobar Syndrome|Multiple Pterygium Syndrome|Multiple Pterygium Syndrome, Nonlethal Type|Pterygium Colli Syndrome|Pterygium Syndrome|Pterygium Universale owl:Class UMLS:C1413413 biolink:NamedThing omim.nt owl:Class https://www.ncbi.nlm.nih.gov/gene/1146 biolink:NamedThing omim.nt http://omim.org/entry/100735 biolink:NamedThing omim.nt True owl:Class http://omim.org/entry/142445 biolink:NamedThing|biolink:Gene NRG1 Neuregulin 1 omim.nt NEUREGULIN 1; NRG1|Acetylcholine Receptor-Inducing Activity, Chick, Homolog of|Glial Growth Factor 2|Heregulin, Alpha|Neu Differentiation Factor|Sensory and Motor Neuron-Derived Factor owl:Class http://omim.org/entry/100740.0001 biolink:NamedThing ACHE, HIS322ASN {1:Bartels et al. (1993)} demonstrated that the wildtype sequence of the ACHE gene, which corresponds to the YT1 blood group antigen ({112100}), has histidine at codon 322 (CAC) and that the rare variant, the YT2 blood group antigen, has asparagine (AAC) at that position. omim.nt GENO:0000002 ClinVar:RCV000020001 biolink:NamedThing omim.nt dbSNP:rs1799805 biolink:NamedThing omim.nt owl:NamedIndividual http://omim.org/entry/100740#0001 biolink:NamedThing omim.nt MONARCH:.well-known/genid/bf1504b7976b12220c6f biolink:NamedThing GRCh38chr7-100889993-100896993-Region omim.nt MONARCH:.well-known/genid/b53f39b5dac1dced35ad faldo:Region MONARCH:.well-known/genid/OMIM100740ref18 biolink:NamedThing Erythrocyte acetylcholinesterase bears the Cartwright blood group antigens. (Abstract) omim.nt IAO:0000310 PMID:10087275 biolink:NamedThing omim.nt IAO:0000013 PMID:10814709 biolink:NamedThing omim.nt IAO:0000013 PMID:11799248 biolink:NamedThing omim.nt IAO:0000013 PMID:11804574 biolink:NamedThing omim.nt IAO:0000013 PMID:12783426 biolink:NamedThing omim.nt IAO:0000013 PMID:1358806 biolink:NamedThing omim.nt IAO:0000013 PMID:1380483 biolink:NamedThing omim.nt IAO:0000013 PMID:14622217 biolink:NamedThing omim.nt IAO:0000013 PMID:1609795 biolink:NamedThing omim.nt IAO:0000013 PMID:1744105 biolink:NamedThing omim.nt IAO:0000013 PMID:17606622 biolink:NamedThing omim.nt IAO:0000013 PMID:19368807 biolink:NamedThing omim.nt IAO:0000013 PMID:20147288 biolink:NamedThing omim.nt IAO:0000013 PMID:2263619 biolink:NamedThing omim.nt IAO:0000013 PMID:2734315 biolink:NamedThing omim.nt IAO:0000013 PMID:3174665 biolink:NamedThing omim.nt IAO:0000013 PMID:5013676 biolink:NamedThing omim.nt IAO:0000013 PMID:694721 biolink:NamedThing omim.nt IAO:0000013 PMID:8299725 biolink:NamedThing omim.nt IAO:0000013 PMID:8488842 biolink:NamedThing omim.nt IAO:0000013 OBO:CHR_9606chr7q22 biolink:NamedThing omim.nt owl:Class http://omim.org/entry/112100 biolink:NamedThing|biolink:Disease Yt Blood Group Antigen Yt Blood Group Antigen omim.nt YT BLOOD GROUP ANTIGEN|Cartwright Antigen owl:Class UMLS:C1412122 biolink:NamedThing omim.nt owl:Class https://www.ncbi.nlm.nih.gov/gene/43 biolink:NamedThing omim.nt http://omim.org/entry/100790.0001 biolink:NamedThing ASCL1, C52A, PRO18THR In a patient with CCHS ({209880}), {5:de Pontual et al. (2003)} identified heterozygosity for a 52C-A transversion in the ASCL1 gene, resulting in a pro18-to-thr substitution. The patient was also heterozygous for a polyalanine expansion mutation in PHOX2B ({603851}), a gene in which mutations are known to cause CCHS. omim.nt GENO:0000002 http://omim.org/entry/100790 biolink:NamedThing|biolink:Gene ASCL1 Achaete-Scute Family Bhlh Transcription Factor 1|distal to PAH and proximal to TRA1 omim.nt ACHAETE-SCUTE FAMILY bHLH TRANSCRIPTION FACTOR 1; ASCL1|Achaete-Scute Complex, Drosophila, Homolog Of, 1|Human Achaete-Scute Homolog 1|Mammalian Achaete-Scute Homolog 1 owl:Class ClinVar:RCV000019998 biolink:NamedThing omim.nt dbSNP:rs267606667 biolink:NamedThing omim.nt owl:NamedIndividual http://omim.org/entry/100790#0001 biolink:NamedThing omim.nt http://omim.org/entry/100790.0002 biolink:NamedThing ASCL1, 15-BP DEL, NT111 In a patient with CCHS ({209880}), {5:de Pontual et al. (2003)} identified heterozygosity for a 15-bp deletion (111-115del15nt) in the ASCL1 gene. The mutation was predicted to result in loss of 5 of 13 alanine residues (ala37-ala41) in a polyalanine tract. omim.nt GENO:0000002 ClinVar:RCV000019999 biolink:NamedThing omim.nt http://omim.org/entry/100790#0002 biolink:NamedThing omim.nt http://omim.org/entry/100790.0003 biolink:NamedThing ASCL1, 24-BP DEL, NT108 In a patient with Haddad syndrome (see {209880}), {5:de Pontual et al. (2003)} identified heterozygosity for a 24-bp deletion (108-131del24nt) in the ASCL1 gene. The mutation was predicted to result in loss of 8 of 13 alanine residues (ala36-ala43) in a polyalanine tract. omim.nt GENO:0000002 ClinVar:RCV000020000 biolink:NamedThing omim.nt http://omim.org/entry/100790#0003 biolink:NamedThing omim.nt MONARCH:.well-known/genid/b11b2f73c93de9437b53 biolink:NamedThing GRCh38chr12-102957673-102960512-Region omim.nt MONARCH:.well-known/genid/ba86df8381e47dc13c20 faldo:Region PMID:12050665 biolink:NamedThing omim.nt IAO:0000013 PMID:14532329 biolink:NamedThing omim.nt IAO:0000013 PMID:15071116 biolink:NamedThing omim.nt IAO:0000013 PMID:15133515 biolink:NamedThing omim.nt IAO:0000013 PMID:17141158 biolink:NamedThing omim.nt IAO:0000013 PMID:18173746 biolink:NamedThing omim.nt IAO:0000013 PMID:20107439 biolink:NamedThing omim.nt IAO:0000013 PMID:21617644 biolink:NamedThing omim.nt IAO:0000013 PMID:21725324 biolink:NamedThing omim.nt IAO:0000013 PMID:21753754 biolink:NamedThing omim.nt IAO:0000013 PMID:24179156 biolink:NamedThing omim.nt IAO:0000013 PMID:24925909 biolink:NamedThing omim.nt IAO:0000013 PMID:27418510 biolink:NamedThing omim.nt IAO:0000013 PMID:28746305 biolink:NamedThing omim.nt IAO:0000013 PMID:8221886 biolink:NamedThing omim.nt IAO:0000013 PMID:8390674 biolink:NamedThing omim.nt IAO:0000013 PMID:8595908 biolink:NamedThing omim.nt IAO:0000013 PMID:8719343 biolink:NamedThing omim.nt IAO:0000013 OBO:CHR_9606chr12q22 biolink:NamedThing omim.nt owl:Class http://omim.org/entry/209880 biolink:NamedThing|biolink:Disease Central Hypoventilation Syndrome, Congenital Central Hypoventilation Syndrome, Congenital omim.nt CENTRAL HYPOVENTILATION SYNDROME, CONGENITAL; CCHS|Autonomic Control, Congenital Failure of|Cchs With Hirschsprung Disease|Haddad Syndrome|Ondine Curse, Congenital|Ondine-Hirschsprung Disease owl:Class UMLS:C1332009 biolink:NamedThing omim.nt owl:Class https://www.ncbi.nlm.nih.gov/gene/429 biolink:NamedThing omim.nt http://omim.org/entry/100800 biolink:NamedThing|biolink:Disease Achondroplasia Achondroplasia omim.nt ACHONDROPLASIA; ACH owl:Class MONARCH:.well-known/genid/OMIM100800ref10 biolink:NamedThing Achondroplasia in two sisters with normal parents. omim.nt IAO:0000310 MONARCH:.well-known/genid/OMIM100800ref101 biolink:NamedThing A reexamination of parental age effect on the occurrence of new mutations for achondroplasia. In: Papadatos, C. J.; Bartsocas, C. S. (eds.): Skeletal Dysplasias. omim.nt IAO:0000310 MONARCH:.well-known/genid/OMIM100800ref102 biolink:NamedThing Achondroplasia due to DNA insertion into the type II collagen gene. (Abstract) omim.nt IAO:0000310 MONARCH:.well-known/genid/OMIM100800ref11 biolink:NamedThing Ueber familiaere Chondrodystrophia foetalis. omim.nt IAO:0000310 MONARCH:.well-known/genid/OMIM100800ref110 biolink:NamedThing Achondroplasia in two first cousins. omim.nt IAO:0000310 MONARCH:.well-known/genid/OMIM100800ref115 biolink:NamedThing Zur Vererbung des Zwergwuchses. omim.nt IAO:0000310 MONARCH:.well-known/genid/OMIM100800ref32 biolink:NamedThing Two probable cases of homozygosity for the achondroplasia gene. omim.nt IAO:0000310 MONARCH:.well-known/genid/OMIM100800ref35 biolink:NamedThing The natural history of achondroplasia. In: Nicoletti, B.; Kopits, S. E.; Ascani, E.; McKusick, V. A. (eds.): Human Achondroplasia: A Multidisciplinary Approach. omim.nt IAO:0000310 MONARCH:.well-known/genid/OMIM100800ref41 biolink:NamedThing Problems of Hereditary Chondrodysplasia. omim.nt IAO:0000310 MONARCH:.well-known/genid/OMIM100800ref45 biolink:NamedThing The chondrodysplasias. In: Royce, P. M.; Steinmann, B. (eds.): Connective Tissue and Its Heritable Disorders: Molecular, Genetic, and Medical Aspects. omim.nt IAO:0000310 MONARCH:.well-known/genid/OMIM100800ref46 biolink:NamedThing Growth plate cartilage studies in achondroplasia. In: Nicoletti, B.; Kopits, S. E.; Ascani, E.; McKusick, V. A. (eds.): Human Achondroplasia: A Multidisciplinary Approach. omim.nt IAO:0000310 MONARCH:.well-known/genid/OMIM100800ref52 biolink:NamedThing Achondroplasia is not tightly linked to the locus for neurofibromatosis 1. (Abstract) omim.nt IAO:0000310 MONARCH:.well-known/genid/OMIM100800ref65 biolink:NamedThing Chondrodystrophic dwarfs in Denmark. omim.nt IAO:0000310 MONARCH:.well-known/genid/OMIM100800ref70 biolink:NamedThing Human Achondroplasia: A Multidisciplinary Approach. omim.nt IAO:0000310 PMID:10360392 biolink:NamedThing omim.nt IAO:0000013 PMID:10360393 biolink:NamedThing omim.nt IAO:0000013 PMID:10375043 biolink:NamedThing omim.nt IAO:0000013 PMID:10445347 biolink:NamedThing omim.nt IAO:0000013 PMID:10678665 biolink:NamedThing omim.nt IAO:0000013 PMID:11186939 biolink:NamedThing omim.nt IAO:0000013 PMID:11186940 biolink:NamedThing omim.nt IAO:0000013 PMID:11343336 biolink:NamedThing omim.nt IAO:0000013 PMID:12397172 biolink:NamedThing omim.nt IAO:0000013 PMID:12816345 biolink:NamedThing omim.nt IAO:0000013 PMID:12923858 biolink:NamedThing omim.nt IAO:0000013 PMID:13243724 biolink:NamedThing omim.nt IAO:0000013 PMID:13372616 biolink:NamedThing omim.nt IAO:0000013 PMID:13507646 biolink:NamedThing omim.nt IAO:0000013 PMID:13885465 biolink:NamedThing omim.nt IAO:0000013 PMID:1453438 biolink:NamedThing omim.nt IAO:0000013 PMID:14702637 biolink:NamedThing omim.nt IAO:0000013 PMID:149212 biolink:NamedThing omim.nt IAO:0000013 PMID:15372518 biolink:NamedThing omim.nt IAO:0000013 PMID:15517832 biolink:NamedThing omim.nt IAO:0000013 PMID:1632435 biolink:NamedThing omim.nt IAO:0000013 PMID:16353253 biolink:NamedThing omim.nt IAO:0000013 PMID:16380966 biolink:NamedThing omim.nt IAO:0000013 PMID:16411219 biolink:NamedThing omim.nt IAO:0000013 PMID:1670752 biolink:NamedThing omim.nt IAO:0000013 PMID:16912704 biolink:NamedThing omim.nt IAO:0000013 PMID:16922718 biolink:NamedThing omim.nt IAO:0000013 PMID:17764078 biolink:NamedThing omim.nt IAO:0000013 PMID:1785636 biolink:NamedThing omim.nt IAO:0000013 PMID:17879967 biolink:NamedThing omim.nt IAO:0000013 PMID:18266238 biolink:NamedThing omim.nt IAO:0000013 PMID:18698630 biolink:NamedThing omim.nt IAO:0000013 PMID:18923003 biolink:NamedThing omim.nt IAO:0000013 PMID:19006207 biolink:NamedThing omim.nt IAO:0000013 PMID:1952787 biolink:NamedThing omim.nt IAO:0000013 PMID:2063907 biolink:NamedThing omim.nt IAO:0000013 PMID:2162805 biolink:NamedThing omim.nt IAO:0000013 PMID:2260574 biolink:NamedThing omim.nt IAO:0000013 PMID:23200862 biolink:NamedThing omim.nt IAO:0000013 PMID:2783977 biolink:NamedThing omim.nt IAO:0000013 PMID:2785882 biolink:NamedThing omim.nt IAO:0000013 PMID:2899736 biolink:NamedThing omim.nt IAO:0000013 PMID:2899976 biolink:NamedThing omim.nt IAO:0000013 PMID:2991928 biolink:NamedThing omim.nt IAO:0000013 PMID:3005580 biolink:NamedThing omim.nt IAO:0000013 PMID:31269546 biolink:NamedThing omim.nt IAO:0000013 PMID:3223492 biolink:NamedThing omim.nt IAO:0000013 PMID:3228140 biolink:NamedThing omim.nt IAO:0000013 PMID:3236371 biolink:NamedThing omim.nt IAO:0000013 PMID:3415202 biolink:NamedThing omim.nt IAO:0000013 PMID:3425618 biolink:NamedThing omim.nt IAO:0000013 PMID:3591840 biolink:NamedThing omim.nt IAO:0000013 PMID:3631079 biolink:NamedThing omim.nt IAO:0000013 PMID:3688033 biolink:NamedThing omim.nt IAO:0000013 PMID:3746832 biolink:NamedThing omim.nt IAO:0000013 PMID:3945286 biolink:NamedThing omim.nt IAO:0000013 PMID:4061493 biolink:NamedThing omim.nt IAO:0000013 PMID:458831 biolink:NamedThing omim.nt IAO:0000013 PMID:4697848 biolink:NamedThing omim.nt IAO:0000013 PMID:474637 biolink:NamedThing omim.nt IAO:0000013 PMID:4989392 biolink:NamedThing omim.nt IAO:0000013 PMID:5298504 biolink:NamedThing omim.nt IAO:0000013 PMID:5480962 biolink:NamedThing omim.nt IAO:0000013 PMID:5504223 biolink:NamedThing omim.nt IAO:0000013 PMID:5699022 biolink:NamedThing omim.nt IAO:0000013 PMID:5889028 biolink:NamedThing omim.nt IAO:0000013 PMID:5917196 biolink:NamedThing omim.nt IAO:0000013 PMID:6023888 biolink:NamedThing omim.nt IAO:0000013 PMID:6359101 biolink:NamedThing omim.nt IAO:0000013 PMID:6507475 biolink:NamedThing omim.nt IAO:0000013 PMID:6507476 biolink:NamedThing omim.nt IAO:0000013 PMID:6627718 biolink:NamedThing omim.nt IAO:0000013 PMID:6660245 biolink:NamedThing omim.nt IAO:0000013 PMID:6707788 biolink:NamedThing omim.nt IAO:0000013 PMID:6707795 biolink:NamedThing omim.nt IAO:0000013 PMID:6733952 biolink:NamedThing omim.nt IAO:0000013 PMID:6881210 biolink:NamedThing omim.nt IAO:0000013 PMID:690757 biolink:NamedThing omim.nt IAO:0000013 PMID:7137217 biolink:NamedThing omim.nt IAO:0000013 PMID:7263742 biolink:NamedThing omim.nt IAO:0000013 PMID:7373371 biolink:NamedThing omim.nt IAO:0000013 PMID:7438842 biolink:NamedThing omim.nt IAO:0000013 PMID:7758520 biolink:NamedThing omim.nt IAO:0000013 PMID:7847369 biolink:NamedThing omim.nt IAO:0000013 PMID:7887429 biolink:NamedThing omim.nt IAO:0000013 PMID:7913883 biolink:NamedThing omim.nt IAO:0000013 PMID:7966194 biolink:NamedThing omim.nt IAO:0000013 PMID:7968151 biolink:NamedThing omim.nt IAO:0000013 PMID:8012397 biolink:NamedThing omim.nt IAO:0000013 PMID:8012398 biolink:NamedThing omim.nt IAO:0000013 PMID:8078586 biolink:NamedThing omim.nt IAO:0000013 PMID:8081365 biolink:NamedThing omim.nt IAO:0000013 PMID:8267011 biolink:NamedThing omim.nt IAO:0000013 PMID:8279481 biolink:NamedThing omim.nt IAO:0000013 PMID:830446 biolink:NamedThing omim.nt IAO:0000013 PMID:8432397 biolink:NamedThing omim.nt IAO:0000013 PMID:8585566 biolink:NamedThing omim.nt IAO:0000013 PMID:868806 biolink:NamedThing omim.nt IAO:0000013 PMID:8834055 biolink:NamedThing omim.nt IAO:0000013 PMID:8882783 biolink:NamedThing omim.nt IAO:0000013 PMID:8923856 biolink:NamedThing omim.nt IAO:0000013 PMID:9066881 biolink:NamedThing omim.nt IAO:0000013 PMID:9326921 biolink:NamedThing omim.nt IAO:0000013 PMID:9326938 biolink:NamedThing omim.nt IAO:0000013 PMID:9733026 biolink:NamedThing omim.nt IAO:0000013 PMID:9797588 biolink:NamedThing omim.nt IAO:0000013 UMLS:C0001080 biolink:NamedThing omim.nt owl:Class ORPHA:15 biolink:NamedThing|biolink:Disease omim.nt owl:Class http://omim.org/entry/100820 biolink:NamedThing|biolink:Disease Achoo Syndrome Achoo Syndrome omim.nt ACHOO SYNDROME|Autosomal Dominant Compelling Helioophthalmic Outburst Syndrome|Peroutka Sneeze|Photic Sneeze Reflex|Sneezing From Light Exposure owl:Class MONARCH:.well-known/genid/OMIM100820ref1 biolink:NamedThing The Complete Works of Aristotle. Vol. 2. omim.nt IAO:0000310 MONARCH:.well-known/genid/OMIM100820ref12 biolink:NamedThing Personal Communication. omim.nt IAO:0000310 MONARCH:.well-known/genid/OMIM100820ref13 biolink:NamedThing Letter to the editor. omim.nt IAO:0000310 MONARCH:.well-known/genid/OMIM100820ref15 biolink:NamedThing ACHOO syndrome: prevalence and inheritance. omim.nt IAO:0000310 MONARCH:.well-known/genid/OMIM100820ref4 biolink:NamedThing The Berenstain Bears Go to the Doctor. omim.nt IAO:0000310 MONARCH:.well-known/genid/OMIM100820ref5 biolink:NamedThing ACHOO syndrome (helio-ophthalmic outburst syndrome). omim.nt IAO:0000310 MONARCH:.well-known/genid/OMIM100820ref6 biolink:NamedThing Personal Communication. omim.nt IAO:0000310 PMID:14144120 biolink:NamedThing omim.nt IAO:0000013 PMID:1854707 biolink:NamedThing omim.nt IAO:0000013 PMID:2275931 biolink:NamedThing omim.nt IAO:0000013 PMID:2304823 biolink:NamedThing omim.nt IAO:0000013 PMID:3820439 biolink:NamedThing omim.nt IAO:0000013 PMID:3988295 biolink:NamedThing omim.nt IAO:0000013 PMID:5804036 biolink:NamedThing omim.nt IAO:0000013 PMID:6674114 biolink:NamedThing omim.nt IAO:0000013 PMID:6694722 biolink:NamedThing omim.nt IAO:0000013 UMLS:C1863416 biolink:NamedThing omim.nt owl:Class http://omim.org/entry/100850.0001 biolink:NamedThing ACO2, SER112ARG In 8 affected individuals from 2 Arab Muslim families with infantile cerebellar-retinal degeneration (ICRD; {614559}), {18:Spiegel et al. (2012)} identified a homozygous 336C-G transversion in the ACO2 gene, resulting in a ser112-to-arg (S112R) substitution in a highly conserved residue. The mutation was found by homozygosity mapping followed by exome sequencing. Haplotype analysis indicated a founder effect. Ten parents and 1 healthy sib were heterozygous for the mutation, which was not found in 128 controls. Cellular aconitase activity measured in 2 patients was reduced to about 10% of normal levels. In vitro functional expression studies in yeast showed that the mutant protein had decreased function under specific physiologic conditions, namely high-requirement conditions such as respiration and growth on 2-carbon substrates. omim.nt GENO:0000002 http://omim.org/entry/100850 biolink:NamedThing|biolink:Gene ACO2 Aconitase, Mitochondrial|distal to Ph1 break; mutation identified in 1 OPA9 family omim.nt ACONITASE, MITOCHONDRIAL; ACO2|Aconm owl:Class ClinVar:RCV000022421 biolink:NamedThing omim.nt dbSNP:rs786200924 biolink:NamedThing omim.nt owl:NamedIndividual http://omim.org/entry/100850#0001 biolink:NamedThing omim.nt http://omim.org/entry/100850.0002 biolink:NamedThing ACO2, LEU74VAL ({dbSNP rs141772938}) In 2 adult French brothers with optic atrophy-9 (OPA9; {616289}), {8:Metodiev et al. (2014)} identified compound heterozygous mutations in the ACO2 gene: a c.220C-G transversion, resulting in a leu74-to-val (L74V) substitution, and a c.1981G-A transition ({VAR c.1981G-A, NM_001098.2}), resulting in a gly661-to-arg (G661R; {100850.0003}) substitution. Both substitutions occurred at highly conserved residues. Patient cells showed decreased ACO2 activity (31-66% of controls) and decreased ACO2 protein levels. The mutant proteins were unable to completely rescue respiratory growth defects in an aco1 ({100880})-deficient yeast strain at 37 degrees Celsius. ACO1 activity was also reduced in patient cells. The mutations, which were found by whole-exome sequencing and confirmed by Sanger sequencing, segregated with the disorder in the family. The L74V variant ({dbSNP rs141772938}) was found at a low frequency (0.003) in the dbSNP database, whereas G661R was not found in that database. omim.nt GENO:0000002 ClinVar:RCV000169730 biolink:NamedThing omim.nt ClinVar:RCV000676884 biolink:NamedThing omim.nt ClinVar:RCV000764399 biolink:NamedThing omim.nt ClinVar:RCV000990458 biolink:NamedThing omim.nt dbSNP:rs141772938 biolink:NamedThing omim.nt owl:NamedIndividual http://omim.org/entry/100850#0002 biolink:NamedThing omim.nt http://omim.org/entry/100850.0003 biolink:NamedThing ACO2, GLY661ARG For discussion of the gly661-to-arg (G661R) mutation in the ACO2 gene that was found in compound heterozygous state in patients with optic atrophy-9 (OPA9; {616289}) by {8:Metodiev et al. (2014)}, see {100850.0002}. omim.nt GENO:0000002 ClinVar:RCV000169731 biolink:NamedThing omim.nt dbSNP:rs752034900 biolink:NamedThing omim.nt owl:NamedIndividual http://omim.org/entry/100850#0003 biolink:NamedThing omim.nt http://omim.org/entry/100850.0004 biolink:NamedThing ACO2, GLY259ASP In 2 sibs, born of consanguineous Algerian parents, with infantile cerebellar-retinal degeneration (ICRD; {614559}), {8:Metodiev et al. (2014)} identified a homozygous c.776G-A transition ({VAR c.776G-A, NM_001098.2}) in the ACO2 gene, resulting in a gly259-to-asp (G259D) substitution at a highly conserved residue. The mutation, which was found by whole-exome sequencing and confirmed by Sanger sequencing, segregated with the disorder in the family and was not found in the dbSNP database. omim.nt GENO:0000002 ClinVar:RCV000169732 biolink:NamedThing omim.nt dbSNP:rs786204828 biolink:NamedThing omim.nt owl:NamedIndividual http://omim.org/entry/100850#0004 biolink:NamedThing omim.nt http://omim.org/entry/100850.0005 biolink:NamedThing ACO2, LYS736ASN In a 10-year-old girl with infantile cerebellar-retinal degeneration (ICRD; {614559}), {8:Metodiev et al. (2014)} identified compound heterozygous mutations in the ACO2 gene: a c.2208G-C transversion, resulting in a lys736-to-asn (K736N) substitution at a highly conserved residue, and a 4-bp deletion ({VAR c.2325_2328delGAAG, NM_001098.2}; {100850.0006}), resulting in a frameshift and premature termination (Lys776AsnfsTer49). The mutation, which was found by whole-exome sequencing and confirmed by Sanger sequencing, segregated with the disorder in the family and was not found in the dbSNP database. (In the article by {8:Metodiev et al. (2014)}, one of the mutations was listed as c.2328_2331delGAAG and as c.2325_2328delGAAG; {11:Rotig (2020)} confirmed that the correct mutation is c.2325_2328delGAAG.) omim.nt GENO:0000002 ClinVar:RCV000169733 biolink:NamedThing omim.nt dbSNP:rs786204829 biolink:NamedThing omim.nt owl:NamedIndividual http://omim.org/entry/100850#0005 biolink:NamedThing omim.nt http://omim.org/entry/100850.0006 biolink:NamedThing ACO2, 4-BP DEL, 2325GAAG For discussion of the 4-bp deletion in the ACO2 gene (c.2325_2328delGAAG) that was found in compound heterozygous state in a patient with infantile cerebellar-retinal degeneration (ICRD; {614559}) by {8:Metodiev et al. (2014)}, see {100850.0005}. omim.nt GENO:0000002 ClinVar:RCV000169734 biolink:NamedThing omim.nt dbSNP:rs786204830 biolink:NamedThing omim.nt owl:NamedIndividual http://omim.org/entry/100850#0006 biolink:NamedThing omim.nt http://omim.org/entry/100850.0007 biolink:NamedThing ACO2, PHE414VAL In 2 sibs, born of consanguineous Arab-Bedouin parents, with a modified phenotype of infantile cerebellar-retinal degeneration (ICRD; {614559}), including spastic paraplegia, impaired intellectual development, and microcephaly without ophthalmologic findings, {3:Bouwkamp et al. (2018)} identified a homozygous c.1240T-G transversion in the ACO2 gene, resulting in a phe414-to-val (F414V) substitution at a highly conserved residue. The mutation was found by linkage analysis and whole-exome sequencing and confirmed by Sanger sequencing. The parents and an unaffected sib were heterozygous for the mutation. The mutation was not present in the dbSNP database and had a minor allele frequency of less than 0.001 in the EVS6500, 1000 Genomes Project, and ExAC databases. Mitochondrial aconitase activity was reduced in lymphoblastoid cells from the affected sibs, and the respiratory control ratio and state 3 respiration were reduced in isolated lymphoblastoid mitochondria from both patients. omim.nt GENO:0000002 ClinVar:RCV001255992 biolink:NamedThing omim.nt http://omim.org/entry/100850#0007 biolink:NamedThing omim.nt http://omim.org/entry/100850.0008 biolink:NamedThing ACO2, HIS596ARG In 2 sibs (patients E2 and E3), aged 8 and 6 years, with infantile cerebellar-retinal degeneration (ICRD; {614559}), {12:Sharkia et al. (2019)} identified compound heterozygous variants in the ACO2 gene: a c.1787A-G transition, resulting in a his596-to-arg substitution (H596R), and a c.2050C-T transition, resulting in an arg684-to-trp (R684W; 100850.0009) substitution. The mutations were found by whole-exome sequencing and validated by Sanger sequencing. Familial segregation was confirmed by Sanger sequencing. Both mutations occurred in evolutionarily conserved regions and were predicted to impair substrate binding. The sibs had moderately impaired intellectual development, hypotonia, seizures, and ataxia. omim.nt GENO:0000002 ClinVar:RCV001255993 biolink:NamedThing omim.nt http://omim.org/entry/100850#0008 biolink:NamedThing omim.nt http://omim.org/entry/100850.0009 biolink:NamedThing ACO2, ARG684TRP For discussion of the c.2050C-T transition in the ACO2 gene that was found in compound heterozygous state in 2 sibs with infantile cerebellar-retinal degeneration (ICRD; {614559}) by {12:Sharkia et al. (2019)}, see {100850.0008}. omim.nt GENO:0000002 ClinVar:RCV000681651 biolink:NamedThing omim.nt dbSNP:rs768950391 biolink:NamedThing omim.nt owl:NamedIndividual http://omim.org/entry/100850#0009 biolink:NamedThing omim.nt http://omim.org/entry/100850.0010 biolink:NamedThing ACO2, c.433-2_443-1delinsCT In a 26-year-old woman (P3) with infantile cerebellar-retinal degeneration (ICRD; {614559}), {1:Blackburn et al. (2020)} identified compound heterozygous mutations in the ACO2 gene: a del/ins mutation ({VAR c.433-2_433-1delinsCT, NM_001098.2}) in intron 3, predicted to result in loss of the exon 4 splice site, and a c.719G-A transition, resulting in a gly240-to-asp (G240D; {100850.0011}) substitution at a highly conserved residue. The mutations were identified by whole-exome sequencing. The mother was heterozygous for the del/ins mutation, but the father was unavailable for testing. The G240D variant was rare in the gnomAD database and was predicted to have a destabilizing effect. omim.nt GENO:0000002 ClinVar:RCV001255994 biolink:NamedThing omim.nt http://omim.org/entry/100850#0010 biolink:NamedThing omim.nt http://omim.org/entry/100850.0011 biolink:NamedThing ACO2, GLY240ASP For discussion of the c.719G-A transition ({VAR c.719G-A, NM_001098.2}) in the ACO2 gene, resulting in a gly240-to-asp (G240D) substitution, that was found in compound heterozygous state in a patient with infantile cerebellar-retinal degeneration (ICRD; {614559}) by {1:Blackburn et al. (2020)}, see {100850.0010}. omim.nt GENO:0000002 ClinVar:RCV000481524 biolink:NamedThing omim.nt ClinVar:RCV001255995 biolink:NamedThing omim.nt dbSNP:rs141878785 biolink:NamedThing omim.nt owl:NamedIndividual http://omim.org/entry/100850#0011 biolink:NamedThing omim.nt http://omim.org/entry/100850.0012 biolink:NamedThing ACO2, 2-BP DEL, 2338CA In an 11-year-old girl (P5) with infantile cerebellar-retinal degeneration (ICRD; {614559}), {1:Blackburn et al. (2020)} identified homozygosity for a 2-bp deletion ({VAR c.2338_2339delCA, NM_001098.2}), resulting in a frameshift (Gln780ValfsTer63). The mutations were identified by whole-exome sequencing, and the parents were confirmed to be mutation carriers by Sanger sequencing. The mutation occurs in the last amino acid before the ACO2 stop codon and is a predicted stop-loss mutation resulting in inclusion of an additional 62 amino acids. The patient had progressive spastic quadriplegia, seizures, hypotonia, absent visually evoked potentials, and severe developmental delay. This patient was previously described in brief (case 17-6359) in a large clinical exome sequencing study of Saudi patients by {10:Monies et al. (2019)}. omim.nt GENO:0000002 ClinVar:RCV000491582 biolink:NamedThing omim.nt dbSNP:rs1114167284 biolink:NamedThing omim.nt owl:NamedIndividual http://omim.org/entry/100850#0012 biolink:NamedThing omim.nt MONARCH:.well-known/genid/baef89c7c587bec8ab7a biolink:NamedThing GRCh38chr22-41468755-41528978-Region omim.nt MONARCH:.well-known/genid/b0ffd4fb000b5a0e202c faldo:Region MONARCH:.well-known/genid/OMIM100850ref11 biolink:NamedThing Personal Communication. omim.nt IAO:0000310 PMID:1052766 biolink:NamedThing omim.nt IAO:0000013 PMID:12198491 biolink:NamedThing omim.nt IAO:0000013 PMID:15247478 biolink:NamedThing omim.nt IAO:0000013 PMID:15692048 biolink:NamedThing omim.nt IAO:0000013 PMID:22405087 biolink:NamedThing omim.nt IAO:0000013 PMID:25351951 biolink:NamedThing omim.nt IAO:0000013 PMID:29577077 biolink:NamedThing omim.nt IAO:0000013 PMID:30689204 biolink:NamedThing omim.nt IAO:0000013 PMID:31130284 biolink:NamedThing omim.nt IAO:0000013 PMID:32519519 biolink:NamedThing omim.nt IAO:0000013 PMID:7192199 biolink:NamedThing omim.nt IAO:0000013 PMID:728065 biolink:NamedThing omim.nt IAO:0000013 PMID:752476 biolink:NamedThing omim.nt IAO:0000013 PMID:752478 biolink:NamedThing omim.nt IAO:0000013 PMID:752479 biolink:NamedThing omim.nt IAO:0000013 PMID:879710 biolink:NamedThing omim.nt IAO:0000013 PMID:9630632 biolink:NamedThing omim.nt IAO:0000013 http://omim.org/entry/616289 biolink:NamedThing|biolink:Disease Optic Atrophy 9 Optic Atrophy 9 omim.nt OPTIC ATROPHY 9; OPA9 owl:Class OBO:CHR_9606chr22q13.2 biolink:NamedThing omim.nt owl:Class http://omim.org/entry/614559 biolink:NamedThing|biolink:Disease Infantile Cerebellar-Retinal Degeneration Infantile Cerebellar-Retinal Degeneration omim.nt INFANTILE CEREBELLAR-RETINAL DEGENERATION; ICRD owl:Class http://www.omim.org/phenotypicSeries/PS165500 biolink:NamedThing|biolink:Disease Optic atrophy omim.nt owl:Class UMLS:C1412127 biolink:NamedThing omim.nt owl:Class https://www.ncbi.nlm.nih.gov/gene/50 biolink:NamedThing omim.nt http://omim.org/entry/100880 biolink:NamedThing|biolink:Gene ACO1 Aconitase 1, Soluble omim.nt ACONITASE 1, SOLUBLE; ACO1|Aconitase, Soluble|Aconitate Hydratase, Soluble|Ire-Binding Protein 1|Iron Regulatory Protein 1|Iron-Responsive Element-Binding Protein 1 owl:Class MONARCH:.well-known/genid/b221fddc5500da3708ed biolink:NamedThing GRCh38chr9-32384642-32454768-Region omim.nt MONARCH:.well-known/genid/bc5d1b4fab4c6a8e10f7 faldo:Region MONARCH:.well-known/genid/OMIM100880ref13 biolink:NamedThing Human Polymorphic Genes: World Distribution. omim.nt IAO:0000310 MONARCH:.well-known/genid/OMIM100880ref14 biolink:NamedThing Genetic variation of aconitate hydratase in man. omim.nt IAO:0000310 MONARCH:.well-known/genid/OMIM100880ref19 biolink:NamedThing Red cell glyoxalase I and placental soluble aconitase polymorphisms in the three major ethnic groups of Malaysia. omim.nt IAO:0000310 PMID:10940348 biolink:NamedThing omim.nt IAO:0000013 PMID:1192837 biolink:NamedThing omim.nt IAO:0000013 PMID:1383764 biolink:NamedThing omim.nt IAO:0000013 PMID:15604406 biolink:NamedThing omim.nt IAO:0000013 PMID:17185597 biolink:NamedThing omim.nt IAO:0000013 PMID:182062 biolink:NamedThing omim.nt IAO:0000013 PMID:196813 biolink:NamedThing omim.nt IAO:0000013 PMID:200168 biolink:NamedThing omim.nt IAO:0000013 PMID:20053667 biolink:NamedThing omim.nt IAO:0000013 PMID:2172968 biolink:NamedThing omim.nt IAO:0000013 PMID:23891004 biolink:NamedThing omim.nt IAO:0000013 PMID:2771641 biolink:NamedThing omim.nt IAO:0000013 PMID:292306 biolink:NamedThing omim.nt IAO:0000013 PMID:496396 biolink:NamedThing omim.nt IAO:0000013 PMID:6297853 biolink:NamedThing omim.nt IAO:0000013 PMID:7140357 biolink:NamedThing omim.nt IAO:0000013 PMID:7774911 biolink:NamedThing omim.nt IAO:0000013 OBO:CHR_9606chr9p21.2 biolink:NamedThing omim.nt owl:Class UMLS:C1412126 biolink:NamedThing omim.nt owl:Class https://www.ncbi.nlm.nih.gov/gene/48 biolink:NamedThing omim.nt http://omim.org/entry/100900 biolink:NamedThing omim.nt True owl:Class http://omim.org/entry/101000 biolink:NamedThing|biolink:Disease Neurofibromatosis, Type 2 Neurofibromatosis, Type 2 omim.nt NEUROFIBROMATOSIS, TYPE II; NF2|Acoustic Neurinoma, Bilateral|Acoustic Schwannomas, Bilateral|Bilateral Acoustic Neurofibromatosis|Neurofibromatosis, Central Type owl:Class MONARCH:.well-known/genid/OMIM101000ref17 biolink:NamedThing Neurofibromatosis 2 (NF2): clinical heterogeneity and natural history based on 39 individuals in 9 families and 16 sporadic cases. (Abstract) omim.nt IAO:0000310 MONARCH:.well-known/genid/OMIM101000ref28 biolink:NamedThing Bilateral acoustic neurofibromas. A clinical study and survey of a family of five generations with bilateral deafness in 38 members. omim.nt IAO:0000310 MONARCH:.well-known/genid/OMIM101000ref29 biolink:NamedThing Hereditary bilateral acoustic tumors. omim.nt IAO:0000310 MONARCH:.well-known/genid/OMIM101000ref30 biolink:NamedThing Bilateral acoustic neurofibromas: further clinical and pathologic data on hereditary deafness and Recklinghausen's disease. omim.nt IAO:0000310 MONARCH:.well-known/genid/OMIM101000ref52 biolink:NamedThing Neurofibromatosis: conference statement. omim.nt IAO:0000310 MONARCH:.well-known/genid/OMIM101000ref53 biolink:NamedThing Neurofibromatosis (3). omim.nt IAO:0000310 MONARCH:.well-known/genid/OMIM101000ref55 biolink:NamedThing Neurofibromatosis 2 (NF2): lens findings in 40 patients in 5 high risk groups. (Abstract) omim.nt IAO:0000310 MONARCH:.well-known/genid/OMIM101000ref59 biolink:NamedThing Bilateral acoustic neurinoma and neurofibromatosis. omim.nt IAO:0000310 MONARCH:.well-known/genid/OMIM101000ref65 biolink:NamedThing Genetic linkage of bilateral acoustic neurofibromatosis to DNA markers on chromosome 22. (Abstract) omim.nt IAO:0000310 MONARCH:.well-known/genid/OMIM101000ref75 biolink:NamedThing Case of tumours in the skull, dura mater, and brain. omim.nt IAO:0000310 MONARCH:.well-known/genid/OMIM101000ref77 biolink:NamedThing Multiple meningeal and perineural tumors with analogous changes in the glia and ependyma (neurofibroblastomatosis). omim.nt IAO:0000310 PMID:10569966 biolink:NamedThing omim.nt IAO:0000013 PMID:10771486 biolink:NamedThing omim.nt IAO:0000013 PMID:11342693 biolink:NamedThing omim.nt IAO:0000013 PMID:11425952 biolink:NamedThing omim.nt IAO:0000013 PMID:11732488 biolink:NamedThing omim.nt IAO:0000013 PMID:12011146 biolink:NamedThing omim.nt IAO:0000013 PMID:12136076 biolink:NamedThing omim.nt IAO:0000013 PMID:12235555 biolink:NamedThing omim.nt IAO:0000013 PMID:12473765 biolink:NamedThing omim.nt IAO:0000013 PMID:12960214 biolink:NamedThing omim.nt IAO:0000013 PMID:14205096 biolink:NamedThing omim.nt IAO:0000013 PMID:1456285 biolink:NamedThing omim.nt IAO:0000013 PMID:14569124 biolink:NamedThing omim.nt IAO:0000013 PMID:1479598 biolink:NamedThing omim.nt IAO:0000013 PMID:1479599 biolink:NamedThing omim.nt IAO:0000013 PMID:1484939 biolink:NamedThing omim.nt IAO:0000013 PMID:1496981 biolink:NamedThing omim.nt IAO:0000013 PMID:1496982 biolink:NamedThing omim.nt IAO:0000013 PMID:15190457 biolink:NamedThing omim.nt IAO:0000013 PMID:15235024 biolink:NamedThing omim.nt IAO:0000013 PMID:15994874 biolink:NamedThing omim.nt IAO:0000013 PMID:17307835 biolink:NamedThing omim.nt IAO:0000013 PMID:17353411 biolink:NamedThing omim.nt IAO:0000013 PMID:1745350 biolink:NamedThing omim.nt IAO:0000013 PMID:1789288 biolink:NamedThing omim.nt IAO:0000013 PMID:19476995 biolink:NamedThing omim.nt IAO:0000013 PMID:19880713 biolink:NamedThing omim.nt IAO:0000013 PMID:20769855 biolink:NamedThing omim.nt IAO:0000013 PMID:2105641 biolink:NamedThing omim.nt IAO:0000013 PMID:21451418 biolink:NamedThing omim.nt IAO:0000013 PMID:2282716 biolink:NamedThing omim.nt IAO:0000013 PMID:2310328 biolink:NamedThing omim.nt IAO:0000013 PMID:2705922 biolink:NamedThing omim.nt IAO:0000013 PMID:2888021 biolink:NamedThing omim.nt IAO:0000013 PMID:3092103 biolink:NamedThing omim.nt IAO:0000013 PMID:3097542 biolink:NamedThing omim.nt IAO:0000013 PMID:3098672 biolink:NamedThing omim.nt IAO:0000013 PMID:3100017 biolink:NamedThing omim.nt IAO:0000013 PMID:3105060 biolink:NamedThing omim.nt IAO:0000013 PMID:3125435 biolink:NamedThing omim.nt IAO:0000013 PMID:3134615 biolink:NamedThing omim.nt IAO:0000013 PMID:3185841 biolink:NamedThing omim.nt IAO:0000013 PMID:4975015 biolink:NamedThing omim.nt IAO:0000013 PMID:4990044 biolink:NamedThing omim.nt IAO:0000013 PMID:5304294 biolink:NamedThing omim.nt IAO:0000013 PMID:5674095 biolink:NamedThing omim.nt IAO:0000013 PMID:6774282 biolink:NamedThing omim.nt IAO:0000013 PMID:6798843 biolink:NamedThing omim.nt IAO:0000013 PMID:7057963 biolink:NamedThing omim.nt IAO:0000013 PMID:7479890 biolink:NamedThing omim.nt IAO:0000013 PMID:7485365 biolink:NamedThing omim.nt IAO:0000013 PMID:7747758 biolink:NamedThing omim.nt IAO:0000013 PMID:805367 biolink:NamedThing omim.nt IAO:0000013 PMID:8102569 biolink:NamedThing omim.nt IAO:0000013 PMID:8304846 biolink:NamedThing omim.nt IAO:0000013 PMID:8318482 biolink:NamedThing omim.nt IAO:0000013 PMID:83481 biolink:NamedThing omim.nt IAO:0000013 PMID:8379998 biolink:NamedThing omim.nt IAO:0000013 PMID:8414026 biolink:NamedThing omim.nt IAO:0000013 PMID:8451014 biolink:NamedThing omim.nt IAO:0000013 PMID:8751853 biolink:NamedThing omim.nt IAO:0000013 PMID:8755919 biolink:NamedThing omim.nt IAO:0000013 PMID:9207339 biolink:NamedThing omim.nt IAO:0000013 PMID:9225971 biolink:NamedThing omim.nt IAO:0000013 PMID:9643284 biolink:NamedThing omim.nt IAO:0000013 PMID:9811917 biolink:NamedThing omim.nt IAO:0000013 PMID:9811925 biolink:NamedThing omim.nt IAO:0000013 PMID:9863591 biolink:NamedThing omim.nt IAO:0000013 UMLS:C0027832 biolink:NamedThing omim.nt owl:Class UMLS:C1136042 biolink:NamedThing omim.nt owl:Class ORPHA:637 biolink:NamedThing|biolink:Disease omim.nt owl:Class http://omim.org/entry/101120 biolink:NamedThing Acrocephalopolysyndactyly Type 3 omim.nt ACROCEPHALOPOLYSYNDACTYLY TYPE III|Acps 3|Acps With Leg Hypoplasia|Sakati-Nyhan Syndrome owl:Class PMID:4253694 biolink:NamedThing omim.nt IAO:0000013 UMLS:C1275079 biolink:NamedThing omim.nt owl:Class http://omim.org/entry/101200 biolink:NamedThing|biolink:Disease Apert Syndrome Apert Syndrome omim.nt APERT SYNDROME|Acrocephalosyndactyly, Type 1|Acrocephalosyndactyly, Type 2|Acs 1|Acs 2|Apert-Crouzon Disease|Vogt Cephalodactyly owl:Class MONARCH:.well-known/genid/OMIM101200ref3 biolink:NamedThing De l'acrocephalosyndactylie. omim.nt IAO:0000310 MONARCH:.well-known/genid/OMIM101200ref32 biolink:NamedThing Das Gehoerorgan bei den angeborenen Kopfmissbildungen. omim.nt IAO:0000310 MONARCH:.well-known/genid/OMIM101200ref35 biolink:NamedThing Acrocephaly and scaphocephaly with symmetrically distributed malformations of the extremities. omim.nt IAO:0000310 MONARCH:.well-known/genid/OMIM101200ref40 biolink:NamedThing Prognosis for mental function in Apert's syndrome. omim.nt IAO:0000310 MONARCH:.well-known/genid/OMIM101200ref41 biolink:NamedThing Apert's acrocephalosyndactyly in mother and daughter: cleft palate in the mother. omim.nt IAO:0000310 MONARCH:.well-known/genid/OMIM101200ref47 biolink:NamedThing Synopsis of hand malformations with particular emphasis on genetic factors. omim.nt IAO:0000310 MONARCH:.well-known/genid/OMIM101200ref48 biolink:NamedThing The Genetics of Hand Malformations. omim.nt IAO:0000310 MONARCH:.well-known/genid/OMIM101200ref51 biolink:NamedThing Dyskephalie (dysostosis craniofacialis, maladie De Crouzon 1912) und eine neuartige Kombination dieser Krankheit mit Syndaktylie der 4 Extremitaeten (Dyskephalodaktylie). omim.nt IAO:0000310 MONARCH:.well-known/genid/OMIM101200ref53 biolink:NamedThing Combined acrocephaly and syndactylism occurring in mother and daughter: a case report. omim.nt IAO:0000310 MONARCH:.well-known/genid/OMIM101200ref54 biolink:NamedThing Two specimens of congenital cranial deformity in infants associated with fusion of the fingers and toes. omim.nt IAO:0000310 MONARCH:.well-known/genid/OMIM101200ref7 biolink:NamedThing An etiologic and nosologic overview of craniosynostosis syndromes. omim.nt IAO:0000310 PMID:10067911 biolink:NamedThing omim.nt IAO:0000013 PMID:10735635 biolink:NamedThing omim.nt IAO:0000013 PMID:12900791 biolink:NamedThing omim.nt IAO:0000013 PMID:1303629 biolink:NamedThing omim.nt IAO:0000013 PMID:13613870 biolink:NamedThing omim.nt IAO:0000013 PMID:13801313 biolink:NamedThing omim.nt IAO:0000013 PMID:1621762 biolink:NamedThing omim.nt IAO:0000013 PMID:1642807 biolink:NamedThing omim.nt IAO:0000013 PMID:16440883 biolink:NamedThing omim.nt IAO:0000013 PMID:16691624 biolink:NamedThing omim.nt IAO:0000013 PMID:16876521 biolink:NamedThing omim.nt IAO:0000013 PMID:16969861 biolink:NamedThing omim.nt IAO:0000013 PMID:20124286 biolink:NamedThing omim.nt IAO:0000013 PMID:2065493 biolink:NamedThing omim.nt IAO:0000013 PMID:23495236 biolink:NamedThing omim.nt IAO:0000013 PMID:2405668 biolink:NamedThing omim.nt IAO:0000013 PMID:2774006 biolink:NamedThing omim.nt IAO:0000013 PMID:2851938 biolink:NamedThing omim.nt IAO:0000013 PMID:3351902 biolink:NamedThing omim.nt IAO:0000013 PMID:3359672 biolink:NamedThing omim.nt IAO:0000013 PMID:3674108 biolink:NamedThing omim.nt IAO:0000013 PMID:3742849 biolink:NamedThing omim.nt IAO:0000013 PMID:4248541 biolink:NamedThing omim.nt IAO:0000013 PMID:4460868 biolink:NamedThing omim.nt IAO:0000013 PMID:5479478 biolink:NamedThing omim.nt IAO:0000013 PMID:5493837 biolink:NamedThing omim.nt IAO:0000013 PMID:5938051 biolink:NamedThing omim.nt IAO:0000013 PMID:7065003 biolink:NamedThing omim.nt IAO:0000013 PMID:7573165 biolink:NamedThing omim.nt IAO:0000013 PMID:7645606 biolink:NamedThing omim.nt IAO:0000013 PMID:7668257 biolink:NamedThing omim.nt IAO:0000013 PMID:7674004 biolink:NamedThing omim.nt IAO:0000013 PMID:7719344 biolink:NamedThing omim.nt IAO:0000013 PMID:7802047 biolink:NamedThing omim.nt IAO:0000013 PMID:8434630 biolink:NamedThing omim.nt IAO:0000013 PMID:8456856 biolink:NamedThing omim.nt IAO:0000013 PMID:8651276 biolink:NamedThing omim.nt IAO:0000013 PMID:8673103 biolink:NamedThing omim.nt IAO:0000013 PMID:9002682 biolink:NamedThing omim.nt IAO:0000013 PMID:925743 biolink:NamedThing omim.nt IAO:0000013 PMID:9375719 biolink:NamedThing omim.nt IAO:0000013 PMID:9502772 biolink:NamedThing omim.nt IAO:0000013 PMID:9664610 biolink:NamedThing omim.nt IAO:0000013 PMID:9973282 biolink:NamedThing omim.nt IAO:0000013 UMLS:C0001193 biolink:NamedThing omim.nt owl:Class UMLS:C1863389 biolink:NamedThing omim.nt owl:Class UMLS:C1863391 biolink:NamedThing omim.nt owl:Class ORPHA:87 biolink:NamedThing|biolink:Disease omim.nt owl:Class http://omim.org/entry/101400 biolink:NamedThing|biolink:Disease Saethre-Chotzen Syndrome Saethre-Chotzen Syndrome omim.nt SAETHRE-CHOTZEN SYNDROME; SCS|Acrocephalosyndactyly, Type 3|Acrocephaly, Skull Asymmetry, and Mild Syndactyly|Acs 3|Blepharophimosis, Epicanthus Inversus, and Ptosis 3, Formerly|Chotzen Syndrome|Saethre-Chotzen Syndrome With Eyelid Anomalies owl:Class MONARCH:.well-known/genid/OMIM101400ref11 biolink:NamedThing Identification of a new TWIST mutation (7p21) with variable eyelid manifestations supports locus homogeneity of BPES at 3q22. (Letter) omim.nt IAO:0000310 MONARCH:.well-known/genid/OMIM101400ref14 biolink:NamedThing Personal Communication. omim.nt IAO:0000310 MONARCH:.well-known/genid/OMIM101400ref16 biolink:NamedThing TWIST1 and the Saethre-Chotzen syndrome. In: Epstein, C. J.; Erickson, R. P.; Wynshaw-Boris, A. (eds.): Inborn Errors of Development. The Molecular Basis of Clinical Disorders of Morphogenesis. (2nd ed.). omim.nt IAO:0000310 MONARCH:.well-known/genid/OMIM101400ref26 biolink:NamedThing Mapping of Saethre-Chotzen syndrome (ACS III) to 7p21. (Abstract) omim.nt IAO:0000310 MONARCH:.well-known/genid/OMIM101400ref29 biolink:NamedThing A case of Saethre-Chotzen syndrome. omim.nt IAO:0000310 MONARCH:.well-known/genid/OMIM101400ref31 biolink:NamedThing The Saethre-Chotzen syndrome. omim.nt IAO:0000310 MONARCH:.well-known/genid/OMIM101400ref37 biolink:NamedThing Ein Beitrag zum Turmschaedelproblem (Pathogenese, Erblichkeit und Symptomatologie). omim.nt IAO:0000310 MONARCH:.well-known/genid/OMIM101400ref39 biolink:NamedThing Genetics and Ophthalmology. Vol 1. omim.nt IAO:0000310 MONARCH:.well-known/genid/OMIM101400ref8 biolink:NamedThing Eine eigenartige familiaere Entwicklungsstoerung (Akrocephalosyndaktylie, Dysostosis craniofacialis und Hypertelorismus). omim.nt IAO:0000310 PMID:11977182 biolink:NamedThing omim.nt IAO:0000013 PMID:12116251 biolink:NamedThing omim.nt IAO:0000013 PMID:1433226 biolink:NamedThing omim.nt IAO:0000013 PMID:16251895 biolink:NamedThing omim.nt IAO:0000013 PMID:17437280 biolink:NamedThing omim.nt IAO:0000013 PMID:1756600 biolink:NamedThing omim.nt IAO:0000013 PMID:1877630 biolink:NamedThing omim.nt IAO:0000013 PMID:2002481 biolink:NamedThing omim.nt IAO:0000013 PMID:2769726 biolink:NamedThing omim.nt IAO:0000013 PMID:2845086 biolink:NamedThing omim.nt IAO:0000013 PMID:4073118 biolink:NamedThing omim.nt IAO:0000013 PMID:4145271 biolink:NamedThing omim.nt IAO:0000013 PMID:4393456 biolink:NamedThing omim.nt IAO:0000013 PMID:4643612 biolink:NamedThing omim.nt IAO:0000013 PMID:5444587 biolink:NamedThing omim.nt IAO:0000013 PMID:7120316 biolink:NamedThing omim.nt IAO:0000013 PMID:7296937 biolink:NamedThing omim.nt IAO:0000013 PMID:7450776 biolink:NamedThing omim.nt IAO:0000013 PMID:7783164 biolink:NamedThing omim.nt IAO:0000013 PMID:7977380 biolink:NamedThing omim.nt IAO:0000013 PMID:7987323 biolink:NamedThing omim.nt IAO:0000013 PMID:8064818 biolink:NamedThing omim.nt IAO:0000013 PMID:8188211 biolink:NamedThing omim.nt IAO:0000013 PMID:8266989 biolink:NamedThing omim.nt IAO:0000013 PMID:862213 biolink:NamedThing omim.nt IAO:0000013 PMID:8698349 biolink:NamedThing omim.nt IAO:0000013 PMID:8968762 biolink:NamedThing omim.nt IAO:0000013 PMID:8988166 biolink:NamedThing omim.nt IAO:0000013 PMID:8988167 biolink:NamedThing omim.nt IAO:0000013 PMID:8995765 biolink:NamedThing omim.nt IAO:0000013 PMID:9585583 biolink:NamedThing omim.nt IAO:0000013 PMID:9792855 biolink:NamedThing omim.nt IAO:0000013 PMID:9792856 biolink:NamedThing omim.nt IAO:0000013 UMLS:C0175699 biolink:NamedThing omim.nt owl:Class UMLS:C1863370 biolink:NamedThing omim.nt owl:Class UMLS:C1863371 biolink:NamedThing omim.nt owl:Class ORPHA:794 biolink:NamedThing|biolink:Disease omim.nt owl:Class http://omim.org/entry/101600 biolink:NamedThing|biolink:Disease Pfeiffer Syndrome Pfeiffer Syndrome omim.nt PFEIFFER SYNDROME|Acrocephalosyndactyly, Type 5|Acs 5|Craniofacial-Skeletal-Dermatologic Dysplasia|Noack Syndrome owl:Class MONARCH:.well-known/genid/OMIM101600ref20 biolink:NamedThing Associated deformities of the head and hands. omim.nt IAO:0000310 MONARCH:.well-known/genid/OMIM101600ref25 biolink:NamedThing Acrocephalopolysyndactyly, type Noack, in a large kindred. omim.nt IAO:0000310 MONARCH:.well-known/genid/OMIM101600ref3 biolink:NamedThing Reply to Dr. Winter. (Letter) omim.nt IAO:0000310 MONARCH:.well-known/genid/OMIM101600ref35 biolink:NamedThing Synopsis of hand malformations with particular emphasis on genetic factors. omim.nt IAO:0000310 PMID:10712195 biolink:NamedThing omim.nt IAO:0000013 PMID:12400058 biolink:NamedThing omim.nt IAO:0000013 PMID:14316612 biolink:NamedThing omim.nt IAO:0000013 PMID:14427428 biolink:NamedThing omim.nt IAO:0000013 PMID:14564217 biolink:NamedThing omim.nt IAO:0000013 PMID:1472357 biolink:NamedThing omim.nt IAO:0000013 PMID:15996217 biolink:NamedThing omim.nt IAO:0000013 PMID:2208766 biolink:NamedThing omim.nt IAO:0000013 PMID:3342547 biolink:NamedThing omim.nt IAO:0000013 PMID:3792393 biolink:NamedThing omim.nt IAO:0000013 PMID:4641185 biolink:NamedThing omim.nt IAO:0000013 PMID:5152131 biolink:NamedThing omim.nt IAO:0000013 PMID:5551881 biolink:NamedThing omim.nt IAO:0000013 PMID:7120318 biolink:NamedThing omim.nt IAO:0000013 PMID:712761 biolink:NamedThing omim.nt IAO:0000013 PMID:7205899 biolink:NamedThing omim.nt IAO:0000013 PMID:7327850 biolink:NamedThing omim.nt IAO:0000013 PMID:7719333 biolink:NamedThing omim.nt IAO:0000013 PMID:7719345 biolink:NamedThing omim.nt IAO:0000013 PMID:7795583 biolink:NamedThing omim.nt IAO:0000013 PMID:7874169 biolink:NamedThing omim.nt IAO:0000013 PMID:7881412 biolink:NamedThing omim.nt IAO:0000013 PMID:8434615 biolink:NamedThing omim.nt IAO:0000013 PMID:8528214 biolink:NamedThing omim.nt IAO:0000013 PMID:856510 biolink:NamedThing omim.nt IAO:0000013 PMID:8644708 biolink:NamedThing omim.nt IAO:0000013 PMID:8841188 biolink:NamedThing omim.nt IAO:0000013 PMID:8939381 biolink:NamedThing omim.nt IAO:0000013 PMID:9150725 biolink:NamedThing omim.nt IAO:0000013 PMID:9475589 biolink:NamedThing omim.nt IAO:0000013 PMID:9475590 biolink:NamedThing omim.nt IAO:0000013 PMID:9475591 biolink:NamedThing omim.nt IAO:0000013 PMID:957376 biolink:NamedThing omim.nt IAO:0000013 UMLS:C0220658 biolink:NamedThing omim.nt owl:Class ORPHA:710 biolink:NamedThing|biolink:Disease omim.nt owl:Class ORPHA:93258 biolink:NamedThing|biolink:Disease omim.nt owl:Class ORPHA:93259 biolink:NamedThing|biolink:Disease omim.nt owl:Class ORPHA:93260 biolink:NamedThing|biolink:Disease omim.nt owl:Class http://omim.org/entry/101800 biolink:NamedThing|biolink:Disease Acrodysostosis 1 With or Without Hormone Resistance Acrodysostosis 1 With or Without Hormone Resistance omim.nt ACRODYSOSTOSIS 1 WITH OR WITHOUT HORMONE RESISTANCE; ACRDYS1|Adohr owl:Class MONARCH:.well-known/genid/OMIM101800ref13 biolink:NamedThing Recognizable Patterns of Human Malformation: Genetic, Embryologic and Clinical Aspects. (3rd ed.) omim.nt IAO:0000310 MONARCH:.well-known/genid/OMIM101800ref3 biolink:NamedThing Die Akrodysostose--eine autosomal-dominant verebte periphere Dysplasie. omim.nt IAO:0000310 PMID:1110452 biolink:NamedThing omim.nt IAO:0000013 PMID:11200992 biolink:NamedThing omim.nt IAO:0000013 PMID:1342871 biolink:NamedThing omim.nt IAO:0000013 PMID:1860254 biolink:NamedThing omim.nt IAO:0000013 PMID:2012131 biolink:NamedThing omim.nt IAO:0000013 PMID:21651393 biolink:NamedThing omim.nt IAO:0000013 PMID:22464250 biolink:NamedThing omim.nt IAO:0000013 PMID:22464252 biolink:NamedThing omim.nt IAO:0000013 PMID:3055990 biolink:NamedThing omim.nt IAO:0000013 PMID:5305130 biolink:NamedThing omim.nt IAO:0000013 PMID:5551869 biolink:NamedThing omim.nt IAO:0000013 PMID:6020652 biolink:NamedThing omim.nt IAO:0000013 PMID:669707 biolink:NamedThing omim.nt IAO:0000013 PMID:9039990 biolink:NamedThing omim.nt IAO:0000013 UMLS:C3276228 biolink:NamedThing omim.nt owl:Class ORPHA:280651 biolink:NamedThing|biolink:Disease omim.nt owl:Class ORPHA:950 biolink:NamedThing|biolink:Disease omim.nt owl:Class http://www.omim.org/phenotypicSeries/PS101800 biolink:NamedThing|biolink:Disease Acrodysostosis omim.nt owl:Class http://omim.org/entry/101805 biolink:NamedThing|biolink:Disease Acrofacial Dysostosis, Catania Type omim.nt ACROFACIAL DYSOSTOSIS, CATANIA TYPE|Afd, Catania Type owl:Class PMID:25945454 biolink:NamedThing omim.nt IAO:0000013 PMID:8266994 biolink:NamedThing omim.nt IAO:0000013 PMID:8826434 biolink:NamedThing omim.nt IAO:0000013 UMLS:C2931762 biolink:NamedThing omim.nt owl:Class ORPHA:1786 biolink:NamedThing|biolink:Disease omim.nt owl:Class http://omim.org/entry/101840 biolink:NamedThing Acrokeratoderma, Hereditary Papulotranslucent omim.nt ACROKERATODERMA, HEREDITARY PAPULOTRANSLUCENT owl:Class MONARCH:.well-known/genid/OMIM101840ref1 biolink:NamedThing Hereditair papulotranslucent keratoderma van de acra als variant van en in combinatie met keratosis punctata palmaris et plantaris. omim.nt IAO:0000310 MONARCH:.well-known/genid/OMIM101840ref3 biolink:NamedThing Hereditary papulotranslucent acrokeratoderma: a case report and literature review. omim.nt IAO:0000310 PMID:4716729 biolink:NamedThing omim.nt IAO:0000013 UMLS:C1863343 biolink:NamedThing omim.nt owl:Class http://omim.org/entry/101850 biolink:NamedThing|biolink:Disease Palmoplantar Keratoderma, Punctate Type 3 Palmoplantar Keratoderma, Punctate Type 3 omim.nt PALMOPLANTAR KERATODERMA, PUNCTATE TYPE III; PPKP3|Acrokeratoelastoidosis|Collagenous Plaques of Hands and Feet owl:Class MONARCH:.well-known/genid/OMIM101850ref2 biolink:NamedThing Ackrokeratoelastoidosis. omim.nt IAO:0000310 PMID:13116681 biolink:NamedThing omim.nt IAO:0000013 PMID:141935 biolink:NamedThing omim.nt IAO:0000013 PMID:4449867 biolink:NamedThing omim.nt IAO:0000013 PMID:4694520 biolink:NamedThing omim.nt IAO:0000013 PMID:6221990 biolink:NamedThing omim.nt IAO:0000013 PMID:8651714 biolink:NamedThing omim.nt IAO:0000013 PMID:9870680 biolink:NamedThing omim.nt IAO:0000013 UMLS:C0545044 biolink:NamedThing omim.nt owl:Class ORPHA:38 biolink:NamedThing|biolink:Disease omim.nt owl:Class http://omim.org/entry/101900 biolink:NamedThing|biolink:Disease Acrokeratosis Verruciformis Acrokeratosis Verruciformis omim.nt ACROKERATOSIS VERRUCIFORMIS; AKV|Hopf Disease owl:Class MONARCH:.well-known/genid/OMIM101900ref2 biolink:NamedThing Acrokeratosis verruciformis (Hopf) and Darier's disease: genetic evidence for a unitary origin. omim.nt IAO:0000310 MONARCH:.well-known/genid/OMIM101900ref4 biolink:NamedThing Acrokeratosis verruciformis (Hopf): a follow-up study. omim.nt IAO:0000310 PMID:12542527 biolink:NamedThing omim.nt IAO:0000013 PMID:20251558 biolink:NamedThing omim.nt IAO:0000013 UMLS:C0265971 biolink:NamedThing omim.nt owl:Class ORPHA:79151 biolink:NamedThing|biolink:Disease omim.nt owl:Class http://omim.org/entry/102000 biolink:NamedThing Acroleukopathy, Symmetric omim.nt ACROLEUKOPATHY, SYMMETRIC owl:Class MONARCH:.well-known/genid/OMIM102000ref1 biolink:NamedThing Symmetric acroleukopathy in mother and daughter. omim.nt IAO:0000310 UMLS:C1863342 biolink:NamedThing omim.nt owl:Class http://omim.org/entry/102100 biolink:NamedThing|biolink:Disease Acromegaloid Changes, Cutis Verticis Gyrata, and Corneal Leukoma Acromegaloid Changes, Cutis Verticis Gyrata, and Corneal Leukoma omim.nt ACROMEGALOID CHANGES, CUTIS VERTICIS GYRATA, AND CORNEAL LEUKOMA|Rosenthal-Kloepfer Syndrome owl:Class MONARCH:.well-known/genid/OMIM102100ref2 biolink:NamedThing Personal Communication. omim.nt IAO:0000310 PMID:13974983 biolink:NamedThing omim.nt IAO:0000013 PMID:5570364 biolink:NamedThing omim.nt IAO:0000013 UMLS:C1321495 biolink:NamedThing omim.nt owl:Class ORPHA:964 biolink:NamedThing|biolink:Disease omim.nt owl:Class http://omim.org/entry/102150 biolink:NamedThing|biolink:Disease Acromegaloid Facial Appearance Syndrome Acromegaloid Facial Appearance Syndrome omim.nt ACROMEGALOID FACIAL APPEARANCE SYNDROME|Afa Syndrome|Thick Lips and Oral Mucosa owl:Class PMID:15365463 biolink:NamedThing omim.nt IAO:0000013 PMID:1619638 biolink:NamedThing omim.nt IAO:0000013 PMID:3989825 biolink:NamedThing omim.nt IAO:0000013 UMLS:C0796280 biolink:NamedThing omim.nt owl:Class ORPHA:965 biolink:NamedThing|biolink:Disease omim.nt owl:Class http://omim.org/entry/102200 biolink:NamedThing|biolink:Disease Pituitary Adenoma 1, Multiple Types Pituitary Adenoma 1, Multiple Types omim.nt PITUITARY ADENOMA 1, MULTIPLE TYPES; PITA1|Acromegaly Due to Pituitary Adenoma 1|Isolated Familial Somatotropinoma|Pagh1|Pituitary Adenoma, Familial Isolated|Pituitary Adenoma Predisposition|Somatotrophinoma, Familial|Somatotropinoma, Familial Isolated owl:Class PMID:10690880 biolink:NamedThing omim.nt IAO:0000013 PMID:11081208 biolink:NamedThing omim.nt IAO:0000013 PMID:11134164 biolink:NamedThing omim.nt IAO:0000013 PMID:11158006 biolink:NamedThing omim.nt IAO:0000013 PMID:11701684 biolink:NamedThing omim.nt IAO:0000013 PMID:12107207 biolink:NamedThing omim.nt IAO:0000013 PMID:14627789 biolink:NamedThing omim.nt IAO:0000013 PMID:16189251 biolink:NamedThing omim.nt IAO:0000013 PMID:16728643 biolink:NamedThing omim.nt IAO:0000013 PMID:17244780 biolink:NamedThing omim.nt IAO:0000013 PMID:17299063 biolink:NamedThing omim.nt IAO:0000013 PMID:17341560 biolink:NamedThing omim.nt IAO:0000013 PMID:17360484 biolink:NamedThing omim.nt IAO:0000013 PMID:17671221 biolink:NamedThing omim.nt IAO:0000013 PMID:18200440 biolink:NamedThing omim.nt IAO:0000013 PMID:18381572 biolink:NamedThing omim.nt IAO:0000013 PMID:20506337 biolink:NamedThing omim.nt IAO:0000013 PMID:21208107 biolink:NamedThing omim.nt IAO:0000013 PMID:2200621 biolink:NamedThing omim.nt IAO:0000013 PMID:25806920 biolink:NamedThing omim.nt IAO:0000013 PMID:25942478 biolink:NamedThing omim.nt IAO:0000013 PMID:26187128 biolink:NamedThing omim.nt IAO:0000013 PMID:2773624 biolink:NamedThing omim.nt IAO:0000013 PMID:3950729 biolink:NamedThing omim.nt IAO:0000013 PMID:4843205 biolink:NamedThing omim.nt IAO:0000013 PMID:5320367 biolink:NamedThing omim.nt IAO:0000013 PMID:6723082 biolink:NamedThing omim.nt IAO:0000013 PMID:7621566 biolink:NamedThing omim.nt IAO:0000013 PMID:8109184 biolink:NamedThing omim.nt IAO:0000013 PMID:8514889 biolink:NamedThing omim.nt IAO:0000013 PMID:9100571 biolink:NamedThing omim.nt IAO:0000013 PMID:9141543 biolink:NamedThing omim.nt IAO:0000013 PMID:9177361 biolink:NamedThing omim.nt IAO:0000013 PMID:9920092 biolink:NamedThing omim.nt IAO:0000013 UMLS:C1863340 biolink:NamedThing omim.nt owl:Class UMLS:C2676191 biolink:NamedThing omim.nt owl:Class UMLS:C3489630 biolink:NamedThing omim.nt owl:Class UMLS:C4538355 biolink:NamedThing omim.nt owl:Class ORPHA:314777 biolink:NamedThing|biolink:Disease omim.nt owl:Class ORPHA:96256 biolink:NamedThing|biolink:Disease omim.nt owl:Class ORPHA:963 biolink:NamedThing|biolink:Disease omim.nt owl:Class ORPHA:99725 biolink:NamedThing|biolink:Disease omim.nt owl:Class http://www.omim.org/phenotypicSeries/PS102200 biolink:NamedThing|biolink:Disease Pituitary adenoma omim.nt owl:Class http://omim.org/entry/102300 biolink:NamedThing|biolink:Disease Restless Legs Syndrome, Susceptibility To, 1 Restless Legs Syndrome, Susceptibility To, 1 omim.nt RESTLESS LEGS SYNDROME, SUSCEPTIBILITY TO, 1; RLS1|Acromelalgia, Hereditary|Ekbom Syndrome owl:Class MONARCH:.well-known/genid/OMIM102300ref14 biolink:NamedThing Personal Communication. omim.nt IAO:0000310 MONARCH:.well-known/genid/OMIM102300ref17 biolink:NamedThing Restless legs: a clinical study. omim.nt IAO:0000310 MONARCH:.well-known/genid/OMIM102300ref6 biolink:NamedThing Restless legs. omim.nt IAO:0000310 PMID:10762522 biolink:NamedThing omim.nt IAO:0000013 PMID:11087794 biolink:NamedThing omim.nt IAO:0000013 PMID:11160969 biolink:NamedThing omim.nt IAO:0000013 PMID:11704926 biolink:NamedThing omim.nt IAO:0000013 PMID:12068378 biolink:NamedThing omim.nt IAO:0000013 PMID:12136060 biolink:NamedThing omim.nt IAO:0000013 PMID:12205641 biolink:NamedThing omim.nt IAO:0000013 PMID:1267623 biolink:NamedThing omim.nt IAO:0000013 PMID:12761367 biolink:NamedThing omim.nt IAO:0000013 PMID:12764067 biolink:NamedThing omim.nt IAO:0000013 PMID:12913188 biolink:NamedThing omim.nt IAO:0000013 PMID:13469127 biolink:NamedThing omim.nt IAO:0000013 PMID:13651496 biolink:NamedThing omim.nt IAO:0000013 PMID:13726241 biolink:NamedThing omim.nt IAO:0000013 PMID:14592341 biolink:NamedThing omim.nt IAO:0000013 PMID:15136682 biolink:NamedThing omim.nt IAO:0000013 PMID:15452299 biolink:NamedThing omim.nt IAO:0000013 PMID:15505786 biolink:NamedThing omim.nt IAO:0000013 PMID:15623686 biolink:NamedThing omim.nt IAO:0000013 PMID:15824258 biolink:NamedThing omim.nt IAO:0000013 PMID:15955944 biolink:NamedThing omim.nt IAO:0000013 PMID:16049930 biolink:NamedThing omim.nt IAO:0000013 PMID:16124010 biolink:NamedThing omim.nt IAO:0000013 PMID:16624598 biolink:NamedThing omim.nt IAO:0000013 PMID:17242339 biolink:NamedThing omim.nt IAO:0000013 PMID:17420405 biolink:NamedThing omim.nt IAO:0000013 PMID:17485653 biolink:NamedThing omim.nt IAO:0000013 PMID:17637780 biolink:NamedThing omim.nt IAO:0000013 PMID:18070136 biolink:NamedThing omim.nt IAO:0000013 PMID:19279021 biolink:NamedThing omim.nt IAO:0000013 PMID:19704085 biolink:NamedThing omim.nt IAO:0000013 PMID:20457962 biolink:NamedThing omim.nt IAO:0000013 PMID:21135386 biolink:NamedThing omim.nt IAO:0000013 PMID:8723377 biolink:NamedThing omim.nt IAO:0000013 PMID:8813218 biolink:NamedThing omim.nt IAO:0000013 UMLS:C1876177 biolink:NamedThing omim.nt owl:Class http://www.omim.org/phenotypicSeries/PS102300 biolink:NamedThing|biolink:Disease Restless legs syndrome omim.nt owl:Class http://omim.org/entry/102350 biolink:NamedThing|biolink:Disease Acromial Dimples Acromial Dimples omim.nt ACROMIAL DIMPLES|Supraspinous Fossae, Congenital owl:Class MONARCH:.well-known/genid/OMIM102350ref3 biolink:NamedThing Personal Communication. omim.nt IAO:0000310 MONARCH:.well-known/genid/OMIM102350ref4 biolink:NamedThing Dominant inheritance of acromial skin dimples. omim.nt IAO:0000310 PMID:16190989 biolink:NamedThing omim.nt IAO:0000013 PMID:1810986 biolink:NamedThing omim.nt IAO:0000013 PMID:18477153 biolink:NamedThing omim.nt IAO:0000013 PMID:2326363 biolink:NamedThing omim.nt IAO:0000013 PMID:3610152 biolink:NamedThing omim.nt IAO:0000013 PMID:4381584 biolink:NamedThing omim.nt IAO:0000013 PMID:4827369 biolink:NamedThing omim.nt IAO:0000013 UMLS:C4023704 biolink:NamedThing omim.nt owl:Class http://omim.org/entry/102370 biolink:NamedThing|biolink:Disease Acromicric Dysplasia Acromicric Dysplasia omim.nt ACROMICRIC DYSPLASIA; ACMICD owl:Class PMID:11694546 biolink:NamedThing omim.nt IAO:0000013 PMID:21683322 biolink:NamedThing omim.nt IAO:0000013 PMID:26860060 biolink:NamedThing omim.nt IAO:0000013 PMID:3728563 biolink:NamedThing omim.nt IAO:0000013 UMLS:C0265287 biolink:NamedThing omim.nt owl:Class ORPHA:969 biolink:NamedThing|biolink:Disease omim.nt owl:Class http://omim.org/entry/102400 biolink:NamedThing|biolink:Disease Acroosteolysis omim.nt ACROOSTEOLYSIS owl:Class MONARCH:.well-known/genid/OMIM102400ref1 biolink:NamedThing Ueber die familiaere Akro-osteolyse. omim.nt IAO:0000310 MONARCH:.well-known/genid/OMIM102400ref4 biolink:NamedThing Personal Communication. omim.nt IAO:0000310 MONARCH:.well-known/genid/OMIM102400ref5 biolink:NamedThing Personal Communication. omim.nt IAO:0000310 MONARCH:.well-known/genid/OMIM102400ref6 biolink:NamedThing An unusual occupational bone change.In: Jelliffe, A. M.; Strickland, B. : Symposium Ossium. omim.nt IAO:0000310 MONARCH:.well-known/genid/OMIM102400ref7 biolink:NamedThing Roentgen-Diagnostics. Vol. 1. Part 1. English translation by J. T. Case. omim.nt IAO:0000310 PMID:14461884 biolink:NamedThing omim.nt IAO:0000013 PMID:6038365 biolink:NamedThing omim.nt IAO:0000013 UMLS:C0917990 biolink:NamedThing omim.nt owl:Class ORPHA:955 biolink:NamedThing|biolink:Disease omim.nt owl:Class http://omim.org/entry/102480 biolink:NamedThing|biolink:Gene ACR Acrosin omim.nt ACROSIN; ACR|Preproacrosin|Proacrosin owl:Class MONARCH:.well-known/genid/b6b6782beb255b7e9144 biolink:NamedThing GRCh38chr22-50738203-50745338-Region omim.nt MONARCH:.well-known/genid/b3f19c8a70b7911f6252 faldo:Region MONARCH:.well-known/genid/OMIM102480ref1 biolink:NamedThing Localization of human preproacrosin to chromosome 22q13-qter by somatic cell hybrid analysis. (Abstract) omim.nt IAO:0000310 MONARCH:.well-known/genid/OMIM102480ref4 biolink:NamedThing Molecular cloning and expression of boar and human proacrosin cDNA. (Abstract) omim.nt IAO:0000310 MONARCH:.well-known/genid/OMIM102480ref6 biolink:NamedThing A reply: the human proacrosin gene. omim.nt IAO:0000310 PMID:1628652 biolink:NamedThing omim.nt IAO:0000013 PMID:1783391 biolink:NamedThing omim.nt IAO:0000013 PMID:1937464 biolink:NamedThing omim.nt IAO:0000013 PMID:2114285 biolink:NamedThing omim.nt IAO:0000013 PMID:2298447 biolink:NamedThing omim.nt IAO:0000013 PMID:2606479 biolink:NamedThing omim.nt IAO:0000013 PMID:6357995 biolink:NamedThing omim.nt IAO:0000013 PMID:7989357 biolink:NamedThing omim.nt IAO:0000013 PMID:9041140 biolink:NamedThing omim.nt IAO:0000013 OBO:CHR_9606chr22q13.33 biolink:NamedThing omim.nt owl:Class UMLS:C1412134 biolink:NamedThing omim.nt owl:Class https://www.ncbi.nlm.nih.gov/gene/49 biolink:NamedThing omim.nt http://omim.org/entry/102490 biolink:NamedThing omim.nt True owl:Class http://omim.org/entry/607323 biolink:NamedThing|biolink:Disease Duane-Radial Ray Syndrome Duane-Radial Ray Syndrome omim.nt DUANE-RADIAL RAY SYNDROME; DRRS|Acrorenoocular Syndrome|Dr Syndrome|Duane Anomaly With Radial Ray Abnormalities and Deafness|Okihiro Syndrome owl:Class http://omim.org/entry/102500 biolink:NamedThing|biolink:Disease Hajdu-Cheney Syndrome Hajdu-Cheney Syndrome omim.nt HAJDU-CHENEY SYNDROME; HJCYS|Acroosteolysis With Osteoporosis and Changes 1N Skull and Mandible|Arthrodentoosteodysplasia|Cheney Syndrome|Serpentine Fibula-Polycystic Kidney Syndrome owl:Class MONARCH:.well-known/genid/OMIM102500ref18 biolink:NamedThing Hajdu-Cheney syndrome associated with severe cardiac valvular and conduction disease. omim.nt IAO:0000310 MONARCH:.well-known/genid/OMIM102500ref28 biolink:NamedThing Acro-osteolysis (Hajdu-Cheney syndrome). In: Bergsma, D.: Skeletal Dysplasias. omim.nt IAO:0000310 MONARCH:.well-known/genid/OMIM102500ref7 biolink:NamedThing Acro-osteolysis (Cheney syndrome). omim.nt IAO:0000310 PMID:11343321 biolink:NamedThing omim.nt IAO:0000013 PMID:1249686 biolink:NamedThing omim.nt IAO:0000013 PMID:1255314 biolink:NamedThing omim.nt IAO:0000013 PMID:14303950 biolink:NamedThing omim.nt IAO:0000013 PMID:15523657 biolink:NamedThing omim.nt IAO:0000013 PMID:17159511 biolink:NamedThing omim.nt IAO:0000013 PMID:1749477 biolink:NamedThing omim.nt IAO:0000013 PMID:18918373 biolink:NamedThing omim.nt IAO:0000013 PMID:21378985 biolink:NamedThing omim.nt IAO:0000013 PMID:21378989 biolink:NamedThing omim.nt IAO:0000013 PMID:21681853 biolink:NamedThing omim.nt IAO:0000013 PMID:21712856 biolink:NamedThing omim.nt IAO:0000013 PMID:3409932 biolink:NamedThing omim.nt IAO:0000013 PMID:3527178 biolink:NamedThing omim.nt IAO:0000013 PMID:3793511 biolink:NamedThing omim.nt IAO:0000013 PMID:4699178 biolink:NamedThing omim.nt IAO:0000013 PMID:4755026 biolink:NamedThing omim.nt IAO:0000013 PMID:707523 biolink:NamedThing omim.nt IAO:0000013 PMID:7158646 biolink:NamedThing omim.nt IAO:0000013 PMID:7747781 biolink:NamedThing omim.nt IAO:0000013 PMID:7778598 biolink:NamedThing omim.nt IAO:0000013 PMID:8203959 biolink:NamedThing omim.nt IAO:0000013 PMID:8276023 biolink:NamedThing omim.nt IAO:0000013 PMID:8445627 biolink:NamedThing omim.nt IAO:0000013 PMID:8723560 biolink:NamedThing omim.nt IAO:0000013 PMID:9184252 biolink:NamedThing omim.nt IAO:0000013 PMID:9220203 biolink:NamedThing omim.nt IAO:0000013 PMID:959555 biolink:NamedThing omim.nt IAO:0000013 PMID:9714016 biolink:NamedThing omim.nt IAO:0000013 UMLS:C0917715 biolink:NamedThing omim.nt owl:Class UMLS:C1838257 biolink:NamedThing omim.nt owl:Class http://omim.org/entry/102510 biolink:NamedThing|biolink:Disease Acropectorovertebral Dysplasia Acropectorovertebral Dysplasia omim.nt ACROPECTOROVERTEBRAL DYSPLASIA; ACRPV|F Syndrome owl:Class MONARCH:.well-known/genid/OMIM102510ref2 biolink:NamedThing The F-form of acropectorovertebral dysplasia: the F-syndrome. omim.nt IAO:0000310 PMID:14985386 biolink:NamedThing omim.nt IAO:0000013 PMID:7677153 biolink:NamedThing omim.nt IAO:0000013 UMLS:C1863307 biolink:NamedThing omim.nt owl:Class ORPHA:957 biolink:NamedThing|biolink:Disease omim.nt owl:Class http://omim.org/entry/102520 biolink:NamedThing|biolink:Disease Acrorenal Syndrome omim.nt ACRORENAL SYNDROME owl:Class MONARCH:.well-known/genid/OMIM102520ref2 biolink:NamedThing Associated acral and renal malformations. omim.nt IAO:0000310 MONARCH:.well-known/genid/OMIM102520ref4 biolink:NamedThing Personal Communication. omim.nt IAO:0000310 PMID:12784306 biolink:NamedThing omim.nt IAO:0000013 PMID:15316969 biolink:NamedThing omim.nt IAO:0000013 PMID:4402497 biolink:NamedThing omim.nt IAO:0000013 UMLS:C3495490 biolink:NamedThing omim.nt owl:Class ORPHA:971 biolink:NamedThing|biolink:Disease omim.nt owl:Class http://omim.org/entry/102525 biolink:NamedThing|biolink:Gene ACRV1 Acrosomal Vesicle Protein 1 omim.nt ACROSOMAL VESICLE PROTEIN 1; ACRV1|Sp-10 Protein owl:Class MONARCH:.well-known/genid/bba03573fb78048017c0 biolink:NamedThing GRCh38chr11-125671521-125680846-Region omim.nt MONARCH:.well-known/genid/bd4cbe2a7d9338ae0c9b faldo:Region MONARCH:.well-known/genid/OMIM102525ref1 biolink:NamedThing Personal Communication. omim.nt IAO:0000310 MONARCH:.well-known/genid/OMIM102525ref3 biolink:NamedThing Assignment of the gene for human intra-acrosomal protein SP-10 (ACRV1) to the p12-q13 region of chromosome 11. (Abstract) omim.nt IAO:0000310 PMID:8288254 biolink:NamedThing omim.nt IAO:0000013 PMID:8373955 biolink:NamedThing omim.nt IAO:0000013 OBO:CHR_9606chr11p12 biolink:NamedThing omim.nt owl:Class UMLS:C1412135 biolink:NamedThing omim.nt owl:Class https://www.ncbi.nlm.nih.gov/gene/56 biolink:NamedThing omim.nt http://omim.org/entry/102530 biolink:NamedThing|biolink:Disease Spermatogenic Failure 6 Spermatogenic Failure 6 omim.nt SPERMATOGENIC FAILURE 6; SPGF6|Acrosome Malformation of Spermatozoa|Globozoospermia|Round-Headed Spermatozoa|Spermatozoa, Round-Headed owl:Class MONARCH:.well-known/genid/OMIM102530ref2 biolink:NamedThing Genetically determined abnormalities of the reproductive system. omim.nt IAO:0000310 MONARCH:.well-known/genid/OMIM102530ref4 biolink:NamedThing Evidence of gene-controlled sterility in bulls. omim.nt IAO:0000310 PMID:12149515 biolink:NamedThing omim.nt IAO:0000013 PMID:1349598 biolink:NamedThing omim.nt IAO:0000013 PMID:15533374 biolink:NamedThing omim.nt IAO:0000013 PMID:17847006 biolink:NamedThing omim.nt IAO:0000013 PMID:3338587 biolink:NamedThing omim.nt IAO:0000013 PMID:4383 biolink:NamedThing omim.nt IAO:0000013 PMID:596658 biolink:NamedThing omim.nt IAO:0000013 PMID:6380341 biolink:NamedThing omim.nt IAO:0000013 PMID:686404 biolink:NamedThing omim.nt IAO:0000013 PMID:9207595 biolink:NamedThing omim.nt IAO:0000013 UMLS:C0403825 biolink:NamedThing omim.nt owl:Class ORPHA:171709 biolink:NamedThing|biolink:Disease omim.nt owl:Class ORPHA:399808 biolink:NamedThing|biolink:Disease omim.nt owl:Class http://www.omim.org/phenotypicSeries/PS258150 biolink:NamedThing|biolink:Disease Spermatogenic failure omim.nt owl:Class http://omim.org/entry/102540.0001 biolink:NamedThing ACTC1, ARG312HIS In a 36-year-old mother and 2 daughters, aged 5 and 2 years, of German ancestry who had dilated cardiomyopathy (CMD1R; {613424}), {22:Olson et al. (1998)} found a G-to-A substitution in codon 312 in exon 5 of the ACTC gene, resulting in an arg312-to-his (R312H) amino acid substitution. A 15-year-old son likewise had inherited the mutation but had not developed dilated cardiomyopathy. omim.nt GENO:0000002 http://omim.org/entry/102540 biolink:NamedThing|biolink:Gene ACTC1 Actin, Alpha, Cardiac Muscle omim.nt ACTIN, ALPHA, CARDIAC MUSCLE; ACTC1|Actc|Actin, Alpha|Smooth Muscle Actin owl:Class ClinVar:RCV000019988 biolink:NamedThing omim.nt ClinVar:RCV000489472 biolink:NamedThing omim.nt ClinVar:RCV000648300 biolink:NamedThing omim.nt ClinVar:RCV001177580 biolink:NamedThing omim.nt dbSNP:rs121912673 biolink:NamedThing omim.nt owl:NamedIndividual http://omim.org/entry/102540#0001 biolink:NamedThing omim.nt http://omim.org/entry/102540.0002 biolink:NamedThing ACTC1, GLU361GLY In a family of Swedish Norwegian ancestry, {22:Olson et al. (1998)} found that a father and son, aged 41 and 14 years, respectively, with dilated cardiomyopathy-1R ({613424}) carried a GAG (glu)-to-GGG (gly) mutation in codon 361 in exon 6 of the ACTC gene. In addition, a 34-year-old woman with a dilated heart and a 9-year-old with borderline heart size also had inherited the mutation. omim.nt GENO:0000002 ClinVar:RCV000019989 biolink:NamedThing omim.nt dbSNP:rs121912674 biolink:NamedThing omim.nt owl:NamedIndividual http://omim.org/entry/102540#0002 biolink:NamedThing omim.nt http://omim.org/entry/102540.0003 biolink:NamedThing ACTC1, ALA295SER In a 3-generation family with autosomal dominant hypertrophic cardiomyopathy ({612098}), {18:Mogensen et al. (1999)} identified a 253G-T transversion in exon 5 of the ACTC gene resulting in an ala295-to-ser substitution. The ala at position 295 is conserved in 19 different species. The expression of the actin mutation in this family gave the impression of a highly penetrant disease with diverse phenotypes and variable age of onset. Only 1 individual of 13 family members carrying the mutant allele was nonpenetrant, and morbidity was low, as only 3 of the 13 carrying the mutant allele had symptoms of the disease. omim.nt GENO:0000002 ClinVar:RCV000019990 biolink:NamedThing omim.nt dbSNP:rs121912675 biolink:NamedThing omim.nt owl:NamedIndividual http://omim.org/entry/102540#0003 biolink:NamedThing omim.nt http://omim.org/entry/102540.0004 biolink:NamedThing ACTC1, HIS90TYR In a child with idiopathic cardiac hypertrophy and presumed sporadic cardiomyopathy ({612098}) who was negative for mutation in 9 of the known CMH genes, {20:Morita et al. (2008)} identified a heterozygous C-to-T transition in the ACTC1 gene resulting in a his90-to-tyr (H90Y) substitution. The parents were not studied. The mutation was not found in unrelated individuals matched by ancestral origin or in more than 1,000 control chromosomes. omim.nt GENO:0000002 ClinVar:RCV000019991 biolink:NamedThing omim.nt ClinVar:RCV000038323 biolink:NamedThing omim.nt ClinVar:RCV000697168 biolink:NamedThing omim.nt dbSNP:rs121912676 biolink:NamedThing omim.nt owl:NamedIndividual http://omim.org/entry/102540#0004 biolink:NamedThing omim.nt http://omim.org/entry/102540.0005 biolink:NamedThing ACTC1, MET123VAL In 20 affected individuals from 2 Swedish families segregating autosomal dominant atrial septal defect (ASD5; {612794}), {16:Matsson et al. (2008)} identified heterozygosity for a 373A-G transition in exon 2 of the ACTC1 gene, predicted to result in a met123-to-val (M123V) substitution. Functional analysis of the M123V-mutant protein showed a reduced affinity for myosin, but retention of actin filament polymerization and actomyosin motor properties. The mutation was not found in 580 control samples. omim.nt GENO:0000002 ClinVar:RCV000019992 biolink:NamedThing omim.nt dbSNP:rs121912677 biolink:NamedThing omim.nt owl:NamedIndividual http://omim.org/entry/102540#0005 biolink:NamedThing omim.nt http://omim.org/entry/102540.0006 biolink:NamedThing ACTC1, 17-BP DEL, NT251 In a 10-year-old girl with a secundum atrial septal defect (ASD5; {612794}), {16:Matsson et al. (2008)} identified heterozygosity for a 17-bp deletion beginning at nucleotide 251 in exon 2 of the ACTC1 gene, predicted to result in a severely truncated protein of 86 amino acids in length. The mutation was also identified in her clinically unaffected 43-year-old father, who was found to have an abnormal echocardiogram with a posteriorly deviated interventricular septum, believed to be associated with a spontaneously closed perimembranous ventricular septal defect, causing aortic valve regurgitation. The deletion was not found in 580 control samples. omim.nt GENO:0000002 ClinVar:RCV000019993 biolink:NamedThing omim.nt dbSNP:rs387906585 biolink:NamedThing omim.nt owl:NamedIndividual http://omim.org/entry/102540#0006 biolink:NamedThing omim.nt http://omim.org/entry/102540.0007 biolink:NamedThing ACTC1, ALA331PRO In a 21-year-old man with hypertrophic cardiomyopathy (CMH11; {612098}), {21:Olson et al. (2000)} identified heterozygosity for a G-C transversion in exon 6 of the ACTC1 gene, resulting in an ala331-to-pro (A331P) substitution at a highly conserved residue. The patient presented at 8 years of age with 2 near-syncopal episodes and was diagnosed with idiopathic CMH. At 10 years of age, he was resuscitated from ventricular fibrillation that occurred while running, and a defibrillator was placed. Cardiac evaluation revealed hypertrophy of the septum and left ventricular apex. His unaffected parents did not carry the mutation, nor was it found in 150 unrelated controls. omim.nt GENO:0000002 ClinVar:RCV000019994 biolink:NamedThing omim.nt ClinVar:RCV001040562 biolink:NamedThing omim.nt dbSNP:rs267606629 biolink:NamedThing omim.nt owl:NamedIndividual http://omim.org/entry/102540#0007 biolink:NamedThing omim.nt http://omim.org/entry/102540.0008 biolink:NamedThing ACTC1, PRO164ALA In a 12-year-old boy with hypertrophic cardiomyopathy-11 ({612098}), {21:Olson et al. (2000)} identified heterozygosity for a C-G transversion in exon 2 of the ACTC1 gene, resulting in a pro164-to-ala (P164A) substitution at a highly conserved residue. The patient was diagnosed with CMH at 17 months of age due to syncopal episodes. He later had occasional episodes of chest pain, dyspnea, and near-syncope, and underwent insertion of a pacemaker. Cardiac evaluation revealed hypertrophy of the septum and left ventricular apex. His unaffected parents did not carry the mutation, nor was it found in 150 unrelated controls. omim.nt GENO:0000002 ClinVar:RCV000019995 biolink:NamedThing omim.nt dbSNP:rs267606628 biolink:NamedThing omim.nt owl:NamedIndividual http://omim.org/entry/102540#0008 biolink:NamedThing omim.nt http://omim.org/entry/102540.0009 biolink:NamedThing ACTC1, GLU101LYS Using a new numbering system, {1:Arad et al. (2005)} designated this mutation GLU101LYS (E101K). In 7 affected members of a 4-generation family segregating autosomal dominant hypertrophic cardiomyopathy (CMH11; {612098}), {21:Olson et al. (2000)} identified heterozygosity for a G-A transition in exon 2 of the ACTC1 gene, resulting in a glu99-to-lys (GLU99LYS) substitution at a highly conserved residue. Apical left ventricular hypertrophy was present in 5 cases and a trabeculated apex in 2 cases; 2 individuals also had marked hypertrophy of the interventricular septum without left ventricular outflow obstruction, and 1 had an atrial septal defect. In affected members of 2 families segregating autosomal dominant apical CMH over 3 generations, {1:Arad et al. (2005)} identified heterozygosity for the E101K mutation in the ACTC1 gene. A shared haplotype was also identified, providing odds greater than 100:1 that E101K represents a founding mutation in the 2 families; however, haplotype data indicated that E101K arose independently in the family reported by {21:Olson et al. (2000)}. Of 18 mutation-positive individuals studied by {1:Arad et al. (2005)}, 2 individuals, ages 10 and 29 years, had no clinical evidence of cardiomyopathy. Isolated apical hypertrophy was found in 5 individuals; 11 others also had mild thickening of the basal segments and/or involvement of the midventricular segment, and 2 also had trabeculation of the apex. Right ventricular endomyocardial biopsy in 1 patient revealed myocyte hypertrophy and disarray with extensive replacement fibrosis that was more marked than that typically seen in CMH associated with other morphologic patterns of hypertrophy. {19:Monserrat et al. (2007)} screened 247 probands with CMH, dilated cardiomyopathy (CMD), or left ventricular noncompaction (see LVNC4, {613424}) for the E101K mutation, and identified the mutation in 4 probands with CMH and 1 with LVNC. The 5 mutation-positive families, 2 of which were previously studied by {1:Arad et al. (2005)}, were all from the same local area in Galicia, Spain, and shared the same 88-bp allele of the intragenic ACTC1 microsatellite marker that cosegregated with disease in the families, suggesting a likely founder effect. Of 46 family members with CMH, 23 fulfilled criteria for LVNC, 22 were diagnosed with apical CMH, and 3 had been diagnosed with restrictive cardiomyopathy. Septal defects were identified in 9 mutation carriers from 4 families (8 atrial defects and 1 ventricular), and were absent in relatives without the mutation. The E101K mutation was not found in 48 unaffected family members. {19:Monserrat et al. (2007)} concluded that LVNC and CMH may appear as overlapping entities, and that E101K should be considered in the genetic diagnosis of LVNC, apical CMH, and septal defects. In a 15-year-old girl and an unrelated 38-year-old woman with LVNC, {13:Klaassen et al. (2008)} identified heterozygosity for the E101K mutation in the ACTC1 gene. Both had inherited the mutation from their affected fathers; haplotype analysis excluded a common ancestor. All 4 patients had noncompaction of the apex and midventricular wall and no other congenital cardiac anomalies. omim.nt GENO:0000002 ClinVar:RCV000019996 biolink:NamedThing omim.nt ClinVar:RCV000019997 biolink:NamedThing omim.nt ClinVar:RCV000029295 biolink:NamedThing omim.nt ClinVar:RCV000157780 biolink:NamedThing omim.nt ClinVar:RCV000684792 biolink:NamedThing omim.nt ClinVar:RCV000769471 biolink:NamedThing omim.nt ClinVar:RCV000844601 biolink:NamedThing omim.nt dbSNP:rs193922680 biolink:NamedThing omim.nt owl:NamedIndividual http://omim.org/entry/102540#0009 biolink:NamedThing omim.nt MONARCH:.well-known/genid/bc8c7e48334a3e1e51b4 biolink:NamedThing GRCh38chr15-34790229-34795548-Region omim.nt MONARCH:.well-known/genid/bdf4e88f0eee1da6afb4 faldo:Region MONARCH:.well-known/genid/OMIM102540ref24 biolink:NamedThing The coexpressed genes for human alpha (ACTA) and cardiac actin (ACTC) are on chromosomes 1 and 15, respectively. (Abstract) omim.nt IAO:0000310 MONARCH:.well-known/genid/OMIM102540ref28 biolink:NamedThing Multigene families of contractile proteins: the actins and myosins. (Abstract) omim.nt IAO:0000310 PMID:10330430 biolink:NamedThing omim.nt IAO:0000013 PMID:10494087 biolink:NamedThing omim.nt IAO:0000013 PMID:10528865 biolink:NamedThing omim.nt IAO:0000013 PMID:10966831 biolink:NamedThing omim.nt IAO:0000013 PMID:1246600 biolink:NamedThing omim.nt IAO:0000013 PMID:16267253 biolink:NamedThing omim.nt IAO:0000013 PMID:1639426 biolink:NamedThing omim.nt IAO:0000013 PMID:17611253 biolink:NamedThing omim.nt IAO:0000013 PMID:17947298 biolink:NamedThing omim.nt IAO:0000013 PMID:18403758 biolink:NamedThing omim.nt IAO:0000013 PMID:18506004 biolink:NamedThing omim.nt IAO:0000013 PMID:23178076 biolink:NamedThing omim.nt IAO:0000013 PMID:2563634 biolink:NamedThing omim.nt IAO:0000013 PMID:2570027 biolink:NamedThing omim.nt IAO:0000013 PMID:2916582 biolink:NamedThing omim.nt IAO:0000013 PMID:2948733 biolink:NamedThing omim.nt IAO:0000013 PMID:3023046 biolink:NamedThing omim.nt IAO:0000013 PMID:3789022 biolink:NamedThing omim.nt IAO:0000013 PMID:6272269 biolink:NamedThing omim.nt IAO:0000013 PMID:6273789 biolink:NamedThing omim.nt IAO:0000013 PMID:6310553 biolink:NamedThing omim.nt IAO:0000013 PMID:6584914 biolink:NamedThing omim.nt IAO:0000013 PMID:6641707 biolink:NamedThing omim.nt IAO:0000013 PMID:6894564 biolink:NamedThing omim.nt IAO:0000013 PMID:7780165 biolink:NamedThing omim.nt IAO:0000013 PMID:9563954 biolink:NamedThing omim.nt IAO:0000013 OBO:CHR_9606chr15q14 biolink:NamedThing omim.nt owl:Class http://omim.org/entry/612098 biolink:NamedThing|biolink:Disease Cardiomyopathy, Familial Hypertrophic, 11 Cardiomyopathy, Familial Hypertrophic, 11 omim.nt CARDIOMYOPATHY, FAMILIAL HYPERTROPHIC, 11; CMH11 owl:Class http://omim.org/entry/612794 biolink:NamedThing|biolink:Disease Atrial Septal Defect 5 Atrial Septal Defect 5 omim.nt ATRIAL SEPTAL DEFECT 5; ASD5 owl:Class http://omim.org/entry/613424 biolink:NamedThing|biolink:Disease Cardiomyopathy, Dilated, 1R Cardiomyopathy, Dilated, 1R omim.nt CARDIOMYOPATHY, DILATED, 1R; CMD1R|Left Ventricular Noncompaction 4 owl:Class http://www.omim.org/phenotypicSeries/PS108800 biolink:NamedThing|biolink:Disease Atrial septal defect omim.nt owl:Class http://www.omim.org/phenotypicSeries/PS115200 biolink:NamedThing|biolink:Disease Dilated cardiomyopathy omim.nt owl:Class http://www.omim.org/phenotypicSeries/PS192600 biolink:NamedThing|biolink:Disease Cardiomyopathy, familial hypertrophic omim.nt owl:Class http://www.omim.org/phenotypicSeries/PS604169 biolink:NamedThing|biolink:Disease Left ventricular noncompaction omim.nt owl:Class UMLS:C1825843 biolink:NamedThing omim.nt owl:Class https://www.ncbi.nlm.nih.gov/gene/70 biolink:NamedThing omim.nt http://omim.org/entry/102545.0001 biolink:NamedThing ACTG2, ARG148SER In 7 affected individuals from over 3 generations of a Finnish family with visceral myopathy (VSCM; {155310}), {3:Lehtonen et al. (2012)} identified heterozygosity for a c.442C-A transversion in exon 5 of the ACTG2 gene, resulting in an arg148-to-ser (R148S) substitution at a highly conserved residue. A 19-year-old member of the family who had only mild abdominal pain and distention and had not yet been diagnosed with visceral myopathy also carried the mutation, but it was not found in 280 Finnish controls. Intestinal smooth muscle from patients showed reduced levels of cytoplasmic ACTG2 compared to controls, as well as abnormal accumulation of the protein in intracellular inclusion bodies. Functional analysis in sarcoma cells showed that the R148S mutant inhibits incorporation of actin monomers into filamentous structures, and gel contraction assay showed substantially decreased contractility with the mutant compared to wildtype. In a 55-year-old Norwegian woman with chronic intestinal pseudoobstruction due to biopsy-proven visceral myopathy, {2:Holla et al. (2014)} performed next-generation sequencing and identified heterozygosity for the ACTG2 R148S mutation, which was not found in her unaffected mother. omim.nt GENO:0000002 http://omim.org/entry/102545 biolink:NamedThing|biolink:Gene ACTG2 Actin, Gamma-2, Smooth Muscle, Enteric omim.nt ACTIN, GAMMA-2, SMOOTH MUSCLE, ENTERIC; ACTG2|Acte|Actin, Alpha-3, Formerly|Actsg owl:Class ClinVar:RCV000119266 biolink:NamedThing omim.nt ClinVar:RCV000210361 biolink:NamedThing omim.nt dbSNP:rs587777383 biolink:NamedThing omim.nt owl:NamedIndividual http://omim.org/entry/102545#0001 biolink:NamedThing omim.nt http://omim.org/entry/102545.0002 biolink:NamedThing ACTG2, ARG178LEU In a 12-year-old girl who had neonatal megacystis, hydronephrosis, and malrotation and pseudoobstruction of the intestine (VSCM; {155310}), {6:Thorson et al. (2014)} identified heterozygosity for a de novo c.533G-T transversion in the ACTG2 gene, resulting in an arg178-to-leu (R178L) substitution at a highly conserved residue within the hinge separating domains III and IV. The mutation was not present in her unaffected parents or in the Exome Variant Server database. Confocal scans of COS-7 cells showed colocalization of wildtype ACTG2 with actin filaments, whereas the R178L mutant showed diffuse localization and poor association with actin filaments. Cell contractility assessment with the mutant showed decreased collagen contraction capacity. omim.nt GENO:0000002 ClinVar:RCV000119267 biolink:NamedThing omim.nt ClinVar:RCV000623686 biolink:NamedThing omim.nt dbSNP:rs587777384 biolink:NamedThing omim.nt owl:NamedIndividual http://omim.org/entry/102545#0002 biolink:NamedThing omim.nt http://omim.org/entry/102545.0003 biolink:NamedThing ACTG2, ARG178CYS In a male infant with megacystis and intestinal pseudoobstruction (VSCM; {155310}), {6:Thorson et al. (2014)} identified heterozygosity for a de novo c.532C-T transition in the ACTG2 gene, resulting in an arg178-to-cys (R178C) substitution at a highly conserved residue within the hinge separating domains III and IV. Confocal scans of COS-7 cells showed colocalization of wildtype ACTG2 with actin filaments, whereas the R178C mutant showed diffuse localization and poor association with actin filaments. Cell contractility assessment with the mutant showed decreased collagen contraction capacity. In a 3-year-old boy prenatally diagnosed with fetal megacystis, {8:Wangler et al. (2014)} identified heterozygosity for a de novo R178C mutation in exon 6 of the ACTG2 gene. The patient had surgery for malrotation shortly after birth, and required 18 hours of total parenteral nutrition (TPN) per day and bladder catheterization every 4 to 6 hours. He also had an undescended testicle. omim.nt GENO:0000002 ClinVar:RCV000119269 biolink:NamedThing omim.nt ClinVar:RCV000326799 biolink:NamedThing omim.nt dbSNP:rs78001248 biolink:NamedThing omim.nt owl:NamedIndividual http://omim.org/entry/102545#0003 biolink:NamedThing omim.nt http://omim.org/entry/102545.0004 biolink:NamedThing ACTG2, ARG178HIS In a 6-year-old girl prenatally diagnosed with fetal megacystis (VSCM; {155310}), {8:Wangler et al. (2014)} identified heterozygosity for a de novo c.533G-A transition in exon 6 of the ACTG2 gene, resulting in an arg178-to-his (R178H) substitution. At birth, the patient had bilious vomiting and was found to have malrotation and microcolon; she required TPN and bladder catheterization throughout her life. {8:Wangler et al. (2014)} also detected heterozygosity for the R178H mutation in the patient's mother and in another patient; no clinical information was provided for the latter 2 patients. omim.nt GENO:0000002 ClinVar:RCV000119270 biolink:NamedThing omim.nt ClinVar:RCV000190653 biolink:NamedThing omim.nt http://omim.org/entry/102545#0004 biolink:NamedThing omim.nt http://omim.org/entry/102545.0005 biolink:NamedThing ACTG2, ARG40HIS In 5 affected individuals from over 4 generations of a family with constipation, intestinal dysmotility, megacystis, and megacolon (VSCM; {155310}), {8:Wangler et al. (2014)} identified heterozygosity for a c.119G-A transition in exon 2 of the ACTG2 gene, resulting in an arg40-to-his (R40H) substitution. The proband, a 1-year-old boy with fetal megacystis, underwent postnatal surgery for malrotation; although he could feed orally, he required bladder catheterization. His father and paternal grandmother, both of whom also carried the mutation, had lifelong constipation and dysmotility; the father underwent surgery for gastrointestinal obstruction and suspected superior mesenteric artery occlusion, whereas the paternal grandmother underwent removal of megacolon in adulthood. {8:Wangler et al. (2014)} also detected heterozygosity for a de novo R40H mutation in a 16-year-old boy who had fetal megacystis and was treated by prenatal bladder diversion; after birth, he was fed by mouth but had frequent constipation and underwent colostomy at age 2 years. Manometric studies at 2 and 4 years of age show no peristaltic activity. At age 16 years, he had lifetime dependence on bladder catheterization but was able to tolerate meals. omim.nt GENO:0000002 ClinVar:RCV000119271 biolink:NamedThing omim.nt ClinVar:RCV000680451 biolink:NamedThing omim.nt ClinVar:RCV000851221 biolink:NamedThing omim.nt ClinVar:RCV001091889 biolink:NamedThing omim.nt dbSNP:rs587777386 biolink:NamedThing omim.nt owl:NamedIndividual http://omim.org/entry/102545#0005 biolink:NamedThing omim.nt http://omim.org/entry/102545.0006 biolink:NamedThing ACTG2, ARG40CYS In a 16-year-old girl with fetal megacystis who underwent vesicostomy at birth and who also had microcolon (VSCM; {155310}) requiring total parenteral nutrition (TPN), {8:Wangler et al. (2014)} identified a de novo c.118C-T transition in exon 2 of the ACTG2 gene, resulting in an arg40-to-cys (R40C) substitution. Despite a period of relative improvement beginning at age 4 years during which she did not require TPN, after age 13, she developed complications, including bowel perforation and multiple infections. At 16 years of age, she was dependent on TPN for 12 hours a day, with additional feedings by gastrostomy, and required bladder catheterization. omim.nt GENO:0000002 ClinVar:RCV000119268 biolink:NamedThing omim.nt ClinVar:RCV000493883 biolink:NamedThing omim.nt dbSNP:rs587777385 biolink:NamedThing omim.nt owl:NamedIndividual http://omim.org/entry/102545#0006 biolink:NamedThing omim.nt http://omim.org/entry/102545.0007 biolink:NamedThing ACTG2, ARG257CYS In 3 unrelated children diagnosed either prenatally or in infancy with megacystis (VSCM; {155310}), 2 of whom also had microcolon and 1 of whom also had intestinal malrotation, {8:Wangler et al. (2014)} identified a de novo c.769C-T transition in exon 7 of the ACTG2 gene, resulting in an arg257-to-cys (R257C) substitution. All 3 patients required total parenteral nutrition (TPN) and 2 required bladder catheterization. One patient developed chronic pancreatitis and died at age 11 years due to infectious complications; another underwent transplantation of small bowel, stomach, pancreas, and colon at 7 years of age and was clinically well at age 13 years, with an ileostomy and a regimen of double-voiding twice a day. The third patient was TPN- and catheterization-dependent at 1 year of age. {8:Wangler et al. (2014)} also identified the R257C mutation in a girl with prenatal megacystis, who had a period of normal bowel and bladder function in the first years of life, followed by progressive pseudoobstruction, and who died at 13 years of age. The mutation was inherited from her mother, for whom medical records were not available, but who was reported to have had irritable bowel syndrome. omim.nt GENO:0000002 ClinVar:RCV000119272 biolink:NamedThing omim.nt ClinVar:RCV000190747 biolink:NamedThing omim.nt ClinVar:RCV000210354 biolink:NamedThing omim.nt ClinVar:RCV000413107 biolink:NamedThing omim.nt ClinVar:RCV000680452 biolink:NamedThing omim.nt ClinVar:RCV000851220 biolink:NamedThing omim.nt dbSNP:rs587777387 biolink:NamedThing omim.nt owl:NamedIndividual http://omim.org/entry/102545#0007 biolink:NamedThing omim.nt http://omim.org/entry/102545.0008 biolink:NamedThing ACTG2, PHE110LEU In 2 sisters with intestinal hypomotility (VSCM; {155310}), {8:Wangler et al. (2014)} identified heterozygosity for a c.330C-A transversion in alternative exon 4 of the ACTG2 gene, resulting in a phe110-to-leu (F110L) substitution. One of the sisters had multiple abdominal surgeries for obstruction and intermittently required TPN from 17 years of age, but did not require bladder catheterization; the other sister experienced years of intestinal symptoms and underwent endoscopy, the results of which suggested gastroparesis, but did not have any surgery. The mutation was not found in their unaffected mother; no information was available regarding their deceased father. omim.nt GENO:0000002 ClinVar:RCV000202559 biolink:NamedThing omim.nt dbSNP:rs768290597 biolink:NamedThing omim.nt owl:NamedIndividual http://omim.org/entry/102545#0008 biolink:NamedThing omim.nt http://omim.org/entry/102545.0009 biolink:NamedThing ACTG2, TYR134ASN In a 25-year-old man who had fetal megacystis with absent abdominal wall musculature noted at birth (VSCM; {155310}), {8:Wangler et al. (2014)} identified a de novo c.412T-A transversion in exon 5 of the ACTG2 gene, resulting in a tyr134-to-asn (Y134N) substitution. The patient was placed on total parenteral nutrition (TPN) in infancy and underwent surgeries for intestinal pseudoobstruction at ages 6 months and 4 years. Additional health issues included ventricular dysfunction, asthma, pectus excavatum requiring surgery, osteoporosis, and endocrine abnormalities. omim.nt GENO:0000002 ClinVar:RCV000119274 biolink:NamedThing omim.nt dbSNP:rs587777388 biolink:NamedThing omim.nt owl:NamedIndividual http://omim.org/entry/102545#0009 biolink:NamedThing omim.nt MONARCH:.well-known/genid/babdbd36b2416875a85c biolink:NamedThing GRCh38chr2-73893007-73919864-Region omim.nt MONARCH:.well-known/genid/b87bbba2c6abcafa2645 faldo:Region PMID:12567189 biolink:NamedThing omim.nt IAO:0000013 PMID:1710027 biolink:NamedThing omim.nt IAO:0000013 PMID:22960657 biolink:NamedThing omim.nt IAO:0000013 PMID:24337657 biolink:NamedThing omim.nt IAO:0000013 PMID:24676022 biolink:NamedThing omim.nt IAO:0000013 PMID:24777424 biolink:NamedThing omim.nt IAO:0000013 PMID:7759108 biolink:NamedThing omim.nt IAO:0000013 PMID:8530021 biolink:NamedThing omim.nt IAO:0000013 OBO:CHR_9606chr2p13.1 biolink:NamedThing omim.nt owl:Class http://omim.org/entry/155310 biolink:NamedThing|biolink:Disease Visceral Myopathy Visceral Myopathy omim.nt VISCERAL MYOPATHY; VSCM|Infantile Visceral Myopathy|Megaduodenum And/Or Megacystis|Pseudoobstruction, Idiopathic Intestinal owl:Class UMLS:C1332010 biolink:NamedThing omim.nt owl:Class https://www.ncbi.nlm.nih.gov/gene/72 biolink:NamedThing omim.nt http://omim.org/entry/102550 biolink:NamedThing omim.nt True owl:Class http://omim.org/entry/102630 biolink:NamedThing|biolink:Gene ACTB ~20 pseudogenes also; mutation identified in twin DJO patients|Actin, Beta omim.nt ACTIN, BETA; ACTB|Actin, Cytoplasmic, 1|Beta-Actin owl:Class http://omim.org/entry/102560.0001 biolink:NamedThing ACTG1, THR89ILE In 17 affected members of a family segregating autosomal dominant progressive sensorineural hearing loss ({604717}), {20:Zhu et al. (2003)} identified a 340C-T transition in exon 3 of the processed ACTG1 mRNA, resulting in a thr89-to-ile (T89I) substitution in subdomain 1. The mutation is in an alpha helix that is thought to participate in the binding of fimbrin (PLS3; {300131}), a bundling protein. This amino acid is perfectly conserved in cytoplasmic actin, in species ranging from nematodes to mammals. The mutation was not identified in 220 control chromosomes. omim.nt GENO:0000002 http://omim.org/entry/102560 biolink:NamedThing|biolink:Gene ACTG1 Actin, Gamma-1 omim.nt ACTIN, GAMMA-1; ACTG1|Actin, Cytoplasmic, 2|Actin, Gamma|Cytoskeletal Gamma-Actin owl:Class ClinVar:RCV000019980 biolink:NamedThing omim.nt dbSNP:rs28999111 biolink:NamedThing omim.nt owl:NamedIndividual http://omim.org/entry/102560#0001 biolink:NamedThing omim.nt http://omim.org/entry/102560.0002 biolink:NamedThing ACTG1, LYS118MET In 8 affected members of a family segregating autosomal dominant progressive sensorineural hearing loss ({604717}), {20:Zhu et al. (2003)} identified a lys118-to-met (K118M) mutation in exon 3 of the ACTG1 gene. The substitution occurs in subdomain 1 of the protein near the fimbrin (PLS3; {300131})-binding domain. The family had been reported by {18:Yang and Smith (2000)}. omim.nt GENO:0000002 ClinVar:RCV000019981 biolink:NamedThing omim.nt ClinVar:RCV000680835 biolink:NamedThing omim.nt dbSNP:rs104894544 biolink:NamedThing omim.nt owl:NamedIndividual http://omim.org/entry/102560#0002 biolink:NamedThing omim.nt http://omim.org/entry/102560.0003 biolink:NamedThing ACTG1, PRO332ALA In 8 affected members of a family segregating autosomal dominant progressive sensorineural hearing loss ({604717}), {20:Zhu et al. (2003)} identified a pro332-to-ala (P332A) missense mutation in the ACTG1 gene. The family had been reported by {18:Yang and Smith (2000)}. P332A is in a 3-amino acid loop in subdomain 3 of the protein; this loop may be part of the primary contact site for myosin. omim.nt GENO:0000002 ClinVar:RCV000019982 biolink:NamedThing omim.nt dbSNP:rs104894545 biolink:NamedThing omim.nt owl:NamedIndividual http://omim.org/entry/102560#0003 biolink:NamedThing omim.nt http://omim.org/entry/102560.0004 biolink:NamedThing ACTG1, PRO264LEU In 11 affected members of a family segregating autosomal dominant progressive sensorineural hearing loss ({604717}) reported by {3:DeWan et al. (2003)}, {20:Zhu et al. (2003)} identified a pro264-to-leu (P264L) missense mutation in the gamma-actin gene. P264L is in a proposed hydrophobic plug for interstrand interactions in subdomain 4 of the protein, near the actin self-assembly site. Affected members had an early age at onset and rapid progression of hearing loss. omim.nt GENO:0000002 ClinVar:RCV000019983 biolink:NamedThing omim.nt ClinVar:RCV000680834 biolink:NamedThing omim.nt dbSNP:rs104894546 biolink:NamedThing omim.nt owl:NamedIndividual http://omim.org/entry/102560#0004 biolink:NamedThing omim.nt http://omim.org/entry/102560.0005 biolink:NamedThing ACTG1, THR278ILE In a Dutch family with autosomal dominant deafness linked to the DFNA20 region ({604717}), {17:Van Wijk et al. (2003)} found that affected members had an 833C-T transition in exon 5 of the ACTG1 gene, resulting in a thr278-to-ile (T278I) substitution. The mutation was identified in helix 9 of the modeled protein structure and was predicted to have a small but significant effect on the gamma-1 actin structure owing to its close proximity to a methionine residue at position 313 in helix 11. The authors suggested that the mutation would interfere with actin polymerization. omim.nt GENO:0000002 ClinVar:RCV000019984 biolink:NamedThing omim.nt dbSNP:rs28999112 biolink:NamedThing omim.nt owl:NamedIndividual http://omim.org/entry/102560#0005 biolink:NamedThing omim.nt http://omim.org/entry/102560.0006 biolink:NamedThing ACTG1, VAL370ALA In 19 affected members of a large Norwegian family with autosomal dominant DFNA20 ({604717}), {11:Rendtorff et al. (2006)} identified a heterozygous 1109T-C transition in exon 6 of the ACTG1 gene, resulting in a val370-to-ala (V370A) substitution in a highly conserved region. Functional expression studies in yeast showed that the mutant protein suppressed growth; computer modeling suggested that the V370A substitution impaired hydrophobic interactions and destabilized the position of the C-terminal tail of the protein. The family had originally been reported by {14:Teig (1968)}. omim.nt GENO:0000002 ClinVar:RCV000019985 biolink:NamedThing omim.nt dbSNP:rs104894547 biolink:NamedThing omim.nt owl:NamedIndividual http://omim.org/entry/102560#0006 biolink:NamedThing omim.nt http://omim.org/entry/102560.0007 biolink:NamedThing ACTG1, LYS118ASN In a Spanish father and daughter with autosomal dominant deafness ({604717}), {9:Morin et al. (2009)} identified heterozygosity for a 354G-C transversion in exon 3 of the ACTG1 gene, resulting in a lys118-to-asn (K118N) substitution in subdomain 1. The mutation was not found in 100 normal unrelated Spanish controls. Both father and daughter showed bilateral, symmetric, progressive sensorineural hearing loss at mid and high frequencies of postlingual onset. The daughter had onset in the third decade, and the father had even later onset. {9:Morin et al. (2009)} showed that the K118N mutation had a very mild effect in yeast. In transiently transfected NIH3T3 cells, K118N-mutant actin was normally incorporated into cytoskeleton structures, although cytoplasmic aggregates were also observed indicating an element of abnormality caused by the K118N mutation in vivo. Gene-gun mediated expression of K118N mutant in mouse cochlear hair cells resulted in no gross alteration in cytoskeletal structures or the morphology of stereocilia. {9:Morin et al. (2009)} supported the hypothesis that the postlingual and progressive nature of the DFNA20/26 hearing loss may be the result of a progressive deterioration of the hair cell cytoskeleton over time. omim.nt GENO:0000002 ClinVar:RCV000019986 biolink:NamedThing omim.nt ClinVar:RCV000059722 biolink:NamedThing omim.nt dbSNP:rs267606630 biolink:NamedThing omim.nt owl:NamedIndividual http://omim.org/entry/102560#0007 biolink:NamedThing omim.nt http://omim.org/entry/102560.0008 biolink:NamedThing ACTG1, GLU241LYS In 4 affected members of a Spanish family with autosomal dominant deafness ({604717}), {9:Morin et al. (2009)} identified heterozygosity for a 721G-A transition in exon 4 of the ACTG1 gene, resulting in a glu241-to-lys (E241K) substitution in subdomain 4. The mutation was not found in 100 normal unrelated Spanish controls. The affected members were referred for hearing loss at school age, with the earliest individual referred at age 6 years. All showed postlingual, bilateral, symmetric, progressive sensorineural hearing loss at mid and high frequencies. In yeast, the E241K mutation resulted in a severe phenotype characterized by a highly compromised ability to grow on glycerol as a carbon source, an aberrant multivacuolar pattern, and deposition of thick F-actin bundles randomly in the cell. The latter feature is consistent with the unusual tendency of the E241K mutant to form bundles in vitro, although this propensity to bundle was neutralized by tropomyosin (TPM1; {191010}) and the E241K filament bundles were hypersensitive to severing in the presence of cofilin (CFL1; {601442}). In transiently transfected NIH3T3 cells, E241K-mutant actin was normally incorporated into cytoskeleton structures, although cytoplasmic aggregates were also observed indicating an element of abnormality caused by the mutations in vivo. Gene-gun mediated expression of the E241K mutant in mouse cochlear hair cells resulted in no gross alteration in cytoskeletal structures or the morphology of stereocilia. {9:Morin et al. (2009)} supported the hypothesis that the postlingual and progressive nature of the DFNA20/26 hearing loss may be the result of a progressive deterioration of the hair cell cytoskeleton over time. omim.nt GENO:0000002 ClinVar:RCV000019987 biolink:NamedThing omim.nt ClinVar:RCV000059728 biolink:NamedThing omim.nt ClinVar:RCV000211710 biolink:NamedThing omim.nt dbSNP:rs267606631 biolink:NamedThing omim.nt owl:NamedIndividual http://omim.org/entry/102560#0008 biolink:NamedThing omim.nt http://omim.org/entry/102560.0009 biolink:NamedThing ACTG1, SER155PHE In 3 unrelated individuals with Baraitser-Winter syndrome-2 (BRWS2; {614583}), {12:Riviere et al. (2012)} identified a heterozygous C-to-T transition at nucleotide 464 of the ACTG1 gene, resulting in a ser-to-phe substitution at codon 155 (S155F). This mutation was proven to have occurred de novo in 2 of the 3; in the third, parental DNA was not available. One of these 3 patients, LP98-096, was reported by {1:Baraitser and Winter (1988)}. This mutation was not identified in 224 control exomes. {12:Riviere et al. (2012)} studied lymphoblastoid cell lines from individuals carrying the S155F mutation and demonstrated that these had increased F-actin content and multiple, anomalous F-actin-rich filopodia-like protrusions compared to control cells, resulting in increased cell perimeter. Cell lines also showed increased sensitivity to treatment with latrunculin A. omim.nt GENO:0000002 ClinVar:RCV000022422 biolink:NamedThing omim.nt ClinVar:RCV000059726 biolink:NamedThing omim.nt dbSNP:rs281875326 biolink:NamedThing omim.nt owl:NamedIndividual http://omim.org/entry/102560#0009 biolink:NamedThing omim.nt http://omim.org/entry/102560.0010 biolink:NamedThing ACTG1, THR120ILE {12:Riviere et al. (2012)} reported a single individual with Baraitser-Winter syndrome-2 (BRWS2; {614583}) carrying a de novo heterozygous mutation in ACTG1, a C-to-T transition at nucleotide 359 resulting in a thr-to-ile substitution at codon 120 (T120I). This mutation was not observed in 244 other exomes sequenced. omim.nt GENO:0000002 ClinVar:RCV000022423 biolink:NamedThing omim.nt ClinVar:RCV000059723 biolink:NamedThing omim.nt dbSNP:rs281875325 biolink:NamedThing omim.nt owl:NamedIndividual http://omim.org/entry/102560#0010 biolink:NamedThing omim.nt http://omim.org/entry/102560.0011 biolink:NamedThing ACTG1, ALA135VAL In an individual with Baraitser-Winter syndrome-2 (BRWS2; {614583}), {12:Riviere et al. (2012)} identified a heterozygous C-to-T transition at nucleotide 404 of the ACTG1 gene, resulting in an ala-to-val substitution at codon 135 (A135V). This mutation occurred de novo in the patient and was not observed in 192 other exomes sequenced. omim.nt GENO:0000002 ClinVar:RCV000022424 biolink:NamedThing omim.nt ClinVar:RCV000059725 biolink:NamedThing omim.nt dbSNP:rs11549190 biolink:NamedThing omim.nt owl:NamedIndividual http://omim.org/entry/102560#0011 biolink:NamedThing omim.nt http://omim.org/entry/102560.0012 biolink:NamedThing ACTG1, THR203LYS In an individual with Baraitser-Winter syndrome-2 (BRWS2; {614583}), {12:Riviere et al. (2012)} identified a heterozygous C-to-A transversion at nucleotide 608 of the ACTG1 gene, resulting in an thr-to-lys substitution at codon 203 (T203K). This mutation occurred de novo in the patient and was not observed in 203 other exomes sequenced. omim.nt GENO:0000002 ClinVar:RCV000022425 biolink:NamedThing omim.nt ClinVar:RCV000059727 biolink:NamedThing omim.nt dbSNP:rs281875327 biolink:NamedThing omim.nt owl:NamedIndividual http://omim.org/entry/102560#0012 biolink:NamedThing omim.nt http://omim.org/entry/102560.0013 biolink:NamedThing ACTG1, ARG254TRP In an individual with Baraitser-Winter syndrome-2 (BRWS2; {614583}), {12:Riviere et al. (2012)} identified a heterozygous C-to-T transition at nucleotide 760 of the ACTG1 gene, resulting in an arg-to-trp substitution at codon 254 (R254W). This mutation occurred de novo in the patient and was not observed in 195 other exomes sequenced. omim.nt GENO:0000002 ClinVar:RCV000022426 biolink:NamedThing omim.nt ClinVar:RCV000059729 biolink:NamedThing omim.nt ClinVar:RCV001291054 biolink:NamedThing omim.nt dbSNP:rs281875328 biolink:NamedThing omim.nt owl:NamedIndividual http://omim.org/entry/102560#0013 biolink:NamedThing omim.nt http://omim.org/entry/102560.0014 biolink:NamedThing ACTG1, ARG256TRP In an individual with Baraitser-Winter syndrome-2 (BRWS2; {614583}), {12:Riviere et al. (2012)} identified a heterozygous C-to-T transition at nucleotide 766 of the ACTG1 gene, resulting in an arg-to-trp substitution at codon 256 (R256W). This mutation occurred de novo in the patient and was not observed in 184 other exomes sequenced. omim.nt GENO:0000002 ClinVar:RCV000022427 biolink:NamedThing omim.nt ClinVar:RCV000059730 biolink:NamedThing omim.nt ClinVar:RCV000770804 biolink:NamedThing omim.nt ClinVar:RCV001291159 biolink:NamedThing omim.nt dbSNP:rs281875329 biolink:NamedThing omim.nt owl:NamedIndividual http://omim.org/entry/102560#0014 biolink:NamedThing omim.nt MONARCH:.well-known/genid/ba7c6503bea04cd1fe47 biolink:NamedThing GRCh38chr17-81509970-81512798-Region omim.nt MONARCH:.well-known/genid/ba26dfcf37b0b0211cbe faldo:Region MONARCH:.well-known/genid/OMIM102560ref18 biolink:NamedThing A novel locus DFNA26 maps to chromosome 17q25 in two unrelated families with progressive autosomal dominant hearing loss. (Abstract) omim.nt IAO:0000310 PMID:10524632 biolink:NamedThing omim.nt IAO:0000013 PMID:10903505 biolink:NamedThing omim.nt IAO:0000013 PMID:11474115 biolink:NamedThing omim.nt IAO:0000013 PMID:12388543 biolink:NamedThing omim.nt IAO:0000013 PMID:12519370 biolink:NamedThing omim.nt IAO:0000013 PMID:13680526 biolink:NamedThing omim.nt IAO:0000013 PMID:14684684 biolink:NamedThing omim.nt IAO:0000013 PMID:16773128 biolink:NamedThing omim.nt IAO:0000013 PMID:16950128 biolink:NamedThing omim.nt IAO:0000013 PMID:19477959 biolink:NamedThing omim.nt IAO:0000013 PMID:20847274 biolink:NamedThing omim.nt IAO:0000013 PMID:22366783 biolink:NamedThing omim.nt IAO:0000013 PMID:2837653 biolink:NamedThing omim.nt IAO:0000013 PMID:3351890 biolink:NamedThing omim.nt IAO:0000013 PMID:3472224 biolink:NamedThing omim.nt IAO:0000013 PMID:3737401 biolink:NamedThing omim.nt IAO:0000013 PMID:5654493 biolink:NamedThing omim.nt IAO:0000013 PMID:6865942 biolink:NamedThing omim.nt IAO:0000013 PMID:8941379 biolink:NamedThing omim.nt IAO:0000013 OBO:CHR_9606chr17q25.3 biolink:NamedThing omim.nt owl:Class http://omim.org/entry/604717 biolink:NamedThing|biolink:Disease Deafness, Autosomal Dominant 20 Deafness, Autosomal Dominant 20 omim.nt DEAFNESS, AUTOSOMAL DOMINANT 20; DFNA20|Dfna26 owl:Class http://omim.org/entry/614583 biolink:NamedThing|biolink:Disease Baraitser-Winter Syndrome 2 Baraitser-Winter Syndrome 2 omim.nt BARAITSER-WINTER SYNDROME 2; BRWS2 owl:Class http://www.omim.org/phenotypicSeries/PS124900 biolink:NamedThing|biolink:Disease Deafness, autosomal dominant omim.nt owl:Class http://www.omim.org/phenotypicSeries/PS243310 biolink:NamedThing|biolink:Disease Baraitser-Winter syndrome omim.nt owl:Class UMLS:C1412149 biolink:NamedThing omim.nt owl:Class https://www.ncbi.nlm.nih.gov/gene/71 biolink:NamedThing omim.nt http://omim.org/entry/102565.0001 biolink:NamedThing FLNC, TRP2710TER, c.8130G-A In affected members of a German family with autosomal dominant myofibrillar myopathy-5 (MFM5; {609524}), {14:Vorgerd et al. (2005)} identified a heterozygous 8130G-A transition in exon 48 of the FLNC gene, resulting in a trp2710-to-ter (W2710X) substitution. The mutation leads to a truncation of the filamin C immunoglobulin domain that is responsible for dimerization. Functional expression studies showed that the W2710X protein had improper folding, was unable to form dimers, and showed abnormal aggregation. The findings implied that dimer formation is essential for the biologic function of filamin. The mutation was not identified in 220 control chromosomes. By in vitro functional expression studies, {9:Lowe et al. (2007)} showed that W2710X-mutant protein was less stable and more susceptible to proteolysis compared to wildtype. The mutant protein did not dimerize properly and formed filamin aggregates in cultured cells. Aggregation of mutant protein did not affect dimerization of wildtype filamin C, and the mutant protein still showed normal binding to actin and sarcoglycans. omim.nt GENO:0000002 http://omim.org/entry/102565 biolink:NamedThing|biolink:Gene FLNC Filamin C omim.nt FILAMIN C; FLNC|Abpa|Actin-Binding Protein 280, Autosomal Form|Actin-Binding Protein-Like|Filamin 2|Filamin, Gamma owl:Class ClinVar:RCV000019978 biolink:NamedThing omim.nt ClinVar:RCV001052798 biolink:NamedThing omim.nt ClinVar:RCV001091493 biolink:NamedThing omim.nt dbSNP:rs121909518 biolink:NamedThing omim.nt owl:NamedIndividual http://omim.org/entry/102565#0001 biolink:NamedThing omim.nt http://omim.org/entry/102565.0002 biolink:NamedThing FLNC, 12-BP DEL, NT2997 In a German mother and daughter with autosomal dominant myofibrillar myopathy-5 ({609524}), {10:Shatunov et al. (2009)} identified a heterozygous 12-bp deletion (2997_3008del) in exon 18 of the FLNC gene, predicted to result in an in-frame deletion of 4 residues (val930 to thr933) in the seventh repeat and confirmed by RT-PCR analysis of muscle tissue from the affected daughter. The phenotype was characterized by adult-onset muscle weakness initially involving proximal muscles of the lower limbs and spreading to the upper limbs and distal muscles of lower extremities. Both had paraspinal and abdominal muscle involvement and winging of the scapula. Cardiac and respiratory muscles were not affected. Skeletal muscle biopsy from the daughter showed marked variation in fiber size, some fibers with internal nuclei, and type 1 fiber predominance. Several fibers showed polymorphous hyaline and nonhyaline myofibrillary FLNC-positive inclusions with a convoluted, serpentine appearance. Ultrastructural examination showed major myofibrillar abnormalities, with accumulation of Z disc debris, granulofilamentous material, and nemaline rods. There were also mitochondrial aggregates. omim.nt GENO:0000002 ClinVar:RCV000019979 biolink:NamedThing omim.nt dbSNP:rs1562995872 biolink:NamedThing omim.nt owl:NamedIndividual http://omim.org/entry/102565#0002 biolink:NamedThing omim.nt http://omim.org/entry/102565.0003 biolink:NamedThing FLNC, MET251THR In affected members of a large Australian family with autosomal dominant distal myopathy-4 (MPD4; {614065}) originally reported by {15:Williams et al. (2005)}, {5:Duff et al. (2011)} identified a heterozygous 752T-C transition in exon 4 of the FLNC gene, resulting in a met251-to-thr (M251T) substitution in a highly conserved residue in the CH2 domain in the actin-binding domain. The mutation was not found in 400 control chromosomes. The mutant protein had slightly decreased thermal stability and showed increased actin-binding activity compared to the wildtype protein. Transfection of the mutant M251T protein into cells showed significantly decreased nuclear localization compared to wildtype and resulted in the formation of intracellular protein aggregates. {5:Duff et al. (2011)} concluded that the disease mechanism somehow involves increased affinity for actin. The phenotype was characterized by adult onset of distal muscle weakness and atrophy affecting the upper and lower limbs, with nonspecific findings on muscle biopsy. omim.nt GENO:0000002 ClinVar:RCV000022428 biolink:NamedThing omim.nt dbSNP:rs387906586 biolink:NamedThing omim.nt owl:NamedIndividual http://omim.org/entry/102565#0003 biolink:NamedThing omim.nt http://omim.org/entry/102565.0004 biolink:NamedThing FLNC, ALA193THR In affected members of an Italian family with autosomal dominant distal myopathy-4 (MPD4; {614065}), {5:Duff et al. (2011)} identified a heterozygous 577G-A transition in exon 2 of the FLNC gene, resulting in an ala193-to-thr (A193T) substitution in a highly conserved residue in the CH2 domain in the actin-binding domain. The mutation was not found in 204 control chromosomes. The mutant protein had slightly decreased thermal stability and showed increased actin-binding activity compared to the wildtype protein. Nuclear localization was unaltered, but transfection resulted in the formation of intracellular protein aggregates. {5:Duff et al. (2011)} concluded that the disease mechanism somehow involves increased affinity for actin. The phenotype was characterized by adult onset of distal muscle weakness and atrophy affecting the upper and lower limbs, with nonspecific findings on muscle biopsy. omim.nt GENO:0000002 ClinVar:RCV000022429 biolink:NamedThing omim.nt ClinVar:RCV000442836 biolink:NamedThing omim.nt ClinVar:RCV000600715 biolink:NamedThing omim.nt dbSNP:rs387906587 biolink:NamedThing omim.nt owl:NamedIndividual http://omim.org/entry/102565#0004 biolink:NamedThing omim.nt http://omim.org/entry/102565.0005 biolink:NamedThing FLNC, ALA1539THR In all affected members of 2 Spanish families with hypertrophic cardiomyopathy (CMH26; {617047}) and a history of sudden death, {12:Valdes-Mas et al. (2014)} identified heterozygosity for a G-A transition ({VAR chr7.128,488,649G-A, GRCh37}) in the FLNC gene, resulting in an ala1539-to-thr (A1539T) substitution at a highly conserved residue within a C-terminal rod repeat. The mutation showed reduced penetrance, being detected in 2 asymptomatic family members from 1 of the families, a 12-year-old girl and a 52-year-old man, both of whom had normal electrocardiography and echocardiogram. The variant was not found in more than 400 Spanish controls, or the 1000 Genomes Project or Exome Sequencing Project databases. Cardiac muscle histology from 1 family member who underwent heart transplantation showed marked sarcomeric abnormalities, including myofibrillar disarray, sarcomeric aggregates, and fibrosis; immunohistochemical staining confirmed the presence of filamin C in the sarcomeric aggregates. In contrast, skeletal muscle biopsy from an affected individual showed intact sarcomeric structures and normal ATPase, SDH, and NADH staining, as well as the absence of the characteristic small aggregates of myofibrillar myopathy. When the A1539T mutant was expressed in rat neonatal cardiac myocytes, large perinuclear filamin-C aggregates were observed. Overexpression of A1539T in C2C12 mouse skeletal muscle myoblasts also resulted in formation of protein aggregates, although they were smaller than those observed in cardiac myocytes, supporting a model in which interaction of these mutants with tissue-specific proteins contributes to the predominant cardiac phenotype. omim.nt GENO:0000002 ClinVar:RCV000239536 biolink:NamedThing omim.nt dbSNP:rs1562999443 biolink:NamedThing omim.nt owl:NamedIndividual http://omim.org/entry/102565#0005 biolink:NamedThing omim.nt http://omim.org/entry/102565.0006 biolink:NamedThing FLNC, HIS2315ASN In 3 affected sibs from a Spanish family with hypertrophic cardiomyopathy (CMH26; {617047}), {12:Valdes-Mas et al. (2014)} identified heterozygosity for a C-A transversion ({VAR chr7.128,494,682C-A, GRCh37}) in the FLNC gene, resulting in a his2315-to-asn (H2315N) substitution at a highly conserved residue within a C-terminal rod repeat. The mutation showed reduced penetrance, being detected in 1 asymptomatic family member, a 29-year-old man with normal electrocardiography and echocardiogram. omim.nt GENO:0000002 ClinVar:RCV000239587 biolink:NamedThing omim.nt dbSNP:rs1563003848 biolink:NamedThing omim.nt owl:NamedIndividual http://omim.org/entry/102565#0006 biolink:NamedThing omim.nt http://omim.org/entry/102565.0007 biolink:NamedThing FLNC, VAL123ALA In a Spanish father and son with hypertrophic cardiomyopathy (CMH26; {617047}), {12:Valdes-Mas et al. (2014)} identified heterozygosity for a T-C transition ({VAR chr7.128,475,395T-C, GRCh37}) in the FLNC gene, resulting in a val123-to-ala (V123A) substitution at a highly conserved residue within the N-terminal actin-binding domain. Western blot analysis of transiently transfected H9C2 rat cardiomyocytes showed that the V123A mutant was detected in the insoluble fraction, with formation of actin aggregates, whereas wildtype FLNC was exclusively present in the insoluble fraction. omim.nt GENO:0000002 ClinVar:RCV000239505 biolink:NamedThing omim.nt dbSNP:rs1562991002 biolink:NamedThing omim.nt owl:NamedIndividual http://omim.org/entry/102565#0007 biolink:NamedThing omim.nt http://omim.org/entry/102565.0008 biolink:NamedThing FLNC, SER1624LEU In a 4-generation Canadian family with restrictive cardiomyopathy (RCM5; see {617047}), {2:Brodehl et al. (2016)} identified heterozygosity for a c.4871C-T transition ({VAR c.4871C-T, NM_001458.4}) in the FLNC gene, resulting in a ser1624-to-leu (S1624L) substitution at a highly conserved residue within the 14th immunoglobulin-like domain. The mutation segregated with disease and was not found in public variant databases, including the ExAC database. Immunohistochemical analysis of explanted cardiac tissue from the left ventricular wall and septum of the proband showed filamin-C aggregates and disturbed Z-disc staining, and did not show the normal intercalated disc localization of desmin (DES; {125660}). Functional analysis in H9C2 rat cardiac myoblasts and C2C12 mouse skeletal myoblasts demonstrated that the S1624L mutant failed to show the wildtype cytoplasmic distribution, instead forming protein aggregates. The proband in this family presented at age 13 years with congestive heart failure and severe biatrial enlargement, and underwent cardiac transplantation at age 14; she later had dizygotic twin daughters, 1 of whom was affected and underwent cardiac transplantation before age 2 years. omim.nt GENO:0000002 ClinVar:RCV000239540 biolink:NamedThing omim.nt ClinVar:RCV001223109 biolink:NamedThing omim.nt ClinVar:RCV001265576 biolink:NamedThing omim.nt dbSNP:rs879255639 biolink:NamedThing omim.nt owl:NamedIndividual http://omim.org/entry/102565#0008 biolink:NamedThing omim.nt http://omim.org/entry/102565.0009 biolink:NamedThing FLNC, ILE2160PHE In a 4-generation Canadian family with restrictive cardiomyopathy (RCM5; see {617047}), {2:Brodehl et al. (2016)} identified heterozygosity for a c.6478A-T transversion ({VAR c.6478A-T, NM_001458.4}) in the FLNC gene, resulting in an ile2160-to-phe (I2160F) substitution at a highly conserved residue within the 19th immunoglobulin-like domain. The mutation segregated with disease and was not found in public variant databases, including the ExAC database. Immunohistochemical analysis of explanted cardiac tissue from the proband revealed that the normal intercalated disc localization of desmin (DES; {125660}) was absent, but no obvious filamin-C aggregates were present. This family was evaluated after the asymptomatic 15-year-old female proband was diagnosed with severe diastolic dysfunction, enlarged atria, and elevated pulmonary pressure, suggesting RCM. Her brother, father, and paternal uncle were known to have cardiomyopathy, with features of RCM on echocardiography. In addition, 2 paternal first cousins had RCM. omim.nt GENO:0000002 ClinVar:RCV000239590 biolink:NamedThing omim.nt dbSNP:rs879255640 biolink:NamedThing omim.nt owl:NamedIndividual http://omim.org/entry/102565#0009 biolink:NamedThing omim.nt http://omim.org/entry/102565.0010 biolink:NamedThing FLNC, TRP2710TER, c.8129G-A In 34 Chinese individuals with autosomal dominant myofibrillar myopathy-5 (MFM5; {609524}) from 9 apparently unrelated families in Hong Kong, {8:Lee et al. (2020)} identified a heterozygous c.8129G-A transition ({VAR c.8129G-A, NM_001458.4}) in the FLNC gene, resulting in a trp2710-to-ter (W2710X) substitution. The mutation, which was found by Sanger sequencing of the FLNC gene, was not present in the Exome Sequencing Project, 1000 Genomes Project, gnomAD, ethnic-specific Chinese Millionome, and Virtual Chinese Genome databases. The mutation affects the same amino acid residue as that in a German family with MFM5 with a different basepair substitution in the same codon (c.8130G-A, {102565.0001}). The mutation is predicted to eliminate the last 16 amino acids at the C terminus, resulting in reduced stability of the dimerization domain. Functional studies were not performed. Polymorphic marker analysis on the 9 probands identified a distinct haplotype that was not detected among 20 ethnically matched control chromosomes. The mutation was estimated to have occurred 42 to 71 generations previously, dating it to 844 to 1,315 years earlier. omim.nt GENO:0000002 ClinVar:RCV000855733 biolink:NamedThing omim.nt ClinVar:RCV001038999 biolink:NamedThing omim.nt ClinVar:RCV001267920 biolink:NamedThing omim.nt ClinVar:RCV001290001 biolink:NamedThing omim.nt dbSNP:rs1585173340 biolink:NamedThing omim.nt owl:NamedIndividual http://omim.org/entry/102565#0010 biolink:NamedThing omim.nt MONARCH:.well-known/genid/b016e025555b52efcbac biolink:NamedThing GRCh38chr7-128830405-128859271-Region omim.nt MONARCH:.well-known/genid/be59d207c9891d6e6c82 faldo:Region PMID:10629222 biolink:NamedThing omim.nt IAO:0000013 PMID:11153914 biolink:NamedThing omim.nt IAO:0000013 PMID:15385448 biolink:NamedThing omim.nt IAO:0000013 PMID:15824355 biolink:NamedThing omim.nt IAO:0000013 PMID:15929027 biolink:NamedThing omim.nt IAO:0000013 PMID:17412757 biolink:NamedThing omim.nt IAO:0000013 PMID:19050726 biolink:NamedThing omim.nt IAO:0000013 PMID:20697107 biolink:NamedThing omim.nt IAO:0000013 PMID:21135393 biolink:NamedThing omim.nt IAO:0000013 PMID:21620354 biolink:NamedThing omim.nt IAO:0000013 PMID:25351925 biolink:NamedThing omim.nt IAO:0000013 PMID:26472074 biolink:NamedThing omim.nt IAO:0000013 PMID:26666891 biolink:NamedThing omim.nt IAO:0000013 PMID:32022900 biolink:NamedThing omim.nt IAO:0000013 PMID:8088838 biolink:NamedThing omim.nt IAO:0000013 PMID:9791010 biolink:NamedThing omim.nt IAO:0000013 OBO:CHR_9606chr7q32 biolink:NamedThing omim.nt owl:Class http://omim.org/entry/609524 biolink:NamedThing|biolink:Disease Myopathy, Myofibrillar, 5 Myopathy, Myofibrillar, 5 omim.nt MYOPATHY, MYOFIBRILLAR, 5; MFM5|Filaminopathy, Autosomal Dominant|Myopathy, Myofibrillar, Filamin C-Related owl:Class http://omim.org/entry/614065 biolink:NamedThing|biolink:Disease Myopathy, Distal, 4 Myopathy, Distal, 4 omim.nt MYOPATHY, DISTAL, 4; MPD4|Williams Distal Myopathy owl:Class http://omim.org/entry/617047 biolink:NamedThing|biolink:Disease Cardiomyopathy, Familial Hypertrophic, 26 Cardiomyopathy, Familial Hypertrophic, 26 omim.nt CARDIOMYOPATHY, FAMILIAL HYPERTROPHIC, 26; CMH26|Cardiomyopathy, Familial Restrictive, 5 owl:Class http://www.omim.org/phenotypicSeries/PS115210 biolink:NamedThing|biolink:Disease Familial restrictive cardiomyopathy omim.nt owl:Class http://www.omim.org/phenotypicSeries/PS601419 biolink:NamedThing|biolink:Disease Myopathy, myofibrillar omim.nt owl:Class UMLS:C1414637 biolink:NamedThing omim.nt owl:Class https://www.ncbi.nlm.nih.gov/gene/2318 biolink:NamedThing omim.nt http://omim.org/entry/102573.0001 biolink:NamedThing ACTN2, GLN9ARG In a 7-year-old girl who died of dilated cardiomyopathy (CMD1AA; {612158}), {10:Mohapatra et al. (2003)} identified heterozygosity for a 26A-G transition in exon 1 of the ACTN2 gene, resulting in a substitution of arg for the conserved residue gln9 (Q9R). The mutation was not found in the unaffected mother or in 200 controls; DNA was not available from the father, who had died from idiopathic CMD at 42 years of age. omim.nt GENO:0000002 http://omim.org/entry/102573 biolink:NamedThing|biolink:Gene ACTN2 Actinin, Alpha-2 omim.nt ACTININ, ALPHA-2; ACTN2 owl:Class ClinVar:RCV000019977 biolink:NamedThing omim.nt ClinVar:RCV000036908 biolink:NamedThing omim.nt ClinVar:RCV000172514 biolink:NamedThing omim.nt ClinVar:RCV000245795 biolink:NamedThing omim.nt ClinVar:RCV000461895 biolink:NamedThing omim.nt ClinVar:RCV000769743 biolink:NamedThing omim.nt dbSNP:rs121434525 biolink:NamedThing omim.nt owl:NamedIndividual http://omim.org/entry/102573#0001 biolink:NamedThing omim.nt http://omim.org/entry/102573.0002 biolink:NamedThing ACTN2, GLY111VAL In a man who was diagnosed with hypertrophic cardiomyopathy (CMH23; see {612158}) at 31 years of age, {13:Theis et al. (2006)} identified heterozygosity for a gly111-to-val (G111V) substitution in the ACTN2 gene. The patient had a maximum left ventricular wall thickness of 20 mm, with a sigmoid septal shape. He was treated with myectomy, and histopathologic analysis showed marked myocyte hypertrophy, focal myocyte disarray, and endocardial fibrosis. There was no family history of CMH or sudden cardiac death. omim.nt GENO:0000002 ClinVar:RCV000169900 biolink:NamedThing omim.nt dbSNP:rs786204949 biolink:NamedThing omim.nt owl:NamedIndividual http://omim.org/entry/102573#0002 biolink:NamedThing omim.nt http://omim.org/entry/102573.0003 biolink:NamedThing ACTN2, THR495MET In a man who was diagnosed with hypertrophic cardiomyopathy (CMH23; see {612158}) at 32 years of age, {13:Theis et al. (2006)} identified heterozygosity for a thr495-to-met (T495M) substitution in the ACTN2 gene. The patient had a maximum left ventricular wall thickness of 16 mm, with a sigmoid septal shape. He was treated with myectomy, and histopathologic analysis showed marked endocardial fibrosis, myocyte hypertrophy, and interstitial fibrosis. There was no family history of CMH or sudden cardiac death. In a European and a South American proband with CMH, {4:Chiu et al. (2010)} identified heterozygosity for the T495M substitution in ACTN2, which the authors noted was located at a highly conserved residue within the second spectrin repeat of the rod domain. SNP analysis indicated that the mutation arose from different founders in the 2 families. One of the probands, who had an affected sister, also had a daughter who carried the T495M mutation. The 15-year-old girl had localized thickening of the interventricular septal wall, indicating early CMH. The other proband was a 20-year-old man with severe hypertrophy. His parents and sister were clinically unaffected but declined genetic testing. {4:Chiu et al. (2010)} noted that in contrast to the patient reported by {13:Theis et al. (2006)}, none of these patients displayed sigmoidal morphology. omim.nt GENO:0000002 ClinVar:RCV000036880 biolink:NamedThing omim.nt ClinVar:RCV000169901 biolink:NamedThing omim.nt ClinVar:RCV000171827 biolink:NamedThing omim.nt ClinVar:RCV000470355 biolink:NamedThing omim.nt ClinVar:RCV000769759 biolink:NamedThing omim.nt dbSNP:rs200248944 biolink:NamedThing omim.nt owl:NamedIndividual http://omim.org/entry/102573#0003 biolink:NamedThing omim.nt http://omim.org/entry/102573.0004 biolink:NamedThing ACTN2, ARG759THR In a man who was diagnosed with hypertrophic cardiomyopathy (CMH23; see {612158}) at 18 years of age, {13:Theis et al. (2006)} identified heterozygosity for an arg759-to-thr (R759T) substitution in the ACTN2 gene. The patient had a maximum left ventricular wall thickness of 16 mm, with a sigmoid septal shape. He was treated with myectomy, but the histopathologic report was unavailable. There was no family history of CMH or sudden cardiac death. omim.nt GENO:0000002 ClinVar:RCV000169902 biolink:NamedThing omim.nt dbSNP:rs786204950 biolink:NamedThing omim.nt owl:NamedIndividual http://omim.org/entry/102573#0004 biolink:NamedThing omim.nt http://omim.org/entry/102573.0005 biolink:NamedThing ACTN2, ALA119THR Dilated Cardiomyopathy 1AA In 4 affected members over 2 generations of an Australian family with marked cardiac phenotype heterogeneity, including dilated cardiomyopathy (CMD1AA; {612158}), left ventricular noncompaction, ventricular fibrillation, and sudden death, {1:Bagnall et al. (2014)} identified heterozygosity for a G-A transition in the ACTN2 gene ({VAR chr1.236,882,307G-A, GRCh37}), resulting in an ala119-to-thr (A119T) substitution. The mutation was also present in an asymptomatic 35-year-old female cousin of the proband, in whom cardiac evaluation at age 29 was normal, including electrocardiography, echocardiography, electrophysiologic study, and 7-day Holter monitor. Haplotype analysis was consistent with a common ancestor shared by this family and the Australian family reported by {4:Chiu et al. (2010)}. Familial Hypertrophic Cardiomyopathy 23 In affected members of a large 3-generation Australian family with clinically heterogeneous CMH mapping to chromosome 1 (CMH23; see {612158}), {4:Chiu et al. (2010)} identified heterozygosity for a G-A transition in exon 3 of the ACTN2 gene, resulting in an A119T substitution at a highly conserved residue within the CH1 domain of the actin-binding domain. Overexpression of the A119T variant in stably transfected myoblast cells resulted in a significant increase in RNA markers of hypertrophy. {4:Chiu et al. (2010)} stated that in contrast to previously reported patients with ACTN2 mutations {13:Theis et al. (2006)}, none of these patients displayed sigmoidal morphology; rather, they exhibited generally mild hypertrophy with a diverse distribution, involving the septum in some individuals, whereas others showed apical, concentric, or right ventricular hypertrophy, with progression to a dilated phenotype and severe heart failure in some cases. omim.nt GENO:0000002 ClinVar:RCV000150148 biolink:NamedThing omim.nt ClinVar:RCV000169904 biolink:NamedThing omim.nt ClinVar:RCV000169905 biolink:NamedThing omim.nt ClinVar:RCV001206449 biolink:NamedThing omim.nt ClinVar:RCV001265546 biolink:NamedThing omim.nt dbSNP:rs727502886 biolink:NamedThing omim.nt owl:NamedIndividual http://omim.org/entry/102573#0005 biolink:NamedThing omim.nt http://omim.org/entry/102573.0006 biolink:NamedThing ACTN2, GLU628GLY In a 44-year-old woman with moderate hypertrophic cardiomyopathy (CMH23; see {612158}), {4:Chiu et al. (2010)} identified heterozygosity for a glu628-to-gly (E628G) substitution at a highly conserved residue within the third spectrin repeat of the rod domain. The proband had 2 sons who also carried the mutation; 1 showed mild asymmetric septal hypertrophy with borderline voltage criteria for left ventricular hypertrophy on electrocardiogram, whereas the other son, who was only 15 years of age, was clinically normal. omim.nt GENO:0000002 ClinVar:RCV000169903 biolink:NamedThing omim.nt dbSNP:rs786204951 biolink:NamedThing omim.nt owl:NamedIndividual http://omim.org/entry/102573#0006 biolink:NamedThing omim.nt http://omim.org/entry/102573.0007 biolink:NamedThing ACTN2, MET228THR In 11 affected members of a large 4-generation Italian family with clinically heterogeneous cardiomyopathic disease comprising variable combinations of asymmetric left ventricular hypertrophy consistent with hypertrophic cardiomyopathy (CMH23; see {612158}) as well as early-onset supraventricular arrhythmias and AV block, and regional left ventricular noncompaction, {5:Girolami et al. (2014)} identified heterozygosity for a c.683T-C transition ({VAR c.683T-C, NM_001103.2}) in the ACTN2 gene, resulting in a met228-to-thr (M228T) substitution at a conserved residue within the actin-binding domain. The mutation, which segregated fully with disease in the family, was not found in 570 control alleles. omim.nt GENO:0000002 ClinVar:RCV000169907 biolink:NamedThing omim.nt ClinVar:RCV000621721 biolink:NamedThing omim.nt dbSNP:rs786205144 biolink:NamedThing omim.nt owl:NamedIndividual http://omim.org/entry/102573#0007 biolink:NamedThing omim.nt http://omim.org/entry/102573.0008 biolink:NamedThing ACTN2, LEU727ARG In a 45-year-old man (patient 1) with congenital myopathy with structured cores and Z-line abnormalities (MYOCOZ; {618654}), {8:Lornage et al. (2019)} identified a de novo heterozygous c.2180T-G transversion ({VAR c.2180T-G, NM_001103.3}) in exon 18 of the ACTN2 gene, resulting in a leu727-to-arg (L727R) substitution at a conserved residue in the fourth spectrin repeat. The mutation, which was found by exome sequencing and confirmed by Sanger sequencing, was not found in the gnomAD database. Western blot analysis of skeletal muscle and analysis of cells transfected with the L727R mutation showed normal protein expression, dimerization, and localization. {8:Lornage et al. (2019)} found that expression of human mutant ACTN2 L727R in zebrafish embryos resulted in hatching defects, smaller myotome, dorsal curvature, and impaired motor function, although levels of protein expression were not affected. Skeletal muscle from mutant fish showed significant myofibrillar disarray, abnormal Z-lines, and abnormal actin-myosin interaction compared to wildtype. AAV-mediated expression of the mutation in skeletal muscle of 3-week-old mice resulted in reduced maximal force as well as abnormal Z-line organization and core formation. The findings in both animal models recapitulated the specific phenotype in humans. omim.nt GENO:0000002 ClinVar:RCV000855691 biolink:NamedThing omim.nt dbSNP:rs1572148902 biolink:NamedThing omim.nt owl:NamedIndividual http://omim.org/entry/102573#0008 biolink:NamedThing omim.nt http://omim.org/entry/102573.0009 biolink:NamedThing ACTN2, 33-BP DEL, NT2194 In a 40-year-old woman (patient 2) with congenital myopathy with structured cores and Z-line abnormalities (MYOCOZ; {618654}), {8:Lornage et al. (2019)} identified a de novo heterozygous 33-bp in-frame deletion ({VAR c.2194_2226del, NM_001103.3}) in exon 18 of the ACTN2 gene, resulting in an Ala732_Ile742del in the fourth spectrin repeat. The mutation, which was found by exome sequencing and confirmed by Sanger sequencing, was not found in the gnomAD database. Functional studies of the variant and studies of patient cells were not performed. omim.nt GENO:0000002 ClinVar:RCV000855692 biolink:NamedThing omim.nt dbSNP:rs1572148914 biolink:NamedThing omim.nt owl:NamedIndividual http://omim.org/entry/102573#0009 biolink:NamedThing omim.nt http://omim.org/entry/102573.0010 biolink:NamedThing ACTN2, CYS487ARG In affected members of 3 unrelated families from northern Spain with autosomal dominant adult-onset distal myopathy-6 (MYD6; {618655}), {11:Savarese et al. (2019)} identified a heterozygous c.1459T-C transition ({VAR c.1459T-C, NM_001103}) in the ACTN2 gene, resulting in a cys487-to-arg (C487R) substitution at a conserved residue in the second spectrin repeat, which is important for dimerization. The variant, which was found by targeted panel sequencing and confirmed by Sanger sequencing, segregated with the disorder in the families. The variant was not found in the gnomAD database. The families all came from the same small village, suggesting a possible founder effect. Functional studies of the variant were not performed, but cDNA analysis showed that the variant did not affect splicing. omim.nt GENO:0000002 ClinVar:RCV000855694 biolink:NamedThing omim.nt dbSNP:rs1572140109 biolink:NamedThing omim.nt owl:NamedIndividual http://omim.org/entry/102573#0010 biolink:NamedThing omim.nt http://omim.org/entry/102573.0011 biolink:NamedThing ACTN2, LEU131PRO In a Swedish father and daughter with autosomal dominant adult-onset distal myopathy-6 (MYD6; {618655}), {11:Savarese et al. (2019)} identified a heterozygous c.392T-C transition ({VAR c.392T-C, NM_001103}) in the ACTN2 gene, resulting in a leu131-to-pro (L131P) substitution in the actin-binding domain. The variant, which was found by targeted panel sequencing and confirmed by Sanger sequencing, segregated with the disorder in the family and was not found in the gnomAD database. Functional studies of the variant and studies of patient cells were not performed. omim.nt GENO:0000002 ClinVar:RCV000855693 biolink:NamedThing omim.nt dbSNP:rs1572114611 biolink:NamedThing omim.nt owl:NamedIndividual http://omim.org/entry/102573#0011 biolink:NamedThing omim.nt MONARCH:.well-known/genid/b1f870443fafc54ebe0d biolink:NamedThing GRCh38chr1-236686498-236764630-Region omim.nt MONARCH:.well-known/genid/b6a14818407a54c553df faldo:Region PMID:11440986 biolink:NamedThing omim.nt IAO:0000013 PMID:12140183 biolink:NamedThing omim.nt IAO:0000013 PMID:1339456 biolink:NamedThing omim.nt IAO:0000013 PMID:14567970 biolink:NamedThing omim.nt IAO:0000013 PMID:1505962 biolink:NamedThing omim.nt IAO:0000013 PMID:17097056 biolink:NamedThing omim.nt IAO:0000013 PMID:20022194 biolink:NamedThing omim.nt IAO:0000013 PMID:21536590 biolink:NamedThing omim.nt IAO:0000013 PMID:22253474 biolink:NamedThing omim.nt IAO:0000013 PMID:25173926 biolink:NamedThing omim.nt IAO:0000013 PMID:25224718 biolink:NamedThing omim.nt IAO:0000013 PMID:30701273 biolink:NamedThing omim.nt IAO:0000013 PMID:30900782 biolink:NamedThing omim.nt IAO:0000013 OBO:CHR_9606chr1q42 biolink:NamedThing omim.nt owl:Class http://omim.org/entry/612158 biolink:NamedThing|biolink:Disease Cardiomyopathy, Dilated, 1Aa, With or Without Left Ventricular Noncompaction Cardiomyopathy, Dilated, 1Aa, With or Without Left Ventricular Noncompaction omim.nt CARDIOMYOPATHY, DILATED, 1AA, WITH OR WITHOUT LEFT VENTRICULAR NONCOMPACTION; CMD1AA|Cardiomyopathy, Familial Hypertrophic, 23, With or Without Ventricular Noncompaction owl:Class http://omim.org/entry/618654 biolink:NamedThing|biolink:Disease Myopathy, Congenital, With Structured Cores and Z-Line Abnormalities Myopathy, Congenital, With Structured Cores and Z-Line Abnormalities omim.nt MYOPATHY, CONGENITAL, WITH STRUCTURED CORES AND Z-LINE ABNORMALITIES; MYOCOZ|Multiple Structured Core Disease owl:Class http://omim.org/entry/618655 biolink:NamedThing|biolink:Disease Myopathy, Distal, 6, Adult-Onset, Autosomal Dominant Myopathy, Distal, 6, Adult-Onset, Autosomal Dominant omim.nt MYOPATHY, DISTAL, 6, ADULT-ONSET, AUTOSOMAL DOMINANT; MPD6 owl:Class UMLS:C1412166 biolink:NamedThing omim.nt owl:Class https://www.ncbi.nlm.nih.gov/gene/88 biolink:NamedThing omim.nt http://omim.org/entry/102574.0001 biolink:NamedThing ACTN3, ARG577TER ({dbSNP rs1815739}) ACTN3 Deficiency {9:North et al. (1999)} identified a C-to-T transition at nucleotide 1747 ({dbSNP rs1815739}) in exon 16 of the ACTN3 gene, which resulted in a stop codon replacing the arg at residue 577 (R577X). This mutation resulted in no protein detectable by Western blot. Sixteen percent of the world population is predicted to be homozygous for this mutation. No disease phenotype is associated; therefore, {9:North et al. (1999)} suggested that the ACTN3 gene is functionally redundant in humans. {6:Mills et al. (2001)} genotyped nonhuman primates and concluded that the R577X null mutation most likely arose in humans. {14:Suminaga et al. (2000)} found an allele frequency of 0.49 for the 1747C-T polymorphism in Japanese. Although the incidence (24.2%) of congenital deficiency of alpha-actinin-3 was high, no evidence could be found that the homozygous state modified the dystrophinopathies Duchenne muscular dystrophy ({310200}) and Becker muscular dystrophy ({300376}). Sprinting Performance {16:Yang et al. (2003)} found that the R577X genotype is associated with human elite athletic performance. Both male and female elite sprint athletes had significantly higher frequencies of the 577R allele than did controls. In female sprint and endurance athletes there was a higher than expected number of R577X heterozygotes among sprint athletes and lower than expected numbers among endurance athletes. The lack of a similar effect in males suggested that the ACTN3 genotype affects athletic performance differently in males and females. The differential effects in sprint and endurance athletes suggested that the R577X polymorphism may have been maintained in the human population by balancing natural selection. {8:Niemi and Majamaa (2005)} determined the ACTN3 R577X genotype in 52 elite Finnish endurance and 89 sprint athletes and found that the frequency of the XX genotype was higher and RR lower among the endurance athletes, and that none of the top Finnish sprinters had the XX genotype. The association of the R577X polymorphism with elite athlete status and human muscle performance suggests that ACTN3 deficiency influences the function of fast muscle fibers. {5:MacArthur et al. (2007)} showed that loss of ACTN3 expression in a knockout mouse model resulted in a shift in muscle metabolism toward the more efficient aerobic pathway and an increase in intrinsic endurance performance. In addition, they demonstrated that the genomic region surrounding the 577X null allele shows low levels of genetic variation and recombination in individuals of European and East Asian descent, consistent with strong, recent positive selection. They proposed that the 577X allele has been positively selected in some human populations owing to its effect on skeletal muscle metabolism. In a study of 992 Greek adolescent boys and girls, {7:Moran et al. (2007)} found a significant association between the ACTN3 R577X polymorphism and 40 meter sprint times in males (p = 0.003) that accounts for 2.3% of phenotypic variance, with the 577R allele contributing to faster times in an additive fashion. The R577X polymorphism was not associated with other predominantly strength/power-related or endurance phenotypes. {12:Saunders et al. (2007)} genotyped 457 Caucasian male triathletes who completed the 2000 and/or 2001 226 km South African Ironman Triathlons and 143 Caucasian controls for the ACTN3 R577X mutation. They found no significant differences in either the genotype (p = 0.486) or allele (p = 0.375) frequencies within the fastest, middle of the field, or slowest Caucasian male finishers and the control population. In 52 white and 23 black elite-level bodybuilders and powerlifters from the U.S., {11:Roth et al. (2008)} found significantly lower XX genotype frequency in strength athletes (6.7%) compared to controls (16.3%; p = 0.005). The XX genotype was significantly lower in white athletes (9.7%) compared to white controls (19.9%; p = 0.018), but did not reach significance in black athletes (0%) compared to black controls (4.8%; p = 0.10). {11:Roth et al. (2008)} concluded that the 577X allele is underrepresented in elite strength athletes in addition to sprint athletes, consistent with previous reports indicating that ACTN3 deficiency appears to impair muscle performance. omim.nt GENO:0000002 http://omim.org/entry/102574 biolink:NamedThing|biolink:Gene ACTN3 Actinin, Alpha-3 omim.nt ACTININ, ALPHA-3; ACTN3 owl:Class ClinVar:RCV000019974 biolink:NamedThing omim.nt ClinVar:RCV000019975 biolink:NamedThing omim.nt ClinVar:RCV000019976 biolink:NamedThing omim.nt dbSNP:rs1815739 biolink:NamedThing omim.nt owl:NamedIndividual http://omim.org/entry/102574#0001 biolink:NamedThing omim.nt MONARCH:.well-known/genid/b5ba2ae91e1da6483cad biolink:NamedThing GRCh38chr11-66546394-66563333-Region omim.nt MONARCH:.well-known/genid/bbaaeeb0530c88b0733a faldo:Region MONARCH:.well-known/genid/OMIM102574ref2 biolink:NamedThing Heritability of locomotor performance and its correlates in a natural population. omim.nt IAO:0000310 PMID:10192379 biolink:NamedThing omim.nt IAO:0000013 PMID:10797427 biolink:NamedThing omim.nt IAO:0000013 PMID:11845199 biolink:NamedThing omim.nt IAO:0000013 PMID:12879365 biolink:NamedThing omim.nt IAO:0000013 PMID:15886711 biolink:NamedThing omim.nt IAO:0000013 PMID:17033684 biolink:NamedThing omim.nt IAO:0000013 PMID:17627799 biolink:NamedThing omim.nt IAO:0000013 PMID:17828264 biolink:NamedThing omim.nt IAO:0000013 PMID:18043716 biolink:NamedThing omim.nt IAO:0000013 PMID:18178581 biolink:NamedThing omim.nt IAO:0000013 PMID:20089531 biolink:NamedThing omim.nt IAO:0000013 PMID:29706347 biolink:NamedThing omim.nt IAO:0000013 OBO:CHR_9606chr11q13 biolink:NamedThing omim.nt owl:Class http://omim.org/entry/617749 biolink:NamedThing|biolink:Disease Actn3 Deficiency Actn3 Deficiency omim.nt ACTN3 DEFICIENCY|Alpha-Actinin-3 Deficiency|Sprinting Performance owl:Class UMLS:C1412167 biolink:NamedThing omim.nt owl:Class https://www.ncbi.nlm.nih.gov/gene/89 biolink:NamedThing omim.nt http://omim.org/entry/102575.0001 biolink:NamedThing ACTN1, VAL105ILE In a Japanese mother and daughter with platelet-type bleeding disorder-15 (BDPLT15; {615193}) manifest as macrothrombocytopenia, {2:Kunishima et al. (2013)} identified a heterozygous 313G-A transition in exon 3 of the ACTN1 gene, resulting in a val105-to-ile (V105I) substitution at a highly conserved residue in the functional N-terminal actin-binding domain. The mutation, which was found by exome sequencing, was not found in several large control databases or in 120 control individuals. Expression of the mutation in CHO cells showed that the mutant protein caused varying degrees of disorganization of the actin filaments, with mutant ACTN1 colocalized with less fine, shortened actin filaments and unbound ACTN1 coarsely distributed within the cytoplasm. Expression of the mutation in mouse fetal liver-derived megakaryocytes showed less organization of the circumferential actin-filament network compared to controls. The findings suggested that the mutation dominantly affected the actin filament assembly, likely resulting in abnormal cytoskeletal organization. Examination of proplatelet formation from megakaryocytes showed that the mutation did not change the rate of proplatelet formation or platelet production, but did reduce the number of proplatelet tips and increase the size of proplatelet tips from megakaryocytes. omim.nt GENO:0000002 http://omim.org/entry/102575 biolink:NamedThing|biolink:Gene ACTN1 Actinin, Alpha-1 omim.nt ACTININ, ALPHA-1; ACTN1 owl:Class ClinVar:RCV000034866 biolink:NamedThing omim.nt ClinVar:RCV000852110 biolink:NamedThing omim.nt dbSNP:rs387907345 biolink:NamedThing omim.nt owl:NamedIndividual http://omim.org/entry/102575#0001 biolink:NamedThing omim.nt http://omim.org/entry/102575.0002 biolink:NamedThing ACTN1, GLN32LYS In a Japanese father and his 2 sons with BDPLT15 ({615193}) manifest as macrothrombocytopenia, {2:Kunishima et al. (2013)} identified a heterozygous 94C-A transversion in exon 1 of the ACTN1 gene, resulting in a gln32-to-lys (Q32K) substitution at a highly conserved residue in the functional N-terminal actin-binding domain. The mutation, which was found by exome sequencing, was not found in several large control databases or in 120 control individuals. Expression of the mutation in CHO cells showed that the mutant protein caused varying degrees of disorganization of the actin filaments, with mutant ACTN1 colocalized with less fine, shortened actin filaments and unbound ACTN1 coarsely distributed within the cytoplasm. Expression of the mutation in mouse fetal liver-derived megakaryocytes showed less organization of the circumferential actin-filament network compared to controls. The findings suggested that the mutation dominantly affected the actin filament assembly, likely resulting in abnormal cytoskeletal organization. Examination of proplatelet formation from megakaryocytes showed that the mutation did not change the rate of proplatelet formation or platelet production, but did reduce the number of proplatelet tips and increase the size of proplatelet tips from megakaryocytes. omim.nt GENO:0000002 ClinVar:RCV000034867 biolink:NamedThing omim.nt dbSNP:rs387907346 biolink:NamedThing omim.nt owl:NamedIndividual http://omim.org/entry/102575#0002 biolink:NamedThing omim.nt http://omim.org/entry/102575.0003 biolink:NamedThing ACTN1, ARG752GLN In a Japanese mother and son with BDPLT15 ({615193}) manifest as macrothrombocytopenia, {2:Kunishima et al. (2013)} identified a heterozygous 2255G-A transition in exon 18 of the ACTN1 gene, resulting in an arg752-to-gln (R752Q) substitution at a highly conserved residue in the functional C-terminal calmodulin-like domain. The mutation, which was identified by sequencing, was not found in several large control databases or in 120 control individuals. omim.nt GENO:0000002 ClinVar:RCV000034868 biolink:NamedThing omim.nt dbSNP:rs387907347 biolink:NamedThing omim.nt owl:NamedIndividual http://omim.org/entry/102575#0003 biolink:NamedThing omim.nt http://omim.org/entry/102575.0004 biolink:NamedThing ACTN1, ARG46GLN In a Japanese father and his 2 daughters with BDPLT15 ({615193}) manifest as macrothrombocytopenia, {2:Kunishima et al. (2013)} identified a heterozygous 137G-A transition in exon 2 of the ACTN1 gene, resulting in an arg46-to-gln (R46Q) substitution at a highly conserved residue in the functional N-terminal actin-binding domain. The mutation was not found in 120 control individuals. omim.nt GENO:0000002 ClinVar:RCV000034869 biolink:NamedThing omim.nt ClinVar:RCV000851589 biolink:NamedThing omim.nt dbSNP:rs387907348 biolink:NamedThing omim.nt owl:NamedIndividual http://omim.org/entry/102575#0004 biolink:NamedThing omim.nt http://omim.org/entry/102575.0005 biolink:NamedThing ACTN1, ARG738TRP In a Japanese patient with BDPLT15 ({615193}) manifest as macrothrombocytopenia, {2:Kunishima et al. (2013)} identified a heterozygous 2212C-T transition in exon 18 of the ACTN1 gene, resulting in an arg738-to-trp (R738W) substitution at a highly conserved residue in the functional C-terminal calmodulin-binding domain. There was a family history of the disorder, but DNA from other family members was not available. The mutation was not found in 120 control individuals. omim.nt GENO:0000002 ClinVar:RCV000034870 biolink:NamedThing omim.nt ClinVar:RCV001003910 biolink:NamedThing omim.nt dbSNP:rs387907349 biolink:NamedThing omim.nt owl:NamedIndividual http://omim.org/entry/102575#0005 biolink:NamedThing omim.nt http://omim.org/entry/102575.0006 biolink:NamedThing ACTN1, GLU225LYS In a Japanese mother and daughter with BDPLT15 ({615193}) manifest as macrothrombocytopenia, {2:Kunishima et al. (2013)} identified a heterozygous 673G-A transition in exon 7 of the ACTN1 gene, resulting in a glu225-to-lys (E225K) substitution at a highly conserved residue in the functional N-terminal actin-binding domain. The mutation was not found in 120 control individuals. omim.nt GENO:0000002 ClinVar:RCV000034871 biolink:NamedThing omim.nt ClinVar:RCV000851847 biolink:NamedThing omim.nt dbSNP:rs387907350 biolink:NamedThing omim.nt owl:NamedIndividual http://omim.org/entry/102575#0006 biolink:NamedThing omim.nt MONARCH:.well-known/genid/be7625ca07fda8a78560 biolink:NamedThing GRCh38chr14-68874122-68979301-Region omim.nt MONARCH:.well-known/genid/b96eb313ad018e9e4eaa faldo:Region PMID:21107430 biolink:NamedThing omim.nt IAO:0000013 PMID:23434115 biolink:NamedThing omim.nt IAO:0000013 PMID:2349951 biolink:NamedThing omim.nt IAO:0000013 OBO:CHR_9606chr14q24.1 biolink:NamedThing omim.nt owl:Class http://omim.org/entry/615193 biolink:NamedThing|biolink:Disease Bleeding Disorder, Platelet-Type, 15 Bleeding Disorder, Platelet-Type, 15 omim.nt BLEEDING DISORDER, PLATELET-TYPE, 15; BDPLT15|Macrothrombocytopenia, Autosomal Dominant, Actn1-Related owl:Class http://www.omim.org/phenotypicSeries/PS231200 biolink:NamedThing|biolink:Disease Bleeding disorder, platelet-type omim.nt owl:Class UMLS:C1412165 biolink:NamedThing omim.nt owl:Class https://www.ncbi.nlm.nih.gov/gene/87 biolink:NamedThing omim.nt http://omim.org/entry/102576.0001 biolink:NamedThing ACVR1, ARG206HIS {19:Shore et al. (2006)} identified heterozygosity for a 617G-A transition in the ACVR1 gene, resulting in an arg206-to-his (R206H) substitution. The mutation was found in all affected members of 7 families with fibrodysplasia ossificans progressiva (FOP; {135100}) and in 32 of 32 de novo cases of FOP. Codon 206 is at the end of a highly conserved glycine-serine (GS) activation domain at the junction of the protein kinase domain. The GS domain is critical for binding and activation of SMAD signaling and is a binding site for FKBP12 (FKBP1A; {186945}), an inhibitory protein that prevents leaky activation of the receptor in the absence of ligand. Protein homology modeling suggested that the R206H mutation may disrupt intramolecular interactions that stabilize ACVR1 and/or alter interactions between the GS domain and other signaling pathway molecules. {19:Shore et al. (2006)} noted that the R206H mutation may be one of the most specific codons in the human genome to be associated with a disease phenotype. In a 3-year-old Taiwanese girl with dysplasia of the first metatarsal bones and progressive heterotopic ossificans of the right thigh due to routine childhood immunizations and several inappropriate surgical interventions, {11:Lin et al. (2006)} identified a de novo R206H mutation in the ACVR1 gene. The mutation was not found in the unaffected parents and brother. {15:Nakajima et al. (2007)} identified the R206H mutation in 3 unrelated sporadic Japanese patients with FOP, indicating that this mutation is common and recurrent in the global population. The authors noted that mutation results from a CpG dinucleotide change. In 15 of 17 unrelated Italian patients with FOP, {3:Bocciardi et al. (2009)} identified heterozygosity for the R206H mutation in the ACVR1 gene. The authors noted that these patients showed extreme variability in severity of the disease. In a study of 112 patients with FOP, {10:Kaplan et al. (2009)} found that all 91 patients with classic FOP as well as 6 patients who had so-called 'FOP-plus' were heterozygous for the recurrent R206H mutation in the ACVR1 gene. In addition to having the classic defining features of FOP, patients who were designated 'FOP-plus' displayed atypical features, including polyostotic fibrous dysplasia (in a patient originally reported by {5:Frame et al., 1972}), thoracic insufficiency syndrome (in a patient previously studied by {9:Kaplan and Glaser, 2005}), aplastic anemia (in a patient previously described by {8:Kaplan et al., 2007}), craniopharyngioma, severe childhood glaucoma, and seizures. Using microarray analysis, {21:Tanaka et al. (2012)} found that expression of mutant ACVR1 with the R206H substitution in transfected mouse myoblasts significantly downregulated their expression of Ogn ({602383}), a secreted factor that enhanced differentiation of mouse osteoblasts in culture. omim.nt GENO:0000002 http://omim.org/entry/102576 biolink:NamedThing|biolink:Gene ACVR1 Activin a Receptor, Type 1 omim.nt ACTIVIN A RECEPTOR, TYPE I; ACVR1|Activin a Receptor, Type Ii-Like Kinase 2|Activin Receptor-Like Kinase 2 owl:Class ClinVar:RCV000019971 biolink:NamedThing omim.nt ClinVar:RCV000422441 biolink:NamedThing omim.nt ClinVar:RCV001267285 biolink:NamedThing omim.nt dbSNP:rs121912678 biolink:NamedThing omim.nt owl:NamedIndividual http://omim.org/entry/102576#0001 biolink:NamedThing omim.nt http://omim.org/entry/102576.0002 biolink:NamedThing ACVR1, GLY356ASP In a 62-year-old Japanese man with slowly progressive fibrodysplasia ossificans progressiva (FOP; {135100}), {6:Furuya et al. (2008)} identified heterozygosity for a de novo 1097G-A transition in exon 7 of the ACVR1 gene, resulting in a gly356-to-asp (G356D) substitution at a conserved residue in the protein kinase domain. The mutation was not found in his 2 unaffected sibs or in 150 controls. {10:Kaplan et al. (2009)} identified the G356D mutation in the ACVR1 gene in 1 patient with so-called 'FOP-plus' and in 3 patients with 'variant FOP.' The patient with FOP-plus had persistence of primary teeth into adulthood and primary amenorrhea in addition to the classic defining features of FOP. One of the 3 patients with variant FOP had the characteristic malformation of the great toes, although it was asymmetric, whereas the other 2 had bilateral absence of or severe reduction deficit of the great toes and thumbs. omim.nt GENO:0000002 ClinVar:RCV000019972 biolink:NamedThing omim.nt dbSNP:rs121912679 biolink:NamedThing omim.nt owl:NamedIndividual http://omim.org/entry/102576#0002 biolink:NamedThing omim.nt http://omim.org/entry/102576.0003 biolink:NamedThing ACVR1, ARG258SER In 2 Italian patients with fibrodysplasia ossificans progressiva (FOP; {135100}), {3:Bocciardi et al. (2009)} identified heterozygosity for a 774G-C transversion in the ACVR1 gene, resulting in an arg258-to-ser (R258S) substitution at a highly conserved residue in the kinase domain. The mutation was not found in the unaffected parents of 1 of the patients or in 104 controls. One of the patients with the R258S mutation displayed an FOP variant phenotype, with typical anatomic distribution of progressive heterotopic ossification but absence of the great toe malformation; the other patient had the great toe malformation, but to a 'rather mild' degree. omim.nt GENO:0000002 ClinVar:RCV000019973 biolink:NamedThing omim.nt dbSNP:rs121912680 biolink:NamedThing omim.nt owl:NamedIndividual http://omim.org/entry/102576#0003 biolink:NamedThing omim.nt http://omim.org/entry/102576.0004 biolink:NamedThing ACVR1, GLY328ARG In 2 probands with fibrodysplasia ossificans progressiva (FOP; {135100}) who had major variations in 1 or both of the classic defining features of FOP, {10:Kaplan et al. (2009)} identified heterozygosity for a 982G-A transition in the ACVR1 gene, resulting in a gly328-to-arg (G328R) substitution in the protein kinase domain. One of the probands was from a family previously reported by {23:Virdi et al. (1999)}, in which a mother and 2 daughters had a mild FOP phenotype with either normal or minimally affected toes and no or late onset of heterotopic ossification. {10:Kaplan et al. (2009)} stated that no substantial progression of FOP had occurred in the mother or daughters since the previous report. The mutation was found in all 3 affected family members, but not in the unaffected father or maternal grandmother. The second proband had normal toes but short thumbs, and did not develop heterotopic ossification until 26 years of age; in addition, CT scan of the head and neck showed a hypoplastic cerebellum. omim.nt GENO:0000002 ClinVar:RCV000022430 biolink:NamedThing omim.nt dbSNP:rs387906588 biolink:NamedThing omim.nt owl:NamedIndividual http://omim.org/entry/102576#0004 biolink:NamedThing omim.nt http://omim.org/entry/102576.0005 biolink:NamedThing ACVR1, GLY328TRP In 2 female probands with fibrodysplasia ossificans progressiva (FOP; {135100}) who had major variations in 1 or both of the classic defining features of FOP, {10:Kaplan et al. (2009)} identified heterozygosity for a 982G-T transversion in the ACVR1 gene, resulting in a gly328-to-trp (G328W) substitution in the protein kinase domain. Both probands had severe reduction deficits of the great toes, with absent toenails in the affected digits, and malformed or reduction deficits of the thumbs. Both developed sparse scalp hair in the second decade of life and had mild cognitive impairment without attention deficit. One of the patients had cerebellar abnormalities noted on CT scan, without associated impairment in movement. The other patient, who had previously been reported by {4:Connor and Evans (1982)}, developed progressive heterotopic ossification in the characteristic anatomic patterns at 8 years of age, and also had mild conductive hearing impairment and short broad femoral necks. omim.nt GENO:0000002 ClinVar:RCV000022431 biolink:NamedThing omim.nt http://omim.org/entry/102576#0005 biolink:NamedThing omim.nt http://omim.org/entry/102576.0006 biolink:NamedThing ACVR1, GLY328GLU In 2 female probands with fibrodysplasia ossificans progressiva (FOP; {135100}) who had major variations in 1 or both of the classic defining features of FOP, {10:Kaplan et al. (2009)} identified heterozygosity for a 983G-A transition in the ACVR1 gene, resulting in a gly328-to-glu (G328E) substitution in the protein kinase domain. The patients, 1 of whom had previously been described by {4:Connor and Evans (1982)}, had severe reduction deficits of the great toes and thumbs at birth, with absent toenails in the affected digits. Both developed sparse scalp hair in the second decade of life and had mild cognitive impairment without attention deficit. In a 52-year-old woman from the UK with fibrodysplasia ossificans progressiva, originally reported by {20:Smith et al. (1976)} and restudied by {4:Connor and Evans (1982)}, {17:Petrie et al. (2009)} identified heterozygosity for a G328E mutation in exon 8 of the ACVR1 gene that was not found in 100 controls. Severe reduction deformities had been noted in all of the patient's digits at birth, and the disease presented as painful lumps on the occiput. By 6 years of age, she had a stiff spine and shoulders; by age 14 years, both elbows and the right hip showed ectopic ossification and she also developed diffuse scalp hair thinning. At 26 years of age, the patient had complete spinal fixation, the shoulders were fixed in adduction, elbows fixed in flexion, hip movement restricted and fixed in slight flexion, and jaw gape was 0.3 cm. She had mild cognitive impairment. omim.nt GENO:0000002 ClinVar:RCV000022432 biolink:NamedThing omim.nt ClinVar:RCV000434306 biolink:NamedThing omim.nt ClinVar:RCV000624246 biolink:NamedThing omim.nt dbSNP:rs387906589 biolink:NamedThing omim.nt owl:NamedIndividual http://omim.org/entry/102576#0006 biolink:NamedThing omim.nt http://omim.org/entry/102576.0007 biolink:NamedThing ACVR1, ARG375PRO In a female proband with fibrodysplasia ossificans progressiva (FOP; {135100}) who had major variations in 1 or both of the classic defining features of FOP, {10:Kaplan et al. (2009)} identified heterozygosity for a 1124G-C transversion in the ACVR1 gene, resulting in an arg375-to-pro (R375P) substitution in the protein kinase domain. The patient had clinically and radiographically normal toes. FOP flare-ups began at 14 years of age and progression of the disease was slow and evanescent. At 40 years of age, she had limited motion of the cervical spine and shoulders with heterotopic ossification in the neck, back, and right hip, but was still ambulatory. omim.nt GENO:0000002 ClinVar:RCV000022433 biolink:NamedThing omim.nt dbSNP:rs387906590 biolink:NamedThing omim.nt owl:NamedIndividual http://omim.org/entry/102576#0007 biolink:NamedThing omim.nt http://omim.org/entry/102576.0008 biolink:NamedThing ACVR1, ARG202ILE In a female patient with fibrodysplasia ossificans progressiva (FOP; {135100}), {17:Petrie et al. (2009)} identified heterozygosity for a 605G-T transversion in exon 6 of the ACVR1 gene, resulting in an arg202-to-ile (R202I) substitution in the GS domain that was not found in 100 controls. The patient was diagnosed at age 14 years when she developed a painful bony lump over her right scapula after a fall and subsequently developed multiple tender bony swellings; the diagnosis was confirmed upon observation of a unilateral short great toe (her other great toe was normal). Her right shoulder was fixed in internal rotation, with fixed flexion deformities of both elbows and restriction of movements of the lumbar spine. She had frequent flare-ups of the condition with inflammatory lesions over the shoulder joints and neck and jaw, and developed fusion of the neck within 6 months of clinical presentation. {17:Petrie et al. (2009)} noted that although the R202I mutation occurs within the same ACVR1 domain as the recurrent R206H mutation ({102576.0001}), this patient's disease had a relatively late age of onset and was less severe than that of a typical FOP patient; the authors also stated that unilateral malformation of the great toe had not previously been documented in an FOP patient. In a female patient with variant FOP, who had normal great toes and late-onset heterotopic ossification and was misdiagnosed with ankylosing spondylitis for several years, {2:Barnett et al. (2011)} identified heterozygosity for the R202I mutation in the ACVR1 gene. omim.nt GENO:0000002 ClinVar:RCV000022434 biolink:NamedThing omim.nt dbSNP:rs387906591 biolink:NamedThing omim.nt owl:NamedIndividual http://omim.org/entry/102576#0008 biolink:NamedThing omim.nt http://omim.org/entry/102576.0009 biolink:NamedThing ACVR1, LEU196PRO In a 45-year-old woman with a late-onset, mild form of fibrodysplasia ossificans progressiva (FOP; {135100}), {7:Gregson et al. (2011)} identified heterozygosity for a c.587T-C transition in exon 6 of the ACVR1 gene, resulting in a leu196-to-pro (L196P) substitution. The mutation was not found in 100 healthy controls. The patient, who had normal toes and bilateral mild camptodactyly of the fifth fingers, was 21 years old when she developed heterotopic ossification following a car accident. Asymptomatic early ossification of cervical spine facet joints was noted at age 42, and she also experienced recurrent episodes of inflammation without subsequent ossification. {7:Gregson et al. (2011)} stated that this patient had the most benign clinical course of any reported FOP case. {16:Ohte et al. (2011)} studied the biologic activity of the ACVR1 L196P mutant in vitro and found that overexpression of L196P mutant protein induced BMP (see {112264})-specific activities, including the suppression of myogenesis and induction of alkaline phosphatase activity, as well as increasing BMP-specific luciferase reporter activity and increasing phosphorylation of SMAD1 ({601595})/5 ({603110}). These activities of the L196P mutant were higher than those of the G356D ACVR1 mutant ({102576.0002}) and the equivalent of the recurrent R206H mutant ({102576.0001}). In addition, L196P was equally or more resistant to inhibitors compared to R206H. {16:Ohte et al. (2011)} suggested that L196P activity might be suppressed by a novel mechanism in the mildly affected patient reported by {7:Gregson et al. (2011)}. In a 22-year-old Japanese man who exhibited delayed onset and a slower, milder course of FOP, {14:Nakahara et al. (2014)} identified heterozygosity for the L196P mutation in ACVR1. The patient first developed heterotopic ossification after a fall from a height of 1 to 2 meters at 17 years of age, and examination at age 22 revealed limited range of motion of cervical and lumbar spine and at the hip joints. He had camptodactyly of the left fifth digit, short toes, and absence of the distal interphalangeal joint of the fourth and fifth toes bilaterally. X-rays showed mature heterotopic calcification bilaterally in the lumbar paraspinal muscles, mild osteosclerotic lesions bilaterally in the inner cortex of the proximal tibia, and slight enlargement of the C6 spinous process with narrowing of the C6-7 intervertebral joint. omim.nt GENO:0000002 ClinVar:RCV000190876 biolink:NamedThing omim.nt dbSNP:rs797045135 biolink:NamedThing omim.nt owl:NamedIndividual http://omim.org/entry/102576#0009 biolink:NamedThing omim.nt MONARCH:.well-known/genid/b529de798b91471b3adb biolink:NamedThing GRCh38chr2-157736445-157876329-Region omim.nt MONARCH:.well-known/genid/b6b0847213f1483e3024 faldo:Region MONARCH:.well-known/genid/OMIM102576ref4 biolink:NamedThing Fibrodysplasia ossificans progressiva: the clinical features and natural history of 34 patients. omim.nt IAO:0000310 MONARCH:.well-known/genid/OMIM102576ref9 biolink:NamedThing Thoracic insufficiency syndrome in patients with fibrodysplasia ossificans progressiva. omim.nt IAO:0000310 PMID:10441661 biolink:NamedThing omim.nt IAO:0000013 PMID:1646080 biolink:NamedThing omim.nt IAO:0000013 PMID:16642017 biolink:NamedThing omim.nt IAO:0000013 PMID:17077940 biolink:NamedThing omim.nt IAO:0000013 PMID:17272450 biolink:NamedThing omim.nt IAO:0000013 PMID:17351709 biolink:NamedThing omim.nt IAO:0000013 PMID:18203193 biolink:NamedThing omim.nt IAO:0000013 PMID:18830232 biolink:NamedThing omim.nt IAO:0000013 PMID:19029982 biolink:NamedThing omim.nt IAO:0000013 PMID:19085907 biolink:NamedThing omim.nt IAO:0000013 PMID:19330033 biolink:NamedThing omim.nt IAO:0000013 PMID:21044902 biolink:NamedThing omim.nt IAO:0000013 PMID:21377447 biolink:NamedThing omim.nt IAO:0000013 PMID:21567927 biolink:NamedThing omim.nt IAO:0000013 PMID:22351757 biolink:NamedThing omim.nt IAO:0000013 PMID:24259422 biolink:NamedThing omim.nt IAO:0000013 PMID:5033743 biolink:NamedThing omim.nt IAO:0000013 PMID:818090 biolink:NamedThing omim.nt IAO:0000013 PMID:8242742 biolink:NamedThing omim.nt IAO:0000013 PMID:8389764 biolink:NamedThing omim.nt IAO:0000013 PMID:8397373 biolink:NamedThing omim.nt IAO:0000013 PMID:9501322 biolink:NamedThing omim.nt IAO:0000013 OBO:CHR_9606chr2q23 biolink:NamedThing omim.nt owl:Class http://omim.org/entry/135100 biolink:NamedThing|biolink:Disease Fibrodysplasia Ossificans Progressiva Fibrodysplasia Ossificans Progressiva omim.nt FIBRODYSPLASIA OSSIFICANS PROGRESSIVA; FOP owl:Class UMLS:C1332012 biolink:NamedThing omim.nt owl:Class https://www.ncbi.nlm.nih.gov/gene/90 biolink:NamedThing omim.nt http://omim.org/entry/102577 biolink:NamedThing|biolink:Gene RFC4 Replication Factor C, Subunit 4 omim.nt REPLICATION FACTOR C, SUBUNIT 4; RFC4|Activator 1, 37-Kd Subunit|Replication Factor C, 37-Kd Subunit|Rfc2, Yeast, Homolog of owl:Class MONARCH:.well-known/genid/baeedeb0e32444aca1e9 biolink:NamedThing GRCh38chr3-186789899-186806481-Region omim.nt MONARCH:.well-known/genid/b3b76c230a51d762fa92 faldo:Region PMID:10783165 biolink:NamedThing omim.nt IAO:0000013 PMID:1351677 biolink:NamedThing omim.nt IAO:0000013 PMID:15201901 biolink:NamedThing omim.nt IAO:0000013 PMID:7774928 biolink:NamedThing omim.nt IAO:0000013 OBO:CHR_9606chr3q27 biolink:NamedThing omim.nt owl:Class UMLS:C1419351 biolink:NamedThing omim.nt owl:Class https://www.ncbi.nlm.nih.gov/gene/5984 biolink:NamedThing omim.nt http://omim.org/entry/102578 biolink:NamedThing|biolink:Gene PML Acute Promyelocytic Leukemia, Inducer of|fused with RARA in APL omim.nt ACUTE PROMYELOCYTIC LEUKEMIA, INDUCER OF; PML|Myl|Pml/Rara Fusion Gene owl:Class MONARCH:.well-known/genid/b42080761cb87cbf9d44 biolink:NamedThing GRCh38chr15-73994715-74047826-Region omim.nt MONARCH:.well-known/genid/bf6b21cf3d5a7fbab618 faldo:Region PMID:10610177 biolink:NamedThing omim.nt IAO:0000013 PMID:10812165 biolink:NamedThing omim.nt IAO:0000013 PMID:10882117 biolink:NamedThing omim.nt IAO:0000013 PMID:10882118 biolink:NamedThing omim.nt IAO:0000013 PMID:10910364 biolink:NamedThing omim.nt IAO:0000013 PMID:11257111 biolink:NamedThing omim.nt IAO:0000013 PMID:11430826 biolink:NamedThing omim.nt IAO:0000013 PMID:11430827 biolink:NamedThing omim.nt IAO:0000013 PMID:11834837 biolink:NamedThing omim.nt IAO:0000013 PMID:12402044 biolink:NamedThing omim.nt IAO:0000013 PMID:12505266 biolink:NamedThing omim.nt IAO:0000013 PMID:1312695 biolink:NamedThing omim.nt IAO:0000013 PMID:1317574 biolink:NamedThing omim.nt IAO:0000013 PMID:1317727 biolink:NamedThing omim.nt IAO:0000013 PMID:14566333 biolink:NamedThing omim.nt IAO:0000013 PMID:14636558 biolink:NamedThing omim.nt IAO:0000013 PMID:15356634 biolink:NamedThing omim.nt IAO:0000013 PMID:15667548 biolink:NamedThing omim.nt IAO:0000013 PMID:16432238 biolink:NamedThing omim.nt IAO:0000013 PMID:1652369 biolink:NamedThing omim.nt IAO:0000013 PMID:16680151 biolink:NamedThing omim.nt IAO:0000013 PMID:16915281 biolink:NamedThing omim.nt IAO:0000013 PMID:17027752 biolink:NamedThing omim.nt IAO:0000013 PMID:17189268 biolink:NamedThing omim.nt IAO:0000013 PMID:1720570 biolink:NamedThing omim.nt IAO:0000013 PMID:17928811 biolink:NamedThing omim.nt IAO:0000013 PMID:18469801 biolink:NamedThing omim.nt IAO:0000013 PMID:18504460 biolink:NamedThing omim.nt IAO:0000013 PMID:18716620 biolink:NamedThing omim.nt IAO:0000013 PMID:1878967 biolink:NamedThing omim.nt IAO:0000013 PMID:20378816 biolink:NamedThing omim.nt IAO:0000013 PMID:21030605 biolink:NamedThing omim.nt IAO:0000013 PMID:2170850 biolink:NamedThing omim.nt IAO:0000013 PMID:7780148 biolink:NamedThing omim.nt IAO:0000013 PMID:8293467 biolink:NamedThing omim.nt IAO:0000013 PMID:8394219 biolink:NamedThing omim.nt IAO:0000013 PMID:8563172 biolink:NamedThing omim.nt IAO:0000013 PMID:9122233 biolink:NamedThing omim.nt IAO:0000013 PMID:9129145 biolink:NamedThing omim.nt IAO:0000013 PMID:9486654 biolink:NamedThing omim.nt IAO:0000013 PMID:9486655 biolink:NamedThing omim.nt IAO:0000013 PMID:9488655 biolink:NamedThing omim.nt IAO:0000013 OBO:CHR_9606chr15q22 biolink:NamedThing omim.nt owl:Class UMLS:C1366903 biolink:NamedThing omim.nt owl:Class UMLS:C3887967 biolink:NamedThing omim.nt owl:Class https://www.ncbi.nlm.nih.gov/gene/5371 biolink:NamedThing omim.nt http://omim.org/entry/102579.0001 biolink:NamedThing RFC1, (AAGGG)n REPEAT EXPANSION In 25 affected individuals from 11 unrelated families with cerebellar ataxia, neuropathy, and vestibular areflexia syndrome (CANVAS; {614575}), {5:Cortese et al. (2019)} identified a homozygous expanded 5-bp intronic repeat, (AAGGG)n, in the RFC1 gene. The variant, which was found by a combination of linkage analysis and whole-genome and whole-exome sequencing, was confirmed by Sanger sequencing. Screening of an additional cohort of 150 patients with sporadic late-onset ataxia identified the homozygous (AAGGG)n expansion in 33 patients (22%). The reference allele, a simple tandem pentanucleotide AAAAG repeat of 11 (AAAAG)11, was replaced by a variable number of expanded pentanucleotide AAGGG repeated units. The expansion size varied across different families, ranging from about 400 to 2,000 repeats, but the majority of cases had about 1,000 repeats. Repeat size was relatively stable in sibs, and there was no association between age at onset and repeat size. There were no instances of vertical transmission; all families studied consisted of affected sibs or first cousins in the same generation. The expansion resides at the 3-prime end of a deep intronic AluSx3 element and increases the size of the poly(A) tail. Haplotype analysis showed that all affected individuals from the 11 families and 32 of the sporadic cases shared the same haplotype, which had had a carrier frequency of 18% in the 1000 Genomes Project database. Biallelic AAGGG repeat expansions were not found in 304 controls, although 0.7% carried an AAGGG expansion in heterozygous state. The region where the expansions occurred was highly polymorphic and often showed interruptions and nucleotide changes in the expanded sequence. Patient cells showed normal expression levels of RFC1 mRNA and protein, and postmortem brain tissue from 1 CANVAS patient had normal levels of RFC1 and FXN ({606829}) compared to controls. However, patient cells showed some evidence of altered pre-mRNA processing with an increase in the retention of intron 2 compared to controls. Patient fibroblasts did not show increased susceptibility to DNA damage. {5:Cortese et al. (2019)} noted that their studies did not show evidence of a loss-of-function effect. omim.nt GENO:0000002 http://omim.org/entry/102579 biolink:NamedThing|biolink:Gene RFC1 Replication Factor C, Subunit 1 omim.nt REPLICATION FACTOR C, SUBUNIT 1; RFC1|Activator 1, 140-Kd Subunit|Replication Factor C, 140-Kd Subunit|Rfc owl:Class ClinVar:RCV000767848 biolink:NamedThing omim.nt http://omim.org/entry/102579#0001 biolink:NamedThing omim.nt http://omim.org/entry/102579.0002 biolink:NamedThing RFC1, (AAAGG)10-25(AAGGG)n REPEAT EXPANSION In 2 patients from a Cook Island Maori family, 6 patients from a New Zealand Maori family, and 5 unrelated New Zealand Maori patients with cerebellar ataxia, neuropathy, and vestibular areflexia syndrome (CANVAS; {614575}), {1:Beecroft et al. (2020)} identified a biallelic (AAAGG)10-25(AAGGG)n intronic repeat expansion of the RFC1 gene. Two of the affected individuals also had an additional repeat, (AAAGG)4-6, at the distal end of the repeat sequence. The mutations were identified by whole-genome sequencing, whole-exome sequencing, or direct gene analysis. The repeat expansions were characterized by repeat-primed PCR. One unaffected individual from each family was found to be a carrier for the repeat expansion. A common haplotype was identified in these patients, suggesting a founder effect with the most recent common ancestor estimated to date to 1369-1499 CE. omim.nt GENO:0000002 ClinVar:RCV001267634 biolink:NamedThing omim.nt http://omim.org/entry/102579#0002 biolink:NamedThing omim.nt MONARCH:.well-known/genid/b68d1891c68c69d145eb biolink:NamedThing GRCh38chr4-39287455-39366380-Region omim.nt MONARCH:.well-known/genid/bb3738477133adea5663 faldo:Region PMID:11336696 biolink:NamedThing omim.nt IAO:0000013 PMID:27760120 biolink:NamedThing omim.nt IAO:0000013 PMID:30926972 biolink:NamedThing omim.nt IAO:0000013 PMID:32814343 biolink:NamedThing omim.nt IAO:0000013 PMID:32814904 biolink:NamedThing omim.nt IAO:0000013 PMID:32851396 biolink:NamedThing omim.nt IAO:0000013 PMID:7719032 biolink:NamedThing omim.nt IAO:0000013 PMID:8114700 biolink:NamedThing omim.nt IAO:0000013 PMID:8248204 biolink:NamedThing omim.nt IAO:0000013 PMID:8954124 biolink:NamedThing omim.nt IAO:0000013 OBO:CHR_9606chr4p14 biolink:NamedThing omim.nt owl:Class http://omim.org/entry/614575 biolink:NamedThing|biolink:Disease Cerebellar Ataxia, Neuropathy, and Vestibular Areflexia Syndrome Cerebellar Ataxia, Neuropathy, and Vestibular Areflexia Syndrome omim.nt CEREBELLAR ATAXIA, NEUROPATHY, AND VESTIBULAR AREFLEXIA SYNDROME; CANVAS owl:Class UMLS:C1419348 biolink:NamedThing omim.nt owl:Class https://www.ncbi.nlm.nih.gov/gene/5981 biolink:NamedThing omim.nt http://omim.org/entry/102581 biolink:NamedThing|biolink:Gene ACVR2A Activin a Receptor, Type 2A omim.nt ACTIVIN A RECEPTOR, TYPE IIA; ACVR2A|Acvr2 owl:Class MONARCH:.well-known/genid/bf95420440d670fc92c0 biolink:NamedThing GRCh38chr2-147844516-147930821-Region omim.nt MONARCH:.well-known/genid/b3df92c6996d07929ebf faldo:Region PMID:10323406 biolink:NamedThing omim.nt IAO:0000013 PMID:10702675 biolink:NamedThing omim.nt IAO:0000013 PMID:1314589 biolink:NamedThing omim.nt IAO:0000013 PMID:16330774 biolink:NamedThing omim.nt IAO:0000013 PMID:17728715 biolink:NamedThing omim.nt IAO:0000013 PMID:7821227 biolink:NamedThing omim.nt IAO:0000013 PMID:7885474 biolink:NamedThing omim.nt IAO:0000013 PMID:8243335 biolink:NamedThing omim.nt IAO:0000013 OBO:CHR_9606chr2q22.2 biolink:NamedThing omim.nt owl:Class UMLS:C1706636 biolink:NamedThing omim.nt owl:Class https://www.ncbi.nlm.nih.gov/gene/92 biolink:NamedThing omim.nt http://omim.org/entry/102582.0001 biolink:NamedThing STAT3, VAL463DEL In 3 presumably unrelated Japanese patients with hyper-IgE syndrome-1 (HIES1; {147060}), {38:Minegishi et al. (2007)} identified heterozygosity for a 3-bp deletion (1387delGTG) in the STAT3 gene, resulting in deletion of a valine at position 463. {24:Holland et al. (2007)} described the same mutation in a Caucasian patient with sporadic HIES1. omim.nt GENO:0000002 http://omim.org/entry/102582 biolink:NamedThing|biolink:Gene STAT3 Signal Transducer and Activator of Transcription 3 omim.nt SIGNAL TRANSDUCER AND ACTIVATOR OF TRANSCRIPTION 3; STAT3|Acute-Phase Response Factor owl:Class ClinVar:RCV000019965 biolink:NamedThing omim.nt ClinVar:RCV000255324 biolink:NamedThing omim.nt dbSNP:rs113994138 biolink:NamedThing omim.nt owl:NamedIndividual http://omim.org/entry/102582#0001 biolink:NamedThing omim.nt http://omim.org/entry/102582.0002 biolink:NamedThing STAT3, ARG382TRP In 2 presumably unrelated Japanese patients with hyper-IgE syndrome-1 (HIES1; {147060}), {38:Minegishi et al. (2007)} identified heterozygosity for a 1144C-T transition in the STAT3 gene, resulting in an arg382-to-trp (R382W) substitution. In affected members of 7 families segregating hyper-IgE syndrome, {24:Holland et al. (2007)} identified heterozygosity for the R382W mutation in the STAT3 gene. Two of the families were black, 1 Hispanic, and the remainder white. In 1 of the original patients with 'Job syndrome' reported by {16:Davis et al. (1966)}, {48:Renner et al. (2007)} found the same heterozygous R382W mutation. Her 2 sons and a grandson were also affected. {48:Renner et al. (2007)} noted that arg382, which is highly conserved and directly involved in DNA binding, accounted for nearly half of the STAT3 mutations identified by {38:Minegishi et al. (2007)} and {24:Holland et al. (2007)}. Also see {102582.0003}. omim.nt GENO:0000002 ClinVar:RCV000019966 biolink:NamedThing omim.nt ClinVar:RCV000259784 biolink:NamedThing omim.nt ClinVar:RCV000814004 biolink:NamedThing omim.nt dbSNP:rs113994135 biolink:NamedThing omim.nt owl:NamedIndividual http://omim.org/entry/102582#0002 biolink:NamedThing omim.nt http://omim.org/entry/102582.0003 biolink:NamedThing STAT3, ARG382GLN In a Japanese patient with hyper-IgE syndrome-1 (HIES1; {147060}), {38:Minegishi et al. (2007)} identified heterozygosity for a 1145G-A transition in the STAT3 gene, resulting in an arg382-to-gln (R382Q) substitution. In affected members of 4 families segregating hyper-IgE syndrome, {24:Holland et al. (2007)} identified heterozygosity for the R382Q mutation in the STAT3 gene. One of the families was black and 3 were white. omim.nt GENO:0000002 ClinVar:RCV000019967 biolink:NamedThing omim.nt ClinVar:RCV001027632 biolink:NamedThing omim.nt ClinVar:RCV001059385 biolink:NamedThing omim.nt dbSNP:rs113994136 biolink:NamedThing omim.nt owl:NamedIndividual http://omim.org/entry/102582#0003 biolink:NamedThing omim.nt http://omim.org/entry/102582.0004 biolink:NamedThing STAT3, ARG423GLN In affected members of 2 families, 1 white and 1 Asian, segregating hyper-IgE syndrome-1 (HIES1; {147060}), {24:Holland et al. (2007)} identified heterozygosity for a 1268G-A transition in the STAT3 gene, resulting in an arg423-to-gln (R423Q) substitution. A parent and daughter were affected in the white family, and parent, son, and daughter in the Asian family. omim.nt GENO:0000002 ClinVar:RCV000019968 biolink:NamedThing omim.nt dbSNP:rs113994137 biolink:NamedThing omim.nt owl:NamedIndividual http://omim.org/entry/102582#0004 biolink:NamedThing omim.nt http://omim.org/entry/102582.0005 biolink:NamedThing STAT3, ARG383LEU In a white-Hispanic patient with sporadic hyper-IgE syndrome-1 (HIES1; {147060}), {24:Holland et al. (2007)} identified heterozygosity for a 1145G-T transversion in the STAT3 gene, resulting in an arg383-to-leu (R383L) substitution. omim.nt GENO:0000002 ClinVar:RCV000019969 biolink:NamedThing omim.nt http://omim.org/entry/102582#0005 biolink:NamedThing omim.nt http://omim.org/entry/102582.0006 biolink:NamedThing STAT3, VAL637MET In affected members of 6 families, all white, with hyper-IgE syndrome-1 (HIES1; {147060}), {24:Holland et al. (2007)} identified heterozygosity for a 1909G-A transition in the STAT3 gene, resulting in a val637-to-met (V637M) substitution. omim.nt GENO:0000002 ClinVar:RCV000019970 biolink:NamedThing omim.nt ClinVar:RCV000317206 biolink:NamedThing omim.nt ClinVar:RCV000587895 biolink:NamedThing omim.nt ClinVar:RCV000653282 biolink:NamedThing omim.nt dbSNP:rs113994139 biolink:NamedThing omim.nt owl:NamedIndividual http://omim.org/entry/102582#0006 biolink:NamedThing omim.nt http://omim.org/entry/102582.0007 biolink:NamedThing STAT3, THR389ILE {15:Crosby et al. (2012)} reported an African-American male with hyper-IgE syndrome-1 (HIES1; {147060}) who presented with dysphagia resistant to proton pump inhibitors. He had a normal blood cell count and differential with 12% eosinophils and total IgE of 2728 kU/L. His HIES score was 53. Genotype analysis revealed a mutation in exon 12 of the STAT3 gene that resulted in a thr389-to-ile (T389I) substitution. omim.nt GENO:0000002 ClinVar:RCV000054835 biolink:NamedThing omim.nt dbSNP:rs397514766 biolink:NamedThing omim.nt owl:NamedIndividual http://omim.org/entry/102582#0007 biolink:NamedThing omim.nt http://omim.org/entry/102582.0008 biolink:NamedThing STAT3, THR716MET In a 6-year-old girl with infantile-onset multisystem autoimmune disease-1 (ADMIO1; {615952}), {18:Flanagan et al. (2014)} identified a de novo heterozygous c.2147C-T transition in the STAT3 gene, resulting in a thr716-to-met (T716M) substitution at a highly conserved residue in the transactivation domain. The mutation, which was found by exome sequencing, was not present in the dbSNP (build 131), 1000 Genomes Project, or Exome Variant server databases, or in the unaffected parents. {37:Milner et al. (2015)} identified a heterozygous T716M mutation ({VAR c.2147C-T, NM_139276})in the STAT3 gene in 3 patients from 2 unrelated families with ADMIO1. The mutation was found by whole-exome sequencing and confirmed by Sanger sequencing. omim.nt GENO:0000002 ClinVar:RCV000210415 biolink:NamedThing omim.nt ClinVar:RCV000224259 biolink:NamedThing omim.nt ClinVar:RCV000653278 biolink:NamedThing omim.nt dbSNP:rs869312892 biolink:NamedThing omim.nt owl:NamedIndividual http://omim.org/entry/102582#0008 biolink:NamedThing omim.nt http://omim.org/entry/102582.0009 biolink:NamedThing STAT3, LYS392ARG In a 15-year-old girl with infantile-onset multisystem autoimmune disease-1 (ADMIO1; {615952}), {18:Flanagan et al. (2014)} identified a de novo heterozygous c.1175A-G transition in the STAT3 gene, resulting in a lys392-to-arg (K392R) substitution at a highly conserved residue in the DNA-binding domain. The mutation was not found in the Exome Variant Server or 1000 Genomes Project databases, or in the unaffected parents. omim.nt GENO:0000002 ClinVar:RCV000133537 biolink:NamedThing omim.nt dbSNP:rs587777648 biolink:NamedThing omim.nt owl:NamedIndividual http://omim.org/entry/102582#0009 biolink:NamedThing omim.nt http://omim.org/entry/102582.0010 biolink:NamedThing STAT3, ASN646LYS In 2 unrelated boys with infantile-onset multisystem autoimmune disease-1 (ADMIO1; {615952}), {18:Flanagan et al. (2014)} identified a de novo heterozygous c.1938C-G transversion in the STAT3 gene, resulting in an asn646-to-lys (N646K) substitution at a highly conserved residue in the SH2 domain. The mutation was not found in the Exome Variant Server or 1000 Genomes Project databases, or in the unaffected parents. omim.nt GENO:0000002 ClinVar:RCV000133538 biolink:NamedThing omim.nt dbSNP:rs587777649 biolink:NamedThing omim.nt owl:NamedIndividual http://omim.org/entry/102582#0010 biolink:NamedThing omim.nt http://omim.org/entry/102582.0011 biolink:NamedThing STAT3, LYS658ASN In a 17-year-old girl with infantile-onset multisystem autoimmune disease-1 (ADMIO1; {615952}), {18:Flanagan et al. (2014)} identified a de novo heterozygous c.1974G-C transversion in the STAT3 gene, resulting in a lys658-to-asn (K658N) substitution at a highly conserved residue in the SH2 domain. The mutation was not found in the Exome Variant Server or 1000 Genomes Project databases, or in the unaffected parents. omim.nt GENO:0000002 ClinVar:RCV000133539 biolink:NamedThing omim.nt dbSNP:rs587777650 biolink:NamedThing omim.nt owl:NamedIndividual http://omim.org/entry/102582#0011 biolink:NamedThing omim.nt http://omim.org/entry/102582.0012 biolink:NamedThing STAT3, THR663ILE In a patient with infantile-onset multisystem autoimmune disease-1 (ADMIO1; {615952}), {37:Milner et al. (2015)} identified a de novo heterozygous c.1988C-T transition ({VAR c.1988C-T, NM_139276}) in the STAT3 gene, resulting in a thr663-to-ile (T663I) substitution in the SH2 domain. The mutation, which was found by whole-exome sequencing and confirmed by Sanger sequencing, was not found in the dbSNP database. omim.nt GENO:0000002 ClinVar:RCV000210428 biolink:NamedThing omim.nt ClinVar:RCV000788237 biolink:NamedThing omim.nt dbSNP:rs869312889 biolink:NamedThing omim.nt owl:NamedIndividual http://omim.org/entry/102582#0012 biolink:NamedThing omim.nt http://omim.org/entry/102582.0013 biolink:NamedThing STAT3, GLN344HIS In a patient with infantile-onset multisystem autoimmune disease-1 (ADMIO1; {615952}), {37:Milner et al. (2015)} identified a de novo heterozygous c.1032G-C transversion ({VAR c.1032G-C, NM_139276}) in the STAT3 gene, resulting in a gln344-to-his (Q344H) substitution in the DNA-binding domain. The mutation, which was found by whole-exome sequencing and confirmed by Sanger sequencing, was not found in the dbSNP database. omim.nt GENO:0000002 ClinVar:RCV000210413 biolink:NamedThing omim.nt dbSNP:rs869312887 biolink:NamedThing omim.nt owl:NamedIndividual http://omim.org/entry/102582#0013 biolink:NamedThing omim.nt http://omim.org/entry/102582.0014 biolink:NamedThing STAT3, ALA703THR In a father and his 2 children with infantile-onset multisystem autoimmune disease-1 (ADMIO1; {615952}), {37:Milner et al. (2015)} identified a heterozygous c.2107G-A transition ({VAR c.2107G-A, NM_139276}) in the STAT3 gene, resulting in an ala703-to-thr (A703T) substitution at a conserved residue in the TA domain. The mutation, which was found by whole-exome sequencing and confirmed by Sanger sequencing, was not present in the dbSNP database. There was evidence of incomplete penetrance in this family. omim.nt GENO:0000002 ClinVar:RCV000210433 biolink:NamedThing omim.nt dbSNP:rs869312894 biolink:NamedThing omim.nt owl:NamedIndividual http://omim.org/entry/102582#0014 biolink:NamedThing omim.nt MONARCH:.well-known/genid/be428ccb40cc04097cd5 biolink:NamedThing GRCh38chr17-42313323-42388501-Region omim.nt MONARCH:.well-known/genid/b026b028b9962c6f49ee faldo:Region PMID:10205054 biolink:NamedThing omim.nt IAO:0000013 PMID:10458605 biolink:NamedThing omim.nt IAO:0000013 PMID:10615050 biolink:NamedThing omim.nt IAO:0000013 PMID:11021801 biolink:NamedThing omim.nt IAO:0000013 PMID:11161808 biolink:NamedThing omim.nt IAO:0000013 PMID:11853668 biolink:NamedThing omim.nt IAO:0000013 PMID:11856732 biolink:NamedThing omim.nt IAO:0000013 PMID:12444102 biolink:NamedThing omim.nt IAO:0000013 PMID:12562765 biolink:NamedThing omim.nt IAO:0000013 PMID:12571365 biolink:NamedThing omim.nt IAO:0000013 PMID:12588893 biolink:NamedThing omim.nt IAO:0000013 PMID:12594516 biolink:NamedThing omim.nt IAO:0000013 PMID:12615922 biolink:NamedThing omim.nt IAO:0000013 PMID:14566054 biolink:NamedThing omim.nt IAO:0000013 PMID:14702106 biolink:NamedThing omim.nt IAO:0000013 PMID:14702634 biolink:NamedThing omim.nt IAO:0000013 PMID:14716305 biolink:NamedThing omim.nt IAO:0000013 PMID:15021879 biolink:NamedThing omim.nt IAO:0000013 PMID:15194489 biolink:NamedThing omim.nt IAO:0000013 PMID:15343391 biolink:NamedThing omim.nt IAO:0000013 PMID:15592573 biolink:NamedThing omim.nt IAO:0000013 PMID:15653507 biolink:NamedThing omim.nt IAO:0000013 PMID:15781265 biolink:NamedThing omim.nt IAO:0000013 PMID:15870198 biolink:NamedThing omim.nt IAO:0000013 PMID:15976028 biolink:NamedThing omim.nt IAO:0000013 PMID:16254185 biolink:NamedThing omim.nt IAO:0000013 PMID:16783372 biolink:NamedThing omim.nt IAO:0000013 PMID:17183270 biolink:NamedThing omim.nt IAO:0000013 PMID:17676033 biolink:NamedThing omim.nt IAO:0000013 PMID:17881745 biolink:NamedThing omim.nt IAO:0000013 PMID:17942886 biolink:NamedThing omim.nt IAO:0000013 PMID:17954917 biolink:NamedThing omim.nt IAO:0000013 PMID:18192275 biolink:NamedThing omim.nt IAO:0000013 PMID:18497825 biolink:NamedThing omim.nt IAO:0000013 PMID:18591410 biolink:NamedThing omim.nt IAO:0000013 PMID:18591412 biolink:NamedThing omim.nt IAO:0000013 PMID:19131594 biolink:NamedThing omim.nt IAO:0000013 PMID:19556508 biolink:NamedThing omim.nt IAO:0000013 PMID:19797626 biolink:NamedThing omim.nt IAO:0000013 PMID:20032975 biolink:NamedThing omim.nt IAO:0000013 PMID:22118528 biolink:NamedThing omim.nt IAO:0000013 PMID:22331430 biolink:NamedThing omim.nt IAO:0000013 PMID:22591296 biolink:NamedThing omim.nt IAO:0000013 PMID:22801499 biolink:NamedThing omim.nt IAO:0000013 PMID:23342295 biolink:NamedThing omim.nt IAO:0000013 PMID:23917203 biolink:NamedThing omim.nt IAO:0000013 PMID:24159173 biolink:NamedThing omim.nt IAO:0000013 PMID:24717441 biolink:NamedThing omim.nt IAO:0000013 PMID:25038750 biolink:NamedThing omim.nt IAO:0000013 PMID:25339666 biolink:NamedThing omim.nt IAO:0000013 PMID:25359994 biolink:NamedThing omim.nt IAO:0000013 PMID:26026268 biolink:NamedThing omim.nt IAO:0000013 PMID:26675719 biolink:NamedThing omim.nt IAO:0000013 PMID:27096320 biolink:NamedThing omim.nt IAO:0000013 PMID:27110918 biolink:NamedThing omim.nt IAO:0000013 PMID:29907690 biolink:NamedThing omim.nt IAO:0000013 PMID:29907691 biolink:NamedThing omim.nt IAO:0000013 PMID:31462771 biolink:NamedThing omim.nt IAO:0000013 PMID:33029007 biolink:NamedThing omim.nt IAO:0000013 PMID:4161105 biolink:NamedThing omim.nt IAO:0000013 PMID:7512451 biolink:NamedThing omim.nt IAO:0000013 PMID:8272872 biolink:NamedThing omim.nt IAO:0000013 PMID:8675499 biolink:NamedThing omim.nt IAO:0000013 PMID:8782827 biolink:NamedThing omim.nt IAO:0000013 PMID:8921406 biolink:NamedThing omim.nt IAO:0000013 PMID:9162009 biolink:NamedThing omim.nt IAO:0000013 PMID:9388184 biolink:NamedThing omim.nt IAO:0000013 OBO:CHR_9606chr17q21 biolink:NamedThing omim.nt owl:Class http://omim.org/entry/147060 biolink:NamedThing|biolink:Disease Hyper-Ige Recurrent Infection Syndrome 1, Autosomal Dominant Hyper-Ige Recurrent Infection Syndrome 1, Autosomal Dominant omim.nt HYPER-IgE RECURRENT INFECTION SYNDROME 1, AUTOSOMAL DOMINANT; HIES1|Hies, Autosomal Dominant|Hyper-Ige Syndrome, Autosomal Dominant|Job Syndrome owl:Class http://omim.org/entry/615952 biolink:NamedThing|biolink:Disease Autoimmune Disease, Multisystem, Infantile-Onset, 1 Autoimmune Disease, Multisystem, Infantile-Onset, 1 omim.nt AUTOIMMUNE DISEASE, MULTISYSTEM, INFANTILE-ONSET, 1; ADMIO1 owl:Class http://www.omim.org/phenotypicSeries/PS147060 biolink:NamedThing|biolink:Disease Hyper-IgE recurrent infection syndrome omim.nt owl:Class http://www.omim.org/phenotypicSeries/PS615952 biolink:NamedThing|biolink:Disease Autoimmune disease, multisystem, infantile-onset omim.nt owl:Class UMLS:C1367307 biolink:NamedThing omim.nt owl:Class https://www.ncbi.nlm.nih.gov/gene/6774 biolink:NamedThing omim.nt http://omim.org/entry/102590 biolink:NamedThing omim.nt True owl:Class http://omim.org/entry/614413 biolink:NamedThing|biolink:Gene ACY3 Aminoacylase 3 omim.nt AMINOACYLASE 3; ACY3|Aa3|Aspartoacylase 3|Hcv Core-Binding Protein 1|Hepatitis C Virus Core-Binding Protein 1 owl:Class http://omim.org/entry/102593 biolink:NamedThing|biolink:Gene AOAH Acyloxyacyl Hydrolase omim.nt ACYLOXYACYL HYDROLASE; AOAH owl:Class MONARCH:.well-known/genid/b617206349f688840a36 biolink:NamedThing GRCh38chr7-36509312-36724543-Region omim.nt MONARCH:.well-known/genid/b5b56f039f236eeb6337 faldo:Region PMID:1883828 biolink:NamedThing omim.nt IAO:0000013 PMID:8088847 biolink:NamedThing omim.nt IAO:0000013 OBO:CHR_9606chr7p14 biolink:NamedThing omim.nt owl:Class UMLS:C1412429 biolink:NamedThing omim.nt owl:Class https://www.ncbi.nlm.nih.gov/gene/313 biolink:NamedThing omim.nt http://omim.org/entry/102595 biolink:NamedThing|biolink:Gene ACYP2 Acylphosphatase 2, Muscle Type omim.nt ACYLPHOSPHATASE 2, MUSCLE TYPE; ACYP2|Acylphosphatase, Muscle owl:Class MONARCH:.well-known/genid/b77fd18740b32c605508 biolink:NamedThing GRCh38chr2-53970837-54305299-Region omim.nt MONARCH:.well-known/genid/bac533ae7bfbf0117430 faldo:Region PMID:8268218 biolink:NamedThing omim.nt IAO:0000013 OBO:CHR_9606chr2p16.2 biolink:NamedThing omim.nt owl:Class UMLS:C1412176 biolink:NamedThing omim.nt owl:Class https://www.ncbi.nlm.nih.gov/gene/98 biolink:NamedThing omim.nt http://omim.org/entry/102600.0001 biolink:NamedThing APRT, 3-BP DEL, 2179TTC In a lymphoblastoid cell line from a Caucasian patient in Belgium with complete APRT deficiency ({614723}), {15:Hidaka et al. (1987)} identified compound heterozygosity for 2 mutations in the APRT gene: a 3-bp deletion (2179delTTC) in exon 4, resulting in the deletion of codon phe173, and a 1-bp insertion (1834insT) immediately adjacent to the splice site at the 5-prime end of intron 4 ({102600.0002}). This insertion led to aberrant splicing, the absence of exon 4, frameshift, and premature termination at amino acid 110. The enzyme activity was less than 1% of normal and the enzyme protein was immunologically undetectable. omim.nt GENO:0000002 http://omim.org/entry/102600 biolink:NamedThing|biolink:Gene APRT Adenine Phosphoribosyltransferase|telomeric to GALNS, transcribed in same cen-tel direction omim.nt ADENINE PHOSPHORIBOSYLTRANSFERASE; APRT owl:Class ClinVar:RCV000019956 biolink:NamedThing omim.nt dbSNP:rs121912681 biolink:NamedThing omim.nt owl:NamedIndividual http://omim.org/entry/102600#0001 biolink:NamedThing omim.nt http://omim.org/entry/102600.0002 biolink:NamedThing APRT, 1-BP INS, 1834T For discussion of the 1-bp insertion in the APRT gene (1834insT) that was found in compound heterozygous state in a lymphoblastoid cell line from a patient with complete APRT deficiency ({614723}) by {15:Hidaka et al. (1987)}, see {102600.0001}. In identical twin brothers born to nonconsanguineous German parents with APRT deficiency, {11:Gathof et al. (1991)} identified a homozygous 1-bp insertion in the splice donor site of intron 4 of the APRT gene (the numbering system used by {11:Gathof et al. (1991)} indicated that the insertion was between bases 1831 and 1832 or 1832 and 1833). The insertion resulted in aberrant splicing. They quoted finding of the same mutation in 2 other Caucasian patients living in the U.S., and as 1 of 2 alleles in a Belgian patient with compound heterozygous APRT mutations ({15:Hidaka et al., 1987}). {29:Menardi et al. (1997)} demonstrated homozygosity for this common T insertion at the exon 4/intron 4 junction, resulting in the lack of exon 4 in the APRT mRNA. This common splice site mutation had always been found in association with a TaqI RFLP, leading to the proposal that this splice site mutation originated from a single event ({4:Chen et al., 1993}). However, {29:Menardi et al. (1997)} found a patient with this mutation who was negative for the TaqI RFLP. The position of this T insertion suggested it was a hotspot for mutational events ({4:Chen et al., 1993}). omim.nt GENO:0000002 ClinVar:RCV000033907 biolink:NamedThing omim.nt dbSNP:rs281860263 biolink:NamedThing omim.nt owl:NamedIndividual http://omim.org/entry/102600#0002 biolink:NamedThing omim.nt http://omim.org/entry/102600.0003 biolink:NamedThing APRT, MET136THR This mutation has been designated APRT*J. In Japanese patients with APRT deficiency ({614723}), {16:Hidaka et al. (1988)} identified a 2069T-C transition in exon 5 of the APRT gene, resulting in a met136-to-thr (M136T) substitution in the putative PRPP-binding site. The mutant enzyme showed abnormal kinetics and activity that was less than 10.3% of normal. By a specific cleavage method using cyanogen bromide (BrCN) to identify the M136T allele, {21:Kamatani et al. (1989)} found that 79% of all Japanese patients with APRT deficiency and more than half of the world's patients have this particular mutation. {20:Kamatani et al. (1990)} found that 24 of 39 Japanese patients with 2,8-dihydroxyadenine urolithiasis had only APRT*J alleles. They found that normal alleles occur in 4 major haplotypes, whereas all APRT*J alleles occurred in only 2. They interpreted this as meaning that all APRT*J alleles had a single origin and that this mutant sequence has been maintained for a long time, as reflected in the frequency of the recombinant alleles. {32:Sahota et al. (1991)} described DHA-lithiasis in a Japanese patient with APRT deficiency who was heterozygous for the M136T mutation. Enzyme studies showed decreased overall activity, with decreased affinity for PRPP. Lithiasis had previously only been observed in homozygotes. The polyamine pathway is thought to be the major source of endogenous adenine in man. Whether increased polyamine synthesis could lead to increased adenine production and predispose to DHA-lithiasis in an APRT heterozygote, remained to be determined. Among 141 defective APRT alleles from 72 different Japanese families, {19:Kamatani et al. (1992)} found the met136-to-thr mutation in 96 (68%). Thirty (21%) and 10 (7%) alleles had the TGG-to-TGA nonsense mutation at codon 98 ({102600.0005}) and duplication of a 4-bp sequence in exon 3 ({102600.0006}), respectively. {23:Kamatani et al. (1996)} noted that the APRT*J mutation is distributed nearly uniformly on the 4 main islands of Japan and Okinawa, suggesting a very early origin. Among 955 random Japanese blood samples, 7 (0.73%) were heterozygous for the APRT*J mutation. None of 231 Taiwanese samples contained heterozygotes for this mutation, whereas 2 (0.53%) of 356 Korean samples were heterozygous. Since the APRT*J mutation was found in Koreans and Okinawans who shared ancestors only before the Yayoi era (3rd century B.C. to 3rd century A.D.), the origin of the APRT*J mutation predates 300 B.C. omim.nt GENO:0000002 ClinVar:RCV000019958 biolink:NamedThing omim.nt ClinVar:RCV000033908 biolink:NamedThing omim.nt dbSNP:rs28999113 biolink:NamedThing omim.nt owl:NamedIndividual http://omim.org/entry/102600#0003 biolink:NamedThing omim.nt http://omim.org/entry/102600.0004 biolink:NamedThing APRT, ASP65VAL In 5 patients from Iceland with complete APRT deficiency ({614723}), {3:Chen et al. (1990)} identified a homozygous 1350A-T transversion in exon 3 of the APRT gene, resulting in an asp65-to-val (D65V) substitution. Common ancestry could only be identified for 2 of the cases. omim.nt GENO:0000002 ClinVar:RCV000033903 biolink:NamedThing omim.nt dbSNP:rs104894506 biolink:NamedThing omim.nt owl:NamedIndividual http://omim.org/entry/102600#0004 biolink:NamedThing omim.nt http://omim.org/entry/102600.0005 biolink:NamedThing APRT, TRP98TER In 4 unrelated Japanese individuals with complete APRT deficiency ({614723}), {30:Mimori et al. (1991)} identified a 1453G-A transition in the APRT gene, resulting in a trp98-to-ter (Y98X) substitution. omim.nt GENO:0000002 ClinVar:RCV000033905 biolink:NamedThing omim.nt dbSNP:rs104894507 biolink:NamedThing omim.nt owl:NamedIndividual http://omim.org/entry/102600#0005 biolink:NamedThing omim.nt http://omim.org/entry/102600.0006 biolink:NamedThing APRT, 4-BP DUP, EX3 Among 141 defective APRT alleles from 72 different Japanese families with APRT deficiency ({614723}), {19:Kamatani et al. (1992)} found that 10 (7%) had duplication of a CCGA sequence in exon 3. The duplication resulted in an APRT*Q0 (null) allele. Two other alleles, APRT*J ({102600.0003}) and trp98-to-ter (Y98X; {102600.0005}), accounted for 68% and 21% mutant alleles, respectively. The different alleles with the same mutation had the same haplotype, except for APRT*J. Evidence for a crossover or a gene conversion event within the APRT gene was observed in an APRT*J mutant allele. omim.nt GENO:0000002 ClinVar:RCV000033904 biolink:NamedThing omim.nt dbSNP:rs281860265 biolink:NamedThing omim.nt owl:NamedIndividual http://omim.org/entry/102600#0006 biolink:NamedThing omim.nt http://omim.org/entry/102600.0007 biolink:NamedThing APRT, LEU110PRO In 2 sisters from Newfoundland with APRT deficiency ({614723}), {33:Sahota et al. (1994)} identified a homozygous mutation in the APRT gene, resulting in a leu110-to-pro (L110P) substitution. One of the sisters exhibited 2,8-dihydroxyadenine urolithiasis, whereas the other was disease-free. omim.nt GENO:0000002 ClinVar:RCV000019962 biolink:NamedThing omim.nt dbSNP:rs104894508 biolink:NamedThing omim.nt owl:NamedIndividual http://omim.org/entry/102600#0007 biolink:NamedThing omim.nt http://omim.org/entry/102600.0008 biolink:NamedThing APRT, 254-BP DEL AND 8-BP INS In a Caucasian patient with complete APRT deficiency ({614723}), {29:Menardi et al. (1997)} found compound heterozygosity for 2 mutations in the APRT gene: a common T insertion at the IVS4 splice donor site ({102600.0002}) and a novel complex mutation involving simultaneous deletion/insertion and repair events. The second mutation involved a deletion of 254 bp and an insertion of 8 bp exactly at the site of the deletion. Downstream of the mutations, {29:Menardi et al. (1997)} found a 14-bp sequence of inverse complementary to this insertion and 6 flanking nucleotides. A more detailed analysis of the region where the deletion had occurred revealed several informative sequence features suitable to explain how the mutation took place. omim.nt GENO:0000002 ClinVar:RCV000019963 biolink:NamedThing omim.nt http://omim.org/entry/102600#0008 biolink:NamedThing omim.nt http://omim.org/entry/102600.0009 biolink:NamedThing APRT, TER-SER In a Japanese man with APRT deficiency ({614723}), {37:Taniguchi et al. (1998)} found that the physiologic stop codon of the gene, TGA, was replaced by TCA. This base substitution generated a new HinfI restriction site, and, using PCR and subsequent digestion by this enzyme, they could confirm that the patient was homozygous for the base substitution. The amount of mRNA in transformed B cells was approximately one-quarter of that in control subjects, and no APRT proteins were detected. In eukaryotes, unlike prokaryotes, no rescue systems for defective polypeptide termination caused by a missing stop codon have been found. Therefore, the outcome of the defect in this patient was unclear from present knowledge about termination of polypeptide synthesis. The stop codon was changed to a serine codon and the reading frame was extended to the poly(A) addition site. The poly(A) signal AGTAAA is located 213 nucleotides downstream of the physiologic stop codon, but there are no stop codons between them ({2:Broderick et al., 1987}). The patient developed pseudoarthrosis after a traumatic broken arm, and was found to have increased serum creatinine and 2,8-dihydroxyadenine crystals in his urine. Imaging showed a small right kidney. omim.nt GENO:0000002 ClinVar:RCV000019964 biolink:NamedThing omim.nt dbSNP:rs387906584 biolink:NamedThing omim.nt owl:NamedIndividual http://omim.org/entry/102600#0009 biolink:NamedThing omim.nt MONARCH:.well-known/genid/b590265fc46d581aedb3 biolink:NamedThing GRCh38chr16-88809338-88811927-Region omim.nt MONARCH:.well-known/genid/b6f4c42216f42c7627ba faldo:Region MONARCH:.well-known/genid/OMIM102600ref1 biolink:NamedThing Regional localization of the human alpha-globin gene to the short arm of chromosome 16 (16p12-pter) using both somatic cell hybrids and in situ hybridization. omim.nt IAO:0000310 MONARCH:.well-known/genid/OMIM102600ref11 biolink:NamedThing Identification of a splice mutation at the adenine phosphoribosyltransferase locus in a German family. omim.nt IAO:0000310 MONARCH:.well-known/genid/OMIM102600ref26 biolink:NamedThing Further evidence for the regional localization of human APRT and DIA4 on chromosome 16. (Abstract) omim.nt IAO:0000310 MONARCH:.well-known/genid/OMIM102600ref3 biolink:NamedThing Demonstration of a common mutation at the adenine phosphoribosyltransferase (APRT) locus in the Icelandic population. (Abstract) omim.nt IAO:0000310 MONARCH:.well-known/genid/OMIM102600ref34 biolink:NamedThing Adenine phosphoribosyltransferase deficiency and 2,8-dihydroxyadenine lithiasis.:In: Scriver, C. R.; Beaudet, A. L.; Sly, W. S.; Valle, D. (eds.) : The Metabolic and Molecular Bases of Inherited Disease. Vol. II. (8th ed.) omim.nt IAO:0000310 PMID:10479485 biolink:NamedThing omim.nt IAO:0000013 PMID:1152988 biolink:NamedThing omim.nt IAO:0000013 PMID:1353080 biolink:NamedThing omim.nt IAO:0000013 PMID:1673292 biolink:NamedThing omim.nt IAO:0000013 PMID:1985452 biolink:NamedThing omim.nt IAO:0000013 PMID:1998341 biolink:NamedThing omim.nt IAO:0000013 PMID:2227951 biolink:NamedThing omim.nt IAO:0000013 PMID:2306728 biolink:NamedThing omim.nt IAO:0000013 PMID:2502918 biolink:NamedThing omim.nt IAO:0000013 PMID:3343350 biolink:NamedThing omim.nt IAO:0000013 PMID:3447590 biolink:NamedThing omim.nt IAO:0000013 PMID:3531209 biolink:NamedThing omim.nt IAO:0000013 PMID:3554238 biolink:NamedThing omim.nt IAO:0000013 PMID:3610146 biolink:NamedThing omim.nt IAO:0000013 PMID:3680503 biolink:NamedThing omim.nt IAO:0000013 PMID:3684585 biolink:NamedThing omim.nt IAO:0000013 PMID:3780312 biolink:NamedThing omim.nt IAO:0000013 PMID:3817810 biolink:NamedThing omim.nt IAO:0000013 PMID:3876264 biolink:NamedThing omim.nt IAO:0000013 PMID:4043967 biolink:NamedThing omim.nt IAO:0000013 PMID:4129802 biolink:NamedThing omim.nt IAO:0000013 PMID:5676523 biolink:NamedThing omim.nt IAO:0000013 PMID:5763607 biolink:NamedThing omim.nt IAO:0000013 PMID:6360556 biolink:NamedThing omim.nt IAO:0000013 PMID:6572371 biolink:NamedThing omim.nt IAO:0000013 PMID:6994264 biolink:NamedThing omim.nt IAO:0000013 PMID:7286981 biolink:NamedThing omim.nt IAO:0000013 PMID:7685481 biolink:NamedThing omim.nt IAO:0000013 PMID:7915931 biolink:NamedThing omim.nt IAO:0000013 PMID:8643571 biolink:NamedThing omim.nt IAO:0000013 PMID:869896 biolink:NamedThing omim.nt IAO:0000013 PMID:8829629 biolink:NamedThing omim.nt IAO:0000013 PMID:8882882 biolink:NamedThing omim.nt IAO:0000013 PMID:9298830 biolink:NamedThing omim.nt IAO:0000013 PMID:9521589 biolink:NamedThing omim.nt IAO:0000013 OBO:CHR_9606chr16q24.3 biolink:NamedThing omim.nt owl:Class http://omim.org/entry/614723 biolink:NamedThing|biolink:Disease Adenine Phosphoribosyltransferase Deficiency Adenine Phosphoribosyltransferase Deficiency omim.nt ADENINE PHOSPHORIBOSYLTRANSFERASE DEFICIENCY; APRTD|Aprt Deficiency|Nephrolithiasis, Dha|Urolithiasis, 2,8-Dihydroxyadenine|Urolithiasis, Dha owl:Class UMLS:C1366623 biolink:NamedThing omim.nt owl:Class https://www.ncbi.nlm.nih.gov/gene/353 biolink:NamedThing omim.nt http://omim.org/entry/102610.0001 biolink:NamedThing ACTA1, LEU94PRO In 2 infant sibs with severe autosomal recessive nemaline myopathy-3 (NEM3; {161800}) leading to death at 5 and 19 days of age, {28:Nowak et al. (1999)} identified compound heterozygosity for 2 mutations in the ACTA1 gene: a T-to-C transition in exon 3, resulting in a leu94-to-pro (L94P) substitution inherited from the unaffected father, and an A-to-G transition in exon 5, resulting in a glu259-to-val (E259V; {102610.0005}) substitution inherited from the unaffected mother. omim.nt GENO:0000002 http://omim.org/entry/102610 biolink:NamedThing|biolink:Gene ACTA1 Actin, Alpha, Skeletal Muscle 1|mutation identified in 1 SHPM family omim.nt ACTIN, ALPHA, SKELETAL MUSCLE 1; ACTA1|Asma owl:Class ClinVar:RCV000019941 biolink:NamedThing omim.nt dbSNP:rs121909519 biolink:NamedThing omim.nt owl:NamedIndividual http://omim.org/entry/102610#0001 biolink:NamedThing omim.nt http://omim.org/entry/102610.0002 biolink:NamedThing ACTA1, ASN115SER In a mother and her 2 children who had nemaline myopathy (NEM3; {161800}), {28:Nowak et al. (1999)} identified a heterozygous A-to-G transition in exon 3 of the ACTA1 gene, resulting in an asn115-to-ser (N115S) substitution. One of the children with a severe form of the disorder was alive at 3 years; the mother and the other child had milder forms, and were alive at 33 and 18 years of age, respectively. {20:Ilkovski et al. (2001)} reported a 35-year-old woman with the N115S mutation. She had typical congenital nemaline myopathy with neonatal onset of feeding difficulties, respiratory tract infections, hypotonia, facial diplegia, and proximal muscle weakness in the first weeks of life. Her disease was very slowly progressive or nonprogressive. She had an affected younger sib and an affected daughter, consistent with autosomal dominant inheritance. omim.nt GENO:0000002 ClinVar:RCV000019942 biolink:NamedThing omim.nt ClinVar:RCV001090700 biolink:NamedThing omim.nt dbSNP:rs121909520 biolink:NamedThing omim.nt owl:NamedIndividual http://omim.org/entry/102610#0002 biolink:NamedThing omim.nt http://omim.org/entry/102610.0003 biolink:NamedThing ACTA1, GLY15ARG In patient with a congenital actin myopathy (see {161800}), previously reported as patient 2 by {13:Goebel et al. (1997)}, {28:Nowak et al. (1999)} identified a heterozygous G-to-C transversion in exon 2 of the ACTA1 gene, resulting in a gly15-to-arg (G15R) substitution. The patient was delivered by emergency Cesarean section at 37 weeks' gestation due to maternal polyhydramnios, had severe hypotonia necessitating ventilatory support, and died at age 3 months. Postmortem examination excluded spinal muscular atrophy ({253300}). Muscle biopsy showed large areas of sarcoplasm devoid of normal myofibrils and mitochondria, and replaced with dense masses of thin filaments that were immunoreactive to actin. Central cores, obvious rods, ragged-red fibers, and necrosis were absent. omim.nt GENO:0000002 ClinVar:RCV000019943 biolink:NamedThing omim.nt dbSNP:rs121909521 biolink:NamedThing omim.nt owl:NamedIndividual http://omim.org/entry/102610#0003 biolink:NamedThing omim.nt http://omim.org/entry/102610.0004 biolink:NamedThing ACTA1, VAL163LEU In 2 unrelated patients with nemaline myopathy-3 (NEM3; {161800}), originally reported by {13:Goebel et al. (1997)}, {28:Nowak et al. (1999)} identified a heterozygous val163-to-leu (V163L) substitution in the ACTA1 gene. However, the amino acid substitution was caused by different nucleotide changes: in a child still alive at 7.5 years of age, codon 163 was changed from GTG (val) to CTG (leu); in an infant who died at 4 months of age, codon 163 was changed from GTG (val) to TTG (leu). One patient was hypotonic from birth, had atrophy of the pelvic and shoulder girdle muscles, and cardiomyopathy. He also had a high-arched palate. Muscle biopsy showed subsarcolemmal regions that were devoid of oxidative activity and filled with actin-immunopositive densely packed thin filaments. Intranuclear nemaline rods were also present. The second patient was hypotonic from birth, had cardiomegaly, and died of cardiorespiratory insufficiency at age 4 months. Muscle biopsy showed a type-1 fiber predominance, subsarcolemmal masses of thin filaments, and intranuclear nemaline rods ({13:Goebel et al., 1997}). omim.nt GENO:0000002 ClinVar:RCV000019944 biolink:NamedThing omim.nt dbSNP:rs121909522 biolink:NamedThing omim.nt owl:NamedIndividual http://omim.org/entry/102610#0004 biolink:NamedThing omim.nt http://omim.org/entry/102610.0005 biolink:NamedThing ACTA1, GLU259VAL For discussion of the glu259-to-val (E259V) mutation in the ACTA1 gene that was found in compound heterozygous state in 2 infant sibs with severe autosomal recessive nemaline myopathy-3 (NEM3; {161800}) by {28:Nowak et al. (1999)}, see {102610.0004}. omim.nt GENO:0000002 ClinVar:RCV000019945 biolink:NamedThing omim.nt ClinVar:RCV001270724 biolink:NamedThing omim.nt dbSNP:rs121909523 biolink:NamedThing omim.nt owl:NamedIndividual http://omim.org/entry/102610#0005 biolink:NamedThing omim.nt http://omim.org/entry/102610.0006 biolink:NamedThing ACTA1, ILE357LEU In a child with severe congenital nemaline myopathy (NEM3; {161800}) who died at the age of 6 months of respiratory failure, {20:Ilkovski et al. (2001)} identified a heterozygous de novo mutation in the ACTA1 gene, resulting in an ile357-to-leu (I357L) substitution. omim.nt GENO:0000002 ClinVar:RCV000019946 biolink:NamedThing omim.nt dbSNP:rs121909524 biolink:NamedThing omim.nt owl:NamedIndividual http://omim.org/entry/102610#0006 biolink:NamedThing omim.nt http://omim.org/entry/102610.0007 biolink:NamedThing ACTA1, GLY268CYS In a male patient with childhood onset of nemaline myopathy (NEM3; {161800}), {20:Ilkovski et al. (2001)} identified a heterozygous gly268-to-cys (G268C) substitution in the ACTA1 gene. omim.nt GENO:0000002 ClinVar:RCV000019947 biolink:NamedThing omim.nt dbSNP:rs121909525 biolink:NamedThing omim.nt owl:NamedIndividual http://omim.org/entry/102610#0007 biolink:NamedThing omim.nt http://omim.org/entry/102610.0008 biolink:NamedThing ACTA1, ILE136MET {20:Ilkovski et al. (2001)} identified a heterozygous ile136-to-met (I136M) substitution in the ACTA1 gene in a 45-year-old man with nemaline myopathy (NEM3; {161800}). Although he had infantile onset and delayed motor development, his weakness was nonprogressive, and he was physically active as an adult and regularly engaged in long-distance competitive cycling. He had a weak cough and frequent respiratory infections. Echocardiography was normal. omim.nt GENO:0000002 ClinVar:RCV000019948 biolink:NamedThing omim.nt dbSNP:rs121909526 biolink:NamedThing omim.nt owl:NamedIndividual http://omim.org/entry/102610#0008 biolink:NamedThing omim.nt http://omim.org/entry/102610.0009 biolink:NamedThing ACTA1, ASP3TYR In 11 affected members in 4 generations and 8 separate sibships of a German family with autosomal dominant congenital myopathy with cores (see {161800}), part of the phenotypic spectrum of nemaline myopathy-3 (NEM3), {23:Kaindl et al. (2004)} identified a heterozygous 110G-T transversion in the ACTA1 gene, resulting in an asp3-to-tyr (D3Y) substitution in the mature protein. omim.nt GENO:0000002 ClinVar:RCV000019949 biolink:NamedThing omim.nt dbSNP:rs121909527 biolink:NamedThing omim.nt owl:NamedIndividual http://omim.org/entry/102610#0009 biolink:NamedThing omim.nt http://omim.org/entry/102610.0010 biolink:NamedThing ACTA1, GLU334ALA In 5 affected members spanning 3 generations of a Chinese family with autosomal dominant congenital myopathy with cores (see {161800}), part of the phenotypic spectrum of nemaline myopathy-3 (NEM3), {23:Kaindl et al. (2004)} identified a 1110A-C transversion in the ACTA1 gene, resulting in a glu334-to-ala (E334A) substitution. Two members of the family developed adult-onset hypertrophic cardiomyopathy and respiratory insufficiency. omim.nt GENO:0000002 ClinVar:RCV000019950 biolink:NamedThing omim.nt dbSNP:rs121909528 biolink:NamedThing omim.nt owl:NamedIndividual http://omim.org/entry/102610#0010 biolink:NamedThing omim.nt http://omim.org/entry/102610.0011 biolink:NamedThing ACTA1, ASP292VAL In a patient with severe congenital fiber-type disproportion myopathy ({255310}), {25:Laing et al. (2004)} identified a heterozygous A-to-T transversion in exon 6 of the ACTA1 gene, resulting in an asp292-to-val (D292V) substitution in a region that forms part of the monomeric actin surface that would be exposed in the F-actin polymer. The mutation was not identified in more than 300 control chromosomes. DNA was not available from any of the patient's relatives. Using mass spectrometry and gel electrophoresis to examine patient skeletal muscle, {6:Clarke et al. (2007)} determined that D292V-actin accounted for 50% of total sarcomeric actin. In vitro assays showed that D292V-actin resulted in decreased motility due to abnormal interactions between actin and tropomyosin, with tropomyosin stabilized in the 'off' position. Cellular transfection studies demonstrated that the mutant protein incorporated into actin filaments and did not result in increased actin aggregation or disruption of the sarcomere. {6:Clarke et al. (2007)} concluded that ACTA1 mutations resulting in CFTD cause weakness by interfering with sarcomeric function rather than structure. omim.nt GENO:0000002 ClinVar:RCV000019951 biolink:NamedThing omim.nt ClinVar:RCV001028007 biolink:NamedThing omim.nt dbSNP:rs121909529 biolink:NamedThing omim.nt owl:NamedIndividual http://omim.org/entry/102610#0011 biolink:NamedThing omim.nt http://omim.org/entry/102610.0012 biolink:NamedThing ACTA1, LEU221PRO In a patient with severe congenital fiber-type disproportion myopathy ({255310}), {25:Laing et al. (2004)} identified a heterozygous T-to-C transition in exon 5 of the ACTA1 gene, resulting in a leu221-to-pro (L221P) substitution in a region that forms part of the monomeric actin surface that would be exposed in the F-actin polymer. The mutation was not identified in more than 300 control chromosomes. DNA was not available from any of the patient's relatives. omim.nt GENO:0000002 ClinVar:RCV000019952 biolink:NamedThing omim.nt dbSNP:rs121909530 biolink:NamedThing omim.nt owl:NamedIndividual http://omim.org/entry/102610#0012 biolink:NamedThing omim.nt http://omim.org/entry/102610.0013 biolink:NamedThing ACTA1, PRO332SER In a patient with severe congenital fiber-type disproportion myopathy ({255310}), {25:Laing et al. (2004)} identified a heterozygous C-to-T transition in exon 7 of the ACTA1 gene, resulting in a pro332-to-ser (P332S) substitution in a region that forms part of the monomeric actin surface that would be exposed in the F-actin polymer. The mutation was not identified in more than 300 control chromosomes. DNA was not available from any of the patient's relatives. omim.nt GENO:0000002 ClinVar:RCV000019953 biolink:NamedThing omim.nt dbSNP:rs121909531 biolink:NamedThing omim.nt owl:NamedIndividual http://omim.org/entry/102610#0013 biolink:NamedThing omim.nt http://omim.org/entry/102610.0014 biolink:NamedThing ACTA1, VAL163MET In affected members of a family with nemaline myopathy-3 (NEM3; {161800}) associated with intranuclear rods on muscle biopsy, {19:Hutchinson et al. (2006)} identified a heterozygous G-to-A transition in exon 4 of the ACTA1 gene, resulting in a val163-to-met (V163M) substitution. Another mutation has been reported in this codon (V163I; {102610.0004}). Clinical features included hypotonia early in life, limb muscle weakness and atrophy, tall thin face, and high-arched palate. Skeletal muscle biopsies varied but tended to show intranuclear rods within myofibers. By electron microscopy of muscle samples from patients reported by {19:Hutchinson et al. (2006)}, {9:Domazetovska et al. (2007)} found mostly normal sarcomere structure with small areas of sarcomeric disarray. Immunohistochemical studies showed that the V163M mutation resulted in sequestration of sarcomeric and Z line proteins into intranuclear aggregates. There was some evidence of muscle regeneration, suggesting a compensatory effect. Cell culture studies showed similar findings. Transgenic V161M-mutant Drosophila were flightless with sarcomeric disorganization and altered Z line structure in muscle. The findings provided a mechanism for muscle weakness. omim.nt GENO:0000002 ClinVar:RCV000019954 biolink:NamedThing omim.nt http://omim.org/entry/102610#0014 biolink:NamedThing omim.nt http://omim.org/entry/102610.0015 biolink:NamedThing ACTA1, GLU74ASP AND HIS75TYR In a male infant with severe fatal nemaline myopathy (NEM3; {161800}), {11:Garcia-Angarita et al. (2009)} identified heterozygosity for an allele carrying 2 de novo mutations in cis affecting adjacent nucleotides in exon 3 of the ACTA1 gene: a 222G-T transversion, resulting in a glu74-to-asp (E74D) substitution, and a 223C-T transition, resulting in a his75-to-tyr (H75Y) substitution. Neither unaffected parent carried either of the mutations, suggesting possible germline mosaicism. {11:Garcia-Angarita et al. (2009)} noted that each mutation had previously been reported in isolation as causative for nemaline myopathy, but had never been reported together on the same allele. The phenotype in their patient was severe, including decreased movements in utero, breech presentation, and congenital contractures. After birth, there was severe hypotonia, lack of spontaneous movements, and death from respiratory failure at age 2 months. Skeletal muscle biopsy showed myofibrillar disorganization and nemaline rods. omim.nt GENO:0000002 ClinVar:RCV000019955 biolink:NamedThing omim.nt dbSNP:rs267606627 biolink:NamedThing omim.nt owl:NamedIndividual http://omim.org/entry/102610#0015 biolink:NamedThing omim.nt http://omim.org/entry/102610.0016 biolink:NamedThing ACTA1, LYS328ASN In an infant with nemaline myopathy-3 (NEM3; {161800}) who presented with an atypical phenotype of stiffness and hypertonicity, {22:Jain et al. (2012)} identified a de novo heterozygous 984G-C transversion in the ACTA1 gene, resulting in a lys328-to-asn (K328N) substitution (K326N in the mature protein). Patient biopsy showed nemaline bodies and 32% mutant actin. In vitro motility analysis of actin thin filaments derived from the patient's tissue showed increased sensitivity to calcium, indicating an activated state. Expression of the mutant in mouse muscle cells did not result in the formation of rod-like structures, suggesting a different mechanism of nemaline body formation. Medical treatment was ineffective, and the patient died at age 9 months in an asystolic episode. The report expanded the phenotypic spectrum associated with ACTA1 mutations to include stiffness, rigidity, and hypertonicity. omim.nt GENO:0000002 ClinVar:RCV000043506 biolink:NamedThing omim.nt dbSNP:rs398122936 biolink:NamedThing omim.nt owl:NamedIndividual http://omim.org/entry/102610#0016 biolink:NamedThing omim.nt http://omim.org/entry/102610.0017 biolink:NamedThing ACTA1, TRP358CYS In a 9-year-old Japanese boy with nemaline myopathy-3 (NEM3; {161800}) who developed fatal dilated cardiomyopathy, {12:Gatayama et al. (2013)} identified a heterozygous c.1074G-T transversion in exon 7 of the ACTA1 gene, resulting in a trp358-to-cys (W358C) substitution. The mutation was not found in 50 Japanese controls. Functional studies of the variant were not performed. The patient had normal motor development in early childhood, but showed mild nonprogressive skeletal muscle weakness, such as slowed running compared to his peers. Other features included hypotonia, myopathic facies, high-arched palate, and mild weakness of proximal and distal muscles. He presented at age 9 years with acute deterioration of cardiac function, and died of cardiac failure 6 months later. Postmortem examination of cardiac muscle showed variation in myocardial fiber size and a few electron-dense fine structures related to Z lines. Skeletal muscle biopsy had previously shown typical nemaline rods. {12:Gatayama et al. (2013)} noted that childhood-onset dilated cardiomyopathy is rare in patients with ACTA1 mutations. omim.nt GENO:0000002 ClinVar:RCV000115017 biolink:NamedThing omim.nt dbSNP:rs587777354 biolink:NamedThing omim.nt owl:NamedIndividual http://omim.org/entry/102610#0017 biolink:NamedThing omim.nt http://omim.org/entry/102610.0018 biolink:NamedThing ACTA1, GLU197ASP In affected members of a large family with scapulohumeroperoneal myopathy (SHPM; {616852}), originally reported by {5:Armstrong et al. (1966)}, {34:Zukosky et al. (2015)} identified a heterozygous c.591C-A transversion in exon 4 of the ACTA1 gene, resulting in a glu197-to-asp (E197D) substitution. The mutation was found by a combination of linkage analysis and whole-exome sequencing and was confirmed by Sanger sequencing. The mutation segregated with the disorder in the family and was not found in the dbSNP or ExAC databases. Transfection of the mutation into COS-7 cells showed that the mutant protein had normal actin localization and did not form nemaline rods. Injection of the mutation into zebrafish embryos did not result in any morphologic abnormalities or abnormal muscle histology up to 6 days after fertilization. {34:Zukosky et al. (2015)} postulated that a fundamentally different pathogenic process than changes in actin cytoarchitecture or rod formation was responsible for the phenotype, such as changes in interaction or force generation, actin filament stability, or differences in the directionality of actin filament growth. omim.nt GENO:0000002 ClinVar:RCV000210030 biolink:NamedThing omim.nt ClinVar:RCV000414423 biolink:NamedThing omim.nt dbSNP:rs869312739 biolink:NamedThing omim.nt owl:NamedIndividual http://omim.org/entry/102610#0018 biolink:NamedThing omim.nt MONARCH:.well-known/genid/b3fdcb82b027274c3579 biolink:NamedThing GRCh38chr1-229431244-229434093-Region omim.nt MONARCH:.well-known/genid/b52b87a92c1265c31808 faldo:Region MONARCH:.well-known/genid/OMIM102610ref16 biolink:NamedThing The actin gene family in man: assignment of the gene for skeletal muscle alpha-actin to chromosome 1, and presence of actin sequences on autosomes 2 and 3, and on the X and Y chromosomes. (Abstract) omim.nt IAO:0000310 MONARCH:.well-known/genid/OMIM102610ref24 biolink:NamedThing Homologies between the X and Y chromosomes analyzed with DNA probes. (Abstract) omim.nt IAO:0000310 MONARCH:.well-known/genid/OMIM102610ref30 biolink:NamedThing The coexpressed genes for human alpha (ACTA) and cardiac actin (ACTC) are on chromosomes 1 and 15, respectively. (Abstract) omim.nt IAO:0000310 PMID:10508519 biolink:NamedThing omim.nt IAO:0000013 PMID:11333380 biolink:NamedThing omim.nt IAO:0000013 PMID:12138199 biolink:NamedThing omim.nt IAO:0000013 PMID:12899878 biolink:NamedThing omim.nt IAO:0000013 PMID:1314333 biolink:NamedThing omim.nt IAO:0000013 PMID:15198992 biolink:NamedThing omim.nt IAO:0000013 PMID:15236405 biolink:NamedThing omim.nt IAO:0000013 PMID:15468086 biolink:NamedThing omim.nt IAO:0000013 PMID:15520409 biolink:NamedThing omim.nt IAO:0000013 PMID:16427282 biolink:NamedThing omim.nt IAO:0000013 PMID:17387733 biolink:NamedThing omim.nt IAO:0000013 PMID:17705262 biolink:NamedThing omim.nt IAO:0000013 PMID:18976909 biolink:NamedThing omim.nt IAO:0000013 PMID:19158791 biolink:NamedThing omim.nt IAO:0000013 PMID:19553116 biolink:NamedThing omim.nt IAO:0000013 PMID:19562689 biolink:NamedThing omim.nt IAO:0000013 PMID:22442437 biolink:NamedThing omim.nt IAO:0000013 PMID:23650303 biolink:NamedThing omim.nt IAO:0000013 PMID:25938801 biolink:NamedThing omim.nt IAO:0000013 PMID:2907503 biolink:NamedThing omim.nt IAO:0000013 PMID:4952447 biolink:NamedThing omim.nt IAO:0000013 PMID:6190133 biolink:NamedThing omim.nt IAO:0000013 PMID:6592095 biolink:NamedThing omim.nt IAO:0000013 PMID:6897916 biolink:NamedThing omim.nt IAO:0000013 PMID:8093670 biolink:NamedThing omim.nt IAO:0000013 PMID:8258301 biolink:NamedThing omim.nt IAO:0000013 PMID:8422497 biolink:NamedThing omim.nt IAO:0000013 PMID:9185179 biolink:NamedThing omim.nt IAO:0000013 http://omim.org/entry/616852 biolink:NamedThing|biolink:Disease Myopathy, Scapulohumeroperoneal Myopathy, Scapulohumeroperoneal omim.nt MYOPATHY, SCAPULOHUMEROPERONEAL; SHPM owl:Class OBO:CHR_9606chr1q42.1 biolink:NamedThing omim.nt owl:Class http://omim.org/entry/161800 biolink:NamedThing|biolink:Disease Nemaline Myopathy 3 Nemaline Myopathy 3 omim.nt NEMALINE MYOPATHY 3; NEM3|Myopathy, Actin, Congenital, With Cores|Myopathy, Actin, Congenital, With Excess of Thin Myofilaments|Nemaline Myopathy 3, With Intranuclear Rods owl:Class http://omim.org/entry/255310 biolink:NamedThing|biolink:Disease Myopathy, Congenital, With Fiber-Type Disproportion Myopathy, Congenital, With Fiber-Type Disproportion omim.nt MYOPATHY, CONGENITAL, WITH FIBER-TYPE DISPROPORTION; CFTD|Fiber-Type Disproportion Myopathy, Congenital owl:Class http://www.omim.org/phenotypicSeries/PS161800 biolink:NamedThing|biolink:Disease Nemaline myopathy omim.nt owl:Class UMLS:C1412136 biolink:NamedThing omim.nt owl:Class https://www.ncbi.nlm.nih.gov/gene/58 biolink:NamedThing omim.nt http://omim.org/entry/102620.0001 biolink:NamedThing ACTA2, ARG149CYS In a large family in which thoracic aortic aneurysm with dissection segregated with reduced penetrance (AAT6; {611788}), {3:Guo et al. (2007)} found a heterozygous 492C-T transition in exon 5 of the ACTA2 gene that caused an arg149-to-cys (R149C) amino acid substitution. In further studies, 4 additional families with the ACTA2 mutation were found; however, each family had a unique haplotype, implying that the mutations arose de novo in multiple families. Livedo reticularis and iris flocculi were found together or separately in some of these families. {4:Guo et al. (2009)} analyzed 45 individuals with the R149C mutation and found that, in addition to the already established predisposition to TAAD, this mutation led to coronary artery disease (24 mutation carriers with TAAD, 12 with coronary artery disease). omim.nt GENO:0000002 http://omim.org/entry/102620 biolink:NamedThing|biolink:Gene ACTA2 Actin, Alpha-2, Smooth Muscle, Aorta omim.nt ACTIN, ALPHA-2, SMOOTH MUSCLE, AORTA; ACTA2|Actin, Alpha, Smooth Muscle, Aortic|Actin, Vascular Smooth Muscle owl:Class ClinVar:RCV000019938 biolink:NamedThing omim.nt ClinVar:RCV000246692 biolink:NamedThing omim.nt ClinVar:RCV000505736 biolink:NamedThing omim.nt ClinVar:RCV000581791 biolink:NamedThing omim.nt ClinVar:RCV000617114 biolink:NamedThing omim.nt dbSNP:rs121434526 biolink:NamedThing omim.nt owl:NamedIndividual http://omim.org/entry/102620#0001 biolink:NamedThing omim.nt http://omim.org/entry/102620.0002 biolink:NamedThing ACTA2, ARG258HIS In a family of European descent with hereditary thoracic aortic aneurysm with dissection (AAT6; {611788}), {3:Guo et al. (2007)} identified an 820G-A transition in exon 7 of the ACTA2 gene, resulting in an arg258-to-his (R258H) substitution. One individual in the family had patent ductus arteriosus. {4:Guo et al. (2009)} analyzed 15 individuals carrying a missense mutation at arg258 and found that, in addition to the already established predisposition to TAAD, mutation at this position was associated with stroke (10 individuals with TAAD, 7 with stroke). In 1 family with the R258H mutation, 3 affected individuals had a phenotype consistent with moyamoya disease-5 (MYMY5; {614042}). Two of these 3 patients had strokes at ages 44 and 46 years, respectively, and also had thoracic aortic aneurysm with dissection; the third had isolated moyamoya disease with stroke at age 16 years. The findings indicated that ACTA2 mutations can cause a spectrum of vascular diseases, even within a single family. omim.nt GENO:0000002 ClinVar:RCV000019939 biolink:NamedThing omim.nt ClinVar:RCV000022435 biolink:NamedThing omim.nt ClinVar:RCV000181027 biolink:NamedThing omim.nt dbSNP:rs121434527 biolink:NamedThing omim.nt owl:NamedIndividual http://omim.org/entry/102620#0002 biolink:NamedThing omim.nt http://omim.org/entry/102620.0003 biolink:NamedThing ACTA2, ARG258CYS In 2 families of European descent with hereditary thoracic aortic aneurysm with dissection (AAT6; {611788}), {3:Guo et al. (2007)} identified an 819C-T transition in exon 7 of the ACTA2 gene, resulting in an arg258-to-cys (R258C) substitution. All 5 mutation carriers in 1 family had patent ductus arteriosus. {4:Guo et al. (2009)} analyzed 15 individuals carrying a missense mutation at arg258 and found that, in addition to the already established predisposition to TAAD, mutation at this position was associated with stroke (10 individuals with TAAD, 7 with stroke). The authors identified a high risk of early-onset strokes in family members carrying the R258C mutation. In 1 family with the R258C mutation, 2 members had a phenotype consistent with moyamoya disease-5 ({614042}), with strokes at ages 39 and 5 years, respectively. The older patient had thoracic aneurysm with dissection at age 32 years, whereas the stroke was fatal in the younger patient. The findings indicated that ACTA2 mutations can cause a spectrum of vascular diseases, even within a single family. omim.nt GENO:0000002 ClinVar:RCV000019940 biolink:NamedThing omim.nt ClinVar:RCV000022436 biolink:NamedThing omim.nt ClinVar:RCV000252066 biolink:NamedThing omim.nt ClinVar:RCV000523600 biolink:NamedThing omim.nt dbSNP:rs121434528 biolink:NamedThing omim.nt owl:NamedIndividual http://omim.org/entry/102620#0003 biolink:NamedThing omim.nt http://omim.org/entry/102620.0004 biolink:NamedThing ACTA2, ARG179HIS Multisystemic Smooth Muscle Dysfunction Syndrome In 7 unrelated patients of northern European descent with multisystemic smooth muscle dysfunction syndrome (MSMDS; {613834}), {9:Milewicz et al. (2010)} identified heterozygosity for a de novo arg179-to-his (R179H) substitution in the ACTA2 gene. The mutation was not identified in parents' DNA samples, confirming the de novo status in 5 patients. Three of the patients had previously been reported ({1:Ades et al., 1999}, {6:Khan et al., 2004}, and {8:Lemire et al., 2004}, respectively). {2:Brodsky et al. (2014)} identified the R179H mutation in a 9-year-old boy diagnosed with congenital mydriasis and prune belly syndrome with megacystis, bilateral hydroureter, and hydronephrosis requiring surgical correction. On echocardiography at age 9 years, he had severe dilatation of the aortic root and mid-ascending aorta. MRI showed massive dilatation of the intracranial arteries and tortuosity of the distal cerebral vasculature. In a review of the clinical history and outcomes of 33 patients with MSMDS, {10:Regalado et al. (2018)} found that 24 of the patients were heterozygous for the R179H mutation. Moyamoya Disease 5 {11:Roder et al. (2011)} identified a heterozygous R179H mutation in 1 of 39 patients of European origin with moyamoya disease-5 (MYMY5; {614042}) and no family history of the disorder. The patient was a girl who had a stroke at age 3 years, but she had no other abnormalities, particularly none of those described by {9:Milewicz et al. (2010)}. omim.nt GENO:0000002 ClinVar:RCV000022437 biolink:NamedThing omim.nt ClinVar:RCV000022438 biolink:NamedThing omim.nt ClinVar:RCV000181023 biolink:NamedThing omim.nt ClinVar:RCV000211886 biolink:NamedThing omim.nt ClinVar:RCV000228180 biolink:NamedThing omim.nt ClinVar:RCV000415107 biolink:NamedThing omim.nt ClinVar:RCV000617113 biolink:NamedThing omim.nt ClinVar:RCV000763224 biolink:NamedThing omim.nt dbSNP:rs387906592 biolink:NamedThing omim.nt owl:NamedIndividual http://omim.org/entry/102620#0004 biolink:NamedThing omim.nt http://omim.org/entry/102620.0005 biolink:NamedThing ACTA2, ARG39CYS In a 3-generation German family with autosomal dominant thoracic aortic aneurysm (AAT6; {611788}), {5:Hoffjan et al. (2011)} identified heterozygosity for a c.115C-T transition in exon 2 of the ACTA2 gene, resulting in an arg39-to-cys (R39C) substitution at a highly conserved residue adjacent to the DNAse-I-binding loop within subdomain 2. The mutation segregated with disease in the family and was not found in 192 control chromosomes or in the GenBank dbSNP library. The vascular phenotype was variable in this family, ranging from mild aortic dilation and insufficiency in a 44-year-old woman to overt aortic aneurysm extending from the ascending to the abdominal aorta in a 25-year-old man. None of the affected individuals showed syndromic features, and there was no history of premature stroke or coronary artery disease. {5:Hoffjan et al. (2011)} noted that although a different mutation at the R39 residue, R39H, had been associated with type A dissections in 2 families and with type B dissections in another family ({4:Guo et al., 2009}), dissections were not observed in the family with the R39C mutation. omim.nt GENO:0000002 ClinVar:RCV000055647 biolink:NamedThing omim.nt ClinVar:RCV000143866 biolink:NamedThing omim.nt ClinVar:RCV000490091 biolink:NamedThing omim.nt dbSNP:rs112901682 biolink:NamedThing omim.nt owl:NamedIndividual http://omim.org/entry/102620#0005 biolink:NamedThing omim.nt http://omim.org/entry/102620.0006 biolink:NamedThing ACTA2, MET49VAL In a German woman who presented with acute aortic dissection at 37 years of age, {5:Hoffjan et al. (2011)} identified heterozygosity for a c.145A-G transition in exon 3 of the ACTA2 gene, resulting in a met49-to-val (M49V) substitution at a highly conserved residue in the DNAse-I-binding loop within subdomain 2. The mutation was not found in 192 control chromosomes or in the GenBank dbSNP library. The patient's brother had died at 29 years of age from acute aortic dissection, and her mother, who suffered from slowly progressive spastic paraplegia over 20 years and cancer, died suddenly at 69 years of age in association with a massive drop in blood pressure. omim.nt GENO:0000002 ClinVar:RCV000055648 biolink:NamedThing omim.nt dbSNP:rs397515325 biolink:NamedThing omim.nt owl:NamedIndividual http://omim.org/entry/102620#0006 biolink:NamedThing omim.nt http://omim.org/entry/102620.0007 biolink:NamedThing ACTA2, ARG179LEU In a review of the clinical history and outcomes of 33 patients with multisystemic smooth muscle dysfunction syndrome (MSMDS; {613834}), {10:Regalado et al. (2018)} found 1 patient who was heterozygous for an arg179-to-leu (R179L) substitution in ACTA2. omim.nt GENO:0000002 ClinVar:RCV001267897 biolink:NamedThing omim.nt http://omim.org/entry/102620#0007 biolink:NamedThing omim.nt http://omim.org/entry/102620.0008 biolink:NamedThing ACTA2, ARG179CYS In a review of the clinical history and outcomes of 33 patients with multisystemic smooth muscle dysfunction syndrome (MSMDS; {613834}), {10:Regalado et al. (2018)} found 7 patients who were heterozygous for an arg179-to-cys (R179C) substitution in ACTA2. omim.nt GENO:0000002 ClinVar:RCV001267898 biolink:NamedThing omim.nt http://omim.org/entry/102620#0008 biolink:NamedThing omim.nt http://omim.org/entry/102620.0009 biolink:NamedThing ACTA2, ARG179SER In a review of the clinical history and outcomes of 33 patients with multisystemic smooth muscle dysfunction syndrome (MSMDS; {613834}), {10:Regalado et al. (2018)} found 1 patient who was heterozygous for an arg179-to-ser (R179S) substitution in ACTA2. omim.nt GENO:0000002 ClinVar:RCV001164780 biolink:NamedThing omim.nt http://omim.org/entry/102620#0009 biolink:NamedThing omim.nt MONARCH:.well-known/genid/be73c41bdd87073a7da4 biolink:NamedThing GRCh38chr10-88935073-88991396-Region omim.nt MONARCH:.well-known/genid/bf7a6a752a45343e5910 faldo:Region PMID:10532176 biolink:NamedThing omim.nt IAO:0000013 PMID:12663487 biolink:NamedThing omim.nt IAO:0000013 PMID:14730227 biolink:NamedThing omim.nt IAO:0000013 PMID:15472996 biolink:NamedThing omim.nt IAO:0000013 PMID:17994018 biolink:NamedThing omim.nt IAO:0000013 PMID:19409525 biolink:NamedThing omim.nt IAO:0000013 PMID:19745835 biolink:NamedThing omim.nt IAO:0000013 PMID:20734336 biolink:NamedThing omim.nt IAO:0000013 PMID:20970362 biolink:NamedThing omim.nt IAO:0000013 PMID:21248741 biolink:NamedThing omim.nt IAO:0000013 PMID:2398629 biolink:NamedThing omim.nt IAO:0000013 PMID:24998021 biolink:NamedThing omim.nt IAO:0000013 PMID:29300374 biolink:NamedThing omim.nt IAO:0000013 PMID:499690 biolink:NamedThing omim.nt IAO:0000013 PMID:6330528 biolink:NamedThing omim.nt IAO:0000013 OBO:CHR_9606chr10q22 biolink:NamedThing omim.nt owl:Class http://omim.org/entry/611788 biolink:NamedThing|biolink:Disease Aortic Aneurysm, Familial Thoracic 6 Aortic Aneurysm, Familial Thoracic 6 omim.nt AORTIC ANEURYSM, FAMILIAL THORACIC 6; AAT6|Familial Thoracic Aortic Aneurysm With Livedo Reticularis and Iris Flocculi owl:Class http://omim.org/entry/613834 biolink:NamedThing|biolink:Disease Multisystemic Smooth Muscle Dysfunction Syndrome Multisystemic Smooth Muscle Dysfunction Syndrome omim.nt MULTISYSTEMIC SMOOTH MUSCLE DYSFUNCTION SYNDROME; MSMDS|Mydriasis, Congenital, With Patent Ductus Arteriosus, Thoracic Aortic Aneurysm, and Vasculopathy owl:Class http://omim.org/entry/614042 biolink:NamedThing|biolink:Disease Moyamoya Disease 5 Moyamoya Disease 5 omim.nt MOYAMOYA DISEASE 5; MYMY5 owl:Class http://www.omim.org/phenotypicSeries/PS252350 biolink:NamedThing|biolink:Disease Moyamoya disease omim.nt owl:Class http://www.omim.org/phenotypicSeries/PS607086 biolink:NamedThing|biolink:Disease Aortic aneurysm, familial thoracic omim.nt owl:Class UMLS:C1412137 biolink:NamedThing omim.nt owl:Class https://www.ncbi.nlm.nih.gov/gene/59 biolink:NamedThing omim.nt http://omim.org/entry/102630.0001 biolink:NamedThing ACTB, ARG183TRP In the twins with juvenile-onset dystonia (DJO; {607371}) originally described by {7:Gearing et al. (2002)}, {23:Procaccio et al. (2006)} detected a heterozygous arg183-to-trp (R183W) mutation in the ACTB gene. The amino acid substitution was the result of a 547C-T transition in exon 4. The constellation of malformations exhibited by the patients resembled Opitz syndrome ({300000}), but no mutations were found in the MID1 gene ({300552}) and no evidence was found for involvement of genes causing the autosomal form of Opitz syndrome. No mutations in ACTB were identified in the mother and 2 half brothers. Paternal samples were not available for analysis. {24:Riviere et al. (2012)} suggested that this report should be interpreted with caution given the absence of replication studies and unavailability of parental DNA. omim.nt GENO:0000002 ClinVar:RCV000019937 biolink:NamedThing omim.nt ClinVar:RCV000503778 biolink:NamedThing omim.nt ClinVar:RCV000624662 biolink:NamedThing omim.nt ClinVar:RCV000680718 biolink:NamedThing omim.nt dbSNP:rs104894003 biolink:NamedThing omim.nt owl:NamedIndividual http://omim.org/entry/102630#0001 biolink:NamedThing omim.nt http://omim.org/entry/102630.0002 biolink:NamedThing ACTB, ARG196HIS In 7 of 10 patients with Baraitser-Winter syndrome-1 (BRWS1; {243310}), {24:Riviere et al. (2012)} identified a heterozygous G-to-A transition at nucleotide 587 of the ACTB gene, resulting in an arg-to-his substitution at codon 196 (R196H). In 2 patients from whom parental DNA was available the mutation was determined to have occurred de novo. This mutation was not identified in 212 other exomes. Lymphoblastoid cell lines established from patients carrying this mutation had greatly increased F-actin content and multiple, anomalous F-actin-rich, filopodia-like protrusions compared to control cells, resulting in an increased cell perimeter. One of the patients found by {24:Riviere et al. (2012)} to carry the R196H mutation had been described by {6:Fryns and Aftimos (2000)} as patient 1 in the original report of Fryns-Aftimos syndrome. omim.nt GENO:0000002 ClinVar:RCV000022439 biolink:NamedThing omim.nt ClinVar:RCV000059721 biolink:NamedThing omim.nt dbSNP:rs281875334 biolink:NamedThing omim.nt owl:NamedIndividual http://omim.org/entry/102630#0002 biolink:NamedThing omim.nt http://omim.org/entry/102630.0003 biolink:NamedThing ACTB, ARG196CYS In an individual with Baraitser-Winter syndrome-1 (BRWS1; {243310}), {24:Riviere et al. (2012)} identified a heterozygous C-to-T transition at nucleotide 586 of the ACTB gene, resulting in an arg-to-cys substitution at codon 196 (R196C). This mutation was not found in 214 other exomes. In a patient (patient 3) with a severe BRWS1 phenotype, previously reported by {3:Der Kaloustian et al. (2001)}, {4:Di Donato et al. (2014)} identified a c.586C-T transition ({VAR c.586C-T, NM_001101.3}) in the ACTB gene, resulting in the R196C mutation. They noted that the patient with the R196C mutation reported by {24:Riviere et al. (2012)} had a mild form of the disorder. {4:Di Donato et al. (2014)} suggested that the more severe phenotype in their patient may be due to an unknown genetic modifier that has an impact on the clinical severity and malformation spectrum. omim.nt GENO:0000002 ClinVar:RCV000022440 biolink:NamedThing omim.nt ClinVar:RCV000059720 biolink:NamedThing omim.nt dbSNP:rs281875333 biolink:NamedThing omim.nt owl:NamedIndividual http://omim.org/entry/102630#0003 biolink:NamedThing omim.nt http://omim.org/entry/102630.0004 biolink:NamedThing ACTB, LEU65VAL In a patient with Baraitser-Winter syndrome-1 (BRWS1; {243310}), {24:Riviere et al. (2012)} identified a de novo mutation, a heterozygous C-to-G transversion at nucleotide 193 of the ACTB gene resulting in a leu-to-val substitution at codon 65 (L65V). This mutation was not identified in 244 other exomes. omim.nt GENO:0000002 ClinVar:RCV000022441 biolink:NamedThing omim.nt ClinVar:RCV000059718 biolink:NamedThing omim.nt dbSNP:rs281875332 biolink:NamedThing omim.nt owl:NamedIndividual http://omim.org/entry/102630#0004 biolink:NamedThing omim.nt http://omim.org/entry/102630.0005 biolink:NamedThing ACTB, ASN12ASP In a patient with Baraitser-Winter syndrome-1 (BRWS1; {243310}), {24:Riviere et al. (2012)} identified a de novo mutation, a heterozygous A-to-G transition at nucleotide 34 of the ACTB gene resulting in an asn-to-asp substitution at codon 12 (N12D). This mutation was not identified in 24 other exomes. omim.nt GENO:0000002 ClinVar:RCV000022442 biolink:NamedThing omim.nt ClinVar:RCV000059719 biolink:NamedThing omim.nt dbSNP:rs281875331 biolink:NamedThing omim.nt owl:NamedIndividual http://omim.org/entry/102630#0005 biolink:NamedThing omim.nt http://omim.org/entry/102630.0006 biolink:NamedThing ACTB, GLU117LYS In a 7-year-old girl with atypical Baraitser-Winter syndrome-1 ({243310}), who had microcephaly, intellectual disability, and facial dysmorphism but no lissencephaly or seizures, {15:Johnston et al. (2013)} identified heterozygosity for a de novo c.349G-A transition in the ACTB gene, resulting in a glu117-to-lys (E117K) substitution. The mutation was not present in either of her unaffected parents. Patient lymphocytes demonstrated significantly decreased ability to adhere to a fibronectin-coated surface and formed few actin-rich protrusions compared to the parents' lymphocytes. Studies in yeast showed virtually complete loss of normal polarization of the cytoskeleton with the mutant, and mutant cells were almost completely resistant to the depolymerizing agent latrunculin A, suggesting that E117K might result in strengthened actin monomer-monomer interactions and increased filament stability. omim.nt GENO:0000002 ClinVar:RCV000056289 biolink:NamedThing omim.nt dbSNP:rs397515470 biolink:NamedThing omim.nt owl:NamedIndividual http://omim.org/entry/102630#0006 biolink:NamedThing omim.nt http://omim.org/entry/102630.0007 biolink:NamedThing ACTB, THR120ILE In a patient (patient 1) with a severe form of Baraitser-Winter syndrome-1 (BRWS1; {243310}), who was previously diagnosed with Fryns-Aftimos syndrome, {4:Di Donato et al. (2014)} identified a c.359C-T transition ({VAR c.359C-T, NM_001101.3}) in the ACTB gene, resulting in a thr120-to-ile (T120I) substitution. The mutation was not found in the dbSNP or Exome Variant Server databases. In 2 patients with severe Baraitser-Winter syndrome-1 (BRWS1; {243310}), who were previously diagnosed with cerebrofrontofacial syndrome ({9:Guion-Almeida and Richieri-Costa, 1992}; {10:Guion-Almeida and Richieri-Costa, 1999}), {28:Verloes et al. (2015)} identified the T120I mutation. {28:Verloes et al. (2015)} suggested that this mutation is associated with a more severe BRWS phenotype. omim.nt GENO:0000002 ClinVar:RCV000133571 biolink:NamedThing omim.nt dbSNP:rs587779774 biolink:NamedThing omim.nt owl:NamedIndividual http://omim.org/entry/102630#0007 biolink:NamedThing omim.nt http://omim.org/entry/102630.0008 biolink:NamedThing ACTB, 1-BP DUP, 1097G In a 12-year-old boy (patient XXIV) with Baraitser-Winter syndrome-1 (BRWS1; {243310}), {2:Cuvertino et al. (2017)} identified a de novo heterozygous 1-bp duplication ({VAR c.1097dupG, NM_001101.3}) in exon 6 of the ACTB gene, predicted to result in a frameshift and premature termination (Ser368LeufsTer13). The mutation, which was found by exome sequencing of a cohort of 4,293 trios in which the offspring had a developmental disorder, was predicted to escape nonsense-mediated mRNA decay, and to result in a loss of function and haploinsufficiency of the ACTB gene. omim.nt GENO:0000002 ClinVar:RCV000585890 biolink:NamedThing omim.nt ClinVar:RCV000624638 biolink:NamedThing omim.nt dbSNP:rs1554329078 biolink:NamedThing omim.nt owl:NamedIndividual http://omim.org/entry/102630#0008 biolink:NamedThing omim.nt http://omim.org/entry/102630.0009 biolink:NamedThing ACTB, LYS373TER In a 14-year-old girl (patient XXV) with Baraitser-Winter syndrome-1 (BRWS1; {243310}), {2:Cuvertino et al. (2017)} identified a de novo heterozygous c.1117A-T transversion ({VAR c.1117A-T, NM_001101.3}) in exon 6 of the ACTB gene, resulting in a lys373-to-ter (K373X) substitution. The mutation, which was found by exome sequencing of a cohort of 4,293 trios in which the offspring had a developmental disorder, was predicted to escape nonsense-mediated mRNA decay, and to result in loss of function and haploinsufficiency of the ACTB gene. omim.nt GENO:0000002 ClinVar:RCV000585888 biolink:NamedThing omim.nt dbSNP:rs1554329068 biolink:NamedThing omim.nt owl:NamedIndividual http://omim.org/entry/102630#0009 biolink:NamedThing omim.nt http://omim.org/entry/102630.0010 biolink:NamedThing ACTB, 1-BP DEL, 329T In an 18-year-old man (patient XXVI) with Baraitser-Winter syndrome-1 (BRWS1; {243310}), {2:Cuvertino et al. (2017)} identified a de novo heterozygous 1-bp deletion ({VAR c.329delT, NM_001101.3}) in exon 3 of the ACTB gene, predicted to result in a frameshift and premature termination (Leu110ArgfsTer10). The mutation, which was found by exome sequencing of a cohort of 4,293 trios in which the offspring had a developmental disorder, was predicted to result in a loss of function and haploinsufficiency of the ACTB gene. omim.nt GENO:0000002 ClinVar:RCV000585889 biolink:NamedThing omim.nt dbSNP:rs1554329523 biolink:NamedThing omim.nt owl:NamedIndividual http://omim.org/entry/102630#0010 biolink:NamedThing omim.nt MONARCH:.well-known/genid/ba2cb3eb8243d5af7c4f biolink:NamedThing GRCh38chr7-5527147-5530600-Region omim.nt MONARCH:.well-known/genid/bd500ed0d2766ec528ea faldo:Region MONARCH:.well-known/genid/OMIM102630ref21 biolink:NamedThing Chromosome 7 assignment of the human beta-actin functional gene (ACTB) and the chromosomal dispersion of pseudogenes. (Abstract) omim.nt IAO:0000310 PMID:10327243 biolink:NamedThing omim.nt IAO:0000013 PMID:10928857 biolink:NamedThing omim.nt IAO:0000013 PMID:11311002 biolink:NamedThing omim.nt IAO:0000013 PMID:12325076 biolink:NamedThing omim.nt IAO:0000013 PMID:1415343 biolink:NamedThing omim.nt IAO:0000013 PMID:1505215 biolink:NamedThing omim.nt IAO:0000013 PMID:16306994 biolink:NamedThing omim.nt IAO:0000013 PMID:16685646 biolink:NamedThing omim.nt IAO:0000013 PMID:16794040 biolink:NamedThing omim.nt IAO:0000013 PMID:17502619 biolink:NamedThing omim.nt IAO:0000013 PMID:20167579 biolink:NamedThing omim.nt IAO:0000013 PMID:23649928 biolink:NamedThing omim.nt IAO:0000013 PMID:23756437 biolink:NamedThing omim.nt IAO:0000013 PMID:24458642 biolink:NamedThing omim.nt IAO:0000013 PMID:25052316 biolink:NamedThing omim.nt IAO:0000013 PMID:274701 biolink:NamedThing omim.nt IAO:0000013 PMID:29220674 biolink:NamedThing omim.nt IAO:0000013 PMID:2994062 biolink:NamedThing omim.nt IAO:0000013 PMID:3837182 biolink:NamedThing omim.nt IAO:0000013 PMID:3842206 biolink:NamedThing omim.nt IAO:0000013 PMID:6202424 biolink:NamedThing omim.nt IAO:0000013 PMID:7199389 biolink:NamedThing omim.nt IAO:0000013 http://omim.org/entry/607371 biolink:NamedThing|biolink:Disease Dystonia, Juvenile-Onset Dystonia, Juvenile-Onset omim.nt DYSTONIA, JUVENILE-ONSET; DJO owl:Class OBO:CHR_9606chr7p22 biolink:NamedThing omim.nt owl:Class http://omim.org/entry/243310 biolink:NamedThing|biolink:Disease Baraitser-Winter Syndrome 1 Baraitser-Winter Syndrome 1 omim.nt BARAITSER-WINTER SYNDROME 1; BRWS1|Cerebrofrontofacial Syndrome|Cerebrooculofacial Lymphatic Syndrome|Chromosome 7P22 Deletion Syndrome|Fryns-Aftimos Syndrome|Iris Coloboma With Ptosis, Hypertelorism, and Mental Retardation|Mental Retardation With Epilepsy and Characteristic Facies|Pachygyria, Mental Retardation, Epilepsy, and Characteristic Facies owl:Class UMLS:C1384510 biolink:NamedThing omim.nt owl:Class https://www.ncbi.nlm.nih.gov/gene/60 biolink:NamedThing omim.nt http://omim.org/entry/102640 biolink:NamedThing omim.nt True owl:Class http://omim.org/entry/102642 biolink:NamedThing|biolink:Gene SOAT1 Sterol O-Acyltransferase 1 omim.nt STEROL O-ACYLTRANSFERASE 1; SOAT1|Acat1|Acyl-Coa:Cholesterol Acyltransferase|Soat|Sterol Acyltransferase owl:Class MONARCH:.well-known/genid/b70aa392db20f97b0eb4 biolink:NamedThing GRCh38chr1-179293718-179358679-Region omim.nt MONARCH:.well-known/genid/b224b40d8944ceb64ccd faldo:Region PMID:10634802 biolink:NamedThing omim.nt IAO:0000013 PMID:10727439 biolink:NamedThing omim.nt IAO:0000013 PMID:11160132 biolink:NamedThing omim.nt IAO:0000013 PMID:11584272 biolink:NamedThing omim.nt IAO:0000013 PMID:15473963 biolink:NamedThing omim.nt IAO:0000013 PMID:16554527 biolink:NamedThing omim.nt IAO:0000013 PMID:2738092 biolink:NamedThing omim.nt IAO:0000013 PMID:3335499 biolink:NamedThing omim.nt IAO:0000013 PMID:8197480 biolink:NamedThing omim.nt IAO:0000013 PMID:8407899 biolink:NamedThing omim.nt IAO:0000013 PMID:8650549 biolink:NamedThing omim.nt IAO:0000013 PMID:8943057 biolink:NamedThing omim.nt IAO:0000013 PMID:9422770 biolink:NamedThing omim.nt IAO:0000013 OBO:CHR_9606chr1q25 biolink:NamedThing omim.nt owl:Class UMLS:C1420304 biolink:NamedThing omim.nt owl:Class https://www.ncbi.nlm.nih.gov/gene/6646 biolink:NamedThing omim.nt http://omim.org/entry/102645 biolink:NamedThing|biolink:Gene APEH Acylaminoacyl-Peptide Hydrolase omim.nt ACYLAMINOACYL-PEPTIDE HYDROLASE; APEH|Acylpeptide Hydrolase|Dnf15S2|N-Acylaminoacylpeptide Hydrolase owl:Class MONARCH:.well-known/genid/be22abf8d999c1c1958d biolink:NamedThing GRCh38chr3-49673101-49683970-Region omim.nt MONARCH:.well-known/genid/b7b1c434c4e67c2b3046 faldo:Region PMID:1550126 biolink:NamedThing omim.nt IAO:0000013 PMID:2006156 biolink:NamedThing omim.nt IAO:0000013 PMID:2565880 biolink:NamedThing omim.nt IAO:0000013 PMID:2569728 biolink:NamedThing omim.nt IAO:0000013 PMID:2571406 biolink:NamedThing omim.nt IAO:0000013 PMID:2691504 biolink:NamedThing omim.nt IAO:0000013 PMID:3010709 biolink:NamedThing omim.nt IAO:0000013 PMID:3010710 biolink:NamedThing omim.nt IAO:0000013 PMID:7273954 biolink:NamedThing omim.nt IAO:0000013 PMID:8020952 biolink:NamedThing omim.nt IAO:0000013 OBO:CHR_9606chr3p21 biolink:NamedThing omim.nt owl:Class UMLS:C1332101 biolink:NamedThing omim.nt owl:Class https://www.ncbi.nlm.nih.gov/gene/327 biolink:NamedThing omim.nt http://omim.org/entry/102650 biolink:NamedThing|biolink:Disease Adactylia, Unilateral omim.nt ADACTYLIA, UNILATERAL|Terminal Transverse Defects of Hand, Unilateral owl:Class PMID:3725479 biolink:NamedThing omim.nt IAO:0000013 UMLS:C0220660 biolink:NamedThing omim.nt owl:Class ORPHA:973 biolink:NamedThing|biolink:Disease omim.nt owl:Class http://omim.org/entry/102660 biolink:NamedThing|biolink:Disease Adamantinoma of Long Bones omim.nt ADAMANTINOMA OF LONG BONES owl:Class PMID:2227936 biolink:NamedThing omim.nt IAO:0000013 PMID:2743266 biolink:NamedThing omim.nt IAO:0000013 UMLS:C0334556 biolink:NamedThing omim.nt owl:Class ORPHA:55881 biolink:NamedThing|biolink:Disease omim.nt owl:Class http://omim.org/entry/102670 biolink:NamedThing|biolink:Gene MADCAM1 Mucosal Vascular Addressin Cell Adhesion Molecule 1 omim.nt MUCOSAL VASCULAR ADDRESSIN CELL ADHESION MOLECULE 1; MADCAM1|Addressin, Mucosal|Mucosal Addressin Cell Adhesion Molecule 1 owl:Class MONARCH:.well-known/genid/bfaff3e9bee998da093a biolink:NamedThing GRCh38chr19-496485-505342-Region omim.nt MONARCH:.well-known/genid/bc9d3a4291a3886909c0 faldo:Region PMID:10790368 biolink:NamedThing omim.nt IAO:0000013 PMID:8502297 biolink:NamedThing omim.nt IAO:0000013 PMID:8609404 biolink:NamedThing omim.nt IAO:0000013 PMID:8989586 biolink:NamedThing omim.nt IAO:0000013 PMID:9162097 biolink:NamedThing omim.nt IAO:0000013 OBO:CHR_9606chr19p13.3 biolink:NamedThing omim.nt owl:Class UMLS:C1416961 biolink:NamedThing omim.nt owl:Class https://www.ncbi.nlm.nih.gov/gene/8174 biolink:NamedThing omim.nt http://omim.org/entry/102680.0001 biolink:NamedThing ADD1, GLY460TRP {6:Cusi et al. (1997)} found a significant association between a gly460-to-trp polymorphism (G460W) in the ADD1 gene and salt sensitivity in patients with essential hypertension (see {145500}). Patients with the W460 allele showed greater sensitivity to changes in sodium balance, and heterozygous hypertensive patients (G/W) showed a greater fall in mean arterial pressure in response to 2 months' treatment with hydrochlorothiazide, than did wildtype homozygous (G/G) hypertensive patients. In controls in an Italian cohort, the G460 allele had a frequency of 86.4% and the W460 allele 13.6%. {18:Manunta et al. (1998)} analyzed the pressure-natriuresis relationship in 108 hypertensive individuals, 80 of whom were wildtype homozygous (G/G), 26 G/W heterozygous, and 2 W/W homozygous. At baseline, the G/W and W/W patients showed lower plasma renin activity and fractional excretion of sodium; these patients also had reduced slope of the pressure-natriuresis relationship after sodium depletion or sodium loading compared to G/G patients. These findings supported the hypothesis that individuals with at least 1 ADD1 460W allele have increased renal tubular sodium reabsorption. Using endogenous lithium and uric acid as markers of proximal tubular sodium reabsorption, {17:Manunta et al. (1999)} investigated the relationship between renal sodium handling and ADD1 polymorphism in 54 untreated hypertensive patients, 29 with the G/G genotype and 25 with the G/W genotype. Fractional excretions of lithium and uric acid were significantly decreased in G/W patients compared to G/G patients; multiple regression analysis showed that adducin genotype was significantly and directly related to the fractional excretion of lithium. {17:Manunta et al. (1999)} concluded that ADD1 represents a 'renal hypertensive gene' that modulates the capacity of tubular epithelial cells to transport sodium and thus affects blood pressure levels. omim.nt GENO:0000002 http://omim.org/entry/102680 biolink:NamedThing|biolink:Gene ADD1 Adducin 1 omim.nt ADDUCIN 1; ADD1|Adducin, Alpha owl:Class ClinVar:RCV000019936 biolink:NamedThing omim.nt ClinVar:RCV000211330 biolink:NamedThing omim.nt dbSNP:rs4961 biolink:NamedThing omim.nt owl:NamedIndividual http://omim.org/entry/102680#0001 biolink:NamedThing omim.nt MONARCH:.well-known/genid/b1a6e867ba049cfab75d biolink:NamedThing GRCh38chr4-2843843-2930064-Region omim.nt MONARCH:.well-known/genid/b115ae1cd45cdadf9d3e faldo:Region PMID:10024330 biolink:NamedThing omim.nt IAO:0000013 PMID:10485892 biolink:NamedThing omim.nt IAO:0000013 PMID:11641285 biolink:NamedThing omim.nt IAO:0000013 PMID:1284592 biolink:NamedThing omim.nt IAO:0000013 PMID:1345173 biolink:NamedThing omim.nt IAO:0000013 PMID:15528469 biolink:NamedThing omim.nt IAO:0000013 PMID:15716695 biolink:NamedThing omim.nt IAO:0000013 PMID:1840603 biolink:NamedThing omim.nt IAO:0000013 PMID:1850845 biolink:NamedThing omim.nt IAO:0000013 PMID:18524856 biolink:NamedThing omim.nt IAO:0000013 PMID:2376589 biolink:NamedThing omim.nt IAO:0000013 PMID:2451672 biolink:NamedThing omim.nt IAO:0000013 PMID:3511042 biolink:NamedThing omim.nt IAO:0000013 PMID:7875756 biolink:NamedThing omim.nt IAO:0000013 PMID:7919654 biolink:NamedThing omim.nt IAO:0000013 PMID:7959767 biolink:NamedThing omim.nt IAO:0000013 PMID:8171025 biolink:NamedThing omim.nt IAO:0000013 PMID:8434261 biolink:NamedThing omim.nt IAO:0000013 PMID:8626479 biolink:NamedThing omim.nt IAO:0000013 PMID:8675693 biolink:NamedThing omim.nt IAO:0000013 PMID:9149697 biolink:NamedThing omim.nt IAO:0000013 PMID:9607177 biolink:NamedThing omim.nt IAO:0000013 http://omim.org/entry/145500 biolink:NamedThing|biolink:Disease Hypertension, Essential Hypertension, Essential omim.nt HYPERTENSION, ESSENTIAL|Eht owl:Class OBO:CHR_9606chr4p16.3 biolink:NamedThing omim.nt owl:Class UMLS:C1412230 biolink:NamedThing omim.nt owl:Class https://www.ncbi.nlm.nih.gov/gene/118 biolink:NamedThing omim.nt http://omim.org/entry/102681 biolink:NamedThing|biolink:Gene ADD2 Adducin 2 omim.nt ADDUCIN 2; ADD2|Adducin, Beta owl:Class MONARCH:.well-known/genid/b5145bce4ad75e4b38b8 biolink:NamedThing GRCh38chr2-70656783-70768199-Region omim.nt MONARCH:.well-known/genid/b798127332154b75115e faldo:Region PMID:10845937 biolink:NamedThing omim.nt IAO:0000013 PMID:17142833 biolink:NamedThing omim.nt IAO:0000013 PMID:21532590 biolink:NamedThing omim.nt IAO:0000013 PMID:7490111 biolink:NamedThing omim.nt IAO:0000013 PMID:8563174 biolink:NamedThing omim.nt IAO:0000013 PMID:8566798 biolink:NamedThing omim.nt IAO:0000013 PMID:9244430 biolink:NamedThing omim.nt IAO:0000013 OBO:CHR_9606chr2p14 biolink:NamedThing omim.nt owl:Class UMLS:C1412231 biolink:NamedThing omim.nt owl:Class https://www.ncbi.nlm.nih.gov/gene/119 biolink:NamedThing omim.nt http://omim.org/entry/102699 biolink:NamedThing Adeno-Associated Virus Integration Site 1 omim.nt ADENO-ASSOCIATED VIRUS INTEGRATION SITE 1; AAVS1 owl:Class PMID:1334463 biolink:NamedThing omim.nt IAO:0000013 PMID:1653762 biolink:NamedThing omim.nt IAO:0000013 PMID:1657596 biolink:NamedThing omim.nt IAO:0000013 PMID:2156265 biolink:NamedThing omim.nt IAO:0000013 UMLS:C3887914 biolink:NamedThing omim.nt owl:Class http://omim.org/entry/102700 biolink:NamedThing|biolink:Disease Severe Combined Immunodeficiency, Autosomal Recessive, T Cell-Negative, B Cell-Negative, Nk Cell-Negative, Due to Adenosine Deaminase Deficiency Severe Combined Immunodeficiency, Autosomal Recessive, T Cell-Negative, B Cell-Negative, Nk Cell-Negative, Due to Adenosine Deaminase Deficiency omim.nt SEVERE COMBINED IMMUNODEFICIENCY, AUTOSOMAL RECESSIVE, T CELL-NEGATIVE, B CELL-NEGATIVE, NK CELL-NEGATIVE, DUE TO ADENOSINE DEAMINASE DEFICIENCY|Ada-Scid|Adenosine Deaminase Deficiency, Partial|Partial Ada Deficiency|Scid Due to Ada Deficiency|Scid Due to Ada Deficiency, Delayed Onset|Scid Due to Ada Deficiency, Early-Onset|Scid Due to Ada Deficiency, Late-Onset owl:Class MONARCH:.well-known/genid/OMIM102700ref23 biolink:NamedThing Gene Therapy: A Primer for Physicians. omim.nt IAO:0000310 MONARCH:.well-known/genid/OMIM102700ref42 biolink:NamedThing A mutant form of adenosine deaminase in severe combined immunodeficiency. (Abstract) omim.nt IAO:0000310 MONARCH:.well-known/genid/OMIM102700ref60 biolink:NamedThing Adenosine deaminase deficiency and severe combined immunodeficiencies. omim.nt IAO:0000310 MONARCH:.well-known/genid/OMIM102700ref92 biolink:NamedThing Adenosine deaminase deficiency in severe combined immunodeficiency: evidence for a posttranslational defect. (Abstract) omim.nt IAO:0000310 MONARCH:.well-known/genid/OMIM102700ref94 biolink:NamedThing Further data on the genetic linkage relations of the adenosine deaminase locus. omim.nt IAO:0000310 PMID:10021471 biolink:NamedThing omim.nt IAO:0000013 PMID:1089440 biolink:NamedThing omim.nt IAO:0000013 PMID:1089883 biolink:NamedThing omim.nt IAO:0000013 PMID:110506 biolink:NamedThing omim.nt IAO:0000013 PMID:11435465 biolink:NamedThing omim.nt IAO:0000013 PMID:11445793 biolink:NamedThing omim.nt IAO:0000013 PMID:11807006 biolink:NamedThing omim.nt IAO:0000013 PMID:12089448 biolink:NamedThing omim.nt IAO:0000013 PMID:12163459 biolink:NamedThing omim.nt IAO:0000013 PMID:14499267 biolink:NamedThing omim.nt IAO:0000013 PMID:1848369 biolink:NamedThing omim.nt IAO:0000013 PMID:18618 biolink:NamedThing omim.nt IAO:0000013 PMID:19179314 biolink:NamedThing omim.nt IAO:0000013 PMID:1974554 biolink:NamedThing omim.nt IAO:0000013 PMID:2166947 biolink:NamedThing omim.nt IAO:0000013 PMID:24216 biolink:NamedThing omim.nt IAO:0000013 PMID:272665 biolink:NamedThing omim.nt IAO:0000013 PMID:2783588 biolink:NamedThing omim.nt IAO:0000013 PMID:3007108 biolink:NamedThing omim.nt IAO:0000013 PMID:310515 biolink:NamedThing omim.nt IAO:0000013 PMID:311004 biolink:NamedThing omim.nt IAO:0000013 PMID:3116034 biolink:NamedThing omim.nt IAO:0000013 PMID:3260944 biolink:NamedThing omim.nt IAO:0000013 PMID:3304460 biolink:NamedThing omim.nt IAO:0000013 PMID:3366897 biolink:NamedThing omim.nt IAO:0000013 PMID:3456164 biolink:NamedThing omim.nt IAO:0000013 PMID:3475710 biolink:NamedThing omim.nt IAO:0000013 PMID:3493485 biolink:NamedThing omim.nt IAO:0000013 PMID:3571974 biolink:NamedThing omim.nt IAO:0000013 PMID:372236 biolink:NamedThing omim.nt IAO:0000013 PMID:3781559 biolink:NamedThing omim.nt IAO:0000013 PMID:3807953 biolink:NamedThing omim.nt IAO:0000013 PMID:38963 biolink:NamedThing omim.nt IAO:0000013 PMID:3946419 biolink:NamedThing omim.nt IAO:0000013 PMID:4014441 biolink:NamedThing omim.nt IAO:0000013 PMID:4117384 biolink:NamedThing omim.nt IAO:0000013 PMID:4117846 biolink:NamedThing omim.nt IAO:0000013 PMID:4125820 biolink:NamedThing omim.nt IAO:0000013 PMID:46025 biolink:NamedThing omim.nt IAO:0000013 PMID:4634454 biolink:NamedThing omim.nt IAO:0000013 PMID:475331 biolink:NamedThing omim.nt IAO:0000013 PMID:477037 biolink:NamedThing omim.nt IAO:0000013 PMID:479373 biolink:NamedThing omim.nt IAO:0000013 PMID:4810724 biolink:NamedThing omim.nt IAO:0000013 PMID:4811750 biolink:NamedThing omim.nt IAO:0000013 PMID:4815083 biolink:NamedThing omim.nt IAO:0000013 PMID:494270 biolink:NamedThing omim.nt IAO:0000013 PMID:498598 biolink:NamedThing omim.nt IAO:0000013 PMID:5144905 biolink:NamedThing omim.nt IAO:0000013 PMID:518903 biolink:NamedThing omim.nt IAO:0000013 PMID:5366284 biolink:NamedThing omim.nt IAO:0000013 PMID:5413970 biolink:NamedThing omim.nt IAO:0000013 PMID:5493847 biolink:NamedThing omim.nt IAO:0000013 PMID:5501699 biolink:NamedThing omim.nt IAO:0000013 PMID:5822324 biolink:NamedThing omim.nt IAO:0000013 PMID:597863 biolink:NamedThing omim.nt IAO:0000013 PMID:6156414 biolink:NamedThing omim.nt IAO:0000013 PMID:6198631 biolink:NamedThing omim.nt IAO:0000013 PMID:6260402 biolink:NamedThing omim.nt IAO:0000013 PMID:6370091 biolink:NamedThing omim.nt IAO:0000013 PMID:6603477 biolink:NamedThing omim.nt IAO:0000013 PMID:6606796 biolink:NamedThing omim.nt IAO:0000013 PMID:6840756 biolink:NamedThing omim.nt IAO:0000013 PMID:6863546 biolink:NamedThing omim.nt IAO:0000013 PMID:6933468 biolink:NamedThing omim.nt IAO:0000013 PMID:6977542 biolink:NamedThing omim.nt IAO:0000013 PMID:715439 biolink:NamedThing omim.nt IAO:0000013 PMID:7241535 biolink:NamedThing omim.nt IAO:0000013 PMID:7263861 biolink:NamedThing omim.nt IAO:0000013 PMID:7371221 biolink:NamedThing omim.nt IAO:0000013 PMID:7436484 biolink:NamedThing omim.nt IAO:0000013 PMID:7485150 biolink:NamedThing omim.nt IAO:0000013 PMID:7570000 biolink:NamedThing omim.nt IAO:0000013 PMID:7570001 biolink:NamedThing omim.nt IAO:0000013 PMID:7670465 biolink:NamedThing omim.nt IAO:0000013 PMID:7731963 biolink:NamedThing omim.nt IAO:0000013 PMID:7749407 biolink:NamedThing omim.nt IAO:0000013 PMID:8023852 biolink:NamedThing omim.nt IAO:0000013 PMID:8031011 biolink:NamedThing omim.nt IAO:0000013 PMID:8051429 biolink:NamedThing omim.nt IAO:0000013 PMID:8099155 biolink:NamedThing omim.nt IAO:0000013 PMID:8120281 biolink:NamedThing omim.nt IAO:0000013 PMID:8178821 biolink:NamedThing omim.nt IAO:0000013 PMID:8227344 biolink:NamedThing omim.nt IAO:0000013 PMID:8614422 biolink:NamedThing omim.nt IAO:0000013 PMID:8673127 biolink:NamedThing omim.nt IAO:0000013 PMID:8900089 biolink:NamedThing omim.nt IAO:0000013 PMID:9108404 biolink:NamedThing omim.nt IAO:0000013 PMID:9414266 biolink:NamedThing omim.nt IAO:0000013 PMID:9475605 biolink:NamedThing omim.nt IAO:0000013 PMID:9478961 biolink:NamedThing omim.nt IAO:0000013 PMID:974246 biolink:NamedThing omim.nt IAO:0000013 PMID:9758612 biolink:NamedThing omim.nt IAO:0000013 PMID:978319 biolink:NamedThing omim.nt IAO:0000013 PMID:980079 biolink:NamedThing omim.nt IAO:0000013 UMLS:C1863236 biolink:NamedThing omim.nt owl:Class UMLS:C1863239 biolink:NamedThing omim.nt owl:Class ORPHA:277 biolink:NamedThing|biolink:Disease omim.nt owl:Class http://omim.org/entry/102710 biolink:NamedThing omim.nt True owl:Class http://omim.org/entry/102720 biolink:NamedThing|biolink:Gene DPP4 Dipeptidyl Peptidase 4 omim.nt DIPEPTIDYL PEPTIDASE IV; DPP4|Adenosine Deaminase Complexing Protein 2|Dipeptidyl Peptidase, Intestinal|T-Cell Activation Antigen Cd26 owl:Class MONARCH:.well-known/genid/b8a7f155483bf3b03f8f biolink:NamedThing GRCh38chr2-161992244-162074214-Region omim.nt MONARCH:.well-known/genid/b079e7165626b3c93e35 faldo:Region MONARCH:.well-known/genid/OMIM102720ref15 biolink:NamedThing Genes on human chromosomes 2 and 6 are required for expression of the adenosine deaminase complexing protein (ADCP) in human-mouse somatic cell hybrids. (Abstract) omim.nt IAO:0000310 PMID:10823914 biolink:NamedThing omim.nt IAO:0000013 PMID:12690074 biolink:NamedThing omim.nt IAO:0000013 PMID:12748388 biolink:NamedThing omim.nt IAO:0000013 PMID:1347043 biolink:NamedThing omim.nt IAO:0000013 PMID:1352704 biolink:NamedThing omim.nt IAO:0000013 PMID:15310902 biolink:NamedThing omim.nt IAO:0000013 PMID:15353589 biolink:NamedThing omim.nt IAO:0000013 PMID:1977364 biolink:NamedThing omim.nt IAO:0000013 PMID:23486063 biolink:NamedThing omim.nt IAO:0000013 PMID:23831647 biolink:NamedThing omim.nt IAO:0000013 PMID:24554656 biolink:NamedThing omim.nt IAO:0000013 PMID:24599590 biolink:NamedThing omim.nt IAO:0000013 PMID:25589660 biolink:NamedThing omim.nt IAO:0000013 PMID:25752900 biolink:NamedThing omim.nt IAO:0000013 PMID:26124093 biolink:NamedThing omim.nt IAO:0000013 PMID:279003 biolink:NamedThing omim.nt IAO:0000013 PMID:29562231 biolink:NamedThing omim.nt IAO:0000013 PMID:6120891 biolink:NamedThing omim.nt IAO:0000013 PMID:6974523 biolink:NamedThing omim.nt IAO:0000013 PMID:7903479 biolink:NamedThing omim.nt IAO:0000013 PMID:7927537 biolink:NamedThing omim.nt IAO:0000013 PMID:7959771 biolink:NamedThing omim.nt IAO:0000013 PMID:7974009 biolink:NamedThing omim.nt IAO:0000013 PMID:8096237 biolink:NamedThing omim.nt IAO:0000013 PMID:8101391 biolink:NamedThing omim.nt IAO:0000013 UMLS:C1414141 biolink:NamedThing omim.nt owl:Class https://www.ncbi.nlm.nih.gov/gene/1803 biolink:NamedThing omim.nt http://omim.org/entry/102730 biolink:NamedThing Adenosine Deaminase, Elevated, Hemolytic Anemia Due to omim.nt ADENOSINE DEAMINASE, ELEVATED, HEMOLYTIC ANEMIA DUE TO owl:Class PMID:3029177 biolink:NamedThing omim.nt IAO:0000013 PMID:3949358 biolink:NamedThing omim.nt IAO:0000013 PMID:6646173 biolink:NamedThing omim.nt IAO:0000013 PMID:7139940 biolink:NamedThing omim.nt IAO:0000013 PMID:736030 biolink:NamedThing omim.nt IAO:0000013 PMID:7440220 biolink:NamedThing omim.nt IAO:0000013 PMID:7919352 biolink:NamedThing omim.nt IAO:0000013 PMID:8213817 biolink:NamedThing omim.nt IAO:0000013 PMID:836588 biolink:NamedThing omim.nt IAO:0000013 UMLS:C1863235 biolink:NamedThing omim.nt owl:Class http://omim.org/entry/102750.0001 biolink:NamedThing ADK, ALA301GLU In 2 Swedish sibs with hypermethioninemia due to adenosine kinase deficiency ({614300}), {1:Bjursell et al. (2011)} identified a homozygous 902C-A transversion in the ADK gene, resulting in an ala301-to-glu (A301E) substitution adjacent to the catalytic site. Each unaffected parent was heterozygous for the mutation, which was not found in 105 controls. In vitro functional expression studies in E. coli showed that the mutant protein had almost no enzymatic activity. omim.nt GENO:0000002 http://omim.org/entry/102750 biolink:NamedThing|biolink:Gene ADK Adenosine Kinase omim.nt ADENOSINE KINASE; ADK owl:Class ClinVar:RCV000022443 biolink:NamedThing omim.nt dbSNP:rs397514452 biolink:NamedThing omim.nt owl:NamedIndividual http://omim.org/entry/102750#0001 biolink:NamedThing omim.nt http://omim.org/entry/102750.0002 biolink:NamedThing ADK, ASP218ALA In 2 Malaysian sibs with hypermethioninemia due to adenosine kinase deficiency ({614300}), {1:Bjursell et al. (2011)} identified a homozygous 653A-C transversion in the ADK gene, resulting in an asp218-to-ala (D218A) substitution in the central beta-sheet domain. Each unaffected parent was heterozygous for the mutation. In vitro functional expression studies in E. coli showed that the mutant protein had about 20% residual enzymatic activity compared to wildtype. omim.nt GENO:0000002 ClinVar:RCV000022444 biolink:NamedThing omim.nt dbSNP:rs397514453 biolink:NamedThing omim.nt owl:NamedIndividual http://omim.org/entry/102750#0002 biolink:NamedThing omim.nt http://omim.org/entry/102750.0003 biolink:NamedThing ADK, GLY13GLU In 2 Malaysian sibs with hypermethioninemia due to adenosine kinase deficiency ({614300}), {1:Bjursell et al. (2011)} identified a homozygous 38G-A transition in the ADK gene, resulting in a gly13-to-glu (G13E) substitution close to the binding site for adenosine. Each unaffected parent was heterozygous for the mutation. In vitro functional expression studies in E. coli showed that the mutant protein had about 10% residual enzymatic activity compared to wildtype. omim.nt GENO:0000002 ClinVar:RCV000022445 biolink:NamedThing omim.nt dbSNP:rs397514454 biolink:NamedThing omim.nt owl:NamedIndividual http://omim.org/entry/102750#0003 biolink:NamedThing omim.nt http://omim.org/entry/102750.0004 biolink:NamedThing ADK, HIS324ARG This variant is classified as a variant of unknown significance because it is unclear whether the phenotype in the family (M173) reported by {7:Najmabadi et al. (2007)} was hypermethioninemia due to adenosine kinase deficiency ({614300}). In a large consanguineous Iranian family (M173) in which 6 individuals had mild to moderate mental retardation and autism spectrum disorder mapped to a 9.7-Mb candidate region on chromosome 10 between SNPs {dbSNP rs1599711} and {dbSNP rs942793} (formerly designated MRT8), {7:Najmabadi et al. (2007)} identified a homozygous his324-to-arg (H324R) substitution in the ADK gene. No additional clinical information was provided, and no metabolic studies of the patients or functional studies of the variant were performed. omim.nt GENO:0000002 ClinVar:RCV000256208 biolink:NamedThing omim.nt dbSNP:rs886039772 biolink:NamedThing omim.nt owl:NamedIndividual http://omim.org/entry/102750#0004 biolink:NamedThing omim.nt MONARCH:.well-known/genid/b5109bae0a641f53befb biolink:NamedThing GRCh38chr10-74151184-74709299-Region omim.nt MONARCH:.well-known/genid/bff46132a8714e1bed8e faldo:Region MONARCH:.well-known/genid/OMIM102750ref4 biolink:NamedThing Regional mapping, by exclusion, of adenosine kinase (ADK) on human chromosome 10 using the gene dosage approach. (Abstract) omim.nt IAO:0000310 PMID:11997462 biolink:NamedThing omim.nt IAO:0000013 PMID:17120046 biolink:NamedThing omim.nt IAO:0000013 PMID:185014 biolink:NamedThing omim.nt IAO:0000013 PMID:204068 biolink:NamedThing omim.nt IAO:0000013 PMID:21963049 biolink:NamedThing omim.nt IAO:0000013 PMID:6146563 biolink:NamedThing omim.nt IAO:0000013 PMID:8577746 biolink:NamedThing omim.nt IAO:0000013 PMID:9070863 biolink:NamedThing omim.nt IAO:0000013 OBO:CHR_9606chr10q11 biolink:NamedThing omim.nt owl:Class http://omim.org/entry/614300 biolink:NamedThing|biolink:Disease Hypermethioninemia Due to Adenosine Kinase Deficiency Hypermethioninemia Due to Adenosine Kinase Deficiency omim.nt HYPERMETHIONINEMIA DUE TO ADENOSINE KINASE DEFICIENCY|Mental Retardation, Autosomal Recessive 8, Formerly owl:Class UMLS:C1412243 biolink:NamedThing omim.nt owl:Class https://www.ncbi.nlm.nih.gov/gene/132 biolink:NamedThing omim.nt http://omim.org/entry/102770.0001 biolink:NamedThing AMPD1, GLN12TER In 11 unrelated individuals with myopathy due to myoadenylate deaminase deficiency (MMDD; {615511}), {7:Morisaki et al. (1992)} identified a homozygous 34C-T transition in exon 2 of the AMPD1 gene, resulting in a gln12-to-ter (Q12X) substitution. Skeletal muscle biopsies showed no immunoreactive AMPD1 peptide in these patients, and variable but significantly decreased AMPD1 activity. All individuals also carried a P48L (143C-T) substitution that was shown to have no effect on enzyme activity. The Q12X mutant allele was found in heterozygosity in 17% of Caucasians and 23% of African Americans, whereas none of 106 Japanese subjects surveyed had this mutant allele. The frequency of the mutant allele would account for the 2% reported incidence of AMPD deficiency in muscle biopsies. The restricted distribution and high frequency of this doubly mutated allele suggested that it arose in a remote ancestor of individuals of western European descent. {2:Castro-Gago et al. (2011)} identified a homozygous Q12X mutation in a Spanish infant with hypotonia due to MMDD. She had severe muscle weakness, hypotonia of the trunk and upper limbs, areflexia, and lacked muscle atrophy. Ocular movements were normal; she also had macrocephaly. Skeletal muscle biopsy showed normal levels of all skeletal proteins tested but loss of AMPD1 enzyme activity. Hypotonia persisted, and the child was unable to sit at age 18 months. omim.nt GENO:0000002 http://omim.org/entry/102770 biolink:NamedThing|biolink:Gene AMPD1 Adenosine Monophosphate Deaminase 1 omim.nt ADENOSINE MONOPHOSPHATE DEAMINASE 1; AMPD1|Amp Deaminase|Myoadenylate Deaminase owl:Class ClinVar:RCV000019933 biolink:NamedThing omim.nt ClinVar:RCV000487355 biolink:NamedThing omim.nt dbSNP:rs17602729 biolink:NamedThing omim.nt owl:NamedIndividual http://omim.org/entry/102770#0001 biolink:NamedThing omim.nt http://omim.org/entry/102770.0002 biolink:NamedThing AMPD1, ARG388TRP In a Japanese woman with adult-onset myopathy due to myoadenylate deaminase deficiency (MMDD; {615511}), {5:Morisaki et al. (2000)} and {1:Abe et al. (2000)} identified compound heterozygous mutations in the AMPD1 gene: arg388-to-trp (R388W) and arg425-to-his (R425H; {102770.0003}) in exon 9 and exon 10, respectively. Neither mutation was found in the control population. omim.nt GENO:0000002 ClinVar:RCV000019934 biolink:NamedThing omim.nt ClinVar:RCV000522883 biolink:NamedThing omim.nt dbSNP:rs35859650 biolink:NamedThing omim.nt owl:NamedIndividual http://omim.org/entry/102770#0002 biolink:NamedThing omim.nt http://omim.org/entry/102770.0003 biolink:NamedThing AMPD1, ARG425HIS For discussion of the arg425-to-his (R425H) mutation in the AMPD1 gene that was found in compound heterozygous state in a patient with adult-onset myopathy due to myoadenylate deaminase deficiency (MMDD; {615511}) by {5:Morisaki et al. (2000)} and {1:Abe et al. (2000)}, see {102770.0002}. omim.nt GENO:0000002 ClinVar:RCV000019935 biolink:NamedThing omim.nt ClinVar:RCV000173624 biolink:NamedThing omim.nt dbSNP:rs121912682 biolink:NamedThing omim.nt owl:NamedIndividual http://omim.org/entry/102770#0003 biolink:NamedThing omim.nt MONARCH:.well-known/genid/b7cd5ae6eb6ad547a5e6 biolink:NamedThing GRCh38chr1-114673097-114695545-Region omim.nt MONARCH:.well-known/genid/ba6aa20164597a1d7209 faldo:Region MONARCH:.well-known/genid/OMIM102770ref9 biolink:NamedThing Human AMP deaminase-1 gene (AMPD1) is mapped to chromosome 1. (Abstract) omim.nt IAO:0000310 PMID:10086964 biolink:NamedThing omim.nt IAO:0000013 PMID:10996775 biolink:NamedThing omim.nt IAO:0000013 PMID:11102975 biolink:NamedThing omim.nt IAO:0000013 PMID:11331279 biolink:NamedThing omim.nt IAO:0000013 PMID:1631143 biolink:NamedThing omim.nt IAO:0000013 PMID:21343608 biolink:NamedThing omim.nt IAO:0000013 PMID:2328996 biolink:NamedThing omim.nt IAO:0000013 PMID:2345176 biolink:NamedThing omim.nt IAO:0000013 PMID:2365682 biolink:NamedThing omim.nt IAO:0000013 PMID:2568582 biolink:NamedThing omim.nt IAO:0000013 PMID:8486786 biolink:NamedThing omim.nt IAO:0000013 OBO:CHR_9606chr1p21 biolink:NamedThing omim.nt owl:Class http://omim.org/entry/615511 biolink:NamedThing|biolink:Disease Myopathy Due to Myoadenylate Deaminase Deficiency Myopathy Due to Myoadenylate Deaminase Deficiency omim.nt MYOPATHY DUE TO MYOADENYLATE DEAMINASE DEFICIENCY; MMDD|Adenosine Monophosphate Deaminase-1 Deficiency, Myopathy Due to|Ampd1 Deficiency|Myoadenylate Deaminase Deficiency, Myopathy Due to owl:Class UMLS:C1412387 biolink:NamedThing omim.nt owl:Class https://www.ncbi.nlm.nih.gov/gene/270 biolink:NamedThing omim.nt http://omim.org/entry/102771.0001 biolink:NamedThing AMPD2, 1-BP DEL, 318T In 2 affected cousins in a highly consanguineous family (family 1526) segregating spastic paraplegia (SPG63; {615686}), {8:Novarino et al. (2014)} identified a 1-bp deletion (318delT) in the AMPD2 gene, resulting in a frameshift and premature termination (Cys107Alafs365Ter). This homozygous mutation was found only in affected individuals of the family. omim.nt GENO:0000002 http://omim.org/entry/102771 biolink:NamedThing|biolink:Gene AMPD2 Adenosine Monophosphate Deaminase 2|mutation identified in 1 SPG63 family omim.nt ADENOSINE MONOPHOSPHATE DEAMINASE 2; AMPD2 owl:Class ClinVar:RCV000087328 biolink:NamedThing omim.nt dbSNP:rs587777769 biolink:NamedThing omim.nt owl:NamedIndividual http://omim.org/entry/102771#0001 biolink:NamedThing omim.nt http://omim.org/entry/102771.0002 biolink:NamedThing AMPD2, 1-BP DEL, 1652G In a Turkish girl with pontocerebellar hypoplasia type 9 (PCH9; {615809}), {1:Akizu et al. (2013)} identified a homozygous 1-bp deletion (c.1652delG) in exon 12 of the AMPD2 gene, resulting in a frameshift and premature termination (Asp552ThrfsTer66). The mutation, which was found by whole-exome sequencing and confirmed by Sanger sequencing, segregated with the disorder in the family. It was not present in publicly available SNP databases or in 1,500 in-house exomes. omim.nt GENO:0000002 ClinVar:RCV000119278 biolink:NamedThing omim.nt dbSNP:rs587777391 biolink:NamedThing omim.nt owl:NamedIndividual http://omim.org/entry/102771#0002 biolink:NamedThing omim.nt http://omim.org/entry/102771.0003 biolink:NamedThing AMPD2, GLU778ASP In 2 Egyptian sisters with pontocerebellar hypoplasia type 9 (PCH9; {615809}), {1:Akizu et al. (2013)} identified a homozygous c.2332G-C transversion in exon 17 of the AMPD2 gene, resulting in a glu778-to-asp (E778D) substitution at a highly conserved residue in an alpha-helix domain important for protein structure. The mutation, which was found by whole-exome sequencing and confirmed by Sanger sequencing, segregated with the disorder in the family. It was not present in publicly available SNP databases or in 1,500 in-house exomes. omim.nt GENO:0000002 ClinVar:RCV000119279 biolink:NamedThing omim.nt dbSNP:rs587777392 biolink:NamedThing omim.nt owl:NamedIndividual http://omim.org/entry/102771#0003 biolink:NamedThing omim.nt http://omim.org/entry/102771.0004 biolink:NamedThing AMPD2, TYR349TER In 2 Saudi brothers with pontocerebellar hypoplasia type 9 (PCH9; {615809}), {1:Akizu et al. (2013)} identified a homozygous c.1047C-A transversion in exon 8 of the AMPD2 gene, resulting in a tyr349-to-ter (Y349X) substitution. The mutation, which was found by whole-exome sequencing and confirmed by Sanger sequencing, segregated with the disorder in the family. It was not present in publicly available SNP databases or in 1,500 in-house exomes. omim.nt GENO:0000002 ClinVar:RCV000119280 biolink:NamedThing omim.nt dbSNP:rs587777393 biolink:NamedThing omim.nt owl:NamedIndividual http://omim.org/entry/102771#0004 biolink:NamedThing omim.nt http://omim.org/entry/102771.0005 biolink:NamedThing AMPD2, ASP793TYR In an Egyptian boy with pontocerebellar hypoplasia type 9 (PCH9; {615809}), {1:Akizu et al. (2013)} identified a homozygous c.2377G-T transversion in exon 17 of the AMPD2 gene, resulting in an asp793-to-tyr (D793Y) substitution at a highly conserved residue in an alpha-helix domain important for protein structure. The mutation, which was found by whole-exome sequencing and confirmed by Sanger sequencing, segregated with the disorder in the family. It was not present in publicly available SNP databases or in 1,500 in-house exomes. omim.nt GENO:0000002 ClinVar:RCV000119281 biolink:NamedThing omim.nt dbSNP:rs587777394 biolink:NamedThing omim.nt owl:NamedIndividual http://omim.org/entry/102771#0005 biolink:NamedThing omim.nt http://omim.org/entry/102771.0006 biolink:NamedThing AMPD2, ARG674HIS In 2 Saudi brothers with pontocerebellar hypoplasia type 9 (PCH9; {615809}), {1:Akizu et al. (2013)} identified a homozygous c.2021G-A transition in exon 14 of the AMPD2 gene, resulting in an arg674-to-his (R674H) substitution at a highly conserved residue in an alpha-helix domain important for protein structure. The mutation, which was found by whole-exome sequencing and confirmed by Sanger sequencing, segregated with the disorder in the family. It was not present in publicly available SNP databases or in 1,500 in-house exomes. omim.nt GENO:0000002 ClinVar:RCV000119282 biolink:NamedThing omim.nt dbSNP:rs587777395 biolink:NamedThing omim.nt owl:NamedIndividual http://omim.org/entry/102771#0006 biolink:NamedThing omim.nt http://omim.org/entry/102771.0007 biolink:NamedThing AMPD2, TYR752TER In 4 sibs, born of consanguineous Middle Eastern parents, with pontocerebellar hypoplasia type 9 (PCH9; {615809}), {5:Marsh et al. (2015)} identified a homozygous c.2256C-G transversion ({VAR c.2256C-G, NM_001257360.1}) in the AMPD2 gene, resulting in a tyr752-to-ter (Y752X) substitution. The mutation, which as found by a combination of linkage analysis and whole-exome sequencing and confirmed by Sanger sequencing, segregated with the disorder in the family. Western blot analysis of patient cells showed complete absence of the AMPD2 protein. Functional studies of the variant were not performed. Two of the patients developed axonal neuropathy in the second decade. omim.nt GENO:0000002 ClinVar:RCV000211051 biolink:NamedThing omim.nt dbSNP:rs875989844 biolink:NamedThing omim.nt owl:NamedIndividual http://omim.org/entry/102771#0007 biolink:NamedThing omim.nt MONARCH:.well-known/genid/b10e599aa41392851aa4 biolink:NamedThing GRCh38chr1-109619836-109632054-Region omim.nt MONARCH:.well-known/genid/bc8b95f83b3124782f77 faldo:Region MONARCH:.well-known/genid/OMIM102771ref3 biolink:NamedThing Distribution of the AMP deaminase multigene family within the human genome: assignment of the AMPD2 to chromosome 1p21-p34 and AMPD3 to chromosome 11p13-pter. (Abstract) omim.nt IAO:0000310 PMID:1429593 biolink:NamedThing omim.nt IAO:0000013 PMID:23911318 biolink:NamedThing omim.nt IAO:0000013 PMID:24482476 biolink:NamedThing omim.nt IAO:0000013 PMID:27066553 biolink:NamedThing omim.nt IAO:0000013 PMID:6107718 biolink:NamedThing omim.nt IAO:0000013 PMID:8764830 biolink:NamedThing omim.nt IAO:0000013 http://omim.org/entry/615686 biolink:NamedThing|biolink:Disease Spastic Paraplegia 63, Autosomal Recessive Spastic Paraplegia 63, Autosomal Recessive omim.nt SPASTIC PARAPLEGIA 63, AUTOSOMAL RECESSIVE; SPG63 owl:Class OBO:CHR_9606chr1p13.3 biolink:NamedThing omim.nt owl:Class http://omim.org/entry/615809 biolink:NamedThing|biolink:Disease Pontocerebellar Hypoplasia, Type 9 Pontocerebellar Hypoplasia, Type 9 omim.nt PONTOCEREBELLAR HYPOPLASIA, TYPE 9; PCH9 owl:Class http://www.omim.org/phenotypicSeries/PS303350 biolink:NamedThing|biolink:Disease Spastic paraplegia omim.nt owl:Class http://www.omim.org/phenotypicSeries/PS607596 biolink:NamedThing|biolink:Disease Pontocerebellar hypoplasia omim.nt owl:Class UMLS:C1412388 biolink:NamedThing omim.nt owl:Class https://www.ncbi.nlm.nih.gov/gene/271 biolink:NamedThing omim.nt http://omim.org/entry/102772.0001 biolink:NamedThing AMPD3, ARG573CYS In 2 individuals with complete deficiency of erythrocyte AMP deaminase ({612874}), {9:Yamada et al. (1994)} identified homozygosity for a 1717C-T transition in the AMPD3 gene, resulting in an amino acid change of arg to cys at codon 573 (R573C). Two individuals with partial deficiency of the enzyme were found to be heterozygous for the mutation. The mutation resulted in a catalytically inactive enzyme. Among 45 Japanese individuals with partial erythrocyte AMP deaminase deficiency, {7:Yamada et al. (1994)} found that all but 16 were heterozygous for the R573C mutation; 2 individuals with complete deficiency were homozygous for the mutation. They concluded that this mutation accounts for 75% of erythrocyte AMP deaminase deficiency in Japan. omim.nt GENO:0000002 http://omim.org/entry/102772 biolink:NamedThing|biolink:Gene AMPD3 Adenosine Monophosphate Deaminase 3 omim.nt ADENOSINE MONOPHOSPHATE DEAMINASE 3; AMPD3 owl:Class ClinVar:RCV000019932 biolink:NamedThing omim.nt dbSNP:rs3741040 biolink:NamedThing omim.nt owl:NamedIndividual http://omim.org/entry/102772#0001 biolink:NamedThing omim.nt MONARCH:.well-known/genid/b70370bcac36cc520db8 biolink:NamedThing GRCh38chr11-10450387-10507578-Region omim.nt MONARCH:.well-known/genid/b5e34b90eaf0cd648043 faldo:Region MONARCH:.well-known/genid/OMIM102772ref1 biolink:NamedThing Distribution of the AMP deaminase multigene family within the human genome: assignment of the AMPD2 to chromosome 1p21-p34 and AMPD3 to chromosome 11p13-pter. (Abstract) omim.nt IAO:0000310 PMID:1400401 biolink:NamedThing omim.nt IAO:0000013 PMID:1420359 biolink:NamedThing omim.nt IAO:0000013 PMID:3804327 biolink:NamedThing omim.nt IAO:0000013 PMID:7881427 biolink:NamedThing omim.nt IAO:0000013 PMID:8004104 biolink:NamedThing omim.nt IAO:0000013 PMID:8611627 biolink:NamedThing omim.nt IAO:0000013 PMID:9291127 biolink:NamedThing omim.nt IAO:0000013 PMID:9321472 biolink:NamedThing omim.nt IAO:0000013 OBO:CHR_9606chr11pter biolink:NamedThing omim.nt owl:Class http://omim.org/entry/612874 biolink:NamedThing|biolink:Disease Erythrocyte Amp Deaminase Deficiency Erythrocyte Amp Deaminase Deficiency omim.nt ERYTHROCYTE AMP DEAMINASE DEFICIENCY owl:Class UMLS:C1412389 biolink:NamedThing omim.nt owl:Class https://www.ncbi.nlm.nih.gov/gene/272 biolink:NamedThing omim.nt http://omim.org/entry/102775.0001 biolink:NamedThing ADORA1, GLY279SER This variant is classified as a variant of unknown significance because its contribution to early-onset Parkinson disease and cognitive dysfunction has not been confirmed. In 2 brothers, born of consanguineous Iranian parents, with early-onset parkinsonism and cognitive dysfunction, {5:Jaberi et al. (2016)} identified a homozygous c.835G-A transition in the ADORA1 gene, resulting in a gly279-to-ser (G279S) substitution at a highly conserved residue in transmembrane 7. The mutation, which was found by a combination of homozygosity mapping and exome sequencing, was confirmed by Sanger sequencing and segregated with the disorder in the family. It was filtered against the dbSNP, 1000 Genomes Project, Exome Variant Server, and ExAC databases, and was found only once in heterozygous state among all these databases. The mutation was not found in 700 Iranian controls. In vitro functional expression studies in HEK293 cells showed that the G279S variant did not disrupt proper expression or localization of the protein, or affect its interaction with the DRD1 receptor ({126449}). {5:Jaberi et al. (2016)} noted that the ADORA1 gene is within the PARK16 locus ({613164}) on chromosome 1q32. However, screening of 100 additional patients with early-onset parkinson disease did not identify any other ADORA1 variants. The patients had onset of foot dragging and abnormal gait in their twenties. Neurologic examination showed features of parkinsonism, as well as spasticity and a distal axonal sensorimotor neuropathy. The patients had onset of psychomotor retardation in childhood and had cognitive impairment as adults; 1 was reported as having severe mental retardation. The brother who underwent exome sequencing also carried a homozygous missense variant in the PTRHD1 gene ({617342.0001}). Segregation and functional studies of the PTRHD1 variant were not pursued because the ADORA1 gene was considered to be the likely candidate due to its previously reported role in neurologic functions. omim.nt GENO:0000002 http://omim.org/entry/102775 biolink:NamedThing|biolink:Gene ADORA1 Adenosine A1 Receptor omim.nt ADENOSINE A1 RECEPTOR; ADORA1|Rdc7 owl:Class ClinVar:RCV000417207 biolink:NamedThing omim.nt dbSNP:rs748346254 biolink:NamedThing omim.nt owl:NamedIndividual http://omim.org/entry/102775#0001 biolink:NamedThing omim.nt MONARCH:.well-known/genid/b501c1fb42707ce08727 biolink:NamedThing GRCh38chr1-203127704-203167404-Region omim.nt MONARCH:.well-known/genid/bd408896ad4dfaae53c3 faldo:Region PMID:11001830 biolink:NamedThing omim.nt IAO:0000013 PMID:11504952 biolink:NamedThing omim.nt IAO:0000013 PMID:13971060 biolink:NamedThing omim.nt IAO:0000013 PMID:15258586 biolink:NamedThing omim.nt IAO:0000013 PMID:1551861 biolink:NamedThing omim.nt IAO:0000013 PMID:15630442 biolink:NamedThing omim.nt IAO:0000013 PMID:1662665 biolink:NamedThing omim.nt IAO:0000013 PMID:16994064 biolink:NamedThing omim.nt IAO:0000013 PMID:2298733 biolink:NamedThing omim.nt IAO:0000013 PMID:27134041 biolink:NamedThing omim.nt IAO:0000013 PMID:7601478 biolink:NamedThing omim.nt IAO:0000013 OBO:CHR_9606chr1q32.1 biolink:NamedThing omim.nt owl:Class UMLS:C1412245 biolink:NamedThing omim.nt owl:Class https://www.ncbi.nlm.nih.gov/gene/134 biolink:NamedThing omim.nt http://omim.org/entry/102776 biolink:NamedThing|biolink:Gene ADORA2A Adenosine A2A Receptor|incorrectly assigned to 11q omim.nt ADENOSINE A2A RECEPTOR; ADORA2A|A2Ar|Adora2|Rdc8 owl:Class MONARCH:.well-known/genid/bbe810e939e621ca6414 biolink:NamedThing GRCh38chr22-24423596-24442356-Region omim.nt MONARCH:.well-known/genid/b1c76842795a3a53ff51 faldo:Region MONARCH:.well-known/genid/OMIM102776ref6 biolink:NamedThing Personal Communication. omim.nt IAO:0000310 MONARCH:.well-known/genid/OMIM102776ref7 biolink:NamedThing Personal Communication. omim.nt IAO:0000310 PMID:10531422 biolink:NamedThing omim.nt IAO:0000013 PMID:11780065 biolink:NamedThing omim.nt IAO:0000013 PMID:1331670 biolink:NamedThing omim.nt IAO:0000013 PMID:15448683 biolink:NamedThing omim.nt IAO:0000013 PMID:15816854 biolink:NamedThing omim.nt IAO:0000013 PMID:15965471 biolink:NamedThing omim.nt IAO:0000013 PMID:17689978 biolink:NamedThing omim.nt IAO:0000013 PMID:18832607 biolink:NamedThing omim.nt IAO:0000013 PMID:19443488 biolink:NamedThing omim.nt IAO:0000013 PMID:21393508 biolink:NamedThing omim.nt IAO:0000013 PMID:21593763 biolink:NamedThing omim.nt IAO:0000013 PMID:22367999 biolink:NamedThing omim.nt IAO:0000013 PMID:24043903 biolink:NamedThing omim.nt IAO:0000013 PMID:29995853 biolink:NamedThing omim.nt IAO:0000013 PMID:8020991 biolink:NamedThing omim.nt IAO:0000013 PMID:8325649 biolink:NamedThing omim.nt IAO:0000013 PMID:8670304 biolink:NamedThing omim.nt IAO:0000013 PMID:9262401 biolink:NamedThing omim.nt IAO:0000013 OBO:CHR_9606chr22q11.2 biolink:NamedThing omim.nt owl:Class UMLS:C1412246 biolink:NamedThing omim.nt owl:Class https://www.ncbi.nlm.nih.gov/gene/135 biolink:NamedThing omim.nt http://omim.org/entry/102777 biolink:NamedThing omim.nt True owl:Class http://omim.org/entry/600446 biolink:NamedThing|biolink:Gene ADORA2B Adenosine A2B Receptor|incorrectly put on 10 omim.nt ADENOSINE A2B RECEPTOR; ADORA2B|A2Br owl:Class http://omim.org/entry/102800 biolink:NamedThing|biolink:Disease Adenosine Triphosphatase Deficiency, Anemia Due to Adenosine Triphosphatase Deficiency, Anemia Due to omim.nt ADENOSINE TRIPHOSPHATASE DEFICIENCY, ANEMIA DUE TO owl:Class MONARCH:.well-known/genid/OMIM102800ref3 biolink:NamedThing Adenine nucleotide reductions associated with a dominantly transmitted form of nonspherocytic hemolytic anemia. (Abstract) omim.nt IAO:0000310 PMID:14149197 biolink:NamedThing omim.nt IAO:0000013 PMID:4257922 biolink:NamedThing omim.nt IAO:0000013 UMLS:C1863225 biolink:NamedThing omim.nt owl:Class http://omim.org/entry/102900 biolink:NamedThing|biolink:Disease Adenosine Triphosphate, Elevated, of Erythrocytes Adenosine Triphosphate, Elevated, of Erythrocytes omim.nt ADENOSINE TRIPHOSPHATE, ELEVATED, OF ERYTHROCYTES|Pyruvate Kinase Hyperactivity owl:Class MONARCH:.well-known/genid/OMIM102900ref2 biolink:NamedThing Personal Communication. omim.nt IAO:0000310 MONARCH:.well-known/genid/OMIM102900ref4 biolink:NamedThing Elevated ATP levels in human erythrocytes. In: Beutler, E. (ed.): Hereditary Disorders of Erythrocyte Metabolism. omim.nt IAO:0000310 PMID:14300761 biolink:NamedThing omim.nt IAO:0000013 PMID:4160306 biolink:NamedThing omim.nt IAO:0000013 PMID:7426754 biolink:NamedThing omim.nt IAO:0000013 PMID:9090535 biolink:NamedThing omim.nt IAO:0000013 UMLS:C1863224 biolink:NamedThing omim.nt owl:Class http://omim.org/entry/102910 biolink:NamedThing|biolink:Gene ATP5F1B Atp Synthase F1, Subunit Beta omim.nt ATP SYNTHASE F1, SUBUNIT BETA; ATP5F1B|Atp5B|Atpsb|Atp Synthase, H+ Transporting, Mitochondrial F1 Complex, Beta Subunit|Mitochondrial Atp Synthase, Beta Subunit owl:Class MONARCH:.well-known/genid/bd17cad6a86ef1861986 biolink:NamedThing GRCh38chr12-56638174-56645983-Region omim.nt MONARCH:.well-known/genid/bade7359092bfa227b05 faldo:Region MONARCH:.well-known/genid/OMIM102910ref2 biolink:NamedThing Assignment of ATP synthase beta subunit (ATPMB) gene to the p13-qter region of human chromosome 12. (Abstract) omim.nt IAO:0000310 MONARCH:.well-known/genid/OMIM102910ref4 biolink:NamedThing The human ATP synthase beta subunit gene has been sequenced and shown to be preferentially expressed in heart and skeletal muscle. (Abstract) omim.nt IAO:0000310 PMID:12511957 biolink:NamedThing omim.nt IAO:0000013 PMID:22219196 biolink:NamedThing omim.nt IAO:0000013 PMID:2687158 biolink:NamedThing omim.nt IAO:0000013 PMID:2900241 biolink:NamedThing omim.nt IAO:0000013 OBO:CHR_9606chr12p13 biolink:NamedThing omim.nt owl:Class UMLS:C1412653 biolink:NamedThing omim.nt owl:Class https://www.ncbi.nlm.nih.gov/gene/506 biolink:NamedThing omim.nt http://omim.org/entry/102980 biolink:NamedThing|biolink:Gene ADCYAP1 Adenylate Cyclase-Activating Polypeptide 1 omim.nt ADENYLATE CYCLASE-ACTIVATING POLYPEPTIDE 1; ADCYAP1|Pacap27|Pacap38|Pacap-Related Peptide|Pituitary Adenylate Cyclase-Activating Polypeptide owl:Class MONARCH:.well-known/genid/b4d1731fbd2a43fd8586 biolink:NamedThing GRCh38chr18-904383-912171-Region omim.nt MONARCH:.well-known/genid/b423d9a6535df5d98fc4 faldo:Region PMID:11687615 biolink:NamedThing omim.nt IAO:0000013 PMID:11756684 biolink:NamedThing omim.nt IAO:0000013 PMID:15048918 biolink:NamedThing omim.nt IAO:0000013 PMID:15067323 biolink:NamedThing omim.nt IAO:0000013 PMID:15620360 biolink:NamedThing omim.nt IAO:0000013 PMID:16505386 biolink:NamedThing omim.nt IAO:0000013 PMID:1730060 biolink:NamedThing omim.nt IAO:0000013 PMID:19190179 biolink:NamedThing omim.nt IAO:0000013 PMID:21350482 biolink:NamedThing omim.nt IAO:0000013 PMID:24487620 biolink:NamedThing omim.nt IAO:0000013 PMID:8353512 biolink:NamedThing omim.nt IAO:0000013 OBO:CHR_9606chr18p11 biolink:NamedThing omim.nt owl:Class UMLS:C1412228 biolink:NamedThing omim.nt owl:Class https://www.ncbi.nlm.nih.gov/gene/116 biolink:NamedThing omim.nt http://omim.org/entry/102981 biolink:NamedThing|biolink:Gene ADCYAP1R1 Adcyap Receptor, Type 1 omim.nt ADCYAP RECEPTOR, TYPE I; ADCYAP1R1|Adenylate Cyclase-Activating Polypeptide 1 Receptor|Pac1|Pacap Receptor, Type 1|Pituitary Adenylate Cyclase-Activating Polypeptide Receptor, Type 1 owl:Class MONARCH:.well-known/genid/b784545828b9efa3edb7 biolink:NamedThing GRCh38chr7-31052307-31111473-Region omim.nt MONARCH:.well-known/genid/b189b0cca4140fe23f9f faldo:Region PMID:10562300 biolink:NamedThing omim.nt IAO:0000013 PMID:1313597 biolink:NamedThing omim.nt IAO:0000013 PMID:16823490 biolink:NamedThing omim.nt IAO:0000013 PMID:7851900 biolink:NamedThing omim.nt IAO:0000013 PMID:7902709 biolink:NamedThing omim.nt IAO:0000013 PMID:8954788 biolink:NamedThing omim.nt IAO:0000013 PMID:9543159 biolink:NamedThing omim.nt IAO:0000013 UMLS:C1412229 biolink:NamedThing omim.nt owl:Class https://www.ncbi.nlm.nih.gov/gene/117 biolink:NamedThing omim.nt http://omim.org/entry/102990 biolink:NamedThing omim.nt True owl:Class http://omim.org/entry/145600 biolink:NamedThing|biolink:Disease Malignant Hyperthermia, Susceptibility To, 1 Malignant Hyperthermia, Susceptibility To, 1 omim.nt MALIGNANT HYPERTHERMIA, SUSCEPTIBILITY TO, 1; MHS1|Hyperpyrexia, Malignant|Hyperthermia of Anesthesia|King-Denborough Syndrome|King Syndrome|Mhs owl:Class http://omim.org/entry/103000.0001 biolink:NamedThing AK1, ARG128TRP In a patient with hemolytic anemia and adenylate kinase deficiency ({612631}), {14:Matsuura et al. (1989)} demonstrated a transition (C-to-T) in exon 6 of the AK1 gene that resulted in an arg-to-trp (CGG-to-TGG) substitution at residue 128 (R128W). Mutant chicken AK1, produced by introducing an arg-to-trp substitution at the same position by oligodeoxynucleotide-directed mutagenesis, showed reduced catalytic activity as well as decreased solubility when expressed in E. coli. omim.nt GENO:0000002 http://omim.org/entry/103000 biolink:NamedThing|biolink:Gene AK1 Adenylate Kinase 1|proximal to Ph1 break, 9q34.1; AK1 to ORM = 17cM omim.nt ADENYLATE KINASE 1; AK1|Adenylate Kinase, Soluble owl:Class ClinVar:RCV000019925 biolink:NamedThing omim.nt dbSNP:rs104894101 biolink:NamedThing omim.nt owl:NamedIndividual http://omim.org/entry/103000#0001 biolink:NamedThing omim.nt http://omim.org/entry/103000.0002 biolink:NamedThing AK1, ARG107TER {2:Bianchi et al. (1999)} described 2 sibs of Italian origin with mild chronic hemolytic anemia, psychomotor impairment, and undetectable adenylate kinase activity ({612631}). The other red cell enzyme activities were normal except for a slight decrease in phosphofructokinase (see PFKM; {610681}). Both sibs showed increased levels of 2,3-DPG. The parents were not consanguineous and displayed intermediate AK values. The sequence of complete erythrocyte AK1 cDNA in the sibs showed homozygosity for a nonsense mutation at codon 107: CGA (arg) to TGA (stop). The mutation resulted in a truncated protein of 107 amino acids in comparison with the normal 194. Moreover, a 37-bp deletion in the first part of exon 6 (nucleotides 326-362 of the cDNA sequence) was detectable in one allele. Because this deletion was localized after the stop codon, the authors thought that it would not have a further effect on the structure of the enzyme. The new variant was named AK Fidenza, from the origin of the patients. omim.nt GENO:0000002 ClinVar:RCV000019926 biolink:NamedThing omim.nt dbSNP:rs104894102 biolink:NamedThing omim.nt owl:NamedIndividual http://omim.org/entry/103000#0002 biolink:NamedThing omim.nt http://omim.org/entry/103000.0003 biolink:NamedThing AK1, TYR164CYS In an Italian child with hemolytic anemia and undetectable erythrocyte adenylate kinase activity ({612631}), {17:Qualtieri et al. (1997)} identified homozygosity for an A-to-G transition in exon 6 of the AK1 gene, resulting in a tyr164-to-cys (Y164C) substitution. Her parents and brother were heterozygous for the mutation and had 50% normal AK1 activity. omim.nt GENO:0000002 ClinVar:RCV000019927 biolink:NamedThing omim.nt dbSNP:rs137853203 biolink:NamedThing omim.nt owl:NamedIndividual http://omim.org/entry/103000#0003 biolink:NamedThing omim.nt http://omim.org/entry/103000.0004 biolink:NamedThing AK1, GLY40ARG In a Spanish boy with chronic nonspherocytic hemolytic anemia and severe red blood cell adenylate kinase deficiency ({612631}), {7:Corrons et al. (2003)} identified compound heterozygosity for 2 mutations in the AK1 gene: a 118G-A transition resulting in a gly40-to-arg (G40R) substitution, and a 190G-A transition resulting in a gly64-to-arg (G64R) substitution ({103000.0005}). The boy exhibited a neonatal icterus and splenomegaly and required blood transfusions until the age of 2 years. omim.nt GENO:0000002 ClinVar:RCV000019928 biolink:NamedThing omim.nt dbSNP:rs137853204 biolink:NamedThing omim.nt owl:NamedIndividual http://omim.org/entry/103000#0004 biolink:NamedThing omim.nt http://omim.org/entry/103000.0005 biolink:NamedThing AK1, GLY64ARG For discussion of the gly64-to-arg (G64R) mutation in the AK1 gene that was found in compound heterozygous state in a patient with chronic nonspherocytic hemolytic anemia and severe red blood cell adenylate kinase deficiency ({612631}) by {7:Corrons et al. (2003)}, see {103000.0004}. omim.nt GENO:0000002 ClinVar:RCV000019929 biolink:NamedThing omim.nt dbSNP:rs137853205 biolink:NamedThing omim.nt owl:NamedIndividual http://omim.org/entry/103000#0005 biolink:NamedThing omim.nt http://omim.org/entry/103000.0006 biolink:NamedThing AK1, 3-BP DEL, 498GAC In a white American infant with chronic nonspherocytic hemolytic anemia and severe red blood cell adenylate kinase deficiency ({612631}), whose parents were first cousins, {7:Corrons et al. (2003)} identified homozygosity for an in-frame deletion (GAC) at nucleotide 498 or 501, predicting deletion of either aspartic acid 140 or 141. omim.nt GENO:0000002 ClinVar:RCV000019930 biolink:NamedThing omim.nt dbSNP:rs387906582 biolink:NamedThing omim.nt owl:NamedIndividual http://omim.org/entry/103000#0006 biolink:NamedThing omim.nt http://omim.org/entry/103000.0007 biolink:NamedThing AK1, 1-BP DEL, 138G In a 3-year-old girl of southern Italian origin with a history of severe hemolytic anemia and low adenylate kinase activity (22% of normal) ({612631}), {10:Fermo et al. (2004)} identified homozygosity for a 1-bp deletion (138delG) in the AK1 gene, causing a frameshift and a premature stop at codon 91. omim.nt GENO:0000002 ClinVar:RCV000019931 biolink:NamedThing omim.nt dbSNP:rs387906583 biolink:NamedThing omim.nt owl:NamedIndividual http://omim.org/entry/103000#0007 biolink:NamedThing omim.nt MONARCH:.well-known/genid/be58cf6674564a000ba9 biolink:NamedThing GRCh38chr9-127866479-127885541-Region omim.nt MONARCH:.well-known/genid/b5c587a95e007478bb14 faldo:Region MONARCH:.well-known/genid/OMIM103000ref12 biolink:NamedThing Characterization of chromosomal abnormalities in chronic myeloid leukemia using somatic cell hybrids. (Abstract) omim.nt IAO:0000310 MONARCH:.well-known/genid/OMIM103000ref19 biolink:NamedThing Human Polymorphic Genes: World Distribution. omim.nt IAO:0000310 MONARCH:.well-known/genid/OMIM103000ref5 biolink:NamedThing Possible linkage between transcobalamin II (TC II) and adenylate kinase (AK). (Abstract) omim.nt IAO:0000310 PMID:10233365 biolink:NamedThing omim.nt IAO:0000013 PMID:11101510 biolink:NamedThing omim.nt IAO:0000013 PMID:12649162 biolink:NamedThing omim.nt IAO:0000013 PMID:15315793 biolink:NamedThing omim.nt IAO:0000013 PMID:173186 biolink:NamedThing omim.nt IAO:0000013 PMID:176661 biolink:NamedThing omim.nt IAO:0000013 PMID:184030 biolink:NamedThing omim.nt IAO:0000013 PMID:204246 biolink:NamedThing omim.nt IAO:0000013 PMID:212360 biolink:NamedThing omim.nt IAO:0000013 PMID:2541064 biolink:NamedThing omim.nt IAO:0000013 PMID:2542324 biolink:NamedThing omim.nt IAO:0000013 PMID:3024483 biolink:NamedThing omim.nt IAO:0000013 PMID:5365762 biolink:NamedThing omim.nt IAO:0000013 PMID:5365763 biolink:NamedThing omim.nt IAO:0000013 PMID:5449947 biolink:NamedThing omim.nt IAO:0000013 PMID:5571743 biolink:NamedThing omim.nt IAO:0000013 PMID:5648746 biolink:NamedThing omim.nt IAO:0000013 PMID:5915956 biolink:NamedThing omim.nt IAO:0000013 PMID:6053088 biolink:NamedThing omim.nt IAO:0000013 PMID:9432020 biolink:NamedThing omim.nt IAO:0000013 OBO:CHR_9606chr9q34.1 biolink:NamedThing omim.nt owl:Class http://omim.org/entry/612631 biolink:NamedThing|biolink:Disease Adenylate Kinase Deficiency, Hemolytic Anemia Due to Adenylate Kinase Deficiency, Hemolytic Anemia Due to omim.nt ADENYLATE KINASE DEFICIENCY, HEMOLYTIC ANEMIA DUE TO owl:Class UMLS:C1412305 biolink:NamedThing omim.nt owl:Class https://www.ncbi.nlm.nih.gov/gene/203 biolink:NamedThing omim.nt http://omim.org/entry/103020.0001 biolink:NamedThing AK2, 5,038-BP DEL In a German male with reticular dysgenesis ({267500}), {9:Pannicke et al. (2009)} identified a homozygous 5,038-bp deletion encompassing parts of exon 6, all of intron 6 and parts of exon 7 reaching into the 3-prime UTR of the AK2 gene. The mutation led to a complete loss of detectable AK2 protein in fibroblasts and in bone marrow mononuclear cells. The parents were heterozygous for the mutation, which was not found in 112 German or 50 Turkish healthy subjects. omim.nt GENO:0000002 http://omim.org/entry/103020 biolink:NamedThing|biolink:Gene AK2 Adenylate Kinase 2 omim.nt ADENYLATE KINASE 2; AK2|Adenylate Kinase, Mitochondrial Myokinase owl:Class ClinVar:RCV000019912 biolink:NamedThing omim.nt http://omim.org/entry/103020#0001 biolink:NamedThing omim.nt http://omim.org/entry/103020.0002 biolink:NamedThing AK2, 1-BP DEL, 118T In a German male with reticular dysgenesis ({267500}), {9:Pannicke et al. (2009)} identified compound heterozygosity for 2 mutations in the AK2 gene: a 1-bp deletion (118delT) leading to a frameshift and early truncation of the protein, and a 1A-G transition leading to a met1-to-val (M1V) substitution ({103020.0003}). The mutation led to a complete loss of detectable AK2 protein in fibroblasts and in bone marrow mononuclear cells. Each parent was heterozygous for one of the mutations. The mutations were not found in 112 German or 50 Turkish healthy subjects. omim.nt GENO:0000002 ClinVar:RCV000019913 biolink:NamedThing omim.nt dbSNP:rs387906581 biolink:NamedThing omim.nt owl:NamedIndividual http://omim.org/entry/103020#0002 biolink:NamedThing omim.nt http://omim.org/entry/103020.0003 biolink:NamedThing AK2, MET1VAL For discussion of the met1-to-val (M1V) mutation in the AK2 gene that was found in compound heterozygous state in a patient with reticular dysgenesis ({267500}) by {9:Pannicke et al. (2009)}, see {103020.0002}. omim.nt GENO:0000002 ClinVar:RCV000019914 biolink:NamedThing omim.nt dbSNP:rs137853206 biolink:NamedThing omim.nt owl:NamedIndividual http://omim.org/entry/103020#0003 biolink:NamedThing omim.nt http://omim.org/entry/103020.0004 biolink:NamedThing AK2, 331, G-A, -1 In a German male with reticular dysgenesis ({267500}), the offspring of consanguineous parents, {9:Pannicke et al. (2009)} identified homozygosity for a splicing mutation, 331-1G-A, in the AK2 gene. The mutation led to a complete loss of detectable AK2 protein in fibroblasts and in bone marrow mononuclear cells. The parents were heterozygous for the mutation, which was not found in 112 German or 50 Turkish healthy subjects. omim.nt GENO:0000002 ClinVar:RCV000019915 biolink:NamedThing omim.nt dbSNP:rs1192619329 biolink:NamedThing omim.nt owl:NamedIndividual http://omim.org/entry/103020#0004 biolink:NamedThing omim.nt http://omim.org/entry/103020.0005 biolink:NamedThing AK2, 1-BP DEL, 453C In male and female Turkish sibs with reticular dysgenesis ({267500}), the offspring of consanguineous parents, {9:Pannicke et al. (2009)} identified homozygosity for a 1-bp deletion (453delC) in the AK2 gene, leading to a frameshift and early truncation of the protein. The mutation led to a complete loss of detectable AK2 protein in fibroblasts and in bone marrow mononuclear cells. The parents were heterozygous for the mutation, which was not found in 112 German or 50 Turkish healthy subjects. omim.nt GENO:0000002 ClinVar:RCV000019916 biolink:NamedThing omim.nt dbSNP:rs1553151177 biolink:NamedThing omim.nt owl:NamedIndividual http://omim.org/entry/103020#0005 biolink:NamedThing omim.nt http://omim.org/entry/103020.0006 biolink:NamedThing AK2, 498, G-A, +1 In a Turkish female with reticular dysgenesis ({267500}), the offspring of consanguineous parents, {9:Pannicke et al. (2009)} identified homozygosity for a splicing mutation, 498+1G-A, in the AK2 gene. The mutation led to a complete loss of detectable AK2 protein in fibroblasts and in bone marrow mononuclear cells. The parents were heterozygous for the mutation, which was not found in 112 German or 50 Turkish healthy subjects. omim.nt GENO:0000002 ClinVar:RCV000019917 biolink:NamedThing omim.nt dbSNP:rs777503956 biolink:NamedThing omim.nt owl:NamedIndividual http://omim.org/entry/103020#0006 biolink:NamedThing omim.nt http://omim.org/entry/103020.0007 biolink:NamedThing AK2, ASP165GLY In 2 separate pedigrees with reticular dysgenesis ({267500}), each of whom was consanguineous, {5:Lagresle-Peyrou et al. (2009)} identified homozygosity for an A-to-G transition at nucleotide 546 in exon 5 of the AK2 gene, resulting in an asp-to-gly substitution in codon 165 (D165G) within the LID domain. This mutation changed a highly conserved amino acid. The parents were found to be carriers, and unaffected sibs were heterozygous or homozygous for the wildtype allele. omim.nt GENO:0000002 ClinVar:RCV000019918 biolink:NamedThing omim.nt dbSNP:rs267606643 biolink:NamedThing omim.nt owl:NamedIndividual http://omim.org/entry/103020#0007 biolink:NamedThing omim.nt http://omim.org/entry/103020.0008 biolink:NamedThing AK2, LEU183TER In a female from a consanguineous family affected with reticular dysgenesis ({267500}), {5:Lagresle-Peyrou et al. (2009)} identified a 1-bp deletion of C at nucleotide 523 in exon 6 of the AK2 gene (523delC), resulting in a substitution of a termination codon for a leucine at codon 183 (L183X). This mutation was not detected in her sister, and each parent was found to be a carrier. omim.nt GENO:0000002 ClinVar:RCV000019919 biolink:NamedThing omim.nt dbSNP:rs1553150995 biolink:NamedThing omim.nt owl:NamedIndividual http://omim.org/entry/103020#0008 biolink:NamedThing omim.nt http://omim.org/entry/103020.0009 biolink:NamedThing AK2, ARG186CYS In a female with reticular dysgenesis ({267500}), {5:Lagresle-Peyrou et al. (2009)} found compound heterozygosity for mutations in the AK2 gene: a C-to-T transition at nucleotide 556 in exon 6, resulting in an arg-to-cys substitution at codon 186 (R186C), and an exon 2 deletion (see {103020.0010}). omim.nt GENO:0000002 ClinVar:RCV000019920 biolink:NamedThing omim.nt dbSNP:rs267606645 biolink:NamedThing omim.nt owl:NamedIndividual http://omim.org/entry/103020#0009 biolink:NamedThing omim.nt http://omim.org/entry/103020.0010 biolink:NamedThing AK2, EX2 DEL In a female with reticular dysgenesis ({267500}) from a nonconsanguineous family, {5:Lagresle-Peyrou et al. (2009)} identified compound heterozygosity for deletion of exon 2 of the AK2 gene and an arg186-to-cys substitution ({103020.0009}). Each parent was a carrier of one of the mutations. omim.nt GENO:0000002 ClinVar:RCV000019921 biolink:NamedThing omim.nt http://omim.org/entry/103020#0010 biolink:NamedThing omim.nt http://omim.org/entry/103020.0011 biolink:NamedThing AK2, ARG103TRP In a female with reticular dysgenesis ({267500}), {5:Lagresle-Peyrou et al. (2009)} identified a C-to-T transition at nucleotide 307 in exon 3 of the AK2 gene, resulting in an arg-to-trp substitution at codon 103 (R103W). Each of her parents was a carrier for this mutation, which occurs in a highly conserved amino acid residue. omim.nt GENO:0000002 ClinVar:RCV000019922 biolink:NamedThing omim.nt dbSNP:rs267606648 biolink:NamedThing omim.nt owl:NamedIndividual http://omim.org/entry/103020#0011 biolink:NamedThing omim.nt http://omim.org/entry/103020.0012 biolink:NamedThing AK2, LYS233TER In a female with reticular dysgenesis ({267500}), {5:Lagresle-Peyrou et al. (2009)} identified a 5-kb deletion following nucleotide 633 (633del5kb), resulting in a lys-to-ter substitution at codon 233 (K233X). The patient was homozygous for this mutation. Two of her 3 unaffected sibs, and each of her unaffected parents, were carriers. omim.nt GENO:0000002 ClinVar:RCV000019923 biolink:NamedThing omim.nt dbSNP:rs267606646 biolink:NamedThing omim.nt owl:NamedIndividual http://omim.org/entry/103020#0012 biolink:NamedThing omim.nt http://omim.org/entry/103020.0013 biolink:NamedThing AK2, GLU9TER In a female with reticular dysgenesis ({267500}), {5:Lagresle-Peyrou et al. (2009)} identified homozygosity for a G-to-T transversion at nucleotide 25 in exon 1 of the AK2 gene, resulting in a glu-to-ter codon substitution at amino acid 9 (E9X). The child was homozygous for this mutation. Each of her parents was a carrier. omim.nt GENO:0000002 ClinVar:RCV000019924 biolink:NamedThing omim.nt dbSNP:rs267606647 biolink:NamedThing omim.nt owl:NamedIndividual http://omim.org/entry/103020#0013 biolink:NamedThing omim.nt MONARCH:.well-known/genid/b5cf847d2d4b3a1f005d biolink:NamedThing GRCh38chr1-33007939-33036882-Region omim.nt MONARCH:.well-known/genid/ba62377bb10f52c79caa faldo:Region PMID:17952061 biolink:NamedThing omim.nt IAO:0000013 PMID:19043416 biolink:NamedThing omim.nt IAO:0000013 PMID:19043417 biolink:NamedThing omim.nt IAO:0000013 PMID:195572 biolink:NamedThing omim.nt IAO:0000013 PMID:24548998 biolink:NamedThing omim.nt IAO:0000013 PMID:4539479 biolink:NamedThing omim.nt IAO:0000013 PMID:561097 biolink:NamedThing omim.nt IAO:0000013 PMID:6961883 biolink:NamedThing omim.nt IAO:0000013 PMID:9434148 biolink:NamedThing omim.nt IAO:0000013 OBO:CHR_9606chr1p34 biolink:NamedThing omim.nt owl:Class http://omim.org/entry/267500 biolink:NamedThing|biolink:Disease Reticular Dysgenesis Reticular Dysgenesis omim.nt RETICULAR DYSGENESIS|Aleukocytosis|Congenital Aleukia|De Vaal Disease|Hematopoietic Hypoplasia, Generalized|Reticular Dysgenesia|Severe Combined Immunodeficiency With Leukopenia owl:Class UMLS:C1412306 biolink:NamedThing omim.nt owl:Class https://www.ncbi.nlm.nih.gov/gene/204 biolink:NamedThing omim.nt http://omim.org/entry/103030 biolink:NamedThing|biolink:Gene AK4 Adenylate Kinase 4 omim.nt ADENYLATE KINASE 4; AK4|Adenylate Kinase 3, Formerly|Adenylate Kinase 3-Like 1|Ak4, Mouse, Homolog of owl:Class MONARCH:.well-known/genid/bc9e7126f49bc3b2aa65 biolink:NamedThing GRCh38chr1-65147341-65232144-Region omim.nt MONARCH:.well-known/genid/bda81531d72ba6c83eee faldo:Region MONARCH:.well-known/genid/OMIM103030ref1 biolink:NamedThing Personal Communication. omim.nt IAO:0000310 PMID:10544043 biolink:NamedThing omim.nt IAO:0000013 PMID:11485571 biolink:NamedThing omim.nt IAO:0000013 PMID:1639383 biolink:NamedThing omim.nt IAO:0000013 PMID:1694727 biolink:NamedThing omim.nt IAO:0000013 PMID:9813319 biolink:NamedThing omim.nt IAO:0000013 OBO:CHR_9606chr1p31.3 biolink:NamedThing omim.nt owl:Class UMLS:C1424944 biolink:NamedThing omim.nt owl:Class https://www.ncbi.nlm.nih.gov/gene/205 biolink:NamedThing omim.nt http://omim.org/entry/103050 biolink:NamedThing|biolink:Disease Adenylosuccinase Deficiency Adenylosuccinase Deficiency omim.nt ADENYLOSUCCINASE DEFICIENCY; ADSLD|Adenylosuccinate Lyase Deficiency|Adsl Deficiency owl:Class PMID:10090474 biolink:NamedThing omim.nt IAO:0000013 PMID:10888601 biolink:NamedThing omim.nt IAO:0000013 PMID:11042421 biolink:NamedThing omim.nt IAO:0000013 PMID:12070256 biolink:NamedThing omim.nt IAO:0000013 PMID:12833398 biolink:NamedThing omim.nt IAO:0000013 PMID:1302001 biolink:NamedThing omim.nt IAO:0000013 PMID:1405483 biolink:NamedThing omim.nt IAO:0000013 PMID:15114530 biolink:NamedThing omim.nt IAO:0000013 PMID:18524658 biolink:NamedThing omim.nt IAO:0000013 PMID:18830228 biolink:NamedThing omim.nt IAO:0000013 PMID:22180458 biolink:NamedThing omim.nt IAO:0000013 PMID:2563072 biolink:NamedThing omim.nt IAO:0000013 PMID:3234432 biolink:NamedThing omim.nt IAO:0000013 PMID:6150139 biolink:NamedThing omim.nt IAO:0000013 PMID:9266351 biolink:NamedThing omim.nt IAO:0000013 PMID:9266401 biolink:NamedThing omim.nt IAO:0000013 UMLS:C0268126 biolink:NamedThing omim.nt owl:Class ORPHA:46 biolink:NamedThing|biolink:Disease omim.nt owl:Class http://omim.org/entry/103060 biolink:NamedThing|biolink:Gene ADSS Adenylosuccinate Synthetase omim.nt ADENYLOSUCCINATE SYNTHETASE; ADSS|Ade(-)H, Complement of owl:Class MONARCH:.well-known/genid/b2570efaf254dcc9d7a0 biolink:NamedThing GRCh38chr1-244408493-244452059-Region omim.nt MONARCH:.well-known/genid/b8218e704a41d9cb7770 faldo:Region MONARCH:.well-known/genid/OMIM103060ref1 biolink:NamedThing Human chromosome 1 corrects the defect in the CHO mutant (Ade-H) deficient in a branch point enzyme in purine de novo biosynthesis. (Abstract) omim.nt IAO:0000310 PMID:1592113 biolink:NamedThing omim.nt IAO:0000013 PMID:2004783 biolink:NamedThing omim.nt IAO:0000013 OBO:CHR_9606chr1cen biolink:NamedThing omim.nt owl:Class UMLS:C1412263 biolink:NamedThing omim.nt owl:Class https://www.ncbi.nlm.nih.gov/gene/159 biolink:NamedThing omim.nt http://omim.org/entry/103070 biolink:NamedThing|biolink:Gene ADCY8 Adenylate Cyclase 8 omim.nt ADENYLATE CYCLASE 8; ADCY8|Adcy8|Adenylate Cyclase 3, Formerly|Adenylyl Cyclase, Brain, Type 1 owl:Class MONARCH:.well-known/genid/bd1e2dc5e0ee5e7f1deb biolink:NamedThing GRCh38chr8-130780299-131041603-Region omim.nt MONARCH:.well-known/genid/b18e8a54bf3c91235501 faldo:Region PMID:10075700 biolink:NamedThing omim.nt IAO:0000013 PMID:12441059 biolink:NamedThing omim.nt IAO:0000013 PMID:12503609 biolink:NamedThing omim.nt IAO:0000013 PMID:1427768 biolink:NamedThing omim.nt IAO:0000013 PMID:16537520 biolink:NamedThing omim.nt IAO:0000013 PMID:16613843 biolink:NamedThing omim.nt IAO:0000013 PMID:1715695 biolink:NamedThing omim.nt IAO:0000013 PMID:8076676 biolink:NamedThing omim.nt IAO:0000013 OBO:CHR_9606chr8q24.2 biolink:NamedThing omim.nt owl:Class UMLS:C1412227 biolink:NamedThing omim.nt owl:Class https://www.ncbi.nlm.nih.gov/gene/114 biolink:NamedThing omim.nt http://omim.org/entry/103071 biolink:NamedThing|biolink:Gene ADCY2 Adenylate Cyclase 2 omim.nt ADENYLATE CYCLASE 2; ADCY2|Adenylyl Cyclase 2|Adenylyl Cyclase, Brain, Type 2 owl:Class MONARCH:.well-known/genid/b62f44b980a16616270c biolink:NamedThing GRCh38chr5-7396137-7830080-Region omim.nt MONARCH:.well-known/genid/bd54c5d42f7d615cadda faldo:Region PMID:11055432 biolink:NamedThing omim.nt IAO:0000013 PMID:7766992 biolink:NamedThing omim.nt IAO:0000013 PMID:7959689 biolink:NamedThing omim.nt IAO:0000013 OBO:CHR_9606chr5p15.3 biolink:NamedThing omim.nt owl:Class UMLS:C1412221 biolink:NamedThing omim.nt owl:Class https://www.ncbi.nlm.nih.gov/gene/108 biolink:NamedThing omim.nt http://omim.org/entry/103072.0001 biolink:NamedThing ADCY1, ARG1038TER In affected members of a Pakistani family with autosomal recessive nonsyndromic hearing loss (DFNB44; {610154}), originally reported by {2:Ansar et al. (2004)}, {7:Santos-Cortez et al. (2014)} identified a homozygous c.3112C-T transition in the ADCY1 gene ({103072.0001}), resulting in an arg1038-to-ter (R1038X) substitution. The mutation, which was found by exome sequencing and confirmed by Sanger sequencing, segregated with hearing loss in the family and was not found in the dbSNP, 1000 Genomes Project, or Exome Variant Server databases, or in 650 ethnically matched control chromosomes. The mutation was predicted to cause the loss of 82 amino acids that form beta sheets of the cytoplasmic C terminus, including a highly conserved motif at the C2 domain at amino acids 1037-1053, as well as the loss of a calmodulin-interacting site. Arg1038 was predicted to lie within the AC catalytic domain and to participate in ATP binding. ADCY1 truncated COS-7 cells did not localize properly to microvilli, suggesting that these conserved elements within the C terminus are necessary not only for catalysis but also for membrane targeting. {7:Santos-Cortez et al. (2014)} generated gene-copy-specific zebrafish morphants, which showed gross hearing defects. omim.nt GENO:0000002 http://omim.org/entry/103072 biolink:NamedThing|biolink:Gene ADCY1 Adenylate Cyclase 1|mutation identified in 1 DFNB44 family omim.nt ADENYLATE CYCLASE 1; ADCY1|Adenylyl Cyclase 1|Adenylyl Cyclase, Fetal Brain, Type 1 owl:Class ClinVar:RCV000128528 biolink:NamedThing omim.nt dbSNP:rs587777497 biolink:NamedThing omim.nt owl:NamedIndividual http://omim.org/entry/103072#0001 biolink:NamedThing omim.nt MONARCH:.well-known/genid/ba13b26ef247d7521efd biolink:NamedThing GRCh38chr7-45574139-45723115-Region omim.nt MONARCH:.well-known/genid/bc660e58f7ccd236509f faldo:Region PMID:12897788 biolink:NamedThing omim.nt IAO:0000013 PMID:15133516 biolink:NamedThing omim.nt IAO:0000013 PMID:15583425 biolink:NamedThing omim.nt IAO:0000013 PMID:24482543 biolink:NamedThing omim.nt IAO:0000013 PMID:8314585 biolink:NamedThing omim.nt IAO:0000013 PMID:8596955 biolink:NamedThing omim.nt IAO:0000013 PMID:9662407 biolink:NamedThing omim.nt IAO:0000013 http://omim.org/entry/610154 biolink:NamedThing|biolink:Disease Deafness, Autosomal Recessive 44 Deafness, Autosomal Recessive 44 omim.nt DEAFNESS, AUTOSOMAL RECESSIVE 44; DFNB44 owl:Class OBO:CHR_9606chr7p13 biolink:NamedThing omim.nt owl:Class http://www.omim.org/phenotypicSeries/PS220290 biolink:NamedThing|biolink:Disease Deafness, autosomal recessive omim.nt owl:Class UMLS:C1412220 biolink:NamedThing omim.nt owl:Class https://www.ncbi.nlm.nih.gov/gene/107 biolink:NamedThing omim.nt http://omim.org/entry/103100 biolink:NamedThing|biolink:Disease Adie Pupil Adie Pupil omim.nt ADIE PUPIL|Adie Syndrome|Holmes-Adie Syndrome|Poorly Reacting Pupils owl:Class MONARCH:.well-known/genid/OMIM103100ref1 biolink:NamedThing Tonic pupils and absent tendon reflexes: a benign disorder sui generis: its complete and incomplete forms. omim.nt IAO:0000310 MONARCH:.well-known/genid/OMIM103100ref2 biolink:NamedThing Tonic pupils with absent tendon reflexes in mother and daughter. omim.nt IAO:0000310 MONARCH:.well-known/genid/OMIM103100ref5 biolink:NamedThing Adie's syndrome: a non-luetic disease simulating tabes dorsalis. omim.nt IAO:0000310 MONARCH:.well-known/genid/OMIM103100ref7 biolink:NamedThing Ueber familiaeres Vorkommen der Pupillotonie. omim.nt IAO:0000310 PMID:16775239 biolink:NamedThing omim.nt IAO:0000013 PMID:3340290 biolink:NamedThing omim.nt IAO:0000013 PMID:4177586 biolink:NamedThing omim.nt IAO:0000013 PMID:5838361 biolink:NamedThing omim.nt IAO:0000013 UMLS:C0001519 biolink:NamedThing omim.nt owl:Class UMLS:C0040416 biolink:NamedThing omim.nt owl:Class ORPHA:454718 biolink:NamedThing|biolink:Disease omim.nt owl:Class http://omim.org/entry/103180.0001 biolink:NamedThing ARF1, TYR35HIS In a 9-year-old boy with periventricular nodular heterotopia-8 (PVNH8; {618185}), {4:Ge et al. (2016)} identified a heterozygous c.103T-C transition ({VAR c.103T-C, NM_001024226}) in the ARF1 gene resulting in a tyr-to-his substitution at codon 35 (Y35H). The Y35H variant occurred as a de novo event and was not reported in ExAC. This variant is located adjacent to the GDP binding site. Expression of the mutant and wildtype allele in 293T cells demonstrated similar levels of expression, but the Y35H allele had markedly diminished nucleotide activation. omim.nt GENO:0000002 http://omim.org/entry/103180 biolink:NamedThing|biolink:Gene ARF1 Adp-Ribosylation Factor 1 omim.nt ADP-RIBOSYLATION FACTOR 1; ARF1 owl:Class ClinVar:RCV000721169 biolink:NamedThing omim.nt dbSNP:rs879036238 biolink:NamedThing omim.nt owl:NamedIndividual http://omim.org/entry/103180#0001 biolink:NamedThing omim.nt http://omim.org/entry/103180.0002 biolink:NamedThing ARF1, LYS127GLU In a 15-year-old girl with periventricular nodular heterotopia-8 (PVNH8; {618185}), {4:Ge et al. (2016)} identified a heterozygous c.379A-G transition ({VAR c.379A-G, NM_001024226}) in the ARF1 gene resulting in a lys-to-glu substitution at codon 127 (K127E). The K127E variant occurred as a de novo event, was not seen in ExAC, and affected the nucleotide-binding site of ARF1. K127 is known to be important in ARF1 functioning in other systems (yeast and Entamoeba histolytica). omim.nt GENO:0000002 ClinVar:RCV000721170 biolink:NamedThing omim.nt dbSNP:rs1558087795 biolink:NamedThing omim.nt owl:NamedIndividual http://omim.org/entry/103180#0002 biolink:NamedThing omim.nt http://omim.org/entry/103180.0003 biolink:NamedThing ARF1, ARG99HIS In a patient with periventricular nodular heterotopia-8 (PVNH8; {618185}), {4:Ge et al. (2016)} identified a heterozygous c.296G-A transition ({VAR c.296G-A, NM_001024226}) in the ARF1 gene resulting in an arg-to-his substitution at codon 99 (R99H). This variant occurred as a de novo event and was not seen in ExAC. {4:Ge et al. (2016)} reported that arginine-99 appears to contact 2 of the GDP-binding residues of ARF1. omim.nt GENO:0000002 ClinVar:RCV000721171 biolink:NamedThing omim.nt dbSNP:rs1558087712 biolink:NamedThing omim.nt owl:NamedIndividual http://omim.org/entry/103180#0003 biolink:NamedThing omim.nt MONARCH:.well-known/genid/bbb4d029b9cdf273d676 biolink:NamedThing GRCh38chr1-228082707-228099211-Region omim.nt MONARCH:.well-known/genid/b2f310eef10ef2f2bc5b faldo:Region PMID:12000962 biolink:NamedThing omim.nt IAO:0000013 PMID:14654833 biolink:NamedThing omim.nt IAO:0000013 PMID:1577740 biolink:NamedThing omim.nt IAO:0000013 PMID:18084285 biolink:NamedThing omim.nt IAO:0000013 PMID:23535599 biolink:NamedThing omim.nt IAO:0000013 PMID:2474826 biolink:NamedThing omim.nt IAO:0000013 PMID:25305484 biolink:NamedThing omim.nt IAO:0000013 PMID:2535313 biolink:NamedThing omim.nt IAO:0000013 PMID:28868155 biolink:NamedThing omim.nt IAO:0000013 PMID:32193326 biolink:NamedThing omim.nt IAO:0000013 PMID:7990966 biolink:NamedThing omim.nt IAO:0000013 PMID:8661066 biolink:NamedThing omim.nt IAO:0000013 PMID:9476900 biolink:NamedThing omim.nt IAO:0000013 http://omim.org/entry/618185 biolink:NamedThing|biolink:Disease Periventricular Nodular Heterotopia 8 Periventricular Nodular Heterotopia 8 omim.nt PERIVENTRICULAR NODULAR HETEROTOPIA 8; PVNH8 owl:Class http://www.omim.org/phenotypicSeries/PS300049 biolink:NamedThing|biolink:Disease Periventricular nodular heterotopia omim.nt owl:Class UMLS:C1412504 biolink:NamedThing omim.nt owl:Class https://www.ncbi.nlm.nih.gov/gene/375 biolink:NamedThing omim.nt http://omim.org/entry/103188 biolink:NamedThing|biolink:Gene ARF5 Adp-Ribosylation Factor 5 omim.nt ADP-RIBOSYLATION FACTOR 5; ARF5 owl:Class MONARCH:.well-known/genid/b97a2f9cdb85071140b3 biolink:NamedThing GRCh38chr7-127588410-127591699-Region omim.nt MONARCH:.well-known/genid/b1b88da2d5607ffd535a faldo:Region PMID:1993656 biolink:NamedThing omim.nt IAO:0000013 PMID:9169151 biolink:NamedThing omim.nt IAO:0000013 OBO:CHR_9606chr7q31.3 biolink:NamedThing omim.nt owl:Class UMLS:C1412510 biolink:NamedThing omim.nt owl:Class https://www.ncbi.nlm.nih.gov/gene/381 biolink:NamedThing omim.nt http://omim.org/entry/103190 biolink:NamedThing|biolink:Gene ARF3 Adp-Ribosylation Factor 3 omim.nt ADP-RIBOSYLATION FACTOR 3; ARF3 owl:Class MONARCH:.well-known/genid/b49a035552f467aecfd3 biolink:NamedThing GRCh38chr12-48930251-48957525-Region omim.nt MONARCH:.well-known/genid/bb91df5040c6d2bf039b faldo:Region PMID:1744102 biolink:NamedThing omim.nt IAO:0000013 OBO:CHR_9606chr12q13 biolink:NamedThing omim.nt owl:Class UMLS:C1412506 biolink:NamedThing omim.nt owl:Class https://www.ncbi.nlm.nih.gov/gene/377 biolink:NamedThing omim.nt http://omim.org/entry/103195 biolink:NamedThing|biolink:Gene PLIN2 Perilipin 2 omim.nt PERILIPIN 2; PLIN2|Adipophilin|Adipose Differentiation-Related Protein owl:Class MONARCH:.well-known/genid/b798b4f0a77a00bc7d27 biolink:NamedThing GRCh38chr9-19108390-19127517-Region omim.nt MONARCH:.well-known/genid/bf9b37935207d4449054 faldo:Region MONARCH:.well-known/genid/OMIM103195ref2 biolink:NamedThing Personal Communication. omim.nt IAO:0000310 PMID:19054096 biolink:NamedThing omim.nt IAO:0000013 PMID:19169702 biolink:NamedThing omim.nt IAO:0000013 PMID:19952355 biolink:NamedThing omim.nt IAO:0000013 PMID:8325636 biolink:NamedThing omim.nt IAO:0000013 PMID:9003395 biolink:NamedThing omim.nt IAO:0000013 PMID:9799447 biolink:NamedThing omim.nt IAO:0000013 OBO:CHR_9606chr9p22.1 biolink:NamedThing omim.nt owl:Class UMLS:C1412234 biolink:NamedThing omim.nt owl:Class https://www.ncbi.nlm.nih.gov/gene/123 biolink:NamedThing omim.nt http://omim.org/entry/103200 biolink:NamedThing|biolink:Disease Adiposis Dolorosa Adiposis Dolorosa omim.nt ADIPOSIS DOLOROSA|Dercum Disease owl:Class MONARCH:.well-known/genid/OMIM103200ref3 biolink:NamedThing Three cases of a hitherto unclassified affection resembling in its grosser aspects obesity, but associated with special nervous symptoms: adiposis dolorosa. omim.nt IAO:0000310 MONARCH:.well-known/genid/OMIM103200ref7 biolink:NamedThing Adipositas dolorosa (Dercum's disease). omim.nt IAO:0000310 PMID:11148491 biolink:NamedThing omim.nt IAO:0000013 PMID:12075486 biolink:NamedThing omim.nt IAO:0000013 PMID:17948485 biolink:NamedThing omim.nt IAO:0000013 PMID:22546240 biolink:NamedThing omim.nt IAO:0000013 PMID:4721343 biolink:NamedThing omim.nt IAO:0000013 UMLS:C0001529 biolink:NamedThing omim.nt owl:Class ORPHA:36397 biolink:NamedThing|biolink:Disease omim.nt owl:Class http://omim.org/entry/103220.0001 biolink:NamedThing SLC25A4, ALA114PRO In 5 Italian families with progressive external ophthalmoplegia with mitochondrial DNA deletions (PEOA2; {609283}), {16:Kaukonen et al. (2000)} identified a G-to-C transversion in exon 2 of the ANT1 gene, resulting in an ala114-to-pro (A114P) substitution. The nucleotide change was present in all affected family members, but not in 860 Finnish or 150 Italian control individuals. Alanine-114 and its flanking sequences are strictly conserved among species. A common disease haplotype with identical markers was shared by all patients in 3 Italian families, suggesting that there is 1 founder mutation and common ancestry, although this could not be genealogically confirmed. Three families had been reported by {15,17:Kaukonen et al. (1996, 1999)}. omim.nt GENO:0000002 http://omim.org/entry/103220 biolink:NamedThing|biolink:Gene SLC25A4 Solute Carrier Family 25 (Mitochondrial Carrier, Adenine Nucleotide Translocator), Member 4 omim.nt SOLUTE CARRIER FAMILY 25 (MITOCHONDRIAL CARRIER, ADENINE NUCLEOTIDE TRANSLOCATOR), MEMBER 4; SLC25A4|Adenine Nucleotide Translocator 1|Adp/Atp Carrier 1|Adp/Atp Translocase 1|Adp/Atp Translocator of Skeletal Muscle owl:Class ClinVar:RCV000019907 biolink:NamedThing omim.nt dbSNP:rs104893873 biolink:NamedThing omim.nt owl:NamedIndividual http://omim.org/entry/103220#0001 biolink:NamedThing omim.nt http://omim.org/entry/103220.0002 biolink:NamedThing SLC25A4, VAL289MET In a sporadic patient with PEOA2 ({609283}) and multiple mitochondrial DNA deletions, {16:Kaukonen et al. (2000)} identified a missense mutation, a G-to-A transition in exon 4 of the ANT1 gene resulting in a val289-to-met (V289M) substitution. omim.nt GENO:0000002 ClinVar:RCV000019908 biolink:NamedThing omim.nt dbSNP:rs104893874 biolink:NamedThing omim.nt owl:NamedIndividual http://omim.org/entry/103220#0002 biolink:NamedThing omim.nt http://omim.org/entry/103220.0003 biolink:NamedThing SLC25A4, LEU98PRO In 3 members of a Greek family with PEOA2 ({609283}), {25:Napoli et al. (2001)} identified a heterozygous 293T-C transition in the ANT1 gene, resulting in a leu98-to-pro (L98P) substitution. The mutation was absent in several unaffected family members and in Italian and Greek controls. omim.nt GENO:0000002 ClinVar:RCV000019909 biolink:NamedThing omim.nt dbSNP:rs104893876 biolink:NamedThing omim.nt owl:NamedIndividual http://omim.org/entry/103220#0003 biolink:NamedThing omim.nt http://omim.org/entry/103220.0004 biolink:NamedThing SLC25A4, ASP104GLY In 4 affected members of a Japanese family with PEOA2 ({609283}), {19:Komaki et al. (2002)} identified a 311A-G heterozygous mutation in exon 2 of the ANT1 gene, resulting in an asp104-to-gly (D104G) substitution. The mutation was not detected in 2 unaffected family members or 120 normal individuals. The authors noted that the mutation converted a highly conserved aspartic acid into a nonpolar glycine in a side chain. omim.nt GENO:0000002 ClinVar:RCV000019910 biolink:NamedThing omim.nt dbSNP:rs28999114 biolink:NamedThing omim.nt owl:NamedIndividual http://omim.org/entry/103220#0004 biolink:NamedThing omim.nt http://omim.org/entry/103220.0005 biolink:NamedThing SLC25A4, ALA123ASP In a 25-year-old Slovenian man with autosomal recessive mitochondrial DNA depletion syndrome-12B (MTDPS12B; {615418}), {27:Palmieri et al. (2005)} identified homozygosity for a 368C-A transversion in the ANT1 gene, resulting in an ala123-to-asp (A123D) substitution in a conserved residue. The unaffected mother was heterozygous for the mutation, and the father was unavailable for testing. The mutation was absent in 500 control individuals. The patient presented with hypertrophic cardiomyopathy, mild myopathy with exercise intolerance, and lactic acidosis but no ophthalmoplegia. Muscle biopsy revealed numerous ragged-red fibers, and Southern blot analysis disclosed multiple deletions of muscle mitochondrial DNA. Muscle tissue was unavailable from the patient's mother, so the presence of subclinical amounts of multiple deletions could not be ruled out. The clinical and biochemical features were different from those found in dominant ANT1 mutations, resembling those described in ANT1-knockout mice. No ATP uptake was measured in proteoliposomes reconstituted with protein extracts from the patient's muscle. The equivalent mutation in AAC2, the yeast ortholog of human ANT1, resulted in a complete loss of transport activity and in the inability to rescue the severe oxidative phosphorylation phenotype displayed by WB-12, an AAC1/AAC2-defective yeast strain. omim.nt GENO:0000002 ClinVar:RCV000019911 biolink:NamedThing omim.nt ClinVar:RCV000414338 biolink:NamedThing omim.nt ClinVar:RCV000626767 biolink:NamedThing omim.nt ClinVar:RCV000626768 biolink:NamedThing omim.nt ClinVar:RCV000626769 biolink:NamedThing omim.nt ClinVar:RCV001198599 biolink:NamedThing omim.nt dbSNP:rs121912683 biolink:NamedThing omim.nt owl:NamedIndividual http://omim.org/entry/103220#0005 biolink:NamedThing omim.nt http://omim.org/entry/103220.0006 biolink:NamedThing SLC25A4, IVS1DS, G-A, +1 In a patient, born of consanguineous Portuguese parents, with autosomal recessive MTDPS12B ({615418}), {5:Echaniz-Laguna et al. (2012)} identified a homozygous G-to-A transition in intron 1 of the SLC25A4 gene (c.111+1G-A). The mutant transcript was undetectable in patient cells, consistent with complete loss of protein expression and function. The clinically unaffected mother, who was heterozygous for the mutation, had low levels (less than 2%) of mtDNA rearrangements in skeletal muscle. The deceased father was reportedly unaffected. The patient had hypertrophic cardiomyopathy, exercise intolerance with muscle weakness and atrophy, congenital cataracts, and lactic acidosis. Muscle biopsy showed ragged-red fibers and multiple mtDNA deletions. omim.nt GENO:0000002 ClinVar:RCV000056253 biolink:NamedThing omim.nt dbSNP:rs398122942 biolink:NamedThing omim.nt owl:NamedIndividual http://omim.org/entry/103220#0006 biolink:NamedThing omim.nt http://omim.org/entry/103220.0007 biolink:NamedThing SLC25A4, 22-BP DEL, NT116 In a 28-year-old man with autosomal recessive mitochondrial DNA depletion syndrome-12B (MTDPS12B; {615418}), previously reported by {1,2:Bakker et al. (1993, 1993)}, {20:Korver-Keularts et al. (2015)} identified compound heterozygous mutations in the SLC25A4 gene: a 22-bp deletion (c.116_137del) in exon 2, resulting in a frameshift and premature termination (Gln39LeufsTer14), and a 707G-C transversion in exon 3, resulting in an arg236-to-pro (R236P; {103220.0008}) substitution at a highly conserved residue in the predicted transmembrane region. Neither mutation was found in the dbSNP, 1000 Genomes Project, or ExAC databases, or in 114 ethnically matched controls. The patient's unaffected father and brother were heterozygous for the R236P mutation; DNA from the deceased mother was not available for study. Cellular studies indicated that the frameshift mutation resulted in nonsense-mediated mRNA decay. Functional studies of the missense mutation were not performed. omim.nt GENO:0000002 ClinVar:RCV000258875 biolink:NamedThing omim.nt dbSNP:rs886041080 biolink:NamedThing omim.nt owl:NamedIndividual http://omim.org/entry/103220#0007 biolink:NamedThing omim.nt http://omim.org/entry/103220.0008 biolink:NamedThing SLC25A4, ARG236PRO For discussion of the c.707G-C transversion in exon 3 of the SLC25A4 gene, resulting in an arg236-to-pro (R236P) substitution that was found in compound heterozygous state in a patient with autosomal recessive mitochondrial DNA depletion syndrome-12B (MTDPS12B; {615418}) by {20:Korver-Keularts et al. (2015)}, see {103220.0007}. omim.nt GENO:0000002 ClinVar:RCV000258878 biolink:NamedThing omim.nt dbSNP:rs770816416 biolink:NamedThing omim.nt owl:NamedIndividual http://omim.org/entry/103220#0008 biolink:NamedThing omim.nt http://omim.org/entry/103220.0009 biolink:NamedThing SLC25A4, ARG80HIS In 4 unrelated children with autosomal dominant mitochondrial DNA depletion syndrome-12A (MTDPS12A; {617184}), {29:Thompson et al. (2016)} identified a recurrent de novo heterozygous c.239G-A transition ({VAR c.239G-A, NM_001151.3}) in the SLC25A4 gene, resulting in an arg80-to-his (R80H) substitution at a highly conserved residue within the phosphate substrate binding site. The mutations, which were found by whole-exome sequencing and confirmed by Sanger sequencing, were filtered against various public databases, including dbSNP, 1000 Genomes Project, and ExAC. Western blot analysis of patient muscle samples showed decreased levels of ANT1 and decreased levels of components of several mitochondrial respiratory complexes compared to controls. In vitro functional expression studies showed that the R80H mutant had only about 24% residual transporter activity. Complementation and transport studies in yeast confirmed that the mutant protein was functionally defective: it was unable to complement an oxidative phosphorylation defect and caused decreased transport activity, but it did not act in a dominant-negative manner. omim.nt GENO:0000002 ClinVar:RCV000258873 biolink:NamedThing omim.nt ClinVar:RCV000479591 biolink:NamedThing omim.nt ClinVar:RCV000491010 biolink:NamedThing omim.nt ClinVar:RCV000624243 biolink:NamedThing omim.nt dbSNP:rs886041081 biolink:NamedThing omim.nt owl:NamedIndividual http://omim.org/entry/103220#0009 biolink:NamedThing omim.nt http://omim.org/entry/103220.0010 biolink:NamedThing SLC25A4, ARG235GLY In 3 patients from 2 unrelated families, including a pair of monozygotic twins, with autosomal dominant mitochondrial DNA depletion syndrome-12A (MTDPS12A; {617184}), {29:Thompson et al. (2016)} identified a recurrent de novo heterozygous c.703C-G transversion ({VAR c.703C-G, NM_001151.3}) in the SLC25A4 gene, resulting in an arg235-to-gly (R235G) substitution at a highly conserved residue affecting a salt bridge required for formation of the matrix network. Western blot analysis of patient muscle samples showed decreased levels of ANT1 and decreased levels of components of several mitochondrial respiratory complexes compared to controls. In vitro functional expression studies showed that the R235G mutant had only about 3% residual transporter activity. Complementation and transport studies in yeast confirmed that the mutant protein was functionally defective: it was unable to complement an oxidative phosphorylation defect and caused decreased transport activity, but it did not act in a dominant-negative manner. omim.nt GENO:0000002 ClinVar:RCV000258874 biolink:NamedThing omim.nt ClinVar:RCV000491457 biolink:NamedThing omim.nt dbSNP:rs886041082 biolink:NamedThing omim.nt owl:NamedIndividual http://omim.org/entry/103220#0010 biolink:NamedThing omim.nt MONARCH:.well-known/genid/badb24821023f7f86c9f biolink:NamedThing GRCh38chr4-185143265-185150381-Region omim.nt MONARCH:.well-known/genid/bf6d587be13ca2f05cd7 faldo:Region MONARCH:.well-known/genid/OMIM103220ref11 biolink:NamedThing Mitochondrial permeability: dual role for the ADP/ATP translocator? Comment on 'The ADP/ATP translocator is not essential for the mitochondrial permeability transition pore'. omim.nt IAO:0000310 MONARCH:.well-known/genid/OMIM103220ref22 biolink:NamedThing Cloning and tissue-differential expression of human heart-skeletal muscle adenine nucleotide translocator gene. (Abstract) omim.nt IAO:0000310 MONARCH:.well-known/genid/OMIM103220ref24 biolink:NamedThing Mapping of the human muscle adenine nucleotide translocator gene (ANT1) to chromosome 4. (Abstract) omim.nt IAO:0000310 PMID:10364542 biolink:NamedThing omim.nt IAO:0000013 PMID:10926541 biolink:NamedThing omim.nt IAO:0000013 PMID:11756613 biolink:NamedThing omim.nt IAO:0000013 PMID:12112115 biolink:NamedThing omim.nt IAO:0000013 PMID:12140186 biolink:NamedThing omim.nt IAO:0000013 PMID:12176321 biolink:NamedThing omim.nt IAO:0000013 PMID:14603310 biolink:NamedThing omim.nt IAO:0000013 PMID:14749836 biolink:NamedThing omim.nt IAO:0000013 PMID:15016764 biolink:NamedThing omim.nt IAO:0000013 PMID:1582253 biolink:NamedThing omim.nt IAO:0000013 PMID:16155110 biolink:NamedThing omim.nt IAO:0000013 PMID:20504995 biolink:NamedThing omim.nt IAO:0000013 PMID:22187496 biolink:NamedThing omim.nt IAO:0000013 PMID:2547778 biolink:NamedThing omim.nt IAO:0000013 PMID:25732997 biolink:NamedThing omim.nt IAO:0000013 PMID:27693233 biolink:NamedThing omim.nt IAO:0000013 PMID:2823266 biolink:NamedThing omim.nt IAO:0000013 PMID:2829183 biolink:NamedThing omim.nt IAO:0000013 PMID:3031073 biolink:NamedThing omim.nt IAO:0000013 PMID:31618756 biolink:NamedThing omim.nt IAO:0000013 PMID:7609449 biolink:NamedThing omim.nt IAO:0000013 PMID:8100217 biolink:NamedThing omim.nt IAO:0000013 PMID:8103757 biolink:NamedThing omim.nt IAO:0000013 PMID:8479824 biolink:NamedThing omim.nt IAO:0000013 PMID:8644740 biolink:NamedThing omim.nt IAO:0000013 PMID:8703133 biolink:NamedThing omim.nt IAO:0000013 PMID:9207786 biolink:NamedThing omim.nt IAO:0000013 OBO:CHR_9606chr4q35 biolink:NamedThing omim.nt owl:Class http://omim.org/entry/609283 biolink:NamedThing|biolink:Disease Progressive External Ophthalmoplegia With Mitochondrial Dna Deletions, Autosomal Dominant 2 Progressive External Ophthalmoplegia With Mitochondrial Dna Deletions, Autosomal Dominant 2 omim.nt PROGRESSIVE EXTERNAL OPHTHALMOPLEGIA WITH MITOCHONDRIAL DNA DELETIONS, AUTOSOMAL DOMINANT 2; PEOA2|Progressive External Ophthalmoplegia, Autosomal Dominant 2 owl:Class http://omim.org/entry/615418 biolink:NamedThing|biolink:Disease Mitochondrial Dna Depletion Syndrome 12B (Cardiomyopathic Type), Autosomal Recessive Mitochondrial Dna Depletion Syndrome 12B (Cardiomyopathic Type), Autosomal Recessive omim.nt MITOCHONDRIAL DNA DEPLETION SYNDROME 12B (CARDIOMYOPATHIC TYPE), AUTOSOMAL RECESSIVE; MTDPS12B owl:Class http://omim.org/entry/617184 biolink:NamedThing|biolink:Disease Mitochondrial Dna Depletion Syndrome 12A (Cardiomyopathic Type), Autosomal Dominant Mitochondrial Dna Depletion Syndrome 12A (Cardiomyopathic Type), Autosomal Dominant omim.nt MITOCHONDRIAL DNA DEPLETION SYNDROME 12A (CARDIOMYOPATHIC TYPE), AUTOSOMAL DOMINANT; MTDPS12A owl:Class http://www.omim.org/phenotypicSeries/PS157640 biolink:NamedThing|biolink:Disease Progressive external ophthalmoplegia with mtDNA deletions omim.nt owl:Class http://www.omim.org/phenotypicSeries/PS603041 biolink:NamedThing|biolink:Disease Mitochondrial DNA depletion syndrome omim.nt owl:Class UMLS:C1335833 biolink:NamedThing omim.nt owl:Class https://www.ncbi.nlm.nih.gov/gene/291 biolink:NamedThing omim.nt http://omim.org/entry/103230 biolink:NamedThing|biolink:Disease Adrenocortical Hypofunction, Chronic Primary Congenital omim.nt ADRENOCORTICAL HYPOFUNCTION, CHRONIC PRIMARY CONGENITAL|Addison Disease, Congenital owl:Class MONARCH:.well-known/genid/OMIM103230ref1 biolink:NamedThing Addison's disease of autosomal dominant inheritance: a report of 11 cases in one family. omim.nt IAO:0000310 UMLS:C0271740 biolink:NamedThing omim.nt owl:Class ORPHA:85138 biolink:NamedThing|biolink:Disease omim.nt owl:Class http://omim.org/entry/103260 biolink:NamedThing|biolink:Gene FDX1 Ferredoxin 1|pseudogene on 20q11-q12 omim.nt FERREDOXIN 1; FDX1|Adrenodoxin owl:Class MONARCH:.well-known/genid/bf110a90fe9906714bd7 biolink:NamedThing GRCh38chr11-110429947-110464883-Region omim.nt MONARCH:.well-known/genid/bfe7713d25fed1f958d3 faldo:Region MONARCH:.well-known/genid/OMIM103260ref7 biolink:NamedThing Two highly homologous genes for adrenodoxin lie on human chromosomes 11 and 20. (Abstract) omim.nt IAO:0000310 PMID:1863359 biolink:NamedThing omim.nt IAO:0000013 PMID:2340092 biolink:NamedThing omim.nt IAO:0000013 PMID:2837084 biolink:NamedThing omim.nt IAO:0000013 PMID:2969697 biolink:NamedThing omim.nt IAO:0000013 PMID:2994043 biolink:NamedThing omim.nt IAO:0000013 PMID:3030718 biolink:NamedThing omim.nt IAO:0000013 PMID:3229285 biolink:NamedThing omim.nt IAO:0000013 PMID:3343244 biolink:NamedThing omim.nt IAO:0000013 PMID:3778538 biolink:NamedThing omim.nt IAO:0000013 PMID:6309754 biolink:NamedThing omim.nt IAO:0000013 OBO:CHR_9606chr11q22 biolink:NamedThing omim.nt owl:Class UMLS:C1414571 biolink:NamedThing omim.nt owl:Class https://www.ncbi.nlm.nih.gov/gene/2230 biolink:NamedThing omim.nt http://omim.org/entry/103270.0001 biolink:NamedThing FDXR, ARG306CYS In 4 members of a consanguineous Tunisian family with auditory neuropathy and optic atrophy (ANOA; {617717}), {2:Paul et al. (2017)} identified a homozygous c.916C-T transition ({VAR c.916C-T, NM_024417.4}) in the FDXR gene, resulting in an arg306-to-cys (R306C) substitution. The mutation, which was found by exome sequencing and confirmed by Sanger sequencing, segregated with the disorder in the family. The variant was found at a low frequency (8.85 x 10(-6)) in the ExAC database. An unrelated patient of Algerian descent was compound heterozygous for the R306C variant and a c.1255C-T transition, resulting in a gln419-to-ter (Q419X; {103270.0002}) substitution. DNA was not available from family members of the Algerian patient; the Q419X variant was not found in the ExAC database. Fibroblasts derived from patients in both families showed decreased levels of FDXR compared to controls. omim.nt GENO:0000002 http://omim.org/entry/103270 biolink:NamedThing|biolink:Gene FDXR Ferredoxin Reductase omim.nt FERREDOXIN REDUCTASE; FDXR|Adrenodoxin Reductase|Ferredoxin:Nadp(+) Reductase owl:Class ClinVar:RCV000509578 biolink:NamedThing omim.nt dbSNP:rs752143061 biolink:NamedThing omim.nt owl:NamedIndividual http://omim.org/entry/103270#0001 biolink:NamedThing omim.nt http://omim.org/entry/103270.0002 biolink:NamedThing FDXR, GLN419TER For discussion of the c.1255C-T transition ({VAR c.1255C-T, NM_024417.4}) in the FDXR gene, resulting in a gln419-to-ter (Q419X) substitution, that was found in compound heterozygous state in a patient with auditory neuropathy and optic atrophy (ANOA; {617717}) by {2:Paul et al. (2017)}, see {103270.0001}. omim.nt GENO:0000002 ClinVar:RCV000509571 biolink:NamedThing omim.nt dbSNP:rs1313895172 biolink:NamedThing omim.nt owl:NamedIndividual http://omim.org/entry/103270#0002 biolink:NamedThing omim.nt http://omim.org/entry/103270.0003 biolink:NamedThing FDXR, LEU215VAL In 2 sibs of Russian descent with auditory neuropathy and optic atrophy (ANOA; {617717}), {2:Paul et al. (2017)} identified compound heterozygous missense mutations in the FDXR gene: a c.643C-G transversion ({VAR c.643C-G, NM_024417.4}), resulting in a leu215-to-val (L215V) substitution, and a c.1429G-A transition, resulting in a glu477-to-lys (E477K; {103270.0004}). The mutations were found by direct sequencing of the FDXR gene; DNA from family members was not available for segregation analysis. Neither mutation was found in the ExAC database. omim.nt GENO:0000002 ClinVar:RCV000509574 biolink:NamedThing omim.nt dbSNP:rs1555620021 biolink:NamedThing omim.nt owl:NamedIndividual http://omim.org/entry/103270#0003 biolink:NamedThing omim.nt http://omim.org/entry/103270.0004 biolink:NamedThing FDXR, GLU477LYS For discussion of the c.1429G-A transition ({VAR c.1429G-A, NM_024417.4}) in the FDXR gene resulting in a glu477-to-lys (E477K) substitution that was found in compound heterozygous state in 2 sibs with auditory neuropathy and optic atrophy (ANOA; {617717}) by {2:Paul et al. (2017)}, see {103270.0003}. omim.nt GENO:0000002 ClinVar:RCV000509579 biolink:NamedThing omim.nt dbSNP:rs997026784 biolink:NamedThing omim.nt owl:NamedIndividual http://omim.org/entry/103270#0004 biolink:NamedThing omim.nt MONARCH:.well-known/genid/b4bff51c020a520a4317 biolink:NamedThing GRCh38chr17-74862496-74872993-Region omim.nt MONARCH:.well-known/genid/bef9a949c910989fda49 faldo:Region PMID:2236061 biolink:NamedThing omim.nt IAO:0000013 PMID:2845396 biolink:NamedThing omim.nt IAO:0000013 PMID:28965846 biolink:NamedThing omim.nt IAO:0000013 OBO:CHR_9606chr17q24 biolink:NamedThing omim.nt owl:Class http://omim.org/entry/617717 biolink:NamedThing|biolink:Disease Auditory Neuropathy and Optic Atrophy Auditory Neuropathy and Optic Atrophy omim.nt AUDITORY NEUROPATHY AND OPTIC ATROPHY; ANOA owl:Class UMLS:C1414575 biolink:NamedThing omim.nt owl:Class https://www.ncbi.nlm.nih.gov/gene/2232 biolink:NamedThing omim.nt http://omim.org/entry/103275 biolink:NamedThing|biolink:Gene ADM Adrenomedullin omim.nt ADRENOMEDULLIN; ADM owl:Class MONARCH:.well-known/genid/b676891bd506b7c5a336 biolink:NamedThing GRCh38chr11-10305072-10307396-Region omim.nt MONARCH:.well-known/genid/b1fd7181a1f3c1371e8c faldo:Region MONARCH:.well-known/genid/OMIM103275ref11 biolink:NamedThing Adrenomedullin. omim.nt IAO:0000310 MONARCH:.well-known/genid/OMIM103275ref13 biolink:NamedThing Report of the committee on the genetic constitution of chromosome 11.In: Cuticchia, A. J.; Pearson, P. L.; Klinger, H. P. (eds.) : Chromosome coordinating meeting, 1992. omim.nt IAO:0000310 PMID:11149956 biolink:NamedThing omim.nt IAO:0000013 PMID:11274089 biolink:NamedThing omim.nt IAO:0000013 PMID:11600589 biolink:NamedThing omim.nt IAO:0000013 PMID:16981008 biolink:NamedThing omim.nt IAO:0000013 PMID:17043245 biolink:NamedThing omim.nt IAO:0000013 PMID:17360661 biolink:NamedThing omim.nt IAO:0000013 PMID:18723674 biolink:NamedThing omim.nt IAO:0000013 PMID:7688224 biolink:NamedThing omim.nt IAO:0000013 PMID:8074714 biolink:NamedThing omim.nt IAO:0000013 PMID:8938454 biolink:NamedThing omim.nt IAO:0000013 PMID:9620797 biolink:NamedThing omim.nt IAO:0000013 OBO:CHR_9606chr11p15.4 biolink:NamedThing omim.nt owl:Class UMLS:C1412244 biolink:NamedThing omim.nt owl:Class https://www.ncbi.nlm.nih.gov/gene/133 biolink:NamedThing omim.nt http://omim.org/entry/103280 biolink:NamedThing|biolink:Gene H19 H19, Imprinted Maternally Expressed Noncoding Transcript|same 200kb fragment as IGF2 omim.nt H19, IMPRINTED MATERNALLY EXPRESSED NONCODING TRANSCRIPT; H19|Adult Skeletal Muscle Gene|Asm1|Lincrna H19|Long Intergenic Noncoding Rna H19 owl:Class MONARCH:.well-known/genid/b1a8832a335081c12067 biolink:NamedThing GRCh38chr11-1995175-2001465-Region omim.nt MONARCH:.well-known/genid/b7c6c2a12cba696cc7f3 faldo:Region MONARCH:.well-known/genid/OMIM103280ref25 biolink:NamedThing Assignment of ASM (adult skeletal muscle) to chromosome 11 (somatic hybrid cell analysis), region 11p15 (in situ hybridization). (Abstract) omim.nt IAO:0000310 PMID:10751088 biolink:NamedThing omim.nt IAO:0000013 PMID:10839546 biolink:NamedThing omim.nt IAO:0000013 PMID:10839547 biolink:NamedThing omim.nt IAO:0000013 PMID:11092765 biolink:NamedThing omim.nt IAO:0000013 PMID:11813134 biolink:NamedThing omim.nt IAO:0000013 PMID:11889182 biolink:NamedThing omim.nt IAO:0000013 PMID:1303252 biolink:NamedThing omim.nt IAO:0000013 PMID:1358794 biolink:NamedThing omim.nt IAO:0000013 PMID:1363808 biolink:NamedThing omim.nt IAO:0000013 PMID:1380925 biolink:NamedThing omim.nt IAO:0000013 PMID:15103378 biolink:NamedThing omim.nt IAO:0000013 PMID:16532391 biolink:NamedThing omim.nt IAO:0000013 PMID:1688465 biolink:NamedThing omim.nt IAO:0000013 PMID:1709450 biolink:NamedThing omim.nt IAO:0000013 PMID:17237358 biolink:NamedThing omim.nt IAO:0000013 PMID:18587395 biolink:NamedThing omim.nt IAO:0000013 PMID:19066168 biolink:NamedThing omim.nt IAO:0000013 PMID:1953776 biolink:NamedThing omim.nt IAO:0000013 PMID:2044956 biolink:NamedThing omim.nt IAO:0000013 PMID:2052093 biolink:NamedThing omim.nt IAO:0000013 PMID:20529846 biolink:NamedThing omim.nt IAO:0000013 PMID:22832245 biolink:NamedThing omim.nt IAO:0000013 PMID:6206499 biolink:NamedThing omim.nt IAO:0000013 PMID:7536897 biolink:NamedThing omim.nt IAO:0000013 PMID:7670470 biolink:NamedThing omim.nt IAO:0000013 PMID:7692725 biolink:NamedThing omim.nt IAO:0000013 PMID:8385745 biolink:NamedThing omim.nt IAO:0000013 PMID:8636440 biolink:NamedThing omim.nt IAO:0000013 PMID:8943029 biolink:NamedThing omim.nt IAO:0000013 PMID:9208812 biolink:NamedThing omim.nt IAO:0000013 PMID:9490417 biolink:NamedThing omim.nt IAO:0000013 PMID:9811943 biolink:NamedThing omim.nt IAO:0000013 PMID:9851976 biolink:NamedThing omim.nt IAO:0000013 OBO:CHR_9606chr11p15.5 biolink:NamedThing omim.nt owl:Class UMLS:C1333887 biolink:NamedThing omim.nt owl:Class https://www.ncbi.nlm.nih.gov/gene/283120 biolink:NamedThing omim.nt http://omim.org/entry/103285 biolink:NamedThing|biolink:Disease Adult Syndrome Adult Syndrome omim.nt ADULT SYNDROME|Acro-Dermato-Ungual-Lacrimal-Tooth Syndrome owl:Class PMID:10607963 biolink:NamedThing omim.nt IAO:0000013 PMID:11462173 biolink:NamedThing omim.nt IAO:0000013 PMID:11528512 biolink:NamedThing omim.nt IAO:0000013 PMID:11929852 biolink:NamedThing omim.nt IAO:0000013 PMID:16114047 biolink:NamedThing omim.nt IAO:0000013 PMID:16724007 biolink:NamedThing omim.nt IAO:0000013 PMID:17041931 biolink:NamedThing omim.nt IAO:0000013 PMID:18603493 biolink:NamedThing omim.nt IAO:0000013 PMID:19530185 biolink:NamedThing omim.nt IAO:0000013 PMID:20814947 biolink:NamedThing omim.nt IAO:0000013 PMID:8456838 biolink:NamedThing omim.nt IAO:0000013 UMLS:C1863204 biolink:NamedThing omim.nt owl:Class ORPHA:978 biolink:NamedThing|biolink:Disease omim.nt owl:Class http://omim.org/entry/103300 biolink:NamedThing|biolink:Disease Hypoglossia-Hypodactylia Hypoglossia-Hypodactylia omim.nt HYPOGLOSSIA-HYPODACTYLIA|Aglossia-Adactylia|Hanhart Syndrome|Oromandibular Limb Hypoplasia|Peromelia With Micrognathism owl:Class MONARCH:.well-known/genid/OMIM103300ref12 biolink:NamedThing Personal Communication. omim.nt IAO:0000310 MONARCH:.well-known/genid/OMIM103300ref14 biolink:NamedThing Discordance in monozygotic twins for aglossia-adactylia, and possible clues to the pathogenesis of the syndrome. omim.nt IAO:0000310 MONARCH:.well-known/genid/OMIM103300ref15 biolink:NamedThing Personal Communication. omim.nt IAO:0000310 MONARCH:.well-known/genid/OMIM103300ref2 biolink:NamedThing Hanhart syndrome in siblings. (Abstract) omim.nt IAO:0000310 MONARCH:.well-known/genid/OMIM103300ref4 biolink:NamedThing Hanhart's syndrome with special reference to temporal bone findings. omim.nt IAO:0000310 MONARCH:.well-known/genid/OMIM103300ref7 biolink:NamedThing Colobomatous microphthalmia in the hypoglossia-hypodactylia syndrome. (Abstract) omim.nt IAO:0000310 MONARCH:.well-known/genid/OMIM103300ref8 biolink:NamedThing Aglossia-adactylia. omim.nt IAO:0000310 MONARCH:.well-known/genid/OMIM103300ref9 biolink:NamedThing Ueber die Kombination von Peromelie mit Mikrognathie, ein neues Syndrom beim Menschen, entsprechend der Akroteriasis congenita von Wriedt und Mohr beim Rind. omim.nt IAO:0000310 PMID:10232758 biolink:NamedThing omim.nt IAO:0000013 PMID:1121025 biolink:NamedThing omim.nt IAO:0000013 PMID:11837603 biolink:NamedThing omim.nt IAO:0000013 PMID:12707967 biolink:NamedThing omim.nt IAO:0000013 PMID:21290964 biolink:NamedThing omim.nt IAO:0000013 PMID:5263276 biolink:NamedThing omim.nt IAO:0000013 PMID:6616945 biolink:NamedThing omim.nt IAO:0000013 PMID:880741 biolink:NamedThing omim.nt IAO:0000013 UMLS:C0595985 biolink:NamedThing omim.nt owl:Class UMLS:C1863203 biolink:NamedThing omim.nt owl:Class ORPHA:989 biolink:NamedThing|biolink:Disease omim.nt owl:Class http://omim.org/entry/103320.0001 biolink:NamedThing AGRN, GLY1709ARG In a sister and brother with congenital myasthenic syndrome-8 (CMS8; {615120}), {9:Huze et al. (2009)} identified a homozygous 5125G-C transversion in exon 29 of the AGRN gene, resulting in a gly1709-to-arg (G1709R) substitution in the C-terminal laminin G-like 2 (LG2) domain. Both patients had been unable to run since childhood and had mild muscle weakness as adults. Neither had diplopia, bulbar symptoms, or dyspnea. The mutation was not found in 200 control alleles. Skeletal muscle biopsy showed pre- and postsynaptic defects at the neuromuscular junction (NMJ), although mutant agrin staining was localized correctly. In vitro functional expression studies in myotubes showed that mutant agrin did not significantly impair AChR clustering, activation of MuSK ({601296}), or the interaction with alpha-dystroglycan (DAG; {128239}). Injection of the mutant protein into rat muscle did not affect AChR recruit or expression at the NMJ. However, the NMJ showed remodeling and denervation: the presynaptic department had disheveled neurofilaments, and the postsynaptic compartment had increased synaptic gutter fragments. {9:Huze et al. (2009)} concluded that the mutant agrin destabilized the preexisting NMJ, suggesting that wildtype agrin is involved in the maintenance of the NMJ. omim.nt GENO:0000002 http://omim.org/entry/103320 biolink:NamedThing|biolink:Gene AGRN Agrin omim.nt AGRIN; AGRN owl:Class ClinVar:RCV000019902 biolink:NamedThing omim.nt ClinVar:RCV000235029 biolink:NamedThing omim.nt dbSNP:rs199476396 biolink:NamedThing omim.nt owl:NamedIndividual http://omim.org/entry/103320#0001 biolink:NamedThing omim.nt http://omim.org/entry/103320.0002 biolink:NamedThing AGRN, VAL1727PHE In a 39-year-old man with congenital myasthenic syndrome-8 (CMS8; {615120}), {12:Maselli et al. (2012)} identified compound heterozygosity for 2 mutations in the AGRN gene: a val1727-to-phe (V1727F) substitution in exon 30, and a gln353-to-ter (Q353X; {103320.0003}) substitution in exon 6. The V1727F mutation occurred in a highly conserved residue in the second LG domain and was not detected in 100 controls or in the 1000 Genomes Project database. The Q353X mutation predicts a truncated and inactive protein. In vitro functional expression studies showed that the V1727F substitution decreased agrin's ability to cluster AChRs by more than 100-fold compared to wildtype. The mutant V1727F protein was associated with decreased levels of MuSK ({601296}) phosphorylation compared to wildtype. Mutant V1727F had increased binding to alpha-dystroglycan (DAG; {128239}) compared to wildtype, which is a property of the nonneural (Z-) agrin isoform. {14:Rudell et al. (2019)} studied the pathogenic effects of the V1727F mutation on agrin function. Expression of agrin with the V1727F mutation in COS cells showed that secretion of neural y+z+ agrin was reduced compared to wildtype, whereas secretion of nonneural y-z- agrin was normal. Protein pull-down experiments showed that the V1727F mutation led to impaired binding of y+z+ agrin to heparin. The mutation also led to impaired binding of y+z+ agrin to low-density lipoprotein receptor-related protein-4 (LRP4; {604270}) coreceptor in HEK293 cells. Protein modeling of agrin with the V1727F mutation suggested that the mutation leads to disrupted packing of beta strands and affects the LG2 domain structure. Functionally, this was predicted to distort the y-splice insert on the LG2 hypervariable surface and impair binding to heparin and the LRP4 coreceptor. omim.nt GENO:0000002 ClinVar:RCV000114427 biolink:NamedThing omim.nt ClinVar:RCV000235038 biolink:NamedThing omim.nt dbSNP:rs587777298 biolink:NamedThing omim.nt owl:NamedIndividual http://omim.org/entry/103320#0002 biolink:NamedThing omim.nt http://omim.org/entry/103320.0003 biolink:NamedThing AGRN, GLN353TER For discussion of the gln353-to-ter (Q353X) mutation in the AGRN gene that was found in compound heterozygous state in a patient with congenital myasthenic syndrome-8 (CMS8; {615120}) by {12:Maselli et al. (2012)}, see {103320.0002}. omim.nt GENO:0000002 ClinVar:RCV000114428 biolink:NamedThing omim.nt ClinVar:RCV000235030 biolink:NamedThing omim.nt dbSNP:rs587777299 biolink:NamedThing omim.nt owl:NamedIndividual http://omim.org/entry/103320#0003 biolink:NamedThing omim.nt MONARCH:.well-known/genid/b1bfef0c2ed9996b0785 biolink:NamedThing GRCh38chr1-1020101-1056118-Region omim.nt MONARCH:.well-known/genid/b0b154c2e461be789530 faldo:Region PMID:10402191 biolink:NamedThing omim.nt IAO:0000013 PMID:11323662 biolink:NamedThing omim.nt IAO:0000013 PMID:11349136 biolink:NamedThing omim.nt IAO:0000013 PMID:12796783 biolink:NamedThing omim.nt IAO:0000013 PMID:1326608 biolink:NamedThing omim.nt IAO:0000013 PMID:14502292 biolink:NamedThing omim.nt IAO:0000013 PMID:1659950 biolink:NamedThing omim.nt IAO:0000013 PMID:16630822 biolink:NamedThing omim.nt IAO:0000013 PMID:1851019 biolink:NamedThing omim.nt IAO:0000013 PMID:19631309 biolink:NamedThing omim.nt IAO:0000013 PMID:1966767 biolink:NamedThing omim.nt IAO:0000013 PMID:22205389 biolink:NamedThing omim.nt IAO:0000013 PMID:28581497 biolink:NamedThing omim.nt IAO:0000013 PMID:30994901 biolink:NamedThing omim.nt IAO:0000013 PMID:8653786 biolink:NamedThing omim.nt IAO:0000013 PMID:8653787 biolink:NamedThing omim.nt IAO:0000013 PMID:8653788 biolink:NamedThing omim.nt IAO:0000013 OBO:CHR_9606chr1pter biolink:NamedThing omim.nt owl:Class http://omim.org/entry/615120 biolink:NamedThing|biolink:Disease Myasthenic Syndrome, Congenital, 8 Myasthenic Syndrome, Congenital, 8 omim.nt MYASTHENIC SYNDROME, CONGENITAL, 8; CMS8|Myasthenic Syndrome, Congenital, Due to Agrin Deficiency|Myasthenic Syndrome, Congenital, With Pre- and Postsynaptic Defects owl:Class UMLS:C1412285 biolink:NamedThing omim.nt owl:Class https://www.ncbi.nlm.nih.gov/gene/375790 biolink:NamedThing omim.nt http://omim.org/entry/103321 biolink:NamedThing omim.nt True owl:Class http://omim.org/entry/128239 biolink:NamedThing|biolink:Gene DAG1 Dystrophin-Associated Glycoprotein 1 omim.nt DYSTROPHIN-ASSOCIATED GLYCOPROTEIN 1; DAG1|Agrin Receptor|Dag|Dystroglycan, Alpha|Dystroglycan, Beta owl:Class http://omim.org/entry/103390 biolink:NamedThing|biolink:Gene AHNAK Ahnak Nucleoprotein omim.nt AHNAK NUCLEOPROTEIN; AHNAK|Desmoyokin owl:Class MONARCH:.well-known/genid/b7407749e18b1c858b34 biolink:NamedThing GRCh38chr11-62433543-62546805-Region omim.nt MONARCH:.well-known/genid/b3a0a7a614bc0000291e faldo:Region PMID:15007166 biolink:NamedThing omim.nt IAO:0000013 PMID:1608957 biolink:NamedThing omim.nt IAO:0000013 PMID:18191595 biolink:NamedThing omim.nt IAO:0000013 PMID:18334579 biolink:NamedThing omim.nt IAO:0000013 PMID:1922057 biolink:NamedThing omim.nt IAO:0000013 PMID:7789175 biolink:NamedThing omim.nt IAO:0000013 PMID:8408266 biolink:NamedThing omim.nt IAO:0000013 PMID:8938448 biolink:NamedThing omim.nt IAO:0000013 OBO:CHR_9606chr11q12 biolink:NamedThing omim.nt owl:Class UMLS:C1412295 biolink:NamedThing omim.nt owl:Class https://www.ncbi.nlm.nih.gov/gene/79026 biolink:NamedThing omim.nt http://omim.org/entry/103400 biolink:NamedThing Ainhum omim.nt AINHUM owl:Class MONARCH:.well-known/genid/OMIM103400ref1 biolink:NamedThing On ainhum. omim.nt IAO:0000310 MONARCH:.well-known/genid/OMIM103400ref2 biolink:NamedThing Ainhum: report of six cases in New York. omim.nt IAO:0000310 MONARCH:.well-known/genid/OMIM103400ref3 biolink:NamedThing Beobachtungen ueber Ainhum. omim.nt IAO:0000310 MONARCH:.well-known/genid/OMIM103400ref4 biolink:NamedThing Ainhum, a family disease. omim.nt IAO:0000310 UMLS:C0001860 biolink:NamedThing omim.nt owl:Class http://omim.org/entry/103420 biolink:NamedThing|biolink:Disease Alacrima, Congenital, Autosomal Dominant Alacrima, Congenital, Autosomal Dominant omim.nt ALACRIMA, CONGENITAL, AUTOSOMAL DOMINANT|Alacrimia Congenita, Autosomal Dominant owl:Class MONARCH:.well-known/genid/OMIM103420ref2 biolink:NamedThing Angeborenes Fehlen der Traenensekretion in einer Familie. omim.nt IAO:0000310 PMID:1815166 biolink:NamedThing omim.nt IAO:0000013 PMID:962658 biolink:NamedThing omim.nt IAO:0000013 UMLS:C4310836 biolink:NamedThing omim.nt owl:Class ORPHA:91416 biolink:NamedThing|biolink:Disease omim.nt owl:Class http://omim.org/entry/103470 biolink:NamedThing omim.nt True owl:Class http://omim.org/entry/193510 biolink:NamedThing|biolink:Disease Waardenburg Syndrome, Type 2A Waardenburg Syndrome, Type 2A omim.nt WAARDENBURG SYNDROME, TYPE 2A; WS2A|Waardenburg Syndrome, Type 2A|Waardenburg Syndrome Without Dystopia Canthorum|Ws2 owl:Class http://omim.org/entry/606952 biolink:NamedThing|biolink:Disease Albinism, Oculocutaneous, Type 1B Albinism, Oculocutaneous, Type 1B omim.nt ALBINISM, OCULOCUTANEOUS, TYPE IB; OCA1B|Albinism, Oculocutaneous, Type I, Temperature-Sensitive|Albinism, Yellow Mutant Type|Oca1-Ts|Oculocutaneous Albinism, Type 1B|Yellow Albinism owl:Class http://omim.org/entry/103500 biolink:NamedThing|biolink:Disease Tietz Albinism-Deafness Syndrome Tietz Albinism-Deafness Syndrome omim.nt TIETZ ALBINISM-DEAFNESS SYNDROME; TADS|Albinism-Deafness of Tietz|Hypopigmentation/Deafness of Tietz|Tietz Syndrome owl:Class PMID:10851256 biolink:NamedThing omim.nt IAO:0000013 PMID:13985019 biolink:NamedThing omim.nt IAO:0000013 PMID:18510545 biolink:NamedThing omim.nt IAO:0000013 PMID:6018993 biolink:NamedThing omim.nt IAO:0000013 PMID:8589691 biolink:NamedThing omim.nt IAO:0000013 PMID:9546825 biolink:NamedThing omim.nt IAO:0000013 UMLS:C0391816 biolink:NamedThing omim.nt owl:Class ORPHA:42665 biolink:NamedThing|biolink:Disease omim.nt owl:Class http://omim.org/entry/103580 biolink:NamedThing|biolink:Disease Pseudohypoparathyroidism, Type 1A Pseudohypoparathyroidism, Type 1A omim.nt PSEUDOHYPOPARATHYROIDISM, TYPE IA; PHP1A|Albright Hereditary Osteodystrophy With Multiple Hormone Resistance|Php 1A owl:Class MONARCH:.well-known/genid/OMIM103580ref1 biolink:NamedThing Pseudo-hypoparathyroidism--an example of 'Seabright-Bantam syndrome': report of three cases. omim.nt IAO:0000310 MONARCH:.well-known/genid/OMIM103580ref30 biolink:NamedThing Genetic mapping of the G(s)-alpha gene and detection of mutations in Albright hereditary osteodystrophy (AHO) by using polymerase chain reaction (PCR), denaturing gradient gel electrophoresis (DGGE) and direct sequencing. (Abstract) omim.nt IAO:0000310 MONARCH:.well-known/genid/OMIM103580ref32 biolink:NamedThing Albright's hereditary poly-osteochondrodystrophy (pseudo-pseudo-hypoparathyroidism with diabetes, hypertension, arteritis and polyarthrosis). omim.nt IAO:0000310 MONARCH:.well-known/genid/OMIM103580ref45 biolink:NamedThing Resistance to multiple hormones in patients with pseudohypoparathyroidism and deficient guanine nucleotide regulatory protein. (Abstract) omim.nt IAO:0000310 MONARCH:.well-known/genid/OMIM103580ref51 biolink:NamedThing Pseudo-pseudohypoparathyroidism developing pseudohypoparathyroidism. omim.nt IAO:0000310 MONARCH:.well-known/genid/OMIM103580ref62 biolink:NamedThing Purification of the regulatory component of adenylate cyclase. omim.nt IAO:0000310 MONARCH:.well-known/genid/OMIM103580ref65 biolink:NamedThing An initiator codon mutation in the gene encoding the alpha subunit of Gs in pseudohypoparathyroidism type IA (PHP IA). (Abstract) omim.nt IAO:0000310 PMID:10099144 biolink:NamedThing omim.nt IAO:0000013 PMID:10322399 biolink:NamedThing omim.nt IAO:0000013 PMID:10566660 biolink:NamedThing omim.nt IAO:0000013 PMID:1083395 biolink:NamedThing omim.nt IAO:0000013 PMID:11073544 biolink:NamedThing omim.nt IAO:0000013 PMID:11095461 biolink:NamedThing omim.nt IAO:0000013 PMID:11254676 biolink:NamedThing omim.nt IAO:0000013 PMID:12407707 biolink:NamedThing omim.nt IAO:0000013 PMID:12970262 biolink:NamedThing omim.nt IAO:0000013 PMID:12970263 biolink:NamedThing omim.nt IAO:0000013 PMID:12970307 biolink:NamedThing omim.nt IAO:0000013 PMID:1356667 biolink:NamedThing omim.nt IAO:0000013 PMID:14117275 biolink:NamedThing omim.nt IAO:0000013 PMID:14430045 biolink:NamedThing omim.nt IAO:0000013 PMID:14469327 biolink:NamedThing omim.nt IAO:0000013 PMID:14799100 biolink:NamedThing omim.nt IAO:0000013 PMID:15070926 biolink:NamedThing omim.nt IAO:0000013 PMID:15711092 biolink:NamedThing omim.nt IAO:0000013 PMID:1621772 biolink:NamedThing omim.nt IAO:0000013 PMID:17161328 biolink:NamedThing omim.nt IAO:0000013 PMID:17405843 biolink:NamedThing omim.nt IAO:0000013 PMID:17652219 biolink:NamedThing omim.nt IAO:0000013 PMID:17962410 biolink:NamedThing omim.nt IAO:0000013 PMID:18182455 biolink:NamedThing omim.nt IAO:0000013 PMID:18372789 biolink:NamedThing omim.nt IAO:0000013 PMID:19858129 biolink:NamedThing omim.nt IAO:0000013 PMID:198661 biolink:NamedThing omim.nt IAO:0000013 PMID:2031618 biolink:NamedThing omim.nt IAO:0000013 PMID:2109828 biolink:NamedThing omim.nt IAO:0000013 PMID:2122458 biolink:NamedThing omim.nt IAO:0000013 PMID:21549 biolink:NamedThing omim.nt IAO:0000013 PMID:2187341 biolink:NamedThing omim.nt IAO:0000013 PMID:219026 biolink:NamedThing omim.nt IAO:0000013 PMID:219790 biolink:NamedThing omim.nt IAO:0000013 PMID:230052 biolink:NamedThing omim.nt IAO:0000013 PMID:2829196 biolink:NamedThing omim.nt IAO:0000013 PMID:2856889 biolink:NamedThing omim.nt IAO:0000013 PMID:2993571 biolink:NamedThing omim.nt IAO:0000013 PMID:3003142 biolink:NamedThing omim.nt IAO:0000013 PMID:3018580 biolink:NamedThing omim.nt IAO:0000013 PMID:3089087 biolink:NamedThing omim.nt IAO:0000013 PMID:3210200 biolink:NamedThing omim.nt IAO:0000013 PMID:3223496 biolink:NamedThing omim.nt IAO:0000013 PMID:3934357 biolink:NamedThing omim.nt IAO:0000013 PMID:401530 biolink:NamedThing omim.nt IAO:0000013 PMID:4309802 biolink:NamedThing omim.nt IAO:0000013 PMID:4359274 biolink:NamedThing omim.nt IAO:0000013 PMID:5125407 biolink:NamedThing omim.nt IAO:0000013 PMID:5635160 biolink:NamedThing omim.nt IAO:0000013 PMID:6090498 biolink:NamedThing omim.nt IAO:0000013 PMID:6247654 biolink:NamedThing omim.nt IAO:0000013 PMID:6249307 biolink:NamedThing omim.nt IAO:0000013 PMID:6251958 biolink:NamedThing omim.nt IAO:0000013 PMID:6252235 biolink:NamedThing omim.nt IAO:0000013 PMID:6265935 biolink:NamedThing omim.nt IAO:0000013 PMID:6267099 biolink:NamedThing omim.nt IAO:0000013 PMID:6278930 biolink:NamedThing omim.nt IAO:0000013 PMID:6287258 biolink:NamedThing omim.nt IAO:0000013 PMID:6301273 biolink:NamedThing omim.nt IAO:0000013 PMID:6302127 biolink:NamedThing omim.nt IAO:0000013 PMID:6325502 biolink:NamedThing omim.nt IAO:0000013 PMID:6344759 biolink:NamedThing omim.nt IAO:0000013 PMID:657576 biolink:NamedThing omim.nt IAO:0000013 PMID:6770678 biolink:NamedThing omim.nt IAO:0000013 PMID:6773975 biolink:NamedThing omim.nt IAO:0000013 PMID:6822662 biolink:NamedThing omim.nt IAO:0000013 PMID:7076801 biolink:NamedThing omim.nt IAO:0000013 PMID:7136683 biolink:NamedThing omim.nt IAO:0000013 PMID:7815417 biolink:NamedThing omim.nt IAO:0000013 PMID:7853365 biolink:NamedThing omim.nt IAO:0000013 PMID:8151649 biolink:NamedThing omim.nt IAO:0000013 PMID:8383205 biolink:NamedThing omim.nt IAO:0000013 PMID:8444241 biolink:NamedThing omim.nt IAO:0000013 PMID:8646317 biolink:NamedThing omim.nt IAO:0000013 PMID:8989268 biolink:NamedThing omim.nt IAO:0000013 PMID:931429 biolink:NamedThing omim.nt IAO:0000013 PMID:9671744 biolink:NamedThing omim.nt IAO:0000013 UMLS:C3494506 biolink:NamedThing omim.nt owl:Class ORPHA:79443 biolink:NamedThing|biolink:Disease omim.nt owl:Class http://omim.org/entry/103581 biolink:NamedThing omim.nt True owl:Class http://omim.org/entry/103600.0001 biolink:NamedThing ALB, ARG-2HIS Substitution of histidine for arginine at position -2 was found in albumin Lille by {1:Abdo et al. (1981)} and {31:Galliano et al. (1988)}, in albumin Fukuoka-2 by {3:Arai et al. (1989)}, in albumin Taipei by {89:Takahashi et al. (1987)}, and in albumin Varese by {35:Galliano et al. (1990)}. A CGT-to-CAT change is responsible for the substitution. omim.nt GENO:0000002 http://omim.org/entry/103600 biolink:NamedThing|biolink:Gene ALB Albumin|linked to GC omim.nt ALBUMIN; ALB owl:Class ClinVar:RCV000019816 biolink:NamedThing omim.nt dbSNP:rs72552709 biolink:NamedThing omim.nt owl:NamedIndividual http://omim.org/entry/103600#0001 biolink:NamedThing omim.nt http://omim.org/entry/103600.0002 biolink:NamedThing ALB, ARG-1GLN Proalbumin Christchurch has also been called proalbumin Gainesville, proalbumin Fukuoka-3, and albumin Honolulu-2. This albumin has an arg(-1)-to-gln change in the preproprotein ({6:Arai et al., 1990}; {13:Brennan and Carrell, 1978}). {13:Brennan and Carrell (1978)} found a family with a circulating variant of proalbumin in members of 4 generations. No clinical abnormality was discernible in any of them. The variant represents 50% of total albumin and shows an additional N-terminal sequence, arg-gly-val-phe-arg-gln. Called 'proalbumin Christchurch,' the variant appears to have a mutation of arginine to glutamine at the last amino acid of this sequence. Thus, 2 basic amino acids must be necessary for cleavage of proalbumin in the Golgi vesicles. Copper binding is expected to be absent in the variant albumin because of blocking of the high affinity binding site. This is a situation comparable to Ehlers-Danlos syndrome type VII-A ({130060}) in which an amino acid substitution at the site of cleavage of procollagen results in persistence of procollagen and, in that case, clinically important abnormalities in collagen fiber formation. omim.nt GENO:0000002 ClinVar:RCV000144686 biolink:NamedThing omim.nt dbSNP:rs74821926 biolink:NamedThing omim.nt owl:NamedIndividual http://omim.org/entry/103600#0002 biolink:NamedThing omim.nt http://omim.org/entry/103600.0003 biolink:NamedThing ALB, ARG-1PRO Proalbumin Takefu has also been called albumin Honolulu-1. Substitution of proline for arginine at position -1 ({89:Takahashi et al., 1987}). This variant has also been called albumin Honolulu-1. omim.nt GENO:0000002 ClinVar:RCV000144687 biolink:NamedThing omim.nt http://omim.org/entry/103600#0003 biolink:NamedThing omim.nt http://omim.org/entry/103600.0004 biolink:NamedThing ALB, ASP1VAL Albumin Blenheim has also been called albumin Bremen and Albumin Iowa City-2. See {6:Arai et al. (1990)} and {12:Brennan et al. (1990)}. {12:Brennan et al. (1990)} suggested that hypermutability of 2 CpG dinucleotides in the codons for the diarginyl sequence may account for the frequency of mutations in the propeptide. {51:Madison et al. (1991)} showed that this mutation is caused by a GAT-to-GTT change. omim.nt GENO:0000002 ClinVar:RCV000144688 biolink:NamedThing omim.nt dbSNP:rs75353611 biolink:NamedThing omim.nt owl:NamedIndividual http://omim.org/entry/103600#0004 biolink:NamedThing omim.nt http://omim.org/entry/103600.0005 biolink:NamedThing ALB, HIS3GLN See {89:Takahashi et al. (1987)}. omim.nt GENO:0000002 ClinVar:RCV000019829 biolink:NamedThing omim.nt dbSNP:rs76285851 biolink:NamedThing omim.nt owl:NamedIndividual http://omim.org/entry/103600#0005 biolink:NamedThing omim.nt http://omim.org/entry/103600.0006 biolink:NamedThing ALB, ARG114GLY See {89:Takahashi et al. (1987)}. omim.nt GENO:0000002 ClinVar:RCV000019830 biolink:NamedThing omim.nt dbSNP:rs77238412 biolink:NamedThing omim.nt owl:NamedIndividual http://omim.org/entry/103600#0006 biolink:NamedThing omim.nt http://omim.org/entry/103600.0007 biolink:NamedThing ALB, GLU119LYS See {6:Arai et al. (1990)}. omim.nt GENO:0000002 ClinVar:RCV000019831 biolink:NamedThing omim.nt dbSNP:rs75522063 biolink:NamedThing omim.nt owl:NamedIndividual http://omim.org/entry/103600#0007 biolink:NamedThing omim.nt http://omim.org/entry/103600.0008 biolink:NamedThing ALB, ASP269GLY This variant has also been called albumin Nagasaki-1. See {3:Arai et al. (1989)}. omim.nt GENO:0000002 ClinVar:RCV000019833 biolink:NamedThing omim.nt dbSNP:rs79744198 biolink:NamedThing omim.nt owl:NamedIndividual http://omim.org/entry/103600#0008 biolink:NamedThing omim.nt http://omim.org/entry/103600.0009 biolink:NamedThing ALB, LYS313ASN This variant has also been called albumin New Guinea and albumin Cooperstown. {39:Huss et al. (1988)} described an electrophoretically fast alloalbumin in a family in New York State and called it albumin Cooperstown. It was found to have a substitution of asparagine for lysine at residue 313 and was shown to be the same as albumins found in Italy and in New Zealand. A change from AAG to AAY is responsible for the substitution; Y = either T or C. {35:Galliano et al. (1990)} found this albumin variant in 49 individuals in the Abruzzo region of Italy. omim.nt GENO:0000002 ClinVar:RCV000019835 biolink:NamedThing omim.nt ClinVar:RCV001154833 biolink:NamedThing omim.nt dbSNP:rs72552710 biolink:NamedThing omim.nt owl:NamedIndividual http://omim.org/entry/103600#0009 biolink:NamedThing omim.nt http://omim.org/entry/103600.0010 biolink:NamedThing ALB, ALA320THR AND ARG-2CYS {12:Brennan et al. (1990)} characterized albumin Redhill, an albumin variant that does not bind nickel and has a molecular mass 2.5 kD higher than normal albumin. Its inability to bind nickel was explained by the finding of an additional residue of arginine at position -1 of the mature protein, but this did not explain the molecular basis of the increase in apparent molecular mass. Further studies showed an ala320-to-thr change, which introduced an asn-tyr-thr oligosaccharide attachment sequence centered at asn318 and explained the increase in molecular mass. DNA sequencing of PCR-amplified genomic DNA encoding the prepro sequence of albumin indicated an additional mutation at position -2 from arg to cys. {12:Brennan et al. (1990)} proposed that the new phe-cys-arg sequence (replacing -phe-arg-arg-) in the propeptide serves as an aberrant signal peptidase cleavage site and that the signal peptidase cleaves the propeptide of albumin Redhill in the lumen of the endoplasmic reticulum before it reaches the Golgi vesicles, which is the site of the diarginyl-specific proalbumin convertase. Thus, albumin Redhill is longer than normal by 1 amino acid at its NH2-terminus. The ARG-2CYS mutation is the basis of proalbumin Malmo ({103600.0030}), a relatively frequent variant. omim.nt GENO:0000002 ClinVar:RCV000019837 biolink:NamedThing omim.nt dbSNP:rs78953271 biolink:NamedThing omim.nt owl:NamedIndividual http://omim.org/entry/103600#0010 biolink:NamedThing omim.nt http://omim.org/entry/103600.0011 biolink:NamedThing ALB, GLU321LYS {31:Galliano et al. (1988)} demonstrated that albumin Roma has a substitution of lysine for glutamic acid at position 321. A GAG-to-AAG change is responsible for the substitution. {35:Galliano et al. (1990)} found this albumin variant in 25 individuals from various parts of Italy. omim.nt GENO:0000002 ClinVar:RCV000019838 biolink:NamedThing omim.nt dbSNP:rs72552711 biolink:NamedThing omim.nt owl:NamedIndividual http://omim.org/entry/103600#0011 biolink:NamedThing omim.nt http://omim.org/entry/103600.0012 biolink:NamedThing ALB, GLU354LYS See {3:Arai et al. (1989)}. omim.nt GENO:0000002 ClinVar:RCV000019839 biolink:NamedThing omim.nt dbSNP:rs76593094 biolink:NamedThing omim.nt owl:NamedIndividual http://omim.org/entry/103600#0012 biolink:NamedThing omim.nt http://omim.org/entry/103600.0013 biolink:NamedThing ALB, GLU358LYS {3:Arai et al. (1989)} reported on amino acid substitutions in albumin variants found in Brazil. A previously unreported amino acid substitution was found in albumins Coari I and Porto Alegre I (glu358-to-lys). omim.nt GENO:0000002 ClinVar:RCV000019840 biolink:NamedThing omim.nt dbSNP:rs75791663 biolink:NamedThing omim.nt owl:NamedIndividual http://omim.org/entry/103600#0013 biolink:NamedThing omim.nt http://omim.org/entry/103600.0014 biolink:NamedThing ALB, ASP365HIS See {17:Brennan (1985)}. omim.nt GENO:0000002 ClinVar:RCV000019842 biolink:NamedThing omim.nt dbSNP:rs77187142 biolink:NamedThing omim.nt owl:NamedIndividual http://omim.org/entry/103600#0014 biolink:NamedThing omim.nt http://omim.org/entry/103600.0015 biolink:NamedThing ALB, LYS372GLU {27:Franklin et al. (1980)} demonstrated apparent identity between the polymorphic albumin variants Naskapi, found chiefly in the Naskapi Indians of Quebec, and Mersin, found in the Eti Turks of southeastern Turkey. They suggested that these were derived from the same mutation occurring in Asia and spreading with the progenitors of the American Indians to the North American continent and with Asiatic invaders to Asia Minor. {89:Takahashi et al. (1987)} found that lysine-372 of normal (common) albumin A was changed to glutamic acid both in albumin Naskapi and in albumin Mersin. Identity of these albumins may have originated through descent from a common mid-Asiatic founder of the 2 migrating ethnic groups, or it may represent identical but independent mutations of the albumin gene. This variant has also been called albumin Mexico-1. omim.nt GENO:0000002 ClinVar:RCV000019844 biolink:NamedThing omim.nt dbSNP:rs78166690 biolink:NamedThing omim.nt owl:NamedIndividual http://omim.org/entry/103600#0015 biolink:NamedThing omim.nt http://omim.org/entry/103600.0016 biolink:NamedThing ALB, ASP375ASN See {89:Takahashi et al. (1987)} and {3:Arai et al. (1989)}. omim.nt GENO:0000002 ClinVar:RCV000019846 biolink:NamedThing omim.nt dbSNP:rs77514449 biolink:NamedThing omim.nt owl:NamedIndividual http://omim.org/entry/103600#0016 biolink:NamedThing omim.nt http://omim.org/entry/103600.0017 biolink:NamedThing ALB, GLU376LYS See {3:Arai et al. (1989)}. omim.nt GENO:0000002 ClinVar:RCV000019847 biolink:NamedThing omim.nt dbSNP:rs79047363 biolink:NamedThing omim.nt owl:NamedIndividual http://omim.org/entry/103600#0017 biolink:NamedThing omim.nt http://omim.org/entry/103600.0018 biolink:NamedThing ALB, GLU382LYS See {3:Arai et al. (1989)}. omim.nt GENO:0000002 ClinVar:RCV000019848 biolink:NamedThing omim.nt dbSNP:rs76483862 biolink:NamedThing omim.nt owl:NamedIndividual http://omim.org/entry/103600#0018 biolink:NamedThing omim.nt http://omim.org/entry/103600.0019 biolink:NamedThing ALB, GLU501LYS {27:Franklin et al. (1980)} found a new variant in Eti Turks, which they termed albumin Adana. By improved methods, {39:Huss et al. (1988)} identified a substitution of lysine for glutamic acid at position 501 in albumins Vancouver and Birmingham, both from families that migrated from northern India, and also in albumin Adana from Turkey. This is the first substitution reported in an alloalbumin originating from the Indian subcontinent. Albumin Porto Alegre II also contains a glutamic acid-to-lysine substitution at position 501. This variant has also been called albumin Lambadi and albumin Manaus-1. omim.nt GENO:0000002 ClinVar:RCV000019851 biolink:NamedThing omim.nt dbSNP:rs75523493 biolink:NamedThing omim.nt owl:NamedIndividual http://omim.org/entry/103600#0019 biolink:NamedThing omim.nt http://omim.org/entry/103600.0020 biolink:NamedThing ALB, LYS541GLU See {89:Takahashi et al. (1987)}. The substitution in albumin Oriximina I is the same as that found in albumin Maku (lysine to glutamic acid at position 541) ({3:Arai et al., 1989}). This variant has also been called albumin Maku(Wapishana). omim.nt GENO:0000002 ClinVar:RCV000019855 biolink:NamedThing omim.nt dbSNP:rs80345158 biolink:NamedThing omim.nt owl:NamedIndividual http://omim.org/entry/103600#0020 biolink:NamedThing omim.nt http://omim.org/entry/103600.0021 biolink:NamedThing ALB, ASP550GLY {27:Franklin et al. (1980)} showed that albumin Mexico is in fact 2 separate, electrophoretically similar variants and that albumin Mexico-2 contains a substitution of glycine for aspartic acid at position 550. Substitution of aspartic acid-550 by glycine was found in albumin Mexico-2 from 4 persons of the Pima tribe ({89:Takahashi et al., 1987}). omim.nt GENO:0000002 ClinVar:RCV000019857 biolink:NamedThing omim.nt dbSNP:rs79738788 biolink:NamedThing omim.nt owl:NamedIndividual http://omim.org/entry/103600#0021 biolink:NamedThing omim.nt http://omim.org/entry/103600.0022 biolink:NamedThing ALB, ASP563ASN See {6:Arai et al. (1990)}. omim.nt GENO:0000002 ClinVar:RCV000019858 biolink:NamedThing omim.nt dbSNP:rs76587671 biolink:NamedThing omim.nt owl:NamedIndividual http://omim.org/entry/103600#0022 biolink:NamedThing omim.nt http://omim.org/entry/103600.0023 biolink:NamedThing ALB, GLU565LYS See {6:Arai et al. (1990)}. omim.nt GENO:0000002 ClinVar:RCV000019859 biolink:NamedThing omim.nt dbSNP:rs75709682 biolink:NamedThing omim.nt owl:NamedIndividual http://omim.org/entry/103600#0023 biolink:NamedThing omim.nt http://omim.org/entry/103600.0024 biolink:NamedThing ALB, GLU570LYS Albumin B has also been called albumin Oliphant, albumin Phnom Penh, albumin Nagano, albumin Osaka-2, and albumin Verona B. {3:Arai et al. (1989)} identified the amino acid substitution characteristic of albumin B (glutamic acid-to-lysine at position 570) in alloalbumins from 6 unrelated persons of 5 different European descents and also in 2 Japanese and 1 Cambodian. A GAG-to-AAG change is responsible for this substitution. {35:Galliano et al. (1990)} found this variant in 103 individuals in the Veneto area of Italy. omim.nt GENO:0000002 ClinVar:RCV000019862 biolink:NamedThing omim.nt dbSNP:rs79228041 biolink:NamedThing omim.nt owl:NamedIndividual http://omim.org/entry/103600#0024 biolink:NamedThing omim.nt http://omim.org/entry/103600.0025 biolink:NamedThing ALB, LYS573GLU This variant has also been called albumin Ghent. An AAA-to-GAA change is responsible for this substitution. {35:Galliano et al. (1990)} found this variant in 80 individuals from the Lombardy area of Italy. Homozygotes have been identified. omim.nt GENO:0000002 ClinVar:RCV000019867 biolink:NamedThing omim.nt dbSNP:rs80106970 biolink:NamedThing omim.nt owl:NamedIndividual http://omim.org/entry/103600#0025 biolink:NamedThing omim.nt http://omim.org/entry/103600.0026 biolink:NamedThing ALB, LYS574ASN See {31:Galliano et al. (1988)}. omim.nt GENO:0000002 ClinVar:RCV000019868 biolink:NamedThing omim.nt dbSNP:rs75738598 biolink:NamedThing omim.nt owl:NamedIndividual http://omim.org/entry/103600#0026 biolink:NamedThing omim.nt http://omim.org/entry/103600.0027 biolink:NamedThing ALB, IVS6AS, A-G, -2 {75:Ruffner and Dugaiczyk (1988)} identified a structural defect in the serum albumin gene of an analbuminemic American Indian girl. Sequence determination of 1.1 kb of the 5-prime regulatory region and of 6 kb across exonic regions revealed a single AG-to-GG mutation within the 3-prime splice site of intron 6 in the defective gene of the analbuminemic person. In an in vitro assay on the RNA transcript, this mutation caused a defect in out-splicing of the intron 6 sequence and in the subsequent ligation of the exon 6/exon 7 sequences. Using polymerase-amplified genomic DNA and allele-specific oligodeoxynucleotide probes, {75:Ruffner and Dugaiczyk (1988)} also showed that the sequence of this intron 6/exon 7 splice junction was normal in a different, unrelated analbuminemic person. omim.nt GENO:0000002 ClinVar:RCV000019869 biolink:NamedThing omim.nt dbSNP:rs77335374 biolink:NamedThing omim.nt owl:NamedIndividual http://omim.org/entry/103600#0027 biolink:NamedThing omim.nt http://omim.org/entry/103600.0028 biolink:NamedThing ALB, EX14DEL {58:Minchiotti et al. (1989)} described the molecular defect of an electrophoretically fast alloalbumin named Venezia, found in about 90 seemingly unrelated families in Italy, mainly in the Veneto region. In heterozygous subjects the total albumin content was in the normal range, with the variant accounting for about 30% of the total protein. Reduced stability of the mutant was thought to account for the lower-than-expected percentage. {58:Minchiotti et al. (1989)} found that albumin Venezia possesses a shortened polypeptide chain, 578 residues instead of 585, completely variant from residue 572 to the COOH-terminus: 572 pro-thr-met-arg-ile-arg-578 glu. This extensive modification can be accounted for by deletion of exon 14 and translation to the first terminator codon of exon 15, which normally does not code for protein. The absence of a basic COOH-terminal dipeptide in the mature molecule can be explained by the probable action of serum carboxypeptidase N. The low serum level of the variant in heterozygous subjects suggests that the carboxy-terminus of the molecule is critical for albumin stability. {35:Galliano et al. (1990)} found this variant in 105 individuals, particularly in the region of Veneto in Italy. omim.nt GENO:0000002 ClinVar:RCV000019870 biolink:NamedThing omim.nt http://omim.org/entry/103600#0028 biolink:NamedThing omim.nt http://omim.org/entry/103600.0029 biolink:NamedThing ALB, LYS536GLU An AAG-to-GAG change is responsible for this substitution. {35:Galliano et al. (1990)} found this variant in 1 individual in Italy. omim.nt GENO:0000002 ClinVar:RCV000019871 biolink:NamedThing omim.nt dbSNP:rs77645174 biolink:NamedThing omim.nt owl:NamedIndividual http://omim.org/entry/103600#0029 biolink:NamedThing omim.nt http://omim.org/entry/103600.0030 biolink:NamedThing ALB, ARG-2CYS In a collaborative effort involving laboratories at Malmo, Sweden; Bloomington, Indiana; Christchurch, New Zealand; Saitama, Japan; and Pavia, Italy, {12:Brennan et al. (1990)} studied the most common Swedish albumin variant, which is expressed in plasma as a broadened electrophoretic band indicative of a slow component at pH 8.6. Present in about 1 per 1,000 persons in Sweden, it was also found in a family of Scottish descent from Kaikoura, New Zealand, and in 5 families in Tradate, Italy. The major variant component was found to be arginyl-albumin, in which arginine at the -1 position of the propeptide is still attached to the processed albumin. A minor component with the amino-terminal sequence of proalbumin was also present as 3 to 6% of the total albumin. The mutation was found to involve a change of arginine to cysteine at the -2 position. (In albumin Redhill ({103600.0010}), the Malmo mutation is combined with another.) A CGT-to-TGT change is responsible for the substitution. This variant has also been called albumin Tradate. In a note added in proof, {12:Brennan et al. (1990)} stated that because of the similarity of the electrophoretic pattern of an anomalous albumin reported in a family by {49:Laurell and Nilehn (1966)}, they obtained the plasma from one of the original subjects from that family and determined that it was the same as albumin Malmo. omim.nt GENO:0000002 ClinVar:RCV000019872 biolink:NamedThing omim.nt ClinVar:RCV001152702 biolink:NamedThing omim.nt dbSNP:rs80008208 biolink:NamedThing omim.nt owl:NamedIndividual http://omim.org/entry/103600#0030 biolink:NamedThing omim.nt http://omim.org/entry/103600.0031 biolink:NamedThing ALB, ARG-1LEU In 2 members of a Tamil family from Jaffna (northern Sri Lanka), {36:Galliano et al. (1989)} found an electrophoretically slow-moving variant of serum albumin. Sequence analysis demonstrated that the variant is an abnormal proalbumin arising from a substitution of leucine for arginine at position -1, which prevents the proteolytic removal of the N-terminal hexapeptide and allows the mutated proalbumin to enter the circulation. omim.nt GENO:0000002 ClinVar:RCV000019874 biolink:NamedThing omim.nt http://omim.org/entry/103600#0031 biolink:NamedThing omim.nt http://omim.org/entry/103600.0032 biolink:NamedThing ALB, 1-BP DEL, C, CODON 580 This variant has also been called albumin GE/CT. This was the fourth albumin variant to be characterized structurally. {34:Galliano et al. (1986)} found a shortened chain with deletion of a cytosine in codon 580, causing frameshift and termination after amino acid 582. The COOH-terminal sequence is leu-val-ala-ala-ser-lys-leu-pro. {35:Galliano et al. (1990)} found this mutation in 62 individuals in Sicily. omim.nt GENO:0000002 ClinVar:RCV000019877 biolink:NamedThing omim.nt dbSNP:rs77158239 biolink:NamedThing omim.nt owl:NamedIndividual http://omim.org/entry/103600#0032 biolink:NamedThing omim.nt http://omim.org/entry/103600.0033 biolink:NamedThing ALB, GLU60LYS {35:Galliano et al. (1990)} found a substitution of lysine for glutamic acid at position 60 resulting from a GAA-to-AAA change in a single Italian patient. omim.nt GENO:0000002 ClinVar:RCV000019878 biolink:NamedThing omim.nt dbSNP:rs77050410 biolink:NamedThing omim.nt owl:NamedIndividual http://omim.org/entry/103600#0033 biolink:NamedThing omim.nt http://omim.org/entry/103600.0034 biolink:NamedThing ALB, GLU82LYS In 2 Italian individuals {35:Galliano et al. (1990)} found a GAA-to-AAA change in codon 82 leading to substitution of lysine for glutamic acid. omim.nt GENO:0000002 ClinVar:RCV000019879 biolink:NamedThing omim.nt dbSNP:rs80296402 biolink:NamedThing omim.nt owl:NamedIndividual http://omim.org/entry/103600#0034 biolink:NamedThing omim.nt http://omim.org/entry/103600.0035 biolink:NamedThing ALB, ASP494ASN In albumin Casebrook, an electrophoretically slow albumin variant with a relative molecular mass of 2.5 kD higher than normal albumin, {67:Peach and Brennan (1991)} identified substitution of asparagine for aspartic acid-494. The mutation introduced an asn-glu-thr N-linked oligosaccharide attachment sequence centered on asn494, which explained the increase in molecular mass. The mutant albumin was associated with no apparent pathology and was detected in 2 unrelated individuals of Anglo-Saxon descent. omim.nt GENO:0000002 ClinVar:RCV000019880 biolink:NamedThing omim.nt ClinVar:RCV001152821 biolink:NamedThing omim.nt dbSNP:rs75920790 biolink:NamedThing omim.nt owl:NamedIndividual http://omim.org/entry/103600#0035 biolink:NamedThing omim.nt http://omim.org/entry/103600.0036 biolink:NamedThing ALB, ASP365VAL In a survey of alloalbumins in patients at 2 major medical centers in the United States and nearly 20,000 blood donors in Japan, {51:Madison et al. (1991)} identified 2 previously unreported alloalbumin types. In one type, found in a Caucasian family and designated Iowa City-1, aspartic acid at position 365 was replaced by valine. This was the second reported mutation at position 365; see albumin Parklands ({103600.0014}). The codon change was GAT-to-GTT. In the second type, found in a Japanese blood donor, histidine-128 was replaced by arginine ({103600.0037}). The codon change was CAT-to-CGT. omim.nt GENO:0000002 ClinVar:RCV000019881 biolink:NamedThing omim.nt ClinVar:RCV001156502 biolink:NamedThing omim.nt dbSNP:rs78538497 biolink:NamedThing omim.nt owl:NamedIndividual http://omim.org/entry/103600#0036 biolink:NamedThing omim.nt http://omim.org/entry/103600.0037 biolink:NamedThing ALB, HIS128ARG See {103600.0036}. omim.nt GENO:0000002 ClinVar:RCV000019882 biolink:NamedThing omim.nt dbSNP:rs80095457 biolink:NamedThing omim.nt owl:NamedIndividual http://omim.org/entry/103600#0037 biolink:NamedThing omim.nt http://omim.org/entry/103600.0038 biolink:NamedThing ALB, IVS13DS, G-C, +1 {68:Peach et al. (1992)} found that 3 members of a family were heterozygous for an electrophoretically fast albumin variant, designated albumin Rugby Park, which constituted only 8% of total serum albumin. Isoelectric focusing indicated an increased negative charge on the C-terminal CNBr peptide. Sequencing of PCR-amplified DNA indicated a G-to-C transversion at position 1 of the intron 13. The replacement of the obligate GT sequence by CT at the exon/intron boundary prevented splicing of intron 13, and translation continued for 21 nucleotides until a stop codon was reached. The new protein lacked the 14 amino acids encoded in exon 14, but these were replaced by 7 new residues, giving a truncated albumin of 578 residues. omim.nt GENO:0000002 ClinVar:RCV000019883 biolink:NamedThing omim.nt dbSNP:rs1800580 biolink:NamedThing omim.nt owl:NamedIndividual http://omim.org/entry/103600#0038 biolink:NamedThing omim.nt http://omim.org/entry/103600.0039 biolink:NamedThing ALB, LYS240GLU {62:Minchiotti et al. (1993)} found that albumin Herborn, a variant discovered in Germany, had a point mutation in codon 240 changing AAA (lys) to GAA (glu). The mutation was in the region implicated in bilirubin binding, but {62:Minchiotti et al. (1993)} found that the binding of bilirubin and biliverdin to albumin Herborn was not significantly reduced. omim.nt GENO:0000002 ClinVar:RCV000019884 biolink:NamedThing omim.nt dbSNP:rs79377490 biolink:NamedThing omim.nt owl:NamedIndividual http://omim.org/entry/103600#0039 biolink:NamedThing omim.nt http://omim.org/entry/103600.0040 biolink:NamedThing ALB, 1-BP DUP, 9156A {98:Watkins et al. (1994)} investigated analbuminemia ({616000}) in an Italian family by analysis of DNA from a mother and her daughter. The mother, whose parents were first cousins, was homozygous for the trait and had a serum albumin value of less than 0.01 g/dl (about 1/500 normal); the daughter was heterozygous for the trait and had a nearly normal albumin value. Molecular cloning and sequence analysis showed that the mutation, called analbuminemia Roma, was a nucleotide insertion in exon 8, producing a frameshift that led to a premature stop 7 codons downstream. {98:Watkins et al. (1994)} used heteroduplex hybridization and single-strand conformation polymorphism to compare the DNA of these 2 individuals with the DNA of 2 unrelated analbuminemic persons, 1 Italian (called Codogno) and 1 American (patient G.M.) and showed that each patient had a different mutation. These mutations also differed from the mutation identified in a Native American ({103600.0027}). Whereas the normal serum albumin gene has 4 A residues as nucleotides 9156-9159, the Roma allele had 5 A residues encompassing 9156-9160. The predicted translation product from the Roma allele would consist of only 273 amino acids instead of the normal 585 amino acid residues found in mature serum albumin. The insertion of the additional adenine changed codon 267 from AAT (asn) to AAA (lys) and changed the reading frame in such a way that codon 274 was changed from AAA (lys) to TAA (stop). omim.nt GENO:0000002 ClinVar:RCV000019885 biolink:NamedThing omim.nt dbSNP:rs77449454 biolink:NamedThing omim.nt owl:NamedIndividual http://omim.org/entry/103600#0040 biolink:NamedThing omim.nt http://omim.org/entry/103600.0041 biolink:NamedThing ALB, ARG218HIS In 2 unrelated patients with dysalbuminemic hyperthyroxinemia (FDAH; {615999}), {69:Petersen et al. (1994)} identified an arg218-to-his substitution which was caused by a G (CGC)-to-A (CAG) transition at nucleotide 653. Abnormal affinity of the albumin from these patients for a thyroxine analog was verified by an adaptation of the procedure used in routine free T4 measurement. Both subjects were heterozygous. During the preparation of the manuscript, a third patient with the same mutation was found, suggesting that R218H may be the most frequent cause of this disorder. The mutation created a new HphI restriction site in exon 7, which was used diagnostically. {86:Sunthornthepvarakul et al. (1994)} identified R218H mutation in affected members of 8 unrelated families with dysalbuminemic hyperthyroxinemia. {72:Pohlenz et al. (2001)} reported a 5-month-old boy with familial dysalbuminemic hyperthyroxinemia and congenital hypothyroidism who had a blood thyrotropin (TSH) level of 479 mU/L but normal T4 and elevated T3 levels. The patient and his euthyroid father and brother all carried the R218H mutation. omim.nt GENO:0000002 ClinVar:RCV000019886 biolink:NamedThing omim.nt dbSNP:rs75002628 biolink:NamedThing omim.nt owl:NamedIndividual http://omim.org/entry/103600#0041 biolink:NamedThing omim.nt http://omim.org/entry/103600.0042 biolink:NamedThing ALB, HIS3TYR {52:Madison et al. (1994)} stated that of the more than 50 different genetic variants of human serum albumin that had been characterized by amino acid or DNA sequence analysis, almost half had been identified in Italy through a long-term electrophoretic survey of serum. They reported 4 other Italian alloalbumins not previously recorded: Larino, his3-to-tyr; Tradate-2, lys225-to-gln ({103600.0043}); Caserta, lys276-to-asn ({103600.0044}); and Bazzano, a carboxyl-terminal variant ({103600.0045}). The first 3 had point mutations that produced a single amino acid substitution; a nucleotide deletion caused a frameshift and an altered and truncated carboxy-terminal sequence in albumin Bazzano. In these 4 instances, the expression of the alloalbumin was variable, ranging from 10 to 70% of the total albumin, in contrast to the usual 50% each for the normal and mutant albumin. {52:Madison et al. (1994)} commented that the distribution of point mutations in the albumin gene is nonrandom; most of the 47 reported point substitutions involved charged amino acid residues on the surface of the molecule that are not concerned with ligand-binding sites. omim.nt GENO:0000002 ClinVar:RCV000019887 biolink:NamedThing omim.nt dbSNP:rs141733599 biolink:NamedThing omim.nt owl:NamedIndividual http://omim.org/entry/103600#0042 biolink:NamedThing omim.nt http://omim.org/entry/103600.0043 biolink:NamedThing ALB, LYS225GLN See {103600.0042}. In a patient from Tradate (Lombardy region), {52:Madison et al. (1994)} demonstrated a substitution of glutamine for lysine-225. An AAA-to-CAA change is responsible for the substitution. Albumin Tradate-2 was present in equimolar ratio with albumin A and had a fast mobility. omim.nt GENO:0000002 ClinVar:RCV000019888 biolink:NamedThing omim.nt ClinVar:RCV001153985 biolink:NamedThing omim.nt dbSNP:rs79804069 biolink:NamedThing omim.nt owl:NamedIndividual http://omim.org/entry/103600#0043 biolink:NamedThing omim.nt http://omim.org/entry/103600.0044 biolink:NamedThing ALB, LYS276ASN See {103600.0042}. In 3 members of a family from Caserta near Naples, {52:Madison et al. (1994)} demonstrated a substitution of asparagine for lysine-276. An AAG-to-AAC change is responsible for the substitution. The alloalbumin was identified by its fast mobility. The 3 subjects were heterozygous, but the variant/normal ratio was 1.5/1 in the serum of the mother, whereas it was about 2/1 in both sibs. In all 3 cases, an increased total albumin content was observed. omim.nt GENO:0000002 ClinVar:RCV000019889 biolink:NamedThing omim.nt dbSNP:rs74718349 biolink:NamedThing omim.nt owl:NamedIndividual http://omim.org/entry/103600#0044 biolink:NamedThing omim.nt http://omim.org/entry/103600.0045 biolink:NamedThing ALB, 1-BP DEL, g.15332T See {103600.0042}. {52:Madison et al. (1994)} found albumin Bazzano in several families from Bazzano, a small town close to Bologna. At pH 8.6 the variant was much slower than normal and comprised only about 18% of the total albumin. In SDS/PAGE, the molecular weight of the variant appeared slightly lower than normal. Sequence analysis revealed deletion of the thymine nucleotide at position 15332 in the genomic sequence. This led to a frameshift and a divergent amino acid sequence of 16 residues beginning at position 567, with early termination after 582. The extensive modification caused an increase in positive charge, which explained the unusually slow mobility of the alloalbumin. The normal termination codon in albumin is 586. Other carboxy-terminal variants are albumin Venezia ({103600.0028}), albumin Rugby Park ({103600.0038}), and albumin Catania ({103600.0032}). omim.nt GENO:0000002 ClinVar:RCV000019890 biolink:NamedThing omim.nt dbSNP:rs74674594 biolink:NamedThing omim.nt owl:NamedIndividual http://omim.org/entry/103600#0045 biolink:NamedThing omim.nt http://omim.org/entry/103600.0046 biolink:NamedThing ALB, TYR140CYS In 2 members of a family living in Asola in Lombardia, Italy, {60:Minchiotti et al. (1995)} detected a slow migrating variant of human serum albumin present in lower amounts than the normal protein by routine clinical electrophoresis at pH 8.6. Isoelectric focusing analysis of CNBr fragments localized the mutation to fragment CNBr3 (amino acid residues 124-298). Amino acid sequence analysis showed a tyr140-to-cys substitution, confirmed by DNA sequence analysis, which resulted from a single transition of TAT to TGT at nucleotide 5074. Despite the presence of an additional cysteine residue, several lines of evidence indicated that albumin Asola had no free sulfhydryl group; therefore, {60:Minchiotti et al. (1995)} proposed that the mutant amino acid, cysteine, was involved in the formation of a new disulfide bond with cys34, the only free sulfydryl group present in the normal protein. omim.nt GENO:0000002 ClinVar:RCV000019891 biolink:NamedThing omim.nt dbSNP:rs78283180 biolink:NamedThing omim.nt owl:NamedIndividual http://omim.org/entry/103600#0046 biolink:NamedThing omim.nt http://omim.org/entry/103600.0047 biolink:NamedThing ALB, ASP63ASN This variant has also been called albumin Dalakarlia-1. {20:Carlson et al. (1992)} demonstrated that albumin Malmo-95 has a substitution of asparagine for aspartic acid-63. A GAC-to-AAC change is responsible for the substitution. omim.nt GENO:0000002 ClinVar:RCV000019892 biolink:NamedThing omim.nt dbSNP:rs78574148 biolink:NamedThing omim.nt owl:NamedIndividual http://omim.org/entry/103600#0047 biolink:NamedThing omim.nt http://omim.org/entry/103600.0048 biolink:NamedThing ALB, CYS177PHE {14:Brennan and Fellowes (1993)} demonstrated that albumin Hawkes Bay has a substitution of phenylalanine for cysteine-177. A TGC-to-TTC change is responsible for the substitution. omim.nt GENO:0000002 ClinVar:RCV000019875 biolink:NamedThing omim.nt dbSNP:rs77656691 biolink:NamedThing omim.nt owl:NamedIndividual http://omim.org/entry/103600#0048 biolink:NamedThing omim.nt http://omim.org/entry/103600.0049 biolink:NamedThing ALB, GLN268ARG This variant has also been called albumin Skaane SA. {20:Carlson et al. (1992)} demonstrated that albumin Malmo-10 has a substitution of arginine for glutamine-268. A CAA-to-CGA change is responsible for the substitution. omim.nt GENO:0000002 ClinVar:RCV000019893 biolink:NamedThing omim.nt dbSNP:rs80002911 biolink:NamedThing omim.nt owl:NamedIndividual http://omim.org/entry/103600#0049 biolink:NamedThing omim.nt http://omim.org/entry/103600.0050 biolink:NamedThing ALB, ASN318LYS This variant has also been called albumin Orebro SW. {20:Carlson et al. (1992)} demonstrated that albumin Malmo-47 has a substitution of lysine for asparagine-318. A change from AAC to AAA or AAG is responsible for the substitution. omim.nt GENO:0000002 ClinVar:RCV000019894 biolink:NamedThing omim.nt dbSNP:rs77544362 biolink:NamedThing omim.nt owl:NamedIndividual http://omim.org/entry/103600#0050 biolink:NamedThing omim.nt http://omim.org/entry/103600.0051 biolink:NamedThing ALB, GLU333LYS {61:Minchiotti et al. (1992)} demonstrated that albumin Sondria has a substitution of lysine for glutamic acid-333. A GAA-to-AAA change is responsible for the substitution. omim.nt GENO:0000002 ClinVar:RCV000019895 biolink:NamedThing omim.nt dbSNP:rs77354753 biolink:NamedThing omim.nt owl:NamedIndividual http://omim.org/entry/103600#0051 biolink:NamedThing omim.nt http://omim.org/entry/103600.0052 biolink:NamedThing ALB, GLU376GLN {20:Carlson et al. (1992)} demonstrated that albumin Malmo-5 has a substitution of glutamine for glutamic acid-376. A GAA-to-CAA change is responsible for the substitution. omim.nt GENO:0000002 ClinVar:RCV000019896 biolink:NamedThing omim.nt http://omim.org/entry/103600#0052 biolink:NamedThing omim.nt http://omim.org/entry/103600.0053 biolink:NamedThing ALB, GLU479LYS {76:Sakamoto et al. (1991)} demonstrated that albumin Dublin has a substitution of lysine for glutamic acid-479. A GAA-to-AAA change is responsible for the substitution. omim.nt GENO:0000002 ClinVar:RCV000019897 biolink:NamedThing omim.nt dbSNP:rs80259813 biolink:NamedThing omim.nt owl:NamedIndividual http://omim.org/entry/103600#0053 biolink:NamedThing omim.nt http://omim.org/entry/103600.0054 biolink:NamedThing ALB, GLU505LYS {33:Galliano et al. (1993)} demonstrated that albumin Ortonovo has a substitution of lysine for glutamic acid-505. A GAA-to-AAA change is responsible for the substitution. omim.nt GENO:0000002 ClinVar:RCV000019898 biolink:NamedThing omim.nt dbSNP:rs74826639 biolink:NamedThing omim.nt owl:NamedIndividual http://omim.org/entry/103600#0054 biolink:NamedThing omim.nt http://omim.org/entry/103600.0055 biolink:NamedThing ALB, ARG218PRO Of 8 members of a 3-generation Japanese family, {96:Wada et al. (1997)} documented 6 who had dysalbuminemic hyperthyroxinemia (FDAH; {615999}). Serum total T4 levels ranged from 1763 to 2741 nmol/L (normal range, 66-165), serum total T3 levels ranged from 2.73-5.62 nmol/L (normal range, 1.47-2.95), and rT3 levels ranged from 1.08 to 2.52 nmol/L (normal range, 0.22-0.60). All affected family members were heterozygous for a G-to-C transition in the second nucleotide of codon 218 of the albumin gene, resulting in an arg218-to-pro substitution. omim.nt GENO:0000002 ClinVar:RCV000019899 biolink:NamedThing omim.nt http://omim.org/entry/103600#0055 biolink:NamedThing omim.nt http://omim.org/entry/103600.0056 biolink:NamedThing ALB, LEU66PRO {87:Sunthornthepvarakul et al. (1998)} reported an abnormal albumin in members of a Thai family that presented with high serum total T3 but not T4 when measured by radioimmunoassay. In contrast, total T3 values were very low when measured by ELISA and chemiluminescence. The subjects did not have a goiter and were clinically euthyroid. Their serum free T4, free T3, and TSH levels were normal (FDAH; {615999}). Spiking of T3 to affected serum showed good recovery by radioimmunoassay but very poor recovery by ELISA and by chemiluminescence. Immunoprecipitation with labeled T3 bound to albumin showed a high percent of precipitation in affected serum. T3-binding studies showed that the association constant of serum albumin in affected subjects, 1.5 x 10(6)M(-1), was 40-fold that of unaffected relatives, 3.9 x 10(4)M(-1). The authors found a T-to-C (CTT-to-CCT) transition in the second nucleotide of codon 66, resulting in replacement of the normal leucine by proline. omim.nt GENO:0000002 ClinVar:RCV000019900 biolink:NamedThing omim.nt dbSNP:rs77892378 biolink:NamedThing omim.nt owl:NamedIndividual http://omim.org/entry/103600#0056 biolink:NamedThing omim.nt http://omim.org/entry/103600.0057 biolink:NamedThing ALB, IVS1DS, G-A, +1 In a male newborn of Iraqi extraction with analbuminemia ({616000}), {18:Campagnoli et al. (2002)} found a G-to-A substitution at nucleotide 118 in the ALB gene. The mutation, involving the first base of intron 1, destroyed the GT dinucleotide consensus sequence found at the 5-prime end of most intervening sequences and caused defective pre-mRNA splicing. The child was homozygous; both parents were heterozygous. The infant presented with low birthweight due to placental infarctions, and mild edema was noted after 1 week. There was no jaundice and the bilirubin level was normal. Only minute amounts of albumin were detected. Hypercholesterolemia developed in spite of total lipid values within the normal range. At 18 months he was in good general condition, without edema, and had normal weight and length for his age. The parents, who were first cousins, had low albumin concentration values: the father 33 g/l and the mother 27 g/l. omim.nt GENO:0000002 ClinVar:RCV000019901 biolink:NamedThing omim.nt dbSNP:rs77408163 biolink:NamedThing omim.nt owl:NamedIndividual http://omim.org/entry/103600#0057 biolink:NamedThing omim.nt http://omim.org/entry/103600.0058 biolink:NamedThing ALB, 1-BP DUP, 1098T In 2 sibs, born to consanguineous Algerian parents, with analbuminemia ({616000}), {19:Caridi et al. (2019)} identified a homozygous 1-bp duplication (c.1098dupT) in exon 9 of the ALB gene, resulting in a frameshift and generation of a premature stop codon (Val367fsTer12). The mother was heterozygous for the mutation; DNA from the father was not available for testing. The variant was not found in the ExAC or gnomAD databases. omim.nt GENO:0000002 ClinVar:RCV000787975 biolink:NamedThing omim.nt dbSNP:rs1577939845 biolink:NamedThing omim.nt owl:NamedIndividual http://omim.org/entry/103600#0058 biolink:NamedThing omim.nt MONARCH:.well-known/genid/bf350aaf75b4f5e802ff biolink:NamedThing GRCh38chr4-73404286-73421481-Region omim.nt MONARCH:.well-known/genid/b6e0cbc707e97bcb0e56 faldo:Region MONARCH:.well-known/genid/OMIM103600ref107 biolink:NamedThing Comparative gene mapping: linkage between the albumin and Gc loci in the horse. (Abstract) omim.nt IAO:0000310 MONARCH:.well-known/genid/OMIM103600ref110 biolink:NamedThing The gene frequency of serum albumin variants in Chinese and the electrophoretic characterization of several serum albumin variants. omim.nt IAO:0000310 MONARCH:.well-known/genid/OMIM103600ref21 biolink:NamedThing Serum albumin. Atlas of Protein Sequence and Structure. Vol. 5. omim.nt IAO:0000310 MONARCH:.well-known/genid/OMIM103600ref25 biolink:NamedThing Identification of the human albumin variant 'Gainesville' with proalbumin 'Christchurch'. omim.nt IAO:0000310 MONARCH:.well-known/genid/OMIM103600ref30 biolink:NamedThing Structural characterization of the human albumin variant 'Pollibauer'. omim.nt IAO:0000310 MONARCH:.well-known/genid/OMIM103600ref32 biolink:NamedThing Genetic variants of human serum albumin. omim.nt IAO:0000310 MONARCH:.well-known/genid/OMIM103600ref41 biolink:NamedThing Albumin Carlisle: occurrence and properties of a new human albumin variant. omim.nt IAO:0000310 MONARCH:.well-known/genid/OMIM103600ref50 biolink:NamedThing Polymorphisms of human albumin gene after DNA restriction by HaeIII endonuclease. omim.nt IAO:0000310 MONARCH:.well-known/genid/OMIM103600ref53 biolink:NamedThing Chromosomal localization of the albumin and alpha-fetoprotein genes in the orangutan (Pongo pygmaeus) and gorilla (Gorilla gorilla). (Abstract) omim.nt IAO:0000310 MONARCH:.well-known/genid/OMIM103600ref57 biolink:NamedThing Albumin polymorphism in man: studies on albumin variants in North American native populations. omim.nt IAO:0000310 MONARCH:.well-known/genid/OMIM103600ref77 biolink:NamedThing Albumin Amsterdam: a new European albumin variant. omim.nt IAO:0000310 MONARCH:.well-known/genid/OMIM103600ref82 biolink:NamedThing The genetics of human serum albumin.In: Rosenoer, V. M.; Oratz, M.; Rothschild, M. A. : Albumin Structure, Function and Uses. omim.nt IAO:0000310 MONARCH:.well-known/genid/OMIM103600ref83 biolink:NamedThing Acquired bisalbuminemia with hyperamylasemia. omim.nt IAO:0000310 MONARCH:.well-known/genid/OMIM103600ref84 biolink:NamedThing Linkage between the loci for serum albumin and vitamin D binding protein (GC) in the Japanese quail. omim.nt IAO:0000310 MONARCH:.well-known/genid/OMIM103600ref9 biolink:NamedThing Albumins Warwick 1 and Warwick 2, two human albumin variants. omim.nt IAO:0000310 PMID:11743520 biolink:NamedThing omim.nt IAO:0000013 PMID:11781148 biolink:NamedThing omim.nt IAO:0000013 PMID:1269174 biolink:NamedThing omim.nt IAO:0000013 PMID:12743361 biolink:NamedThing omim.nt IAO:0000013 PMID:1347703 biolink:NamedThing omim.nt IAO:0000013 PMID:13655663 biolink:NamedThing omim.nt IAO:0000013 PMID:13673098 biolink:NamedThing omim.nt IAO:0000013 PMID:13785411 biolink:NamedThing omim.nt IAO:0000013 PMID:13844624 biolink:NamedThing omim.nt IAO:0000013 PMID:1390939 biolink:NamedThing omim.nt IAO:0000013 PMID:14187073 biolink:NamedThing omim.nt IAO:0000013 PMID:14224515 biolink:NamedThing omim.nt IAO:0000013 PMID:14497189 biolink:NamedThing omim.nt IAO:0000013 PMID:1518850 biolink:NamedThing omim.nt IAO:0000013 PMID:158758 biolink:NamedThing omim.nt IAO:0000013 PMID:16592818 biolink:NamedThing omim.nt IAO:0000013 PMID:16608438 biolink:NamedThing omim.nt IAO:0000013 PMID:1819460 biolink:NamedThing omim.nt IAO:0000013 PMID:18459107 biolink:NamedThing omim.nt IAO:0000013 PMID:1859851 biolink:NamedThing omim.nt IAO:0000013 PMID:1946412 biolink:NamedThing omim.nt IAO:0000013 PMID:19556507 biolink:NamedThing omim.nt IAO:0000013 PMID:2104980 biolink:NamedThing omim.nt IAO:0000013 PMID:2247440 biolink:NamedThing omim.nt IAO:0000013 PMID:2339130 biolink:NamedThing omim.nt IAO:0000013 PMID:2404284 biolink:NamedThing omim.nt IAO:0000013 PMID:2430733 biolink:NamedThing omim.nt IAO:0000013 PMID:2452956 biolink:NamedThing omim.nt IAO:0000013 PMID:2564675 biolink:NamedThing omim.nt IAO:0000013 PMID:2762316 biolink:NamedThing omim.nt IAO:0000013 PMID:2792379 biolink:NamedThing omim.nt IAO:0000013 PMID:2898383 biolink:NamedThing omim.nt IAO:0000013 PMID:2901102 biolink:NamedThing omim.nt IAO:0000013 PMID:2911589 biolink:NamedThing omim.nt IAO:0000013 PMID:2914956 biolink:NamedThing omim.nt IAO:0000013 PMID:29981851 biolink:NamedThing omim.nt IAO:0000013 PMID:3009475 biolink:NamedThing omim.nt IAO:0000013 PMID:3081519 biolink:NamedThing omim.nt IAO:0000013 PMID:3338164 biolink:NamedThing omim.nt IAO:0000013 PMID:3353369 biolink:NamedThing omim.nt IAO:0000013 PMID:3474609 biolink:NamedThing omim.nt IAO:0000013 PMID:3478700 biolink:NamedThing omim.nt IAO:0000013 PMID:3479777 biolink:NamedThing omim.nt IAO:0000013 PMID:3578276 biolink:NamedThing omim.nt IAO:0000013 PMID:3678824 biolink:NamedThing omim.nt IAO:0000013 PMID:3828358 biolink:NamedThing omim.nt IAO:0000013 PMID:4027254 biolink:NamedThing omim.nt IAO:0000013 PMID:4168022 biolink:NamedThing omim.nt IAO:0000013 PMID:429006 biolink:NamedThing omim.nt IAO:0000013 PMID:4634450 biolink:NamedThing omim.nt IAO:0000013 PMID:4675003 biolink:NamedThing omim.nt IAO:0000013 PMID:4748758 biolink:NamedThing omim.nt IAO:0000013 PMID:5009795 biolink:NamedThing omim.nt IAO:0000013 PMID:5365516 biolink:NamedThing omim.nt IAO:0000013 PMID:5366285 biolink:NamedThing omim.nt IAO:0000013 PMID:5444873 biolink:NamedThing omim.nt IAO:0000013 PMID:5641132 biolink:NamedThing omim.nt IAO:0000013 PMID:5661865 biolink:NamedThing omim.nt IAO:0000013 PMID:5687087 biolink:NamedThing omim.nt IAO:0000013 PMID:5694042 biolink:NamedThing omim.nt IAO:0000013 PMID:5766779 biolink:NamedThing omim.nt IAO:0000013 PMID:5798598 biolink:NamedThing omim.nt IAO:0000013 PMID:5917081 biolink:NamedThing omim.nt IAO:0000013 PMID:5926635 biolink:NamedThing omim.nt IAO:0000013 PMID:5927876 biolink:NamedThing omim.nt IAO:0000013 PMID:5971057 biolink:NamedThing omim.nt IAO:0000013 PMID:6052735 biolink:NamedThing omim.nt IAO:0000013 PMID:6072616 biolink:NamedThing omim.nt IAO:0000013 PMID:6085063 biolink:NamedThing omim.nt IAO:0000013 PMID:6155699 biolink:NamedThing omim.nt IAO:0000013 PMID:6174977 biolink:NamedThing omim.nt IAO:0000013 PMID:6192711 biolink:NamedThing omim.nt IAO:0000013 PMID:6275391 biolink:NamedThing omim.nt IAO:0000013 PMID:6292049 biolink:NamedThing omim.nt IAO:0000013 PMID:6328518 biolink:NamedThing omim.nt IAO:0000013 PMID:677290 biolink:NamedThing omim.nt IAO:0000013 PMID:6800289 biolink:NamedThing omim.nt IAO:0000013 PMID:683332 biolink:NamedThing omim.nt IAO:0000013 PMID:6897630 biolink:NamedThing omim.nt IAO:0000013 PMID:6933567 biolink:NamedThing omim.nt IAO:0000013 PMID:7166310 biolink:NamedThing omim.nt IAO:0000013 PMID:7180851 biolink:NamedThing omim.nt IAO:0000013 PMID:7213917 biolink:NamedThing omim.nt IAO:0000013 PMID:7266640 biolink:NamedThing omim.nt IAO:0000013 PMID:7297678 biolink:NamedThing omim.nt IAO:0000013 PMID:7882997 biolink:NamedThing omim.nt IAO:0000013 PMID:7902134 biolink:NamedThing omim.nt IAO:0000013 PMID:8022807 biolink:NamedThing omim.nt IAO:0000013 PMID:8048949 biolink:NamedThing omim.nt IAO:0000013 PMID:8064810 biolink:NamedThing omim.nt IAO:0000013 PMID:8134387 biolink:NamedThing omim.nt IAO:0000013 PMID:8347685 biolink:NamedThing omim.nt IAO:0000013 PMID:8513793 biolink:NamedThing omim.nt IAO:0000013 PMID:9329347 biolink:NamedThing omim.nt IAO:0000013 PMID:9589637 biolink:NamedThing omim.nt IAO:0000013 OBO:CHR_9606chr4q11 biolink:NamedThing omim.nt owl:Class http://omim.org/entry/615999 biolink:NamedThing|biolink:Disease Hyperthyroxinemia, Familial Dysalbuminemic Hyperthyroxinemia, Familial Dysalbuminemic omim.nt HYPERTHYROXINEMIA, FAMILIAL DYSALBUMINEMIC; FDAH|Euthyroid Hyperthyroxinemia 1|Fdh owl:Class http://omim.org/entry/616000 biolink:NamedThing|biolink:Disease Analbuminemia Analbuminemia omim.nt ANALBUMINEMIA; ANALBA owl:Class UMLS:C1412332 biolink:NamedThing omim.nt owl:Class https://www.ncbi.nlm.nih.gov/gene/213 biolink:NamedThing omim.nt http://omim.org/entry/103700 biolink:NamedThing|biolink:Gene ADH1A Alcohol Dehydrogenase 1A, Class I, Alpha Polypeptide omim.nt ALCOHOL DEHYDROGENASE 1A, CLASS I, ALPHA POLYPEPTIDE; ADH1A|Adh, Alpha Subunit|Alcohol Dehydrogenase 1 owl:Class MONARCH:.well-known/genid/be011136d78e3e81c2e4 biolink:NamedThing GRCh38chr4-99276368-99290984-Region omim.nt MONARCH:.well-known/genid/b9c19f6dcccdcf0c4139 faldo:Region MONARCH:.well-known/genid/OMIM103700ref13 biolink:NamedThing Derivation of probes for molecular genetic analysis of human class I alcohol dehydrogenase (ADH), a polymorphic gene family on chromosome 4. (Abstract) omim.nt IAO:0000310 MONARCH:.well-known/genid/OMIM103700ref14 biolink:NamedThing Assignment of ADH1, ADH2 and ADH3 genes (class I ADH) to human chromosome 4q21-4q25, through use of DNA probes. (Abstract) omim.nt IAO:0000310 MONARCH:.well-known/genid/OMIM103700ref17 biolink:NamedThing Studies on the properties of the human alcohol dehydrogenase isozymes determined by the different loci ADH(1), ADH(2) and ADH(3). omim.nt IAO:0000310 MONARCH:.well-known/genid/OMIM103700ref23 biolink:NamedThing Personal Communication. omim.nt IAO:0000310 MONARCH:.well-known/genid/OMIM103700ref26 biolink:NamedThing The organization of human class I alcohol dehydrogenase gene cluster. (Abstract) omim.nt IAO:0000310 MONARCH:.well-known/genid/OMIM103700ref28 biolink:NamedThing Molecular characterization of cDNA clones encoding the human alcohol dehydrogenase beta-1 and the evolutionary relationship to the other class I subunits alpha and gamma. omim.nt IAO:0000310 MONARCH:.well-known/genid/OMIM103700ref4 biolink:NamedThing Atlas of Protein Sequence and Structure. Dehydrogenases. Vol. 5. omim.nt IAO:0000310 PMID:10697413 biolink:NamedThing omim.nt IAO:0000013 PMID:1200030 biolink:NamedThing omim.nt IAO:0000013 PMID:12050823 biolink:NamedThing omim.nt IAO:0000013 PMID:17718394 biolink:NamedThing omim.nt IAO:0000013 PMID:230779 biolink:NamedThing omim.nt IAO:0000013 PMID:2347582 biolink:NamedThing omim.nt IAO:0000013 PMID:2737681 biolink:NamedThing omim.nt IAO:0000013 PMID:2748595 biolink:NamedThing omim.nt IAO:0000013 PMID:2934088 biolink:NamedThing omim.nt IAO:0000013 PMID:2935875 biolink:NamedThing omim.nt IAO:0000013 PMID:3006456 biolink:NamedThing omim.nt IAO:0000013 PMID:3013304 biolink:NamedThing omim.nt IAO:0000013 PMID:4313164 biolink:NamedThing omim.nt IAO:0000013 PMID:4504607 biolink:NamedThing omim.nt IAO:0000013 PMID:4748759 biolink:NamedThing omim.nt IAO:0000013 PMID:5548434 biolink:NamedThing omim.nt IAO:0000013 PMID:655629 biolink:NamedThing omim.nt IAO:0000013 PMID:8279483 biolink:NamedThing omim.nt IAO:0000013 PMID:8834044 biolink:NamedThing omim.nt IAO:0000013 PMID:9982 biolink:NamedThing omim.nt IAO:0000013 OBO:CHR_9606chr4q22 biolink:NamedThing omim.nt owl:Class UMLS:C1412235 biolink:NamedThing omim.nt owl:Class https://www.ncbi.nlm.nih.gov/gene/124 biolink:NamedThing omim.nt http://omim.org/entry/103710.0001 biolink:NamedThing ADH5, 1-BP DEL, 966G In 5 children from 3 unrelated Japanese families (families 1, 4, and 6), with AMED syndrome (AMEDS; {619151}), {16:Oka et al. (2020)} identified a homozygous 1-bp deletion (c.966delG) in exon 8 of the ADH5 gene, resulting in a frameshift and premature termination (trp322 to ter, W322X). Four additional patients (from families 3, 5, 7, and 8) with the disorder were compound heterozygous for W322X and a c.832G-C transversion in exon 7 of the ADH5 gene, resulting in an ala278-to-pro (A278P; {103710.0003}) substitution. All patients also carried a homozygous or heterozygous E504K variant in the ALDH2 gene ({100650.0001}), resulting in deficiency of that enzyme and confirming a digenic disorder. The mutations, which were found by whole-exome sequencing (ADH5) or direct sequencing (ALDH2), segregated with the disorders in the families in whom parental DNA was available. No homozygous ADH5 loss-of-function variants were identified in gnomAD or in several large Japanese control databases. Immunoblot analysis of fibroblasts from some of the patients showed a significant reduction in ADH5 protein levels compared to controls, consistent with a loss-of-function effect. Patient cells showed increased sensitivity to formaldehyde treatment and inhibition of DNA replication compared to controls. omim.nt GENO:0000002 http://omim.org/entry/103710 biolink:NamedThing|biolink:Gene ADH5 Alcohol Dehydrogenase 5, Chi Polypeptide|AMEDS is digenic with ALDH2 omim.nt ALCOHOL DEHYDROGENASE 5, CHI POLYPEPTIDE; ADH5|Adh, Class 3|Alcohol Dehydrogenase, Chi Isozyme|Formaldehyde Dehydrogenase|Formaldehyde Dehydrogenase, Glutathione-Dependent|S-Nitrosoglutathione Reductase owl:Class ClinVar:RCV001290002 biolink:NamedThing omim.nt http://omim.org/entry/103710#0001 biolink:NamedThing omim.nt http://omim.org/entry/103710.0002 biolink:NamedThing ADH5, IVS5DS, G-A, +1 In a Japanese girl (patient N0611) with AMED syndrome (AMEDS; {619151}), {16:Oka et al. (2020)} identified compound heterozygous mutations in the ADH5 gene: a G-to-A transition in intron 5 (c.564+1G-A) of the ADH5 gene, resulting in a splice site defect, and A278P ({103710.0003}). She also carried a heterozygous E504K variant in the ALDH2 gene ({100650.0001}), resulting in deficiency of that enzyme and confirming a digenic disorder. The mutations, which were found by whole-exome sequencing (ADH5) or direct sequencing (ALDH2), segregated with the disorder in the family. Immunoblot analysis of patient fibroblasts showed a significant reduction in ADH5 protein levels compared to controls, consistent with a loss-of-function effect. Patient cells showed increased sensitivity to formaldehyde treatment and inhibition of DNA replication compared to controls. omim.nt GENO:0000002 ClinVar:RCV001290003 biolink:NamedThing omim.nt http://omim.org/entry/103710#0002 biolink:NamedThing omim.nt http://omim.org/entry/103710.0003 biolink:NamedThing ADH5, ALA278PRO For discussion of the c.832G-C transversion in exon 7 of the ADH5 gene, resulting in an ala278-to-pro (A278P) substitution, that was found in compound heterozygous state in 5 unrelated Japanese patients with AMED syndrome (AMEDS; {619151}) by {16:Oka et al. (2020)}, see {103710.0001} and {103710.0002}. omim.nt GENO:0000002 ClinVar:RCV001290004 biolink:NamedThing omim.nt http://omim.org/entry/103710#0003 biolink:NamedThing omim.nt MONARCH:.well-known/genid/b45e386f3b2022c49066 biolink:NamedThing GRCh38chr4-99070977-99088787-Region omim.nt MONARCH:.well-known/genid/b8337774d82caedec99d faldo:Region MONARCH:.well-known/genid/OMIM103710ref20 biolink:NamedThing Formaldehyde dehydrogenase and chromosome 4. (Abstract) omim.nt IAO:0000310 MONARCH:.well-known/genid/OMIM103710ref21 biolink:NamedThing Localization of human FDH to 4q21-qter. (Abstract) omim.nt IAO:0000310 MONARCH:.well-known/genid/OMIM103710ref4 biolink:NamedThing Assignment of the gene coding for class III ADH to human chromosome 4: 4q21-4q25. (Abstract) omim.nt IAO:0000310 MONARCH:.well-known/genid/OMIM103710ref7 biolink:NamedThing Class III alcohol dehydrogenase (ADH5): widespread expression and synteny with other ADHs in both mouse and man. (Abstract) omim.nt IAO:0000310 MONARCH:.well-known/genid/OMIM103710ref8 biolink:NamedThing Regional assignment of human formaldehyde dehydrogenase (FDH) to 4q21-4q25. (Abstract) omim.nt IAO:0000310 PMID:11260719 biolink:NamedThing omim.nt IAO:0000013 PMID:1446828 biolink:NamedThing omim.nt IAO:0000013 PMID:14980227 biolink:NamedThing omim.nt IAO:0000013 PMID:15919956 biolink:NamedThing omim.nt IAO:0000013 PMID:1783415 biolink:NamedThing omim.nt IAO:0000013 PMID:1872853 biolink:NamedThing omim.nt IAO:0000013 PMID:2294756 biolink:NamedThing omim.nt IAO:0000013 PMID:2679557 biolink:NamedThing omim.nt IAO:0000013 PMID:2806555 biolink:NamedThing omim.nt IAO:0000013 PMID:2818582 biolink:NamedThing omim.nt IAO:0000013 PMID:2934732 biolink:NamedThing omim.nt IAO:0000013 PMID:6424546 biolink:NamedThing omim.nt IAO:0000013 PMID:6467984 biolink:NamedThing omim.nt IAO:0000013 PMID:8460164 biolink:NamedThing omim.nt IAO:0000013 OBO:CHR_9606chr4q21 biolink:NamedThing omim.nt owl:Class http://omim.org/entry/619151 biolink:NamedThing|biolink:Disease Amed Syndrome, Digenic Amed Syndrome, Digenic omim.nt AMED SYNDROME, DIGENIC; AMEDS|Bone Marrow Failure Syndrome 7, Digenic owl:Class http://www.omim.org/phenotypicSeries/PS614675 biolink:NamedThing|biolink:Disease Bone marrow failure syndrome omim.nt owl:Class UMLS:C1412239 biolink:NamedThing omim.nt owl:Class https://www.ncbi.nlm.nih.gov/gene/128 biolink:NamedThing omim.nt http://omim.org/entry/103720.0001 biolink:NamedThing ADH1B, ARG48HIS, ({dbSNP rs1229984}) The ARG47HIS variant has been designated as R48H based on numbering which includes the translation initiation codon ({12:Edenberg, 2007}). The HIS variant is associated with more rapid ethanol oxidation to acetaldehyde compared to the ARG variant. The arg48 and his48 variants of ADH1B are often referred to as ADH1B*1 and ADH1B*2, respectively. However, {33:Osier et al. (2002)} noted that ADH1B*1 and ADH1B*2 are alleles that also include the ADH1B R370C variant ({103720.0002}). {24:Jornvall et al. (1984)} determined that the 'atypical' variant of ADH1B, commonly found in persons of Asian origin, results from an arg48-to-his (R48H) substitution in exon 3 of the gene, in a position that binds the pyrophosphate group of coenzyme NAD(H); this change explains the functional differences between the 2 isozymes, including both a lower pH optimum and higher turnover of the atypical variant. {30:Matsuo et al. (1989)} also showed that the 'typical' and 'atypical' forms of ADH1B differ by only a single amino acid: R48H, resulting from a G-to-A transition. The ADH1B*1 typical allele has an arg48 (CGC), whereas the ADH1B*2 atypical allele has his48 (CAC). The kinetic properties of the 2 variants in the coenzyme binding site were found to differ considerably: the V(max) of ethanol oxidation to acetaldehyde was increased by 100-fold in homozygotes for the his48 allele compared to homozygotes for the arg48 allele. Using site-directed mutagenesis, {21:Hurley et al. (1990)} studied the effects of substitution of lysine, histidine, glutamine, and glycine for arginine-48 in beta-1/beta-1. They expressed the enzymes in E. coli and compared their kinetics. Alcohol Dependence, Protection Against {32:Osier et al. (1999)} showed that the arg48-to-his (R48H) site of ADH1B is in linkage disequilibrium with the ADH1C ile350-to-val (I350V; {103730.0002}) site, and identified R48H as being responsible for differences in ethanol metabolism and alcoholism among Taiwanese, with the I350V site showing association only because of linkage disequilibrium. {35:Shea et al. (2001)} evaluated 84 Ashkenazi Jewish American college students to determine the prevalence of the ADH1B*2 allele (his48) (0.31). Carriers of the ADH1B*2 allele reported significantly fewer drinking days per month. ADH1B*2 was not related to alcohol use disorders, alcohol-induced flushing and associated symptoms, number of binge drinking episodes in the previous 90 days, maximum number of drinks ever consumed, or self-reported levels of response to alcohol. The results suggested that Ashkenazi Jewish Americans with ADH1B*2 alleles drink less frequently, which may contribute to the overall lower rates of alcohol dependence ({103780}) in this population. {6:Carr et al. (2002)} studied the ADH1B polymorphisms in 4 groups of Jewish subjects (males and females in college age and general populations) to determine whether there was an association between the ADH1B*2 allele, which has a higher frequency in Jewish than in other Caucasian groups, and alcohol consumption. Both groups of men with the ADH1B*2 allele reported more unpleasant reactions following alcohol consumption. Men in the general population with the ADH1B*2 allele drank alcohol less frequently; there was a similar trend among women. The college students consumed considerably more alcohol than the general population, suggesting that social setting and age have a stronger influence on alcohol drinking than the ADH1B*2 effect. {43:Whitfield (2002)} commented on differences in the effects of the R47H mutation between Europeans and 2 major east Asian populations, Chinese and Japanese, and offered explanations. {25:Kidd et al. (2002)} disagreed with some of the conclusions of {43:Whitfield (2002)} and offered other explanations. {38:Suzuki et al. (2004)} found an association between the ADH1B*1 allele and increased risk of lacunae and cerebral infarction in a cohort of over 1,000 Japanese men. The association was not seen in women. {7:Chai et al. (2005)} examined ADH1B, ADH1C ({103730}), and ALDH2 ({100650}) polymorphisms in 72 alcoholic and 38 nonalcoholic healthy Korean men. Forty-eight of the alcoholic men had Cloninger type 1 and 24 had Cloninger type 2 alcoholism (see {103780}). The frequency of ADH1B*1 and ADH1C*2 (see {103730.0001}) alleles was significantly higher in men with type 2 alcoholism than in men with type 1 alcoholism and in healthy men. The frequency of the ALDH2*1 ({100650.0001}) allele was significantly higher in men with alcohol dependence than in healthy men. {7:Chai et al. (2005)} suggested that the genetic characteristics of alcohol metabolism in type I alcoholism fall between nonalcoholism and type II alcoholism. Because the common belief that selection has operated on the ADH1B his48 allele in East Asian populations lacks direct biologic or statistical evidence, {14:Han et al. (2007)} used genomic data to test the hypothesis. Data consisted of 54 SNPs across the ADH clusters in a global sampling of 42 populations. Both the F(st) statistic and the long-range haplotype (LRH) test provided positive evidence of selection in several East Asian populations. The ADH1B R48H functional polymorphism had the highest F(st) of the 54 SNPs in the ADH cluster, and it was significantly above the mean F(st) of 382 presumably neutral sites tested on the same 42 population samples. The LRH test that used cores including that site and extending on both sides also gave significant evidence of positive selection in some East Asian populations for a specific haplotype carrying the ADH1B his48 allele. Interestingly, this haplotype is present in high frequency in only some East Asian populations, whereas the specific allele also exists in other East Asian populations and in the Near East and Europe but does not show evidence of selection with use of the LRH test. Although the ADH1B his48 allele conveys a well-confirmed protection against alcoholism, that modern phenotypic manifestation does not easily translate into a positive selective force, and the nature of that selective force remained speculative. The ADH1B R48H polymorphism ({dbSNP rs1229984}) is the SNP generally regarded as the most important with respect to alcoholism (or alcoholism protection) in the ADH gene family in Asia. The his48 frequency is particularly high in eastern Asian populations, often exceeding 80%, but the allele is almost absent in sub-Saharan, European, and Native American populations. The high frequency of the derived allele in Asia could have resulted from either of 2 possible evolutionary processes: (1) a selective advantage existing only in eastern Asia for the allele, or (2) random genetic drift increasing the frequency of the allele in eastern Asia. {28:Li et al. (2007)} pointed to the high frequency of the his48 allele not only in eastern Asian populations but also in southwestern Asia and in populations deriving from southwestern Asia. In a metaanalysis, {28:Li et al. (2007)} reported new frequency data confirming the observation that there is a low frequency of this allele in the region between eastern and western Asia. In western Asia, the highest frequencies were found in the Persians, Turks, Samaritans, and Jewish individuals from a variety of regions. The distribution suggested that the derived allele increased in frequency independently in western and eastern Asia after humans had spread across Eurasia. Among 9,080 Caucasian Danish men and women, {40:Tolstrup et al. (2008)} found that men and women homozygous for the slower metabolizing arg48 allele had a higher alcohol intake compared to those with the his48 allele. Individuals with the arg48 allele also had higher rates of alcoholism and alcohol-related hospitalizations. Among 1,032 Korean individuals, {26:Kim et al. (2008)} found that the combination of the ADH1B his48 allele and the ALDH2 lys504 allele ({100650.0001}) offered protection against alcoholism. Individuals who carried both susceptibility alleles (arg48 and glu504, respectively) had a significantly increased risk for alcoholism (OR, 91.43; p = 1.4 x 10(-32)). Individuals with 1 protective and 1 susceptibility allele had a lesser increased risk for alcoholism (OR, 11.40; p = 3.5 x 10(-15)) compared to those with both protective alleles. {26:Kim et al. (2008)} calculated that alcoholism in the Korean population is 86.5% attributable to the detrimental effect of the ADH1B arg48 and the ALDH2 glu504 alleles. {2:Borinskaya et al. (2009)} presented population frequencies for central Asia and Siberia that differed slightly from previous reports, particularly that of {28:Li et al. (2007)}. {2:Borinskaya et al. (2009)} found a mean frequency of 4.9% among 1,019 Russian individuals, and 20.4% among the southern Turkmen near northern Iran, both lower than reported by {28:Li et al. (2007)}. The overall allele frequencies of 3,408 individuals in 46 additional populations from southwest Asia was closer to those in central Asia (19% to 32%), suggesting a less pronounced discontinuity between west and east Asia. {2:Borinskaya et al. (2009)} presented a refined geographic map of the distribution of the R48H allele including 172 populations from Africa and Eurasia. The southwest Asian local maximum reaches 30% frequency and is connected with the southeast Asian maximum via the Asian steppe belt, where the average allele frequency is 20 to 30%. The frequency from the steppe region toward the North and West declines gradually to 10 to 16% in populations across the Caucasus and Volga-Ural regions, with the exception of the Kalmyk population (26.3%), who have ancestor roots from Mongol-Oirat tribes who migrated from central Asia approximately 300 years ago. In a response, {27:Li and Kidd (2009)} agreed that there is a more continuous low-frequency distribution of the his48 allele across central Asia. However, haplotype analysis suggested that the his48 allele occurred on 2 haplotypes in western Asia that were not seen in eastern Asia. They presented additional frequencies for western Asia, and noted that the frequency is always higher in Jewish populations from Africa, Europe, and the Middle East (26 to 41%) and the Druze population (27%) than in Arab populations (9.5 to 15.7%). The population frequency of his48, which has now reached over 300 different populations, continues to be collected and deposited in an online resource (ALFRED). {29:Macgregor et al. (2009)} tested for associations between 9 polymorphisms in the ALDH2 gene and 41 in the ADH genes, and alcohol-related flushing, alcohol use, and dependence symptom scores in 4,597 Australian twins, predominantly of European ancestry. The vast majority (4,296 individuals) had consumed alcohol in the previous year, with 547 meeting DSM-IIIR criteria for alcohol dependence. There were study-wide significant associations between {dbSNP rs1229984} and flushing and consumption, but only nominally significant associations (p less than 0.01) with alcohol dependence. Individuals carrying the G allele/arg48 reported a lower prevalence of flushing after alcohol, consumed alcohol on more occasions, had a higher maximum number of alcoholic drinks in a single day and a higher overall alcohol consumption in the previous year than those with the less common A allele/his48. After controlling for {dbSNP rs1229984}, an independent association was observed between {dbSNP rs1042026} in the ADH1B gene and alcohol intake and suggestive associations between alcohol consumption phenotypes and {dbSNP rs1693482} in the ADH1C gene (see {103730.0001}), {dbSNP rs1230165} (ADH5; {103710}) and {dbSNP rs3762894} (ADH4; {103740}). ALDH2 variation was not associated with flushing or alcohol consumption, but was weakly associated with alcohol dependence measures. These results bridge the gap between DNA sequence variation and alcohol-related behavior, confirming that the ADH1B R48H polymorphism affects both alcohol-related flushing in Europeans and alcohol intake. Alcohol-Related Aerodigestive Tract Cancer, Protection Against Cancers of the upper aerodigestive tract, comprising the oral cavity, pharynx, larynx, and esophagus, are common cancers. Taken together, they account for 5.2% of all cancer cases worldwide. Tobacco and alcohol represent important risk factors for these cancers, with evidence of a synergistic interaction. The mechanism for alcohol drinking as a risk factor of upper aerodigestive tract cancers is unclear: it may act as a solvent for tobacco carcinogens, or it is also possible that acetaldehyde, the metabolite of ethanol, is the primary carcinogen ({16:Hashibe et al., 2006}). {17:Hashibe et al. (2008)} genotyped 6 genetic variants of the alcohol dehydrogenase genes (ADH) in 3 cohorts from Europe and Latin America, including an expanded central European study group previously reported by {16:Hashibe et al. (2006)}. The total study population comprised 3,876 patients with squamous cell cancer of the aerodigestive tract, including 1,790 cancers of the oral cavity or pharynx, 1,659 of the hypopharynx or larynx, and 427 cancers of the esophagus, and 5,278 controls. A significant protective effect was observed for {dbSNP rs1229984} in the ADH1B gene (R48H) with a combined p value of 8.0 x 10(-10) and for {dbSNP rs1573496} in the ADH7 gene ({600086}) with a combined p value of 3.0 x 10(-9). Although both the ADH1B and ADH7 genes map to the same cluster on chromosome 4q22, there was no evidence of linkage disequilibrium between these 2 variants, indicating independent effects. Stratification by cancer type showed heterogeneity: the highest protection offered by the ADH1B R48H was against laryngeal cancer, whereas the highest protection offered by the ADH7 SNP was against esophageal cancer ({133239}). For both variants, there was an increasing protective effect with increasing alcohol consumption ({103780}); in fact there was no protective effect in never-drinkers for either variant. The data suggested that the protective effects of these gene-environment interactions was due to their role in changing the carcinogenic effects of alcohol. omim.nt GENO:0000002 http://omim.org/entry/103720 biolink:NamedThing|biolink:Gene ADH1B Alcohol Dehydrogenase 1B, Class I, Beta Polypeptide omim.nt ALCOHOL DEHYDROGENASE 1B, CLASS I, BETA POLYPEPTIDE; ADH1B|Adh, Beta Subunit|Alcohol Dehydrogenase 2 owl:Class ClinVar:RCV000019813 biolink:NamedThing omim.nt ClinVar:RCV000019814 biolink:NamedThing omim.nt dbSNP:rs1229984 biolink:NamedThing omim.nt owl:NamedIndividual http://omim.org/entry/103720#0001 biolink:NamedThing omim.nt http://omim.org/entry/103720.0002 biolink:NamedThing ADH1B, ARG370CYS The ARG369CYS variant has been designated as R370C ({dbSNP rs2066702}) based on numbering which includes the translation initiation codon ({12:Edenberg, 2007}). The cys369 variant of ADH1B is often referred to as ADH1B*3. However, {12:Edenberg (2007)} noted that ADH1B*3 is an allele that also includes the arg48 ADH1B variant ({103720.0001}). {3:Bosron et al. (1980)} described a novel molecular isoform of human ADH1B, designated ADH(Indianapolis), in 29% of liver specimens from African Americans. {4:Bosron et al. (1983)} found that the frequency of the Indianapolis variant was 0.16 in African Americans and was not found in any of 63 livers from white Americans. {1:Agarwal et al. (1981)} could find no instance of the Indianapolis variant in Germany or Japan. {5:Burnell et al. (1987)} demonstrated that the variant observed in African Americans results from an arg370-to-cys substitution in exon 9 of the ADH1B gene: they referred to this variant as ADH1B*3. {5:Burnell et al. (1987)} predicted that arg370 interacts with the nicotinamide phosphate moiety of NAD(H) and that this accounts for the effect of the R370C substitution in decreasing the isoenzyme's affinity for coenzyme, which results in higher turnover rate during ethanol oxidation. {10:Edenberg et al. (2006)} presented evidence suggesting that the ADH1B*3 allele has a protective effect against alcohol dependence (see {103780}) among African Americans. omim.nt GENO:0000002 ClinVar:RCV000019815 biolink:NamedThing omim.nt dbSNP:rs2066702 biolink:NamedThing omim.nt owl:NamedIndividual http://omim.org/entry/103720#0002 biolink:NamedThing omim.nt MONARCH:.well-known/genid/b53b821fbaaaf09aea94 biolink:NamedThing GRCh38chr4-99304970-99321400-Region omim.nt MONARCH:.well-known/genid/b89ab0be391a1f910f3b faldo:Region MONARCH:.well-known/genid/OMIM103720ref25 biolink:NamedThing Reply to Whitfield. (Letter) omim.nt IAO:0000310 MONARCH:.well-known/genid/OMIM103720ref27 biolink:NamedThing Low allele frequency of ADH1B*47his in west China and different ADH1B haplotypes in western and eastern Asia. (Letter) omim.nt IAO:0000310 MONARCH:.well-known/genid/OMIM103720ref34 biolink:NamedThing Human Polymorphic Genes: World Distribution. omim.nt IAO:0000310 MONARCH:.well-known/genid/OMIM103720ref46 biolink:NamedThing Molecular characterization of cDNA clones encoding the human alcohol dehydrogenase beta-1 and the evolutionary relationship to the other class I subunits alpha and gamma. omim.nt IAO:0000310 PMID:10090900 biolink:NamedThing omim.nt IAO:0000013 PMID:11545539 biolink:NamedThing omim.nt IAO:0000013 PMID:12244546 biolink:NamedThing omim.nt IAO:0000013 PMID:12452180 biolink:NamedThing omim.nt IAO:0000013 PMID:15534263 biolink:NamedThing omim.nt IAO:0000013 PMID:16571603 biolink:NamedThing omim.nt IAO:0000013 PMID:16614111 biolink:NamedThing omim.nt IAO:0000013 PMID:17273965 biolink:NamedThing omim.nt IAO:0000013 PMID:17847010 biolink:NamedThing omim.nt IAO:0000013 PMID:17923853 biolink:NamedThing omim.nt IAO:0000013 PMID:18500343 biolink:NamedThing omim.nt IAO:0000013 PMID:18996923 biolink:NamedThing omim.nt IAO:0000013 PMID:19124091 biolink:NamedThing omim.nt IAO:0000013 PMID:2398055 biolink:NamedThing omim.nt IAO:0000013 PMID:2547609 biolink:NamedThing omim.nt IAO:0000013 PMID:2986130 biolink:NamedThing omim.nt IAO:0000013 PMID:3000832 biolink:NamedThing omim.nt IAO:0000013 PMID:3397059 biolink:NamedThing omim.nt IAO:0000013 PMID:3619918 biolink:NamedThing omim.nt IAO:0000013 PMID:6330735 biolink:NamedThing omim.nt IAO:0000013 PMID:6354175 biolink:NamedThing omim.nt IAO:0000013 PMID:6370230 biolink:NamedThing omim.nt IAO:0000013 PMID:6374651 biolink:NamedThing omim.nt IAO:0000013 PMID:7003596 biolink:NamedThing omim.nt IAO:0000013 PMID:7035335 biolink:NamedThing omim.nt IAO:0000013 PMID:8834233 biolink:NamedThing omim.nt IAO:0000013 PMID:8834237 biolink:NamedThing omim.nt IAO:0000013 http://omim.org/entry/103780 biolink:NamedThing|biolink:Disease Alcohol Dependence Alcohol Dependence omim.nt ALCOHOL DEPENDENCE|Aerodigestive Tract Cancer, Squamous Cell, Alcohol-Related, Protection Against|Alcohol Dependence, Protection Against|Alcoholism owl:Class UMLS:C1412236 biolink:NamedThing omim.nt owl:Class https://www.ncbi.nlm.nih.gov/gene/125 biolink:NamedThing omim.nt http://omim.org/entry/103730.0001 biolink:NamedThing ADH1C, ARG272GLN ({dbSNP rs1693482}) The ARG271GLN variant has been designated as R272Q based on numbering which includes the translation initiation codon ({6:Edenberg, 2007}). {9:Hoog et al. (1986)} found 2 amino acid differences between the gamma-1 and gamma-2 alleles: an arg272-to-gln ({dbSNP rs1693482}) substitution in exon 6 and an ile350-to-val (I350V; {103730.0002}) substitution in exon 8 of the ADH1C gene. They determined that the R272Q substitution was responsible for the differences in enzymatic properties, whereas the I350V substitution had no special importance. The location of R272Q appeared important for total charge and catalytic properties, as well as NADH coenzyme interaction. The gamma-1 allele, now known as ADH1C*1, was originally defined as a gamma subunit that has arg272 and ile350 ({9:Hoog et al., 1986}). In almost all cases, these 2 SNPs are in linkage disequilibrium with one another. The gamma-2 allele, now known as ADH1C*2, has gln272 and val350. Homozygosity for the ADH1C*1 allele has a 70% higher turnover rate than homozygosity for ADH1C*2 allele ({6:Edenberg, 2007}). {5:Chai et al. (2005)} examined ADH1B, ADH1C, and ALDH2 polymorphisms in 72 alcoholic and 38 nonalcoholic healthy Korean men; 48 patients had type I alcoholism, and 24 had type II alcoholism. The frequency of ADH1B*1 ({103720.0001}) and ADH1C*2 alleles was significantly higher in men with type II alcoholism than in men with type I alcoholism and in healthy men. The frequency of the ALDH2*1 ({100650.0001}) allele was significantly higher in men with alcohol dependence ({103780}) than in healthy men. {5:Chai et al. (2005)} suggested that the genetic characteristics of alcohol metabolism in type I alcoholism fall between nonalcoholism and type II alcoholism. Among 9,080 Caucasian Danish men and women using the Michigan Alcohol Screening Test, {17:Tolstrup et al. (2008)} found that men heterozygous or homozygous for the slower metabolizing ADH1C*2 allele had a 40 to 70% higher risk for heavy or excessive alcohol intake compared to those homozygous for the fast metabolizing ADH1C*1 allele. Similar results were found for women, but effect sizes were smaller and reached significance only for heavy drinking. omim.nt GENO:0000002 http://omim.org/entry/103730 biolink:NamedThing|biolink:Gene ADH1C Alcohol Dehydrogenase 1C, Gamma Polypeptide omim.nt ALCOHOL DEHYDROGENASE 1C, GAMMA POLYPEPTIDE; ADH1C|Adh, Gamma Subunit|Alcohol Dehydrogenase 3 owl:Class ClinVar:RCV000019810 biolink:NamedThing omim.nt dbSNP:rs1693482 biolink:NamedThing omim.nt owl:NamedIndividual http://omim.org/entry/103730#0001 biolink:NamedThing omim.nt http://omim.org/entry/103730.0002 biolink:NamedThing ADH1C, ILE350VAL ({dbSNP rs698}) The ILE349VAL variant has been designated as I350V based on numbering which includes the translation initiation codon ({6:Edenberg, 2007}). {9:Hoog et al. (1986)} found 2 amino acid differences between the gamma-1 and gamma-2 alleles: an arg271-to-gln (R271Q; {103730.0001}) substitution in exon 6 and an ile349-to-val ({dbSNP rs698}) substitution in exon 8 of the ADH1C gene. They determined that the R272Q substitution was responsible for the differences in enzymatic properties, whereas the I350V substitution had no special importance. The location of R272Q appeared important for total charge and catalytic properties, as well as NADH coenzyme interaction. The gamma-1 allele, now known as ADH1C*1, was originally defined as a gamma subunit that has arg272 and ile350 ({9:Hoog et al., 1986}). In almost all cases, these 2 SNPs are in linkage disequilibrium with one another. The gamma-2 allele, now known as ADH1C*2, has gln272 and val350. Homozygosity for the ADH1C*1 allele has a 70% higher turnover rate than homozygosity for ADH1C*2 allele ({6:Edenberg, 2007}). {18:Xu et al. (1988)} used the I350V substitution to distinguish ADH1C*1 from ADH1C*2 by means of allele-specific oligonucleotide probes. {13:Osier et al. (1999)} showed that I350V substitution is in linkage disequilibrium with the ADH1B arg48-to-his (R48H; {103720.0001}) substitution, and identified the R48H variant as being responsible for differences in ethanol metabolism and alcoholism ({103780}) among Taiwanese, with the I350V variant showing association only because of linkage disequilibrium. {5:Chai et al. (2005)} examined ADH1B, ADH1C, and ALDH2 polymorphisms in 72 alcoholic and 38 nonalcoholic healthy Korean men; 48 patients had type I alcoholism, and 24 had type II alcoholism. The frequency of ADH1B*1 ({103720.0001}) and ADH1C*2 alleles was significantly higher in men with type II alcoholism ({103780}) than in men with type I alcoholism and in healthy men. The frequency of the ALDH2*1 ({100650.0001}) allele was significantly higher in men with alcohol dependence than in healthy men. {5:Chai et al. (2005)} suggested that the genetic characteristics of alcohol metabolism in type I alcoholism fall between nonalcoholism and type II alcoholism. Among 9,080 Caucasian Danish men and women using the Michigan Alcohol Screening Test, {17:Tolstrup et al. (2008)} found that men heterozygous or homozygous for the slower metabolizing ADH1C*2 allele had a 40 to 70% higher risk for heavy or excessive alcohol intake compared to those homozygous for the fast metabolizing ADH1C*1 allele. Similar results were found for women, but effect sizes were smaller and reached significance only for heavy drinking. omim.nt GENO:0000002 ClinVar:RCV000019811 biolink:NamedThing omim.nt dbSNP:rs698 biolink:NamedThing omim.nt owl:NamedIndividual http://omim.org/entry/103730#0002 biolink:NamedThing omim.nt http://omim.org/entry/103730.0003 biolink:NamedThing ADH1C, GLY78TER {3:Buervenich et al. (2005)} found an association between a G-to-T transversion in exon 3 of the ADH1C gene ({dbSNP rs283413}), resulting in a gly78-to-ter (G78X) polymorphism, and the development of Parkinson disease ({168600}). The G78X substitution was found in 22 (2%) of 1,076 PD patients of European ancestry and 6 (0.6%) of 940 controls, which was statistically significant and conferred an odds ratio of 3.25 for development of the disease. In addition, the G78X variant was identified in 4 (10%) of 40 Caucasian index PD patients, 3 of whom had a family history of the disorder. {3:Buervenich et al. (2005)} noted that ADH1C plays a role in detoxification, and suggested that defects in this enzyme may render some individuals more susceptible to environmental toxins, which may contribute to the development of PD. omim.nt GENO:0000002 ClinVar:RCV000019812 biolink:NamedThing omim.nt dbSNP:rs283413 biolink:NamedThing omim.nt owl:NamedIndividual http://omim.org/entry/103730#0003 biolink:NamedThing omim.nt MONARCH:.well-known/genid/b2eaa100c34efb8c39a0 biolink:NamedThing GRCh38chr4-99336496-99352745-Region omim.nt MONARCH:.well-known/genid/bc1d0a9b0eebaa85c70c faldo:Region MONARCH:.well-known/genid/OMIM103730ref11 biolink:NamedThing A new chromosome 4q marker, D4S138, closely linked to the ADH3 locus. (Abstract) omim.nt IAO:0000310 MONARCH:.well-known/genid/OMIM103730ref14 biolink:NamedThing Human Polymorphic Genes: World Distribution. omim.nt IAO:0000310 PMID:11207350 biolink:NamedThing omim.nt IAO:0000013 PMID:1275443 biolink:NamedThing omim.nt IAO:0000013 PMID:12884000 biolink:NamedThing omim.nt IAO:0000013 PMID:15642852 biolink:NamedThing omim.nt IAO:0000013 PMID:19193628 biolink:NamedThing omim.nt IAO:0000013 PMID:3758060 biolink:NamedThing omim.nt IAO:0000013 PMID:5072686 biolink:NamedThing omim.nt IAO:0000013 PMID:518534 biolink:NamedThing omim.nt IAO:0000013 PMID:6387702 biolink:NamedThing omim.nt IAO:0000013 PMID:9126489 biolink:NamedThing omim.nt IAO:0000013 http://omim.org/entry/168600 biolink:NamedThing|biolink:Disease Parkinson Disease, Late-Onset Parkinson Disease, Late-Onset omim.nt PARKINSON DISEASE, LATE-ONSET; PD|Park owl:Class http://www.omim.org/phenotypicSeries/PS168600 biolink:NamedThing|biolink:Disease Parkinson disease omim.nt owl:Class UMLS:C1412237 biolink:NamedThing omim.nt owl:Class https://www.ncbi.nlm.nih.gov/gene/126 biolink:NamedThing omim.nt http://omim.org/entry/103735 biolink:NamedThing|biolink:Gene ADH6 Alcohol Dehydrogenase 6 omim.nt ALCOHOL DEHYDROGENASE 6; ADH6 owl:Class MONARCH:.well-known/genid/b378eaee6d581a4a9025 biolink:NamedThing GRCh38chr4-99202638-99219245-Region omim.nt MONARCH:.well-known/genid/b1e332970ad451700e9b faldo:Region PMID:1881901 biolink:NamedThing omim.nt IAO:0000013 OBO:CHR_9606chr4q23 biolink:NamedThing omim.nt owl:Class UMLS:C1412241 biolink:NamedThing omim.nt owl:Class https://www.ncbi.nlm.nih.gov/gene/130 biolink:NamedThing omim.nt http://omim.org/entry/103740 biolink:NamedThing|biolink:Gene ADH4 Alcohol Dehydrogenase 4 omim.nt ALCOHOL DEHYDROGENASE 4; ADH4|Adh, Class 2|Alcohol Dehydrogenase, Pi Isozyme owl:Class MONARCH:.well-known/genid/ba9e9b61b4942c19e947 biolink:NamedThing GRCh38chr4-99123657-99144296-Region omim.nt MONARCH:.well-known/genid/bc2913aca9237ec30eb8 faldo:Region MONARCH:.well-known/genid/OMIM103740ref4 biolink:NamedThing Mapping of the class II alcohol dehydrogenase gene locus to 4q22. (Abstract) omim.nt IAO:0000310 MONARCH:.well-known/genid/OMIM103740ref5 biolink:NamedThing Isozymes of human liver alcohol dehydrogenase. In: Rattazzi, M. C.; Scandalios, J. G.; Whitt, G. S. (eds.): Isozymes. Current Topics in Biological and Medical Research. Vol. 8. omim.nt IAO:0000310 PMID:1362387 biolink:NamedThing omim.nt IAO:0000013 PMID:270680 biolink:NamedThing omim.nt IAO:0000013 PMID:3466164 biolink:NamedThing omim.nt IAO:0000013 UMLS:C1412238 biolink:NamedThing omim.nt owl:Class https://www.ncbi.nlm.nih.gov/gene/127 biolink:NamedThing omim.nt MONARCH:.well-known/genid/OMIM103780ref21 biolink:NamedThing Is Alcoholism Hereditary? omim.nt IAO:0000310 MONARCH:.well-known/genid/OMIM103780ref45 biolink:NamedThing Human brain electrophysiology and alcoholism. In: Tarter, D. V.; Thiel, D. V. (eds.): Alcohol and the Brain. omim.nt IAO:0000310 PMID:10089015 biolink:NamedThing omim.nt IAO:0000013 PMID:10395222 biolink:NamedThing omim.nt IAO:0000013 PMID:10819022 biolink:NamedThing omim.nt IAO:0000013 PMID:10869113 biolink:NamedThing omim.nt IAO:0000013 PMID:10923994 biolink:NamedThing omim.nt IAO:0000013 PMID:11102287 biolink:NamedThing omim.nt IAO:0000013 PMID:11329392 biolink:NamedThing omim.nt IAO:0000013 PMID:12215082 biolink:NamedThing omim.nt IAO:0000013 PMID:12665621 biolink:NamedThing omim.nt IAO:0000013 PMID:12749054 biolink:NamedThing omim.nt IAO:0000013 PMID:12915525 biolink:NamedThing omim.nt IAO:0000013 PMID:15094791 biolink:NamedThing omim.nt IAO:0000013 PMID:15211641 biolink:NamedThing omim.nt IAO:0000013 PMID:15229186 biolink:NamedThing omim.nt IAO:0000013 PMID:15274051 biolink:NamedThing omim.nt IAO:0000013 PMID:15389757 biolink:NamedThing omim.nt IAO:0000013 PMID:15630072 biolink:NamedThing omim.nt IAO:0000013 PMID:15635638 biolink:NamedThing omim.nt IAO:0000013 PMID:15729746 biolink:NamedThing omim.nt IAO:0000013 PMID:15731118 biolink:NamedThing omim.nt IAO:0000013 PMID:16000316 biolink:NamedThing omim.nt IAO:0000013 PMID:16385453 biolink:NamedThing omim.nt IAO:0000013 PMID:16534506 biolink:NamedThing omim.nt IAO:0000013 PMID:17250611 biolink:NamedThing omim.nt IAO:0000013 PMID:17622222 biolink:NamedThing omim.nt IAO:0000013 PMID:17804423 biolink:NamedThing omim.nt IAO:0000013 PMID:17921519 biolink:NamedThing omim.nt IAO:0000013 PMID:17928304 biolink:NamedThing omim.nt IAO:0000013 PMID:18276852 biolink:NamedThing omim.nt IAO:0000013 PMID:18319328 biolink:NamedThing omim.nt IAO:0000013 PMID:18541917 biolink:NamedThing omim.nt IAO:0000013 PMID:1969501 biolink:NamedThing omim.nt IAO:0000013 PMID:1979357 biolink:NamedThing omim.nt IAO:0000013 PMID:20332099 biolink:NamedThing omim.nt IAO:0000013 PMID:23239122 biolink:NamedThing omim.nt IAO:0000013 PMID:2339688 biolink:NamedThing omim.nt IAO:0000013 PMID:24268660 biolink:NamedThing omim.nt IAO:0000013 PMID:2882604 biolink:NamedThing omim.nt IAO:0000013 PMID:3189329 biolink:NamedThing omim.nt IAO:0000013 PMID:4036659 biolink:NamedThing omim.nt IAO:0000013 PMID:545 biolink:NamedThing omim.nt IAO:0000013 PMID:6474187 biolink:NamedThing omim.nt IAO:0000013 PMID:758678 biolink:NamedThing omim.nt IAO:0000013 PMID:8807664 biolink:NamedThing omim.nt IAO:0000013 PMID:9603606 biolink:NamedThing omim.nt IAO:0000013 PMID:9603607 biolink:NamedThing omim.nt IAO:0000013 PMID:9880654 biolink:NamedThing omim.nt IAO:0000013 UMLS:C0001973 biolink:NamedThing omim.nt owl:Class UMLS:C2751719 biolink:NamedThing omim.nt owl:Class UMLS:C3887915 biolink:NamedThing omim.nt owl:Class http://omim.org/entry/103800 biolink:NamedThing omim.nt True owl:Class http://omim.org/entry/253200 biolink:NamedThing|biolink:Disease Mucopolysaccharidosis, Type 6 Mucopolysaccharidosis, Type 6 omim.nt MUCOPOLYSACCHARIDOSIS, TYPE VI; MPS6|Arsb Deficiency|Arylsulfatase B Deficiency|Maroteaux-Lamy Syndrome|Mps 6|N-Acetylgalactosamine-4-Sulfatase Deficiency owl:Class http://omim.org/entry/258870 biolink:NamedThing|biolink:Disease Gyrate Atrophy of Choroid and Retina Gyrate Atrophy of Choroid and Retina omim.nt GYRATE ATROPHY OF CHOROID AND RETINA; GACR|Gyrate Atrophy|Hyperornithinemia With Gyrate Atrophy of Choroid and Retina|Oat Deficiency|Okt Deficiency|Ornithine Aminotransferase Deficiency|Ornithine-Delta-Aminotransferase Deficiency|Ornithine Keto Acid Aminotransferase Deficiency owl:Class http://omim.org/entry/103830 biolink:NamedThing|biolink:Gene AKR1A1 Aldo-Keto Reductase Family 1, Member A1 omim.nt ALDO-KETO REDUCTASE FAMILY 1, MEMBER A1; AKR1A1|Aldehyde Reductase owl:Class MONARCH:.well-known/genid/bc4d85651bdeddad21e3 biolink:NamedThing GRCh38chr1-45550778-45570050-Region omim.nt MONARCH:.well-known/genid/b58401fdc6c1f93a60a0 faldo:Region MONARCH:.well-known/genid/OMIM103830ref3 biolink:NamedThing Biochemical and genetic interrelationship between aldose reductase, aldose reductase M and aldehyde reductase in human tissues. (Abstract) omim.nt IAO:0000310 PMID:10393438 biolink:NamedThing omim.nt IAO:0000013 PMID:2498333 biolink:NamedThing omim.nt IAO:0000013 PMID:30487609 biolink:NamedThing omim.nt IAO:0000013 OBO:CHR_9606chr1p33 biolink:NamedThing omim.nt owl:Class UMLS:C1412321 biolink:NamedThing omim.nt owl:Class https://www.ncbi.nlm.nih.gov/gene/10327 biolink:NamedThing omim.nt http://omim.org/entry/103850.0001 biolink:NamedThing ALDOA, ASP128GLY In a patient with red cell aldolase deficiency, or glycogen storage disease XII (GSD12; {611881}), {8:Kishi et al. (1987)} identified an A-G transition at nucleotide 386 in the codon for the 128th amino acid, leading to a change from aspartic acid (GAU) to glycine (GGU) (D128G) in the aldolase protein. The patient's enzyme from red cells and from cultured lymphoblastoid cells was highly thermolabile, and the enzyme expressed in E. coli was likewise thermolabile. Since asp128 is conserved in aldolase A, B ({612724}), and C ({103870}) of eukaryotes, including Drosophila, this residue likely has a crucial role in maintaining the correct spatial structure or in performing the catalytic function of the enzyme. The parents had intermediate levels of red cell aldolase A. The change in the aspartic acid codon extinguished an Fok1 restriction site (GGATG to GGGTG). Southern blot analysis of genomic DNA showed that the patient was homozygous for a mutation that was heterozygous in both parents. omim.nt GENO:0000002 http://omim.org/entry/103850 biolink:NamedThing|biolink:Gene ALDOA Aldolase A, Fructose-Bisphosphate|pseudogenes on 3 and 10 omim.nt ALDOLASE A, FRUCTOSE-BISPHOSPHATE; ALDOA|Aldolase 1|Aldolase a|Fructoaldolase a|Fructose-1,6-Bisphosphate Aldolase a owl:Class ClinVar:RCV000019808 biolink:NamedThing omim.nt dbSNP:rs121909533 biolink:NamedThing omim.nt owl:NamedIndividual http://omim.org/entry/103850#0001 biolink:NamedThing omim.nt http://omim.org/entry/103850.0002 biolink:NamedThing ALDOA, GLU206LYS {9:Kreuder et al. (1996)} described a 4 1/2-year-old boy with predominantly myopathic symptoms of aldolase A deficiency (GSD12; {611881}) due to substitution of a single amino acid within the subunit interface most essential for the tetrameric structure of the enzyme. The patient showed muscle weakness and premature muscle fatigue. He was unable to walk for more than 10 minutes or climb more than 20 steps at a time. Several unexplained episodes of jaundice and anemia required blood transfusions during the first year of life. The parents were healthy and nonconsanguineous. The patient showed slight jaundice, diminished muscle mass, reduced muscle tone, and proximal muscle weakness. The liver and spleen were somewhat enlarged. Creatine kinase was markedly elevated in the blood of this patient, and several muscle enzymes, as well as serum bilirubin, were increased. Codon 206 of the ALDOA gene was found to have a homozygous transition from GAG (glu) to AAG (lys) (E206K). The authors noted that a glutamate is present in all human aldolases at position 206 of the enzyme. Both parents and a healthy brother were heterozygous for the mutation. omim.nt GENO:0000002 ClinVar:RCV000019809 biolink:NamedThing omim.nt dbSNP:rs121909534 biolink:NamedThing omim.nt owl:NamedIndividual http://omim.org/entry/103850#0002 biolink:NamedThing omim.nt MONARCH:.well-known/genid/b6c33890b094d8be4646 biolink:NamedThing GRCh38chr16-30064278-30070419-Region omim.nt MONARCH:.well-known/genid/b37802c21e16edaad100 faldo:Region MONARCH:.well-known/genid/OMIM103850ref1 biolink:NamedThing Personal Communication. omim.nt IAO:0000310 MONARCH:.well-known/genid/OMIM103850ref11 biolink:NamedThing Molecular gene mapping of the structural gene for human aldolase A (ALDOA) to chromosome 22.(Abstract) omim.nt IAO:0000310 MONARCH:.well-known/genid/OMIM103850ref12 biolink:NamedThing Ancient linkage groups and frozen accidents. omim.nt IAO:0000310 MONARCH:.well-known/genid/OMIM103850ref3 biolink:NamedThing The human aldolase A gene is on chromosome 16.(Abstract) omim.nt IAO:0000310 MONARCH:.well-known/genid/OMIM103850ref6 biolink:NamedThing Personal Communication. omim.nt IAO:0000310 PMID:2825199 biolink:NamedThing omim.nt IAO:0000013 PMID:2828224 biolink:NamedThing omim.nt IAO:0000013 PMID:3355497 biolink:NamedThing omim.nt IAO:0000013 PMID:3391172 biolink:NamedThing omim.nt IAO:0000013 PMID:3570299 biolink:NamedThing omim.nt IAO:0000013 PMID:3674018 biolink:NamedThing omim.nt IAO:0000013 PMID:3840020 biolink:NamedThing omim.nt IAO:0000013 PMID:4561854 biolink:NamedThing omim.nt IAO:0000013 PMID:5073693 biolink:NamedThing omim.nt IAO:0000013 PMID:5230152 biolink:NamedThing omim.nt IAO:0000013 PMID:6585824 biolink:NamedThing omim.nt IAO:0000013 PMID:8598869 biolink:NamedThing omim.nt IAO:0000013 OBO:CHR_9606chr16p11.2 biolink:NamedThing omim.nt owl:Class http://omim.org/entry/611881 biolink:NamedThing|biolink:Disease Glycogen Storage Disease 12 Glycogen Storage Disease 12 omim.nt GLYCOGEN STORAGE DISEASE XII; GSD12|Aldoa Deficiency|Aldolase a Deficiency|Aldolase Deficiency, Red Cell|Gsd 12|Red Cell Aldolase Deficiency owl:Class UMLS:C1412344 biolink:NamedThing omim.nt owl:Class https://www.ncbi.nlm.nih.gov/gene/226 biolink:NamedThing omim.nt http://omim.org/entry/103870 biolink:NamedThing|biolink:Gene ALDOC Aldolase C, Fructose-Bisphosphate omim.nt ALDOLASE C, FRUCTOSE-BISPHOSPHATE; ALDOC|Aldolase 3|Fructoaldolase C owl:Class MONARCH:.well-known/genid/be94a79095f5ae26969e biolink:NamedThing GRCh38chr17-28573114-28576962-Region omim.nt MONARCH:.well-known/genid/be1f2fae34fa4ef85c28 faldo:Region PMID:2731939 biolink:NamedThing omim.nt IAO:0000013 PMID:3105602 biolink:NamedThing omim.nt IAO:0000013 PMID:3267224 biolink:NamedThing omim.nt IAO:0000013 OBO:CHR_9606chr17cen biolink:NamedThing omim.nt owl:Class UMLS:C1412348 biolink:NamedThing omim.nt owl:Class https://www.ncbi.nlm.nih.gov/gene/230 biolink:NamedThing omim.nt http://omim.org/entry/103880 biolink:NamedThing|biolink:Gene AKR1B1 Aldo-Keto Reductase Family 1, Member B1 omim.nt ALDO-KETO REDUCTASE FAMILY 1, MEMBER B1; AKR1B1|Aldehyde Reductase 1|Aldose Reductase owl:Class MONARCH:.well-known/genid/bac3b786e0f6bcd42077 biolink:NamedThing GRCh38chr7-134442349-134459238-Region omim.nt MONARCH:.well-known/genid/bcb3f4ed30e4fa690a0c faldo:Region PMID:15181092 biolink:NamedThing omim.nt IAO:0000013 PMID:1612607 biolink:NamedThing omim.nt IAO:0000013 PMID:1901827 biolink:NamedThing omim.nt IAO:0000013 PMID:1901857 biolink:NamedThing omim.nt IAO:0000013 PMID:2112546 biolink:NamedThing omim.nt IAO:0000013 PMID:2504709 biolink:NamedThing omim.nt IAO:0000013 PMID:8244370 biolink:NamedThing omim.nt IAO:0000013 PMID:9215310 biolink:NamedThing omim.nt IAO:0000013 OBO:CHR_9606chr7q35 biolink:NamedThing omim.nt owl:Class UMLS:C1412322 biolink:NamedThing omim.nt owl:Class https://www.ncbi.nlm.nih.gov/gene/231 biolink:NamedThing omim.nt http://omim.org/entry/103890 biolink:Gene|biolink:NamedThing ARM Aldose Reductase M omim.nt ALDOSE REDUCTASE M; ARM owl:Class UMLS:C1863110 biolink:NamedThing omim.nt owl:Class http://omim.org/entry/103900 biolink:NamedThing|biolink:Disease Hyperaldosteronism, Familial, Type 1 Hyperaldosteronism, Familial, Type 1 omim.nt HYPERALDOSTERONISM, FAMILIAL, TYPE I; HALD1|Acth-Dependent Hyperaldosteronism Syndrome|Aldosteronism, Sensitive to Dexamethasone|Fh 1|Glucocorticoid-Remediable Aldosteronism|Glucocorticoid-Suppressible Hyperaldosteronism owl:Class MONARCH:.well-known/genid/OMIM103900ref16 biolink:NamedThing Mutations in the CYP11B1 (11-beta-hydroxylase) and CYP11B2 (aldosterone synthase) genes causing CMOII deficiency, 11-hydroxylase deficiency and glucocorticoid suppressible hyperaldosteronism. (Abstract) omim.nt IAO:0000310 MONARCH:.well-known/genid/OMIM103900ref23 biolink:NamedThing Personal Communication. omim.nt IAO:0000310 PMID:10566645 biolink:NamedThing omim.nt IAO:0000013 PMID:10852446 biolink:NamedThing omim.nt IAO:0000013 PMID:10999827 biolink:NamedThing omim.nt IAO:0000013 PMID:11549669 biolink:NamedThing omim.nt IAO:0000013 PMID:11600544 biolink:NamedThing omim.nt IAO:0000013 PMID:12107222 biolink:NamedThing omim.nt IAO:0000013 PMID:1472060 biolink:NamedThing omim.nt IAO:0000013 PMID:1731223 biolink:NamedThing omim.nt IAO:0000013 PMID:4288576 biolink:NamedThing omim.nt IAO:0000013 PMID:4346813 biolink:NamedThing omim.nt IAO:0000013 PMID:5793351 biolink:NamedThing omim.nt IAO:0000013 PMID:6018580 biolink:NamedThing omim.nt IAO:0000013 PMID:6268977 biolink:NamedThing omim.nt IAO:0000013 PMID:6268979 biolink:NamedThing omim.nt IAO:0000013 PMID:6987607 biolink:NamedThing omim.nt IAO:0000013 PMID:7026592 biolink:NamedThing omim.nt IAO:0000013 PMID:7550315 biolink:NamedThing omim.nt IAO:0000013 PMID:7593610 biolink:NamedThing omim.nt IAO:0000013 PMID:8825044 biolink:NamedThing omim.nt IAO:0000013 PMID:8964867 biolink:NamedThing omim.nt IAO:0000013 PMID:9851772 biolink:NamedThing omim.nt IAO:0000013 UMLS:C1260386 biolink:NamedThing omim.nt owl:Class ORPHA:403 biolink:NamedThing|biolink:Disease omim.nt owl:Class http://www.omim.org/phenotypicSeries/PS103900 biolink:NamedThing|biolink:Disease Hyperaldosteronism omim.nt owl:Class http://omim.org/entry/103920 biolink:NamedThing|biolink:Disease Allergic Bronchopulmonary Aspergillosis, Familial omim.nt ALLERGIC BRONCHOPULMONARY ASPERGILLOSIS, FAMILIAL owl:Class MONARCH:.well-known/genid/OMIM103920ref3 biolink:NamedThing Allergic aspergillosis in a family. omim.nt IAO:0000310 PMID:382935 biolink:NamedThing omim.nt IAO:0000013 PMID:75074 biolink:NamedThing omim.nt IAO:0000013 UMLS:C3278302 biolink:NamedThing omim.nt owl:Class ORPHA:1164 biolink:NamedThing|biolink:Disease omim.nt owl:Class http://omim.org/entry/103950.0001 biolink:NamedThing A2M, VAL1000ILE By direct genomic sequencing of the 2 exons encoding the bait region and the exon encoding the thiolester site in 30 healthy individuals and in 30 patients with chronic lung disease, {24:Poller et al. (1992)} found a sequence polymorphism near the thiolester site of the gene, changing val1000 (GTC) to ile (ATC); the 2 alleles had frequencies of 0.30 and 0.70, respectively. No difference of A2M serum levels was observed for these 2 alleles. The proteinase inhibitor alpha-2-macroglobulin is found in association with senile plaques in Alzheimer disease (AD; {104300}). A2M has been implicated biochemically in binding and degradation of the amyloid beta protein which accumulates in senile plaques. In an initial exploratory dataset (90 controls and 171 AD cases), {16:Liao et al. (1998)} noted an increased frequency of the G/G genotype from 0.07 in controls to 0.12 in AD. An additional independent dataset of 359 controls and 566 AD patients were studied. In this hypothesis testing cohort, the G/G genotype again increased from 0.07 in controls to 0.12 in AD. The odds ratio for AD associated with the G/G genotype was 1.77 and in combination with APOE4 (see {107741}) was 9.68. In a study of 148 patients from southern Italy with sporadic Alzheimer disease, {32:Zappia et al. (2004)} found an increase in the val/val genotype compared to controls, conferring an odds ratio of 3.58 for development of the disease. In combination with a myeloperoxidase promoter polymorphism genotype, -463G/G ({606989.0008}), the odds ratio increased to 23.19. The authors suggested that the synergistic effect of the 2 genotypes may represent a facilitation of beta-amyloid deposition or a decrease in amyloid clearance. The findings were independent of APOE4 status. omim.nt GENO:0000002 http://omim.org/entry/103950 biolink:NamedThing|biolink:Gene A2M Alpha-2-Macroglobulin|cluster of genes omim.nt ALPHA-2-MACROGLOBULIN; A2M|Macroglobulin, Alpha-2 owl:Class ClinVar:RCV000019801 biolink:NamedThing omim.nt ClinVar:RCV000019802 biolink:NamedThing omim.nt dbSNP:rs669 biolink:NamedThing omim.nt owl:NamedIndividual http://omim.org/entry/103950#0001 biolink:NamedThing omim.nt http://omim.org/entry/103950.0002 biolink:NamedThing A2M, CYS972TYR In 1 of 30 patients with chronic lung disease and in none of the 30 healthy persons studied by {24:Poller et al. (1992)}, a mutation within the thiolester site, changing cys972 (TGT) to tyr (TAT), was found. Since activation of the internal thiolester formed between cys972 and gln975 in each of the subunits of the tetrameric A2M molecule is involved in the covalent crosslinking of the activating proteinase, this mutation was predicted to interfere with A2M function. The A2M serum level was within the normal range in this patient. omim.nt GENO:0000002 ClinVar:RCV000019803 biolink:NamedThing omim.nt dbSNP:rs1800433 biolink:NamedThing omim.nt owl:NamedIndividual http://omim.org/entry/103950#0002 biolink:NamedThing omim.nt http://omim.org/entry/103950.0003 biolink:NamedThing A2M, IVS1DEL In 1 healthy individual, {24:Poller et al. (1992)} found a deletion of the intron that ordinarily separates exons 1 and 2. As a result, the 2 exons that code the bait domain of the alpha-2-macroglobulin gene were fused. omim.nt GENO:0000002 ClinVar:RCV000019804 biolink:NamedThing omim.nt http://omim.org/entry/103950#0003 biolink:NamedThing omim.nt http://omim.org/entry/103950.0004 biolink:NamedThing A2M, ARG681HIS {20:Matthijs et al. (1992)} demonstrated an amino acid polymorphism in the bait domain of the alpha-2-macroglobulin molecule which defines the specific interaction of the molecule with proteinases. A G-to-A transition in exon 17 was detected in 1 person out of a group of 132 tested. The change predicted an arginine-to-his substitution at position 681. In the mutant allele an MaeII restriction site was lost and a new NspHI site was created. omim.nt GENO:0000002 ClinVar:RCV000019805 biolink:NamedThing omim.nt dbSNP:rs1800434 biolink:NamedThing omim.nt owl:NamedIndividual http://omim.org/entry/103950#0004 biolink:NamedThing omim.nt http://omim.org/entry/103950.0005 biolink:NamedThing A2M, EX18DEL {21:Matthijs and Marynen (1991)} described a deletion polymorphism of the A2M gene, a 5-prime splice site deletion in exon 18. This exon encodes 'exon II' of the bait domain of alpha-2-microglobulin, which functions to attract and trap proteases. {6:Blacker et al. (1998)} found that this deletion, referred to as A2M-2, conferred increased risk for Alzheimer disease ({104300}). The possibility increased risk for AD but without modifying age of onset. It is possible that association of A2M-2 with AD reflected linkage disequilibrium with another mutation in A2M or a nearby gene. omim.nt GENO:0000002 ClinVar:RCV000019806 biolink:NamedThing omim.nt ClinVar:RCV000019807 biolink:NamedThing omim.nt ClinVar:RCV000454529 biolink:NamedThing omim.nt http://omim.org/entry/103950#0005 biolink:NamedThing omim.nt http://omim.org/entry/103950.0006 biolink:NamedThing A2M, 5-BP DEL {21:Matthijs and Marynen (1991)} described a deletion polymorphism of the A2M gene: 5 bases from -7 to -3 from the 5-prime splice site of exon 2. Codominant segregation of the polymorphism was shown in 2 informative families. omim.nt GENO:0000002 dbSNP:rs1799759 biolink:NamedThing omim.nt owl:NamedIndividual http://omim.org/entry/103950#0006 biolink:NamedThing omim.nt MONARCH:.well-known/genid/bccf1302742dd872603c biolink:NamedThing GRCh38chr12-9067707-9116228-Region omim.nt MONARCH:.well-known/genid/b6574be665dac8574566 faldo:Region MONARCH:.well-known/genid/OMIM103950ref1 biolink:NamedThing Freely associating. (Editorial) omim.nt IAO:0000310 MONARCH:.well-known/genid/OMIM103950ref12 biolink:NamedThing Alpha-2-macroglobulin polymorphism: a new genetic system detected by immuno-electrophoresis. omim.nt IAO:0000310 MONARCH:.well-known/genid/OMIM103950ref19 biolink:NamedThing Alpha-2-macroglobulin, pregnancy zone protein and an alpha-2-macroglobulin pseudogene map to chromosome 12p12.2-p13. (Abstract) omim.nt IAO:0000310 MONARCH:.well-known/genid/OMIM103950ref5 biolink:NamedThing Reply to Rudrasingham et al. (Letter) omim.nt IAO:0000310 PMID:10319853 biolink:NamedThing omim.nt IAO:0000013 PMID:10319854 biolink:NamedThing omim.nt IAO:0000013 PMID:10319855 biolink:NamedThing omim.nt IAO:0000013 PMID:12966032 biolink:NamedThing omim.nt IAO:0000013 PMID:1370808 biolink:NamedThing omim.nt IAO:0000013 PMID:1374237 biolink:NamedThing omim.nt IAO:0000013 PMID:1379499 biolink:NamedThing omim.nt IAO:0000013 PMID:15023809 biolink:NamedThing omim.nt IAO:0000013 PMID:16040006 biolink:NamedThing omim.nt IAO:0000013 PMID:1717945 biolink:NamedThing omim.nt IAO:0000013 PMID:18499670 biolink:NamedThing omim.nt IAO:0000013 PMID:19380872 biolink:NamedThing omim.nt IAO:0000013 PMID:19639019 biolink:NamedThing omim.nt IAO:0000013 PMID:2408344 biolink:NamedThing omim.nt IAO:0000013 PMID:2415929 biolink:NamedThing omim.nt IAO:0000013 PMID:2434923 biolink:NamedThing omim.nt IAO:0000013 PMID:2460294 biolink:NamedThing omim.nt IAO:0000013 PMID:2475424 biolink:NamedThing omim.nt IAO:0000013 PMID:2478422 biolink:NamedThing omim.nt IAO:0000013 PMID:2578664 biolink:NamedThing omim.nt IAO:0000013 PMID:2581245 biolink:NamedThing omim.nt IAO:0000013 PMID:4622731 biolink:NamedThing omim.nt IAO:0000013 PMID:7528166 biolink:NamedThing omim.nt IAO:0000013 PMID:7544347 biolink:NamedThing omim.nt IAO:0000013 PMID:8798779 biolink:NamedThing omim.nt IAO:0000013 PMID:94459 biolink:NamedThing omim.nt IAO:0000013 PMID:9697696 biolink:NamedThing omim.nt IAO:0000013 PMID:9811940 biolink:NamedThing omim.nt IAO:0000013 http://omim.org/entry/104300 biolink:NamedThing|biolink:Disease Alzheimer Disease Alzheimer Disease omim.nt ALZHEIMER DISEASE; AD|Alzheimer Disease, Early-Onset, With Cerebral Amyloid Angiopathy|Alzheimer Disease, Familial, 1|Alzheimer Disease, Protection Against|Presenile and Senile Dementia owl:Class OBO:CHR_9606chr12p13.3 biolink:NamedThing omim.nt owl:Class UMLS:C1412046 biolink:NamedThing omim.nt owl:Class https://www.ncbi.nlm.nih.gov/gene/2 biolink:NamedThing omim.nt http://omim.org/entry/104000 biolink:NamedThing|biolink:Disease Alopecia Areata 1 Alopecia Areata 1 omim.nt ALOPECIA AREATA 1; AA1|Alopecia Universalis owl:Class PMID:10942113 biolink:NamedThing omim.nt IAO:0000013 PMID:12880440 biolink:NamedThing omim.nt IAO:0000013 PMID:1361288 biolink:NamedThing omim.nt IAO:0000013 PMID:1363876 biolink:NamedThing omim.nt IAO:0000013 PMID:143244 biolink:NamedThing omim.nt IAO:0000013 PMID:14418648 biolink:NamedThing omim.nt IAO:0000013 PMID:1503208 biolink:NamedThing omim.nt IAO:0000013 PMID:15245428 biolink:NamedThing omim.nt IAO:0000013 PMID:1575541 biolink:NamedThing omim.nt IAO:0000013 PMID:16338213 biolink:NamedThing omim.nt IAO:0000013 PMID:17236136 biolink:NamedThing omim.nt IAO:0000013 PMID:20596022 biolink:NamedThing omim.nt IAO:0000013 PMID:2247886 biolink:NamedThing omim.nt IAO:0000013 PMID:2408426 biolink:NamedThing omim.nt IAO:0000013 PMID:2916584 biolink:NamedThing omim.nt IAO:0000013 PMID:6231002 biolink:NamedThing omim.nt IAO:0000013 PMID:7557966 biolink:NamedThing omim.nt IAO:0000013 PMID:7843038 biolink:NamedThing omim.nt IAO:0000013 PMID:7903959 biolink:NamedThing omim.nt IAO:0000013 PMID:87773 biolink:NamedThing omim.nt IAO:0000013 PMID:9520023 biolink:NamedThing omim.nt IAO:0000013 UMLS:C0263505 biolink:NamedThing omim.nt owl:Class UMLS:C1863094 biolink:NamedThing omim.nt owl:Class ORPHA:700 biolink:NamedThing|biolink:Disease omim.nt owl:Class ORPHA:701 biolink:NamedThing|biolink:Disease omim.nt owl:Class http://www.omim.org/phenotypicSeries/PS203655 biolink:NamedThing|biolink:Disease Alopecia, isolated omim.nt owl:Class http://omim.org/entry/104100 biolink:NamedThing|biolink:Disease Palmoplantar Keratoderma and Congenital Alopecia 1 Palmoplantar Keratoderma and Congenital Alopecia 1 omim.nt PALMOPLANTAR KERATODERMA AND CONGENITAL ALOPECIA 1; PPKCA1|Keratoderma-Hypotrichosis-Leukonychia Totalis Syndrome|Ppkca, Stevanovic Type owl:Class PMID:13834517 biolink:NamedThing omim.nt IAO:0000013 PMID:20635335 biolink:NamedThing omim.nt IAO:0000013 PMID:25168385 biolink:NamedThing omim.nt IAO:0000013 PMID:7577599 biolink:NamedThing omim.nt IAO:0000013 PMID:8488878 biolink:NamedThing omim.nt IAO:0000013 UMLS:C3151468 biolink:NamedThing omim.nt owl:Class ORPHA:1010 biolink:NamedThing|biolink:Disease omim.nt owl:Class http://omim.org/entry/104110 biolink:NamedThing Alopecia, Familial Focal omim.nt ALOPECIA, FAMILIAL FOCAL; ALPF owl:Class PMID:3813597 biolink:NamedThing omim.nt IAO:0000013 UMLS:C1863092 biolink:NamedThing omim.nt owl:Class http://omim.org/entry/104130 biolink:NamedThing|biolink:Disease Alopecia, Psychomotor Epilepsy, Pyorrhea, and Mental Subnormality Alopecia, Psychomotor Epilepsy, Pyorrhea, and Mental Subnormality omim.nt ALOPECIA, PSYCHOMOTOR EPILEPSY, PYORRHEA, AND MENTAL SUBNORMALITY|Shokeir Syndrome owl:Class PMID:8275563 biolink:NamedThing omim.nt IAO:0000013 PMID:830443 biolink:NamedThing omim.nt IAO:0000013 UMLS:C1863090 biolink:NamedThing omim.nt owl:Class ORPHA:1008 biolink:NamedThing|biolink:Disease omim.nt owl:Class http://omim.org/entry/104145 biolink:NamedThing|biolink:Gene AFM 10kb 3' of AFP|Afamin omim.nt AFAMIN; AFM|Alpha-Albumin owl:Class MONARCH:.well-known/genid/b608eb94c238a5361b3a biolink:NamedThing GRCh38chr4-73481744-73504000-Region omim.nt MONARCH:.well-known/genid/bfb9d098f24dbb92e8f5 faldo:Region PMID:10400926 biolink:NamedThing omim.nt IAO:0000013 PMID:7509788 biolink:NamedThing omim.nt IAO:0000013 PMID:7517938 biolink:NamedThing omim.nt IAO:0000013 PMID:8755513 biolink:NamedThing omim.nt IAO:0000013 UMLS:C1412275 biolink:NamedThing omim.nt owl:Class https://www.ncbi.nlm.nih.gov/gene/173 biolink:NamedThing omim.nt http://omim.org/entry/104150.0001 biolink:NamedThing AFP, -119G-A, PROMOTER As part of an extensive screening program for spina bifida, a large Scottish kindred spanning 5 generations was identified as having hereditary persistence of alpha-fetoprotein (HPAFP; {615970}). Affected persons had mean serum AFP levels 23-fold higher than normal controls. These raised levels were, however, far below the levels seen in the fetus. {14:McVey et al. (1993)} showed by sequence analysis of the 5-prime flanking sequences of the AFP gene that in this family a G-to-A transition at position -119 was associated with the trait. This substitution occurs in a potential HNF1 binding site and increases the similarity of the sequence to a consensus HNF1 recognition site. In a competitive gel retardation assay, the mutant sequence bound HNF1-alpha ({142410}) more tightly than the wildtype sequence. Furthermore, 5-prime-flanking sequences of the human AFP gene containing the G-to-A substitution directed a higher level of chloramphenicol acetyltransferase (CAT) expression in transfected human hepatoma cells than the wildtype sequences. The findings not only provided an explanation for the findings in this family, but also highlighted the importance of this HNF1 binding site in the developmental regulation of the AFP gene. The substitution is similar to those that cause hereditary persistence of fetal hemoglobin (e.g., {142200.0026}; a G-A substitution at -117 of the HBG1 gene). {1:Alj et al. (2004)} identified a heterozygous -119G-A mutation in the AFP gene in 4 members of an Indian family with HPAFP. The mutation occurs in the distal HNF1 binding site of the promoter. omim.nt GENO:0000002 http://omim.org/entry/104150 biolink:NamedThing|biolink:Gene AFP Alpha-Fetoprotein|order: 5'-ALB-3'--5'-AFP-3' omim.nt ALPHA-FETOPROTEIN; AFP owl:Class ClinVar:RCV000019798 biolink:NamedThing omim.nt dbSNP:rs587776861 biolink:NamedThing omim.nt owl:NamedIndividual http://omim.org/entry/104150#0001 biolink:NamedThing omim.nt http://omim.org/entry/104150.0002 biolink:NamedThing AFP, 2-BP DEL, 882CT {20:Petit et al. (2009)} referred to this deletion as c.882delCT based on numbering from the ATG start codon. In 2 Arab families with congenital deficiency of AFP (AFPD; {615969}), {24:Sharony et al. (2004)} identified a 2-bp deletion in exon 8 of the AFP gene, c.930_931delCT, resulting in a frameshift and stop codon (Thr294fs25Ter) that truncated the protein to 318 amino acids. All affected children were homozygous for the deletion, as was 1 of the fathers; affected individuals were asymptomatic and developed normally. {24:Sharony et al. (2004)} stated that this was the first demonstration that deficiency of AFP is compatible with normal human fetal development and normal reproduction in males. omim.nt GENO:0000002 ClinVar:RCV000019799 biolink:NamedThing omim.nt dbSNP:rs387906580 biolink:NamedThing omim.nt owl:NamedIndividual http://omim.org/entry/104150#0002 biolink:NamedThing omim.nt http://omim.org/entry/104150.0003 biolink:NamedThing AFP, TRP181TER In an Algerian male infant with congenital deficiency of AFP (AFPD; {615969}), {20:Petit et al. (2009)} identified a homozygous c.543G-A transition in exon 5 of the AFP gene, resulting in a trp181-to-ter (W181X) substitution. There was no detectable AFP in the mother's serum or amniotic fluid during the second trimester of pregnancy, but fetal ultrasounds were normal, and the infant was healthy at birth. In the amniotic fluid, albumin was decreased, whereas alpha-1 and beta protein fractions were increased, suggesting that AFP deficiency may modify the distribution of protein fractions as a compensatory mechanism. omim.nt GENO:0000002 ClinVar:RCV000019800 biolink:NamedThing omim.nt dbSNP:rs121912685 biolink:NamedThing omim.nt owl:NamedIndividual http://omim.org/entry/104150#0003 biolink:NamedThing omim.nt http://omim.org/entry/104150.0004 biolink:NamedThing AFP, -55C-A, PROMOTER In affected members of an Italian family with hereditary persistence of alpha-fetoprotein (HPAFP; {615970}), {1:Alj et al. (2004)} identified a heterozygous -55C-A transversion in a conserved region in the proximal putative HNF1 ({142410}) binding region of the AFP promoter. The mutation was not found in 50 control individuals. In vitro functional expression studies showed that the mutation resulted in increased affinity of the promoter for HNF1, resulting in increased levels of gene transcription. omim.nt GENO:0000002 ClinVar:RCV000190821 biolink:NamedThing omim.nt http://omim.org/entry/104150#0004 biolink:NamedThing omim.nt MONARCH:.well-known/genid/b47528f5c612e8abdf47 biolink:NamedThing GRCh38chr4-73436220-73456173-Region omim.nt MONARCH:.well-known/genid/b94c8837bfa032152a7d faldo:Region MONARCH:.well-known/genid/OMIM104150ref13 biolink:NamedThing Chromosomal localization of the albumin and alpha-fetoprotein genes in the orangutan (Pongo pygmaeus) and gorilla (Gorilla gorilla). (Abstract) omim.nt IAO:0000310 MONARCH:.well-known/genid/OMIM104150ref9 biolink:NamedThing Diversity of alpha-fetoprotein gene expression in mice is generated by a combination of separate enhancer elements. omim.nt IAO:0000310 PMID:12297623 biolink:NamedThing omim.nt IAO:0000013 PMID:14699509 biolink:NamedThing omim.nt IAO:0000013 PMID:15280901 biolink:NamedThing omim.nt IAO:0000013 PMID:15626755 biolink:NamedThing omim.nt IAO:0000013 PMID:18669658 biolink:NamedThing omim.nt IAO:0000013 PMID:18854864 biolink:NamedThing omim.nt IAO:0000013 PMID:24120489 biolink:NamedThing omim.nt IAO:0000013 PMID:2415443 biolink:NamedThing omim.nt IAO:0000013 PMID:2431238 biolink:NamedThing omim.nt IAO:0000013 PMID:2435718 biolink:NamedThing omim.nt IAO:0000013 PMID:2436297 biolink:NamedThing omim.nt IAO:0000013 PMID:2436661 biolink:NamedThing omim.nt IAO:0000013 PMID:2580830 biolink:NamedThing omim.nt IAO:0000013 PMID:57576 biolink:NamedThing omim.nt IAO:0000013 PMID:6154931 biolink:NamedThing omim.nt IAO:0000013 PMID:6167988 biolink:NamedThing omim.nt IAO:0000013 PMID:6170120 biolink:NamedThing omim.nt IAO:0000013 PMID:6170978 biolink:NamedThing omim.nt IAO:0000013 PMID:6172714 biolink:NamedThing omim.nt IAO:0000013 PMID:6182563 biolink:NamedThing omim.nt IAO:0000013 PMID:6186903 biolink:NamedThing omim.nt IAO:0000013 PMID:6187626 biolink:NamedThing omim.nt IAO:0000013 PMID:6192439 biolink:NamedThing omim.nt IAO:0000013 PMID:6205824 biolink:NamedThing omim.nt IAO:0000013 PMID:67170 biolink:NamedThing omim.nt IAO:0000013 PMID:7543998 biolink:NamedThing omim.nt IAO:0000013 PMID:7684942 biolink:NamedThing omim.nt IAO:0000013 http://omim.org/entry/615970 biolink:NamedThing|biolink:Disease Alpha-Fetoprotein, Hereditary Persistence of Alpha-Fetoprotein, Hereditary Persistence of omim.nt ALPHA-FETOPROTEIN, HEREDITARY PERSISTENCE OF; HPAFP owl:Class http://omim.org/entry/615969 biolink:NamedThing|biolink:Disease Alpha-Fetoprotein Deficiency Alpha-Fetoprotein Deficiency omim.nt ALPHA-FETOPROTEIN DEFICIENCY; AFPD owl:Class UMLS:C1367597 biolink:NamedThing omim.nt owl:Class https://www.ncbi.nlm.nih.gov/gene/174 biolink:NamedThing omim.nt http://omim.org/entry/104155.0001 biolink:NamedThing ZFHX3, 24-BP DEL, NT10814 In 4 cases of low- to midgrade primary prostate cancer ({176807}), {4:Sun et al. (2005)} identified a 24-bp deletion in exon 10 of the ATBF1 gene, 10814del24, resulting in loss of 8 amino acids, beginning with codon 3381, in a glutamine-rich domain. The deletion was also identified in a microdissected high-grade primary metastasis. omim.nt GENO:0000002 http://omim.org/entry/104155 biolink:NamedThing|biolink:Gene ZFHX3 Zinc Finger Homeobox 3 omim.nt ZINC FINGER HOMEOBOX 3; ZFHX3|Alpha-Fetoprotein Enhancer-Binding Protein|At-Binding Transcription Factor 1|At Motif-Binding Factor 1 owl:Class ClinVar:RCV000019797 biolink:NamedThing omim.nt ClinVar:RCV000996316 biolink:NamedThing omim.nt dbSNP:rs727502780 biolink:NamedThing omim.nt owl:NamedIndividual http://omim.org/entry/104155#0001 biolink:NamedThing omim.nt MONARCH:.well-known/genid/bdadd11dd7eb6bb5d64d biolink:NamedThing GRCh38chr16-72782884-73891930-Region omim.nt MONARCH:.well-known/genid/bedb9d4f3ada69c0da65 faldo:Region PMID:15750593 biolink:NamedThing omim.nt IAO:0000013 PMID:1719379 biolink:NamedThing omim.nt IAO:0000013 PMID:18272476 biolink:NamedThing omim.nt IAO:0000013 PMID:20720010 biolink:NamedThing omim.nt IAO:0000013 PMID:8666409 biolink:NamedThing omim.nt IAO:0000013 PMID:8995484 biolink:NamedThing omim.nt IAO:0000013 OBO:CHR_9606chr16q22.3 biolink:NamedThing omim.nt owl:Class http://omim.org/entry/176807 biolink:NamedThing|biolink:Disease Prostate Cancer Prostate Cancer omim.nt PROSTATE CANCER owl:Class UMLS:C1412611 biolink:NamedThing omim.nt owl:Class https://www.ncbi.nlm.nih.gov/gene/463 biolink:NamedThing omim.nt http://omim.org/entry/104160.0001 biolink:NamedThing GANAB, ARG422LEU In an adult father and daughter (family M263) with polycystic kidney disease-3 with polycystic liver disease (PKD3; {600666}), {4:Porath et al. (2016)} identified a heterozygous c.1265G-T transversion ({VAR c.1265G-T, NM_198335.3}) in exon 12 of the GANAB gene, resulting in an arg422-to-leu (R422L) substitution at a highly conserved residue. The mutation, which was found by whole-exome sequencing and confirmed by Sanger sequencing, was filtered against the ExAC database and segregated with the disorder in the family. Transfection of the mutation into GANAB-null renal cells failed to rescue the lack of surface PKD1 ({601313}) expression, indicating that the mutation resulted in a loss of enzyme function. omim.nt GENO:0000002 http://omim.org/entry/104160 biolink:NamedThing|biolink:Gene GANAB Glucosidase, Alpha, Neutral Ab omim.nt GLUCOSIDASE, ALPHA, NEUTRAL AB; GANAB|Alpha-Glucosidase, Neutral, Ab Form|Glucosidase Ii, Alpha Subunit owl:Class ClinVar:RCV000239504 biolink:NamedThing omim.nt dbSNP:rs770519542 biolink:NamedThing omim.nt owl:NamedIndividual http://omim.org/entry/104160#0001 biolink:NamedThing omim.nt http://omim.org/entry/104160.0002 biolink:NamedThing GANAB, 2-BP DEL, 1914AG In 4 members of 2 unrelated families (M641 and 290100) with polycystic kidney disease-3 with or without polycystic liver disease (PKD3; {600666}), {4:Porath et al. (2016)} identified a heterozygous 2-bp deletion ({VAR c.1914_1915delAG, NM_198335.3}) in the GANAB gene, resulting in a frameshift and premature termination (Asp640GlnfsTer77). The mutation, which was found by Sanger sequencing of the GANAB gene, was not found in the ExAC or Exome Variant Server databases. omim.nt GENO:0000002 ClinVar:RCV000239562 biolink:NamedThing omim.nt dbSNP:rs879255641 biolink:NamedThing omim.nt owl:NamedIndividual http://omim.org/entry/104160#0002 biolink:NamedThing omim.nt http://omim.org/entry/104160.0003 biolink:NamedThing GANAB, THR405ARG In 3 members of a 3-generation family (P1174) with polycystic kidney disease-3 without polycystic liver disease (PKD3; {600666}), {4:Porath et al. (2016)} identified a heterozygous c.1214C-G transversion ({VAR c.1214C-G, NM_198335.3}) in exon 11 of the GANAB gene, resulting in a thr405-to-arg (T405R) substitution at a highly conserved residue. The mutation, which was found by Sanger sequencing of the GANAB gene, was not found in the ExAC or Exome Variant Server databases. Transfection of the mutation into GANAB-null renal cells failed to rescue the lack of surface PKD1 ({601313}) expression, indicating that the mutation resulted in a loss of enzyme function. One of the patients had 1 liver cyst. omim.nt GENO:0000002 ClinVar:RCV000239474 biolink:NamedThing omim.nt dbSNP:rs879255642 biolink:NamedThing omim.nt owl:NamedIndividual http://omim.org/entry/104160#0003 biolink:NamedThing omim.nt http://omim.org/entry/104160.0004 biolink:NamedThing GANAB, 6-BP DEL, IVS23 In 4 members of a family (M656) with polycystic kidney disease-3 with polycystic liver disease (PKD3; {600666}), {4:Porath et al. (2016)} identified a homozygous 6-bp deletion in intron 23 of the GANAB gene ({VAR c.2690+2_+7del, NM_198335.3}), resulting in a splice site mutation. The mutation, which was found by Sanger sequencing of the GANAB gene, was not found in the ExAC or Exome Variant Server databases. omim.nt GENO:0000002 ClinVar:RCV000239507 biolink:NamedThing omim.nt dbSNP:rs886037848 biolink:NamedThing omim.nt owl:NamedIndividual http://omim.org/entry/104160#0004 biolink:NamedThing omim.nt http://omim.org/entry/104160.0005 biolink:NamedThing GANAB, ARG839TRP In 3 members of a family (P1073) with polycystic kidney disease-3 with polycystic liver disease (PKD3; {600666}), {4:Porath et al. (2016)} identified a heterozygous c.2515C-T transition ({VAR c.2515C-T, NM_198335.3}) in the GANAB gene, resulting in an arg839-to-trp (R839W) substitution at a highly conserved residue. The mutation, which was found by Sanger sequencing of the GANAB gene, was not found in the ExAC or Exome Variant Server databases. Transfection of the mutation into GANAB-null renal cells failed to rescue the lack of surface PKD1 ({601313}) expression, indicating that the mutation resulted in a loss of enzyme function. All 3 patients also had liver cysts; one patient's liver disease was so severe that she required a liver transplant. omim.nt GENO:0000002 ClinVar:RCV000239561 biolink:NamedThing omim.nt dbSNP:rs879255643 biolink:NamedThing omim.nt owl:NamedIndividual http://omim.org/entry/104160#0005 biolink:NamedThing omim.nt http://omim.org/entry/104160.0006 biolink:NamedThing GANAB, 2-BP DEL, 152GA In a 58-year-old woman (family M472) with polycystic kidney disease-3 with polycystic liver disease (PKD3; {600666}), {4:Porath et al. (2016)} identified a heterozygous 2-bp deletion ({VAR c.152_153GA, NM_198335.3}) in the GANAB gene, resulting in a frameshift and premature termination (Arg51LysfsTer21). The mutation, which was found by Sanger sequencing of the GANAB gene, was found once (1 in 60,706 unrelated individuals) in the ExAC database, but not in the Exome Variant Server database. The patient had severe polycystic liver disease, requiring surgical intervention. Her sister had a similar disorder, but genetic studies were not performed. omim.nt GENO:0000002 ClinVar:RCV000239461 biolink:NamedThing omim.nt dbSNP:rs752158933 biolink:NamedThing omim.nt owl:NamedIndividual http://omim.org/entry/104160#0006 biolink:NamedThing omim.nt http://omim.org/entry/104160.0007 biolink:NamedThing GANAB, IVS24DS, 9-BP DEL In 5 sibs (family T90) with polycystic kidney disease-3 with polycystic liver disease (PKD3; {600666}) manifest as isolated polycystic liver disease, {1:Besse et al. (2018)} identified a heterozygous 9-bp deletion in the vicinity of the splice donor site of exon 24 of the GANAB gene ({VAR c.2791+4_2791+12del, NM_198335.3}). The mutation was found by a combination of linkage analysis and direct sequencing after whole-exome sequencing did not yield results; it was confirmed by Sanger sequencing and segregated with the disorder in the family. The deletion was not found in the 1000 Genomes Project, Exome Variant Server, or gnomAD databases. A minigene assay showed that the deletion resulted in the skipping of exon 24, a frameshift, and premature termination in cell lines and primary human cholangiocytes. omim.nt GENO:0000002 ClinVar:RCV000584790 biolink:NamedThing omim.nt dbSNP:rs1590789370 biolink:NamedThing omim.nt owl:NamedIndividual http://omim.org/entry/104160#0007 biolink:NamedThing omim.nt MONARCH:.well-known/genid/bf3b484ce5f9aa9b4daf biolink:NamedThing GRCh38chr11-62624828-62646612-Region omim.nt MONARCH:.well-known/genid/ba9126a7e7cf1a38fbe3 faldo:Region MONARCH:.well-known/genid/OMIM104160ref2 biolink:NamedThing Assignment of the gene for neutral alpha-glucosidase AB to chromosome 11. (Abstract) omim.nt IAO:0000310 PMID:27259053 biolink:NamedThing omim.nt IAO:0000013 PMID:29243290 biolink:NamedThing omim.nt IAO:0000013 PMID:6342981 biolink:NamedThing omim.nt IAO:0000013 PMID:8910335 biolink:NamedThing omim.nt IAO:0000013 http://omim.org/entry/600666 biolink:NamedThing|biolink:Disease Polycystic Kidney Disease 3 With or Without Polycystic Liver Disease Polycystic Kidney Disease 3 With or Without Polycystic Liver Disease omim.nt POLYCYSTIC KIDNEY DISEASE 3 WITH OR WITHOUT POLYCYSTIC LIVER DISEASE; PKD3|Polycystic Kidney Disease, Adult, Type 3 owl:Class http://www.omim.org/phenotypicSeries/PS173900 biolink:NamedThing|biolink:Disease Polycystic kidney disease omim.nt owl:Class UMLS:C1414965 biolink:NamedThing omim.nt owl:Class https://www.ncbi.nlm.nih.gov/gene/23193 biolink:NamedThing omim.nt http://omim.org/entry/104170.0001 biolink:NamedThing NAGA, GLU325LYS In the 2 German boys first described with Schindler disease ({609241}) ({11,12:van Diggelen et al., 1987, 1988}), {17:Wang et al. (1990)} identified a homozygous 973G-A transition in exon 8 of the NAGA gene, resulting in a glu325-to-lys (E325K) substitution. {9:Keulemans et al. (1996)} identified a distant affected relative of the 2 boys who had the E325K homozygous mutation. The boys had approximately 1% residual NAGA activity. {1:Bakker et al. (2001)} reported homozygosity for the E325K mutation in a 3-year-old Moroccan boy with alpha-NAGA deficiency. He was born of consanguineous parents. The proband and his 7-year-old healthy brother had undetectable alpha-NAGA activity in leukocytes and a profound deficiency in fibroblasts. The parents had alpha-NAGA activity consistent with heterozygosity. Mutation analysis revealed homozygosity for the E325K mutation in the proband and his healthy brother, whereas a third sib and both parents were heterozygous. The family demonstrated the extreme clinical heterogeneity of alpha-NAGA deficiency, as the homozygous brother at the age of 7 years showed no clinical or neurologic symptoms. omim.nt GENO:0000002 http://omim.org/entry/104170 biolink:NamedThing|biolink:Gene NAGA N-Acetyl-Alpha-D-Galactosaminidase|proximal to Ph1 break omim.nt N-ACETYL-ALPHA-D-GALACTOSAMINIDASE; NAGA|Alpha-Galactosidase B owl:Class ClinVar:RCV000019792 biolink:NamedThing omim.nt ClinVar:RCV000256069 biolink:NamedThing omim.nt ClinVar:RCV000501877 biolink:NamedThing omim.nt ClinVar:RCV000660647 biolink:NamedThing omim.nt ClinVar:RCV001148412 biolink:NamedThing omim.nt ClinVar:RCV001195394 biolink:NamedThing omim.nt dbSNP:rs121434529 biolink:NamedThing omim.nt owl:NamedIndividual http://omim.org/entry/104170#0001 biolink:NamedThing omim.nt http://omim.org/entry/104170.0002 biolink:NamedThing NAGA, ARG329TRP In a Japanese woman with disseminated angiokeratoma ({609242}) reported by {8:Kanzaki et al. (1989)}, {18,16:Wang et al. (1990, 1994)} identified a homozygous 985C-T transition in the NAGA gene, resulting in an arg329-to-trp (R329W) substitution. The base substitution was confirmed by hybridization of PCR-amplified genomic DNA from family members with allele-specific oligonucleotides. {16:Wang et al. (1994)} showed that in transiently expressed COS-1 cells, both the infantile-onset E325K ({104170.0001}) and the adult-onset R329W precursors were processed to the mature form; however, the E325K mutant polypeptide was more rapidly degraded than the R329W subunit, thereby providing a basis for the distinctly different infantile- and adult-onset phenotypes. omim.nt GENO:0000002 ClinVar:RCV000019793 biolink:NamedThing omim.nt dbSNP:rs121434530 biolink:NamedThing omim.nt owl:NamedIndividual http://omim.org/entry/104170#0002 biolink:NamedThing omim.nt http://omim.org/entry/104170.0003 biolink:NamedThing NAGA, GLU193TER {9:Keulemans et al. (1996)} showed by PCR and sequence analysis that the Spanish brother and sister with manifestations of Kanzaki disease ({609242}) described by {2:Chabas et al. (1994)} were homozygous for a 5371G-T transversion in exon 5 of the NAGA gene (numbering according to {20:Yamauchi et al., 1990}), resulting in a glu193-to-ter (E193X) substitution, premature termination, and complete loss of the NAGA protein. omim.nt GENO:0000002 ClinVar:RCV000019794 biolink:NamedThing omim.nt dbSNP:rs121434531 biolink:NamedThing omim.nt owl:NamedIndividual http://omim.org/entry/104170#0003 biolink:NamedThing omim.nt http://omim.org/entry/104170.0004 biolink:NamedThing NAGA, SER160CYS In a Dutch girl with type III NAGA deficiency ({609241}) reported by {4:de Jong et al. (1994)}, {9:Keulemans et al. (1996)} identified compound heterozygosity for 2 mutations in the NAGA gene: E325K ({104170.0001}) and a 4969C-G transversion in exon 4 (numbering according to {20:Yamauchi et al., 1990}), resulting in a ser160-to-cys (S160C) substitution. The same genotype was found in the clinically unaffected 3-year-old brother of the proband, and the authors suggested that the brother might be a preclinical case of NAGA deficiency; the brother's twin sister did not have the genotype. Residual enzyme activity in the proband was approximately 4% of controls. The S160C allele was not identified in 80 Dutch control alleles. omim.nt GENO:0000002 ClinVar:RCV000019795 biolink:NamedThing omim.nt ClinVar:RCV000169668 biolink:NamedThing omim.nt ClinVar:RCV001092858 biolink:NamedThing omim.nt ClinVar:RCV001145759 biolink:NamedThing omim.nt dbSNP:rs121434532 biolink:NamedThing omim.nt owl:NamedIndividual http://omim.org/entry/104170#0004 biolink:NamedThing omim.nt http://omim.org/entry/104170.0005 biolink:NamedThing NAGA, ARG329GLN In a Japanese woman with Kanzaki disease ({609242}), {10:Kodama et al. (2001)} identified a homozygous 986G-A transition in the NAGA gene, resulting in an arg329-to-gln (R329Q) substitution. The patient had angiokeratoma corporis diffusum, Meniere syndrome, and no mental retardation. Her parents were consanguineous. omim.nt GENO:0000002 ClinVar:RCV000019796 biolink:NamedThing omim.nt ClinVar:RCV000778663 biolink:NamedThing omim.nt dbSNP:rs121434533 biolink:NamedThing omim.nt owl:NamedIndividual http://omim.org/entry/104170#0005 biolink:NamedThing omim.nt MONARCH:.well-known/genid/b8bd4cd8340690994510 biolink:NamedThing GRCh38chr22-42058333-42070841-Region omim.nt MONARCH:.well-known/genid/bed3be59117e2661fb9a faldo:Region MONARCH:.well-known/genid/OMIM104170ref18 biolink:NamedThing Alpha-N-acetylgalactosaminidase gene: homology with human alpha-galactosidase A, and identification and confirmation of the mutations causing type I and II Schindler disease. (Abstract) omim.nt IAO:0000310 MONARCH:.well-known/genid/OMIM104170ref19 biolink:NamedThing Schindler disease: generation of a murine model by targeted disruption of the alpha-N-acetylgalactosaminidase gene. (Abstract) omim.nt IAO:0000310 MONARCH:.well-known/genid/OMIM104170ref5 biolink:NamedThing Alpha-N-acetylgalactosaminidase deficiency: Schindler disease.In: Scriver, C. R.; Beaudet, A. L.; Sly, W. S.; Valle, D. (eds.) : The Metabolic and Molecular Bases of Inherited Disease. Vol. III. (8th ed.) omim.nt IAO:0000310 MONARCH:.well-known/genid/OMIM104170ref6 biolink:NamedThing Regional localization of NAGA and ACO2 on human chromosome 22. (Abstract) omim.nt IAO:0000310 PMID:11251574 biolink:NamedThing omim.nt IAO:0000013 PMID:11313741 biolink:NamedThing omim.nt IAO:0000013 PMID:1646157 biolink:NamedThing omim.nt IAO:0000013 PMID:215508 biolink:NamedThing omim.nt IAO:0000013 PMID:2174888 biolink:NamedThing omim.nt IAO:0000013 PMID:2243144 biolink:NamedThing omim.nt IAO:0000013 PMID:2372288 biolink:NamedThing omim.nt IAO:0000013 PMID:2564952 biolink:NamedThing omim.nt IAO:0000013 PMID:2889023 biolink:NamedThing omim.nt IAO:0000013 PMID:3149698 biolink:NamedThing omim.nt IAO:0000013 PMID:7707696 biolink:NamedThing omim.nt IAO:0000013 PMID:8040340 biolink:NamedThing omim.nt IAO:0000013 PMID:8071745 biolink:NamedThing omim.nt IAO:0000013 PMID:8782044 biolink:NamedThing omim.nt IAO:0000013 PMID:9787108 biolink:NamedThing omim.nt IAO:0000013 OBO:CHR_9606chr22q11 biolink:NamedThing omim.nt owl:Class http://omim.org/entry/609241 biolink:NamedThing|biolink:Disease Schindler Disease, Type 1 Schindler Disease, Type 1 omim.nt SCHINDLER DISEASE, TYPE I|Alpha-N-Acetylgalactosaminidase Deficiency, Type 1|Alpha-N-Acetylgalactosaminidase Deficiency, Type 3|Naga Deficiency, Type 1|Naga Deficiency, Type 3|Neuroaxonal Dystrophy, Schindler Type|Schindler Disease, Type 3 owl:Class http://omim.org/entry/609242 biolink:NamedThing|biolink:Disease Kanzaki Disease Kanzaki Disease omim.nt KANZAKI DISEASE|Alpha-N-Acetylgalactosaminidase Deficiency, Adult-Onset|Alpha-N-Acetylgalactosaminidase Deficiency, Type 2|Naga Deficiency, Type 2|Schindler Disease, Type 2 owl:Class UMLS:C1417592 biolink:NamedThing omim.nt owl:Class https://www.ncbi.nlm.nih.gov/gene/4668 biolink:NamedThing omim.nt http://omim.org/entry/104175 biolink:NamedThing|biolink:Gene GGTA1P Glycoprotein, Alpha-Galactosyltransferase 1 Pseudogene|processed pseudogene GGTA1P on 12q14-q15 omim.nt GLYCOPROTEIN, ALPHA-GALACTOSYLTRANSFERASE 1 PSEUDOGENE; GGTA1P|Alpha-1,3-Galactosyltransferase|Ggta1 owl:Class MONARCH:.well-known/genid/b578bce19b554803a327 biolink:NamedThing GRCh38chr9-121444989-121499843-Region omim.nt MONARCH:.well-known/genid/bd684f368098734c8e31 faldo:Region PMID:11778012 biolink:NamedThing omim.nt IAO:0000013 PMID:12493821 biolink:NamedThing omim.nt IAO:0000013 PMID:1559713 biolink:NamedThing omim.nt IAO:0000013 PMID:1901427 biolink:NamedThing omim.nt IAO:0000013 PMID:1901859 biolink:NamedThing omim.nt IAO:0000013 PMID:19218399 biolink:NamedThing omim.nt IAO:0000013 PMID:2503516 biolink:NamedThing omim.nt IAO:0000013 OBO:CHR_9606chr9q33 biolink:NamedThing omim.nt owl:Class UMLS:C1415056 biolink:NamedThing omim.nt owl:Class https://www.ncbi.nlm.nih.gov/gene/2681 biolink:NamedThing omim.nt http://omim.org/entry/104180 biolink:NamedThing|biolink:Gene GANC Glucosidase, Alpha, Neutral C omim.nt GLUCOSIDASE, ALPHA, NEUTRAL C; GANC|Alpha-Glucosidase C, Neutral owl:Class MONARCH:.well-known/genid/b63cc41cf07a7ca9289d biolink:NamedThing GRCh38chr15-42273486-42353665-Region omim.nt MONARCH:.well-known/genid/be71132299c73c757153 faldo:Region MONARCH:.well-known/genid/OMIM104180ref5 biolink:NamedThing Assignment of human neutral alpha-glucosidase C to chromosome 15. (Abstract) omim.nt IAO:0000310 PMID:12370436 biolink:NamedThing omim.nt IAO:0000013 PMID:6994494 biolink:NamedThing omim.nt IAO:0000013 PMID:6995030 biolink:NamedThing omim.nt IAO:0000013 PMID:8640221 biolink:NamedThing omim.nt IAO:0000013 PMID:9988276 biolink:NamedThing omim.nt IAO:0000013 OBO:CHR_9606chr15q15.1 biolink:NamedThing omim.nt owl:Class UMLS:C1414966 biolink:NamedThing omim.nt owl:Class https://www.ncbi.nlm.nih.gov/gene/2595 biolink:NamedThing omim.nt http://omim.org/entry/104200 biolink:NamedThing|biolink:Disease Alport Syndrome 3, Autosomal Dominant Alport Syndrome 3, Autosomal Dominant omim.nt ALPORT SYNDROME 3, AUTOSOMAL DOMINANT; ATS3 owl:Class MONARCH:.well-known/genid/OMIM104200ref8 biolink:NamedThing A follow-up study of hereditary chronic nephritis. omim.nt IAO:0000310 MONARCH:.well-known/genid/OMIM104200ref9 biolink:NamedThing A clinical study of hereditary interstitial pyelonephritis. omim.nt IAO:0000310 PMID:11044206 biolink:NamedThing omim.nt IAO:0000013 PMID:11134255 biolink:NamedThing omim.nt IAO:0000013 PMID:17948465 biolink:NamedThing omim.nt IAO:0000013 PMID:20773074 biolink:NamedThing omim.nt IAO:0000013 PMID:25575550 biolink:NamedThing omim.nt IAO:0000013 PMID:4010153 biolink:NamedThing omim.nt IAO:0000013 PMID:626446 biolink:NamedThing omim.nt IAO:0000013 PMID:7371220 biolink:NamedThing omim.nt IAO:0000013 PMID:9269635 biolink:NamedThing omim.nt IAO:0000013 UMLS:C4746547 biolink:NamedThing omim.nt owl:Class ORPHA:63 biolink:NamedThing|biolink:Disease omim.nt owl:Class ORPHA:88918 biolink:NamedThing|biolink:Disease omim.nt owl:Class http://www.omim.org/phenotypicSeries/PS301050 biolink:NamedThing|biolink:Disease Alport syndrome omim.nt owl:Class http://omim.org/entry/104210 biolink:NamedThing|biolink:Gene ADRA2A Alpha-2A-Adrenergic Receptor omim.nt ALPHA-2A-ADRENERGIC RECEPTOR; ADRA2A|Adrar|Adrenoceptor, Alpha-2A|Alpha-2-Adrenergic Receptor, Platelet Type owl:Class MONARCH:.well-known/genid/b9f132bc95a8401a69a7 biolink:NamedThing GRCh38chr10-111077028-111080906-Region omim.nt MONARCH:.well-known/genid/bd4e360468c18ddf264b faldo:Region MONARCH:.well-known/genid/OMIM104210ref14 biolink:NamedThing Chromosomal assignment of genes for an alpha-adrenergic receptor (ADRAR) and for another member of this receptor family coupled to guanine nucleotide regulatory proteins (RG21). (Abstract) omim.nt IAO:0000310 MONARCH:.well-known/genid/OMIM104210ref4 biolink:NamedThing Genetic mapping of adrenergic receptor genes. (Abstract) omim.nt IAO:0000310 PMID:10334470 biolink:NamedThing omim.nt IAO:0000013 PMID:10647009 biolink:NamedThing omim.nt IAO:0000013 PMID:12068299 biolink:NamedThing omim.nt IAO:0000013 PMID:12529373 biolink:NamedThing omim.nt IAO:0000013 PMID:12815749 biolink:NamedThing omim.nt IAO:0000013 PMID:1354394 biolink:NamedThing omim.nt IAO:0000013 PMID:16172611 biolink:NamedThing omim.nt IAO:0000013 PMID:1676978 biolink:NamedThing omim.nt IAO:0000013 PMID:19965390 biolink:NamedThing omim.nt IAO:0000013 PMID:2823383 biolink:NamedThing omim.nt IAO:0000013 PMID:2902571 biolink:NamedThing omim.nt IAO:0000013 PMID:9401330 biolink:NamedThing omim.nt IAO:0000013 OBO:CHR_9606chr10q24 biolink:NamedThing omim.nt owl:Class UMLS:C1332028 biolink:NamedThing omim.nt owl:Class https://www.ncbi.nlm.nih.gov/gene/150 biolink:NamedThing omim.nt http://omim.org/entry/104219 biolink:NamedThing|biolink:Gene ADRA1D Alpha-1D-Adrenergic Receptor|incorrectly assigned to 5q omim.nt ALPHA-1D-ADRENERGIC RECEPTOR; ADRA1D|Alpha-1A-Adrenergic Receptor, Formerly owl:Class MONARCH:.well-known/genid/b4147fcb109de252abf4 biolink:NamedThing GRCh38chr20-4220629-4249286-Region omim.nt MONARCH:.well-known/genid/b9a86dfafcb3089ccbcb faldo:Region PMID:1359975 biolink:NamedThing omim.nt IAO:0000013 PMID:1656955 biolink:NamedThing omim.nt IAO:0000013 PMID:1706716 biolink:NamedThing omim.nt IAO:0000013 PMID:7746284 biolink:NamedThing omim.nt IAO:0000013 PMID:7815325 biolink:NamedThing omim.nt IAO:0000013 PMID:8024574 biolink:NamedThing omim.nt IAO:0000013 PMID:8039425 biolink:NamedThing omim.nt IAO:0000013 PMID:8125015 biolink:NamedThing omim.nt IAO:0000013 PMID:8183249 biolink:NamedThing omim.nt IAO:0000013 PMID:8288218 biolink:NamedThing omim.nt IAO:0000013 OBO:CHR_9606chr20p13 biolink:NamedThing omim.nt owl:Class UMLS:C1412260 biolink:NamedThing omim.nt owl:Class https://www.ncbi.nlm.nih.gov/gene/146 biolink:NamedThing omim.nt http://omim.org/entry/104220 biolink:NamedThing|biolink:Gene ADRA1B Alpha-1B-Adrenergic Receptor omim.nt ALPHA-1B-ADRENERGIC RECEPTOR; ADRA1B|Alpha-1-Adrenergic Receptor owl:Class MONARCH:.well-known/genid/bd5540d21af54bb82540 biolink:NamedThing GRCh38chr5-159916481-159989204-Region omim.nt MONARCH:.well-known/genid/b913e4c51997bc2c7c86 faldo:Region PMID:1328250 biolink:NamedThing omim.nt IAO:0000013 PMID:1662393 biolink:NamedThing omim.nt IAO:0000013 PMID:2154750 biolink:NamedThing omim.nt IAO:0000013 PMID:9326654 biolink:NamedThing omim.nt IAO:0000013 PMID:9700190 biolink:NamedThing omim.nt IAO:0000013 OBO:CHR_9606chr5q33 biolink:NamedThing omim.nt owl:Class UMLS:C1332027 biolink:NamedThing omim.nt owl:Class https://www.ncbi.nlm.nih.gov/gene/147 biolink:NamedThing omim.nt http://omim.org/entry/104221 biolink:NamedThing|biolink:Gene ADRA1A .03cM from NEFL|Alpha-1A-Adrenergic Receptor omim.nt ALPHA-1A-ADRENERGIC RECEPTOR; ADRA1A|Alpha-1C-Adrenergic Receptor, Formerly owl:Class MONARCH:.well-known/genid/ba71044fc398d33f6877 biolink:NamedThing GRCh38chr8-26738112-26870993-Region omim.nt MONARCH:.well-known/genid/bae6c4d26092c909f776 faldo:Region PMID:1363873 biolink:NamedThing omim.nt IAO:0000013 PMID:1970822 biolink:NamedThing omim.nt IAO:0000013 PMID:7737411 biolink:NamedThing omim.nt IAO:0000013 PMID:8396931 biolink:NamedThing omim.nt IAO:0000013 PMID:8564208 biolink:NamedThing omim.nt IAO:0000013 PMID:9490024 biolink:NamedThing omim.nt IAO:0000013 OBO:CHR_9606chr8p21 biolink:NamedThing omim.nt owl:Class UMLS:C1332026 biolink:NamedThing omim.nt owl:Class https://www.ncbi.nlm.nih.gov/gene/148 biolink:NamedThing omim.nt http://omim.org/entry/104222 biolink:NamedThing omim.nt True owl:Class http://omim.org/entry/104225.0001 biolink:NamedThing LRPAP1, 1-BP DEL, 605A In 3 sibs from a consanguineous Saudi Arabian family with extreme myopia (MYP23; {615431}), {1:Aldahmesh et al. (2013)} identified homozygosity for a 1-bp deletion (c.605delA) in exon 5 of the LRPAP1 gene, causing a frameshift predicted to result in a premature termination codon (Asn202ThrfsTer8) in the D3 domain. The mutation segregated fully with myopia in the family and was not found in 210 Saudi exome files or in the SNP databases of the 1000 Genomes Project or Exome Variant Server. Immunoblot analysis in the proband revealed nearly total absence of LRPAP1 as well as a marked reduction in LRP1 ({107770}) and a greater than 2-fold increase in TGFB ({190180}) compared to controls. omim.nt GENO:0000002 http://omim.org/entry/104225 biolink:NamedThing|biolink:Gene LRPAP1 Low Density Lipoprotein Receptor-Related Protein-Associated Protein 1 omim.nt LOW DENSITY LIPOPROTEIN RECEPTOR-RELATED PROTEIN-ASSOCIATED PROTEIN 1; LRPAP1|Alpha-2-Macroglobulin Receptor-Associated Protein owl:Class ClinVar:RCV000055654 biolink:NamedThing omim.nt dbSNP:rs786205127 biolink:NamedThing omim.nt owl:NamedIndividual http://omim.org/entry/104225#0001 biolink:NamedThing omim.nt http://omim.org/entry/104225.0002 biolink:NamedThing LRPAP1, 2-BP DEL, 863GA In 5 sibs from 2 unrelated consanguineous Saudi Arabian families with extreme myopia (MYP23; {615431}), {1:Aldahmesh et al. (2013)} identified homozygosity for a 2-bp deletion (c.863_864del) in exon 7 of the LRPAP1 gene, causing a frameshift predicted to result in a premature termination codon (Ile288ArgfsTer118) in the D4 domain. The mutation segregated fully with myopia in each family and was not found in 210 Saudi exome files or in the SNP databases of the 1000 Genomes Project or Exome Variant Server. Immunoblot analysis in the 2 probands revealed nearly total absence of LRPAP1 as well as marked reduction in LRP1 ({107770}) and a greater than 2-fold increase in TGFB ({190180}) compared to controls. omim.nt GENO:0000002 ClinVar:RCV000055655 biolink:NamedThing omim.nt dbSNP:rs398122836 biolink:NamedThing omim.nt owl:NamedIndividual http://omim.org/entry/104225#0002 biolink:NamedThing omim.nt http://omim.org/entry/104225.0003 biolink:NamedThing LRPAP1, 1-BP DEL, 199C In a 5-year-old Chinese boy (HM759), born to consanguineous parents, with bilateral high myopia (MYP23; {615431}), {3:Jiang et al. (2015)} identified homozygosity for a 1-bp deletion in the LRPAP1 gene (c.199delC), resulting in a frameshift and premature termination (Gln67SerfsTer8). The parents were unaffected, but their DNA was not available for study. The mutation was not found in the Exome Variant Server or the 1000 Genomes Project databases or in 2,010 alleles of Chinese controls. Functional studies were not performed. omim.nt GENO:0000002 ClinVar:RCV000170452 biolink:NamedThing omim.nt dbSNP:rs786205216 biolink:NamedThing omim.nt owl:NamedIndividual http://omim.org/entry/104225#0003 biolink:NamedThing omim.nt MONARCH:.well-known/genid/b50c165887a5200e8593 biolink:NamedThing GRCh38chr4-3503611-3532496-Region omim.nt MONARCH:.well-known/genid/b69bc90ac3d9a0eb699e faldo:Region MONARCH:.well-known/genid/OMIM104225ref3 biolink:NamedThing Detection of mutations in LRPAP1, CTSH, LEPREL1, ZNF644, SLC39A5, and SCO2 in 298 families with early-onset high myopia by exome sequencing. omim.nt IAO:0000310 PMID:1400426 biolink:NamedThing omim.nt IAO:0000013 PMID:1712782 biolink:NamedThing omim.nt IAO:0000013 PMID:23830514 biolink:NamedThing omim.nt IAO:0000013 PMID:3266596 biolink:NamedThing omim.nt IAO:0000013 PMID:7535288 biolink:NamedThing omim.nt IAO:0000013 PMID:7538675 biolink:NamedThing omim.nt IAO:0000013 PMID:7789983 biolink:NamedThing omim.nt IAO:0000013 PMID:7959795 biolink:NamedThing omim.nt IAO:0000013 PMID:8654360 biolink:NamedThing omim.nt IAO:0000013 PMID:9207124 biolink:NamedThing omim.nt IAO:0000013 http://omim.org/entry/615431 biolink:NamedThing|biolink:Disease Myopia 23, Autosomal Recessive Myopia 23, Autosomal Recessive omim.nt MYOPIA 23, AUTOSOMAL RECESSIVE; MYP23 owl:Class http://www.omim.org/phenotypicSeries/PS160700 biolink:NamedThing|biolink:Disease Myopia omim.nt owl:Class UMLS:C1416920 biolink:NamedThing omim.nt owl:Class https://www.ncbi.nlm.nih.gov/gene/4043 biolink:NamedThing omim.nt http://omim.org/entry/104230 biolink:NamedThing|biolink:Gene FUT4 Fucosyltransferase 4 omim.nt FUCOSYLTRANSFERASE 4; FUT4|Alpha-3-Fucosyltransferase owl:Class MONARCH:.well-known/genid/bba19a8c61f76b1a1f00 biolink:NamedThing GRCh38chr11-94543920-94549894-Region omim.nt MONARCH:.well-known/genid/bf65d501143804689def faldo:Region MONARCH:.well-known/genid/OMIM104230ref4 biolink:NamedThing Localization of human myeloid-associated surface antigen detected by a panel of 20 monoclonal antibodies to the q12-qter region of chromosome 11. omim.nt IAO:0000310 PMID:10929005 biolink:NamedThing omim.nt IAO:0000013 PMID:11278338 biolink:NamedThing omim.nt IAO:0000013 PMID:1672847 biolink:NamedThing omim.nt IAO:0000013 PMID:3680240 biolink:NamedThing omim.nt IAO:0000013 PMID:7559635 biolink:NamedThing omim.nt IAO:0000013 PMID:7782074 biolink:NamedThing omim.nt IAO:0000013 PMID:8287679 biolink:NamedThing omim.nt IAO:0000013 OBO:CHR_9606chr11q21 biolink:NamedThing omim.nt owl:Class UMLS:C1414865 biolink:NamedThing omim.nt owl:Class https://www.ncbi.nlm.nih.gov/gene/2526 biolink:NamedThing omim.nt http://omim.org/entry/104240 biolink:NamedThing|biolink:Gene ST3GAL4 St3 Beta-Galactoside Alpha-2,3-Sialyltransferase 4 omim.nt ST3 BETA-GALACTOSIDE ALPHA-2,3-SIALYLTRANSFERASE 4; ST3GAL4|Alpha-3-N-Acetylneuraminyltransferase|Cgs23|Cmp-N-Acetylneuraminate-Beta-Galactosidase Alpha-2,3-Sialyltransferase|Nanta3|Sialyltransferase 4C|St3O/N owl:Class MONARCH:.well-known/genid/bfeee2be46a45dae20fe biolink:NamedThing GRCh38chr11-126355685-126414637-Region omim.nt MONARCH:.well-known/genid/bb58ad0bb5fad309026e faldo:Region PMID:12097641 biolink:NamedThing omim.nt IAO:0000013 PMID:18488037 biolink:NamedThing omim.nt IAO:0000013 PMID:2449951 biolink:NamedThing omim.nt IAO:0000013 PMID:24970085 biolink:NamedThing omim.nt IAO:0000013 PMID:7655169 biolink:NamedThing omim.nt IAO:0000013 PMID:8027041 biolink:NamedThing omim.nt IAO:0000013 PMID:8557707 biolink:NamedThing omim.nt IAO:0000013 OBO:CHR_9606chr11q24.2 biolink:NamedThing omim.nt owl:Class UMLS:C1539862 biolink:NamedThing omim.nt owl:Class https://www.ncbi.nlm.nih.gov/gene/6484 biolink:NamedThing omim.nt http://omim.org/entry/104250.0001 biolink:NamedThing ADRA2C, 12-BP DEL, NT964 In transfected cells, a polymorphic alpha-2C-adrenergic receptor (322-325del) has decreased function, and a variant of the beta-1-adrenergic receptor (R389C; {109630.0001}) has increased function. {8:Small et al. (2002)} hypothesized that this combination of receptor variance, which results in increased synaptic norepinephrine release and enhanced receptor function at the myocyte, would predispose persons to heart failure. They performed genotyping at these loci in 159 patients with heart failure and 189 controls. Among black subjects, the adjusted odds ratio for heart failure among persons who were homozygous for the 322-325del as compared with those with the other alpha-2C-adrenergic receptor genotypes was 5.65. There was no increase in risk with the arg389 allele alone. However, there was a marked increase in the risk of heart failure among persons who were homozygous for both arg389 and 322-325del (adjusted odds ratio, 10.11). The patients with heart failure did not differ from the controls in the frequencies of 9 short tandem repeat alleles. Among white subjects, there were too few who were homozygous for both polymorphisms to allow an adequate assessment of risk. {8:Small et al. (2002)} concluded that these 2 polymorphisms act synergistically to increase the risk of heart failure in blacks. Genotyping at these loci may be a useful approach for identification of persons at risk for heart failure or its progression who may be candidates for early preventive measures. {4:Lobmeyer et al. (2007)} genotyped 54 patients with congestive heart failure for the R389G and del322-325 polymorphisms in the ADRB1 and ADRA2C genes, respectively, and performed echocardiography before and after treatment with the beta-blocker metoprolol. The authors found that patients homozygous for arg389 who also carried del322-325 showed a significantly higher ejection fraction increase with metoprolol than all the other genotype combination groups, and concluded that the ADRB1 and ADRA2C polymorphisms synergistically influence the ejection fraction response to beta-blocker therapy of heart failure patients. omim.nt GENO:0000002 http://omim.org/entry/104250 biolink:NamedThing|biolink:Gene ADRA2C Alpha-2C-Adrenergic Receptor|linked to D4S10 omim.nt ALPHA-2C-ADRENERGIC RECEPTOR; ADRA2C|Alpha-2-Adrenergic Receptor, Renal Type|Congestive Heart Failure and Beta-Blocker Response, Modifier of owl:Class ClinVar:RCV000019790 biolink:NamedThing omim.nt dbSNP:rs61767072 biolink:NamedThing omim.nt owl:NamedIndividual http://omim.org/entry/104250#0001 biolink:NamedThing omim.nt MONARCH:.well-known/genid/bbdeca7d88a3592c7fb8 biolink:NamedThing GRCh38chr4-3766384-3768525-Region omim.nt MONARCH:.well-known/genid/bc98f7c3189d99892f28 faldo:Region MONARCH:.well-known/genid/OMIM104250ref3 biolink:NamedThing Genetic mapping of adrenergic receptor genes. (Abstract) omim.nt IAO:0000310 PMID:12374873 biolink:NamedThing omim.nt IAO:0000013 PMID:17496726 biolink:NamedThing omim.nt IAO:0000013 PMID:2842764 biolink:NamedThing omim.nt IAO:0000013 PMID:7688069 biolink:NamedThing omim.nt IAO:0000013 PMID:8188260 biolink:NamedThing omim.nt IAO:0000013 PMID:9371698 biolink:NamedThing omim.nt IAO:0000013 OBO:CHR_9606chr4p16.1 biolink:NamedThing omim.nt owl:Class UMLS:C1412261 biolink:NamedThing omim.nt owl:Class UMLS:C2676080 biolink:NamedThing omim.nt owl:Class https://www.ncbi.nlm.nih.gov/gene/152 biolink:NamedThing omim.nt http://omim.org/entry/104260.0001 biolink:NamedThing ADRA2B, INS/DEL, NT675 This variant, formerly titled EPILEPSY, FAMILIAL ADULT MYOCLONIC, 2 based on the report of {2:De Fusco et al. (2014)}, has been reclassified based on the report of {1:Corbett et al. (2019)}. In affected members of 2 large multigenerational Italian families with familial adult myoclonic epilepsy-2 (FAME2; {607876}), {2:De Fusco et al. (2014)} identified a heterozygous in-frame insertion/deletion (c.675_686del/ins), resulting in the substitution of 5 amino acids (HGGAL) with 4 new residues (QFGR) (H225_L229delinsQ225_F_G_R228). The variant, which was found by sequencing genes in the candidate region on chromosome 2p1.1-q1.2 identified by linkage analysis ({4:Guerrini et al., 2001}), segregated with the disorder in the families. It was not found in the dbSNP, Exome Variant Server, and 1000 Genomes Project databases, or in 575 unrelated controls from Tuscany. Haplotype analysis suggested a founder effect. The variant occurred in the third intracellular loop, a crucial conserved domain for receptor localization and signal transduction. In vitro functional expression assays in cells and Xenopus oocytes showed that the variant interfered with receptor binding to the scaffolding protein spinophilin (PPP1R9B; {603325}) upon neurotransmitter activation, thus resulting in increased epinephrine-stimulated calcium signaling, consistent with a gain of function. In affected members of the families with FAME2 reported by {2:De Fusco et al. (2014)} and {4:Guerrini et al. (2001)}, {1:Corbett et al. (2019)} identified a heterozygous 5-bp repeat expansion (ATTTC)n in intron 1 of the STARD7 gene ({616712.0001}). The findings suggested that the ADRA2B allele is not causative. omim.nt GENO:0000002 http://omim.org/entry/104260 biolink:NamedThing|biolink:Gene ADRA2B Alpha-2B-Adrenergic Receptor omim.nt ALPHA-2B-ADRENERGIC RECEPTOR; ADRA2B|Adra2L1|Alpha-2-Adrenergic Receptor-Like 1 owl:Class ClinVar:RCV000172992 biolink:NamedThing omim.nt dbSNP:rs879255577 biolink:NamedThing omim.nt owl:NamedIndividual http://omim.org/entry/104260#0001 biolink:NamedThing omim.nt MONARCH:.well-known/genid/bc1a8c60b5244f7ebfd8 biolink:NamedThing GRCh38chr2-96112875-96116570-Region omim.nt MONARCH:.well-known/genid/b7fc8bba716b72edfd29 faldo:Region MONARCH:.well-known/genid/OMIM104260ref3 biolink:NamedThing Personal Communication. omim.nt IAO:0000310 PMID:10404816 biolink:NamedThing omim.nt IAO:0000013 PMID:11701600 biolink:NamedThing omim.nt IAO:0000013 PMID:12629104 biolink:NamedThing omim.nt IAO:0000013 PMID:2164221 biolink:NamedThing omim.nt IAO:0000013 PMID:24114805 biolink:NamedThing omim.nt IAO:0000013 PMID:31664034 biolink:NamedThing omim.nt IAO:0000013 OBO:CHR_9606chr2q11.2 biolink:NamedThing omim.nt owl:Class UMLS:C1332029 biolink:NamedThing omim.nt owl:Class https://www.ncbi.nlm.nih.gov/gene/151 biolink:NamedThing omim.nt http://omim.org/entry/104290 biolink:NamedThing|biolink:Disease Alternating Hemiplegia of Childhood 1 Alternating Hemiplegia of Childhood 1 omim.nt ALTERNATING HEMIPLEGIA OF CHILDHOOD 1; AHC1 owl:Class PMID:10695898 biolink:NamedThing omim.nt IAO:0000013 PMID:1361034 biolink:NamedThing omim.nt IAO:0000013 PMID:14667076 biolink:NamedThing omim.nt IAO:0000013 PMID:15174025 biolink:NamedThing omim.nt IAO:0000013 PMID:15286158 biolink:NamedThing omim.nt IAO:0000013 PMID:19996082 biolink:NamedThing omim.nt IAO:0000013 PMID:8496742 biolink:NamedThing omim.nt IAO:0000013 UMLS:C3549447 biolink:NamedThing omim.nt owl:Class ORPHA:2131 biolink:NamedThing|biolink:Disease omim.nt owl:Class http://www.omim.org/phenotypicSeries/PS104290 biolink:NamedThing|biolink:Disease Alternating hemiplegia of childhood omim.nt owl:Class MONARCH:.well-known/genid/OMIM104300ref117 biolink:NamedThing Familial organic psychosis (Alzheimer's type). omim.nt IAO:0000310 MONARCH:.well-known/genid/OMIM104300ref128 biolink:NamedThing Familial presenile dementia: report of a case with clinical and pathological features of Alzheimer's disease. omim.nt IAO:0000310 MONARCH:.well-known/genid/OMIM104300ref145 biolink:NamedThing Physical mapping of the long arm of chromosome 21. (Abstract) omim.nt IAO:0000310 MONARCH:.well-known/genid/OMIM104300ref15 biolink:NamedThing Regional mapping of ETS 2 on chromosome 21 in normal Alzheimer disease individuals. (Abstract) omim.nt IAO:0000310 MONARCH:.well-known/genid/OMIM104300ref156 biolink:NamedThing Physical order of DNA probes linked to familial Alzheimer disease. (Abstract) omim.nt IAO:0000310 MONARCH:.well-known/genid/OMIM104300ref17 biolink:NamedThing Alois Alzheimer. omim.nt IAO:0000310 MONARCH:.well-known/genid/OMIM104300ref171 biolink:NamedThing Isolation of neural cDNA sequences from chromosome 21. (Abstract) omim.nt IAO:0000310 MONARCH:.well-known/genid/OMIM104300ref177 biolink:NamedThing Ueber praesenile Verbloedungen. omim.nt IAO:0000310 MONARCH:.well-known/genid/OMIM104300ref185 biolink:NamedThing Morbus Alzheimer and morbus Pick: a genetic, clinical and patho-anatomical study. omim.nt IAO:0000310 MONARCH:.well-known/genid/OMIM104300ref186 biolink:NamedThing Alzheimer's Lebenswerk. omim.nt IAO:0000310 MONARCH:.well-known/genid/OMIM104300ref197 biolink:NamedThing Genetic linkage analysis of the Alzheimer's associated amyloid beta protein gene with familial Alzheimer's disease and chromosome 21.(Abstract) omim.nt IAO:0000310 MONARCH:.well-known/genid/OMIM104300ref205 biolink:NamedThing Linkage analysis of two extended Alzheimer families with chromosome 21 DNA markers. (Abstract) omim.nt IAO:0000310 MONARCH:.well-known/genid/OMIM104300ref207 biolink:NamedThing The familial Alzheimer's disease gene is located close to the centromere of chromosome 21. (Abstract) omim.nt IAO:0000310 MONARCH:.well-known/genid/OMIM104300ref208 biolink:NamedThing Selection of human chromosome 21 specific DNA probes for genetic analysis in Alzheimer's dementia and Down syndrome. (Abstract) omim.nt IAO:0000310 MONARCH:.well-known/genid/OMIM104300ref220 biolink:NamedThing Alzheimer's Disease and Related Conditions (Ciba Foundation Symposium). omim.nt IAO:0000310 MONARCH:.well-known/genid/OMIM104300ref4 biolink:NamedThing Ueber eine eigenartige Erkrankung der Himrinde. omim.nt IAO:0000310 MONARCH:.well-known/genid/OMIM104300ref5 biolink:NamedThing Ueber eigenartige Krankheitsfalle des spateren Alters. omim.nt IAO:0000310 MONARCH:.well-known/genid/OMIM104300ref62 biolink:NamedThing On the uniform source of amyloid in plaques, tangles and vascular deposits. omim.nt IAO:0000310 MONARCH:.well-known/genid/OMIM104300ref73 biolink:NamedThing Linkage of familial Alzheimer disease to markers on chromosome 21. (Abstract) omim.nt IAO:0000310 PMID:10053018 biolink:NamedThing omim.nt IAO:0000013 PMID:10391244 biolink:NamedThing omim.nt IAO:0000013 PMID:10441572 biolink:NamedThing omim.nt IAO:0000013 PMID:10482953 biolink:NamedThing omim.nt IAO:0000013 PMID:10600748 biolink:NamedThing omim.nt IAO:0000013 PMID:10631141 biolink:NamedThing omim.nt IAO:0000013 PMID:10631151 biolink:NamedThing omim.nt IAO:0000013 PMID:10653020 biolink:NamedThing omim.nt IAO:0000013 PMID:10699053 biolink:NamedThing omim.nt IAO:0000013 PMID:10735278 biolink:NamedThing omim.nt IAO:0000013 PMID:10737127 biolink:NamedThing omim.nt IAO:0000013 PMID:10905250 biolink:NamedThing omim.nt IAO:0000013 PMID:10978362 biolink:NamedThing omim.nt IAO:0000013 PMID:10980749 biolink:NamedThing omim.nt IAO:0000013 PMID:10986048 biolink:NamedThing omim.nt IAO:0000013 PMID:11005793 biolink:NamedThing omim.nt IAO:0000013 PMID:11284991 biolink:NamedThing omim.nt IAO:0000013 PMID:11436125 biolink:NamedThing omim.nt IAO:0000013 PMID:11500807 biolink:NamedThing omim.nt IAO:0000013 PMID:11506396 biolink:NamedThing omim.nt IAO:0000013 PMID:11673588 biolink:NamedThing omim.nt IAO:0000013 PMID:11735772 biolink:NamedThing omim.nt IAO:0000013 PMID:11844848 biolink:NamedThing omim.nt IAO:0000013 PMID:11875758 biolink:NamedThing omim.nt IAO:0000013 PMID:11914406 biolink:NamedThing omim.nt IAO:0000013 PMID:11914421 biolink:NamedThing omim.nt IAO:0000013 PMID:12016588 biolink:NamedThing omim.nt IAO:0000013 PMID:12177374 biolink:NamedThing omim.nt IAO:0000013 PMID:12212789 biolink:NamedThing omim.nt IAO:0000013 PMID:12417360 biolink:NamedThing omim.nt IAO:0000013 PMID:12490529 biolink:NamedThing omim.nt IAO:0000013 PMID:12533083 biolink:NamedThing omim.nt IAO:0000013 PMID:12533085 biolink:NamedThing omim.nt IAO:0000013 PMID:12702875 biolink:NamedThing omim.nt IAO:0000013 PMID:12709467 biolink:NamedThing omim.nt IAO:0000013 PMID:12891359 biolink:NamedThing omim.nt IAO:0000013 PMID:1302033 biolink:NamedThing omim.nt IAO:0000013 PMID:13844275 biolink:NamedThing omim.nt IAO:0000013 PMID:142459 biolink:NamedThing omim.nt IAO:0000013 PMID:14533778 biolink:NamedThing omim.nt IAO:0000013 PMID:14564669 biolink:NamedThing omim.nt IAO:0000013 PMID:14570706 biolink:NamedThing omim.nt IAO:0000013 PMID:14581683 biolink:NamedThing omim.nt IAO:0000013 PMID:14583441 biolink:NamedThing omim.nt IAO:0000013 PMID:14872014 biolink:NamedThing omim.nt IAO:0000013 PMID:1492744 biolink:NamedThing omim.nt IAO:0000013 PMID:15024730 biolink:NamedThing omim.nt IAO:0000013 PMID:15060098 biolink:NamedThing omim.nt IAO:0000013 PMID:15159498 biolink:NamedThing omim.nt IAO:0000013 PMID:15184629 biolink:NamedThing omim.nt IAO:0000013 PMID:1520398 biolink:NamedThing omim.nt IAO:0000013 PMID:15365148 biolink:NamedThing omim.nt IAO:0000013 PMID:15455399 biolink:NamedThing omim.nt IAO:0000013 PMID:15649702 biolink:NamedThing omim.nt IAO:0000013 PMID:15668448 biolink:NamedThing omim.nt IAO:0000013 PMID:15714520 biolink:NamedThing omim.nt IAO:0000013 PMID:15729734 biolink:NamedThing omim.nt IAO:0000013 PMID:15731448 biolink:NamedThing omim.nt IAO:0000013 PMID:15824371 biolink:NamedThing omim.nt IAO:0000013 PMID:15883264 biolink:NamedThing omim.nt IAO:0000013 PMID:16027741 biolink:NamedThing omim.nt IAO:0000013 PMID:16082692 biolink:NamedThing omim.nt IAO:0000013 PMID:16226260 biolink:NamedThing omim.nt IAO:0000013 PMID:16247771 biolink:NamedThing omim.nt IAO:0000013 PMID:16288313 biolink:NamedThing omim.nt IAO:0000013 PMID:16302009 biolink:NamedThing omim.nt IAO:0000013 PMID:16341549 biolink:NamedThing omim.nt IAO:0000013 PMID:16369530 biolink:NamedThing omim.nt IAO:0000013 PMID:16372134 biolink:NamedThing omim.nt IAO:0000013 PMID:16401740 biolink:NamedThing omim.nt IAO:0000013 PMID:16446437 biolink:NamedThing omim.nt IAO:0000013 PMID:16461860 biolink:NamedThing omim.nt IAO:0000013 PMID:16541076 biolink:NamedThing omim.nt IAO:0000013 PMID:16567017 biolink:NamedThing omim.nt IAO:0000013 PMID:16567613 biolink:NamedThing omim.nt IAO:0000013 PMID:1671712 biolink:NamedThing omim.nt IAO:0000013 PMID:1676700 biolink:NamedThing omim.nt IAO:0000013 PMID:1678058 biolink:NamedThing omim.nt IAO:0000013 PMID:16831961 biolink:NamedThing omim.nt IAO:0000013 PMID:16858073 biolink:NamedThing omim.nt IAO:0000013 PMID:16908746 biolink:NamedThing omim.nt IAO:0000013 PMID:17080199 biolink:NamedThing omim.nt IAO:0000013 PMID:17115048 biolink:NamedThing omim.nt IAO:0000013 PMID:17121991 biolink:NamedThing omim.nt IAO:0000013 PMID:17220890 biolink:NamedThing omim.nt IAO:0000013 PMID:17360687 biolink:NamedThing omim.nt IAO:0000013 PMID:17420311 biolink:NamedThing omim.nt IAO:0000013 PMID:17553421 biolink:NamedThing omim.nt IAO:0000013 PMID:1763890 biolink:NamedThing omim.nt IAO:0000013 PMID:17756099 biolink:NamedThing omim.nt IAO:0000013 PMID:18071042 biolink:NamedThing omim.nt IAO:0000013 PMID:18272374 biolink:NamedThing omim.nt IAO:0000013 PMID:1867282 biolink:NamedThing omim.nt IAO:0000013 PMID:18802001 biolink:NamedThing omim.nt IAO:0000013 PMID:18836460 biolink:NamedThing omim.nt IAO:0000013 PMID:18854865 biolink:NamedThing omim.nt IAO:0000013 PMID:1908231 biolink:NamedThing omim.nt IAO:0000013 PMID:19098903 biolink:NamedThing omim.nt IAO:0000013 PMID:19198615 biolink:NamedThing omim.nt IAO:0000013 PMID:1925564 biolink:NamedThing omim.nt IAO:0000013 PMID:19273754 biolink:NamedThing omim.nt IAO:0000013 PMID:19286555 biolink:NamedThing omim.nt IAO:0000013 PMID:1939107 biolink:NamedThing omim.nt IAO:0000013 PMID:19606474 biolink:NamedThing omim.nt IAO:0000013 PMID:19734902 biolink:NamedThing omim.nt IAO:0000013 PMID:19734903 biolink:NamedThing omim.nt IAO:0000013 PMID:19738170 biolink:NamedThing omim.nt IAO:0000013 PMID:19822782 biolink:NamedThing omim.nt IAO:0000013 PMID:19923550 biolink:NamedThing omim.nt IAO:0000013 PMID:20167577 biolink:NamedThing omim.nt IAO:0000013 PMID:2035522 biolink:NamedThing omim.nt IAO:0000013 PMID:2035523 biolink:NamedThing omim.nt IAO:0000013 PMID:20457965 biolink:NamedThing omim.nt IAO:0000013 PMID:20554627 biolink:NamedThing omim.nt IAO:0000013 PMID:20697030 biolink:NamedThing omim.nt IAO:0000013 PMID:20826309 biolink:NamedThing omim.nt IAO:0000013 PMID:21059989 biolink:NamedThing omim.nt IAO:0000013 PMID:21148344 biolink:NamedThing omim.nt IAO:0000013 PMID:21220680 biolink:NamedThing omim.nt IAO:0000013 PMID:21391232 biolink:NamedThing omim.nt IAO:0000013 PMID:21460840 biolink:NamedThing omim.nt IAO:0000013 PMID:21640374 biolink:NamedThing omim.nt IAO:0000013 PMID:21823155 biolink:NamedThing omim.nt IAO:0000013 PMID:22033521 biolink:NamedThing omim.nt IAO:0000013 PMID:22278060 biolink:NamedThing omim.nt IAO:0000013 PMID:22323736 biolink:NamedThing omim.nt IAO:0000013 PMID:22403391 biolink:NamedThing omim.nt IAO:0000013 PMID:22660329 biolink:NamedThing omim.nt IAO:0000013 PMID:22784036 biolink:NamedThing omim.nt IAO:0000013 PMID:22801501 biolink:NamedThing omim.nt IAO:0000013 PMID:2314579 biolink:NamedThing omim.nt IAO:0000013 PMID:23704552 biolink:NamedThing omim.nt IAO:0000013 PMID:23704553 biolink:NamedThing omim.nt IAO:0000013 PMID:23704554 biolink:NamedThing omim.nt IAO:0000013 PMID:23704555 biolink:NamedThing omim.nt IAO:0000013 PMID:23704556 biolink:NamedThing omim.nt IAO:0000013 PMID:2395471 biolink:NamedThing omim.nt IAO:0000013 PMID:24162737 biolink:NamedThing omim.nt IAO:0000013 PMID:2448646 biolink:NamedThing omim.nt IAO:0000013 PMID:2457908 biolink:NamedThing omim.nt IAO:0000013 PMID:24786080 biolink:NamedThing omim.nt IAO:0000013 PMID:24821909 biolink:NamedThing omim.nt IAO:0000013 PMID:2528696 biolink:NamedThing omim.nt IAO:0000013 PMID:2531979 biolink:NamedThing omim.nt IAO:0000013 PMID:2563508 biolink:NamedThing omim.nt IAO:0000013 PMID:27033548 biolink:NamedThing omim.nt IAO:0000013 PMID:28052060 biolink:NamedThing omim.nt IAO:0000013 PMID:2856948 biolink:NamedThing omim.nt IAO:0000013 PMID:2880399 biolink:NamedThing omim.nt IAO:0000013 PMID:28806762 biolink:NamedThing omim.nt IAO:0000013 PMID:2888020 biolink:NamedThing omim.nt IAO:0000013 PMID:2901095 biolink:NamedThing omim.nt IAO:0000013 PMID:2902440 biolink:NamedThing omim.nt IAO:0000013 PMID:29293211 biolink:NamedThing omim.nt IAO:0000013 PMID:2964224 biolink:NamedThing omim.nt IAO:0000013 PMID:2970636 biolink:NamedThing omim.nt IAO:0000013 PMID:30046111 biolink:NamedThing omim.nt IAO:0000013 PMID:3126980 biolink:NamedThing omim.nt IAO:0000013 PMID:31395777 biolink:NamedThing omim.nt IAO:0000013 PMID:31645758 biolink:NamedThing omim.nt IAO:0000013 PMID:31727856 biolink:NamedThing omim.nt IAO:0000013 PMID:31748742 biolink:NamedThing omim.nt IAO:0000013 PMID:3257719 biolink:NamedThing omim.nt IAO:0000013 PMID:3277188 biolink:NamedThing omim.nt IAO:0000013 PMID:3306405 biolink:NamedThing omim.nt IAO:0000013 PMID:3340281 biolink:NamedThing omim.nt IAO:0000013 PMID:3350531 biolink:NamedThing omim.nt IAO:0000013 PMID:3354615 biolink:NamedThing omim.nt IAO:0000013 PMID:3495222 biolink:NamedThing omim.nt IAO:0000013 PMID:363103 biolink:NamedThing omim.nt IAO:0000013 PMID:3662454 biolink:NamedThing omim.nt IAO:0000013 PMID:3690426 biolink:NamedThing omim.nt IAO:0000013 PMID:384295 biolink:NamedThing omim.nt IAO:0000013 PMID:394671 biolink:NamedThing omim.nt IAO:0000013 PMID:474626 biolink:NamedThing omim.nt IAO:0000013 PMID:567976 biolink:NamedThing omim.nt IAO:0000013 PMID:5912002 biolink:NamedThing omim.nt IAO:0000013 PMID:6102203 biolink:NamedThing omim.nt IAO:0000013 PMID:6228188 biolink:NamedThing omim.nt IAO:0000013 PMID:6251745 biolink:NamedThing omim.nt IAO:0000013 PMID:6536726 biolink:NamedThing omim.nt IAO:0000013 PMID:6538270 biolink:NamedThing omim.nt IAO:0000013 PMID:6600923 biolink:NamedThing omim.nt IAO:0000013 PMID:6610841 biolink:NamedThing omim.nt IAO:0000013 PMID:6738605 biolink:NamedThing omim.nt IAO:0000013 PMID:6859040 biolink:NamedThing omim.nt IAO:0000013 PMID:6881929 biolink:NamedThing omim.nt IAO:0000013 PMID:6992964 biolink:NamedThing omim.nt IAO:0000013 PMID:7004610 biolink:NamedThing omim.nt IAO:0000013 PMID:7023604 biolink:NamedThing omim.nt IAO:0000013 PMID:7205322 biolink:NamedThing omim.nt IAO:0000013 PMID:7294063 biolink:NamedThing omim.nt IAO:0000013 PMID:7581446 biolink:NamedThing omim.nt IAO:0000013 PMID:8035925 biolink:NamedThing omim.nt IAO:0000013 PMID:8290042 biolink:NamedThing omim.nt IAO:0000013 PMID:8346443 biolink:NamedThing omim.nt IAO:0000013 PMID:8411049 biolink:NamedThing omim.nt IAO:0000013 PMID:85165 biolink:NamedThing omim.nt IAO:0000013 PMID:8649554 biolink:NamedThing omim.nt IAO:0000013 PMID:8658185 biolink:NamedThing omim.nt IAO:0000013 PMID:8751438 biolink:NamedThing omim.nt IAO:0000013 PMID:8751868 biolink:NamedThing omim.nt IAO:0000013 PMID:8756120 biolink:NamedThing omim.nt IAO:0000013 PMID:9050898 biolink:NamedThing omim.nt IAO:0000013 PMID:9122152 biolink:NamedThing omim.nt IAO:0000013 PMID:9167474 biolink:NamedThing omim.nt IAO:0000013 PMID:9241262 biolink:NamedThing omim.nt IAO:0000013 PMID:9626772 biolink:NamedThing omim.nt IAO:0000013 PMID:9653640 biolink:NamedThing omim.nt IAO:0000013 UMLS:C0002395 biolink:NamedThing omim.nt owl:Class UMLS:C1863052 biolink:NamedThing omim.nt owl:Class UMLS:C1863053 biolink:NamedThing omim.nt owl:Class UMLS:C3549448 biolink:NamedThing omim.nt owl:Class ORPHA:1020 biolink:NamedThing|biolink:Disease omim.nt owl:Class http://omim.org/entry/104310 biolink:NamedThing|biolink:Disease Alzheimer Disease 2 Alzheimer Disease 2 omim.nt ALZHEIMER DISEASE 2; AD2|Alzheimer Disease 2, Late-Onset|Alzheimer Disease Associated With Apoe4 owl:Class MONARCH:.well-known/genid/OMIM104310ref10 biolink:NamedThing Linkage studies in familial Alzheimer's disease. (Abstract) omim.nt IAO:0000310 MONARCH:.well-known/genid/OMIM104310ref9 biolink:NamedThing Linkage studies in familial Alzheimer's disease: evidence for chromosome 19 linkage. (Abstract) omim.nt IAO:0000310 PMID:11248079 biolink:NamedThing omim.nt IAO:0000013 PMID:11790235 biolink:NamedThing omim.nt IAO:0000013 PMID:1349467 biolink:NamedThing omim.nt IAO:0000013 PMID:14688411 biolink:NamedThing omim.nt IAO:0000013 PMID:15385439 biolink:NamedThing omim.nt IAO:0000013 PMID:16401842 biolink:NamedThing omim.nt IAO:0000013 PMID:16894123 biolink:NamedThing omim.nt IAO:0000013 PMID:17310043 biolink:NamedThing omim.nt IAO:0000013 PMID:1998342 biolink:NamedThing omim.nt IAO:0000013 PMID:2035524 biolink:NamedThing omim.nt IAO:0000013 PMID:20479234 biolink:NamedThing omim.nt IAO:0000013 PMID:26494756 biolink:NamedThing omim.nt IAO:0000013 PMID:3197787 biolink:NamedThing omim.nt IAO:0000013 PMID:32376954 biolink:NamedThing omim.nt IAO:0000013 PMID:3422543 biolink:NamedThing omim.nt IAO:0000013 PMID:3669048 biolink:NamedThing omim.nt IAO:0000013 PMID:8592548 biolink:NamedThing omim.nt IAO:0000013 UMLS:C1863051 biolink:NamedThing omim.nt owl:Class http://omim.org/entry/104311.0001 biolink:NamedThing PSEN1, MET146LEU In 2 unrelated families with chromosome 14-linked early-onset Alzheimer disease (AD3; {607822}), {124:Sherrington et al. (1995)} identified a mutation in the PSEN1 gene, resulting in a met146-to-leu (M146L) substitution. The authors detected the mutation in affected family members but not in asymptomatic family members aged more than 2 standard deviations beyond the mean age of onset and not on 284 chromosomes from unrelated, neurologically normal subjects drawn from comparable ethnic origins. The 2 families reported by {124:Sherrington et al. (1995)} were from southern Italy. {127:Sorbi et al. (1995)} studied 15 unrelated Italian families with necropsy-proven early-onset familial AD and found the met146-to-leu substitution in 3. {90:Morelli et al. (1998)} described this mutation, due to an A-to-T transversion at the first position of codon 146, in an Argentinian family with early-onset FAD. {44:Halliday et al. (2005)} identified the M146L substitution in 2 Australian sibs with early-onset FAD. Family history suggested that their father was also affected. Neuropathologic examination of both patients showed numerous cortical plaques and neurofibrillary tangles, consistent with AD. In addition, both cases showed ballooned neurons and numerous tau (MAPT; {157140})-immunoreactive Pick bodies in upper frontotemporal cortical layers and in the hippocampal dentate gyrus. {44:Halliday et al. (2005)} suggested that the M146L mutation may specifically predispose to both AD and Pick pathology by affecting multiple intracellular pathways involving tau phosphorylation. {11:Bruni et al. (2010)} identified an AD3 family from Naples, Italy, with the M146L mutation. The 40-year-old proband showed memory loss with attention and planning deficits. Six other family members spanning 4 generations had developed dementia. {11:Bruni et al. (2010)} retrospectively identified 7 articles reporting AD3 families with the M146L mutation, including those reported by {127:Sorbi et al. (1995)} and {44:Halliday et al. (2005)}. They also reviewed the Calabrian families reported by {124:Sherrington et al. (1995)}. The reconstituted Calabrian families, the family from Naples, and the Australian family comprised 148 affected individuals, and a genealogic link from the 17th century was established for all the patients with the M146L mutation. The ancestral mutation originated from southern Italy. Phenotypic cluster analysis applied to 50 patients at onset and during the first 2 years identified 4 subgroups: 2 with a cognitive onset (58%), including memory loss or disorientation, and 2 with a behavioral onset (42%), including apathy, depression, and executive dysfunction. Neuropathologic examination of 2 patients showed substantial beta-amyloid and phosphorylated tau immunoreactivity throughout the cortex, deep brain regions, and brainstem, consistent with AD. For 2 other mutations in the same codon, see met146-to-val ({104311.0007}) and met146-to-ile ({104311.0015}). omim.nt GENO:0000002 http://omim.org/entry/104311 biolink:NamedThing|biolink:Gene PSEN1 mutation identified in 1 ACNINV3 family|Presenilin 1 omim.nt PRESENILIN 1; PSEN1|Ps1|S182 owl:Class ClinVar:RCV000019751 biolink:NamedThing omim.nt ClinVar:RCV001248367 biolink:NamedThing omim.nt dbSNP:rs63750306 biolink:NamedThing omim.nt owl:NamedIndividual http://omim.org/entry/104311#0001 biolink:NamedThing omim.nt http://omim.org/entry/104311.0002 biolink:NamedThing PSEN1, HIS163ARG In an American pedigree with chromosome 14-linked Alzheimer disease (AD3; {607822}), {124:Sherrington et al. (1995)} found a mutation in the PSEN1 gene, resulting in a his163-to-arg (H163R) substitution. The same mutation was found in a small French Canadian pedigree with early-onset Alzheimer disease. omim.nt GENO:0000002 ClinVar:RCV000019752 biolink:NamedThing omim.nt ClinVar:RCV000084318 biolink:NamedThing omim.nt ClinVar:RCV000534810 biolink:NamedThing omim.nt dbSNP:rs63750590 biolink:NamedThing omim.nt owl:NamedIndividual http://omim.org/entry/104311#0002 biolink:NamedThing omim.nt http://omim.org/entry/104311.0003 biolink:NamedThing PSEN1, ALA246GLU In a pedigree with chromosome 14-linked early-onset Alzheimer disease (AD3; {607822}), {124:Sherrington et al. (1995)} identified a mutation in the PSEN1 gene, resulting in an ala246-to-glu substitution (A246E). omim.nt GENO:0000002 ClinVar:RCV000019753 biolink:NamedThing omim.nt ClinVar:RCV000084361 biolink:NamedThing omim.nt ClinVar:RCV000542870 biolink:NamedThing omim.nt dbSNP:rs63750526 biolink:NamedThing omim.nt owl:NamedIndividual http://omim.org/entry/104311#0003 biolink:NamedThing omim.nt http://omim.org/entry/104311.0004 biolink:NamedThing PSEN1, LEU286VAL In a pedigree with chromosome 14-linked early-onset Alzheimer disease (AD3; {607822}), {124:Sherrington et al. (1995)} identified a mutation in the PSEN1 gene, resulting in a leu286-to-val (L286V) substitution. omim.nt GENO:0000002 ClinVar:RCV000019754 biolink:NamedThing omim.nt ClinVar:RCV000084387 biolink:NamedThing omim.nt dbSNP:rs63751235 biolink:NamedThing omim.nt owl:NamedIndividual http://omim.org/entry/104311#0004 biolink:NamedThing omim.nt http://omim.org/entry/104311.0005 biolink:NamedThing PSEN1, CYS410TYR In 2 pedigrees with early-onset Alzheimer disease (AD3; {607822}), {124:Sherrington et al. (1995)} identified a mutation in the PSEN1 gene, resulting in a cys410-to-tyr (C410Y) substitution. omim.nt GENO:0000002 ClinVar:RCV000019755 biolink:NamedThing omim.nt ClinVar:RCV000084407 biolink:NamedThing omim.nt ClinVar:RCV000640605 biolink:NamedThing omim.nt dbSNP:rs661 biolink:NamedThing omim.nt owl:NamedIndividual http://omim.org/entry/104311#0005 biolink:NamedThing omim.nt http://omim.org/entry/104311.0006 biolink:NamedThing PSEN1, MET139VAL In 2 families with early-onset Alzheimer disease (AD3; {607822}), the {1:Alzheimer's Disease Collaborative Group (1995)} detected a mutation in the PSEN1 gene, resulting in a met139-to-val (M139V) substitution. In both families, the mean age of onset was 39 to 41 years. {51:Hull et al. (1998)} described a German family with early-onset Alzheimer disease caused by the M139V mutation. From the age of 43 years, the proband had complained of deficits in short-term memory. Relatives had noticed his symptoms even earlier and dated the onset of deficits to age 38 years when he showed increasing interruptions during speech followed by social withdrawal. There was a strong family history of dementia. Through 3 generations the onset of dementia in this family was between 42 and 45 years. {35:Fox et al. (1997)} reported on this mutation in a British family. {115:Rippon et al. (2003)} reported an African American family with atypical early-onset AD caused by the M139V mutation. omim.nt GENO:0000002 ClinVar:RCV000019756 biolink:NamedThing omim.nt ClinVar:RCV000084304 biolink:NamedThing omim.nt dbSNP:rs63751037 biolink:NamedThing omim.nt owl:NamedIndividual http://omim.org/entry/104311#0006 biolink:NamedThing omim.nt http://omim.org/entry/104311.0007 biolink:NamedThing PSEN1, MET146VAL In 3 unrelated early-onset Alzheimer disease families (AD3; {607822}), the {1:Alzheimer's Disease Collaborative Group (1995)} found a met146-to-val (M146V) mutation in the PSEN1 gene. See also the M146L mutation ({104311.0001}). The age of onset was unusually early in these 3 families, between 36 and 40 years. omim.nt GENO:0000002 ClinVar:RCV000019757 biolink:NamedThing omim.nt http://omim.org/entry/104311#0007 biolink:NamedThing omim.nt http://omim.org/entry/104311.0008 biolink:NamedThing PSEN1, HIS163TYR In a Swedish family in which 8 members had early-onset Alzheimer disease (AD3; {607822}), the {1:Alzheimer's Disease Collaborative Group (1995)} identified an his163-to-tyr (H163Y) mutation. The average age of onset was 47 years. See also the H163R mutation ({104311.0002}). omim.nt GENO:0000002 ClinVar:RCV000019758 biolink:NamedThing omim.nt ClinVar:RCV000084317 biolink:NamedThing omim.nt dbSNP:rs63749885 biolink:NamedThing omim.nt owl:NamedIndividual http://omim.org/entry/104311#0008 biolink:NamedThing omim.nt http://omim.org/entry/104311.0009 biolink:NamedThing PSEN1, GLU280ALA In 4 families with onset of Alzheimer disease in their late forties (AD3; {607822}), the {1:Alzheimer's Disease Collaborative Group (1995)} found a glu280-to-ala (E280A) mutation in the AD3 gene. With this and other missense mutations in the PS1 gene, increased levels of amyloid beta-peptides ending at residue 42 are found in plasma and skin fibroblast media of gene carriers. A-beta-42 aggregates readily and appears to provide a nidus for the subsequent aggregations of A-beta-40, resulting in the formation of innumerable neuritic plaques. To obtain in vivo information about how PS1 mutations cause AD pathology at such early ages, {77:Lemere et al. (1996)} characterized the neuropathologic phenotype of 4 patients from a large Colombian kindred bearing the glu280-to-ala substitution in PS1. Using antibodies specific to the alternative C-termini of A-beta, they detected massive deposition of A-beta-42 (the earliest and predominant form of plaque A-beta to occur in AD) in many brain regions. Quantification revealed a significant increase in the A-beta-42 form, but not the A-beta-40 form, in the brains from 4 patients with the PS1 mutation compared with those from 12 sporadic AD patients. Thus, {77:Lemere et al. (1996)} concluded that the mutant PS1 protein appears to alter the proteolytic processing of the beta-amyloid precursor protein at the C-terminus of A-beta to favor deposition of A-beta-42. {83:Lopera et al. (1997)} screened all members of 5 extended families (nearly 3,000 individuals) in a community based in Antioquia, Colombia, where early-onset Alzheimer disease due to the glu280-to-ala mutation had been shown to be unusually frequent. Using standard diagnostic criteria, a case series of 128 individuals was identified, of which 6 had definitive (autopsy-proven) early-onset AD, 93 had probable early-onset AD, and 29 had possible early-onset AD. The patients had a mean age at onset of 46.8 years (range, 34 to 62 years). The average interval until death was 8 years. Headache was noted in affected individuals significantly more frequently than in those not affected. The most frequent presentations were memory loss followed by behavioral and personality changes and progressive loss of language ability. In the final stages, gait disturbances, seizures, and myoclonus were frequent. {65:Kosik et al. (2015)} identified 6 homozygous carriers of the E280A mutation among the large cohort of extended families from Colombia reported by {83:Lopera et al. (1997)}. Two of the individuals (age range 44-46 years old) had dementia for 1 to 7 years before the time of ascertainment (range of dementia onset 37 to 45 years). These individuals presented 5 and 13 years before the mean age at onset of dementia for the entire kindred. Five of the 6 homozygous individuals were female. The findings indicated that homozygosity for the E280A mutation exists and is not lethal, and may be associated with an accelerated age at dementia onset compared to heterozygous mutation carriers. {56:Johnson et al. (2001)} demonstrated that regional cerebral perfusion abnormalities based on SPECT are detectable before development of the clinical symptoms of Alzheimer disease in carriers of the glu280-to-ala PS1 mutation. By genotype analysis of a large Colombian kindred with 109 carriers of the E280A PS1 mutation, including 52 members with AD, {102:Pastor et al. (2003)} found that those with at least 1 APOE4 allele (see {107741}) were more likely to develop AD at an earlier age than those without an APOE4 allele, indicating an epistatic effect. Promoter APOE variants did not influence either the onset or the duration of the disease. In a woman from the very large Colombian family with early-onset Alzheimer disease caused by a heterozygous E280A mutation in the PSEN1 gene, who did not develop mild cognitive impairment until her seventies, {2:Arboleda-Velasquez et al. (2019)} detected homozygosity for an arginine-to-serine substitution at amino acid 136 (R136S) on the APOE3 allele of APOE ({107741.0034}). The R136S mutation in APOE is known as the Christchurch mutation, and the authors referred to the APOE allele in this individual as APOE3ch. omim.nt GENO:0000002 ClinVar:RCV000019759 biolink:NamedThing omim.nt ClinVar:RCV000701892 biolink:NamedThing omim.nt dbSNP:rs63750231 biolink:NamedThing omim.nt owl:NamedIndividual http://omim.org/entry/104311#0009 biolink:NamedThing omim.nt http://omim.org/entry/104311.0010 biolink:NamedThing PSEN1, GLU280GLY In 2 families with multiple cases of Alzheimer disease with onset in the early forties (AD3; {607822}), the {1:Alzheimer's Disease Collaborative Group (1995)} found a glu280-to-gly (E280G) mutation in the AD3 gene. See also the E280A mutation ({104311.0009}). In 1 of the families with the E280G mutation reported by the {1:Alzheimer's Disease Collaborative Group (1995)}, {98:O'Riordan et al. (2002)} described an atypical disease pattern in 3 additional members from the third generation who developed symptoms in their forties (see {607822}). One had cognitive impairment, spastic paraparesis, and white matter abnormalities on MRI. One of his sibs developed dementia and myoclonus and had white matter abnormalities on MRI. Another sib had ophthalmoplegia, spastic-ataxic quadriparesis, and cotton-wool plaques with amyloid angiopathy on brain biopsy (MRI was not performed). The authors suggested that the MRI findings may reflect an ischemic leukoencephalopathy due to amyloid angiopathy affecting meningocortical vessels. In a patient with Alzheimer disease with spastic paraparesis and cotton-wool plaques with onset at age 52 years, {118:Rogaeva et al. (2003)} identified the E280G mutation, which they incorrectly reported as E280Q. {119:Rogaeva (2004)} reported the correct mutation as E280G. There were 4 other affected members in the patient's family. omim.nt GENO:0000002 ClinVar:RCV000019760 biolink:NamedThing omim.nt ClinVar:RCV000019761 biolink:NamedThing omim.nt ClinVar:RCV000084381 biolink:NamedThing omim.nt http://omim.org/entry/104311#0010 biolink:NamedThing omim.nt http://omim.org/entry/104311.0011 biolink:NamedThing PSEN1, PRO267SER In 1 family with early-onset Alzheimer disease (AD3; {607822}) with a mean onset of 35 years, the {1:Alzheimer's Disease Collaborative Group (1995)} detected a pro267-to-ser (P267S) mutation in the AD3 gene. omim.nt GENO:0000002 ClinVar:RCV000019762 biolink:NamedThing omim.nt ClinVar:RCV000084371 biolink:NamedThing omim.nt dbSNP:rs63751229 biolink:NamedThing omim.nt owl:NamedIndividual http://omim.org/entry/104311#0011 biolink:NamedThing omim.nt http://omim.org/entry/104311.0012 biolink:NamedThing PSEN1, IVS8AS, G-T, -1 {104:Perez-Tur et al. (1995)} found a heterozygous mutation changing G to T in the splice acceptor site for exon 9 in a family segregating Alzheimer disease with linkage to chromosome 14 (AD3; {607822}). RT-PCR of cDNA isolated from lymphoblasts of affected members demonstrated an aberrant band in the sequence of which exon 9 was deleted in-frame, removing amino acids 290 to 319. The authors suggested that since the predicted protein structure would retain the same overall topology as the wildtype protein, exon 9 was of particular relevance to the abnormal physiology of presenilin 1 in Alzheimer disease. {139:Thinakaran et al. (1996)} demonstrated that PS1 undergoes endoproteolytic processing in vivo to yield 27-kD N-terminal and 17-kD C-terminal derivatives, cleaved between amino acids 260 and 320. In a British FAD pedigree with the PS1 exon 9 deletion, there was no cleavage of PS1. {18:Crook et al. (1998)} described the same deletion of exon 9 in a Finnish pedigree with 17 affected individuals of both sexes in 3 generations suffering from a novel variant of Alzheimer disease. The mechanism of the deletion of exon 9 in this family was not a mutation in the acceptor splice site, however, and remained to be determined. The disorder in the Finnish pedigree was characterized by progressive dementia that was in most cases preceded by spastic paraparesis (see {607822}). Neuropathologic investigations showed numerous distinct, large, round, and eosinophilic plaques, as well as neurofibrillary tangles and amyloid angiopathy throughout the cerebral cortex. The predominant plaques resembled cotton-wool balls and were immunoreactive for A-beta, but lacked a congophilic dense core or marked plaque-related neuritic pathology. {18:Crook et al. (1998)} referred to this mutation as the delta-9 mutation. They stated that it was the only known structural mutation in the PSEN1 gene; previously identified mutations had been missense mutations. The delta-9 mutant protein is not metabolized to the stable 18-kD N-terminal and the 28-kD C-terminal fragments, and thus the mutant holoprotein accumulates. Unlike the missense mutations, the delta-9 mutation rescues the egl phenotype caused by mutations in sel-12, the C. elegans homolog of the presenilins. Of the mutations described in the PSEN1 gene, the delta-9 mutation has the greatest effect on A-beta-42(43) production. The missense mutations in the PSEN1 gene give rise to phenotypic manifestations that differ very little from classic AD, apart from an unusually early onset. {70:Kwok et al. (1997)} reported another family with an association between a splice acceptor site mutation of PSEN1 (resulting in the delta-9 deletion) and presenile AD with spastic paraparesis. {70:Kwok et al. (1997)} reported a second family in which an arg278-to-thr missense mutation ({104311.0017}) was associated with presenile AD and spastic paraparesis. In a fourth case, reported by {70:Kwok et al. (1997)}, the mutation was not identified. As summarized by {18:Crook et al. (1998)}, spastic paraparesis had been reported in 2 of 4 families with the delta-9 mutation and in 2 other families. Thus, the association of this syndrome with the delta-9 mutation is not a simple one. In this variant form of Alzheimer disease, spastic paraparesis precedes dementia and large A-beta-amyloid plaques resembling cotton-wool balls are a leading neuropathologic feature. The disorder has been described in a Finnish pedigree ({144:Verkkoniemi et al., 2000}; {18:Crook et al., 1998}) and in an Australian pedigree ({125:Smith et al., 2001}). In the family of {125:Smith et al. (2001)}, the onset of dementia was delayed and modified in subjects with spastic paraparesis. This phenotypic variation suggested that modifying factors are associated with exon 9 deletions. omim.nt GENO:0000002 ClinVar:RCV000019763 biolink:NamedThing omim.nt ClinVar:RCV000019764 biolink:NamedThing omim.nt http://omim.org/entry/104311#0012 biolink:NamedThing omim.nt http://omim.org/entry/104311.0013 biolink:NamedThing PSEN1, GLU120ASP {113:Reznik-Wolf et al. (1996)} used denaturing gradient gel electrophoresis to examine the PS1 gene in several Israeli families with early-onset Alzheimer disease (AD3; {607822}). They found that 2 siblings with early-onset AD carried a missense mutation changing codon 120 from glutamic acid to aspartic acid. This allele was not found in 118 control individuals. omim.nt GENO:0000002 ClinVar:RCV000019765 biolink:NamedThing omim.nt ClinVar:RCV000084300 biolink:NamedThing omim.nt dbSNP:rs63751272 biolink:NamedThing omim.nt owl:NamedIndividual http://omim.org/entry/104311#0013 biolink:NamedThing omim.nt http://omim.org/entry/104311.0014 biolink:NamedThing PSEN1, ALA426PRO In a Scottish-Irish family with early-onset Alzheimer disease (AD3; {607822}), {109:Poorkaj et al. (1998)} identified an A-to-C change at nucleotide 1278 in the PSEN1 gene that resulted in an ala426-to-pro (A426P) substitution. omim.nt GENO:0000002 ClinVar:RCV000019766 biolink:NamedThing omim.nt ClinVar:RCV000084411 biolink:NamedThing omim.nt ClinVar:RCV000763348 biolink:NamedThing omim.nt dbSNP:rs63751223 biolink:NamedThing omim.nt owl:NamedIndividual http://omim.org/entry/104311#0014 biolink:NamedThing omim.nt http://omim.org/entry/104311.0015 biolink:NamedThing PSEN1, MET146ILE In a Danish family with autosomal dominant early-onset Alzheimer disease (AD3; {607822}) spanning 3 generations, {57:Jorgensen et al. (1996)} identified a G-A transition in the PSEN1 gene, resulting in a met146-to-ile (M146I) substitution. The average age of disease onset was 44 years. In a Swedish family with Alzheimer disease in 4 consecutive generations, {43:Gustafson et al. (1998)} identified a single base substitution (ATG to ATC) in codon 146 of the PSEN1 gene, resulting in an M146I substitution. omim.nt GENO:0000002 ClinVar:RCV000019767 biolink:NamedThing omim.nt dbSNP:rs63750391 biolink:NamedThing omim.nt owl:NamedIndividual http://omim.org/entry/104311#0015 biolink:NamedThing omim.nt http://omim.org/entry/104311.0016 biolink:NamedThing PSEN1, LEU250SER {47:Harvey et al. (1998)} described a family in which 7 members had early-onset Alzheimer disease (AD3; {607822}) due to a leu250-to-ser (L250S) missense mutation in the PSEN1 gene. Detailed clinical information was available on 5 members. All had an early age at onset, with a median age of 52 years. Age at onset varied between 49 and 56 years, with duration of illness varying between 6 years and 15 years. Myoclonus, depression, and psychosis were features in this family; seizures were not reported. omim.nt GENO:0000002 ClinVar:RCV000019768 biolink:NamedThing omim.nt ClinVar:RCV000084363 biolink:NamedThing omim.nt dbSNP:rs63751163 biolink:NamedThing omim.nt owl:NamedIndividual http://omim.org/entry/104311#0016 biolink:NamedThing omim.nt http://omim.org/entry/104311.0017 biolink:NamedThing PSEN1, ARG278THR {70:Kwok et al. (1997)} described an arg278-to-thr mutation of the PSEN1 gene associated with Alzheimer disease with spastic paraparesis and distinctive large eosinophilic plaques (see {607822}), as well as neurofibrillary tangles and amyloid angiopathy throughout the cerebral cortex. The predominant plaques resembled cotton-wool balls and were immunoreactive for A-beta, but lacked a congophilic dense core or marked plaque-related neuritic pathology. This pathologic change was seen in 2 families with deletion of exon 9 of the PSEN1 gene ({104311.0012}). omim.nt GENO:0000002 ClinVar:RCV000019769 biolink:NamedThing omim.nt dbSNP:rs63749891 biolink:NamedThing omim.nt owl:NamedIndividual http://omim.org/entry/104311#0017 biolink:NamedThing omim.nt http://omim.org/entry/104311.0018 biolink:NamedThing PSEN1, IVS4DS, 1-BP DEL, G In 2 autopsy-confirmed cases with early-onset Alzheimer disease (AD3; {607822}), {143:Tysoe et al. (1998)} identified a single-base deletion of a G at the splice donor site of intron 4 of the PSEN1 gene. {22:De Jonghe et al. (1999)} identified the same mutation in 4 additional, unrelated early-onset AD cases and demonstrated that the mutation segregates in an autosomal dominant manner and that all cases have 1 common ancestor. {22:De Jonghe et al. (1999)} showed that the intron 4 mutation produces 3 different transcripts, 2 deletion transcripts (1 involving a deletion of all of exon 4 and the other involving a deletion of part of exon 4), and a transcript that results in insertion of a threonine between codons 113 and 114. The truncated proteins were not detectable in vivo in brain homogenates or in lymphoblast lysates of mutation carriers. In vitro, HEK293 cells overexpressing the insertion cDNA construct or either of the deletion constructs showed amyloid beta-42 secretion approximately 3 to 4 times greater than normal only for the insertion cDNA construct. Increased amyloid beta-42 production was also observed in brain homogenates. {22:De Jonghe et al. (1999)} concluded that in the case of the intron 4 mutation, the Alzheimer disease pathophysiology results from increased amyloid beta-42 secretion by the insertion transcript, comparable with cases carrying a dominant PSEN1 missense mutation. omim.nt GENO:0000002 ClinVar:RCV000019770 biolink:NamedThing omim.nt http://omim.org/entry/104311#0018 biolink:NamedThing omim.nt http://omim.org/entry/104311.0019 biolink:NamedThing PSEN1, 1548GC-TG {28:Devi et al. (2000)} studied 2 children who developed dementia in their late twenties (AD3; {607822}). Their father had early-onset, autopsy-confirmed Alzheimer disease. The younger of the 2 children had AD confirmed at autopsy. Sequencing of the coding region of the PSEN1 gene revealed a GC-to-TG substitution at nucleotides 1548-1549, affecting codon 434. There was no DNA source available on their father for mutation analysis. The disease course in these 3 individuals was characterized by cognitive and behavioral problems accompanied by myoclonus, seizures, and aphasia within 5 years after onset. omim.nt GENO:0000002 ClinVar:RCV000019771 biolink:NamedThing omim.nt ClinVar:RCV000084588 biolink:NamedThing omim.nt dbSNP:rs281875357 biolink:NamedThing omim.nt owl:NamedIndividual http://omim.org/entry/104311#0019 biolink:NamedThing omim.nt http://omim.org/entry/104311.0020 biolink:NamedThing PSEN1, CYS92SER {78:Lewis et al. (2000)} showed that cys92-to-ser (C92S), the PS1 homolog of the C. elegans sel-12 loss of function mutation cys60 to ser, increased amyloid beta-42 production when expressed in a neuroglioma cell line, similar to other pathogenic PS1 mutations. They noted, but did not cite, a report identifying C92S as the pathogenic mutation in an Italian family with familial Alzheimer disease (AD3; {607822}). The results suggested that all FAD-linked PS1 mutations result in increased amyloid beta-42 production through a partial loss of function mechanism. omim.nt GENO:0000002 ClinVar:RCV000019772 biolink:NamedThing omim.nt ClinVar:RCV000084286 biolink:NamedThing omim.nt dbSNP:rs63751141 biolink:NamedThing omim.nt owl:NamedIndividual http://omim.org/entry/104311#0020 biolink:NamedThing omim.nt http://omim.org/entry/104311.0021 biolink:NamedThing PSEN1, GLY206ALA {4:Athan et al. (2001)} found that among 206 Caribbean Hispanic families with 2 or more living members with AD, 19 (9.2%) had at least 1 individual with onset of Alzheimer disease before the age of 55 years (AD3; {607822}). In 8 of these 19 families, a gly206-to-ala mutation in the PSEN1 gene was identified. Although not known to be related, all carriers of the G206A mutation tested shared a variant allele at 2 nearby microsatellite polymorphisms, indicating a common ancestor. omim.nt GENO:0000002 ClinVar:RCV000019773 biolink:NamedThing omim.nt ClinVar:RCV000518563 biolink:NamedThing omim.nt ClinVar:RCV000640609 biolink:NamedThing omim.nt dbSNP:rs63750082 biolink:NamedThing omim.nt owl:NamedIndividual http://omim.org/entry/104311#0021 biolink:NamedThing omim.nt http://omim.org/entry/104311.0022 biolink:NamedThing PSEN1, GLY266SER In a Japanese family with 6 individuals of both genders in 2 generations affected by a variant form of Alzheimer disease characterized by senile dementia preceded by spastic paraparesis and apraxia (see {607822}), {86:Matsubara-Tsutsui et al. (2002)} identified a G-to-A transition in codon 266 of exon 8 of the PSEN1 gene, resulting in a gly-to-ser (G266S) substitution. The deceased patients were between 48 and 51 years of age. omim.nt GENO:0000002 ClinVar:RCV000019774 biolink:NamedThing omim.nt dbSNP:rs121917807 biolink:NamedThing omim.nt owl:NamedIndividual http://omim.org/entry/104311#0022 biolink:NamedThing omim.nt http://omim.org/entry/104311.0023 biolink:NamedThing PSEN1, LEU113PRO {111:Raux et al. (2000)} reported 6 members of a family with early-onset frontotemporal dementia (see {600274}), confirmed by imaging studies, in an autosomal dominant inheritance pattern. In 2 patients available for testing, the authors found a novel heterozygous T-to-A mutation in the PSEN1 gene, resulting in a leu113-to-pro substitution. The mutation was absent in a healthy sister and in 50 unrelated patients. {111:Raux et al. (2000)} noted that this phenotype is usually associated with mutation in the MAPT gene ({157140}). omim.nt GENO:0000002 ClinVar:RCV000019775 biolink:NamedThing omim.nt ClinVar:RCV000020084 biolink:NamedThing omim.nt ClinVar:RCV000084292 biolink:NamedThing omim.nt ClinVar:RCV001228362 biolink:NamedThing omim.nt dbSNP:rs63751399 biolink:NamedThing omim.nt owl:NamedIndividual http://omim.org/entry/104311#0023 biolink:NamedThing omim.nt http://omim.org/entry/104311.0024 biolink:NamedThing PSEN1, LEU166PRO {88:Moehlmann et al. (2002)} identified a leu166-to-pro (L166P) mutation in the PSEN1 gene in a female proband in whom the onset of familial Alzheimer disease was in adolescence (AD3; {607822}). Generalized seizures began at age 15, major depression occurred at age 19, memory was clearly impaired by 24, ataxia and spastic paraplegia were recorded by 27, and moderate stage dementia by 28. Dementia, ataxia, and spasticity progressed until death at age 35. Numerous A-beta-immunopositive neuritic and cotton-wool plaques were seen throughout the cerebral cortex and A-beta-immunopositive amyloid cores were abundant in the cerebellar cortex. This was stated to be 1 of 11 mutations associated with FAD and located in the third transmembrane domain (TM3) of PSEN1. An analysis of other FAD-associated and artificial L166 mutants showed increased A-beta(42) levels in all, suggesting that leucine-166 is critically required for the specificity of gamma-secretase cleavage. However, none of the L166 mutations inhibited gamma-secretase activity. omim.nt GENO:0000002 ClinVar:RCV000019776 biolink:NamedThing omim.nt dbSNP:rs63750265 biolink:NamedThing omim.nt owl:NamedIndividual http://omim.org/entry/104311#0024 biolink:NamedThing omim.nt http://omim.org/entry/104311.0025 biolink:NamedThing PSEN1, LEU174MET {9:Bertoli Avella et al. (2002)} studied a Cuban family with autosomal dominant presenile Alzheimer disease (AD3; {607822}) through 6 generations that descended from a Spanish founder who migrated from the Canary Islands in the early 19th century. Mean age at onset was 59 years. Memory impairment was the main symptom in all patients; ischemic episodes were described in 4. Neuropathologic examination of brain material in 1 patient revealed neuronal loss, amyloid plaques, and neurofibrillary tangles. A maximum lod score of 3.79 at theta = 0.0 was obtained for marker D14S43, located in a 9-cM interval of the PSEN1 gene in which all patients shared the same haplotype. Sequencing of the PSEN1 gene revealed a heterozygous 520C-A substitution in exon 6, which was predicted to cause a leu174-to-met (L174M) substitution in the third transmembrane domain of the protein. Leu174 is highly conserved among species and is identical in presenilin-1 and presenilin-2 proteins. omim.nt GENO:0000002 ClinVar:RCV000019777 biolink:NamedThing omim.nt ClinVar:RCV000084329 biolink:NamedThing omim.nt dbSNP:rs63751144 biolink:NamedThing omim.nt owl:NamedIndividual http://omim.org/entry/104311#0025 biolink:NamedThing omim.nt http://omim.org/entry/104311.0026 biolink:NamedThing PSEN1, LEU271VAL In a family with autosomal dominant early-onset Alzheimer disease (see {607822}), {69:Kwok et al. (2003)} identified a C-T mutation in the PSEN1 gene, resulting in a leu271-to-val (L271V) substitution and deletion of exon 8. Mean age of disease onset was 49 years, and although no affected family members had spastic paraparesis, all developed myoclonus late in the illness. Neuropathologic examination of 2 patients revealed a large number of neocortical large spherical plaques without defined cores or neuritic dystrophy, reminiscent of cotton wool plaques. Biochemical analysis of the mutated protein showed that it resulted in increased secretion of the amyloid-beta-42 peptide. omim.nt GENO:0000002 ClinVar:RCV000019778 biolink:NamedThing omim.nt ClinVar:RCV000084375 biolink:NamedThing omim.nt ClinVar:RCV000984888 biolink:NamedThing omim.nt ClinVar:RCV001204170 biolink:NamedThing omim.nt dbSNP:rs63750886 biolink:NamedThing omim.nt owl:NamedIndividual http://omim.org/entry/104311#0026 biolink:NamedThing omim.nt http://omim.org/entry/104311.0027 biolink:NamedThing PSEN1, GLY183VAL In a patient with Pick disease ({172700}), {27:Dermaut et al. (2004)} identified a G-to-T transversion in exon 6 of the PSEN1 gene, resulting in a gly183-to-val (G183V) substitution. The mutation occurs at a conserved residue within a splice signal. The mutation was not detected in more than 1,000 patients with dementia and normal controls. Four sibs of the proband had the mutation; 1 was clearly affected and 3 others showed evidence compatible with cognitive deterioration or early-stage cognitive decline. Neuropathologic examination of the proband showed tau (MAPT; {157140})-immunoreactive Pick bodies without beta-amyloid plaques. {27:Dermaut et al. (2004)} suggested that the G183V mutation results in a partial loss of function of the PSEN1 protein. omim.nt GENO:0000002 ClinVar:RCV000019779 biolink:NamedThing omim.nt ClinVar:RCV000020085 biolink:NamedThing omim.nt ClinVar:RCV000084335 biolink:NamedThing omim.nt dbSNP:rs63751068 biolink:NamedThing omim.nt owl:NamedIndividual http://omim.org/entry/104311#0027 biolink:NamedThing omim.nt http://omim.org/entry/104311.0028 biolink:NamedThing PSEN1, PRO436GLN {7:Beck et al. (2004)} reported a patient with sporadic early-onset Alzheimer disease (AD3; {607822}) who was a somatic mosaic for a 71111C-A transversion in exon 12 of the PSEN1 gene. The mutation, which had been described by {132:Taddei et al. (1998)}, was predicted to result in substitution of glutamine at proline-436 (P436Q). The index patient presented at age 52 years with a 10-year history of progressive parkinsonian syndrome, spastic paraparesis, and dementia; she died 6 years later. The degree of mosaicism was 8% in peripheral lymphocytes and 14% in the cerebral cortex of the index patient. Her daughter, who presented at age 27 years with progressive cerebellar syndrome, spastic paraparesis, and dementia, was heterozygous for the mutation; she died 12 years after diagnosis. The authors hypothesized that mosaicism may be an important mechanism in the etiology of sporadic AD and other apparently sporadic neurodegenerative diseases such as Parkinson disease (see {168601}), motor neuron disease, and Creutzfeldt-Jakob disease ({123400}). omim.nt GENO:0000002 ClinVar:RCV000019780 biolink:NamedThing omim.nt ClinVar:RCV000084580 biolink:NamedThing omim.nt dbSNP:rs121917808 biolink:NamedThing omim.nt owl:NamedIndividual http://omim.org/entry/104311#0028 biolink:NamedThing omim.nt http://omim.org/entry/104311.0029 biolink:NamedThing PSEN1, 6-BP INS, NT715 In 2 sibs with early-onset Alzheimer disease with spastic paraparesis and unusual plaques (see {607822}), {91:Moretti et al. (2004)} identified a heterozygous 6-bp insertion (715insTTATAT) in exon 3 of the PSEN1 gene, resulting in the addition of phenylalanine and isoleucine between codons 156 and 157. The affected region encodes the intracellular loop between transmembrane domains 2 and 3 of PSEN1 and is highly conserved. The patients showed an unusually aggressive form of disease, with early onset and rapid progression. omim.nt GENO:0000002 ClinVar:RCV000019781 biolink:NamedThing omim.nt http://omim.org/entry/104311#0029 biolink:NamedThing omim.nt http://omim.org/entry/104311.0030 biolink:NamedThing PSEN1, ARG278ILE In 2 sibs with early-onset Alzheimer disease (AD3; {607822}) presenting as language impairment, {39:Godbolt et al. (2004)} identified a heterozygous mutation in the PSEN1 gene, resulting in an arg278-to-ile (R278I) substitution. Both patients presented at around age 50 with difficulty in word finding and impaired frontal executive function, but with relative preservation of memory. Although neither patient fulfilled clinical consensus criteria for AD, the authors noted that a different mutation at the same codon, R278T ({104311.0017}), had been associated with an atypical AD phenotype characterized by spastic paraparesis. Codon 278 lies in the cytoplasmic region between transmembrane regions 6 and 7 which is active in the formation of the gamma-secretase complex that mediates beta-amyloid generation ({135:Takasugi et al., 2003}). omim.nt GENO:0000002 ClinVar:RCV000019782 biolink:NamedThing omim.nt ClinVar:RCV000084379 biolink:NamedThing omim.nt http://omim.org/entry/104311#0030 biolink:NamedThing omim.nt http://omim.org/entry/104311.0031 biolink:NamedThing PSEN1, LEU85PRO In a patient with very-early-onset Alzheimer disease with spastic paraparesis and apraxia (see {607822}), {3:Ataka et al. (2004)} identified a heterozygous 254T-C transition in exon 4 of the PSEN1 gene, resulting in a leu85-to-pro (L85P) substitution. Functional expression studies showed that the L85P mutation resulted in a 2-fold increase in amyloid-beta-42 production. The patient had onset at age 26 years, and symptoms and neuroimaging were consistent with the 'visual variant' of AD in which there is a visuospatial cognitive deficit. omim.nt GENO:0000002 ClinVar:RCV000019783 biolink:NamedThing omim.nt ClinVar:RCV000084284 biolink:NamedThing omim.nt dbSNP:rs63750599 biolink:NamedThing omim.nt owl:NamedIndividual http://omim.org/entry/104311#0031 biolink:NamedThing omim.nt http://omim.org/entry/104311.0032 biolink:NamedThing PSEN1, 3-BP DEL In a Japanese patient with a phenotype with overlapping features of early-onset Alzheimer disease with spastic paraparesis and unusual plaques (see {607822}) and Lewy body dementia (DLB; {127750}), {53:Ishikawa et al. (2005)} identified a 3-bp deletion (ACC) in exon 12 of the PSEN1 gene, resulting in the absence of residue thr440 at the cytoplasmic C-terminus of the protein. The patient's father had early-onset dementia with the onset of parkinsonism 9 years later, consistent with Lewy body dementia. However, the patient had early-onset parkinsonism with the onset of dementia 7 years later, and developed seizures and features of spasticity late in the illness. Neuropathologic examination of the patient showed severe neuronal loss with gliosis in various brain regions, as well as alpha-synuclein (SNCA; {163890})-immunopositive Lewy bodies, amyloid (APP; {104760})-immunopositive cotton-wool plaques, cerebral amyloid angiopathy, and corticospinal degeneration. The patient's clinical diagnosis was Parkinson disease with dementia, and the pathologic diagnosis was AD with spastic paraparesis. No mutations were identified in the SNCA or APP genes. {53:Ishikawa et al. (2005)} emphasized the unusual phenotypic features in this patient. The thr440 deletion induced both alpha-synuclein and beta-amyloid pathology to equal extents, suggesting that normal PSEN1 protein may play a role in interactions between the 2 molecules. omim.nt GENO:0000002 ClinVar:RCV000019784 biolink:NamedThing omim.nt http://omim.org/entry/104311#0032 biolink:NamedThing omim.nt http://omim.org/entry/104311.0033 biolink:NamedThing PSEN1, ALA431GLU In affected members of 9 Mexican families with early-onset Alzheimer disease-3 (AD3; {607822}), {154:Yescas et al. (2006)} identified a heterozygous mutation in exon 12 of the PSEN1 gene, resulting in an ala431-to-glu (A431E) substitution. The A431E mutation was found in 19 (32%) of 60 apparently unaffected family members, suggesting either a presymptomatic state or reduced penetrance. All families were from the state of Jalisco in western Mexico, and haplotype analysis indicated a founder effect. The A431E mutation was not identified in 100 control individuals. {93:Murrell et al. (2006)} found the A431E mutation in 20 individuals with AD3 from 15 families identified in Guadalajara, southern California, and Chicago. Age at disease onset ranged from 33 to 44 years, and spasticity was a common clinical feature. Fourteen families were of Mexican mestizo descent, and of these families, 9 could trace the illness to ancestors from the state of Jalisco in Mexico. The remaining proband had a more remote Mexican ancestry. The findings further supported a founder effect for the A431E mutation. omim.nt GENO:0000002 ClinVar:RCV000019785 biolink:NamedThing omim.nt ClinVar:RCV000517533 biolink:NamedThing omim.nt ClinVar:RCV000640606 biolink:NamedThing omim.nt dbSNP:rs63750083 biolink:NamedThing omim.nt owl:NamedIndividual http://omim.org/entry/104311#0033 biolink:NamedThing omim.nt http://omim.org/entry/104311.0034 biolink:NamedThing PSEN1, ASP333GLY {79:Li et al. (2006)} described heterozygosity for a novel PSEN1 missense mutation, asp333 to gly (D333G), associated with dilated cardiomyopathy (CMD1U; {613694}) in 1 African American family. The amino acid substitution arose from a 1539A-G transition in exon 10. Affected members were identified in 3 generations. The PSEN1 mutation was associated with complete penetrance and progressive disease that resulted in the necessity of cardiac transplantation or in death. omim.nt GENO:0000002 ClinVar:RCV000019786 biolink:NamedThing omim.nt ClinVar:RCV000171844 biolink:NamedThing omim.nt ClinVar:RCV000877625 biolink:NamedThing omim.nt dbSNP:rs121917809 biolink:NamedThing omim.nt owl:NamedIndividual http://omim.org/entry/104311#0034 biolink:NamedThing omim.nt http://omim.org/entry/104311.0035 biolink:NamedThing PSEN1, ALA79VAL In 3 affected members of a family with Alzheimer disease (AD3; {607822}), {63:Kauwe et al. (2007)} identified a heterozygous C-to-T transition in exon 4 of the PSEN1 gene, resulting in an ala79-to-val (A79V) substitution. The patients had late-onset AD (greater than 75 years) that was confirmed at autopsy. An unaffected mutation carrier in the family was found to have increased CSF beta-amyloid-42, suggesting that this may be used as an endophenotype or marker for the disease. In vitro functional expression studies in mouse embryonic fibroblasts transfected with the A79V mutation showed increased beta-amyloid-42 compared to controls. omim.nt GENO:0000002 ClinVar:RCV000019787 biolink:NamedThing omim.nt ClinVar:RCV000084281 biolink:NamedThing omim.nt ClinVar:RCV000529477 biolink:NamedThing omim.nt dbSNP:rs63749824 biolink:NamedThing omim.nt owl:NamedIndividual http://omim.org/entry/104311#0035 biolink:NamedThing omim.nt http://omim.org/entry/104311.0036 biolink:NamedThing PSEN1, SER170PHE In 3 affected members of a family with early-onset Alzheimer disease (AD3; {607822}), {126:Snider et al. (2005)} identified a heterozygous C-to-T transition in exon 6 of the PSEN1 gene, resulting in a ser170-to-phe (S170F) substitution. All 3 patients developed gradual onset of memory loss beginning at 26 to 27 years of age, with an average duration of disease of 11 years before death. The clinical courses were complicated by myoclonus, seizures, and extrapyramidal signs. Postmortem examination confirmed AD in all 3 patients. The proband also had widespread Lewy body pathology in the brainstem, limbic system, and neocortex; specific staining for Lewy bodies was not performed in the other 2 family members. In a man with early-onset AD associated with cerebellar ataxia, {106:Piccini et al. (2007)} identified a heterozygous S170F mutation in the PSEN1 gene, which was not identified in 94 control individuals. The patient presented at age 28 years with delusions and lower limb jerks accompanied by intentional myoclonus and cerebellar ataxia. He had rapid progression with global impairment of all cognitive functions and became bedridden, anarthric, and incontinent by age 33. He died of bronchopneumonia at age 35. Postmortem examination showed severe beta-amyloid deposition in the cerebral and cerebellar cortices, amyloid angiopathy, and severe loss of Purkinje cells and fibers in the cerebellum. Neurofibrillary tangles were also present in the cerebral cortex. In vitro cellular studies indicated that the S170F mutation resulted in a 2.8-fold increase of both beta-amyloid-42 and -40 as well as a 60% increase of secreted APP compared to wildtype PSEN1. Soluble and insoluble fractions of the patient's brain tissue showed a prevalence of N-terminally truncated beta-amyloid species at residues 40 and 42. {106:Piccini et al. (2007)} suggested that the unique processing pattern of APP and high levels of N-terminally truncated species was correlated with the severity of the phenotype in this patient, but also noted the different phenotype from that described by {126:Snider et al. (2005)}. omim.nt GENO:0000002 ClinVar:RCV000019788 biolink:NamedThing omim.nt ClinVar:RCV000084326 biolink:NamedThing omim.nt dbSNP:rs63750577 biolink:NamedThing omim.nt owl:NamedIndividual http://omim.org/entry/104311#0036 biolink:NamedThing omim.nt http://omim.org/entry/104311.0037 biolink:NamedThing PSEN1, GLY217ARG In 2 affected members of a family of Irish/English descent with Alzheimer disease with unusual cotton wool plaques (see {607822}), {97:Norton et al. (2009)} identified a heterozygous G-to-C transversion in the PSEN1 gene, resulting in a gly217-to-arg (G217R) substitution. There were 8 affected family members. The mean age at onset was 45.5 years, and the mean age at death was 55.5 years. Postmortem examination of 1 affected family member showed classic Alzheimer disease changes and large cotton wool plaques. Spastic paraparesis was not a clinical feature. In vitro functional expression assays showed that the G217R mutation increased the ratio of beta-amyloid 42/40, confirming its pathogenicity. omim.nt GENO:0000002 ClinVar:RCV000019789 biolink:NamedThing omim.nt dbSNP:rs267606983 biolink:NamedThing omim.nt owl:NamedIndividual http://omim.org/entry/104311#0037 biolink:NamedThing omim.nt http://omim.org/entry/104311.0038 biolink:NamedThing PSEN1, 1-BP DEL, 725C In a Han Chinese family segregating autosomal dominant familial acne inversa (ACNINV3; {613737}), {145:Wang et al. (2010)} identified heterozygosity for a single-basepair deletion at nucleotide 725 of the PSEN1 gene (725delC). The mutation resulted in frameshift and a premature termination codon (Pro242LeufsTer11). No affected individual 50 years old or older had symptoms of Alzheimer disease or dementia. This mutation was not identified in chromosomes from 200 ethnically matched control individuals. omim.nt GENO:0000002 ClinVar:RCV000022446 biolink:NamedThing omim.nt dbSNP:rs1595035030 biolink:NamedThing omim.nt owl:NamedIndividual http://omim.org/entry/104311#0038 biolink:NamedThing omim.nt http://omim.org/entry/104311.0039 biolink:NamedThing PSEN1, LEU381PHE In 3 brothers with early-onset Alzheimer disease with spastic paraparesis (see {607822}) and unusually rapid progression, {30:Dolzhanskaya et al. (2014)} identified a heterozygous c.1141C-T transition in the PSEN1 gene, resulting in a leu381-to-phe (L381F) substitution at a highly conserved residue. The mutation, which was found by whole-exome sequencing and confirmed by Sanger sequencing, was not found in the Exome Variant Server database and segregated with the disorder in the family. The boys' father and paternal grandmother were reportedly similarly affected. The brothers had onset of progressive dementia and ataxia between ages 29 and 32 years; 2 died by age 32 and the other at age 36. The proband presented with memory deficits and ataxia, and later developed dysarthria, and spastic paraparesis. Electron microscopy of a skin biopsy showed lipofuscin-containing phagocytic cells and distinct curvilinear lysosomal inclusion bodies, suggestive of neuronal ceroid lipofuscinosis. Neuropathologic examination showed changes consistent with Alzheimer disease, including neuritic and amyloid-containing plaques and neurofibrillary tangles. Additional findings included Hirano bodies and granulovacuolar degeneration in the hippocampus. The proband was originally ascertained from a cohort of patients clinically thought to have autosomal dominant adult-onset neuronal ceroid lipofuscinosis (CLN4B; {162350}) who were negative for mutations in the DNAJC5 gene ({611203}). Functional studies of the L381F variant were not performed. omim.nt GENO:0000002 ClinVar:RCV000106293 biolink:NamedThing omim.nt ClinVar:RCV000625969 biolink:NamedThing omim.nt dbSNP:rs63750687 biolink:NamedThing omim.nt owl:NamedIndividual http://omim.org/entry/104311#0039 biolink:NamedThing omim.nt MONARCH:.well-known/genid/baab58e0fb8076fd5773 biolink:NamedThing GRCh38chr14-73136435-73223690-Region omim.nt MONARCH:.well-known/genid/b2a66342a35a502e93c9 faldo:Region MONARCH:.well-known/genid/OMIM104311ref119 biolink:NamedThing Personal Communication. omim.nt IAO:0000310 PMID:10206644 biolink:NamedThing omim.nt IAO:0000013 PMID:10206645 biolink:NamedThing omim.nt IAO:0000013 PMID:10206646 biolink:NamedThing omim.nt IAO:0000013 PMID:10206647 biolink:NamedThing omim.nt IAO:0000013 PMID:10401002 biolink:NamedThing omim.nt IAO:0000013 PMID:10557208 biolink:NamedThing omim.nt IAO:0000013 PMID:10635315 biolink:NamedThing omim.nt IAO:0000013 PMID:10655540 biolink:NamedThing omim.nt IAO:0000013 PMID:10720282 biolink:NamedThing omim.nt IAO:0000013 PMID:10811821 biolink:NamedThing omim.nt IAO:0000013 PMID:10821758 biolink:NamedThing omim.nt IAO:0000013 PMID:10850703 biolink:NamedThing omim.nt IAO:0000013 PMID:10864326 biolink:NamedThing omim.nt IAO:0000013 PMID:10917532 biolink:NamedThing omim.nt IAO:0000013 PMID:10932180 biolink:NamedThing omim.nt IAO:0000013 PMID:11027672 biolink:NamedThing omim.nt IAO:0000013 PMID:11030342 biolink:NamedThing omim.nt IAO:0000013 PMID:11030797 biolink:NamedThing omim.nt IAO:0000013 PMID:11070093 biolink:NamedThing omim.nt IAO:0000013 PMID:11090127 biolink:NamedThing omim.nt IAO:0000013 PMID:11094121 biolink:NamedThing omim.nt IAO:0000013 PMID:11140686 biolink:NamedThing omim.nt IAO:0000013 PMID:11144355 biolink:NamedThing omim.nt IAO:0000013 PMID:11198283 biolink:NamedThing omim.nt IAO:0000013 PMID:11389157 biolink:NamedThing omim.nt IAO:0000013 PMID:11402113 biolink:NamedThing omim.nt IAO:0000013 PMID:11517342 biolink:NamedThing omim.nt IAO:0000013 PMID:11524469 biolink:NamedThing omim.nt IAO:0000013 PMID:11551913 biolink:NamedThing omim.nt IAO:0000013 PMID:11553799 biolink:NamedThing omim.nt IAO:0000013 PMID:11567612 biolink:NamedThing omim.nt IAO:0000013 PMID:11679632 biolink:NamedThing omim.nt IAO:0000013 PMID:11710891 biolink:NamedThing omim.nt IAO:0000013 PMID:11738035 biolink:NamedThing omim.nt IAO:0000013 PMID:11740561 biolink:NamedThing omim.nt IAO:0000013 PMID:11912199 biolink:NamedThing omim.nt IAO:0000013 PMID:11920851 biolink:NamedThing omim.nt IAO:0000013 PMID:11978763 biolink:NamedThing omim.nt IAO:0000013 PMID:12048239 biolink:NamedThing omim.nt IAO:0000013 PMID:12058025 biolink:NamedThing omim.nt IAO:0000013 PMID:12110170 biolink:NamedThing omim.nt IAO:0000013 PMID:12145638 biolink:NamedThing omim.nt IAO:0000013 PMID:12163019 biolink:NamedThing omim.nt IAO:0000013 PMID:12198112 biolink:NamedThing omim.nt IAO:0000013 PMID:12297048 biolink:NamedThing omim.nt IAO:0000013 PMID:12297508 biolink:NamedThing omim.nt IAO:0000013 PMID:12370477 biolink:NamedThing omim.nt IAO:0000013 PMID:12484344 biolink:NamedThing omim.nt IAO:0000013 PMID:12493737 biolink:NamedThing omim.nt IAO:0000013 PMID:12551931 biolink:NamedThing omim.nt IAO:0000013 PMID:12660785 biolink:NamedThing omim.nt IAO:0000013 PMID:12668610 biolink:NamedThing omim.nt IAO:0000013 PMID:12691659 biolink:NamedThing omim.nt IAO:0000013 PMID:12736250 biolink:NamedThing omim.nt IAO:0000013 PMID:12761548 biolink:NamedThing omim.nt IAO:0000013 PMID:12810495 biolink:NamedThing omim.nt IAO:0000013 PMID:12891668 biolink:NamedThing omim.nt IAO:0000013 PMID:12944419 biolink:NamedThing omim.nt IAO:0000013 PMID:13678586 biolink:NamedThing omim.nt IAO:0000013 PMID:14557582 biolink:NamedThing omim.nt IAO:0000013 PMID:14645205 biolink:NamedThing omim.nt IAO:0000013 PMID:15066262 biolink:NamedThing omim.nt IAO:0000013 PMID:15087467 biolink:NamedThing omim.nt IAO:0000013 PMID:15115757 biolink:NamedThing omim.nt IAO:0000013 PMID:15122701 biolink:NamedThing omim.nt IAO:0000013 PMID:15128703 biolink:NamedThing omim.nt IAO:0000013 PMID:15159497 biolink:NamedThing omim.nt IAO:0000013 PMID:15345711 biolink:NamedThing omim.nt IAO:0000013 PMID:15448688 biolink:NamedThing omim.nt IAO:0000013 PMID:15452145 biolink:NamedThing omim.nt IAO:0000013 PMID:15534188 biolink:NamedThing omim.nt IAO:0000013 PMID:15534260 biolink:NamedThing omim.nt IAO:0000013 PMID:15549135 biolink:NamedThing omim.nt IAO:0000013 PMID:15622541 biolink:NamedThing omim.nt IAO:0000013 PMID:15732120 biolink:NamedThing omim.nt IAO:0000013 PMID:15766532 biolink:NamedThing omim.nt IAO:0000013 PMID:16033913 biolink:NamedThing omim.nt IAO:0000013 PMID:16043812 biolink:NamedThing omim.nt IAO:0000013 PMID:16046406 biolink:NamedThing omim.nt IAO:0000013 PMID:16093313 biolink:NamedThing omim.nt IAO:0000013 PMID:16116115 biolink:NamedThing omim.nt IAO:0000013 PMID:16216949 biolink:NamedThing omim.nt IAO:0000013 PMID:16344340 biolink:NamedThing omim.nt IAO:0000013 PMID:16449385 biolink:NamedThing omim.nt IAO:0000013 PMID:16449386 biolink:NamedThing omim.nt IAO:0000013 PMID:16628450 biolink:NamedThing omim.nt IAO:0000013 PMID:16752394 biolink:NamedThing omim.nt IAO:0000013 PMID:16897084 biolink:NamedThing omim.nt IAO:0000013 PMID:16959576 biolink:NamedThing omim.nt IAO:0000013 PMID:17126306 biolink:NamedThing omim.nt IAO:0000013 PMID:17158800 biolink:NamedThing omim.nt IAO:0000013 PMID:17186461 biolink:NamedThing omim.nt IAO:0000013 PMID:17366635 biolink:NamedThing omim.nt IAO:0000013 PMID:17502474 biolink:NamedThing omim.nt IAO:0000013 PMID:17947293 biolink:NamedThing omim.nt IAO:0000013 PMID:17981814 biolink:NamedThing omim.nt IAO:0000013 PMID:1946377 biolink:NamedThing omim.nt IAO:0000013 PMID:19641596 biolink:NamedThing omim.nt IAO:0000013 PMID:19667325 biolink:NamedThing omim.nt IAO:0000013 PMID:20164095 biolink:NamedThing omim.nt IAO:0000013 PMID:20929727 biolink:NamedThing omim.nt IAO:0000013 PMID:21215373 biolink:NamedThing omim.nt IAO:0000013 PMID:22355194 biolink:NamedThing omim.nt IAO:0000013 PMID:22461631 biolink:NamedThing omim.nt IAO:0000013 PMID:23254930 biolink:NamedThing omim.nt IAO:0000013 PMID:24121961 biolink:NamedThing omim.nt IAO:0000013 PMID:25043039 biolink:NamedThing omim.nt IAO:0000013 PMID:25471389 biolink:NamedThing omim.nt IAO:0000013 PMID:26280335 biolink:NamedThing omim.nt IAO:0000013 PMID:30598546 biolink:NamedThing omim.nt IAO:0000013 PMID:30630874 biolink:NamedThing omim.nt IAO:0000013 PMID:31686034 biolink:NamedThing omim.nt IAO:0000013 PMID:7550356 biolink:NamedThing omim.nt IAO:0000013 PMID:7585193 biolink:NamedThing omim.nt IAO:0000013 PMID:7596406 biolink:NamedThing omim.nt IAO:0000013 PMID:7623584 biolink:NamedThing omim.nt IAO:0000013 PMID:8490014 biolink:NamedThing omim.nt IAO:0000013 PMID:8574969 biolink:NamedThing omim.nt IAO:0000013 PMID:8643637 biolink:NamedThing omim.nt IAO:0000013 PMID:8705854 biolink:NamedThing omim.nt IAO:0000013 PMID:8742474 biolink:NamedThing omim.nt IAO:0000013 PMID:8755489 biolink:NamedThing omim.nt IAO:0000013 PMID:8766720 biolink:NamedThing omim.nt IAO:0000013 PMID:8810256 biolink:NamedThing omim.nt IAO:0000013 PMID:8837617 biolink:NamedThing omim.nt IAO:0000013 PMID:8878479 biolink:NamedThing omim.nt IAO:0000013 PMID:8878531 biolink:NamedThing omim.nt IAO:0000013 PMID:8931704 biolink:NamedThing omim.nt IAO:0000013 PMID:8938131 biolink:NamedThing omim.nt IAO:0000013 PMID:8943053 biolink:NamedThing omim.nt IAO:0000013 PMID:8986743 biolink:NamedThing omim.nt IAO:0000013 PMID:9007311 biolink:NamedThing omim.nt IAO:0000013 PMID:9052708 biolink:NamedThing omim.nt IAO:0000013 PMID:9073509 biolink:NamedThing omim.nt IAO:0000013 PMID:9126060 biolink:NamedThing omim.nt IAO:0000013 PMID:9160754 biolink:NamedThing omim.nt IAO:0000013 PMID:9172170 biolink:NamedThing omim.nt IAO:0000013 PMID:9246481 biolink:NamedThing omim.nt IAO:0000013 PMID:9246482 biolink:NamedThing omim.nt IAO:0000013 PMID:9298903 biolink:NamedThing omim.nt IAO:0000013 PMID:9384602 biolink:NamedThing omim.nt IAO:0000013 PMID:9436726 biolink:NamedThing omim.nt IAO:0000013 PMID:9443865 biolink:NamedThing omim.nt IAO:0000013 PMID:9450754 biolink:NamedThing omim.nt IAO:0000013 PMID:9521418 biolink:NamedThing omim.nt IAO:0000013 PMID:9521423 biolink:NamedThing omim.nt IAO:0000013 PMID:9539132 biolink:NamedThing omim.nt IAO:0000013 PMID:9539133 biolink:NamedThing omim.nt IAO:0000013 PMID:9544835 biolink:NamedThing omim.nt IAO:0000013 PMID:9546792 biolink:NamedThing omim.nt IAO:0000013 PMID:9712537 biolink:NamedThing omim.nt IAO:0000013 PMID:9728730 biolink:NamedThing omim.nt IAO:0000013 PMID:9790190 biolink:NamedThing omim.nt IAO:0000013 PMID:9831473 biolink:NamedThing omim.nt IAO:0000013 PMID:9915968 biolink:NamedThing omim.nt IAO:0000013 http://omim.org/entry/613737 biolink:NamedThing|biolink:Disease Acne Inversa, Familial, 3 Acne Inversa, Familial, 3 omim.nt ACNE INVERSA, FAMILIAL, 3; ACNINV3 owl:Class OBO:CHR_9606chr14q24.3 biolink:NamedThing omim.nt owl:Class http://omim.org/entry/172700 biolink:NamedThing|biolink:Disease Pick Disease of Brain Pick Disease of Brain omim.nt PICK DISEASE OF BRAIN|Dementia With Lobar Atrophy and Neuronal Cytoplasmic Inclusions|Lobar Atrophy of Brain owl:Class http://omim.org/entry/600274 biolink:NamedThing|biolink:Disease Frontotemporal Dementia Frontotemporal Dementia omim.nt FRONTOTEMPORAL DEMENTIA; FTD|Dementia, Frontotemporal, With Parkinsonism|Disinhibition-Dementia-Parkinsonism-Amyotrophy Complex|Frontotemporal Dementia With Parkinsonism|Frontotemporal Lobar Degeneration With Tau Inclusions|Frontotemporal Lobe Dementia|Ftdp17|Ftld With Tau Inclusions|Multiple System Tauopathy With Presenile Dementia|Pallidopontonigral Degeneration|Pick Complex|Wilhelmsen-Lynch Disease owl:Class http://omim.org/entry/607822 biolink:NamedThing|biolink:Disease Alzheimer Disease 3 Alzheimer Disease 3 omim.nt ALZHEIMER DISEASE 3; AD|Alzheimer Disease 3, Early-Onset|Alzheimer Disease, Familial, 3|Alzheimer Disease, Familial, 3, With Spastic Paraparesis and Apraxia|Alzheimer Disease, Familial, 3, With Spastic Paraparesis and Unusual Plaques owl:Class http://omim.org/entry/613694 biolink:NamedThing|biolink:Disease Cardiomyopathy, Dilated, 1U Cardiomyopathy, Dilated, 1U omim.nt CARDIOMYOPATHY, DILATED, 1U; CMD1U owl:Class http://www.omim.org/phenotypicSeries/PS142690 biolink:NamedThing|biolink:Disease Acne inversa omim.nt owl:Class UMLS:C1418985 biolink:NamedThing omim.nt owl:Class https://www.ncbi.nlm.nih.gov/gene/5663 biolink:NamedThing omim.nt http://omim.org/entry/104350 biolink:NamedThing Amastia, Bilateral, With Ureteral Triplication and Dysmorphism omim.nt AMASTIA, BILATERAL, WITH URETERAL TRIPLICATION AND DYSMORPHISM owl:Class PMID:3795344 biolink:NamedThing omim.nt IAO:0000013 UMLS:C1863015 biolink:NamedThing omim.nt owl:Class http://omim.org/entry/104400 biolink:NamedThing Amelia and Terminal Transverse Hemimelia omim.nt AMELIA AND TERMINAL TRANSVERSE HEMIMELIA owl:Class MONARCH:.well-known/genid/OMIM104400ref2 biolink:NamedThing The Genetics of Hand Malformations. omim.nt IAO:0000310 PMID:22002956 biolink:NamedThing omim.nt IAO:0000013 UMLS:C1863014 biolink:NamedThing omim.nt owl:Class http://omim.org/entry/104500 biolink:NamedThing|biolink:Disease Amelogenesis Imperfecta, Type 1B Amelogenesis Imperfecta, Type 1B omim.nt AMELOGENESIS IMPERFECTA, TYPE IB; AI1B|Aih2|Amelogenesis Imperfecta, Hypoplastic Local, Autosomal Dominant|Enamel Hypoplasia, Hereditary Localized owl:Class MONARCH:.well-known/genid/OMIM104500ref11 biolink:NamedThing Hereditary disturbances of enamel formation and calcification. omim.nt IAO:0000310 MONARCH:.well-known/genid/OMIM104500ref12 biolink:NamedThing Heritable defects of enamel.In: Stewart, R. E.; Prescott, G. H. : Oral Facial Genetics. omim.nt IAO:0000310 PMID:11487571 biolink:NamedThing omim.nt IAO:0000013 PMID:11978766 biolink:NamedThing omim.nt IAO:0000013 PMID:13469154 biolink:NamedThing omim.nt IAO:0000013 PMID:13655172 biolink:NamedThing omim.nt IAO:0000013 PMID:17125728 biolink:NamedThing omim.nt IAO:0000013 PMID:25143514 biolink:NamedThing omim.nt IAO:0000013 PMID:3169793 biolink:NamedThing omim.nt IAO:0000013 PMID:4625727 biolink:NamedThing omim.nt IAO:0000013 PMID:6957136 biolink:NamedThing omim.nt IAO:0000013 PMID:7833920 biolink:NamedThing omim.nt IAO:0000013 PMID:9027503 biolink:NamedThing omim.nt IAO:0000013 UMLS:C0399368 biolink:NamedThing omim.nt owl:Class ORPHA:100031 biolink:NamedThing|biolink:Disease omim.nt owl:Class ORPHA:88661 biolink:NamedThing|biolink:Disease omim.nt owl:Class http://www.omim.org/phenotypicSeries/PS104500 biolink:NamedThing|biolink:Disease Amelogenesis imperfecta omim.nt owl:Class http://omim.org/entry/104510 biolink:NamedThing|biolink:Disease Amelogenesis Imperfecta, Type 4 Amelogenesis Imperfecta, Type 4 omim.nt AMELOGENESIS IMPERFECTA, TYPE IV; AI4|Amelogenesis Imperfecta, Hypomaturation-Hypoplastic Type, With Taurodontism owl:Class PMID:10466415 biolink:NamedThing omim.nt IAO:0000013 PMID:15666299 biolink:NamedThing omim.nt IAO:0000013 PMID:18203197 biolink:NamedThing omim.nt IAO:0000013 PMID:2387085 biolink:NamedThing omim.nt IAO:0000013 PMID:292959 biolink:NamedThing omim.nt IAO:0000013 PMID:3422811 biolink:NamedThing omim.nt IAO:0000013 PMID:8375104 biolink:NamedThing omim.nt IAO:0000013 PMID:9382143 biolink:NamedThing omim.nt IAO:0000013 UMLS:C1863012 biolink:NamedThing omim.nt owl:Class ORPHA:100034 biolink:NamedThing|biolink:Disease omim.nt owl:Class http://omim.org/entry/104530 biolink:NamedThing|biolink:Disease Amelogenesis Imperfecta, Type 1A Amelogenesis Imperfecta, Type 1A omim.nt AMELOGENESIS IMPERFECTA, TYPE IA; AI1A|Amelogenesis Imperfecta, Hypoplastic Type 1A owl:Class MONARCH:.well-known/genid/OMIM104530ref10 biolink:NamedThing Heritable defects of enamel.In: Stewart, R. E.; Prescott, G. H. : Oral Facial Genetics. omim.nt IAO:0000310 MONARCH:.well-known/genid/OMIM104530ref5 biolink:NamedThing Hereditary generalized microdontia. omim.nt IAO:0000310 MONARCH:.well-known/genid/OMIM104530ref9 biolink:NamedThing Inherited defects in tooth structure. omim.nt IAO:0000310 PMID:162891 biolink:NamedThing omim.nt IAO:0000013 PMID:16674655 biolink:NamedThing omim.nt IAO:0000013 PMID:23632796 biolink:NamedThing omim.nt IAO:0000013 PMID:23958762 biolink:NamedThing omim.nt IAO:0000013 PMID:265269 biolink:NamedThing omim.nt IAO:0000013 PMID:292722 biolink:NamedThing omim.nt IAO:0000013 PMID:3150442 biolink:NamedThing omim.nt IAO:0000013 UMLS:C4011403 biolink:NamedThing omim.nt owl:Class http://omim.org/entry/104570 biolink:NamedThing|biolink:Disease Ameloonychohypohidrotic Syndrome Ameloonychohypohidrotic Syndrome omim.nt AMELOONYCHOHYPOHIDROTIC SYNDROME owl:Class MONARCH:.well-known/genid/OMIM104570ref1 biolink:NamedThing Personal Communication. omim.nt IAO:0000310 MONARCH:.well-known/genid/OMIM104570ref3 biolink:NamedThing Heritable defects of enamel.In: Stewart, R. E.; Prescott, G. H. : Oral Facial Genetics. omim.nt IAO:0000310 PMID:122795 biolink:NamedThing omim.nt IAO:0000013 UMLS:C1863006 biolink:NamedThing omim.nt owl:Class ORPHA:1028 biolink:NamedThing|biolink:Disease omim.nt owl:Class http://omim.org/entry/104600 biolink:NamedThing Amenorrhea-Galactorrhea Syndrome omim.nt AMENORRHEA-GALACTORRHEA SYNDROME owl:Class MONARCH:.well-known/genid/OMIM104600ref2 biolink:NamedThing Genetic Disorders of the Endocrine Glands. omim.nt IAO:0000310 PMID:4299353 biolink:NamedThing omim.nt IAO:0000013 PMID:6067055 biolink:NamedThing omim.nt IAO:0000013 UMLS:C0271556 biolink:NamedThing omim.nt owl:Class http://omim.org/entry/104610 biolink:NamedThing|biolink:Gene ABP1 Amiloride-Binding Protein 1 omim.nt AMILORIDE-BINDING PROTEIN 1; ABP1|Abp|Dao1|Diamine Oxidase owl:Class MONARCH:.well-known/genid/b64d8c8267f1ed8986dd biolink:NamedThing GRCh38chr7-150824874-150861503-Region omim.nt MONARCH:.well-known/genid/b31c9392661c4c2d77c2 faldo:Region PMID:2217167 biolink:NamedThing omim.nt IAO:0000013 PMID:2227949 biolink:NamedThing omim.nt IAO:0000013 PMID:8144586 biolink:NamedThing omim.nt IAO:0000013 PMID:8182053 biolink:NamedThing omim.nt IAO:0000013 PMID:8375402 biolink:NamedThing omim.nt IAO:0000013 OBO:CHR_9606chr7q31 biolink:NamedThing omim.nt owl:Class UMLS:C1412100 biolink:NamedThing omim.nt owl:Class https://www.ncbi.nlm.nih.gov/gene/26 biolink:NamedThing omim.nt http://omim.org/entry/104613 biolink:NamedThing|biolink:Gene CCT6A Chaperonin Containing T-Complex Polypeptide 1, Subunit 6A omim.nt CHAPERONIN CONTAINING T-COMPLEX POLYPEPTIDE 1, SUBUNIT 6A; CCT6A|Amino Acid Transport Defect-Complementing|Cct6|Histidine Transport Regulator 3|T-Complex Homolog Tcp20 owl:Class MONARCH:.well-known/genid/bf53131c50c123818b3d biolink:NamedThing GRCh38chr7-56051764-56063988-Region omim.nt MONARCH:.well-known/genid/b5e4f4b9102a3331b2fe faldo:Region PMID:1352881 biolink:NamedThing omim.nt IAO:0000013 PMID:8034610 biolink:NamedThing omim.nt IAO:0000013 OBO:CHR_9606chr7p11.2 biolink:NamedThing omim.nt owl:Class UMLS:C1413198 biolink:NamedThing omim.nt owl:Class https://www.ncbi.nlm.nih.gov/gene/908 biolink:NamedThing omim.nt http://omim.org/entry/104614.0001 biolink:NamedThing SLC3A1, MET467THR {4:Calonge et al. (1994)} detected a met467-to-thr mutation in the SLC3A1 gene in 3 sibs with cystinuria defined as type I (see {220100}). The mutation nearly abolished the amino acid transport activity induced by the SLC3A1 gene in Xenopus oocytes. {3:Bisceglia et al. (1996)} noted that this was the most common allele detected in the Spanish and Italian population analyzed by them. In a 34-year-old Swedish man with cystinuria and cystine stones ({220100}), {12:Harnevik et al. (2001)} identified compound heterozygosity for an M467T substitution in 1 allele of the SLC3A1 gene and a 1085G-A transition in exon 6 of the SLC3A1 gene in the other allele, resulting in an arg362-to-his (R362H; {104614.0008}) substitution. This patient was subsequently found by {11:Harnevik et al. (2003)} to have a mutation in the SLC7A9 gene ({604144.0010}) as well. In 2 sisters with a mixed cystinuria phenotype (see {220100}), {8:Font-Llitjos et al. (2005)} identified 3 mutations: an M467T substitution in 1 allele of the SLC3A1 gene and a duplication of exons 5 to 9 of the SLC3A1 gene ({104614.0007}) in the other allele, and a 789+2C-to-T transition in 1 allele of the SLC7A9 gene ({604144.0013}). One sister had very high amino acid levels in the urine; the other was on dialysis. M467T heterozygotes in this family had a type I excretion pattern, whereas heterozygotes with duplication of exons 5 to 9 had a non-I phenotype. In a patient with a mixed cystinuria phenotype (see {220100}), {8:Font-Llitjos et al. (2005)} identified 3 mutations: an M467T substitution in the SLC3A1 gene, and compound heterozygosity for the SLC7A9 mutations G105R ({604144.0001}) and Y232C ({604144.0012}). The patient had very low urine amino acid levels. Double heterozygotes in this family (G105R/+ and M467T/+) had higher urinary excretion levels than single heterozygotes (G105R/+ or M467T/+), suggesting digenic cystinuria. omim.nt GENO:0000002 http://omim.org/entry/104614 biolink:NamedThing|biolink:Gene SLC3A1 Solute Carrier Family 3 (Cystine, Dibasic, and Neutral Amino Acid Transporter), Member 1 omim.nt SOLUTE CARRIER FAMILY 3 (CYSTINE, DIBASIC, AND NEUTRAL AMINO ACID TRANSPORTER), MEMBER 1; SLC3A1|Amino Acid Transporter 1|D2H|Rbat owl:Class ClinVar:RCV000019743 biolink:NamedThing omim.nt ClinVar:RCV000413736 biolink:NamedThing omim.nt dbSNP:rs121912691 biolink:NamedThing omim.nt owl:NamedIndividual http://omim.org/entry/104614#0001 biolink:NamedThing omim.nt http://omim.org/entry/104614.0002 biolink:NamedThing SLC3A1, MET467LYS {4:Calonge et al. (1994)} found a met467-to-lys mutation in a patient with cystinuria defined as type I (see {220100}) who was a compound heterozygote for this and an L678P mutation ({104614.0003}). This mutation is in the same codon and, indeed, in the same nucleotide, T1400, as the M467T mutation ({104614.0001}). omim.nt GENO:0000002 ClinVar:RCV000019744 biolink:NamedThing omim.nt http://omim.org/entry/104614#0002 biolink:NamedThing omim.nt http://omim.org/entry/104614.0003 biolink:NamedThing SLC3A1, LEU678PRO For discussion of the leu678-to-pro (L678P) mutation in the SLC3A1 gene that was found in compound heterozygous state in a patient with cystinuria defined as type I (see {220100}) by {4:Calonge et al. (1994)}, see {104614.0002}. omim.nt GENO:0000002 ClinVar:RCV000019745 biolink:NamedThing omim.nt dbSNP:rs121912693 biolink:NamedThing omim.nt owl:NamedIndividual http://omim.org/entry/104614#0003 biolink:NamedThing omim.nt http://omim.org/entry/104614.0004 biolink:NamedThing SLC3A1, ARG181GLN In a patient with cystinuria defined as type I (see {220100}), {4:Calonge et al. (1994)} found compound heterozygosity for 2 mutations, R181Q and T652R ({104614.0005}). omim.nt GENO:0000002 ClinVar:RCV000019746 biolink:NamedThing omim.nt dbSNP:rs121912694 biolink:NamedThing omim.nt owl:NamedIndividual http://omim.org/entry/104614#0004 biolink:NamedThing omim.nt http://omim.org/entry/104614.0005 biolink:NamedThing SLC3A1, THR652ARG For discussion of the thr652-to-arg (T652R) mutation in the SLC3A1 gene that was found in compound heterozygous state in a patient with cystinuria defined as type I (see {220100}) by {4:Calonge et al. (1994)}, see {104614.0004}. omim.nt GENO:0000002 ClinVar:RCV000019747 biolink:NamedThing omim.nt dbSNP:rs121912695 biolink:NamedThing omim.nt owl:NamedIndividual http://omim.org/entry/104614#0005 biolink:NamedThing omim.nt http://omim.org/entry/104614.0006 biolink:NamedThing SLC3A1, PRO615THR In a patient with cystinuria defined as type I (see {220100}), {4:Calonge et al. (1994)} demonstrated a P615T mutation in the SLC3A1 gene. omim.nt GENO:0000002 ClinVar:RCV000019748 biolink:NamedThing omim.nt ClinVar:RCV001170048 biolink:NamedThing omim.nt dbSNP:rs121912696 biolink:NamedThing omim.nt owl:NamedIndividual http://omim.org/entry/104614#0006 biolink:NamedThing omim.nt http://omim.org/entry/104614.0007 biolink:NamedThing SLC3A1, EX5-9DUP Using quantitative real-time PCR in 7 unrelated, unclassified, stone-forming German cystinuria patients (see {220100}), {24:Schmidt et al. (2003)} identified a tandem duplication of exons 5 to 9 of the SLC3A1 gene, accompanied by a small inversion of 25 bp and a 2-bp deletion in intron 9. The duplication does not shift the reading frame and involves the extracellular domain of the heavy subunit of the renal amino acid transporter. In 4 of 6 heterozygotes with duplication of exons 5 to 9 of the SLC3A1 gene, {8:Font-Llitjos et al. (2005)} found the urinary excretion of cystine and dibasic amino acids to be within the range of non-I phenotype heterozygotes. The other 2 heterozygotes had aminoaciduria within the control range, indicating phenotype I. The authors stated that this was the first SLC3A1 mutation associated with the non-I phenotype in heterozygotes. See {104614.0001} and {8:Font-Llitjos et al. (2005)}. omim.nt GENO:0000002 ClinVar:RCV000019749 biolink:NamedThing omim.nt http://omim.org/entry/104614#0007 biolink:NamedThing omim.nt http://omim.org/entry/104614.0008 biolink:NamedThing SLC3A1, ARG362HIS For discussion of the arg362-to-his (R362H) mutation in the SLC3A1 gene that was found in compound heterozygous state in a patient with cystinuria and cystine stones ({220100}) by {12:Harnevik et al. (2001)} and {11:Harnevik et al. (2003)}, see {104614.0001}. omim.nt GENO:0000002 ClinVar:RCV000019750 biolink:NamedThing omim.nt dbSNP:rs121912697 biolink:NamedThing omim.nt owl:NamedIndividual http://omim.org/entry/104614#0008 biolink:NamedThing omim.nt http://omim.org/entry/104614.0009 biolink:NamedThing SLC3A1, TYR533ASN In a Portuguese patient with cystinuria ({220100}), {1:Barbosa et al. (2012)} identified a homozygous 1597T-A transversion in exon 9 of the SLC3A1 gene, resulting in a tyr533-to-asn (Y533N) substitution in a highly conserved region in the extracellular domain. The mutation was not found in 200 control alleles. The patient was a 53-year-old man who developed nephrolithiasis at age 14 years. omim.nt GENO:0000002 ClinVar:RCV000030727 biolink:NamedThing omim.nt dbSNP:rs387907276 biolink:NamedThing omim.nt owl:NamedIndividual http://omim.org/entry/104614#0009 biolink:NamedThing omim.nt MONARCH:.well-known/genid/ba6ec37e50c66fc96d6d biolink:NamedThing GRCh38chr2-44275463-44321493-Region omim.nt MONARCH:.well-known/genid/b814d61bbdc98bd6415e faldo:Region PMID:11129328 biolink:NamedThing omim.nt IAO:0000013 PMID:11524703 biolink:NamedThing omim.nt IAO:0000013 PMID:11748844 biolink:NamedThing omim.nt IAO:0000013 PMID:12239244 biolink:NamedThing omim.nt IAO:0000013 PMID:12820697 biolink:NamedThing omim.nt IAO:0000013 PMID:12923163 biolink:NamedThing omim.nt IAO:0000013 PMID:1376924 biolink:NamedThing omim.nt IAO:0000013 PMID:14531788 biolink:NamedThing omim.nt IAO:0000013 PMID:15635077 biolink:NamedThing omim.nt IAO:0000013 PMID:15913950 biolink:NamedThing omim.nt IAO:0000013 PMID:18332091 biolink:NamedThing omim.nt IAO:0000013 PMID:21255007 biolink:NamedThing omim.nt IAO:0000013 PMID:5904553 biolink:NamedThing omim.nt IAO:0000013 PMID:7539209 biolink:NamedThing omim.nt IAO:0000013 PMID:7568194 biolink:NamedThing omim.nt IAO:0000013 PMID:7698775 biolink:NamedThing omim.nt IAO:0000013 PMID:7789946 biolink:NamedThing omim.nt IAO:0000013 PMID:8052618 biolink:NamedThing omim.nt IAO:0000013 PMID:8054985 biolink:NamedThing omim.nt IAO:0000013 PMID:8054986 biolink:NamedThing omim.nt IAO:0000013 PMID:8463902 biolink:NamedThing omim.nt IAO:0000013 PMID:8486766 biolink:NamedThing omim.nt IAO:0000013 PMID:8731106 biolink:NamedThing omim.nt IAO:0000013 PMID:8792820 biolink:NamedThing omim.nt IAO:0000013 PMID:8812428 biolink:NamedThing omim.nt IAO:0000013 PMID:8921402 biolink:NamedThing omim.nt IAO:0000013 PMID:9768685 biolink:NamedThing omim.nt IAO:0000013 OBO:CHR_9606chr2p16.3 biolink:NamedThing omim.nt owl:Class http://omim.org/entry/220100 biolink:NamedThing|biolink:Disease Cystinuria Cystinuria omim.nt CYSTINURIA|Csnu|Cystinuria, Type a|Cystinuria, Type A/B|Cystinuria, Type B|Cystinuria, Type I, Formerly|Cystinuria, Type Ii, Formerly|Cystinuria, Type Iii, Formerly|Cystinuria, Type Non-I, Formerly owl:Class UMLS:C1420191 biolink:NamedThing omim.nt owl:Class https://www.ncbi.nlm.nih.gov/gene/6519 biolink:NamedThing omim.nt http://omim.org/entry/104615 biolink:NamedThing|biolink:Gene SLC7A1 distal to ATP1AL1|Solute Carrier Family 7 (Cationic Amino Acid Transporter, Y+ System), Member 1 omim.nt SOLUTE CARRIER FAMILY 7 (CATIONIC AMINO ACID TRANSPORTER, y+ SYSTEM), MEMBER 1; SLC7A1|Amino Acid Transporter, Cationic 1|Cationic Amino Acid Transporter 1 owl:Class MONARCH:.well-known/genid/b5976aef49d75412dfd9 biolink:NamedThing GRCh38chr13-29509409-29595687-Region omim.nt MONARCH:.well-known/genid/bccbd2b8b570df4dcb66 faldo:Region PMID:1348489 biolink:NamedThing omim.nt IAO:0000013 PMID:1652100 biolink:NamedThing omim.nt IAO:0000013 PMID:16777601 biolink:NamedThing omim.nt IAO:0000013 PMID:212501 biolink:NamedThing omim.nt IAO:0000013 PMID:2159567 biolink:NamedThing omim.nt IAO:0000013 PMID:566388 biolink:NamedThing omim.nt IAO:0000013 PMID:8314586 biolink:NamedThing omim.nt IAO:0000013 OBO:CHR_9606chr13q12.3 biolink:NamedThing omim.nt owl:Class UMLS:C1442751 biolink:NamedThing omim.nt owl:Class https://www.ncbi.nlm.nih.gov/gene/6541 biolink:NamedThing omim.nt http://omim.org/entry/104620.0001 biolink:NamedThing ACY1, 2-BP INS, 1105AC In the offspring of consanguineous Turkish parents, residing in Germany, {14:Sass et al. (2006)} detected aminoacylase-1 deficiency (ACY1D; {609924}) by the presence of N-acetylamino acids in the urine in the course of selective screening for inborn errors of metabolism. The subject's development appeared to be normal. He attended high school. He started walking at age 1 year. At age 3 years, the parents first observed muscle weakness that prompted a thorough investigation at age 11 years. During that examination the boy presented with low normal muscle tone and a shambling gait. Extensive studies revealed no significant myopathologic abnormalities. {14:Sass et al. (2006)} identified a homozygous loss-of-function mutation in the ACY1 gene predicting aberrant translation, a 2-bp insertion, 1105_1106insAC. The 2-bp insertion predicted a frameshift beginning with amino acid residue 369 (369ProfsTer46). Notably, the mutation did not lead to premature termination of translation but predicted a C-terminal mutated protein longer than the wildtype protein (408 amino acid residues) and affected the C-terminal peptidase domain. Both parents were heterozygous carriers. omim.nt GENO:0000002 http://omim.org/entry/104620 biolink:NamedThing|biolink:Gene ACY1 Aminoacylase 1 omim.nt AMINOACYLASE 1; ACY1|Acylase|N-Acyl-L-Amino Acid Amidohydrolase owl:Class ClinVar:RCV000019737 biolink:NamedThing omim.nt dbSNP:rs387906579 biolink:NamedThing omim.nt owl:NamedIndividual http://omim.org/entry/104620#0001 biolink:NamedThing omim.nt http://omim.org/entry/104620.0002 biolink:NamedThing ACY1, ARG353CYS In a patient with aminoacylase-1 deficiency (ACY1D; {609924}), {16:Van Coster et al. (2005)} identified a homozygous 1057C-T transition in exon 14 of the ACY1 gene, resulting in an arg353-to-cys (R353C) substitution. Both parents were heterozygous for the mutation, and it was identified in the heterozygous state in 5 of 161 controls. In vitro functional expression studies showed complete absence of enzyme activity. {14:Sass et al. (2006)} described ACY1 deficiency in the child of nonconsanguineous German parents. The boy was identified in a general neonatal screening as being biotinidase deficient ({253260}), for which he was given treatment with 5 mg biotin per day. Under this medication his cognitive and motor skills developed completely normally to the time of reporting at age 17 months. He was found to be homozygous for the R353C mutation. Each parent was heterozygous for the mutation. The R353C mutation was found in another patient in compound heterozygosity with another missense mutation ({104620.0003}). {14:Sass et al. (2006)} also found this mutation in 1 of 210 control chromosomes, consistent with this allele being a rare polymorphism or a more common mutation. {15:Sass et al. (2007)} identified the R353C mutation in 2 additional children with ACY1 deficiency. One was homozygous for the mutation and the other compound heterozygous with R393H ({104620.0006}). Both patients presented at around 1 year of age with seizures. One showed complete recovery, and the other had moderate mental retardation. omim.nt GENO:0000002 ClinVar:RCV000019738 biolink:NamedThing omim.nt ClinVar:RCV000514755 biolink:NamedThing omim.nt dbSNP:rs121912698 biolink:NamedThing omim.nt owl:NamedIndividual http://omim.org/entry/104620#0002 biolink:NamedThing omim.nt http://omim.org/entry/104620.0003 biolink:NamedThing ACY1, GLU233ASP {14:Sass et al. (2006)} found compound heterozygosity for 2 missense mutations of the ACY1 gene as the apparent basis of aminoacylase-1 deficiency (ACY1D; {609924}) in the daughter of healthy parents of German (mother) and Italian (father) origin. One mutation in the child was R353C ({104620.0002}). The other was a 699A-C transversion in exon 10 that resulted in a glu233-to-asp change (E233D). At age 2 years, a neuropediatric evaluation was initiated because of moderately retarded cognitive and motor development. omim.nt GENO:0000002 ClinVar:RCV000019739 biolink:NamedThing omim.nt ClinVar:RCV001169855 biolink:NamedThing omim.nt dbSNP:rs121912699 biolink:NamedThing omim.nt owl:NamedIndividual http://omim.org/entry/104620#0003 biolink:NamedThing omim.nt http://omim.org/entry/104620.0004 biolink:NamedThing ACY1, IVS5AS, -1, G-A In a boy with aminoacylase-1 deficiency (ACY1D; {609924}), the son of consanguineous Turkish parents, {14:Sass et al. (2006)} found homozygosity for a splice site mutation in the ACY1 gene. The homozygous mutation IVS5-1G-A predicted malfunction of the acceptor splice site of exon 6, skipping of exon 6 (amino acid residues 121 to 146), and a premature stop codon. Both parents were heterozygous for this mutation. The child had been investigated because of early impaired psychomotor development characterized by markedly disturbed central coordination and low muscle tone. Cerebellar hypoplasia had been suggested prenatally by sonography. Magnetic resonance imaging of the head and spine at the age of 3 months demonstrated hypoplasia of the corpus callosum and vermis cerebelli, as well as delayed myelination of the supratentorial white matter. The lumbar spinal cord exhibited syringomyelia with a length of 3.5 cm. omim.nt GENO:0000002 ClinVar:RCV000019740 biolink:NamedThing omim.nt dbSNP:rs672601330 biolink:NamedThing omim.nt owl:NamedIndividual http://omim.org/entry/104620#0004 biolink:NamedThing omim.nt http://omim.org/entry/104620.0005 biolink:NamedThing ACY1, ARG197TRP In an Asian girl, born of consanguineous parents, with aminoacylase-1 deficiency (ACY1D; {609924}), {15:Sass et al. (2007)} identified a homozygous 589C-T transition in the ACY1 gene, resulting in an arg197-to-trp (R197W) substitution. She was originally detected by newborn screening. At age 11 months, she presented with febrile seizures, followed by another episode of seizures 3 months later. She showed delayed speech and language development at age 4 years. omim.nt GENO:0000002 ClinVar:RCV000019741 biolink:NamedThing omim.nt dbSNP:rs121912700 biolink:NamedThing omim.nt owl:NamedIndividual http://omim.org/entry/104620#0005 biolink:NamedThing omim.nt http://omim.org/entry/104620.0006 biolink:NamedThing ACY1, ARG393HIS In an English girl with aminoacylase-1 deficiency (ACY1D; {609924}), {15:Sass et al. (2007)} identified compound heterozygosity for 2 mutations in the ACY1 gene: a 1178G-A transition, resulting in an arg393-to-his (R393H) substitution, and the R353C mutation ({104620.0002}). omim.nt GENO:0000002 ClinVar:RCV000019742 biolink:NamedThing omim.nt ClinVar:RCV000292281 biolink:NamedThing omim.nt ClinVar:RCV000488111 biolink:NamedThing omim.nt dbSNP:rs121912701 biolink:NamedThing omim.nt owl:NamedIndividual http://omim.org/entry/104620#0006 biolink:NamedThing omim.nt http://omim.org/entry/104620.0007 biolink:NamedThing ACY1, 6-BP DEL, NT1001 In a 6-year-old girl, born of consanguineous parents, with aminoacylase-1 deficiency (ACY1D; {609924}) and severe neurologic impairment, {3:Ferri et al. (2014)} identified a homozygous 6-bp deletion (c.1001_1001+5_del6) involving the last nucleotide of exon 13 and the first 5 nucleotides of intron 13. PCR analysis of patient cells showed the absence of exon 13 in the mRNA, resulting in a frameshift and premature termination (Lys308GlufsTer7). Patient fibroblasts showed absent ACY1 enzymatic activity. Parental DNA was not available for segregation analysis. omim.nt GENO:0000002 ClinVar:RCV000149440 biolink:NamedThing omim.nt dbSNP:rs672601350 biolink:NamedThing omim.nt owl:NamedIndividual http://omim.org/entry/104620#0007 biolink:NamedThing omim.nt MONARCH:.well-known/genid/b3a9758037d73e2fad32 biolink:NamedThing GRCh38chr3-51983534-51989196-Region omim.nt MONARCH:.well-known/genid/bf3fe1371a7596652377 faldo:Region MONARCH:.well-known/genid/OMIM104620ref8 biolink:NamedThing Aminoacylase-1: cDNA isolation, regional assignment to chromosome 3p21.1 and identification of a cross-hybridizing sequence on chromosome 18. (Abstract) omim.nt IAO:0000310 PMID:15196915 biolink:NamedThing omim.nt IAO:0000013 PMID:16274666 biolink:NamedThing omim.nt IAO:0000013 PMID:16465618 biolink:NamedThing omim.nt IAO:0000013 PMID:1662666 biolink:NamedThing omim.nt IAO:0000013 PMID:1707030 biolink:NamedThing omim.nt IAO:0000013 PMID:17562838 biolink:NamedThing omim.nt IAO:0000013 PMID:24117009 biolink:NamedThing omim.nt IAO:0000013 PMID:2542383 biolink:NamedThing omim.nt IAO:0000013 PMID:3106151 biolink:NamedThing omim.nt IAO:0000013 PMID:373141 biolink:NamedThing omim.nt IAO:0000013 PMID:6803586 biolink:NamedThing omim.nt IAO:0000013 PMID:6948533 biolink:NamedThing omim.nt IAO:0000013 PMID:8394326 biolink:NamedThing omim.nt IAO:0000013 OBO:CHR_9606chr3p21.1 biolink:NamedThing omim.nt owl:Class http://omim.org/entry/609924 biolink:NamedThing|biolink:Disease Aminoacylase 1 Deficiency Aminoacylase 1 Deficiency omim.nt AMINOACYLASE 1 DEFICIENCY; ACY1D owl:Class UMLS:C1412173 biolink:NamedThing omim.nt owl:Class https://www.ncbi.nlm.nih.gov/gene/95 biolink:NamedThing omim.nt http://omim.org/entry/104640 biolink:NamedThing|biolink:Gene AREG Amphiregulin omim.nt AMPHIREGULIN; AREG|Schwannoma-Derived Growth Factor owl:Class MONARCH:.well-known/genid/bd41dc743d887ecb21cb biolink:NamedThing GRCh38chr4-74445135-74455004-Region omim.nt MONARCH:.well-known/genid/b7a399d7318c5ae9c15a faldo:Region MONARCH:.well-known/genid/OMIM104640ref3 biolink:NamedThing Mapping of the amphiregulin and the platelet-growth factor receptor alpha genes to the proximal long arm of chromosome 4. (Abstract) omim.nt IAO:0000310 PMID:14726596 biolink:NamedThing omim.nt IAO:0000013 PMID:17170297 biolink:NamedThing omim.nt IAO:0000013 PMID:17369357 biolink:NamedThing omim.nt IAO:0000013 PMID:1954899 biolink:NamedThing omim.nt IAO:0000013 PMID:2234093 biolink:NamedThing omim.nt IAO:0000013 PMID:2466334 biolink:NamedThing omim.nt IAO:0000013 PMID:3413110 biolink:NamedThing omim.nt IAO:0000013 PMID:7590736 biolink:NamedThing omim.nt IAO:0000013 PMID:9410906 biolink:NamedThing omim.nt IAO:0000013 OBO:CHR_9606chr4q13 biolink:NamedThing omim.nt owl:Class UMLS:C1332109 biolink:NamedThing omim.nt owl:Class https://www.ncbi.nlm.nih.gov/gene/374 biolink:NamedThing omim.nt http://omim.org/entry/104650 biolink:NamedThing|biolink:Gene AMY2A Amylase, Pancreatic, a omim.nt AMYLASE, PANCREATIC, A; AMY2A|Amy2 owl:Class MONARCH:.well-known/genid/b06d3da8154bc6688888 biolink:NamedThing GRCh38chr1-103617426-103625779-Region omim.nt MONARCH:.well-known/genid/bd203c1a6d3f1ec673f4 faldo:Region MONARCH:.well-known/genid/OMIM104650ref20 biolink:NamedThing Human Polymorphic Genes: World Distribution. omim.nt IAO:0000310 PMID:15286789 biolink:NamedThing omim.nt IAO:0000013 PMID:1679752 biolink:NamedThing omim.nt IAO:0000013 PMID:1710200 biolink:NamedThing omim.nt IAO:0000013 PMID:2081604 biolink:NamedThing omim.nt IAO:0000013 PMID:25788522 biolink:NamedThing omim.nt IAO:0000013 PMID:2788608 biolink:NamedThing omim.nt IAO:0000013 PMID:309725 biolink:NamedThing omim.nt IAO:0000013 PMID:3260028 biolink:NamedThing omim.nt IAO:0000013 PMID:3260546 biolink:NamedThing omim.nt IAO:0000013 PMID:4507806 biolink:NamedThing omim.nt IAO:0000013 PMID:4551225 biolink:NamedThing omim.nt IAO:0000013 PMID:4741846 biolink:NamedThing omim.nt IAO:0000013 PMID:4741847 biolink:NamedThing omim.nt IAO:0000013 PMID:5101659 biolink:NamedThing omim.nt IAO:0000013 PMID:5246559 biolink:NamedThing omim.nt IAO:0000013 PMID:6160849 biolink:NamedThing omim.nt IAO:0000013 PMID:6162570 biolink:NamedThing omim.nt IAO:0000013 PMID:6176528 biolink:NamedThing omim.nt IAO:0000013 PMID:6200983 biolink:NamedThing omim.nt IAO:0000013 PMID:6608795 biolink:NamedThing omim.nt IAO:0000013 PMID:8528071 biolink:NamedThing omim.nt IAO:0000013 PMID:955637 biolink:NamedThing omim.nt IAO:0000013 UMLS:C1412394 biolink:NamedThing omim.nt owl:Class https://www.ncbi.nlm.nih.gov/gene/279 biolink:NamedThing omim.nt http://omim.org/entry/104660 biolink:NamedThing|biolink:Gene AMY2B Amylase, Pancreatic, B|distal to NGFB omim.nt AMYLASE, PANCREATIC, B; AMY2B owl:Class MONARCH:.well-known/genid/b1c7288bc0d5278925ea biolink:NamedThing GRCh38chr1-103554643-103579533-Region omim.nt MONARCH:.well-known/genid/b818607ae8a321a7cd3b faldo:Region MONARCH:.well-known/genid/OMIM104660ref8 biolink:NamedThing Human Polymorphic Genes: World Distribution. omim.nt IAO:0000310 UMLS:C1412395 biolink:NamedThing omim.nt owl:Class https://www.ncbi.nlm.nih.gov/gene/280 biolink:NamedThing omim.nt http://omim.org/entry/104700 biolink:NamedThing|biolink:Gene AMY1A Amylase, Salivary, a|multiple amylase genes omim.nt AMYLASE, SALIVARY, A; AMY1A|Amylase, Salivary owl:Class MONARCH:.well-known/genid/b72c98c37ae5254ed99f biolink:NamedThing GRCh38chr1-103655518-103664553-Region omim.nt MONARCH:.well-known/genid/b874a3ce306f9e6f24d8 faldo:Region MONARCH:.well-known/genid/OMIM104700ref13 biolink:NamedThing Comparative analysis of mouse-human hybrids with rearranged chromosomes 1 by in situ hybridization and Southern blotting: high resolution mapping of NRAS, NGFB, and AMY on chromosome 1. omim.nt IAO:0000310 MONARCH:.well-known/genid/OMIM104700ref18 biolink:NamedThing Human Polymorphic Genes: World Distribution. omim.nt IAO:0000310 MONARCH:.well-known/genid/OMIM104700ref21 biolink:NamedThing Genetics of amylase isozymes in the mouse. omim.nt IAO:0000310 MONARCH:.well-known/genid/OMIM104700ref22 biolink:NamedThing Assignment of alpha-amylase genes to the p22.1-p21 region of chromosome 1. (Abstract) omim.nt IAO:0000310 PMID:15273396 biolink:NamedThing omim.nt IAO:0000013 PMID:15340426 biolink:NamedThing omim.nt IAO:0000013 PMID:1692298 biolink:NamedThing omim.nt IAO:0000013 PMID:17828263 biolink:NamedThing omim.nt IAO:0000013 PMID:22965187 biolink:NamedThing omim.nt IAO:0000013 PMID:2410924 biolink:NamedThing omim.nt IAO:0000013 PMID:2423416 biolink:NamedThing omim.nt IAO:0000013 PMID:2452973 biolink:NamedThing omim.nt IAO:0000013 PMID:2998973 biolink:NamedThing omim.nt IAO:0000013 PMID:4180439 biolink:NamedThing omim.nt IAO:0000013 PMID:5097906 biolink:NamedThing omim.nt IAO:0000013 PMID:5869482 biolink:NamedThing omim.nt IAO:0000013 PMID:6010879 biolink:NamedThing omim.nt IAO:0000013 PMID:6196780 biolink:NamedThing omim.nt IAO:0000013 PMID:6207099 biolink:NamedThing omim.nt IAO:0000013 PMID:738721 biolink:NamedThing omim.nt IAO:0000013 UMLS:C1412391 biolink:NamedThing omim.nt owl:Class https://www.ncbi.nlm.nih.gov/gene/276 biolink:NamedThing omim.nt http://omim.org/entry/104701 biolink:NamedThing|biolink:Gene AMY1B Amylase, Salivary, B omim.nt AMYLASE, SALIVARY, B; AMY1B owl:Class MONARCH:.well-known/genid/b589390bc177b5a4cf7e biolink:NamedThing GRCh38chr1-103687414-103696452-Region omim.nt MONARCH:.well-known/genid/b6aa5ccefa37b3351119 faldo:Region MONARCH:.well-known/genid/OMIM104701ref10 biolink:NamedThing Human Polymorphic Genes: World Distribution. omim.nt IAO:0000310 UMLS:C1412392 biolink:NamedThing omim.nt owl:Class https://www.ncbi.nlm.nih.gov/gene/277 biolink:NamedThing omim.nt http://omim.org/entry/104702 biolink:NamedThing|biolink:Gene AMY1C Amylase, Salivary, C omim.nt AMYLASE, SALIVARY, C; AMY1C owl:Class MONARCH:.well-known/genid/b3ea3362f6166cb09183 biolink:NamedThing GRCh38chr1-103745429-103758691-Region omim.nt MONARCH:.well-known/genid/b6c88ab12dd55c42e6e4 faldo:Region MONARCH:.well-known/genid/OMIM104702ref10 biolink:NamedThing Human Polymorphic Genes: World Distribution. omim.nt IAO:0000310 UMLS:C1412393 biolink:NamedThing omim.nt owl:Class https://www.ncbi.nlm.nih.gov/gene/278 biolink:NamedThing omim.nt http://omim.org/entry/104740 biolink:NamedThing omim.nt True owl:Class http://omim.org/entry/602414 biolink:NamedThing|biolink:Gene APBA1 Amyloid Beta A4 Precursor Protein-Binding, Family A, Member 1 omim.nt AMYLOID BETA A4 PRECURSOR PROTEIN-BINDING, FAMILY A, MEMBER 1; APBA1|D9S411E|Munc18-1-Interacting Protein 1|Vertebrate Lin10 Homolog|X11|X11-Alpha owl:Class http://omim.org/entry/104750.0001 biolink:NamedThing SAA1, GLY72ASP By isoelectric focusing, {9:Kluve-Beckerman et al. (1991)} identified an allelic variant of SAA in a family of Turkish origin: a G-to-A transition in codon 72, which resulted in substitution of aspartic acid for glycine. {4:Beach et al. (1992)} found the same gly72-to-asp allelic variant. omim.nt GENO:0000002 http://omim.org/entry/104750 biolink:NamedThing|biolink:Gene SAA1 Serum Amyloid A1 omim.nt SERUM AMYLOID A1; SAA1|Amyloid A, Serum owl:Class ClinVar:RCV000019735 biolink:NamedThing omim.nt ClinVar:RCV000950760 biolink:NamedThing omim.nt dbSNP:rs79681911 biolink:NamedThing omim.nt owl:NamedIndividual http://omim.org/entry/104750#0001 biolink:NamedThing omim.nt http://omim.org/entry/104750.0002 biolink:NamedThing SAA1, VAL52ALA {1:Baba et al. (1995)} described an allelic variant of the SAA1 gene that they proposed may represent an important risk factor for the development of reactive amyloid systemic amyloidosis, also called AA-amyloidosis. The variant, termed SAA1-gamma, was found in pooled acute-phase serum, using mass spectrometry. SAA1-gamma has alanines at amino acid positions 52 and 57, whereas the previously known SAA1 variants, SAA1-alpha and SAA1-beta, have a valine at position 52 or 57, respectively, instead of an alanine. These SAA1s are the 3 major isoforms of human SAA1. {1:Baba et al. (1995)} found that SAA1-gamma differed from SAA1-alpha at only 1 base; codon 52 was GCC (ala) in SAA1-gamma and GTC (val) in SAA1-alpha. They found a difference in the distribution of SAA1 genotypes with an increased frequency of gamma/gamma homozygotes in the AA-amyloid group (0.60 vs 0.18). omim.nt GENO:0000002 ClinVar:RCV000019736 biolink:NamedThing omim.nt ClinVar:RCV000761767 biolink:NamedThing omim.nt dbSNP:rs1136743 biolink:NamedThing omim.nt owl:NamedIndividual http://omim.org/entry/104750#0002 biolink:NamedThing omim.nt MONARCH:.well-known/genid/b759046ae205643977a9 biolink:NamedThing GRCh38chr11-18266263-18269966-Region omim.nt MONARCH:.well-known/genid/bb3ed516f4289b536997 faldo:Region PMID:11017802 biolink:NamedThing omim.nt IAO:0000013 PMID:12011456 biolink:NamedThing omim.nt IAO:0000013 PMID:12952844 biolink:NamedThing omim.nt IAO:0000013 PMID:1546977 biolink:NamedThing omim.nt IAO:0000013 PMID:1656519 biolink:NamedThing omim.nt IAO:0000013 PMID:1755958 biolink:NamedThing omim.nt IAO:0000013 PMID:1764061 biolink:NamedThing omim.nt IAO:0000013 PMID:2564214 biolink:NamedThing omim.nt IAO:0000013 PMID:2808379 biolink:NamedThing omim.nt IAO:0000013 PMID:3015139 biolink:NamedThing omim.nt IAO:0000013 PMID:3800865 biolink:NamedThing omim.nt IAO:0000013 PMID:3839415 biolink:NamedThing omim.nt IAO:0000013 PMID:6088946 biolink:NamedThing omim.nt IAO:0000013 PMID:6301947 biolink:NamedThing omim.nt IAO:0000013 PMID:6774048 biolink:NamedThing omim.nt IAO:0000013 PMID:6810934 biolink:NamedThing omim.nt IAO:0000013 PMID:7622070 biolink:NamedThing omim.nt IAO:0000013 PMID:7655463 biolink:NamedThing omim.nt IAO:0000013 PMID:7835903 biolink:NamedThing omim.nt IAO:0000013 PMID:7851899 biolink:NamedThing omim.nt IAO:0000013 PMID:8094371 biolink:NamedThing omim.nt IAO:0000013 PMID:8188252 biolink:NamedThing omim.nt IAO:0000013 OBO:CHR_9606chr11p15.1 biolink:NamedThing omim.nt owl:Class UMLS:C1419799 biolink:NamedThing omim.nt owl:Class https://www.ncbi.nlm.nih.gov/gene/6288 biolink:NamedThing omim.nt http://omim.org/entry/104751 biolink:NamedThing|biolink:Gene SAA2 pseudogene = SAA3|Serum Amyloid A2 omim.nt SERUM AMYLOID A2; SAA2|Amyloid A, Serum, 2 owl:Class MONARCH:.well-known/genid/b92ae7a878670d7ff2df biolink:NamedThing GRCh38chr11-18238235-18248667-Region omim.nt MONARCH:.well-known/genid/b8a9987e4a280775a8be faldo:Region PMID:3130100 biolink:NamedThing omim.nt IAO:0000013 PMID:7686132 biolink:NamedThing omim.nt IAO:0000013 PMID:8325654 biolink:NamedThing omim.nt IAO:0000013 UMLS:C1419800 biolink:NamedThing omim.nt owl:Class https://www.ncbi.nlm.nih.gov/gene/6289 biolink:NamedThing omim.nt http://omim.org/entry/104752 biolink:NamedThing|biolink:Gene SAA4 Serum Amyloid A4 omim.nt SERUM AMYLOID A4; SAA4|Amyloid A, Serum, 4|Serum Amyloid A4, Constitutive owl:Class MONARCH:.well-known/genid/bc8eaf3ea3eefd0f5a6d biolink:NamedThing GRCh38chr11-18231354-18236801-Region omim.nt MONARCH:.well-known/genid/b222938e8eb72067147d faldo:Region PMID:1439582 biolink:NamedThing omim.nt IAO:0000013 PMID:1740433 biolink:NamedThing omim.nt IAO:0000013 PMID:8661036 biolink:NamedThing omim.nt IAO:0000013 UMLS:C1419802 biolink:NamedThing omim.nt owl:Class https://www.ncbi.nlm.nih.gov/gene/6291 biolink:NamedThing omim.nt http://omim.org/entry/104760.0001 biolink:NamedThing APP, GLU693GLN In 2 patients with hereditary cerebral hemorrhage with amyloidosis of the Dutch type (HCHWAD; {605714}), {121:Levy et al. (1990)} identified a 1852G-C transversion in the APP gene, resulting in a glu693-to-gln (E693Q) substitution. The change is referred to as E22Q in the processed amyloid beta peptide. Affected patients usually presented with cerebral lobar hemorrhages before 50 years of age due to the severe cerebral arterial amyloidosis. However, in these patients, parenchymal amyloid deposits were rare, and neurofibrillary tangles were consistently absent, features that clearly distinguished the Dutch phenotype from those related to the 'Flemish' (A692G; {104760.0005}) and 'Arctic' (E693G; {104760.0013}) mutations ({136:Miravalle et al., 2000}). {5:Bakker et al. (1991)} described the use of an E693Q mutation-specific oligonucleotide in the diagnosis of Dutch hereditary cerebral hemorrhage with amyloidosis. {36:De Jonghe et al. (1998)} showed that the E693Q mutation did not result in increased secretion of fibrillogenic beta-amyloid-40 or beta-amyloid-42, consistent with the lack of AD pathology found in patients with this mutation. In contrast, the A692G mutation ({104760.0005}) upregulated both beta-amyloid-40 and beta-amyloid-42 secretion, consistent with the findings of AD pathology in patients with that mutation. These data corroborated previous findings that increased beta-amyloid secretion, particularly beta-amyloid-42, is specific for AD pathology. {136:Miravalle et al. (2000)} demonstrated in vitro that the E693Q mutation resulted in a high content of beta-sheet amyloid conformation and fast aggregation/fibrillization properties. The E693Q mutant induced cerebral endothelial cell apoptosis, whereas the E693K mutant ({104760.0014}) did not. The data suggested that different amino acids at codon 693 conferred distinct structural properties to the peptides that appeared to influence the age at onset and aggressiveness of the disease rather than the phenotype. omim.nt GENO:0000002 http://omim.org/entry/104760 biolink:NamedThing|biolink:Gene APP Amyloid Beta A4 Precursor Protein|proximal to SOD; very distal q21 or boundary with q22 omim.nt AMYLOID BETA A4 PRECURSOR PROTEIN; APP|Amyloid of Aging and Alzheimer Disease|Cerebral Vascular Amyloid Peptide|Protease Nexin 2 owl:Class ClinVar:RCV000019713 biolink:NamedThing omim.nt dbSNP:rs63750579 biolink:NamedThing omim.nt owl:NamedIndividual http://omim.org/entry/104760#0001 biolink:NamedThing omim.nt http://omim.org/entry/104760.0002 biolink:NamedThing APP, VAL717ILE In affected members of 2 families with early-onset Alzheimer disease-1 ({104300}), {64:Goate et al. (1991)} identified a heterozygous 2149C-T transition in exon 17 of the APP gene, resulting in a val717-to-ile (V717I) substitution. The mutation may have involved a CpG dinucleotide. The substitution created a BclI restriction site which allowed detection of the corresponding change within the PCR product. {150:Naruse et al. (1991)} identified the V717I mutation in 2 unrelated Japanese patients with familial early-onset Alzheimer disease, and {239:Yoshioka et al. (1991)} identified it in a third Japanese family. Failing to find the V717I mutation in 100 patients with early-onset AD, {221:van Duijn et al. (1991)} concluded that it accounts for less than 3.6% of all cases with early-onset AD. {187:Schellenberg et al. (1991)} did not identify the V717I mutation in 76 families with familial Alzheimer disease, 127 subjects with presumably sporadic Alzheimer disease, 16 patients with Down syndrome, or 256 normal controls. {103:Karlinsky et al. (1992)} reported an AD family from Toronto with the V717I mutation. The family immigrated to Canada from the British Isles in the 18th century. Relationship to one or both of the pedigrees reported by {64:Goate et al. (1991)} could not be excluded. In a follow-up report of the family reported by {103:Karlinsky et al. (1992)}, {200:St. George-Hyslop et al. (1994)} noted that 1 family member with the V717I mutation remained clinically healthy with no sign of disease on neurologic or neuropsychologic tests or on brain imaging. The authors suggested that this might be due to the fact that this individual lacked the E4 allele at the APOE locus ({107741}), his genotype being E2/E3. All 3 living clinically affected family members with the V717I mutation were considerably younger and had the E3/E4 genotype. {200:St. George-Hyslop et al. (1994)} suggested that there is an interaction between the development of Alzheimer disease due to mutations in the APP gene and the E4 allele. In contrast, they observed no relationship between the APOE genotype and age of onset or other clinical features in affected members of a large pedigree in which familial AD was linked to chromosome 14 (AD3; {607822}). {130:Maruyama et al. (1996)} explored the significance of the fact that 3 mutations in the val717 residue of APP (V717I; V717F; {104760.0003}, and V717G; {104760.0004}) had been found in patients with familial Alzheimer disease and that these mutations resulted in increased secretion of A-beta-42(43). Functional expression studies showed that the FAD-linked mutations at residue 717 increased the levels or ratios of A-beta-42(43), whereas the secretion of A-beta-40 was decreased. Mutations at residue 717 irrelevant to FAD, except V717K, had little effect on the ratio of beta-42(43). V717K decreased the secretion of beta-42. Overall, the results suggested a specific role of the val717 residue in APP processing and gamma-cleavage. omim.nt GENO:0000002 ClinVar:RCV000019714 biolink:NamedThing omim.nt ClinVar:RCV000020308 biolink:NamedThing omim.nt ClinVar:RCV000084575 biolink:NamedThing omim.nt dbSNP:rs63750264 biolink:NamedThing omim.nt owl:NamedIndividual http://omim.org/entry/104760#0002 biolink:NamedThing omim.nt http://omim.org/entry/104760.0003 biolink:NamedThing APP, VAL717PHE In affected members of a large Indiana kindred with autopsy-proven Alzheimer disease ({104300}), {147:Murrell et al. (1991)} identified a G-to-T transversion in the APP gene, resulting in a val717-to-phe (V717F) substitution. The substitution is 2 residues beyond the carboxyl terminus of the beta-amyloid peptide subunit isolated from amyloid fibrils. See also V717I ({104760.0002}) and V717G ({104760.0004}). {242:Zeldenrust et al. (1993)} identified the V717F substitution in 9 of 34 at-risk members of the original Indiana kindred reported by {147:Murrell et al. (1991)}. {61:Games et al. (1995)} found that brains of transgenic mice overexpressing the V717F mutant protein showed typical pathologic findings of AD, including numerous extracellular thioflavine S-positive A-beta deposits, neuritic plaques, synaptic loss, astrocytosis, and microgliosis. {7:Bales et al. (1999)} quantified the amount of amyloid beta-peptide immunoreactivity as well as amyloid deposits in a large cohort of transgenic mice overexpressing the V717F human APP mutation, with zero, 1, or 2 mouse ApoE ({107741}) alleles at various ages. Remarkably, no amyloid deposits were found in any brain region of V717F heterozygous mice that were ApoE -/- as old as 22 months of age, whereas age-matched V717F heterozygous animals which were either ApoE +/- or ApoE +/+ displayed abundant amyloid deposition. The amount of A-beta immunoreactivity in the hippocampus was also markedly reduced in an ApoE gene dose-dependent manner, and no A-beta immunoreactivity was detected in the cerebral cortex of V717F heterozygous mice that were ApoE -/- at any of the time points examined. Because the absence of ApoE altered neither the transcription nor the translation of the APP(V717F) transgene nor its processing to A-beta peptide(s), {7:Bales et al. (1999)} postulated that ApoE promotes both the deposition and fibrillization of A-beta, ultimately affecting clearance of protease-resistant A-beta/ApoE aggregates. ApoE appears to play an essential role in amyloid deposition in brain, one of the neuropathologic hallmarks of Alzheimer disease. {40:DeMattos et al. (2004)} generated transgenic mice with the V717F mutation that were also null for ApoE, ApoJ ({185430}), or null for both Apo genes. The double Apo-knockout mice showed early-onset beta-amyloid deposition beginning at 6 months of age and a marked increase in amyloid deposition compared to the other mice. The amyloid plaques were compact and diffuse, were thioflavine S-positive indicating true fibrillar amyloid, and were distributed throughout the hippocampus and some parts of the cortex, contributing to neuritic plaques. The findings suggested that ApoE and ApoJ are not required for amyloid fibril formation. The double Apo knockout mice also had increased levels of intracellular soluble beta-amyloid compared to the other mice. Insoluble beta-42 was similar to the ApoE-null mice, suggesting that ApoE has a selective effect on beta-42. As APP is produced and secreted by neurons in the CNS, and apoE and apoJ are produced and secreted primarily by astrocytes in the CNS, the interaction between the apolipoproteins and beta-amyloid must occur in the interstitial fluid of the brain, an extracellular compartment that is continuous with the CSF. {40:DeMattos et al. (2004)} found that ApoE-null and ApoE/ApoJ-null mice had increased levels of beta-amyloid in the CSF and interstitial space, suggesting that ApoE, and perhaps ApoJ, play a role in regulating extracellular CNS beta-amyloid clearance independent of beta-amyloid synthesis. The data suggested that, in the mouse, ApoE and ApoJ cooperatively suppress beta-amyloid deposition. omim.nt GENO:0000002 ClinVar:RCV000019715 biolink:NamedThing omim.nt ClinVar:RCV000815476 biolink:NamedThing omim.nt http://omim.org/entry/104760#0003 biolink:NamedThing omim.nt http://omim.org/entry/104760.0004 biolink:NamedThing APP, VAL717GLY In affected members of a family with early-onset Alzheimer disease ({104300}), {21:Chartier-Harlin et al. (1991)} identified a 2150T-G transversion in exon 17 of the APP gene, resulting in a val717-to-glu (V717G) substitution. Average age at onset was 59 years. It was the third mutation identified in codon 717 of the APP gene in families with Alzheimer disease (see V717I, {104760.0002} and V717F, {104760.0003}). omim.nt GENO:0000002 ClinVar:RCV000019716 biolink:NamedThing omim.nt ClinVar:RCV000084576 biolink:NamedThing omim.nt dbSNP:rs63749964 biolink:NamedThing omim.nt owl:NamedIndividual http://omim.org/entry/104760#0004 biolink:NamedThing omim.nt http://omim.org/entry/104760.0005 biolink:NamedThing APP, ALA692GLY In affected members of a 4-generation Dutch family with early-onset Alzheimer disease ({104300}) and hereditary amyloidosis, {77:Hendriks et al. (1992)} identified a C-to-G transversion in the APP gene, resulting in an ala692-to-gly (A692G) substitution, which corresponds to A21G in the beta-amyloid protein. {34:Cras et al. (1998)} described the postmortem examination of 2 demented patients with the A692G mutation. The autopsy findings supported the diagnosis of Alzheimer disease in both patients. The neuropathologic abnormalities were remarkable for the large amyloid core senile plaques, the presence of neurofibrillary tangles, and extensive amyloid angiopathy. Leptomeningeal and parenchymal vessels showed extensive deposition of A-beta-amyloid protein. The morphology of the senile plaques was clearly distinct from that described in sporadic AD, in chromosome 14-linked AD patients (AD3; {607822}), in AD patients with the APP V717I mutation ({104760.0002}), and in patients with the APP E693Q mutation ({104760.0001}) causing the Dutch form of cerebroarterial amyloidosis ({605714}). {36:De Jonghe et al. (1998)} provided evidence that the A692G mutation resulted in increased secretion of fibrillogenic beta-amyloid-40 and beta-amyloid-42, consistent with the findings of AD pathology in patients with this mutation. These data corroborated the previous findings that increased beta-amyloid secretion, particularly beta-amyloid-42, is specific for AD pathology. By in vitro functional studies, {226:Walsh et al. (2001)} found that the A692G substitution, which they referred to as the 'Flemish variant,' increased the solubility of processed beta-amyloid peptides and increased the stability of peptide oligomers. They concluded that conformational changes in the peptide induced by this mutation would facilitate peptide adherence to the vascular endothelium, creating nidi for amyloid growth. Increased peptide solubility and assembly stability would favor formation of larger amyloid deposits and inhibit their elimination. omim.nt GENO:0000002 ClinVar:RCV000019717 biolink:NamedThing omim.nt ClinVar:RCV000019718 biolink:NamedThing omim.nt ClinVar:RCV000020306 biolink:NamedThing omim.nt ClinVar:RCV000084561 biolink:NamedThing omim.nt dbSNP:rs63750671 biolink:NamedThing omim.nt owl:NamedIndividual http://omim.org/entry/104760#0005 biolink:NamedThing omim.nt http://omim.org/entry/104760.0007 biolink:NamedThing APP, 2124C-T In 2 out of 12 AD patients, in 1 out of 60 non-AD patients, and in 1 out of 30 healthy persons, {6:Balbin et al. (1992)} identified a 2124C-T transition in exon 17 of the APP gene, resulting in a silent substitution at the protein level. The authors suggested that the variant could be used as a marker for linkage studies involving the APP gene. omim.nt GENO:0000002 ClinVar:RCV000019719 biolink:NamedThing omim.nt ClinVar:RCV000710591 biolink:NamedThing omim.nt ClinVar:RCV001082457 biolink:NamedThing omim.nt dbSNP:rs148888161 biolink:NamedThing omim.nt owl:NamedIndividual http://omim.org/entry/104760#0007 biolink:NamedThing omim.nt http://omim.org/entry/104760.0008 biolink:NamedThing APP, LYS670ASN AND MET671LEU In affected members of 2 large Swedish families with early-onset familial Alzheimer disease ({104300}), {141:Mullan et al. (1992)} identified a double mutation in exon 16 of the APP gene: a G-to-T transversion, resulting in lys670-to-asn (K670N) substitution, and an A-to-C transversion, resulting in a met671-to-leu (M671L) substitution. {141:Mullan et al. (1992)} suggested that this mutation, which occurs at the amino terminal of beta-amyloid, may be pathogenic because it occurs at or close to the endosomal/lysosomal cleavage site of the molecule. The mean age at onset was 55 years. The 2 families were found to be linked by genealogy. {29:Citron et al. (1992)} reported that cultured cells that express an APP cDNA bearing this double mutation produced 6 to 8 times more amyloid beta-protein than cells expressing the normal APP gene. They showed that the met596-to-leu mutation was principally responsible for the increase. (MET596LEU in the APP695 transcript is the equivalent of MET671LEU in the APP770 transcript, which was the basis of the numbering system used by {141:Mullan et al. (1992)}.) These findings established a direct link between genotype and phenotype. {57:Felsenstein et al. (1994)} found that a neuroglioma cell line expressing the Swedish FAD double mutation showed a consistent 5- to 7-fold increase in the level of the 11-kD potentially amyloidogenic C-terminal fragment. The increase appeared to result from altered cleavage specificity in the secretory pathway from the nonamyloidogenic alpha-secretase site at lys16 to an alternative site at or near the N terminus of the beta protein. {30:Citron et al. (1994)} found that fibroblasts isolated from the Swedish family with the double APP mutation, continuously secreted a homogeneous population of beta-amyloid molecules starting at asp-1 (D672 of beta-APP). There was a consistent and significant elevation of approximately 3-fold of beta-amyloid release from all biopsied skin fibroblasts bearing the FAD mutation. The elevated beta-amyloid levels were found in cells from both patients with clinical Alzheimer disease and presymptomatic subjects, indicating that it is not a secondary event and may play a causal role in the development of the disease. {75:Haass et al. (1995)} showed that the increased production of amyloid beta peptide associated with the 'Swedish mutation' resulted from a cellular mechanism which differs substantially from that responsible for the production of amyloid beta peptide from the wildtype gene. In the latter case, A-beta generation requires reinternalization and recycling of the precursor protein. In the Swedish mutation, the N-terminal beta-secretase cleavage of A-beta occurred in Golgi-derived vesicles, most likely within secretory vesicles. Therefore, this cleavage occurred in the same compartment as the alpha-secretase cleavage, which normally prevents A-beta production, explaining the increased A-beta generation by a competition between alpha- and beta-secretase. {203:Sturchler-Pierrat et al. (1997)} observed pathologic features reminiscent of AD in 2 lines of transgenic mice expressing human APP mutations. A 2-fold overexpression of human APP with the Swedish double mutation at positions 670 to 671 combined with the V717I mutation ({104760.0002}) caused amyloid beta deposition in neocortex and hippocampus of 18-month-old transgenic mice. The deposits were mostly of the diffuse type; however, some congophilic plaques could be detected. In mice with 7-fold overexpression of human APP harboring the Swedish mutation alone, typical plaques appeared at 6 months, which increased with age and were Congo Red-positive at first detection. These congophilic plaques were accompanied by neuritic changes and dystrophic cholinergic fibers. Furthermore, inflammatory processes indicated by a massive glial reaction were apparent. Most notably, the plaques were immunoreactive for hyperphosphorylated tau (MAPT; {157140}), reminiscent of early tau pathology. These findings supported a central role of beta-amyloid in the pathogenesis of AD. {16:Calhoun et al. (1998)} studied the pattern of neuron loss in transgenic mice expressing mutant human APP with the 'Swedish mutation.' These mice develop APP-immunoreactive plaques, primarily in neocortex and hippocampus, progressively with age ({203:Sturchler-Pierrat et al., 1997}). {16:Calhoun et al. (1998)} showed that formation of amyloid plaques led to region-specific loss of neurons in the transgenic mouse. Neuron loss was observed primarily in the vicinity of plaques, but intraneuronal amyloidogenic APP processing could not be excluded as an additional cause. The extent of the observed loss was less than that reported in end-stage AD, possibly because overexpression of APP in the transgenic mouse had a neuroprotective effect. {81:Hsiao et al. (1996)} found that transgenic mice overexpressing the Swedish double mutation had normal learning and memory in spatial reference and alternation tasks at 3 months of age, but showed impairment by 9 to 10 months of age. Brains of the older mice showed a 5-fold increase in the concentration of beta-amyloid derivatives and classic senile plaques with dense amyloid cores. omim.nt GENO:0000002 ClinVar:RCV000019720 biolink:NamedThing omim.nt ClinVar:RCV000034924 biolink:NamedThing omim.nt ClinVar:RCV000084589 biolink:NamedThing omim.nt http://omim.org/entry/104760#0008 biolink:NamedThing omim.nt http://omim.org/entry/104760.0009 biolink:NamedThing APP, ALA713THR In 1 of 130 early-onset AD ({104300}) patients from hospitals throughout France, {19:Carter et al. (1992)} identified 2 mutations in the APP gene: a G-to-A transition, resulting in an ala713-to-thr (A713T) substitution, and a G-to-A transition, resulting in a silent change at codon 715. The 713 mutation changes residue 42 of the beta-amyloid protein, considered to be the penultimate or terminal amino acid of this molecule, and thus could potentially alter both endosomal/lysosomal cleavage and the C-terminal sequence of the resulting beta-peptide. The double mutation was present also in 4 healthy sibs and a paternal aunt who was also healthy at age 88. This experience may represent reduced penetrance; additional environmental factors may be necessary for expression of the disorder or an independent genetic factor absent in the affected sib may suppress amyloid formation in the unaffected members of the kindred. {183:Rossi et al. (2004)} reported a family in which at least 6 members spanning 3 generations had Alzheimer disease and strokes associated with a heterozygous A713T mutation. Neuropathologic examination showed neurofibrillary tangles and A-beta-40 and 42-immunoreactive deposits in the neuropil. The vessel walls showed only A-beta-40 deposits, consistent with amyloid angiopathy. There were also multiple white matter infarcts along the long penetrating arteries. {183:Rossi et al. (2004)} noted that the A713T mutation lies within the beta-amyloid sequence and adjacent to the gamma-secretase cleavage site. omim.nt GENO:0000002 ClinVar:RCV000019721 biolink:NamedThing omim.nt ClinVar:RCV000084566 biolink:NamedThing omim.nt ClinVar:RCV000547582 biolink:NamedThing omim.nt ClinVar:RCV000826088 biolink:NamedThing omim.nt dbSNP:rs63750066 biolink:NamedThing omim.nt owl:NamedIndividual http://omim.org/entry/104760#0009 biolink:NamedThing omim.nt http://omim.org/entry/104760.0010 biolink:NamedThing APP, GLU665ASP {166:Peacock et al. (1994)} used reverse transcription-polymerase chain reaction, denaturing gradient gel electrophoresis, and direct DNA sequencing to analyze APP exons 16 and 17 from patients with histologically confirmed Alzheimer disease ({104300}). One patient, who died at age 92, was found to have a 2119C-G transversion, resulting in a glu665-to-asp (E665D) substitution. A sister had died with dementia between 80 and 85 years of age. The same mutation was present in a nondemented relative older than 65 years. Thus, although the mutation was not found in 40 control subjects and 127 dementia patients, its relationship to Alzheimer disease was uncertain. Hitherto, no evidence had been forthcoming that APP mutations are involved in late-onset or sporadic Alzheimer disease. omim.nt GENO:0000002 ClinVar:RCV000019722 biolink:NamedThing omim.nt ClinVar:RCV000084557 biolink:NamedThing omim.nt dbSNP:rs63750363 biolink:NamedThing omim.nt owl:NamedIndividual http://omim.org/entry/104760#0010 biolink:NamedThing omim.nt http://omim.org/entry/104760.0011 biolink:NamedThing APP, ILE716VAL In affected members of a family with early-onset AD ({104300}), {50:Eckman et al. (1997)} identified a mutation in the APP gene, resulting in an ile716-to-val (I716V) substitution. The mean age at onset was approximately 53 years. Cells transfected with cDNAs bearing the I716V mutation produced more of A-beta-42(43) protein than those transfected with wildtype APP. omim.nt GENO:0000002 ClinVar:RCV000019723 biolink:NamedThing omim.nt ClinVar:RCV000084573 biolink:NamedThing omim.nt dbSNP:rs63750399 biolink:NamedThing omim.nt owl:NamedIndividual http://omim.org/entry/104760#0011 biolink:NamedThing omim.nt http://omim.org/entry/104760.0012 biolink:NamedThing APP, VAL715MET In affected members of a family with early-onset AD ({104300}), {3:Ancolio et al. (1999)} identified a mutation in the APP gene, resulting in a val715-to-met (V715M) substitution. Overexpression of V715M in human HEK293 cells and murine neurons reduced total A-beta production and increased the recovery of the physiologically secreted product, APP-alpha. The V715M mutation significantly reduced A-beta-40 secretion without affecting A-beta-42 production in HEK293 cells. However, a marked increase in N-terminally truncated A-beta ending at position 42 was observed, whereas its counterpart ending at position 40 was not affected. These results suggested that, in some cases, familial AD may be associated with a reduction in the overall production of A-beta, but may be caused by increased production of truncated forms of A-beta ending at position 42. This family with the V715M mutation was also reported by {17:Campion et al. (1999)}, the same family having been ascertained through a population-based survey of early-onset Alzheimer disease. omim.nt GENO:0000002 ClinVar:RCV000019724 biolink:NamedThing omim.nt ClinVar:RCV000084570 biolink:NamedThing omim.nt dbSNP:rs63750734 biolink:NamedThing omim.nt owl:NamedIndividual http://omim.org/entry/104760#0012 biolink:NamedThing omim.nt http://omim.org/entry/104760.0013 biolink:NamedThing APP, GLU693GLY In a patient with early-onset familial Alzheimer disease ({104300}), {97:Kamino et al. (1992)} identified an A-to-G transition in the APP gene, resulting in a glu693-to-gly (E693G) substitution. The mutation is referred to as E22G in the processed beta-amyloid protein. The proband was from a family with early-onset familial Alzheimer disease spanning 3 generations. He had onset of disease at age 56 years, and postmortem examination found neuritic amyloid plaques and tau-positive neurofibrillary tangles. Moderate to severe amyloid was deposited in the cortical and leptomeningeal arteries. The mutation was not identified in 126 other FAD families. Other mutations of codon 693 cause hereditary cerebral hemorrhage and amyloidosis (see {609095}) of the Dutch type (E693Q; {104760.0001}) and Italian type (E693K; {104760.0014}). {136:Miravalle et al. (2000)} referred to the E693G mutation as the 'Arctic mutation.' {154:Nilsberth et al. (2001)} identified the E693G mutation in affected members of a large Swedish family with AD. Mutation carriers had decreased levels of plasma beta-amyloid-40 and -42. Cells transfected with the mutation showed increased rates and amounts of protofibril formation. {154:Nilsberth et al. (2001)} postulated that the pathogenic mechanism for AD in patients with the E693G mutation may involve rapid beta-amyloid protofibril formation leading to accelerated buildup of insoluble beta-amyloid intra- and/or extracellularly. In vitro, the Arctic mutant form of A-beta forms protofibrils and fibrils at higher rates and in larger quantities than wildtype A-beta. In transgenic mice that expressed the Arctic mutant in neurons, {23:Cheng et al. (2004)} found that amyloid plaques formed faster and were more extensive compared to control mice. {23:Cheng et al. (2004)} concluded that the Arctic mutation is highly amyloidogenic in vivo. {9:Basun et al. (2008)} restudied the clinical features of the American and Swedish families with the E693G mutation reported by {97:Kamino et al. (1992)} and {154:Nilsberth et al. (2001)}, respectively. They noted that the American family was descended from Swedish immigrants. Affected individuals typically presented between age 52 and 65 years, with slow deterioration of cognitive function typical of AD, as well as some additional symptoms such as disorientation, dysphasia, and dyspraxia. None of the patients had a history of cerebrovascular events. Neuropathologic examination of 2 patients showed severe congophilic angiopathy of multiple vessels, amyloid plaques in a ring form without a core, neurofibrillary tangles, and neuronal loss. The amyloid plaques were strongly immunopositive for beta-amyloid-40 and -42, showed neuritic features, and were negative for Congo red. omim.nt GENO:0000002 ClinVar:RCV000019725 biolink:NamedThing omim.nt ClinVar:RCV000019726 biolink:NamedThing omim.nt ClinVar:RCV000020307 biolink:NamedThing omim.nt ClinVar:RCV000084563 biolink:NamedThing omim.nt dbSNP:rs63751039 biolink:NamedThing omim.nt owl:NamedIndividual http://omim.org/entry/104760#0013 biolink:NamedThing omim.nt http://omim.org/entry/104760.0014 biolink:NamedThing APP, GLU693LYS {136:Miravalle et al. (2000)} reported that a glu693-to-lys (E693K) mutation had been identified in affected members of 3 Italian families with cerebroarterial amyloidosis ({605714}). The mutation is referred to as E22K in the processed beta-amyloid peptide. The patients presented between 60 and 70 years of age, which was significantly later than those with the Dutch type of cerebral amyloidosis and hemorrhage who have a mutation in the same codon (E693Q; {104760.0001}). Neuropathologic examination of 1 Italian patient who had onset at age 45 years revealed extensive beta-amyloid deposits in leptomeningeal and cortical vessels and, to a lesser extent, amyloid plaques in the neuropil of the cerebral cortex. Vascular deposits were primarily labeled by anti-A40 antibody, whereas parenchymal deposits were predominantly revealed by anti-A42 antibody, as in AD. However, neurofibrillary changes were very mild and restricted to the archicortex. {136:Miravalle et al. (2000)} demonstrated in vitro that the E693Q mutation resulted in a high content of beta-sheet amyloid conformation and fast aggregation/fibrillization properties. The E693Q mutant induced cerebral endothelial cell apoptosis, whereas the E693K mutant did not. The data suggested that different amino acids at codon 693 confer distinct structural properties to the peptides that appeared to influence the age at onset and aggressiveness of the disease rather than the phenotype. {13:Bugiani et al. (2010)} reported 4 unrelated Italian families with autosomal dominant hereditary cerebral hemorrhage with amyloidosis caused by the heterozygous E693K mutation. Affected individuals presented with recurrent headache and multiple hemorrhagic strokes between age 44 and 63, followed by epilepsy and cognitive decline in most of them. Several affected individuals became comatose or bedridden, and some died as a result of cerebral hemorrhage. Neuroimaging demonstrated small to large hematomas, subarachnoid bleeding, scars with hemosiderin deposits, multi-infarct encephalopathy, and leukoaraiosis. Multiple brain regions were involved, including both gray and white matter. Postmortem examination of 1 patient showed many small vessels with thickened and/or split walls due to a hyaline congophilic material that was immunoreactive for beta-amyloid-40. Most of the abnormal vessels were in the leptomeninges, in the cerebral and cerebellar cortex, and in the white matter close to the cortex. Beta-amyloid-40 was also detectable in cortical capillaries, and beta-amyloid-42 was found in neuropil of the gray structures. Neurofibrillary tangles and neuritic plaques were not present. The progression of the clinical phenotype correlated with that pathologic findings. omim.nt GENO:0000002 ClinVar:RCV000019727 biolink:NamedThing omim.nt ClinVar:RCV000084562 biolink:NamedThing omim.nt http://omim.org/entry/104760#0014 biolink:NamedThing omim.nt http://omim.org/entry/104760.0015 biolink:NamedThing APP, THR714ILE {111:Kumar-Singh et al. (2000)} described an aggressive form of Alzheimer disease ({104300}) caused by a 2208C-T transition in exon 17 of the APP gene, resulting in a thr714-to-ile (T714I) substitution. The mutation directly involved gamma-secretase cleavages of APP, resulting in alteration of the A-beta-42/A-beta-40 ratio 11-fold in vitro. The findings coincided with brain deposition of abundant, predominantly nonfibrillar preamyloid plaques composed primarily of N-truncated A-beta-42 in the absence of A-beta-40. The authors hypothesized that diffuse nonfibrillar plaques of N-truncated A-beta-42 have an essential role in AD pathology. {51:Edwards-Lee et al. (2005)} reported an African American family in which multiple members spanning 3 generations had early-onset AD. Two sibs who were tested were heterozygous for the T714I mutation ({104760.0015}). The distinctive clinical features in this family were a rapidly progressive dementia starting in the fourth decade, seizures, myoclonus, parkinsonism, and spasticity. Variable features included aggressiveness, visual disturbances, and pathologic laughter. omim.nt GENO:0000002 ClinVar:RCV000019728 biolink:NamedThing omim.nt ClinVar:RCV000084569 biolink:NamedThing omim.nt dbSNP:rs63750973 biolink:NamedThing omim.nt owl:NamedIndividual http://omim.org/entry/104760#0015 biolink:NamedThing omim.nt http://omim.org/entry/104760.0016 biolink:NamedThing APP, ASP694ASN In 2 brothers from Iowa with autosomal dominant cerebroarterial amyloidosis ({605714}), {68:Grabowski et al. (2001)} identified a mutation in the APP gene, resulting in an asp694-to-asn (D694N) substitution. This corresponds to residue N23D of the beta-amyloid peptide. Neither brother had symptomatic hemorrhagic stroke. Neuropathologic examination of the proband revealed severe cerebral amyloid angiopathy, widespread neurofibrillary tangles, and unusually extensive distribution of beta-amyloid-40 in plaques. {69:Greenberg et al. (2003)} identified the D694N mutation in 2 affected members of a Spanish family with autosomal dominant dementia, occipital calcifications, leukoencephalopathy, and hemorrhagic strokes (see {605714}). omim.nt GENO:0000002 ClinVar:RCV000019729 biolink:NamedThing omim.nt ClinVar:RCV000084564 biolink:NamedThing omim.nt ClinVar:RCV000687111 biolink:NamedThing omim.nt dbSNP:rs63749810 biolink:NamedThing omim.nt owl:NamedIndividual http://omim.org/entry/104760#0016 biolink:NamedThing omim.nt http://omim.org/entry/104760.0017 biolink:NamedThing APP, THR714ALA {161:Pasalar et al. (2002)} reported an Iranian family with 9 individuals in 3 generations affected by Alzheimer disease ({104300}) with an average age of onset of 55 years. Two patients who were genotyped had a 2207A-G mutation in exon 17 of the APP gene, resulting in a thr714-to-ala (T714A) substitution. {161:Pasalar et al. (2002)} noted that this mutation is one of several reported in the cluster between codons 714 and 717 (1 helical turn) just outside the C terminus of the beta-amyloid sequence, and is likely to disrupt APP processing such that more beta-amyloid-42 would be produced. omim.nt GENO:0000002 ClinVar:RCV000019730 biolink:NamedThing omim.nt ClinVar:RCV000084568 biolink:NamedThing omim.nt dbSNP:rs63750643 biolink:NamedThing omim.nt owl:NamedIndividual http://omim.org/entry/104760#0017 biolink:NamedThing omim.nt http://omim.org/entry/104760.0018 biolink:NamedThing|biolink:SequenceVariant omim.nt True owl:NamedIndividual http://omim.org/entry/104760.0019 biolink:NamedThing APP, LEU705VAL In 4 affected members of an Italian family with autosomal dominant cerebral amyloid angiopathy ({605714}), {156:Obici et al. (2005)} identified a G-to-C transversion in the APP gene, resulting in a leu705-to-val (L705V) substitution, corresponding to residue 34 of the beta-amyloid protein. The mutation was not identified in 100 controls. Clinically, the patients had multiple intracerebral hemorrhages, but only 1 affected family member had cognitive impairment. Neuropathologic analysis of 2 patients showed severe selective cerebral arterial amyloidosis in leptomeningeal and cortical vessel walls without parenchymal amyloid plaques or neurofibrillary tangles. {178:Revesz et al. (2009)} referred to the L705V change as the Piedmont variant. omim.nt GENO:0000002 ClinVar:RCV000019731 biolink:NamedThing omim.nt ClinVar:RCV000084565 biolink:NamedThing omim.nt dbSNP:rs63750921 biolink:NamedThing omim.nt owl:NamedIndividual http://omim.org/entry/104760#0019 biolink:NamedThing omim.nt http://omim.org/entry/104760.0020 biolink:NamedThing APP, DUP In a cohort of 65 families with autosomal dominant early-onset Alzheimer disease (ADEOAD), 5 had severe associated cerebral amyloid angiopathy (see {104300} and {605714}). {184:Rovelet-Lecrux et al. (2006)} found duplication of the APP locus in these 5 index cases. In the corresponding families, the duplication was found only in affected members and not in healthy subjects over 60 years of age. {73:Guyant-Marechal et al. (2008)} reported a family in which 3 individuals with a 0.55-Mb duplication of the APP locus showed highly variable phenotypes. The proband developed bradykinesia, memory problems, and apraxia at age 44. She later had paranoid delusions with visual hallucinations associated with bilateral tremor and rigidity, and died at age 55. Neuropathologic examination showed cerebral amyloid angiopathy, amyloid plaques, neurofibrillary tangles, and numerous Lewy bodies. A second mutation carrier had had partial visual seizures at age 52 associated with white matter changes and multiple microbleeds on MRI. Cognitive assessment was normal 1 year later. The third mutation carrier developed memory complaints at age 52 and showed mild cognitive decline 5 years later. MRI showed a left frontal intracranial hemorrhage. omim.nt GENO:0000002 ClinVar:RCV000019732 biolink:NamedThing omim.nt http://omim.org/entry/104760#0020 biolink:NamedThing omim.nt http://omim.org/entry/104760.0021 biolink:NamedThing APP, VAL717LEU In 2 sibs with early-onset AD ({104300}), {148:Murrell et al. (2000)} identified a heterozygous G-to-C transversion in exon 17 of the APP gene, resulting in a val717-to-leu (V717L) substitution. Age at onset was in the late thirties. Other mutations at residue 717 include V717I ({104760.0002}), V717F ({104760.0003}), and V717G ({104760.0004}). {65:Godbolt et al. (2006)} identified the V717L substitution in affected members of a second family with AD. Two patients reported hallucinations. Age at onset ranged from 48 to 57, later than that in the family reported by {148:Murrell et al. (2000)}. omim.nt GENO:0000002 ClinVar:RCV000019733 biolink:NamedThing omim.nt ClinVar:RCV000518713 biolink:NamedThing omim.nt http://omim.org/entry/104760#0021 biolink:NamedThing omim.nt http://omim.org/entry/104760.0022 biolink:NamedThing APP, ALA673VAL In a patient with early-onset progressive Alzheimer disease ({104300}), {41:Di Fede et al. (2009)} identified a homozygous C-to-T transition in exon 16 of the APP gene resulting in an ala673-to-val substitution (A673V), corresponding to position 2 of amyloid beta. The mutation was also found in homozygosity in the proband's younger sister, who had multiple domain mild cognitive impairment (MCI), believed to a high risk condition for the development of clinically probable Alzheimer disease ({167:Petersen et al., 2001}). The proband developed progressive dementia at age 36 and was noncommunicative and could not walk by age 44. Serial MRI showed progressive cortico-subcortical atrophy. Cerebrospinal fluid analysis showed decreased A-beta-1-42 and increased total and 181T-phosphorylated tau compared to controls and similar to subjects with Alzheimer disease. In the plasma of both the patient and his homozygous sister, amyloid-beta-1-40 and amyloid-beta-1-42 were higher than in nondemented controls, whereas the A673V heterozygous carriers from the family that were tested had intermediate amounts. None of 6 heterozygous individuals in the family had any evidence of dementia when tested at ages ranging from 21 to 88. The A673V mutation affected APP processing, resulting in enhanced beta-amyloid production and formation of amyloid fibrils in vitro. Coincubation of mutated and wildtype peptides conferred instability on amyloid beta aggregates and inhibited amyloidogenesis and neurotoxicity. {41:Di Fede et al. (2009)} concluded that the interaction between mutant and wildtype amyloid beta, favored by the A-to-V substitution at position 2, interferes with nucleation or nucleation-dependent polymerization or both, hindering amyloidogenesis and neurotoxicity and thus protecting the heterozygous carriers. omim.nt GENO:0000002 ClinVar:RCV000019734 biolink:NamedThing omim.nt dbSNP:rs193922916 biolink:NamedThing omim.nt owl:NamedIndividual http://omim.org/entry/104760#0022 biolink:NamedThing omim.nt http://omim.org/entry/104760.0023 biolink:NamedThing APP, ALA673THR ({dbSNP rs63750847}) Using whole-genome sequence data from 1,795 Icelanders, {93:Jonsson et al. (2012)} identified a coding SNP in the APP gene, {dbSNP rs63750847} (A673T). This SNP was significantly more common in a control group of individuals aged 85 years or older without a diagnosis of Alzheimer disease ({104300}) than in a group of Alzheimer disease patients (0.62% vs 0.13%, respectively; OR = 5.29; p = 4.78 x 10(-7)). The SNP was enriched among a group of controls who were cognitively intact at age 85 years (0.79%; OR = 7.52; p = 6.92 x 10(-6)). Among 3,673 noncarriers and 41 carriers of the A673T variant, all without a diagnosis of Alzheimer disease, {93:Jonsson et al. (2012)} found on average a 1.03-unit difference across the 80 to 100 age range on a test of cognitive performance (average 6.49 and 6.39 determinations per individual, respectively), with the carriers having a score indicative of better conserved cognition. By Western blot analysis of cell supernatants, {93:Jonsson et al. (2012)} found that the A673T variant results in reduced production of extracellular APP fragments generated by processing at the beta site with a slight increase in fragments produced using the alpha site. This observation was confirmed by immunoassay. {93:Jonsson et al. (2012)} also found that the production of amyloidogenic peptides A-beta-40 and A-beta-42 was approximately 40% less by the A673T variant than by wildtype APP. In contrast to A673T, the A673V substitution ({104760.0022}) resulted in markedly increased APP processing at the beta site, decreased processing at the alpha site, and greatly enhanced A-beta-40 and A-beta-42 production. These results were consistent with a protective effect of the A673T variant and illustrated clearly that position 673 of APP is capable of regulating proteolytic processing by BACE1 ({604252}). omim.nt GENO:0000002 ClinVar:RCV000030774 biolink:NamedThing omim.nt ClinVar:RCV000084558 biolink:NamedThing omim.nt dbSNP:rs63750847 biolink:NamedThing omim.nt owl:NamedIndividual http://omim.org/entry/104760#0023 biolink:NamedThing omim.nt MONARCH:.well-known/genid/b48f6e55df6787bf233a biolink:NamedThing GRCh38chr21-25880549-26171127-Region omim.nt MONARCH:.well-known/genid/bc86a26ea0face1ba88b faldo:Region MONARCH:.well-known/genid/OMIM104760ref10 biolink:NamedThing In situ hybridization of the beta amyloid protein (APP) cDNA to the vicinity of the interface of 21q21 and q22 in normal and Alzheimer's disease individuals. (Abstract) omim.nt IAO:0000310 MONARCH:.well-known/genid/OMIM104760ref194 biolink:NamedThing Alzheimer's and prion disease: do they share a pathogenic mechanism? omim.nt IAO:0000310 MONARCH:.well-known/genid/OMIM104760ref214 biolink:NamedThing Genetic linkage analysis of the Alzheimer's associated amyloid beta protein gene with familial Alzheimer's disease and chromosome 21. (Abstract) omim.nt IAO:0000310 MONARCH:.well-known/genid/OMIM104760ref24 biolink:NamedThing Synteny in man and mouse of DNA markers from the chromosomal region linked to familial Alzheimer's disease and Down syndrome. (Abstract) omim.nt IAO:0000310 MONARCH:.well-known/genid/OMIM104760ref241 biolink:NamedThing Sublocalization of the gene for the precursor of Alzheimer's disease amyloid A4 protein on chromosome 21. (Abstract) omim.nt IAO:0000310 PMID:10097173 biolink:NamedThing omim.nt IAO:0000013 PMID:10319819 biolink:NamedThing omim.nt IAO:0000013 PMID:10408445 biolink:NamedThing omim.nt IAO:0000013 PMID:10531052 biolink:NamedThing omim.nt IAO:0000013 PMID:10591213 biolink:NamedThing omim.nt IAO:0000013 PMID:10611368 biolink:NamedThing omim.nt IAO:0000013 PMID:10769385 biolink:NamedThing omim.nt IAO:0000013 PMID:10821838 biolink:NamedThing omim.nt IAO:0000013 PMID:10867787 biolink:NamedThing omim.nt IAO:0000013 PMID:11063718 biolink:NamedThing omim.nt IAO:0000013 PMID:11067868 biolink:NamedThing omim.nt IAO:0000013 PMID:11140685 biolink:NamedThing omim.nt IAO:0000013 PMID:11144356 biolink:NamedThing omim.nt IAO:0000013 PMID:11309494 biolink:NamedThing omim.nt IAO:0000013 PMID:11311152 biolink:NamedThing omim.nt IAO:0000013 PMID:11329064 biolink:NamedThing omim.nt IAO:0000013 PMID:11337275 biolink:NamedThing omim.nt IAO:0000013 PMID:11375493 biolink:NamedThing omim.nt IAO:0000013 PMID:11406613 biolink:NamedThing omim.nt IAO:0000013 PMID:11409420 biolink:NamedThing omim.nt IAO:0000013 PMID:11430801 biolink:NamedThing omim.nt IAO:0000013 PMID:11441186 biolink:NamedThing omim.nt IAO:0000013 PMID:11487570 biolink:NamedThing omim.nt IAO:0000013 PMID:11520987 biolink:NamedThing omim.nt IAO:0000013 PMID:11520988 biolink:NamedThing omim.nt IAO:0000013 PMID:11528419 biolink:NamedThing omim.nt IAO:0000013 PMID:11700559 biolink:NamedThing omim.nt IAO:0000013 PMID:11823458 biolink:NamedThing omim.nt IAO:0000013 PMID:11910111 biolink:NamedThing omim.nt IAO:0000013 PMID:11932737 biolink:NamedThing omim.nt IAO:0000013 PMID:11932745 biolink:NamedThing omim.nt IAO:0000013 PMID:11941374 biolink:NamedThing omim.nt IAO:0000013 PMID:11972038 biolink:NamedThing omim.nt IAO:0000013 PMID:12023290 biolink:NamedThing omim.nt IAO:0000013 PMID:12034808 biolink:NamedThing omim.nt IAO:0000013 PMID:12124613 biolink:NamedThing omim.nt IAO:0000013 PMID:12135352 biolink:NamedThing omim.nt IAO:0000013 PMID:12150997 biolink:NamedThing omim.nt IAO:0000013 PMID:12360327 biolink:NamedThing omim.nt IAO:0000013 PMID:12434053 biolink:NamedThing omim.nt IAO:0000013 PMID:12634421 biolink:NamedThing omim.nt IAO:0000013 PMID:12654973 biolink:NamedThing omim.nt IAO:0000013 PMID:12670422 biolink:NamedThing omim.nt IAO:0000013 PMID:12695513 biolink:NamedThing omim.nt IAO:0000013 PMID:12900421 biolink:NamedThing omim.nt IAO:0000013 PMID:1303239 biolink:NamedThing omim.nt IAO:0000013 PMID:1303244 biolink:NamedThing omim.nt IAO:0000013 PMID:1303275 biolink:NamedThing omim.nt IAO:0000013 PMID:1307241 biolink:NamedThing omim.nt IAO:0000013 PMID:1415269 biolink:NamedThing omim.nt IAO:0000013 PMID:14506131 biolink:NamedThing omim.nt IAO:0000013 PMID:14523244 biolink:NamedThing omim.nt IAO:0000013 PMID:14615541 biolink:NamedThing omim.nt IAO:0000013 PMID:1465129 biolink:NamedThing omim.nt IAO:0000013 PMID:14687544 biolink:NamedThing omim.nt IAO:0000013 PMID:14715132 biolink:NamedThing omim.nt IAO:0000013 PMID:14722157 biolink:NamedThing omim.nt IAO:0000013 PMID:14741101 biolink:NamedThing omim.nt IAO:0000013 PMID:15069204 biolink:NamedThing omim.nt IAO:0000013 PMID:15087549 biolink:NamedThing omim.nt IAO:0000013 PMID:15115763 biolink:NamedThing omim.nt IAO:0000013 PMID:15146243 biolink:NamedThing omim.nt IAO:0000013 PMID:15254013 biolink:NamedThing omim.nt IAO:0000013 PMID:15502844 biolink:NamedThing omim.nt IAO:0000013 PMID:15642747 biolink:NamedThing omim.nt IAO:0000013 PMID:15653506 biolink:NamedThing omim.nt IAO:0000013 PMID:15657137 biolink:NamedThing omim.nt IAO:0000013 PMID:15778722 biolink:NamedThing omim.nt IAO:0000013 PMID:15944124 biolink:NamedThing omim.nt IAO:0000013 PMID:16039562 biolink:NamedThing omim.nt IAO:0000013 PMID:16178030 biolink:NamedThing omim.nt IAO:0000013 PMID:16227967 biolink:NamedThing omim.nt IAO:0000013 PMID:1634237 biolink:NamedThing omim.nt IAO:0000013 PMID:16365303 biolink:NamedThing omim.nt IAO:0000013 PMID:1642228 biolink:NamedThing omim.nt IAO:0000013 PMID:16432153 biolink:NamedThing omim.nt IAO:0000013 PMID:1645961 biolink:NamedThing omim.nt IAO:0000013 PMID:16505331 biolink:NamedThing omim.nt IAO:0000013 PMID:16554819 biolink:NamedThing omim.nt IAO:0000013 PMID:16641106 biolink:NamedThing omim.nt IAO:0000013 PMID:16685645 biolink:NamedThing omim.nt IAO:0000013 PMID:16698938 biolink:NamedThing omim.nt IAO:0000013 PMID:1678057 biolink:NamedThing omim.nt IAO:0000013 PMID:1679288 biolink:NamedThing omim.nt IAO:0000013 PMID:1679289 biolink:NamedThing omim.nt IAO:0000013 PMID:16908860 biolink:NamedThing omim.nt IAO:0000013 PMID:16982417 biolink:NamedThing omim.nt IAO:0000013 PMID:16990547 biolink:NamedThing omim.nt IAO:0000013 PMID:1702541 biolink:NamedThing omim.nt IAO:0000013 PMID:17296549 biolink:NamedThing omim.nt IAO:0000013 PMID:17296550 biolink:NamedThing omim.nt IAO:0000013 PMID:17325276 biolink:NamedThing omim.nt IAO:0000013 PMID:17332749 biolink:NamedThing omim.nt IAO:0000013 PMID:17351623 biolink:NamedThing omim.nt IAO:0000013 PMID:17404210 biolink:NamedThing omim.nt IAO:0000013 PMID:17920016 biolink:NamedThing omim.nt IAO:0000013 PMID:18025470 biolink:NamedThing omim.nt IAO:0000013 PMID:18256671 biolink:NamedThing omim.nt IAO:0000013 PMID:18353773 biolink:NamedThing omim.nt IAO:0000013 PMID:18413473 biolink:NamedThing omim.nt IAO:0000013 PMID:18516051 biolink:NamedThing omim.nt IAO:0000013 PMID:18587408 biolink:NamedThing omim.nt IAO:0000013 PMID:18755980 biolink:NamedThing omim.nt IAO:0000013 PMID:18806802 biolink:NamedThing omim.nt IAO:0000013 PMID:19047566 biolink:NamedThing omim.nt IAO:0000013 PMID:19225519 biolink:NamedThing omim.nt IAO:0000013 PMID:19225789 biolink:NamedThing omim.nt IAO:0000013 PMID:19242475 biolink:NamedThing omim.nt IAO:0000013 PMID:19287391 biolink:NamedThing omim.nt IAO:0000013 PMID:19334058 biolink:NamedThing omim.nt IAO:0000013 PMID:19414486 biolink:NamedThing omim.nt IAO:0000013 PMID:1944558 biolink:NamedThing omim.nt IAO:0000013 PMID:19483198 biolink:NamedThing omim.nt IAO:0000013 PMID:19548013 biolink:NamedThing omim.nt IAO:0000013 PMID:19744962 biolink:NamedThing omim.nt IAO:0000013 PMID:19779148 biolink:NamedThing omim.nt IAO:0000013 PMID:20159774 biolink:NamedThing omim.nt IAO:0000013 PMID:20452985 biolink:NamedThing omim.nt IAO:0000013 PMID:20466736 biolink:NamedThing omim.nt IAO:0000013 PMID:20697050 biolink:NamedThing omim.nt IAO:0000013 PMID:20817278 biolink:NamedThing omim.nt IAO:0000013 PMID:20966215 biolink:NamedThing omim.nt IAO:0000013 PMID:2110105 biolink:NamedThing omim.nt IAO:0000013 PMID:21113149 biolink:NamedThing omim.nt IAO:0000013 PMID:2111583 biolink:NamedThing omim.nt IAO:0000013 PMID:2111584 biolink:NamedThing omim.nt IAO:0000013 PMID:2111585 biolink:NamedThing omim.nt IAO:0000013 PMID:21280074 biolink:NamedThing omim.nt IAO:0000013 PMID:21795536 biolink:NamedThing omim.nt IAO:0000013 PMID:21852239 biolink:NamedThing omim.nt IAO:0000013 PMID:22351782 biolink:NamedThing omim.nt IAO:0000013 PMID:22654059 biolink:NamedThing omim.nt IAO:0000013 PMID:2507928 biolink:NamedThing omim.nt IAO:0000013 PMID:2527801 biolink:NamedThing omim.nt IAO:0000013 PMID:25557959 biolink:NamedThing omim.nt IAO:0000013 PMID:26322584 biolink:NamedThing omim.nt IAO:0000013 PMID:27563067 biolink:NamedThing omim.nt IAO:0000013 PMID:27856911 biolink:NamedThing omim.nt IAO:0000013 PMID:2859120 biolink:NamedThing omim.nt IAO:0000013 PMID:2880184 biolink:NamedThing omim.nt IAO:0000013 PMID:2881207 biolink:NamedThing omim.nt IAO:0000013 PMID:2890206 biolink:NamedThing omim.nt IAO:0000013 PMID:2890207 biolink:NamedThing omim.nt IAO:0000013 PMID:2893289 biolink:NamedThing omim.nt IAO:0000013 PMID:2893290 biolink:NamedThing omim.nt IAO:0000013 PMID:2893291 biolink:NamedThing omim.nt IAO:0000013 PMID:2949367 biolink:NamedThing omim.nt IAO:0000013 PMID:2950593 biolink:NamedThing omim.nt IAO:0000013 PMID:2960019 biolink:NamedThing omim.nt IAO:0000013 PMID:2966761 biolink:NamedThing omim.nt IAO:0000013 PMID:2973063 biolink:NamedThing omim.nt IAO:0000013 PMID:29739836 biolink:NamedThing omim.nt IAO:0000013 PMID:30143535 biolink:NamedThing omim.nt IAO:0000013 PMID:3035574 biolink:NamedThing omim.nt IAO:0000013 PMID:30464338 biolink:NamedThing omim.nt IAO:0000013 PMID:30630900 biolink:NamedThing omim.nt IAO:0000013 PMID:3159021 biolink:NamedThing omim.nt IAO:0000013 PMID:3277160 biolink:NamedThing omim.nt IAO:0000013 PMID:3279948 biolink:NamedThing omim.nt IAO:0000013 PMID:3544219 biolink:NamedThing omim.nt IAO:0000013 PMID:3555492 biolink:NamedThing omim.nt IAO:0000013 PMID:3810169 biolink:NamedThing omim.nt IAO:0000013 PMID:6375662 biolink:NamedThing omim.nt IAO:0000013 PMID:7489411 biolink:NamedThing omim.nt IAO:0000013 PMID:7543026 biolink:NamedThing omim.nt IAO:0000013 PMID:7595555 biolink:NamedThing omim.nt IAO:0000013 PMID:7686976 biolink:NamedThing omim.nt IAO:0000013 PMID:7704018 biolink:NamedThing omim.nt IAO:0000013 PMID:7845465 biolink:NamedThing omim.nt IAO:0000013 PMID:7991571 biolink:NamedThing omim.nt IAO:0000013 PMID:8012386 biolink:NamedThing omim.nt IAO:0000013 PMID:8102836 biolink:NamedThing omim.nt IAO:0000013 PMID:8154870 biolink:NamedThing omim.nt IAO:0000013 PMID:8191290 biolink:NamedThing omim.nt IAO:0000013 PMID:8227367 biolink:NamedThing omim.nt IAO:0000013 PMID:8288617 biolink:NamedThing omim.nt IAO:0000013 PMID:8290965 biolink:NamedThing omim.nt IAO:0000013 PMID:8499923 biolink:NamedThing omim.nt IAO:0000013 PMID:8596911 biolink:NamedThing omim.nt IAO:0000013 PMID:8650548 biolink:NamedThing omim.nt IAO:0000013 PMID:8709781 biolink:NamedThing omim.nt IAO:0000013 PMID:8886002 biolink:NamedThing omim.nt IAO:0000013 PMID:9108116 biolink:NamedThing omim.nt IAO:0000013 PMID:9328472 biolink:NamedThing omim.nt IAO:0000013 PMID:9335500 biolink:NamedThing omim.nt IAO:0000013 PMID:9349534 biolink:NamedThing omim.nt IAO:0000013 PMID:9371838 biolink:NamedThing omim.nt IAO:0000013 PMID:9422699 biolink:NamedThing omim.nt IAO:0000013 PMID:9546791 biolink:NamedThing omim.nt IAO:0000013 PMID:9600988 biolink:NamedThing omim.nt IAO:0000013 PMID:9740113 biolink:NamedThing omim.nt IAO:0000013 PMID:9754958 biolink:NamedThing omim.nt IAO:0000013 PMID:9770440 biolink:NamedThing omim.nt IAO:0000013 PMID:9770546 biolink:NamedThing omim.nt IAO:0000013 PMID:9796810 biolink:NamedThing omim.nt IAO:0000013 PMID:9848098 biolink:NamedThing omim.nt IAO:0000013 OBO:CHR_9606chr21q21 biolink:NamedThing omim.nt owl:Class http://omim.org/entry/605714 biolink:NamedThing|biolink:Disease Cerebral Amyloid Angiopathy, App-Related Cerebral Amyloid Angiopathy, App-Related omim.nt CEREBRAL AMYLOID ANGIOPATHY, APP-RELATED|Amyloidosis, Cerebroarterial, App-Related|Amyloidosis, Hereditary, With Cerebral Hemorrhage, Dutch Variant|Cerebral Amyloid Angiopathy, App-Related, Arctic Variant|Cerebral Amyloid Angiopathy, App-Related, Dutch Variant|Cerebral Amyloid Angiopathy, App-Related, Flemish Variant|Cerebral Amyloid Angiopathy, App-Related, Iowa Variant|Cerebral Amyloid Angiopathy, App-Related, Italian Variant owl:Class UMLS:C1364818 biolink:NamedThing omim.nt owl:Class https://www.ncbi.nlm.nih.gov/gene/351 biolink:NamedThing omim.nt http://omim.org/entry/104770 biolink:NamedThing|biolink:Gene APCS Amyloid P Component, Serum|probably close to CRP omim.nt AMYLOID P COMPONENT, SERUM; APCS|Pentraxin 2, Short|Serum Amyloid P owl:Class MONARCH:.well-known/genid/b4c287577ab9d5d3ae6a biolink:NamedThing GRCh38chr1-159587825-159588864-Region omim.nt MONARCH:.well-known/genid/be9b75999bd998adb61c faldo:Region MONARCH:.well-known/genid/OMIM104770ref12 biolink:NamedThing A genetic marker for systemic amyloidosis in juvenile arthritis. omim.nt IAO:0000310 MONARCH:.well-known/genid/OMIM104770ref4 biolink:NamedThing Human serum amyloid P component (SAP) is located on the proximal long arm of chromosome 1. (Abstract) omim.nt IAO:0000310 PMID:12015594 biolink:NamedThing omim.nt IAO:0000013 PMID:19011614 biolink:NamedThing omim.nt IAO:0000013 PMID:20962779 biolink:NamedThing omim.nt IAO:0000013 PMID:2987268 biolink:NamedThing omim.nt IAO:0000013 PMID:3169883 biolink:NamedThing omim.nt IAO:0000013 PMID:3691191 biolink:NamedThing omim.nt IAO:0000013 PMID:3759147 biolink:NamedThing omim.nt IAO:0000013 PMID:4054960 biolink:NamedThing omim.nt IAO:0000013 PMID:4055725 biolink:NamedThing omim.nt IAO:0000013 PMID:9256275 biolink:NamedThing omim.nt IAO:0000013 OBO:CHR_9606chr1q21 biolink:NamedThing omim.nt owl:Class UMLS:C1456795 biolink:NamedThing omim.nt owl:Class https://www.ncbi.nlm.nih.gov/gene/325 biolink:NamedThing omim.nt http://omim.org/entry/104775 biolink:NamedThing|biolink:Gene APLP1 Amyloid Beta A4 Precursor-Like Protein 1 omim.nt AMYLOID BETA A4 PRECURSOR-LIKE PROTEIN 1; APLP1|Amyloid Precursor-Like Protein|Amyloid Precursor-Like Protein 1 owl:Class MONARCH:.well-known/genid/b9f1febd605657b09073 biolink:NamedThing GRCh38chr19-35868569-35879794-Region omim.nt MONARCH:.well-known/genid/b1c68422378d9fc2a59a faldo:Region PMID:1279693 biolink:NamedThing omim.nt IAO:0000013 PMID:16344553 biolink:NamedThing omim.nt IAO:0000013 PMID:8432545 biolink:NamedThing omim.nt IAO:0000013 PMID:9521588 biolink:NamedThing omim.nt IAO:0000013 OBO:CHR_9606chr19q13.2 biolink:NamedThing omim.nt owl:Class UMLS:C1412466 biolink:NamedThing omim.nt owl:Class https://www.ncbi.nlm.nih.gov/gene/333 biolink:NamedThing omim.nt http://omim.org/entry/104776 biolink:NamedThing|biolink:Gene APLP2 Amyloid Beta A4 Precursor-Like Protein 2 omim.nt AMYLOID BETA A4 PRECURSOR-LIKE PROTEIN 2; APLP2|Amyloid Precursor-Like Protein 2|Cdei-Binding Protein|Sperm Membrane Protein owl:Class MONARCH:.well-known/genid/b2dd0d1eb8ccdd792b09 biolink:NamedThing GRCh38chr11-130069893-130144804-Region omim.nt MONARCH:.well-known/genid/b8f0c3d21b0be71cd710 faldo:Region PMID:10702673 biolink:NamedThing omim.nt IAO:0000013 PMID:1690887 biolink:NamedThing omim.nt IAO:0000013 PMID:7592716 biolink:NamedThing omim.nt IAO:0000013 PMID:8020984 biolink:NamedThing omim.nt IAO:0000013 PMID:8661100 biolink:NamedThing omim.nt IAO:0000013 OBO:CHR_9606chr11q24 biolink:NamedThing omim.nt owl:Class UMLS:C1412467 biolink:NamedThing omim.nt owl:Class https://www.ncbi.nlm.nih.gov/gene/334 biolink:NamedThing omim.nt http://omim.org/entry/105120 biolink:NamedThing|biolink:Disease Amyloidosis, Finnish Type Amyloidosis, Finnish Type omim.nt AMYLOIDOSIS, FINNISH TYPE|Amyloid Cranial Neuropathy With Lattice Corneal Dystrophy|Amyloidosis 5|Amyloidosis Due to Mutant Gelsolin|Amyloidosis, Meretoja Type|Cerebral Amyloid Angiopathy, Gsn-Related|Corneal Dystrophy, Lattice Type 2|Lattice Corneal Dystrophy, Type 2 owl:Class MONARCH:.well-known/genid/OMIM105120ref16 biolink:NamedThing Inherited Systemic Amyloidosis with Lattice Corneal Dystrophy. omim.nt IAO:0000310 MONARCH:.well-known/genid/OMIM105120ref9 biolink:NamedThing Familial occurrence of a bulbar paralytic form of amyotrophic lateral sclerosis with reticular corneal dystrophy and cutis hyperelastica in 3 sisters. omim.nt IAO:0000310 PMID:11754099 biolink:NamedThing omim.nt IAO:0000013 PMID:1311149 biolink:NamedThing omim.nt IAO:0000013 PMID:1315718 biolink:NamedThing omim.nt IAO:0000013 PMID:1322359 biolink:NamedThing omim.nt IAO:0000013 PMID:1333716 biolink:NamedThing omim.nt IAO:0000013 PMID:1923356 biolink:NamedThing omim.nt IAO:0000013 PMID:2153578 biolink:NamedThing omim.nt IAO:0000013 PMID:2162627 biolink:NamedThing omim.nt IAO:0000013 PMID:2176164 biolink:NamedThing omim.nt IAO:0000013 PMID:228009 biolink:NamedThing omim.nt IAO:0000013 PMID:305513 biolink:NamedThing omim.nt IAO:0000013 PMID:3513049 biolink:NamedThing omim.nt IAO:0000013 PMID:4109360 biolink:NamedThing omim.nt IAO:0000013 PMID:4163628 biolink:NamedThing omim.nt IAO:0000013 PMID:4543600 biolink:NamedThing omim.nt IAO:0000013 PMID:6610849 biolink:NamedThing omim.nt IAO:0000013 PMID:6975851 biolink:NamedThing omim.nt IAO:0000013 PMID:7836945 biolink:NamedThing omim.nt IAO:0000013 PMID:8395367 biolink:NamedThing omim.nt IAO:0000013 PMID:8684801 biolink:NamedThing omim.nt IAO:0000013 UMLS:C1622345 biolink:NamedThing omim.nt owl:Class UMLS:C1628319 biolink:NamedThing omim.nt owl:Class UMLS:C2751493 biolink:NamedThing omim.nt owl:Class ORPHA:85448 biolink:NamedThing|biolink:Disease omim.nt owl:Class http://omim.org/entry/105150 biolink:NamedThing|biolink:Disease Cerebral Amyloid Angiopathy, Cst3-Related Cerebral Amyloid Angiopathy, Cst3-Related omim.nt CEREBRAL AMYLOID ANGIOPATHY, CST3-RELATED|Amyloidosis 6|Amyloidosis, Cerebroarterial, Icelandic Type|Cerebral Hemorrhage, Hereditary, With Amyloidosis|Hereditary Cerebral Hemorrhage With Amyloidosis owl:Class MONARCH:.well-known/genid/OMIM105150ref12 biolink:NamedThing Cystatin C (gamma-trace) amyloidosis.In: Turk, V. : Cysteine Proteinases and their Inhibitors. omim.nt IAO:0000310 MONARCH:.well-known/genid/OMIM105150ref3 biolink:NamedThing Apoplexie und ihre Vererbung. omim.nt IAO:0000310 PMID:1352269 biolink:NamedThing omim.nt IAO:0000013 PMID:20241165 biolink:NamedThing omim.nt IAO:0000013 PMID:2436360 biolink:NamedThing omim.nt IAO:0000013 PMID:2689007 biolink:NamedThing omim.nt IAO:0000013 PMID:2900981 biolink:NamedThing omim.nt IAO:0000013 PMID:3475718 biolink:NamedThing omim.nt IAO:0000013 PMID:3495457 biolink:NamedThing omim.nt IAO:0000013 PMID:3517880 biolink:NamedThing omim.nt IAO:0000013 PMID:3551211 biolink:NamedThing omim.nt IAO:0000013 PMID:3673496 biolink:NamedThing omim.nt IAO:0000013 PMID:3707586 biolink:NamedThing omim.nt IAO:0000013 PMID:3982473 biolink:NamedThing omim.nt IAO:0000013 PMID:4056910 biolink:NamedThing omim.nt IAO:0000013 PMID:4056911 biolink:NamedThing omim.nt IAO:0000013 PMID:4655034 biolink:NamedThing omim.nt IAO:0000013 PMID:637762 biolink:NamedThing omim.nt IAO:0000013 PMID:6390199 biolink:NamedThing omim.nt IAO:0000013 PMID:6886625 biolink:NamedThing omim.nt IAO:0000013 PMID:7396423 biolink:NamedThing omim.nt IAO:0000013 PMID:7945009 biolink:NamedThing omim.nt IAO:0000013 PMID:9748011 biolink:NamedThing omim.nt IAO:0000013 UMLS:C1510489 biolink:NamedThing omim.nt owl:Class UMLS:C1527338 biolink:NamedThing omim.nt owl:Class ORPHA:100008 biolink:NamedThing|biolink:Disease omim.nt owl:Class ORPHA:85458 biolink:NamedThing|biolink:Disease omim.nt owl:Class http://omim.org/entry/105200 biolink:NamedThing|biolink:Disease Amyloidosis, Familial Visceral Amyloidosis, Familial Visceral omim.nt AMYLOIDOSIS, FAMILIAL VISCERAL|Amyloidosis 8|Amyloidosis, Familial Renal|Amyloidosis, Systemic Nonneuropathic|German Type Amyloidosis|Ostertag Type Amyloidosis owl:Class MONARCH:.well-known/genid/OMIM105200ref10 biolink:NamedThing A 43-year-old woman with hepatic failure after renal transplantation because of amyloidosis. omim.nt IAO:0000310 MONARCH:.well-known/genid/OMIM105200ref11 biolink:NamedThing Familial amyloidosis with case reports. omim.nt IAO:0000310 MONARCH:.well-known/genid/OMIM105200ref12 biolink:NamedThing Personal Communication. omim.nt IAO:0000310 MONARCH:.well-known/genid/OMIM105200ref15 biolink:NamedThing Demonstration einer eigenartigen familiaeren Paramyloidose. omim.nt IAO:0000310 MONARCH:.well-known/genid/OMIM105200ref16 biolink:NamedThing Familiaere Amyloid-erkrankung. omim.nt IAO:0000310 MONARCH:.well-known/genid/OMIM105200ref18 biolink:NamedThing Fibrinogen Indianapolis: a fibrinogen A-alpha chain associated with hereditary amyloidosis. (Abstract) omim.nt IAO:0000310 MONARCH:.well-known/genid/OMIM105200ref2 biolink:NamedThing Renal amyloidosis with a frame shift mutation in fibrinogen A(alpha)-chain gene producing a novel amyloid protein. omim.nt IAO:0000310 MONARCH:.well-known/genid/OMIM105200ref24 biolink:NamedThing Amyloid nephropathy of Ostertag: report of a kindred. omim.nt IAO:0000310 MONARCH:.well-known/genid/OMIM105200ref7 biolink:NamedThing Personal Communication. omim.nt IAO:0000310 PMID:1138543 biolink:NamedThing omim.nt IAO:0000013 PMID:12050338 biolink:NamedThing omim.nt IAO:0000013 PMID:12208391 biolink:NamedThing omim.nt IAO:0000013 PMID:15745733 biolink:NamedThing omim.nt IAO:0000013 PMID:1808634 biolink:NamedThing omim.nt IAO:0000013 PMID:22693999 biolink:NamedThing omim.nt IAO:0000013 PMID:3912110 biolink:NamedThing omim.nt IAO:0000013 PMID:4728894 biolink:NamedThing omim.nt IAO:0000013 PMID:7111672 biolink:NamedThing omim.nt IAO:0000013 PMID:7124780 biolink:NamedThing omim.nt IAO:0000013 PMID:7344220 biolink:NamedThing omim.nt IAO:0000013 PMID:8097946 biolink:NamedThing omim.nt IAO:0000013 PMID:8113408 biolink:NamedThing omim.nt IAO:0000013 PMID:8464497 biolink:NamedThing omim.nt IAO:0000013 PMID:8639778 biolink:NamedThing omim.nt IAO:0000013 UMLS:C0268389 biolink:NamedThing omim.nt owl:Class ORPHA:85450 biolink:NamedThing|biolink:Disease omim.nt owl:Class http://omim.org/entry/105210 biolink:NamedThing|biolink:Disease Amyloidosis, Hereditary, Transthyretin-Related Amyloidosis, Hereditary, Transthyretin-Related omim.nt AMYLOIDOSIS, HEREDITARY, TRANSTHYRETIN-RELATED|Amyloid Cardiomyopathy, Transthyretin-Related|Amyloidosis, Leptomeningeal, Transthyretin-Related|Amyloid Polyneuropathy, Familial|Hereditary Amyloidosis, Transthyretin-Related|Transthyretin Amyloidosis owl:Class MONARCH:.well-known/genid/OMIM105210ref10 biolink:NamedThing Personal Communication. omim.nt IAO:0000310 MONARCH:.well-known/genid/OMIM105210ref12 biolink:NamedThing Amyloidosis. In: Scriver, C. R.; Beaudet, A. L.; Sly, W. S.; Valle, D. (eds.): The Metabolic and Molecular Bases of Inherited Disease. Vol. 4. (8th ed.) omim.nt IAO:0000310 MONARCH:.well-known/genid/OMIM105210ref20 biolink:NamedThing Familial amyloidotic polyneuropathy and Machado-Joseph disease: two rare autosomal dominant neurologic diseases in the same family: the 'Iiyama type' of FAP? (Abstract) omim.nt IAO:0000310 MONARCH:.well-known/genid/OMIM105210ref22 biolink:NamedThing A case of the progressive hypertrophic polyneuritis of Dejerine and Sottas, with pathological examination. omim.nt IAO:0000310 MONARCH:.well-known/genid/OMIM105210ref23 biolink:NamedThing A case of primary generalized amyloid disease with involvement of the nerves. omim.nt IAO:0000310 MONARCH:.well-known/genid/OMIM105210ref33 biolink:NamedThing 'Senile' cardiac amyloidosis: isolation of fibrils and immunohistological identity with heredofamilial neuropathic amyloid due to tissue deposition of prealbumin. (Abstract) omim.nt IAO:0000310 MONARCH:.well-known/genid/OMIM105210ref66 biolink:NamedThing Personal Communication. omim.nt IAO:0000310 MONARCH:.well-known/genid/OMIM105210ref67 biolink:NamedThing In memoriam: George G. Glenner, M.D. (1927-1995). omim.nt IAO:0000310 MONARCH:.well-known/genid/OMIM105210ref8 biolink:NamedThing Characterization of an amyloid fibril protein in heredofamilial amyloidosis. (Abstract) omim.nt IAO:0000310 PMID:10468546 biolink:NamedThing omim.nt IAO:0000013 PMID:10488818 biolink:NamedThing omim.nt IAO:0000013 PMID:10541593 biolink:NamedThing omim.nt IAO:0000013 PMID:11261421 biolink:NamedThing omim.nt IAO:0000013 PMID:11385707 biolink:NamedThing omim.nt IAO:0000013 PMID:11552976 biolink:NamedThing omim.nt IAO:0000013 PMID:11940682 biolink:NamedThing omim.nt IAO:0000013 PMID:12771253 biolink:NamedThing omim.nt IAO:0000013 PMID:12978172 biolink:NamedThing omim.nt IAO:0000013 PMID:1351039 biolink:NamedThing omim.nt IAO:0000013 PMID:13593935 biolink:NamedThing omim.nt IAO:0000013 PMID:14404854 biolink:NamedThing omim.nt IAO:0000013 PMID:14477245 biolink:NamedThing omim.nt IAO:0000013 PMID:14981241 biolink:NamedThing omim.nt IAO:0000013 PMID:14987380 biolink:NamedThing omim.nt IAO:0000013 PMID:15079068 biolink:NamedThing omim.nt IAO:0000013 PMID:15249622 biolink:NamedThing omim.nt IAO:0000013 PMID:15820680 biolink:NamedThing omim.nt IAO:0000013 PMID:16009758 biolink:NamedThing omim.nt IAO:0000013 PMID:1685359 biolink:NamedThing omim.nt IAO:0000013 PMID:1685700 biolink:NamedThing omim.nt IAO:0000013 PMID:17200500 biolink:NamedThing omim.nt IAO:0000013 PMID:18022643 biolink:NamedThing omim.nt IAO:0000013 PMID:1848299 biolink:NamedThing omim.nt IAO:0000013 PMID:192115 biolink:NamedThing omim.nt IAO:0000013 PMID:19365058 biolink:NamedThing omim.nt IAO:0000013 PMID:1992765 biolink:NamedThing omim.nt IAO:0000013 PMID:202208 biolink:NamedThing omim.nt IAO:0000013 PMID:20697105 biolink:NamedThing omim.nt IAO:0000013 PMID:2320592 biolink:NamedThing omim.nt IAO:0000013 PMID:23984729 biolink:NamedThing omim.nt IAO:0000013 PMID:279930 biolink:NamedThing omim.nt IAO:0000013 PMID:2828557 biolink:NamedThing omim.nt IAO:0000013 PMID:2829057 biolink:NamedThing omim.nt IAO:0000013 PMID:29972757 biolink:NamedThing omim.nt IAO:0000013 PMID:3032328 biolink:NamedThing omim.nt IAO:0000013 PMID:3037905 biolink:NamedThing omim.nt IAO:0000013 PMID:3178532 biolink:NamedThing omim.nt IAO:0000013 PMID:3229002 biolink:NamedThing omim.nt IAO:0000013 PMID:3379433 biolink:NamedThing omim.nt IAO:0000013 PMID:3479441 biolink:NamedThing omim.nt IAO:0000013 PMID:4102463 biolink:NamedThing omim.nt IAO:0000013 PMID:4328329 biolink:NamedThing omim.nt IAO:0000013 PMID:4328330 biolink:NamedThing omim.nt IAO:0000013 PMID:4443557 biolink:NamedThing omim.nt IAO:0000013 PMID:4884226 biolink:NamedThing omim.nt IAO:0000013 PMID:4952599 biolink:NamedThing omim.nt IAO:0000013 PMID:5089749 biolink:NamedThing omim.nt IAO:0000013 PMID:6691355 biolink:NamedThing omim.nt IAO:0000013 PMID:6736244 biolink:NamedThing omim.nt IAO:0000013 PMID:6782125 biolink:NamedThing omim.nt IAO:0000013 PMID:7018469 biolink:NamedThing omim.nt IAO:0000013 PMID:7033114 biolink:NamedThing omim.nt IAO:0000013 PMID:7417777 biolink:NamedThing omim.nt IAO:0000013 PMID:7794243 biolink:NamedThing omim.nt IAO:0000013 PMID:7839813 biolink:NamedThing omim.nt IAO:0000013 PMID:7844317 biolink:NamedThing omim.nt IAO:0000013 PMID:8064809 biolink:NamedThing omim.nt IAO:0000013 PMID:8071954 biolink:NamedThing omim.nt IAO:0000013 PMID:8097803 biolink:NamedThing omim.nt IAO:0000013 PMID:8100581 biolink:NamedThing omim.nt IAO:0000013 PMID:8579098 biolink:NamedThing omim.nt IAO:0000013 PMID:8778271 biolink:NamedThing omim.nt IAO:0000013 PMID:8857732 biolink:NamedThing omim.nt IAO:0000013 PMID:8960746 biolink:NamedThing omim.nt IAO:0000013 PMID:9017939 biolink:NamedThing omim.nt IAO:0000013 PMID:9066351 biolink:NamedThing omim.nt IAO:0000013 UMLS:C2751492 biolink:NamedThing omim.nt owl:Class UMLS:C3151470 biolink:NamedThing omim.nt owl:Class UMLS:C3151471 biolink:NamedThing omim.nt owl:Class ORPHA:85447 biolink:NamedThing|biolink:Disease omim.nt owl:Class ORPHA:85451 biolink:NamedThing|biolink:Disease omim.nt owl:Class http://omim.org/entry/105250 biolink:NamedThing|biolink:Disease Amyloidosis, Primary Localized Cutaneous, 1 Amyloidosis, Primary Localized Cutaneous, 1 omim.nt AMYLOIDOSIS, PRIMARY LOCALIZED CUTANEOUS, 1; PLCA1|Amyloidosis 9|Amyloidosis, Familial Cutaneous Lichen|Amyloidosis, Primary Cutaneous, 1|Lichen Amyloidosis, Familial|Pca owl:Class MONARCH:.well-known/genid/OMIM105250ref17 biolink:NamedThing Genodermatosis in Singapore. omim.nt IAO:0000310 PMID:13976058 biolink:NamedThing omim.nt IAO:0000013 PMID:15656797 biolink:NamedThing omim.nt IAO:0000013 PMID:17107390 biolink:NamedThing omim.nt IAO:0000013 PMID:18179886 biolink:NamedThing omim.nt IAO:0000013 PMID:19663869 biolink:NamedThing omim.nt IAO:0000013 PMID:19690585 biolink:NamedThing omim.nt IAO:0000013 PMID:3970841 biolink:NamedThing omim.nt IAO:0000013 PMID:5057380 biolink:NamedThing omim.nt IAO:0000013 PMID:5430314 biolink:NamedThing omim.nt IAO:0000013 PMID:6724776 biolink:NamedThing omim.nt IAO:0000013 PMID:6945068 biolink:NamedThing omim.nt IAO:0000013 PMID:7914213 biolink:NamedThing omim.nt IAO:0000013 PMID:8752835 biolink:NamedThing omim.nt IAO:0000013 PMID:8757765 biolink:NamedThing omim.nt IAO:0000013 PMID:9111993 biolink:NamedThing omim.nt IAO:0000013 PMID:993396 biolink:NamedThing omim.nt IAO:0000013 UMLS:C4551501 biolink:NamedThing omim.nt owl:Class ORPHA:353220 biolink:NamedThing|biolink:Disease omim.nt owl:Class http://www.omim.org/phenotypicSeries/PS105250 biolink:NamedThing|biolink:Disease Amyloidosis, primary localized cutaneous omim.nt owl:Class http://omim.org/entry/105300 biolink:NamedThing Amyotrophic Dystonic Paraplegia omim.nt AMYOTROPHIC DYSTONIC PARAPLEGIA owl:Class PMID:14152212 biolink:NamedThing omim.nt IAO:0000013 UMLS:C1862956 biolink:NamedThing omim.nt owl:Class http://omim.org/entry/105400 biolink:NamedThing|biolink:Disease Amyotrophic Lateral Sclerosis 1 Amyotrophic Lateral Sclerosis 1 omim.nt AMYOTROPHIC LATERAL SCLEROSIS 1; ALS1|Amyotrophic Lateral Sclerosis 1, Autosomal Dominant|Amyotrophic Lateral Sclerosis 1, Autosomal Recessive|Amyotrophic Lateral Sclerosis 1, Familial|Amyotrophic Lateral Sclerosis, Sporadic owl:Class MONARCH:.well-known/genid/OMIM105400ref108 biolink:NamedThing X-linked dominant locus for late-onset familial amyotrophic lateral sclerosis. (Abstract) omim.nt IAO:0000310 MONARCH:.well-known/genid/OMIM105400ref109 biolink:NamedThing Linkage in familial amyotrophic lateral sclerosis (ALS). (Abstract) omim.nt IAO:0000310 MONARCH:.well-known/genid/OMIM105400ref110 biolink:NamedThing Genetic linkage analysis in familial amyotrophic lateral sclerosis. (Abstract) omim.nt IAO:0000310 MONARCH:.well-known/genid/OMIM105400ref112 biolink:NamedThing Personal Communication. omim.nt IAO:0000310 MONARCH:.well-known/genid/OMIM105400ref126 biolink:NamedThing Dominantly inherited amyotrophic lateral sclerosis (motor neuron disease). omim.nt IAO:0000310 MONARCH:.well-known/genid/OMIM105400ref3 biolink:NamedThing Tuesdays with Morrie: an old man, a young man, and the last great lesson. omim.nt IAO:0000310 MONARCH:.well-known/genid/OMIM105400ref34 biolink:NamedThing Personal Communication. omim.nt IAO:0000310 MONARCH:.well-known/genid/OMIM105400ref35 biolink:NamedThing Hereditary amyotrophic lateral sclerosis: a clinical and pathologic report with comments on classification. omim.nt IAO:0000310 MONARCH:.well-known/genid/OMIM105400ref41 biolink:NamedThing Hereditary adult motor neuron disease. omim.nt IAO:0000310 MONARCH:.well-known/genid/OMIM105400ref48 biolink:NamedThing Ergebnisse einer neurologisch-genetischen Studie im nordwestdeutschen Raum. In: Gedda, L. (ed.): Proceedings of the Second International Congress of Human Genetics, Rome, Sept. 6-12, 1961. Vol. 3. omim.nt IAO:0000310 MONARCH:.well-known/genid/OMIM105400ref49 biolink:NamedThing A Treatise on the Diseases of the Nervous System. (7th ed.) omim.nt IAO:0000310 MONARCH:.well-known/genid/OMIM105400ref83 biolink:NamedThing On heredity in progressive muscular atrophy as illustrated in the Farr family of Vermont. omim.nt IAO:0000310 MONARCH:.well-known/genid/OMIM105400ref85 biolink:NamedThing Familial amyotrophic lateral sclerosis: an evaluation of genetic counseling. (Abstract) omim.nt IAO:0000310 MONARCH:.well-known/genid/OMIM105400ref88 biolink:NamedThing Wetherbee ail: documentation of a neurological disease in a Vermont family 90 years later. omim.nt IAO:0000310 PMID:1003176 biolink:NamedThing omim.nt IAO:0000013 PMID:10195181 biolink:NamedThing omim.nt IAO:0000013 PMID:10688913 biolink:NamedThing omim.nt IAO:0000013 PMID:10737125 biolink:NamedThing omim.nt IAO:0000013 PMID:10764647 biolink:NamedThing omim.nt IAO:0000013 PMID:11160962 biolink:NamedThing omim.nt IAO:0000013 PMID:11343650 biolink:NamedThing omim.nt IAO:0000013 PMID:11386269 biolink:NamedThing omim.nt IAO:0000013 PMID:11555629 biolink:NamedThing omim.nt IAO:0000013 PMID:11835381 biolink:NamedThing omim.nt IAO:0000013 PMID:11951178 biolink:NamedThing omim.nt IAO:0000013 PMID:12060716 biolink:NamedThing omim.nt IAO:0000013 PMID:12062019 biolink:NamedThing omim.nt IAO:0000013 PMID:12354397 biolink:NamedThing omim.nt IAO:0000013 PMID:12447931 biolink:NamedThing omim.nt IAO:0000013 PMID:12535368 biolink:NamedThing omim.nt IAO:0000013 PMID:12907804 biolink:NamedThing omim.nt IAO:0000013 PMID:1349424 biolink:NamedThing omim.nt IAO:0000013 PMID:1365052 biolink:NamedThing omim.nt IAO:0000013 PMID:13708181 biolink:NamedThing omim.nt IAO:0000013 PMID:13710241 biolink:NamedThing omim.nt IAO:0000013 PMID:13804989 biolink:NamedThing omim.nt IAO:0000013 PMID:13849712 biolink:NamedThing omim.nt IAO:0000013 PMID:14349945 biolink:NamedThing omim.nt IAO:0000013 PMID:14356347 biolink:NamedThing omim.nt IAO:0000013 PMID:14675609 biolink:NamedThing omim.nt IAO:0000013 PMID:14875225 biolink:NamedThing omim.nt IAO:0000013 PMID:14985749 biolink:NamedThing omim.nt IAO:0000013 PMID:15164063 biolink:NamedThing omim.nt IAO:0000013 PMID:15294873 biolink:NamedThing omim.nt IAO:0000013 PMID:15322088 biolink:NamedThing omim.nt IAO:0000013 PMID:15326253 biolink:NamedThing omim.nt IAO:0000013 PMID:15478096 biolink:NamedThing omim.nt IAO:0000013 PMID:15568021 biolink:NamedThing omim.nt IAO:0000013 PMID:15623718 biolink:NamedThing omim.nt IAO:0000013 PMID:15883330 biolink:NamedThing omim.nt IAO:0000013 PMID:16093455 biolink:NamedThing omim.nt IAO:0000013 PMID:16291929 biolink:NamedThing omim.nt IAO:0000013 PMID:1639406 biolink:NamedThing omim.nt IAO:0000013 PMID:16476815 biolink:NamedThing omim.nt IAO:0000013 PMID:16581901 biolink:NamedThing omim.nt IAO:0000013 PMID:16741123 biolink:NamedThing omim.nt IAO:0000013 PMID:16931506 biolink:NamedThing omim.nt IAO:0000013 PMID:17023659 biolink:NamedThing omim.nt IAO:0000013 PMID:17164329 biolink:NamedThing omim.nt IAO:0000013 PMID:17277077 biolink:NamedThing omim.nt IAO:0000013 PMID:17455292 biolink:NamedThing omim.nt IAO:0000013 PMID:17486090 biolink:NamedThing omim.nt IAO:0000013 PMID:17671248 biolink:NamedThing omim.nt IAO:0000013 PMID:17702029 biolink:NamedThing omim.nt IAO:0000013 PMID:17853944 biolink:NamedThing omim.nt IAO:0000013 PMID:17894379 biolink:NamedThing omim.nt IAO:0000013 PMID:18077368 biolink:NamedThing omim.nt IAO:0000013 PMID:18250315 biolink:NamedThing omim.nt IAO:0000013 PMID:18268245 biolink:NamedThing omim.nt IAO:0000013 PMID:18413368 biolink:NamedThing omim.nt IAO:0000013 PMID:18669821 biolink:NamedThing omim.nt IAO:0000013 PMID:18996918 biolink:NamedThing omim.nt IAO:0000013 PMID:19088126 biolink:NamedThing omim.nt IAO:0000013 PMID:19188595 biolink:NamedThing omim.nt IAO:0000013 PMID:19321847 biolink:NamedThing omim.nt IAO:0000013 PMID:19451621 biolink:NamedThing omim.nt IAO:0000013 PMID:19628475 biolink:NamedThing omim.nt IAO:0000013 PMID:19670443 biolink:NamedThing omim.nt IAO:0000013 PMID:19670447 biolink:NamedThing omim.nt IAO:0000013 PMID:19734901 biolink:NamedThing omim.nt IAO:0000013 PMID:19864493 biolink:NamedThing omim.nt IAO:0000013 PMID:20007902 biolink:NamedThing omim.nt IAO:0000013 PMID:2020294 biolink:NamedThing omim.nt IAO:0000013 PMID:20223753 biolink:NamedThing omim.nt IAO:0000013 PMID:20348957 biolink:NamedThing omim.nt IAO:0000013 PMID:20368421 biolink:NamedThing omim.nt IAO:0000013 PMID:20460269 biolink:NamedThing omim.nt IAO:0000013 PMID:20530642 biolink:NamedThing omim.nt IAO:0000013 PMID:20577002 biolink:NamedThing omim.nt IAO:0000013 PMID:20616033 biolink:NamedThing omim.nt IAO:0000013 PMID:20650960 biolink:NamedThing omim.nt IAO:0000013 PMID:20829229 biolink:NamedThing omim.nt IAO:0000013 PMID:22323753 biolink:NamedThing omim.nt IAO:0000013 PMID:23104007 biolink:NamedThing omim.nt IAO:0000013 PMID:2370562 biolink:NamedThing omim.nt IAO:0000013 PMID:31330533 biolink:NamedThing omim.nt IAO:0000013 PMID:32733193 biolink:NamedThing omim.nt IAO:0000013 PMID:32750315 biolink:NamedThing omim.nt IAO:0000013 PMID:4115557 biolink:NamedThing omim.nt IAO:0000013 PMID:5096760 biolink:NamedThing omim.nt IAO:0000013 PMID:5790363 biolink:NamedThing omim.nt IAO:0000013 PMID:5843014 biolink:NamedThing omim.nt IAO:0000013 PMID:6018874 biolink:NamedThing omim.nt IAO:0000013 PMID:6181766 biolink:NamedThing omim.nt IAO:0000013 PMID:7016254 biolink:NamedThing omim.nt IAO:0000013 PMID:7229665 biolink:NamedThing omim.nt IAO:0000013 PMID:7438491 biolink:NamedThing omim.nt IAO:0000013 PMID:7605627 biolink:NamedThing omim.nt IAO:0000013 PMID:7647793 biolink:NamedThing omim.nt IAO:0000013 PMID:7845611 biolink:NamedThing omim.nt IAO:0000013 PMID:7846037 biolink:NamedThing omim.nt IAO:0000013 PMID:7887412 biolink:NamedThing omim.nt IAO:0000013 PMID:8105280 biolink:NamedThing omim.nt IAO:0000013 PMID:8209258 biolink:NamedThing omim.nt IAO:0000013 PMID:824491 biolink:NamedThing omim.nt IAO:0000013 PMID:8351519 biolink:NamedThing omim.nt IAO:0000013 PMID:835533 biolink:NamedThing omim.nt IAO:0000013 PMID:8446170 biolink:NamedThing omim.nt IAO:0000013 PMID:8487280 biolink:NamedThing omim.nt IAO:0000013 PMID:8592323 biolink:NamedThing omim.nt IAO:0000013 PMID:8610185 biolink:NamedThing omim.nt IAO:0000013 PMID:8875253 biolink:NamedThing omim.nt IAO:0000013 PMID:9029070 biolink:NamedThing omim.nt IAO:0000013 PMID:911233 biolink:NamedThing omim.nt IAO:0000013 PMID:944398 biolink:NamedThing omim.nt IAO:0000013 PMID:954772 biolink:NamedThing omim.nt IAO:0000013 PMID:9753713 biolink:NamedThing omim.nt IAO:0000013 PMID:9753716 biolink:NamedThing omim.nt IAO:0000013 PMID:9817920 biolink:NamedThing omim.nt IAO:0000013 PMID:9818932 biolink:NamedThing omim.nt IAO:0000013 UMLS:C1862939 biolink:NamedThing omim.nt owl:Class UMLS:C1862941 biolink:NamedThing omim.nt owl:Class UMLS:C3542025 biolink:NamedThing omim.nt owl:Class ORPHA:803 biolink:NamedThing|biolink:Disease omim.nt owl:Class http://www.omim.org/phenotypicSeries/PS105400 biolink:NamedThing|biolink:Disease Amyotrophic lateral sclerosis omim.nt owl:Class http://omim.org/entry/105500 biolink:NamedThing|biolink:Disease Amyotrophic Lateral Sclerosis-Parkinsonism/Dementia Complex 1 Amyotrophic Lateral Sclerosis-Parkinsonism/Dementia Complex 1 omim.nt AMYOTROPHIC LATERAL SCLEROSIS-PARKINSONISM/DEMENTIA COMPLEX 1|Als-Pdc|Amyotrophic Lateral Sclerosis-Parkinsonism/Dementia Complex of Guam|Guam Disease owl:Class MONARCH:.well-known/genid/OMIM105500ref15 biolink:NamedThing Epidemiological and geomedical studies on ALS and allied diseases in Kii peninsula (Japan): preliminary report. omim.nt IAO:0000310 MONARCH:.well-known/genid/OMIM105500ref4 biolink:NamedThing Calcium aluminum silicon deposits in neurons lead to paired helical filaments identical to those of AD and Down's patients. omim.nt IAO:0000310 PMID:10732812 biolink:NamedThing omim.nt IAO:0000013 PMID:11310628 biolink:NamedThing omim.nt IAO:0000013 PMID:11708997 biolink:NamedThing omim.nt IAO:0000013 PMID:13907609 biolink:NamedThing omim.nt IAO:0000013 PMID:16051700 biolink:NamedThing omim.nt IAO:0000013 PMID:16990532 biolink:NamedThing omim.nt IAO:0000013 PMID:17185385 biolink:NamedThing omim.nt IAO:0000013 PMID:17515539 biolink:NamedThing omim.nt IAO:0000013 PMID:18490618 biolink:NamedThing omim.nt IAO:0000013 PMID:19405049 biolink:NamedThing omim.nt IAO:0000013 PMID:19567404 biolink:NamedThing omim.nt IAO:0000013 PMID:22637429 biolink:NamedThing omim.nt IAO:0000013 PMID:2396931 biolink:NamedThing omim.nt IAO:0000013 PMID:3470778 biolink:NamedThing omim.nt IAO:0000013 PMID:3603037 biolink:NamedThing omim.nt IAO:0000013 PMID:3969206 biolink:NamedThing omim.nt IAO:0000013 PMID:5770171 biolink:NamedThing omim.nt IAO:0000013 PMID:6573136 biolink:NamedThing omim.nt IAO:0000013 PMID:6573137 biolink:NamedThing omim.nt IAO:0000013 PMID:7212649 biolink:NamedThing omim.nt IAO:0000013 PMID:7936240 biolink:NamedThing omim.nt IAO:0000013 PMID:8332906 biolink:NamedThing omim.nt IAO:0000013 PMID:8418664 biolink:NamedThing omim.nt IAO:0000013 UMLS:C0543859 biolink:NamedThing omim.nt owl:Class ORPHA:90020 biolink:NamedThing|biolink:Disease omim.nt owl:Class http://omim.org/entry/105550 biolink:NamedThing|biolink:Disease Frontotemporal Dementia And/Or Amyotrophic Lateral Sclerosis 1 Frontotemporal Dementia And/Or Amyotrophic Lateral Sclerosis 1 omim.nt FRONTOTEMPORAL DEMENTIA AND/OR AMYOTROPHIC LATERAL SCLEROSIS 1; FTDALS1|Amyotrophic Lateral Sclerosis And/Or Frontotemporal Dementia|Frontotemporal Dementia And/Or Amyotrophic Lateral Sclerosis|Frontotemporal Dementia And/Or Motor Neuron Disease owl:Class MONARCH:.well-known/genid/OMIM105550ref44 biolink:NamedThing Progressive bulbar paralysis showing heredofamilial incidence and intellectual impairment. omim.nt IAO:0000310 MONARCH:.well-known/genid/OMIM105550ref7 biolink:NamedThing Sulla sclerosa laterale amiotrofica familiare. Contributo clinico. omim.nt IAO:0000310 PMID:11015796 biolink:NamedThing omim.nt IAO:0000013 PMID:1139787 biolink:NamedThing omim.nt IAO:0000013 PMID:12840784 biolink:NamedThing omim.nt IAO:0000013 PMID:16421333 biolink:NamedThing omim.nt IAO:0000013 PMID:16495328 biolink:NamedThing omim.nt IAO:0000013 PMID:17296840 biolink:NamedThing omim.nt IAO:0000013 PMID:17805587 biolink:NamedThing omim.nt IAO:0000013 PMID:18755042 biolink:NamedThing omim.nt IAO:0000013 PMID:19433740 biolink:NamedThing omim.nt IAO:0000013 PMID:20562461 biolink:NamedThing omim.nt IAO:0000013 PMID:20801718 biolink:NamedThing omim.nt IAO:0000013 PMID:21031579 biolink:NamedThing omim.nt IAO:0000013 PMID:21072532 biolink:NamedThing omim.nt IAO:0000013 PMID:21925771 biolink:NamedThing omim.nt IAO:0000013 PMID:21944778 biolink:NamedThing omim.nt IAO:0000013 PMID:21944779 biolink:NamedThing omim.nt IAO:0000013 PMID:22499346 biolink:NamedThing omim.nt IAO:0000013 PMID:22637471 biolink:NamedThing omim.nt IAO:0000013 PMID:22650353 biolink:NamedThing omim.nt IAO:0000013 PMID:22692064 biolink:NamedThing omim.nt IAO:0000013 PMID:22739338 biolink:NamedThing omim.nt IAO:0000013 PMID:22843265 biolink:NamedThing omim.nt IAO:0000013 PMID:22936364 biolink:NamedThing omim.nt IAO:0000013 PMID:22964910 biolink:NamedThing omim.nt IAO:0000013 PMID:22964911 biolink:NamedThing omim.nt IAO:0000013 PMID:23111906 biolink:NamedThing omim.nt IAO:0000013 PMID:23284068 biolink:NamedThing omim.nt IAO:0000013 PMID:23393093 biolink:NamedThing omim.nt IAO:0000013 PMID:23423380 biolink:NamedThing omim.nt IAO:0000013 PMID:23434116 biolink:NamedThing omim.nt IAO:0000013 PMID:23437264 biolink:NamedThing omim.nt IAO:0000013 PMID:23551834 biolink:NamedThing omim.nt IAO:0000013 PMID:23597494 biolink:NamedThing omim.nt IAO:0000013 PMID:23720273 biolink:NamedThing omim.nt IAO:0000013 PMID:23731538 biolink:NamedThing omim.nt IAO:0000013 PMID:24027057 biolink:NamedThing omim.nt IAO:0000013 PMID:24057670 biolink:NamedThing omim.nt IAO:0000013 PMID:24139042 biolink:NamedThing omim.nt IAO:0000013 PMID:24363131 biolink:NamedThing omim.nt IAO:0000013 PMID:24598541 biolink:NamedThing omim.nt IAO:0000013 PMID:24706941 biolink:NamedThing omim.nt IAO:0000013 PMID:25081482 biolink:NamedThing omim.nt IAO:0000013 PMID:25103406 biolink:NamedThing omim.nt IAO:0000013 PMID:25209579 biolink:NamedThing omim.nt IAO:0000013 PMID:25712133 biolink:NamedThing omim.nt IAO:0000013 PMID:26004200 biolink:NamedThing omim.nt IAO:0000013 PMID:26088964 biolink:NamedThing omim.nt IAO:0000013 PMID:26308891 biolink:NamedThing omim.nt IAO:0000013 PMID:26308899 biolink:NamedThing omim.nt IAO:0000013 PMID:27516603 biolink:NamedThing omim.nt IAO:0000013 PMID:28562589 biolink:NamedThing omim.nt IAO:0000013 PMID:32814898 biolink:NamedThing omim.nt IAO:0000013 PMID:4769153 biolink:NamedThing omim.nt IAO:0000013 UMLS:C3888102 biolink:NamedThing omim.nt owl:Class ORPHA:275872 biolink:NamedThing|biolink:Disease omim.nt owl:Class http://www.omim.org/phenotypicSeries/PS105550 biolink:NamedThing|biolink:Disease Frontotemporal dementia and/or Amyotrophic Lateral Sclerosis omim.nt owl:Class http://omim.org/entry/105563 biolink:NamedThing Anal Sphincter Dysplasia omim.nt ANAL SPHINCTER DYSPLASIA; ASDP owl:Class MONARCH:.well-known/genid/OMIM105563ref1 biolink:NamedThing Analsphinkterdysplasie als Ursache chronischer Defaekationsstoerungen: eine klinische und genetische Studie. omim.nt IAO:0000310 PMID:1947952 biolink:NamedThing omim.nt IAO:0000013 UMLS:C1862936 biolink:NamedThing omim.nt owl:Class http://omim.org/entry/105565 biolink:NamedThing Anal Sphincter Myopathy, Internal omim.nt ANAL SPHINCTER MYOPATHY, INTERNAL|Proctalgia Fugax Due to Anal Sphincter Myopathy owl:Class PMID:1993504 biolink:NamedThing omim.nt IAO:0000013 PMID:7737568 biolink:NamedThing omim.nt IAO:0000013 UMLS:C1862935 biolink:NamedThing omim.nt owl:Class http://omim.org/entry/105570 biolink:NamedThing Androstenone, Ability to Smell omim.nt ANDROSTENONE, ABILITY TO SMELL owl:Class MONARCH:.well-known/genid/OMIM105570ref1 biolink:NamedThing Biochemistry of Taste and Olfaction. omim.nt IAO:0000310 PMID:2813372 biolink:NamedThing omim.nt IAO:0000013 PMID:6589634 biolink:NamedThing omim.nt IAO:0000013 PMID:9246445 biolink:NamedThing omim.nt IAO:0000013 UMLS:C1862934 biolink:NamedThing omim.nt owl:Class http://omim.org/entry/105580 biolink:NamedThing Anal Canal Carcinoma omim.nt ANAL CANAL CARCINOMA|Cloacogenic Carcinoma owl:Class PMID:3570551 biolink:NamedThing omim.nt IAO:0000013 UMLS:C0334273 biolink:NamedThing omim.nt owl:Class UMLS:C0563211 biolink:NamedThing omim.nt owl:Class http://omim.org/entry/105590.0001 biolink:NamedThing ALK, ARG1275GLN In 5 independent families segregating neuroblastoma ({613014}), {14:Mosse et al. (2008)} identified a 3824G-A transition in the ALK gene, resulting in an arg1275-to-gln (R1275Q) substitution. The mutation manifested incomplete penetrance but was not identified in 218 normal control chromosomes. The mutation occurs in the kinase activation loop of the protein and has a 91% probability of being an activating mutation. In 1 family an unaffected mutation-carrying mother transmitted the mutation to 3 offspring by 3 different fathers; each of these 3 offspring developed neuroblastoma. {9:Janoueix-Lerosey et al. (2008)} identified 1 family in which an unaffected mutation-carrying mother transmitted the mutation to 2 affected offspring, each by a different father. {8:George et al. (2008)} identified this mutation in a patient with neuroblastoma. {3:Chen et al. (2008)} identified the R1275Q substitution as a somatic mutation in several neuroblastoma tumor samples. {2:Bourdeaut et al. (2012)} identified a de novo heterozygous germline R1275Q mutation in a patient with perinatal onset of multifocal neuroblastoma. The mutation was also found in several tumors. omim.nt GENO:0000002 http://omim.org/entry/105590 biolink:NamedThing|biolink:Gene ALK Anaplastic Lymphoma Kinase omim.nt ANAPLASTIC LYMPHOMA KINASE; ALK|Alk/Cars Fusion Gene|Alk/Cltc Fusion Gene|Alk/Eml4 Fusion Gene|Alk/Npm1 Fusion Gene|Alk/Rnf213 Fusion Gene owl:Class ClinVar:RCV000019709 biolink:NamedThing omim.nt ClinVar:RCV000423720 biolink:NamedThing omim.nt ClinVar:RCV000432041 biolink:NamedThing omim.nt ClinVar:RCV000440978 biolink:NamedThing omim.nt ClinVar:RCV001268655 biolink:NamedThing omim.nt dbSNP:rs113994087 biolink:NamedThing omim.nt owl:NamedIndividual http://omim.org/entry/105590#0001 biolink:NamedThing omim.nt http://omim.org/entry/105590.0002 biolink:NamedThing ALK, GLY1128ALA In a large 3-generation pedigree segregating familial neuroblastoma ({613014}), {14:Mosse et al. (2008)} identified a G-to-C transversion at nucleotide 3383 in the ALK gene, resulting in a glycine-to-alanine substitution at codon 1128 (G1128A). Five individuals with the mutation developed neuroblastoma, but several carriers did not, indicating incomplete penetrance. This mutation occurred in the P loop of the protein and was considered to have 95% probability of being an activating mutation. This mutation was not identified in 218 normal control alleles. omim.nt GENO:0000002 ClinVar:RCV000019710 biolink:NamedThing omim.nt ClinVar:RCV000421391 biolink:NamedThing omim.nt ClinVar:RCV000438595 biolink:NamedThing omim.nt dbSNP:rs113994088 biolink:NamedThing omim.nt owl:NamedIndividual http://omim.org/entry/105590#0002 biolink:NamedThing omim.nt http://omim.org/entry/105590.0003 biolink:NamedThing ALK, ARG1192PRO In 2 families segregating neuroblastoma ({613014}), {14:Mosse et al. (2008)} identified a G-to-C transversion at nucleotide 3575 of the ALK gene, resulting in an arginine-to-proline substitution at codon 1192 (R1192P). This mutation manifested incomplete penetrance. The mutation occurred in the beta-4 strand of the protein and was predicted with 96% probability to be an activating mutation. The mutation was not identified in 218 control chromosomes. {9:Janoueix-Lerosey et al. (2008)} independently identified a family segregating neuroblastoma and carrying the R1192P allele. In this 3-generation pedigree, the grandmother was unaffected. The daughter developed a ganglioneuroblastoma at 12 years of age, and 2 grandchildren developed stage 4 neuroblastomas at 3 and 4 months of age, respectively. In addition to the grandmother, the parents of the affected grandchildren were also unaffected. {2:Bourdeaut et al. (2012)} identified a heterozygous germline R1192P mutation in a child who developed neuroblastoma at age 6 months and later developed multiple ganglioneuromas in various places up to age 6 years. The mutation was found in all tumors tested. However, this germline mutation was also found in 3 unaffected family members, including the patient's mother, indicating incomplete penetrance. omim.nt GENO:0000002 ClinVar:RCV000019711 biolink:NamedThing omim.nt ClinVar:RCV000422453 biolink:NamedThing omim.nt ClinVar:RCV000427890 biolink:NamedThing omim.nt dbSNP:rs113994089 biolink:NamedThing omim.nt owl:NamedIndividual http://omim.org/entry/105590#0003 biolink:NamedThing omim.nt http://omim.org/entry/105590.0004 biolink:NamedThing ALK, THR1151MET In a patient with neuroblastoma ({613014}), {8:George et al. (2008)} identified a 3452C-T transition in the ALK gene, resulting in a threonine-to-methionine substitution at codon 1151 (T1151M) in the kinase domain of ALK. omim.nt GENO:0000002 ClinVar:RCV000019712 biolink:NamedThing omim.nt ClinVar:RCV000439097 biolink:NamedThing omim.nt ClinVar:RCV001020341 biolink:NamedThing omim.nt dbSNP:rs113994091 biolink:NamedThing omim.nt owl:NamedIndividual http://omim.org/entry/105590#0004 biolink:NamedThing omim.nt MONARCH:.well-known/genid/b281f063d821597eaa00 biolink:NamedThing GRCh38chr2-29190991-29921588-Region omim.nt MONARCH:.well-known/genid/b846431fd000feadc6ca faldo:Region PMID:12112524 biolink:NamedThing omim.nt IAO:0000013 PMID:14523446 biolink:NamedThing omim.nt IAO:0000013 PMID:14523447 biolink:NamedThing omim.nt IAO:0000013 PMID:17111047 biolink:NamedThing omim.nt IAO:0000013 PMID:17625570 biolink:NamedThing omim.nt IAO:0000013 PMID:17922009 biolink:NamedThing omim.nt IAO:0000013 PMID:18469826 biolink:NamedThing omim.nt IAO:0000013 PMID:18724359 biolink:NamedThing omim.nt IAO:0000013 PMID:18923523 biolink:NamedThing omim.nt IAO:0000013 PMID:18923524 biolink:NamedThing omim.nt IAO:0000013 PMID:18923525 biolink:NamedThing omim.nt IAO:0000013 PMID:20971950 biolink:NamedThing omim.nt IAO:0000013 PMID:20979473 biolink:NamedThing omim.nt IAO:0000013 PMID:22071890 biolink:NamedThing omim.nt IAO:0000013 PMID:23360421 biolink:NamedThing omim.nt IAO:0000013 PMID:25337876 biolink:NamedThing omim.nt IAO:0000013 PMID:26444240 biolink:NamedThing omim.nt IAO:0000013 PMID:7736780 biolink:NamedThing omim.nt IAO:0000013 PMID:8122112 biolink:NamedThing omim.nt IAO:0000013 PMID:9490693 biolink:NamedThing omim.nt IAO:0000013 http://omim.org/entry/613014 biolink:NamedThing|biolink:Disease Neuroblastoma, Susceptibility To, 3 Neuroblastoma, Susceptibility To, 3 omim.nt NEUROBLASTOMA, SUSCEPTIBILITY TO, 3; NBLST3 owl:Class OBO:CHR_9606chr2p23 biolink:NamedThing omim.nt owl:Class UMLS:C1332080 biolink:NamedThing omim.nt owl:Class UMLS:C3151472 biolink:NamedThing omim.nt owl:Class UMLS:C3151473 biolink:NamedThing omim.nt owl:Class UMLS:C3151474 biolink:NamedThing omim.nt owl:Class https://www.ncbi.nlm.nih.gov/gene/238 biolink:NamedThing omim.nt http://omim.org/entry/105600 biolink:NamedThing|biolink:Disease Anemia, Congenital Dyserythropoietic, Type 3 Anemia, Congenital Dyserythropoietic, Type 3 omim.nt ANEMIA, CONGENITAL DYSERYTHROPOIETIC, TYPE III; CDAN3|Anemia With Multinucleated Erythroblasts|Cda 3|Dyserythropoietic Anemia, Congenital, Type 3|Erythroreticulosis, Hereditary Benign owl:Class MONARCH:.well-known/genid/OMIM105600ref3 biolink:NamedThing Dyserythropoiese congenitale: etude de 6 observations. omim.nt IAO:0000310 MONARCH:.well-known/genid/OMIM105600ref5 biolink:NamedThing Personal Communication. omim.nt IAO:0000310 MONARCH:.well-known/genid/OMIM105600ref8 biolink:NamedThing The locus for congenital dyserythropoietic anemia type III (CDA III), associated with monoclonal gammopathy and myeloma, is localized on chromosome 15q21. (Abstract) omim.nt IAO:0000310 PMID:13867810 biolink:NamedThing omim.nt IAO:0000013 PMID:14458656 biolink:NamedThing omim.nt IAO:0000013 PMID:14886400 biolink:NamedThing omim.nt IAO:0000013 PMID:3345287 biolink:NamedThing omim.nt IAO:0000013 PMID:4432872 biolink:NamedThing omim.nt IAO:0000013 PMID:5045964 biolink:NamedThing omim.nt IAO:0000013 PMID:6182166 biolink:NamedThing omim.nt IAO:0000013 PMID:638061 biolink:NamedThing omim.nt IAO:0000013 PMID:7711721 biolink:NamedThing omim.nt IAO:0000013 PMID:8299769 biolink:NamedThing omim.nt IAO:0000013 PMID:8500603 biolink:NamedThing omim.nt IAO:0000013 UMLS:C0271934 biolink:NamedThing omim.nt owl:Class ORPHA:98870 biolink:NamedThing|biolink:Disease omim.nt owl:Class http://www.omim.org/phenotypicSeries/PS224120 biolink:NamedThing|biolink:Disease Anemia, congenital dyserythropoietic omim.nt owl:Class http://omim.org/entry/105650 biolink:NamedThing|biolink:Disease Diamond-Blackfan Anemia 1 Diamond-Blackfan Anemia 1 omim.nt DIAMOND-BLACKFAN ANEMIA 1; DBA1|Aase-Smith Syndrome 2|Aase Syndrome|Anemia, Congenital Erythroid Hypoplastic|Anemia, Congenital Hypoplastic, of Blackfan and Diamond|Aregenerative Anemia, Chronic Congenital|Blackfan-Diamond Syndrome|Dba|Erythrogenesis Imperfecta|Red Cell Aplasia, Pure, Hereditary owl:Class MONARCH:.well-known/genid/OMIM105650ref14 biolink:NamedThing Hypoplastic anemia. omim.nt IAO:0000310 MONARCH:.well-known/genid/OMIM105650ref41 biolink:NamedThing Anaemia of infancy and early childhood. omim.nt IAO:0000310 MONARCH:.well-known/genid/OMIM105650ref57 biolink:NamedThing Congenital hypoplastic anemia of Blackfan and Diamond in sibs. omim.nt IAO:0000310 PMID:10192448 biolink:NamedThing omim.nt IAO:0000013 PMID:10541318 biolink:NamedThing omim.nt IAO:0000013 PMID:10590074 biolink:NamedThing omim.nt IAO:0000013 PMID:11264183 biolink:NamedThing omim.nt IAO:0000013 PMID:12406103 biolink:NamedThing omim.nt IAO:0000013 PMID:1282827 biolink:NamedThing omim.nt IAO:0000013 PMID:13079761 biolink:NamedThing omim.nt IAO:0000013 PMID:13111217 biolink:NamedThing omim.nt IAO:0000013 PMID:13155070 biolink:NamedThing omim.nt IAO:0000013 PMID:13368831 biolink:NamedThing omim.nt IAO:0000013 PMID:13400593 biolink:NamedThing omim.nt IAO:0000013 PMID:13722603 biolink:NamedThing omim.nt IAO:0000013 PMID:13958671 biolink:NamedThing omim.nt IAO:0000013 PMID:14616996 biolink:NamedThing omim.nt IAO:0000013 PMID:14790824 biolink:NamedThing omim.nt IAO:0000013 PMID:16741228 biolink:NamedThing omim.nt IAO:0000013 PMID:16990592 biolink:NamedThing omim.nt IAO:0000013 PMID:1718487 biolink:NamedThing omim.nt IAO:0000013 PMID:1718488 biolink:NamedThing omim.nt IAO:0000013 PMID:1718489 biolink:NamedThing omim.nt IAO:0000013 PMID:1718490 biolink:NamedThing omim.nt IAO:0000013 PMID:17186470 biolink:NamedThing omim.nt IAO:0000013 PMID:1746615 biolink:NamedThing omim.nt IAO:0000013 PMID:19061985 biolink:NamedThing omim.nt IAO:0000013 PMID:19208100 biolink:NamedThing omim.nt IAO:0000013 PMID:1958491 biolink:NamedThing omim.nt IAO:0000013 PMID:20252731 biolink:NamedThing omim.nt IAO:0000013 PMID:20960466 biolink:NamedThing omim.nt IAO:0000013 PMID:22431104 biolink:NamedThing omim.nt IAO:0000013 PMID:2309764 biolink:NamedThing omim.nt IAO:0000013 PMID:23718193 biolink:NamedThing omim.nt IAO:0000013 PMID:23812780 biolink:NamedThing omim.nt IAO:0000013 PMID:25424902 biolink:NamedThing omim.nt IAO:0000013 PMID:2694854 biolink:NamedThing omim.nt IAO:0000013 PMID:273451 biolink:NamedThing omim.nt IAO:0000013 PMID:276838 biolink:NamedThing omim.nt IAO:0000013 PMID:29364875 biolink:NamedThing omim.nt IAO:0000013 PMID:3732321 biolink:NamedThing omim.nt IAO:0000013 PMID:4432558 biolink:NamedThing omim.nt IAO:0000013 PMID:4445826 biolink:NamedThing omim.nt IAO:0000013 PMID:4742263 biolink:NamedThing omim.nt IAO:0000013 PMID:4818099 biolink:NamedThing omim.nt IAO:0000013 PMID:5025485 biolink:NamedThing omim.nt IAO:0000013 PMID:5042496 biolink:NamedThing omim.nt IAO:0000013 PMID:5086730 biolink:NamedThing omim.nt IAO:0000013 PMID:5356983 biolink:NamedThing omim.nt IAO:0000013 PMID:6150395 biolink:NamedThing omim.nt IAO:0000013 PMID:6178949 biolink:NamedThing omim.nt IAO:0000013 PMID:621285 biolink:NamedThing omim.nt IAO:0000013 PMID:660362 biolink:NamedThing omim.nt IAO:0000013 PMID:6865981 biolink:NamedThing omim.nt IAO:0000013 PMID:714597 biolink:NamedThing omim.nt IAO:0000013 PMID:745221 biolink:NamedThing omim.nt IAO:0000013 PMID:747771 biolink:NamedThing omim.nt IAO:0000013 PMID:7684626 biolink:NamedThing omim.nt IAO:0000013 PMID:8160759 biolink:NamedThing omim.nt IAO:0000013 PMID:8630424 biolink:NamedThing omim.nt IAO:0000013 PMID:8734811 biolink:NamedThing omim.nt IAO:0000013 PMID:8826887 biolink:NamedThing omim.nt IAO:0000013 PMID:909014 biolink:NamedThing omim.nt IAO:0000013 PMID:9241274 biolink:NamedThing omim.nt IAO:0000013 PMID:9321770 biolink:NamedThing omim.nt IAO:0000013 PMID:9792865 biolink:NamedThing omim.nt IAO:0000013 PMID:986086 biolink:NamedThing omim.nt IAO:0000013 PMID:9988267 biolink:NamedThing omim.nt IAO:0000013 UMLS:C2676137 biolink:NamedThing omim.nt owl:Class ORPHA:124 biolink:NamedThing|biolink:Disease omim.nt owl:Class http://www.omim.org/phenotypicSeries/PS105650 biolink:NamedThing|biolink:Disease Diamond-Blackfan anemia omim.nt owl:Class http://omim.org/entry/105800 biolink:NamedThing|biolink:Disease Aneurysm, Intracranial Berry, 1 Aneurysm, Intracranial Berry, 1 omim.nt ANEURYSM, INTRACRANIAL BERRY, 1; ANIB1|Aneurysmal Subarachnoid Hemorrhage, Familial owl:Class MONARCH:.well-known/genid/OMIM105800ref22 biolink:NamedThing Intracranial aneurysm and heredity. (Letter) omim.nt IAO:0000310 PMID:10470812 biolink:NamedThing omim.nt IAO:0000013 PMID:10536126 biolink:NamedThing omim.nt IAO:0000013 PMID:11536080 biolink:NamedThing omim.nt IAO:0000013 PMID:12750963 biolink:NamedThing omim.nt IAO:0000013 PMID:13840303 biolink:NamedThing omim.nt IAO:0000013 PMID:14512962 biolink:NamedThing omim.nt IAO:0000013 PMID:14605871 biolink:NamedThing omim.nt IAO:0000013 PMID:16611674 biolink:NamedThing omim.nt IAO:0000013 PMID:16736093 biolink:NamedThing omim.nt IAO:0000013 PMID:19237697 biolink:NamedThing omim.nt IAO:0000013 PMID:20364137 biolink:NamedThing omim.nt IAO:0000013 PMID:22286173 biolink:NamedThing omim.nt IAO:0000013 PMID:4643949 biolink:NamedThing omim.nt IAO:0000013 PMID:4649154 biolink:NamedThing omim.nt IAO:0000013 PMID:4673261 biolink:NamedThing omim.nt IAO:0000013 PMID:5069384 biolink:NamedThing omim.nt IAO:0000013 PMID:5090946 biolink:NamedThing omim.nt IAO:0000013 PMID:5418178 biolink:NamedThing omim.nt IAO:0000013 PMID:5461057 biolink:NamedThing omim.nt IAO:0000013 PMID:5576485 biolink:NamedThing omim.nt IAO:0000013 PMID:5684401 biolink:NamedThing omim.nt IAO:0000013 PMID:5901575 biolink:NamedThing omim.nt IAO:0000013 PMID:5921322 biolink:NamedThing omim.nt IAO:0000013 PMID:6646412 biolink:NamedThing omim.nt IAO:0000013 PMID:6859129 biolink:NamedThing omim.nt IAO:0000013 PMID:697608 biolink:NamedThing omim.nt IAO:0000013 PMID:7666217 biolink:NamedThing omim.nt IAO:0000013 PMID:7762046 biolink:NamedThing omim.nt IAO:0000013 PMID:8042229 biolink:NamedThing omim.nt IAO:0000013 PMID:8091449 biolink:NamedThing omim.nt IAO:0000013 PMID:8264874 biolink:NamedThing omim.nt IAO:0000013 PMID:845628 biolink:NamedThing omim.nt IAO:0000013 PMID:8526466 biolink:NamedThing omim.nt IAO:0000013 PMID:8559290 biolink:NamedThing omim.nt IAO:0000013 PMID:9398980 biolink:NamedThing omim.nt IAO:0000013 UMLS:C1862932 biolink:NamedThing omim.nt owl:Class ORPHA:231160 biolink:NamedThing|biolink:Disease omim.nt owl:Class http://www.omim.org/phenotypicSeries/PS105800 biolink:NamedThing|biolink:Disease Aneurysm, intracranial berry omim.nt owl:Class http://omim.org/entry/105805 biolink:NamedThing|biolink:Disease Aneurysm of Interventricular Septum omim.nt ANEURYSM OF INTERVENTRICULAR SEPTUM owl:Class PMID:1867942 biolink:NamedThing omim.nt IAO:0000013 PMID:3360529 biolink:NamedThing omim.nt IAO:0000013 PMID:3394619 biolink:NamedThing omim.nt IAO:0000013 UMLS:C1387721 biolink:NamedThing omim.nt owl:Class ORPHA:99092 biolink:NamedThing|biolink:Disease omim.nt owl:Class http://omim.org/entry/105830 biolink:NamedThing|biolink:Disease Angelman Syndrome Angelman Syndrome omim.nt ANGELMAN SYNDROME; AS|Angelman Syndrome Chromosome Region|Happy Puppet Syndrome, Formerly owl:Class MONARCH:.well-known/genid/OMIM105830ref124 biolink:NamedThing Incidence of 15q deletions in the Angelman syndrome: a survey of 14 affected persons. (Abstract) omim.nt IAO:0000310 MONARCH:.well-known/genid/OMIM105830ref31 biolink:NamedThing Ocular and genetic findings in Angelman's syndrome. (Abstract) omim.nt IAO:0000310 MONARCH:.well-known/genid/OMIM105830ref32 biolink:NamedThing Two siblings with Angelman's 'happy puppet' syndrome. (Abstract) omim.nt IAO:0000310 MONARCH:.well-known/genid/OMIM105830ref4 biolink:NamedThing 'Puppet children': a report of three cases. omim.nt IAO:0000310 MONARCH:.well-known/genid/OMIM105830ref48 biolink:NamedThing Prader-Willi and Angelman syndromes in one kindred with expression consistent with genetic imprinting. (Abstract) omim.nt IAO:0000310 MONARCH:.well-known/genid/OMIM105830ref78 biolink:NamedThing Angelman happy puppet and Prader Willi syndromes: do they share an identical deletion? (Abstract) omim.nt IAO:0000310 MONARCH:.well-known/genid/OMIM105830ref80 biolink:NamedThing Molecular genetic studies of Angelman's syndrome. (Abstract) omim.nt IAO:0000310 MONARCH:.well-known/genid/OMIM105830ref94 biolink:NamedThing The association of Angelman syndrome and deletions within 15q11-13. (Abstract) omim.nt IAO:0000310 PMID:10196695 biolink:NamedThing omim.nt IAO:0000013 PMID:10417280 biolink:NamedThing omim.nt IAO:0000013 PMID:10482951 biolink:NamedThing omim.nt IAO:0000013 PMID:10861661 biolink:NamedThing omim.nt IAO:0000013 PMID:10982040 biolink:NamedThing omim.nt IAO:0000013 PMID:11078565 biolink:NamedThing omim.nt IAO:0000013 PMID:11258627 biolink:NamedThing omim.nt IAO:0000013 PMID:11283796 biolink:NamedThing omim.nt IAO:0000013 PMID:11343340 biolink:NamedThing omim.nt IAO:0000013 PMID:11748306 biolink:NamedThing omim.nt IAO:0000013 PMID:11896453 biolink:NamedThing omim.nt IAO:0000013 PMID:11977186 biolink:NamedThing omim.nt IAO:0000013 PMID:12016591 biolink:NamedThing omim.nt IAO:0000013 PMID:12210318 biolink:NamedThing omim.nt IAO:0000013 PMID:12376950 biolink:NamedThing omim.nt IAO:0000013 PMID:12549484 biolink:NamedThing omim.nt IAO:0000013 PMID:12668608 biolink:NamedThing omim.nt IAO:0000013 PMID:1303278 biolink:NamedThing omim.nt IAO:0000013 PMID:1338769 biolink:NamedThing omim.nt IAO:0000013 PMID:1357962 biolink:NamedThing omim.nt IAO:0000013 PMID:1360768 biolink:NamedThing omim.nt IAO:0000013 PMID:1362220 biolink:NamedThing omim.nt IAO:0000013 PMID:1363801 biolink:NamedThing omim.nt IAO:0000013 PMID:1486699 biolink:NamedThing omim.nt IAO:0000013 PMID:15150776 biolink:NamedThing omim.nt IAO:0000013 PMID:1519953 biolink:NamedThing omim.nt IAO:0000013 PMID:15385437 biolink:NamedThing omim.nt IAO:0000013 PMID:15470370 biolink:NamedThing omim.nt IAO:0000013 PMID:15805153 biolink:NamedThing omim.nt IAO:0000013 PMID:1598916 biolink:NamedThing omim.nt IAO:0000013 PMID:1619637 biolink:NamedThing omim.nt IAO:0000013 PMID:16401744 biolink:NamedThing omim.nt IAO:0000013 PMID:16470747 biolink:NamedThing omim.nt IAO:0000013 PMID:1672177 biolink:NamedThing omim.nt IAO:0000013 PMID:1679180 biolink:NamedThing omim.nt IAO:0000013 PMID:1683160 biolink:NamedThing omim.nt IAO:0000013 PMID:17152063 biolink:NamedThing omim.nt IAO:0000013 PMID:1740313 biolink:NamedThing omim.nt IAO:0000013 PMID:18627066 biolink:NamedThing omim.nt IAO:0000013 PMID:1867202 biolink:NamedThing omim.nt IAO:0000013 PMID:18701717 biolink:NamedThing omim.nt IAO:0000013 PMID:19455185 biolink:NamedThing omim.nt IAO:0000013 PMID:1971993 biolink:NamedThing omim.nt IAO:0000013 PMID:1985457 biolink:NamedThing omim.nt IAO:0000013 PMID:20034088 biolink:NamedThing omim.nt IAO:0000013 PMID:2012134 biolink:NamedThing omim.nt IAO:0000013 PMID:2035528 biolink:NamedThing omim.nt IAO:0000013 PMID:21204213 biolink:NamedThing omim.nt IAO:0000013 PMID:21596294 biolink:NamedThing omim.nt IAO:0000013 PMID:21844811 biolink:NamedThing omim.nt IAO:0000013 PMID:22190039 biolink:NamedThing omim.nt IAO:0000013 PMID:2309778 biolink:NamedThing omim.nt IAO:0000013 PMID:2309780 biolink:NamedThing omim.nt IAO:0000013 PMID:2309781 biolink:NamedThing omim.nt IAO:0000013 PMID:2325111 biolink:NamedThing omim.nt IAO:0000013 PMID:2466440 biolink:NamedThing omim.nt IAO:0000013 PMID:25428759 biolink:NamedThing omim.nt IAO:0000013 PMID:25470045 biolink:NamedThing omim.nt IAO:0000013 PMID:2564739 biolink:NamedThing omim.nt IAO:0000013 PMID:2729353 biolink:NamedThing omim.nt IAO:0000013 PMID:2769727 biolink:NamedThing omim.nt IAO:0000013 PMID:2774001 biolink:NamedThing omim.nt IAO:0000013 PMID:2893543 biolink:NamedThing omim.nt IAO:0000013 PMID:2918545 biolink:NamedThing omim.nt IAO:0000013 PMID:3063533 biolink:NamedThing omim.nt IAO:0000013 PMID:3198109 biolink:NamedThing omim.nt IAO:0000013 PMID:33087932 biolink:NamedThing omim.nt IAO:0000013 PMID:3321989 biolink:NamedThing omim.nt IAO:0000013 PMID:3409926 biolink:NamedThing omim.nt IAO:0000013 PMID:3585943 biolink:NamedThing omim.nt IAO:0000013 PMID:3608219 biolink:NamedThing omim.nt IAO:0000013 PMID:3674117 biolink:NamedThing omim.nt IAO:0000013 PMID:3688021 biolink:NamedThing omim.nt IAO:0000013 PMID:4000278 biolink:NamedThing omim.nt IAO:0000013 PMID:4740440 biolink:NamedThing omim.nt IAO:0000013 PMID:5010558 biolink:NamedThing omim.nt IAO:0000013 PMID:6025370 biolink:NamedThing omim.nt IAO:0000013 PMID:7091188 biolink:NamedThing omim.nt IAO:0000013 PMID:7180875 biolink:NamedThing omim.nt IAO:0000013 PMID:7192492 biolink:NamedThing omim.nt IAO:0000013 PMID:7246489 biolink:NamedThing omim.nt IAO:0000013 PMID:7319144 biolink:NamedThing omim.nt IAO:0000013 PMID:7450780 biolink:NamedThing omim.nt IAO:0000013 PMID:7625442 biolink:NamedThing omim.nt IAO:0000013 PMID:7677166 biolink:NamedThing omim.nt IAO:0000013 PMID:7684188 biolink:NamedThing omim.nt IAO:0000013 PMID:7795645 biolink:NamedThing omim.nt IAO:0000013 PMID:7802001 biolink:NamedThing omim.nt IAO:0000013 PMID:7905534 biolink:NamedThing omim.nt IAO:0000013 PMID:7987324 biolink:NamedThing omim.nt IAO:0000013 PMID:8093396 biolink:NamedThing omim.nt IAO:0000013 PMID:8103288 biolink:NamedThing omim.nt IAO:0000013 PMID:8178815 biolink:NamedThing omim.nt IAO:0000013 PMID:8317476 biolink:NamedThing omim.nt IAO:0000013 PMID:8352279 biolink:NamedThing omim.nt IAO:0000013 PMID:8362910 biolink:NamedThing omim.nt IAO:0000013 PMID:8364575 biolink:NamedThing omim.nt IAO:0000013 PMID:8456836 biolink:NamedThing omim.nt IAO:0000013 PMID:8494033 biolink:NamedThing omim.nt IAO:0000013 PMID:8499948 biolink:NamedThing omim.nt IAO:0000013 PMID:8576558 biolink:NamedThing omim.nt IAO:0000013 PMID:8644742 biolink:NamedThing omim.nt IAO:0000013 PMID:8651269 biolink:NamedThing omim.nt IAO:0000013 PMID:8786067 biolink:NamedThing omim.nt IAO:0000013 PMID:8929945 biolink:NamedThing omim.nt IAO:0000013 PMID:8988171 biolink:NamedThing omim.nt IAO:0000013 PMID:8988172 biolink:NamedThing omim.nt IAO:0000013 PMID:9042916 biolink:NamedThing omim.nt IAO:0000013 PMID:9182785 biolink:NamedThing omim.nt IAO:0000013 PMID:9195990 biolink:NamedThing omim.nt IAO:0000013 PMID:9245988 biolink:NamedThing omim.nt IAO:0000013 PMID:9321755 biolink:NamedThing omim.nt IAO:0000013 PMID:9546330 biolink:NamedThing omim.nt IAO:0000013 PMID:9556704 biolink:NamedThing omim.nt IAO:0000013 PMID:9557895 biolink:NamedThing omim.nt IAO:0000013 PMID:955942 biolink:NamedThing omim.nt IAO:0000013 PMID:960285 biolink:NamedThing omim.nt IAO:0000013 PMID:9634532 biolink:NamedThing omim.nt IAO:0000013 PMID:9808466 biolink:NamedThing omim.nt IAO:0000013 PMID:9831341 biolink:NamedThing omim.nt IAO:0000013 PMID:9949213 biolink:NamedThing omim.nt IAO:0000013 PMID:9973277 biolink:NamedThing omim.nt IAO:0000013 UMLS:C0162635 biolink:NamedThing omim.nt owl:Class UMLS:C1412397 biolink:NamedThing omim.nt owl:Class ORPHA:72 biolink:NamedThing|biolink:Disease omim.nt owl:Class http://omim.org/entry/105835 biolink:NamedThing|biolink:Disease Angel-Shaped Phalangoepiphyseal Dysplasia omim.nt ANGEL-SHAPED PHALANGOEPIPHYSEAL DYSPLASIA; ASPED owl:Class PMID:6018472 biolink:NamedThing omim.nt IAO:0000013 PMID:8267010 biolink:NamedThing omim.nt IAO:0000013 UMLS:C1739384 biolink:NamedThing omim.nt owl:Class ORPHA:63442 biolink:NamedThing|biolink:Disease omim.nt owl:Class http://omim.org/entry/105850.0001 biolink:NamedThing ANG, GLN12LEU In a Scottish patient and an Irish/Scottish patient with amyotrophic lateral sclerosis (ALS9; {611895}), {6:Greenway et al. (2006)} identified a heterozygous 107A-T transversion in the ANG gene, resulting in a gln12-to-leu (Q12L) substitution. There were no other affected members of the family. omim.nt GENO:0000002 http://omim.org/entry/105850 biolink:NamedThing|biolink:Gene ANG Angiogenin|proximal to TCRA/TCRD omim.nt ANGIOGENIN; ANG|Ribonuclease a Family, 5 owl:Class ClinVar:RCV000019699 biolink:NamedThing omim.nt dbSNP:rs121909535 biolink:NamedThing omim.nt owl:NamedIndividual http://omim.org/entry/105850#0001 biolink:NamedThing omim.nt http://omim.org/entry/105850.0002 biolink:NamedThing ANG, LYS17ILE In an Irish and an Irish/Scottish patient with amyotrophic lateral sclerosis (ALS9; {611895}), {6:Greenway et al. (2006)} identified a heterozygous 122A-T transversion in the ANG gene, resulting in a lys17-to-ile (K17I) substitution. Both patients had onset at 53 years with involvement of the limbs. A common haplotype was observed across the ANG locus and flanking region in these individuals, indicative of a founder effect. The K17I mutation was also found in an apparently healthy 65-year-old male of European descent. {20:Wu et al. (2007)} identified heterozygosity for the K17I mutation in a North American patient with ALS. In vitro functional expression studies showed that the mutant protein had less than 5% residual ribonucleolytic activity and complete loss of angiogenic function. {17:Van Es et al. (2009)} reported a 4-generation family in which ALS segregated with the K17I mutation. Affected individuals had classic signs of the disorder, but 1 patient presented with parkinsonism and later developed signs of frontotemporal dementia. One obligate carrier did not develop the disease by age 75, indicating incomplete penetrance. {11:Millecamps et al. (2010)} identified the K17I mutation in 2 (0.6%) of 162 French probands with familial ALS. Both showed dominant inheritance. However, 1 of the K17I carriers was also found to carry a heterozygous mutation in the FUS gene (R521C; {137070.0004}), which causes ALS6 ({608030}). omim.nt GENO:0000002 ClinVar:RCV000019700 biolink:NamedThing omim.nt ClinVar:RCV000517735 biolink:NamedThing omim.nt dbSNP:rs121909536 biolink:NamedThing omim.nt owl:NamedIndividual http://omim.org/entry/105850#0002 biolink:NamedThing omim.nt http://omim.org/entry/105850.0003 biolink:NamedThing ANG, LYS17GLU In an individual of Swedish ethnicity and 1 of northern Irish ethnicity with amyotrophic lateral sclerosis (ALS9; {611895}), {6:Greenway et al. (2006)} identified a heterozygous 121A-G transition in the ANG gene, resulting in a lys17-to-glu (K17E) substitution. The individuals shared a unique haplotype for the K17E mutation. omim.nt GENO:0000002 ClinVar:RCV000019701 biolink:NamedThing omim.nt dbSNP:rs121909537 biolink:NamedThing omim.nt owl:NamedIndividual http://omim.org/entry/105850#0003 biolink:NamedThing omim.nt http://omim.org/entry/105850.0004 biolink:NamedThing ANG, ARG31LYS In an individual of Irish/English descent with a sporadic case of amyotrophic lateral sclerosis (ALS9; {611895}), {6:Greenway et al. (2006)} identified a heterozygous 164G-A transition in the ANG gene, resulting in an arg31-to-lys (R31K) substitution. omim.nt GENO:0000002 ClinVar:RCV000019702 biolink:NamedThing omim.nt dbSNP:rs121909538 biolink:NamedThing omim.nt owl:NamedIndividual http://omim.org/entry/105850#0004 biolink:NamedThing omim.nt http://omim.org/entry/105850.0005 biolink:NamedThing ANG, CYS39TRP {6:Greenway et al. (2006)} identified heterozygosity for a 189C-G transversion in the ANG gene, resulting in a cys39-to-trp (C39W) substitution, in 2 familial cases of amyotrophic lateral sclerosis (ALS9; {611895}) with European ethnicity. In each case 3 members of the family were affected. omim.nt GENO:0000002 ClinVar:RCV000019703 biolink:NamedThing omim.nt dbSNP:rs121909539 biolink:NamedThing omim.nt owl:NamedIndividual http://omim.org/entry/105850#0005 biolink:NamedThing omim.nt http://omim.org/entry/105850.0006 biolink:NamedThing ANG, LYS40ILE In 3 individuals with amyotrophic lateral sclerosis (ALS9; {611895}), 2 Irish and 1 Scottish, {6:Greenway et al. (2006)} identified a heterozygous 191A-T transversion in the ANG gene, resulting in a lys40-to-ile (K40I) substitution. omim.nt GENO:0000002 ClinVar:RCV000019704 biolink:NamedThing omim.nt dbSNP:rs121909540 biolink:NamedThing omim.nt owl:NamedIndividual http://omim.org/entry/105850#0006 biolink:NamedThing omim.nt http://omim.org/entry/105850.0007 biolink:NamedThing ANG, ILE46VAL In 3 Scottish individuals with amyotrophic lateral sclerosis (ALS9; {611895}), {6:Greenway et al. (2006)} identified a heterozygous 208A-G transition in the ANG gene, resulting in an ile46-to-val (I46V) substitution. Two of the cases were familial. {4:Gellera et al. (2008)} identified the I46V mutation in 6 Italian ALS patients and 4 controls (0.8% in both groups), suggesting that it is a rare polymorphism in the Italian population. {12:Paubel et al. (2008)} identified the I46V mutation in 2 of 855 French patients with sporadic ALS. The mutation was found in 0.2% of healthy controls. omim.nt GENO:0000002 ClinVar:RCV000019705 biolink:NamedThing omim.nt ClinVar:RCV000335176 biolink:NamedThing omim.nt dbSNP:rs121909541 biolink:NamedThing omim.nt owl:NamedIndividual http://omim.org/entry/105850#0007 biolink:NamedThing omim.nt http://omim.org/entry/105850.0008 biolink:NamedThing ANG, SER28ASN In a North American patient with amyotrophic lateral sclerosis (ALS9; {611895}), {20:Wu et al. (2007)} identified a heterozygous G-to-A transition in the ANG gene, resulting in a ser28-to-asn (S28N) substitution adjacent to the nuclear localization sequence of the protein. In vitro functional expression studies showed that the mutant protein had 9% residual ribonucleolytic activity with complete loss of angiogenic function. The mutant protein was unable to translocate to the nucleus. omim.nt GENO:0000002 ClinVar:RCV000019706 biolink:NamedThing omim.nt dbSNP:rs121909542 biolink:NamedThing omim.nt owl:NamedIndividual http://omim.org/entry/105850#0008 biolink:NamedThing omim.nt http://omim.org/entry/105850.0009 biolink:NamedThing ANG, PRO112LEU In a North American patient with amyotrophic lateral sclerosis (ALS9; {611895}), {20:Wu et al. (2007)} identified a heterozygous C-to-T transition in the ANG gene, resulting in a pro112-to-leu (P112L) substitution. In vitro functional expression studies showed that the mutant protein had 14% residual ribonucleolytic activity with complete loss of angiogenic function. The mutant protein was unable to translocate to the nucleus. omim.nt GENO:0000002 ClinVar:RCV000019707 biolink:NamedThing omim.nt dbSNP:rs121909543 biolink:NamedThing omim.nt owl:NamedIndividual http://omim.org/entry/105850#0009 biolink:NamedThing omim.nt http://omim.org/entry/105850.0010 biolink:NamedThing ANG, VAL113ILE In 2 Italian sibs and their mother with amyotrophic lateral sclerosis (ALS9; {611895}), {4:Gellera et al. (2008)} identified a heterozygous 409G-A transition in the ANG gene, resulting in a val113-to-ile (V113I) substitution. The mutation was also identified in an unrelated patient with sporadic ALS who had a predominantly upper motor neuron phenotype. The mutation was not identified in 515 control individuals. omim.nt GENO:0000002 ClinVar:RCV000019708 biolink:NamedThing omim.nt dbSNP:rs121909544 biolink:NamedThing omim.nt owl:NamedIndividual http://omim.org/entry/105850#0010 biolink:NamedThing omim.nt MONARCH:.well-known/genid/bc4b10a1a30e92d8309d biolink:NamedThing GRCh38chr14-20684176-20694185-Region omim.nt MONARCH:.well-known/genid/b3c7a3a69090016aed04 faldo:Region MONARCH:.well-known/genid/OMIM105850ref19 biolink:NamedThing Assignment of human angiogenin gene to chromosome 14q11-q13. (Abstract) omim.nt IAO:0000310 PMID:10371543 biolink:NamedThing omim.nt IAO:0000013 PMID:12548285 biolink:NamedThing omim.nt IAO:0000013 PMID:12847526 biolink:NamedThing omim.nt IAO:0000013 PMID:1346389 biolink:NamedThing omim.nt IAO:0000013 PMID:15557516 biolink:NamedThing omim.nt IAO:0000013 PMID:16501576 biolink:NamedThing omim.nt IAO:0000013 PMID:17886298 biolink:NamedThing omim.nt IAO:0000013 PMID:17900154 biolink:NamedThing omim.nt IAO:0000013 PMID:17916583 biolink:NamedThing omim.nt IAO:0000013 PMID:17991437 biolink:NamedThing omim.nt IAO:0000013 PMID:18087731 biolink:NamedThing omim.nt IAO:0000013 PMID:18852347 biolink:NamedThing omim.nt IAO:0000013 PMID:19153377 biolink:NamedThing omim.nt IAO:0000013 PMID:1978563 biolink:NamedThing omim.nt IAO:0000013 PMID:2866794 biolink:NamedThing omim.nt IAO:0000013 PMID:2866795 biolink:NamedThing omim.nt IAO:0000013 PMID:3619929 biolink:NamedThing omim.nt IAO:0000013 PMID:8530072 biolink:NamedThing omim.nt IAO:0000013 OBO:CHR_9606chr14q11.2 biolink:NamedThing omim.nt owl:Class http://omim.org/entry/611895 biolink:NamedThing|biolink:Disease Amyotrophic Lateral Sclerosis 9 Amyotrophic Lateral Sclerosis 9 omim.nt AMYOTROPHIC LATERAL SCLEROSIS 9; ALS9 owl:Class UMLS:C1367482 biolink:NamedThing omim.nt owl:Class https://www.ncbi.nlm.nih.gov/gene/283 biolink:NamedThing omim.nt http://omim.org/entry/106050 biolink:NamedThing|biolink:Disease Angioma Serpiginosum, Autosomal Dominant omim.nt ANGIOMA SERPIGINOSUM, AUTOSOMAL DOMINANT owl:Class MONARCH:.well-known/genid/OMIM106050ref5 biolink:NamedThing A peculiar form of serpiginous and infective naevoid disease. omim.nt IAO:0000310 PMID:1220816 biolink:NamedThing omim.nt IAO:0000013 PMID:12657019 biolink:NamedThing omim.nt IAO:0000013 PMID:15649209 biolink:NamedThing omim.nt IAO:0000013 PMID:17033175 biolink:NamedThing omim.nt IAO:0000013 PMID:17342156 biolink:NamedThing omim.nt IAO:0000013 PMID:7451703 biolink:NamedThing omim.nt IAO:0000013 PMID:8567268 biolink:NamedThing omim.nt IAO:0000013 UMLS:C1970130 biolink:NamedThing omim.nt owl:Class ORPHA:95429 biolink:NamedThing|biolink:Disease omim.nt owl:Class http://omim.org/entry/106070 biolink:NamedThing|biolink:Disease Angioma, Hereditary Neurocutaneous Angioma, Hereditary Neurocutaneous omim.nt ANGIOMA, HEREDITARY NEUROCUTANEOUS|Hemangiomatosis, Disseminated|Spinal Arterial Venous Malformations With Cutaneous Hemangiomas owl:Class PMID:14186663 biolink:NamedThing omim.nt IAO:0000013 PMID:3342546 biolink:NamedThing omim.nt IAO:0000013 PMID:537017 biolink:NamedThing omim.nt IAO:0000013 PMID:7189031 biolink:NamedThing omim.nt IAO:0000013 PMID:7191526 biolink:NamedThing omim.nt IAO:0000013 PMID:998575 biolink:NamedThing omim.nt IAO:0000013 UMLS:C1275084 biolink:NamedThing omim.nt owl:Class UMLS:C1862897 biolink:NamedThing omim.nt owl:Class UMLS:C1862898 biolink:NamedThing omim.nt owl:Class ORPHA:1062 biolink:NamedThing|biolink:Disease omim.nt owl:Class http://omim.org/entry/106100 biolink:NamedThing|biolink:Disease Angioedema, Hereditary, Type 1 Angioedema, Hereditary, Type 1 omim.nt ANGIOEDEMA, HEREDITARY, TYPE I; HAE1|Angioedema, Hereditary, Type 2|Angioneurotic Edema, Hereditary|C1 Esterase Inhibitor, Deficiency of owl:Class MONARCH:.well-known/genid/OMIM106100ref10 biolink:NamedThing Hereditary angioedema. Complex symptoms can make diagnosis difficult. omim.nt IAO:0000310 MONARCH:.well-known/genid/OMIM106100ref15 biolink:NamedThing Reply to Giavina-Bianchi et al. (Letter) omim.nt IAO:0000310 MONARCH:.well-known/genid/OMIM106100ref48 biolink:NamedThing Reply to Wuillemin. (Letter) omim.nt IAO:0000310 MONARCH:.well-known/genid/OMIM106100ref51 biolink:NamedThing Hereditary angioneurotic edema: linkage study in a Norwegian kindred. (Abstract) omim.nt IAO:0000310 MONARCH:.well-known/genid/OMIM106100ref52 biolink:NamedThing Hereditary angio-neurotic oedema. omim.nt IAO:0000310 MONARCH:.well-known/genid/OMIM106100ref56 biolink:NamedThing Concerning the acute localized oedema of the skin. omim.nt IAO:0000310 MONARCH:.well-known/genid/OMIM106100ref62 biolink:NamedThing Hereditary angioedema: a decade of management with stanozolol. omim.nt IAO:0000310 MONARCH:.well-known/genid/OMIM106100ref65 biolink:NamedThing Methyltestosterone therapy for hereditary episodic edema (hereditary angioneurotic edema). omim.nt IAO:0000310 MONARCH:.well-known/genid/OMIM106100ref68 biolink:NamedThing Regional chromosomal assignment of the human C1 inhibitor gene to 11q11-q13.1. (Abstract) omim.nt IAO:0000310 MONARCH:.well-known/genid/OMIM106100ref76 biolink:NamedThing Genetically determined disorders of the complement system. In: Scriver, C. R.; Beaudet, A. L.; Sly, W. S.; Valle, D. (eds.): The Metabolic Basis of Inherited Disease. Vol. II. (6th ed.) omim.nt IAO:0000310 MONARCH:.well-known/genid/OMIM106100ref83 biolink:NamedThing Reply to Wuillemin. (Letter) omim.nt IAO:0000310 PMID:11161971 biolink:NamedThing omim.nt IAO:0000013 PMID:11700154 biolink:NamedThing omim.nt IAO:0000013 PMID:1333923 biolink:NamedThing omim.nt IAO:0000013 PMID:13484317 biolink:NamedThing omim.nt IAO:0000013 PMID:13694388 biolink:NamedThing omim.nt IAO:0000013 PMID:13778063 biolink:NamedThing omim.nt IAO:0000013 PMID:14046003 biolink:NamedThing omim.nt IAO:0000013 PMID:14223932 biolink:NamedThing omim.nt IAO:0000013 PMID:14257837 biolink:NamedThing omim.nt IAO:0000013 PMID:14277836 biolink:NamedThing omim.nt IAO:0000013 PMID:14461961 biolink:NamedThing omim.nt IAO:0000013 PMID:1518394 biolink:NamedThing omim.nt IAO:0000013 PMID:16813612 biolink:NamedThing omim.nt IAO:0000013 PMID:17137866 biolink:NamedThing omim.nt IAO:0000013 PMID:17502473 biolink:NamedThing omim.nt IAO:0000013 PMID:18768946 biolink:NamedThing omim.nt IAO:0000013 PMID:20818886 biolink:NamedThing omim.nt IAO:0000013 PMID:20818887 biolink:NamedThing omim.nt IAO:0000013 PMID:20818888 biolink:NamedThing omim.nt IAO:0000013 PMID:20818894 biolink:NamedThing omim.nt IAO:0000013 PMID:21208116 biolink:NamedThing omim.nt IAO:0000013 PMID:21208117 biolink:NamedThing omim.nt IAO:0000013 PMID:2296585 biolink:NamedThing omim.nt IAO:0000013 PMID:2323781 biolink:NamedThing omim.nt IAO:0000013 PMID:23688413 biolink:NamedThing omim.nt IAO:0000013 PMID:2454251 biolink:NamedThing omim.nt IAO:0000013 PMID:2687589 biolink:NamedThing omim.nt IAO:0000013 PMID:2723063 biolink:NamedThing omim.nt IAO:0000013 PMID:2895279 biolink:NamedThing omim.nt IAO:0000013 PMID:292793 biolink:NamedThing omim.nt IAO:0000013 PMID:294325 biolink:NamedThing omim.nt IAO:0000013 PMID:29640127 biolink:NamedThing omim.nt IAO:0000013 PMID:30480729 biolink:NamedThing omim.nt IAO:0000013 PMID:3056508 biolink:NamedThing omim.nt IAO:0000013 PMID:3494945 biolink:NamedThing omim.nt IAO:0000013 PMID:3534579 biolink:NamedThing omim.nt IAO:0000013 PMID:3584502 biolink:NamedThing omim.nt IAO:0000013 PMID:3587308 biolink:NamedThing omim.nt IAO:0000013 PMID:3653633 biolink:NamedThing omim.nt IAO:0000013 PMID:3734104 biolink:NamedThing omim.nt IAO:0000013 PMID:3818946 biolink:NamedThing omim.nt IAO:0000013 PMID:4107267 biolink:NamedThing omim.nt IAO:0000013 PMID:4128807 biolink:NamedThing omim.nt IAO:0000013 PMID:4179348 biolink:NamedThing omim.nt IAO:0000013 PMID:4207178 biolink:NamedThing omim.nt IAO:0000013 PMID:4393526 biolink:NamedThing omim.nt IAO:0000013 PMID:449665 biolink:NamedThing omim.nt IAO:0000013 PMID:4551861 biolink:NamedThing omim.nt IAO:0000013 PMID:4558045 biolink:NamedThing omim.nt IAO:0000013 PMID:4935379 biolink:NamedThing omim.nt IAO:0000013 PMID:6354379 biolink:NamedThing omim.nt IAO:0000013 PMID:6405274 biolink:NamedThing omim.nt IAO:0000013 PMID:6702887 biolink:NamedThing omim.nt IAO:0000013 PMID:6727934 biolink:NamedThing omim.nt IAO:0000013 PMID:676240 biolink:NamedThing omim.nt IAO:0000013 PMID:6781937 biolink:NamedThing omim.nt IAO:0000013 PMID:6794961 biolink:NamedThing omim.nt IAO:0000013 PMID:6824488 biolink:NamedThing omim.nt IAO:0000013 PMID:6833491 biolink:NamedThing omim.nt IAO:0000013 PMID:7091182 biolink:NamedThing omim.nt IAO:0000013 PMID:712188 biolink:NamedThing omim.nt IAO:0000013 PMID:7165360 biolink:NamedThing omim.nt IAO:0000013 PMID:7351888 biolink:NamedThing omim.nt IAO:0000013 PMID:7352788 biolink:NamedThing omim.nt IAO:0000013 PMID:7359956 biolink:NamedThing omim.nt IAO:0000013 PMID:7618673 biolink:NamedThing omim.nt IAO:0000013 PMID:792688 biolink:NamedThing omim.nt IAO:0000013 PMID:8105195 biolink:NamedThing omim.nt IAO:0000013 PMID:8450054 biolink:NamedThing omim.nt IAO:0000013 PMID:8628358 biolink:NamedThing omim.nt IAO:0000013 PMID:8628365 biolink:NamedThing omim.nt IAO:0000013 PMID:8755917 biolink:NamedThing omim.nt IAO:0000013 UMLS:C0019243 biolink:NamedThing omim.nt owl:Class UMLS:C1862892 biolink:NamedThing omim.nt owl:Class UMLS:C2717906 biolink:NamedThing omim.nt owl:Class ORPHA:100050 biolink:NamedThing|biolink:Disease omim.nt owl:Class ORPHA:100051 biolink:NamedThing|biolink:Disease omim.nt owl:Class ORPHA:91378 biolink:NamedThing|biolink:Disease omim.nt owl:Class http://omim.org/entry/106150.0001 biolink:NamedThing AGT, MET235THR By 3 sets of observations, i.e., genetic linkage, allelic associations, and differences in plasma angiotensinogen concentrations among AGT genotypes, in a sample of families from 2 different populations, Salt Lake City and Paris, {31:Jeunemaitre et al. (1992)} demonstrated involvement of the AGT gene in essential hypertension. Hypertension showed association with 2 distinct amino acid substitutions, M235T and T174M. The 2 variants showed complete linkage disequilibrium; T174M occurred on a subset of the haplotypes carrying the M235T variant, and both haplotypes were observed at higher frequency among hypertensives. Whether M235T directly mediates a predisposition to hypertension, or an unidentified risk factor is common to both haplotypes, or each haplotype harbors a distinct factor is uncertain. {39:Lifton et al. (1993)} found the M235T variant to be very frequent among African Americans who as a group have a high prevalence of hypertension. The frequency of T235 homozygotes was 70%, with 28% for T235 heterozygotes and only 2% for M235 homozygotes; the corresponding figures were 12%, 46%, and 42% in Caucasians. {39:Lifton et al. (1993)} suggested that the T235 allele may have been the ancestral form, and, in an earlier period of salt scarcity, increased salt and water retention associated with T235 may have been an advantage. After the Diaspora from Africa to salt-rich areas, M235 may have become fixed or had some advantage. {53:Russ et al. (1993)} described a rapid method for detection of the M235T polymorphism. It is well known that blood pressure increases faster over time in black children than in white children and that in adults, hypertension is more prevalent in blacks. In a study of 148 white and 62 black normotensive children, {5:Bloem et al. (1995)} found that the frequency of the T235 allele was 0.81 in blacks and 0.42 in whites. The mean angiotensinogen level was 19% higher in blacks than in whites. This racial difference in the renin-angiotensin system may contribute to the disparity in blood pressure levels in white and black young people. In Rochester, Minnesota, {12:Fornage et al. (1995)} studied a population-based sample consisting of 104 subjects diagnosed with hypertension before age 60 and 195 matched normotensive individuals to determine the relationship between M235T and essential hypertension. The authors used 2 methods: contingency chi-square analysis of association and a multivariable conditional logistic regression for variation at the M235T polymorphism as a significant predictor of the probability of having essential hypertension. They detected no statistically significant association in either gender or in a subset of severely hypertensive subjects requiring 2 or more antihypertensive medications. Furthermore, variation in the number of M235T alleles made no significant contribution to predicting the probability of having hypertension, either alone or in conjunction with other predictor variables. See also {50:Niu et al. (1998)}. {14:Frossard et al. (1998)} studied the association between the M235T and T174M variants in residents of the United Arab Emirates (Emirati), an ethnic group characterized by no alcohol intake and no cigarette smoking. T174M showed no correlation with any of the 4 clinical entities included in the study (essential hypertension, left ventricular hypertrophy, ischemic heart disease, and myocardial infarction), but the T235 allele occurred more frequently in the essential hypertension group and less frequently in the group of myocardial infarction survivors. They also found that the T235 allele frequencies decreased with age, suggesting that in the Emirati population, T235 alleles are associated with a reduced life span. Preeclampsia Susceptibility In a series of Caucasian women with pregnancy-induced hypertension, {62:Ward et al. (1993)} observed significant association of preeclampsia (see {189800}) with the M235T variant. The finding was corroborated in a sample ascertained in Japan. {3:Arngrimsson et al. (1993)} studied involvement of the ATG gene in preeclampsia and eclampsia by linkage studies with a highly informative dinucleotide repeat from the 3-prime flanking region of the ATG gene. They used a nonparametric method, i.e., one in which the mode of inheritance, gene frequency, and penetrance did not have to be specified. Their results supported the findings of {62:Ward et al. (1993)}. In a study of 150 'coloured' South African patients, 50 with normal pregnancies, 50 with severe preeclampsia, and 50 with abruptio placentae, {24:Hillermann et al. (2005)} found no association between the M235T variant of the AGT gene and preeclampsia or abruptio placentae. Progression to Renal Failure in IgA Nephropathy Studying the met235-to-thr polymorphism of the AGT gene in 168 Caucasian patients with IgA nephropathy ({161950}), {52:Pei et al. (1997)} found that patients with the AGT MT (79) and TT (29) genotypes had a faster rate of deterioration of creatinine clearance than those with the MM (60) genotype. Similarly, patients with AGT MT and TT genotypes had higher maximal values of proteinuria than those with the MM genotype. Multivariant analysis detected an interaction between the AGT and ACE gene polymorphisms, with the presence of ACE/DD polymorphism ({106180.0001}) adversely affecting disease progression only in patients with the AGT/MM genotype. Neither of these gene polymorphisms was associated with systemic hypertension. Thus, {52:Pei et al. (1997)} suggested that polymorphisms at the AGT and ACE gene loci are important markers for predicting progression to chronic renal failure in Caucasian patients with IgA nephropathy. omim.nt GENO:0000002 http://omim.org/entry/106150 biolink:NamedThing|biolink:Gene AGT Angiotensinogen omim.nt ANGIOTENSINOGEN; AGT|Angiotensin 1|Angiotensin 2|Iga Nephropathy, Progression to Renal Failure In, Susceptibility to|Serpina8 owl:Class ClinVar:RCV000019691 biolink:NamedThing omim.nt ClinVar:RCV000019692 biolink:NamedThing omim.nt ClinVar:RCV000019693 biolink:NamedThing omim.nt ClinVar:RCV000242838 biolink:NamedThing omim.nt ClinVar:RCV000405686 biolink:NamedThing omim.nt ClinVar:RCV000835695 biolink:NamedThing omim.nt dbSNP:rs699 biolink:NamedThing omim.nt owl:NamedIndividual http://omim.org/entry/106150#0001 biolink:NamedThing omim.nt http://omim.org/entry/106150.0002 biolink:NamedThing AGT, -6A HAPLOTYPE {27:Inoue et al. (1997)} found that a common variant in the proximal promoter of the ATG gene, an adenine instead of a guanine 6 bp upstream from the site of transcription initiation (-6G-A), is in very tight linkage disequilibrium with T235 ({106150.0001}) and marks the original form of the gene. Tests of promoter function in cultured cells and studies of binding between AGT oligonucleotides and nuclear proteins strongly suggested that the substitution at nucleotide -6 affects specific interactions between at least 1 trans-acting nuclear factor and the promoter of AGT, thereby influencing the basal rate of transcription of the gene. These observations suggested a biologic mechanism by which individual differences in the AGT gene may predispose carriers to the development of essential hypertension. They also suggested an evolutionary scenario to account for the emergence of common human disorders, which may fit the 'thrifty genotype' hypothesis advanced by {49:Neel (1962)}. See {48:Neel et al. (1998)} for an update on this hypothesis. The geographic distribution of the A allele of the -6G-A polymorphism in the AGT gene leads to the hypothesis that the G allele has been selectively advantageous outside Africa. To test this hypothesis, {47:Nakajima et al. (2004)} investigated the roles of population history and natural selection in shaping patterns of genetic diversity in AGT by sequencing the entire AGT gene (14,400 bp) in 736 chromosomes from Africa, Asia, and Europe. They found that the A allele was present at higher frequency in African populations than in non-African populations. Neutrality tests found no evidence of a departure from selective neutrality, when whole AGT sequences were compared. However, tests restricted to sites in the vicinity of the -6G-A polymorphism found evidence of a selective sweep. Sliding window analyses showed that evidence of the sweep was restricted to sites in tight linkage disequilibrium with the -6G-A polymorphism. Furthermore, haplotypes carrying the G allele showed elevated levels of linkage disequilibrium, suggesting that they have risen to high frequency relatively recently (the G allele was estimated to have arisen 22,500 to 44,500 years ago). Departures from neutral expectation in some but not all regions of AGT indicated that patterns of diversity in the gene cannot be accounted for solely by population history, which would affect all regions equally. Taken together, patterns of genetic diversity in AGT suggested that natural selection has generally favored the G allele over the A allele in non-African populations. In a study of 2 cohorts of Australian patients with inflammatory bowel disease (see {266600}) and age- and sex-matched controls, {26:Hume et al. (2006)} found that the AGT -6 A/A genotype was significantly associated with Crohn disease in 1 cohort and in the 2 cohorts combined (p = 0.007 and p = 0.008, respectively). TDT analysis of 148 Crohn families showed moderately significant overtransmission of the variant A allele (p = 0.03). {30:Jain et al. (2010)} presented evidence that the SNP at -6 of the AGT gene is a haplotype marker rather than a functional polymorphism. They identified 3 additional SNPs in the promoter region of the AGT gene at positions -1670, -1562, and -1561. Variants -1670A, -1562C, and -1561T almost always occurred with -6A and were designated the -6A haplotype, and variants -1670G, -1562G, and -1561G almost always occurred with -6G and were designated -6G haplotype. Chromatin immunoprecipitation analysis showed that both HNF1-alpha (HNF1A; {142410}) and glucocorticoid receptor (GR, or GCCR; {138040}) had higher affinity for the -6A haplotype than the -6G haplotype. Within the -6A haplotype, HNF1-alpha preferentially bound sequence around -1670A, and GR preferentially bound sequence containing -1562C and -1561T. An intact HNF1 site was required for GR-induced promoter activity in vitro. {30:Jain et al. (2010)} engineered transgenic mice expressing human BACs covering 116 kb of the 5-prime flanking region of the AGT gene of either haplotype, plus all 5 exons and 4 introns and 54 kb of the 3-prime flanking region. Mice expressing the human AGT gene of the -6A haplotype showed increased plasma AGT levels and increased blood pressure compared with mice expressing the -6G haplotype. omim.nt GENO:0000002 ClinVar:RCV000019694 biolink:NamedThing omim.nt ClinVar:RCV000019695 biolink:NamedThing omim.nt http://omim.org/entry/106150#0002 biolink:NamedThing omim.nt http://omim.org/entry/106150.0003 biolink:NamedThing AGT, ARG375GLN In a consanguineous family of Turkish derivation with renal tubular dysgenesis (RTD; {267430}), {17:Gribouval et al. (2005)} found an arg375-to-gln (R375Q) mutation in the AGT gene. The nucleotide substitution, 1124G-A, involved the last nucleotide of exon 3. There were 2 affected sisters in this family reported by {35:Kemper et al. (2001)}. One sister survived after several days of anuria; she had severe and persistent hypotension at birth, requiring fluid infusion, adrenaline, and dopamine treatment. The other sister, who died at 4 days of life, also had very low blood pressure. omim.nt GENO:0000002 ClinVar:RCV000019696 biolink:NamedThing omim.nt dbSNP:rs74315283 biolink:NamedThing omim.nt owl:NamedIndividual http://omim.org/entry/106150#0003 biolink:NamedThing omim.nt http://omim.org/entry/106150.0004 biolink:NamedThing AGT, GLU202TER In a Japanese female infant with renal tubular dysgenesis (RTD; {267430}), {60:Uematsu et al. (2006)} identified compound heterozygosity for 2 mutations in the AGT gene: a 604C-T transition in exon 2, resulting in a glu202-to-ter (E202X) substitution, and a 1-bp deletion (1290delT; {106150.0005}) in exon 5, resulting in a frameshift and a premature stop codon at position 454. The patient was born at 35 weeks' gestation with Potter syndrome, hypoplastic lungs, and severe hypotension. Treatment with fresh frozen plasma and peritoneal dialysis resulted in clinical improvement and she had spontaneous urination at day 29. At age 18 months, she had no obvious motor or mental retardation. An older brother with similar features had died a few days after birth. {18:Gribouval et al. (2012)} stated that the frameshift and premature stop caused by the 1290delT mutation was Phe430LeufsTer25. omim.nt GENO:0000002 ClinVar:RCV000019697 biolink:NamedThing omim.nt dbSNP:rs121912702 biolink:NamedThing omim.nt owl:NamedIndividual http://omim.org/entry/106150#0004 biolink:NamedThing omim.nt http://omim.org/entry/106150.0005 biolink:NamedThing AGT, 1-BP DEL, 1290T For discussion of the 1-bp deletion (1290delT) in the AGT gene that was found in compound heterozygous state in a Japanese female infant with renal tubular dysgenesis (RTD; {267430}) by {60:Uematsu et al. (2006)}, see {106150.0004}. omim.nt GENO:0000002 ClinVar:RCV000019698 biolink:NamedThing omim.nt dbSNP:rs387906578 biolink:NamedThing omim.nt owl:NamedIndividual http://omim.org/entry/106150#0005 biolink:NamedThing omim.nt MONARCH:.well-known/genid/b0c522a4d1460df3600b biolink:NamedThing GRCh38chr1-230702522-230745582-Region omim.nt MONARCH:.well-known/genid/b44dca2d78ac59fdc338 faldo:Region MONARCH:.well-known/genid/OMIM106150ref25 biolink:NamedThing Hutterite Society. omim.nt IAO:0000310 MONARCH:.well-known/genid/OMIM106150ref29 biolink:NamedThing Regional chromosomal localization of the human angiotensinogen gene to 1q4.42-4.43 band. (Abstract) omim.nt IAO:0000310 MONARCH:.well-known/genid/OMIM106150ref39 biolink:NamedThing High prevalence of hypertension-associated angiotensinogen variant T235 in African Americans. (Abstract) omim.nt IAO:0000310 PMID:10528248 biolink:NamedThing omim.nt IAO:0000013 PMID:10585456 biolink:NamedThing omim.nt IAO:0000013 PMID:10738541 biolink:NamedThing omim.nt IAO:0000013 PMID:11095476 biolink:NamedThing omim.nt IAO:0000013 PMID:11096065 biolink:NamedThing omim.nt IAO:0000013 PMID:11731937 biolink:NamedThing omim.nt IAO:0000013 PMID:11770813 biolink:NamedThing omim.nt IAO:0000013 PMID:11829142 biolink:NamedThing omim.nt IAO:0000013 PMID:11904385 biolink:NamedThing omim.nt IAO:0000013 PMID:12399452 biolink:NamedThing omim.nt IAO:0000013 PMID:12404103 biolink:NamedThing omim.nt IAO:0000013 PMID:12915681 biolink:NamedThing omim.nt IAO:0000013 PMID:13428291 biolink:NamedThing omim.nt IAO:0000013 PMID:13937884 biolink:NamedThing omim.nt IAO:0000013 PMID:1394429 biolink:NamedThing omim.nt IAO:0000013 PMID:14216273 biolink:NamedThing omim.nt IAO:0000013 PMID:15023884 biolink:NamedThing omim.nt IAO:0000013 PMID:15077204 biolink:NamedThing omim.nt IAO:0000013 PMID:15652490 biolink:NamedThing omim.nt IAO:0000013 PMID:16041383 biolink:NamedThing omim.nt IAO:0000013 PMID:16059745 biolink:NamedThing omim.nt IAO:0000013 PMID:16116425 biolink:NamedThing omim.nt IAO:0000013 PMID:16138193 biolink:NamedThing omim.nt IAO:0000013 PMID:16210856 biolink:NamedThing omim.nt IAO:0000013 PMID:16293694 biolink:NamedThing omim.nt IAO:0000013 PMID:16352906 biolink:NamedThing omim.nt IAO:0000013 PMID:17036344 biolink:NamedThing omim.nt IAO:0000013 PMID:17047091 biolink:NamedThing omim.nt IAO:0000013 PMID:18025526 biolink:NamedThing omim.nt IAO:0000013 PMID:20927107 biolink:NamedThing omim.nt IAO:0000013 PMID:20978123 biolink:NamedThing omim.nt IAO:0000013 PMID:22095942 biolink:NamedThing omim.nt IAO:0000013 PMID:2286380 biolink:NamedThing omim.nt IAO:0000013 PMID:2407641 biolink:NamedThing omim.nt IAO:0000013 PMID:2924688 biolink:NamedThing omim.nt IAO:0000013 PMID:3034901 biolink:NamedThing omim.nt IAO:0000013 PMID:4300938 biolink:NamedThing omim.nt IAO:0000013 PMID:6089875 biolink:NamedThing omim.nt IAO:0000013 PMID:6572971 biolink:NamedThing omim.nt IAO:0000013 PMID:7635961 biolink:NamedThing omim.nt IAO:0000013 PMID:7649545 biolink:NamedThing omim.nt IAO:0000013 PMID:7783537 biolink:NamedThing omim.nt IAO:0000013 PMID:7883995 biolink:NamedThing omim.nt IAO:0000013 PMID:7955175 biolink:NamedThing omim.nt IAO:0000013 PMID:7989296 biolink:NamedThing omim.nt IAO:0000013 PMID:8132767 biolink:NamedThing omim.nt IAO:0000013 PMID:8177268 biolink:NamedThing omim.nt IAO:0000013 PMID:8252633 biolink:NamedThing omim.nt IAO:0000013 PMID:8348146 biolink:NamedThing omim.nt IAO:0000013 PMID:8513325 biolink:NamedThing omim.nt IAO:0000013 PMID:8518804 biolink:NamedThing omim.nt IAO:0000013 PMID:8567057 biolink:NamedThing omim.nt IAO:0000013 PMID:9077534 biolink:NamedThing omim.nt IAO:0000013 PMID:9120002 biolink:NamedThing omim.nt IAO:0000013 PMID:9120024 biolink:NamedThing omim.nt IAO:0000013 PMID:9259580 biolink:NamedThing omim.nt IAO:0000013 PMID:9421481 biolink:NamedThing omim.nt IAO:0000013 PMID:9814470 biolink:NamedThing omim.nt IAO:0000013 PMID:9831339 biolink:NamedThing omim.nt IAO:0000013 PMID:9894356 biolink:NamedThing omim.nt IAO:0000013 http://omim.org/entry/267430 biolink:NamedThing|biolink:Disease Renal Tubular Dysgenesis Renal Tubular Dysgenesis omim.nt RENAL TUBULAR DYSGENESIS; RTD|Primitive Renal Tubule Syndrome|Renal Tubular Dysgenesis With Choanal Atresia and Athelia owl:Class UMLS:C1366631 biolink:NamedThing omim.nt owl:Class UMLS:C1862886 biolink:NamedThing omim.nt owl:Class https://www.ncbi.nlm.nih.gov/gene/183 biolink:NamedThing omim.nt http://omim.org/entry/106160 biolink:NamedThing omim.nt True owl:Class http://omim.org/entry/106165 biolink:NamedThing|biolink:Gene AGTR1 Angiotensin Receptor 1 omim.nt ANGIOTENSIN RECEPTOR 1; AGTR1|Angiotensin 2 Receptor, Vascular Type 1|Angiotensin Receptor 1A|Angiotensin Receptor 1B|At1R owl:Class http://omim.org/entry/106165.0001 biolink:NamedThing AGTR1, 1166A-C, 3-PRIME UTR ({dbSNP rs5186}) Variants in the human AGTR1A gene may affect blood pressure. {5:Bonnardeaux et al. (1994)} identified an association between several AGTR1A gene polymorphisms and hypertension ({145500}). Specifically, an A-to-C variant in the 3-prime UTR at nucleotide 1166 (cDNA numbering from the ATG start codon) showed a significantly elevated frequency in 206 Caucasian patients with essential hypertension. {43:Wang et al. (1997)} did a case-control study of the 1166A-C variant in 108 Caucasian hypertensive patients with a strong family history (2 affected parents) and early onset disease. The frequency of the 1166C allele was 0.40 in hypertensives and 0.29 in normotensives. {20:Kobashi et al. (2004)} genotyped 114 Japanese patients with severe hypertension in pregnancy (HP) and 291 normal pregnancy controls. Among primiparous patients, the frequency of the AC and CC genotypes at nucleotide 1166 of the AGTR1 gene was significantly higher in severe HP than in the controls. A multivariate analysis with the AC and CC genotypes at nucleotide 1166 of the AGTR1 gene and TT genotype at codon 235 of the AGT gene ({106150.0001}) revealed that these were independently associated with primiparous severe HP. Animal miRNAs regulate gene expression through base pairing to their targets within the 3-prime untranslated region (UTR) of protein-coding genes. Single-nucleotide polymorphisms (SNPs) located within such target sites can affect miRNA regulation. {38:Sethupathy et al. (2007)} mapped annotated SNPs onto a collection of experimentally supported human miRNA targets. Of the 143 experimentally supported human target sites, 9 contained 12 SNPs. They further experimentally investigated one of these target sites for miR155 (see {609337}), that within the 3-prime UTR of the human AGTR1 gene, which contains SNP {dbSNP rs5186}. Using reporter silencing assays, they showed that miR155 downregulates the expression only of the 1166A, and not the 1166C, allele of {dbSNP rs5186}. Since the 1166C allele has been associated with hypertension in many studies, the 1166C allele may be functionally associated with hypertension by abrogating regulation by miR155, thereby elevating AGTR1 levels. Since miR155 is on chromosome 21, {38:Sethupathy et al. (2007)} hypothesized that the observed lower blood pressure in trisomy 21 is partially caused by the overexpression of miR155 leading to allele-specific underexpression of AGTR1. Indeed, they showed in fibroblasts from monozygotic twins discordant for trisomy 21 that levels of AGTR1 protein are lower in trisomy 21. omim.nt GENO:0000002 ClinVar:RCV000019688 biolink:NamedThing omim.nt ClinVar:RCV000374969 biolink:NamedThing omim.nt dbSNP:rs5186 biolink:NamedThing omim.nt owl:NamedIndividual http://omim.org/entry/106165#0001 biolink:NamedThing omim.nt http://omim.org/entry/106165.0003 biolink:NamedThing AGTR1, 1-BP INS, 110T In 2 sibs with renal tubular dysgenesis ({267430}) from a nonconsanguineous family, {11:Gribouval et al. (2005)} found compound heterozygosity for 2 mutations in the AGTR1 gene. The mutation inherited from the heterozygous mother, who was of Slovenian derivation, was a 1-bp insertion, 110_111insT, resulting in a frameshift and a premature stop codon (Ile38HisfsTer37). The mutation inherited from the heterozygous father, who was of Italian ancestry, was an 845C-T transition in exon 4, resulting in a thr282-met (T282M; {106165.0004}) substitution. omim.nt GENO:0000002 ClinVar:RCV000019689 biolink:NamedThing omim.nt dbSNP:rs387906577 biolink:NamedThing omim.nt owl:NamedIndividual http://omim.org/entry/106165#0003 biolink:NamedThing omim.nt http://omim.org/entry/106165.0004 biolink:NamedThing AGTR1, THR282MET For discussion of the thr282-to-met (T282M) mutation in the AGTR1 gene that was found in compound heterozygous state in patients with renal tubular dysgenesis ({267430}) by {11:Gribouval et al. (2005)}, see {106165.0003}. omim.nt GENO:0000002 ClinVar:RCV000019690 biolink:NamedThing omim.nt dbSNP:rs104893677 biolink:NamedThing omim.nt owl:NamedIndividual http://omim.org/entry/106165#0004 biolink:NamedThing omim.nt http://omim.org/entry/106165.0005 biolink:NamedThing AGTR1, TRP84TER In a North African girl, born of consanguineous parents, with renal tubular dysgenesis ({267430}) resulting in stillbirth, {12:Gribouval et al. (2012)} identified a homozygous 251G-A transition in exon 3 of the AGTR1 gene, resulting in a trp84-to-ter (W84X) substitution. omim.nt GENO:0000002 ClinVar:RCV000043468 biolink:NamedThing omim.nt dbSNP:rs398122935 biolink:NamedThing omim.nt owl:NamedIndividual http://omim.org/entry/106165#0005 biolink:NamedThing omim.nt http://omim.org/entry/106165.0006 biolink:NamedThing AGTR1, ARG126TER In 2 Pakistani sibs, born of consanguineous parents, with renal tubular dysgenesis ({267430}), {12:Gribouval et al. (2012)} identified a homozygous 376C-T transition in exon 3 of the AGTR1 gene, resulting in an arg126-to-ter (R126X) substitution. Both infants died on the first day of life. omim.nt GENO:0000002 ClinVar:RCV000043469 biolink:NamedThing omim.nt dbSNP:rs397514687 biolink:NamedThing omim.nt owl:NamedIndividual http://omim.org/entry/106165#0006 biolink:NamedThing omim.nt MONARCH:.well-known/genid/bbb60ddf08ce481dae8b biolink:NamedThing GRCh38chr3-148697902-148743002-Region omim.nt MONARCH:.well-known/genid/b724f6d4e2a56207e429 faldo:Region MONARCH:.well-known/genid/OMIM106165ref37 biolink:NamedThing Personal Communication. omim.nt IAO:0000310 PMID:10194466 biolink:NamedThing omim.nt IAO:0000013 PMID:10639182 biolink:NamedThing omim.nt IAO:0000013 PMID:10993080 biolink:NamedThing omim.nt IAO:0000013 PMID:11158334 biolink:NamedThing omim.nt IAO:0000013 PMID:11877468 biolink:NamedThing omim.nt IAO:0000013 PMID:1378723 biolink:NamedThing omim.nt IAO:0000013 PMID:15042429 biolink:NamedThing omim.nt IAO:0000013 PMID:1508224 biolink:NamedThing omim.nt IAO:0000013 PMID:1543512 biolink:NamedThing omim.nt IAO:0000013 PMID:1550596 biolink:NamedThing omim.nt IAO:0000013 PMID:15507206 biolink:NamedThing omim.nt IAO:0000013 PMID:1567413 biolink:NamedThing omim.nt IAO:0000013 PMID:1575725 biolink:NamedThing omim.nt IAO:0000013 PMID:16007097 biolink:NamedThing omim.nt IAO:0000013 PMID:16675453 biolink:NamedThing omim.nt IAO:0000013 PMID:1683828 biolink:NamedThing omim.nt IAO:0000013 PMID:17090678 biolink:NamedThing omim.nt IAO:0000013 PMID:17588946 biolink:NamedThing omim.nt IAO:0000013 PMID:17607364 biolink:NamedThing omim.nt IAO:0000013 PMID:17668390 biolink:NamedThing omim.nt IAO:0000013 PMID:18464932 biolink:NamedThing omim.nt IAO:0000013 PMID:2041569 biolink:NamedThing omim.nt IAO:0000013 PMID:2041570 biolink:NamedThing omim.nt IAO:0000013 PMID:20558762 biolink:NamedThing omim.nt IAO:0000013 PMID:4050847 biolink:NamedThing omim.nt IAO:0000013 PMID:7724593 biolink:NamedThing omim.nt IAO:0000013 PMID:8021009 biolink:NamedThing omim.nt IAO:0000013 PMID:8135787 biolink:NamedThing omim.nt IAO:0000013 PMID:8166699 biolink:NamedThing omim.nt IAO:0000013 PMID:8227010 biolink:NamedThing omim.nt IAO:0000013 PMID:8227011 biolink:NamedThing omim.nt IAO:0000013 PMID:8254174 biolink:NamedThing omim.nt IAO:0000013 PMID:8567682 biolink:NamedThing omim.nt IAO:0000013 PMID:8790439 biolink:NamedThing omim.nt IAO:0000013 PMID:9054850 biolink:NamedThing omim.nt IAO:0000013 PMID:9084931 biolink:NamedThing omim.nt IAO:0000013 PMID:9207128 biolink:NamedThing omim.nt IAO:0000013 PMID:9466969 biolink:NamedThing omim.nt IAO:0000013 PMID:9468203 biolink:NamedThing omim.nt IAO:0000013 PMID:9482944 biolink:NamedThing omim.nt IAO:0000013 PMID:9860997 biolink:NamedThing omim.nt IAO:0000013 OBO:CHR_9606chr3q21 biolink:NamedThing omim.nt owl:Class UMLS:C1439284 biolink:NamedThing omim.nt owl:Class https://www.ncbi.nlm.nih.gov/gene/185 biolink:NamedThing omim.nt http://omim.org/entry/106180.0001 biolink:NamedThing ACE, INS/DEL ({dbSNP rs1799752}) {9:Cambien et al. (1992)} stated that the ACE enzyme plays a key role in the production of angiotensin I/I and in the catabolism of bradykinin, 2 peptides involved in the modulation of vascular tone and in the proliferation of smooth muscle cells. {8:Cambien et al. (1988)} showed that about 50% of the interindividual variability of plasma ACE concentration is determined by a major gene effect. {80:Soubrier et al. (1988)} cloned the ACE gene, and {84:Tiret et al. (1992)} demonstrated that this major gene effect is associated with an insertion (I)/deletion (D) polymorphism involving about 250 bp situated in intron 16 of the ACE gene, the so-called ACE/ID polymorphism. {69:Rigat et al. (1990)} found that the ACE/ID polymorphism was strongly associated with the level of circulating enzyme. The mean plasma ACE level of DD subjects was about twice that of II subjects, with ID subjects having intermediate levels. {70:Rigat et al. (1992)} determined that the ACE insertion corresponds to an Alu repetitive sequence and is 287 bp long. {36:Jeffery et al. (1999)} studied 97 Ghanaian individuals and found significantly lower ACE levels in those with the II genotype than in those with the ID or DD genotype, but no difference between the ID or DD groups. {36:Jeffery et al. (1999)} concluded that the D allele shows dominance rather than codominance relative to the I allele. Pharmacologic ACE inhibition enhances survival of human endothelial cells (ECs) by upregulating genes involved in cell growth, survival, and immortalization. {25:Hamdi and Castellon (2004)} found that human ECs with the II genotype showed enhanced growth, increased cell survival in culture after slow starvation, and reduced angiotensin II levels compared with ECs with the DD genotype. The ACE inhibitor captopril significantly enhanced the viability of DD cells, but it had little effect on II cells. {25:Hamdi and Castellon (2004)} concluded that ACE inhibitors protect DD cells by upregulating genes involved in cell survival and renewal. Association with Coronary Artery Disease and Myocardial Infarction Factors involved in the pathogenesis of atherosclerosis, thrombosis, and vasoconstriction contribute to the development of coronary heart disease. In a study comparing patients after myocardial infarction (MI) with controls, {9:Cambien et al. (1992)} found association between coronary heart disease and the ACE/ID polymorphism. They determined that the frequency of the ACE/DD genotype in the 'general population' is approximately 0.27. The ACE polymorphism was unrelated to blood pressure and hypertension. {9:Cambien et al. (1992)} estimated that in the low-risk group, i.e., those without tobacco usage, high blood pressure, diabetes, obesity, or hypercholesterolemia, the ACE/DD genotype may account for 35% of cases of myocardial infarction. The results of these studies correlate with those of {67:Pfeffer et al. (1992)}, which showed that administration of an ACE inhibitor not only decreased the risk of developing heart failure but also reduced the risk for recurrent myocardial infarction. Experimental studies had shown that ACE gene expression is increased in myocardial tissue after coronary artery occlusion. Among 185 male and 49 female survivors of myocardial infarction below 56 and 61 years of age, respectively, {5:Bohn et al. (1993)} failed to find results similar to those reported by {9:Cambien et al. (1992)}. They offered several possible explanations for the different results. {6:Bohn et al. (1993)} also studied the possible association between premature parental myocardial infarction (before age 61 in mothers and/or before age 56 years in fathers) and the I/D polymorphism in the ACE gene in 181 male and 48 female myocardial infarction survivors. In the total series, the frequency of premature parental MI was 14% in DD, 10.6% in ID, and 6.1% in II individuals. Thus, the ACE polymorphism may be an important genetic marker of MI risk and contribute to clustering of premature MI in families. {73:Schachter et al. (1994)} undertook a case-control study of 338 centenarians in comparison with adults aged 20 to 70 years. Surprisingly, they found that the DD genotype, which predisposes to coronary heart disease, has an increased frequency in centenarians. {71:Ruiz et al. (1994)} compared the frequency of the deletion polymorphism in 132 unrelated individuals with noninsulin-dependent diabetes mellitus (NIDDM; {125853}) who had had myocardial infarction or significant coronary stenoses and 184 NIDDM individuals with no history of coronary heart disease. They found that the D allele was a strong and independent risk factor for coronary heart disease in NIDDM patients. It was associated with early-onset coronary heart disease in NIDDM, independently of hypertension and lipid values. A progressively increasing relative risk was observed in individuals heterozygous and homozygous for the D allele, suggesting a codominant effect. The percentage of coronary heart disease attributable to the ACE deletion allele was 24% in this NIDDM population. {17:Evans et al. (1994)} determined the frequency of the ACE I/D polymorphism in 313 fatal cases of definite and possible myocardial infarction that came to autopsy in the Belfast, Northern Ireland area. In comparison to controls from the same population, the autopsy cases had an increased frequency of the ACE D allele (p less than 0.02). The overall odds ratios were 2.2 for DD versus II, and 1.8 for ID versus II. {53:Lindpaintner et al. (1995)} were unable to confirm the association between the D allele and increased risk of ischemic heart disease or myocardial infarction in a large, prospectively followed population of U.S. male physicians. In an angiographically defined study sample, {88:Winkelmann et al. (1996)} failed to find an association between ACE I/D gene polymorphism and coronary artery disease, although an effect on plasma ACE activity could be demonstrated. On the other hand, in a study of 388 white Italian patients of whom 255 had proven coronary atherosclerosis and 133 had angiographically normal coronary arteries, {3:Arbustini et al. (1995)} found that the deletion allele, whether homozygous or heterozygous, was the strongest risk factor for atherosclerosis, and that the D allele was significantly associated with the risk of infarction (although to a lesser extent than with permanent atherosclerosis). Hypertension proved to be unrelated with the ACE genotype. {64:Oike et al. (1995)} suggested that the DD genotype relates to a greater risk for myocardial infarction in patients with coronary artery spasm (CAS). This would explain the greater risk for myocardial infarction of persons with the D allele, especially persons normally considered to be at low risk. Coronary artery spasm is considered to be one mechanism for developing MI. {64:Oike et al. (1995)} studied 150 angiographically assessed Japanese males, all more than 60 years of age. Coronary artery spasm was detected using intracoronary injection of ergonovine maleate. The subjects were divided into 3 groups: those with CAS, those without CAS but with fixed organic stenosis, and those without CAS and no organic stenosis. DD subjects were significantly represented in group 1 when compared with groups 2 and 3. {63:Ohishi et al. (1993)} presented data indicating that the DD genotype is associated with an increased risk of restenosis after percutaneous transluminal angioplasty for widening the lumen of coronary arteries stenosed by atherosclerotic lesions. {2:Amant et al. (1997)} examined the relationship between the ACE I/D polymorphism and restenosis following coronary artery stenting in 146 consecutive patients. They found that restenosis was more than twice as common in those patients with the DD genotype than in those with the II genotype, possibly implicating the renin-angiotensin system in the pathogenesis of restenosis after coronary stenting. In 2,267 male Caucasians, {20:Gardemann et al. (1998)} found an association of the D allele with coronary artery disease in subjects less than 61.7 years of age but not in patients 61.7 years or older. Exclusion of individuals with other cardiovascular risk factors (e.g., high body mass index) produced an even stronger association of the D allele with coronary artery disease. {42:Keavney et al. (2000)} compared 4,629 myocardial infarction cases and 5,934 controls for presence or absence of the ACE I/D polymorphism. The ACE DD genotype was found in 1,359 (29.4%) of the myocardial infarction cases and in 1,637 (27.6%) of the controls (risk ratio 1.10 with a 95% confidence interval of 1.00 to 1.21). The association between myocardial infarction and the DD genotype did not seem to be stronger in the subgroup defined as low risk by previously used criteria or in any other subgroup. Nor was the ACE ID genotype predictive of subsequent survival. {42:Keavney et al. (2000)} also performed a metaanalysis of previously published studies, and found the risk ratio for myocardial infarction with the DD genotype to lie between 1.0 and 1.1. Although an increase in risk of up to 10 to 15% cannot be ruled out, substantially more extreme risks can be. {72:Sayed-Tabatabaei et al. (2005)} determined the ACE I/D polymorphism and smoking status in 6,714 individuals and recorded fatal and nonfatal myocardial infarctions and mortality events. Among smokers, they found an increased risk of cardiovascular mortality for younger (below the median age of 68.2 years) carriers of the D allele (p = 0.03). No association was observed between ACE genotype and myocardial infarction. {76:Schurks et al. (2009)} found no association between the ACE I/D polymorphism ({dbSNP rs1799752}) and cardiovascular disease or migraine ({157300}) in a cohort of 25,000 white women. Association with IgA Nephropathy {92:Yoshida et al. (1995)} found that the deletion polymorphism in the ACE gene is a risk factor for progression to chronic renal failure in IgA nephropathy ({161950}), and that the deletion polymorphism predicts therapeutic efficacy of ACE inhibition on proteinuria and, potentially, on progressive deterioration of renal function. They found that 43% of patients who showed decline of renal function had the DD homozygous genotype, whereas it was present in only 7% of age-matched individuals without a history of the proteinuria and in only 16% of a group of patients with IgA nephropathy and stable renal function. After 48 weeks of ACE inhibitor administration, proteinuria significantly decreased in patients with the DD genotype but not in those with ID or II genotypes. Using multivariant analysis, {66:Pei et al. (1997)} found that the presence of the ACE DD polymorphism adversely affected disease progression in IgA nephropathy only in patients with the met235/met235 (MM) genotype of the AGT gene ({106150.0001}). {91:Yoon et al. (2002)} investigated the interdependent action of the insertion/deletion polymorphism of the ACE gene and the ala379-to-val polymorphism in exon 11 of PLA2G7 ({601690.0003}), which encodes a functional agonist of platelet-activating factor (PAF) on the progression of IgA nephropathy. They analyzed both polymorphisms in patients with primary IgA nephropathy who were followed up for longer than 3 years. During the follow-up, the disease progressed in 38 of the 191 patients. The D allele of the ACE gene in the absence of the T allele of the PLA2G7 gene did not affect the prognosis, nor did the T allele in the absence of the D allele. However, the presence of both was a significant prognostic factor. The results suggested that the interdependent effects of ACE and PLA2G7 polymorphisms on the progression of IgA nephropathy may be more important than the effect of the individual polymorphisms. Association with Alzheimer Disease Following reports that the DCP1*D allele of the common I/D polymorphism in the DCP1 gene is associated with increased longevity ({73:Schachter et al., 1994}), {45:Kehoe et al. (1999)} hypothesized that DCP1*D may protect against the development of Alzheimer disease (AD; {104300}) and that, conversely, the DCP1*I allele may confer increased risk. They tested this hypothesis in samples from Cardiff, London, and Belfast. They reported findings suggesting that genetic variation at the DCP1 locus predisposes to AD in a manner that is independent of APOE variation. They considered the possibility that the low frequency of the DD homozygous genotype in AD may have been due to the exclusion of cases with cardiovascular disease. They thought this possibility unlikely for a number of reasons: first, the impact of the DD genotype on cardiovascular disease is controversial, relatively small, and restricted to specific geographic areas and to patient subgroups with highly heterogeneous clinical manifestations. Second, cases with vascular symptoms were only excluded from the groups of patients they studied if they had histories of obvious stepwise cognitive deterioration consistent with vascular dementia. Third, vascular dementia cases were also excluded from the screened age-matched control groups. Fourth, their control allele and genotype frequencies were similar to those reported for the general population by a number of studies, including 1 from a very similar geographic location. Finally, analysis of DCP1 genotypes in 15 additional vascular dementia cases, and in 21 dementia cases with a history of stroke excluded from the London sample, showed an excess of the DCP1*I allele rather than an excess of the DD genotype. {32:Hu et al. (1999)} studied the ACE I/D polymorphism in 133 Japanese sporadic AD patients and 257 controls and found that the ACE II genotype was associated with susceptibility to AD. The frequency of the II genotype was 1.4 times higher in AD than controls, while that of the DD genotype was only 0.4 times higher in AD than controls. {15:Elkins et al. (2004)} performed a metaanalysis of 23 independent published studies that investigated the association between Alzheimer disease and the ACE I/D polymorphism. Review of the data showed that the OR for AD in individuals with the I allele (II or ID genotype) was 1.27 compared to those with the DD genotype. The risk of AD was higher among Asians (OR of 2.44) and in patients younger than 75 years of age (OR of 1.54). {15:Elkins et al. (2004)} concluded that the ACE I allele is associated with an increased risk of late-onset AD, but noted that the risk is very small compared to the effects of other alleles, especially APOE4 (see {107741}). Association with Microvascular Complications of Diabetes 3 {55:Marre et al. (1994)} and {13:Doria et al. (1994)} reported that the I/D polymorphism of the ACE gene is associated with diabetic nephropathy (MVCD3; {612634}), but this association was disputed by others, e.g., {82:Tarnow et al. (1995)} and {74:Schmidt et al. (1995)}. {56:Marre et al. (1997)} undertook a large-scale, multicenter study on insulin-dependent diabetic subjects at risk of kidney complications due to long-term exposure to hyperglycemia, i.e., those who had developed proliferative diabetic retinopathy, to test the relationship between genetic factors and renal involvement in insulin-dependent diabetes mellitus ({222100}). The study concluded that the ACE gene is involved in both the susceptibility to diabetic nephropathy and its progression toward renal failure, and an interaction between ACE I/D and an M235T polymorphism in the AGT gene ({106150.0001}) was found that could account for the degree of renal involvement in the patients studied. {86:Vleming et al. (1999)} studied the contribution of the I/D polymorphism in 79 patients with end-stage renal failure due to diabetic nephropathy and in 82 age-matched controls with 15 years of IDDM but without microalbuminuria. There was significant overrepresentation of the DD genotype with a significant increase of the D-allele frequency in the cases compared to controls. The presence of the DD genotype increased the risk of end-stage renal failure compared to other genotypes (odds ratio, 2.1; 95% CI, 1.1-4.0). However, the presence of 1 D-allele did not increase the risk. In mice rendered diabetic, {33:Huang et al. (2001)} demonstrated that those mice who had a third copy of the Ace gene, and as a result higher enzyme levels (comparable to those associated with the variant D allele), developed increased blood pressures and overt proteinuria indicative of nephropathy. Association with Type 2 Diabetes The I allele of the I/D ACE polymorphism appears to be protective against the complications of type 2 diabetes ({125853}). Low birth weight, a marker of an adverse intrauterine environment, is associated with higher rates of type 2 diabetes. {39:Kajantie et al. (2004)} examined whether the ACE I/D polymorphism could explain or modify the association between low birth weight and adulthood glucose tolerance. They measured plasma glucose and insulin concentrations after an oral glucose challenge in a group of 423 men and women, ages 65 to 75 years, with measurements at birth recorded. The presence of the I allele was associated with shorter duration of gestation (p = 0.006) and, relative to gestational age, higher birth weight (p = 0.008) and length (p = 0.02). The I allele was associated with lower glucose at 120 minutes (p = 0.04) and a greater insulin response (p = 0.03 for insulin at 30 minutes and p = 0.06 for insulin area under the curve) to a standard oral glucose tolerance test. However, the associations between the ACE genotype and adulthood insulin secretion were present only in people with low birth weight. The authors concluded that the ACE I allele is associated with shorter duration of gestation and higher birth weight. The association between the presence of the ACE I allele and increased indices of adult insulin secretion is confined to subjects with low birth weight. The authors suggested that these findings reflect interactions between genotype and intrauterine environment with resulting changes in gene expression. Association with Meningococcal Disease {27:Harding et al. (2002)} recorded illness severity for 110 consecutive white pediatric patients with meningococcal disease and analyzed the results in terms of the ACE I/D polymorphism. Compared to children with an I allele, those with the DD genotype had a higher predicted risk of mortality (p = 0.01), worse Glasgow Meningococcal Septicemia Prognostic Scores (p = 0.014), greater need for inotropes (p = 0.034) and ventilation (p = 0.044), and longer stays in the pediatric intensive care unit (p = 0.021). DD genotype was 6% for the 18 children who did not require PICU care, 33% for the 84 PICU survivors, and 45% for those who died (p = 0.013). {27:Harding et al. (2002)} concluded that the ACE DD genotype is associated with increased illness severity in meningococcal disease. Association with Preterm Cardiorespiratory Disease {28:Harding et al. (2003)} determined ACE genotype in 148 preterm infants and prospectively obtained intensive care data. Infants with the DD genotype required higher oxygen (p = 0.028) and more blood pressure support (p = 0.039), and had worse base deficits (p = 0.020) than those with the ID or II genotype. {28:Harding et al. (2003)} concluded that ACE polymorphism has a role in the development of preterm cardiorespiratory disease and that the DD genotype, which encodes higher ACE activity, may adversely affect the early health status of preterm infants. Association with Myophosphorylase Deficiency In 47 patients with myophosphorylase deficiency ({232600}), {57:Martinuzzi et al. (2003)} found an association between increased clinical severity and the ACE D allele. The authors noted that because the ACE I/D polymorphism had been shown to be associated with muscle function, it may modulate some clinical aspects of myophosphorylase deficiency, accounting for some of the phenotypic variability of the disorder. Association with Hemorrhagic Stroke {79:Slowik et al. (2004)} found an association between the ACE DD genotype and spontaneous intracerebral hemorrhagic stroke (ICH; {614519}) in deep brain structures in 58 Polish patients (OR of 2.46). No association was found between the DD genotype and 140 controls or 70 Polish patients with small vessel disease and ischemic stroke. Association with Ischemic Stroke In a comprehensive metaanalysis of 11 case-control studies including 2,990 white adult patients, {10:Casas et al. (2004)} found a statistically significant association between ischemic stroke ({601367}) and the ACE DD genotype compared to the II or ID genotypes (OR of 1.21). Association with Severe Acute Respiratory Syndrome {34:Itoyama et al. (2004)} genotyped 44 Vietnamese severe acute respiratory syndrome (SARS) cases along with 103 healthy exposed and 50 unexposed controls. They divided the SARS cases into hypoxemic and nonhypoxemic groups, both of which had 22 individuals. The frequency of the D allele of ACE1 was significantly higher in the hypoxemic group compared with the nonhypoxemic group (20 of 44 alleles vs 9 of 44 alleles), whereas there was no significant difference between the SARS cases and controls, regardless of contact history. {34:Itoyama et al. (2004)} proposed that ACE1 may influence the progression to pneumonia in SARS. Association with Athletic Excellence {21:Gayagay et al. (1998)} concluded that the ACE I allele may be a genetic marker associated with athletic excellence. They found that the I allele was present in excess (P less than 0.02), as was also the homozygous II genotype (p = 0.03), in 64 Australian national rowers, compared with a normal population. They proposed that the underlying mechanism related to a healthier cardiovascular system. omim.nt GENO:0000002 http://omim.org/entry/106180 biolink:NamedThing|biolink:Gene ACE Angiotensin I-Converting Enzyme omim.nt ANGIOTENSIN I-CONVERTING ENZYME; ACE|Ace1|Angiotensin I-Converting Enzyme, Benign Serum Increase|Angiotensin I-Converting Enzyme, Plasma Level of|Angiotensin I-Converting Enzyme, Testicular|Dipeptidyl Carboxypeptidase 1|Iga Nephropathy, Progression to Renal Failure In, Susceptibility to|Kininase 2 owl:Class ClinVar:RCV000019678 biolink:NamedThing omim.nt ClinVar:RCV000019679 biolink:NamedThing omim.nt ClinVar:RCV000019680 biolink:NamedThing omim.nt ClinVar:RCV000019681 biolink:NamedThing omim.nt ClinVar:RCV000019682 biolink:NamedThing omim.nt ClinVar:RCV000019683 biolink:NamedThing omim.nt ClinVar:RCV000019684 biolink:NamedThing omim.nt http://omim.org/entry/106180#0001 biolink:NamedThing omim.nt http://omim.org/entry/106180.0002 biolink:NamedThing ACE, PRO1199LEU In affected members of 8 families with an autosomal dominant increase in serum ACE activity, {49:Kramers et al. (2001)} identified a heterozygous 3705C-T transition in the ACE gene, resulting in a pro1199-to-leu (P1199L) substitution in the stalk region of the protein. In all families, the proband was investigated for ACE activity because of a suspicion of sarcoidosis; the diagnosis was not made in any of the individuals. ACE values in affected members from the 8 families showed a 5-fold increase compared to normal. Elevated ACE was not accompanied by any apparent clinical abnormality. Analysis of leukocytes and dendritic cells from individuals with the mutation showed a normal amount of ACE on the cell surface, but there was a significant increase in the amount of secreted ACE. {49:Kramers et al. (2001)} suggested that the P1199L mutation results in more efficient cleavage of somatic ACE. In 3 unrelated patients with high plasma ACE levels, {19:Eyries et al. (2001)} identified the P1199L mutation. In vitro analysis revealed that the shedding of the mutant protein was enhanced compared to wildtype; the rate of solubilization was on average 2.5-fold higher than wildtype. Two-dimensional structural analyses showed that the mutated residue was critical for the positioning of a specific loop containing the cleavage site, leading to more accessibility at the stalk region. {54:Linnebank et al. (2003)} reported a 49-year-old woman with arterial hypertension, transitory neurologic symptoms, and suspected neurosarcoidosis based on elevated plasma and CSF levels of ACE. The P1199L mutation was identified in the patient, as well as in her mother and daughter who also had elevated serum ACE. There was no evidence of neurosarcoidosis in the proband. {54:Linnebank et al. (2003)} emphasized the importance of considering this benign inherited phenotype in order to avoid unnecessary and potentially harmful treatment. omim.nt GENO:0000002 ClinVar:RCV000019685 biolink:NamedThing omim.nt dbSNP:rs121912703 biolink:NamedThing omim.nt owl:NamedIndividual http://omim.org/entry/106180#0002 biolink:NamedThing omim.nt http://omim.org/entry/106180.0003 biolink:NamedThing ACE, TYR266TER In 2 sibs with renal tubular dysgenesis ({267430}) in a family of Italian and French origin, {22:Gribouval et al. (2005)} found a tyr266-to-ter (Y266X) mutation in the ACE gene, arising from a 798C-G transversion in exon 5. It was the only mutation found, inherited from the father. omim.nt GENO:0000002 ClinVar:RCV000019686 biolink:NamedThing omim.nt dbSNP:rs121912704 biolink:NamedThing omim.nt owl:NamedIndividual http://omim.org/entry/106180#0003 biolink:NamedThing omim.nt http://omim.org/entry/106180.0004 biolink:NamedThing ACE, 4-BP DEL, 1319TGGA In 2 sibs with renal tubular dysgenesis ({267430}) from a consanguineous Turkish family, {22:Gribouval et al. (2005)} found homozygosity for a frameshift mutation in exon 8 of the ACE gene. Deletion of 4 nucleotides, 1319_1322del TGGA, resulted in a frameshift at leucine-440 and a premature stop at codon 455. omim.nt GENO:0000002 ClinVar:RCV000019687 biolink:NamedThing omim.nt dbSNP:rs387906576 biolink:NamedThing omim.nt owl:NamedIndividual http://omim.org/entry/106180#0004 biolink:NamedThing omim.nt http://omim.org/entry/106180.0005 biolink:NamedThing ACE, ARG496TER In a girl with renal tubular dysgenesis ({267430}), who was born to consanguineous Swiss parents, {23:Gribouval et al. (2012)} identified a homozygous c.1486C-T transition in exon 9 of the ACE gene, resulting in an arg496-to-ter (R496X) substitution. She died in the second hour of life. omim.nt GENO:0000002 ClinVar:RCV000043470 biolink:NamedThing omim.nt ClinVar:RCV000321927 biolink:NamedThing omim.nt dbSNP:rs397514688 biolink:NamedThing omim.nt owl:NamedIndividual http://omim.org/entry/106180#0005 biolink:NamedThing omim.nt http://omim.org/entry/106180.0006 biolink:NamedThing ACE, ARG791TER In an Italian boy with renal tubular dysgenesis ({267430}), who was born to consanguineous parents, {23:Gribouval et al. (2012)} identified a homozygous c.2371C-T transition in exon 16 of ACE gene, resulting in an arg791-to-ter (R791X) substitution. He died on the seventh day of life. omim.nt GENO:0000002 ClinVar:RCV000043471 biolink:NamedThing omim.nt ClinVar:RCV000579372 biolink:NamedThing omim.nt dbSNP:rs397514689 biolink:NamedThing omim.nt owl:NamedIndividual http://omim.org/entry/106180#0006 biolink:NamedThing omim.nt MONARCH:.well-known/genid/b9052f190dbce1d9ecb6 biolink:NamedThing GRCh38chr17-63477060-63498372-Region omim.nt MONARCH:.well-known/genid/bb0b117d78562de5ea12 faldo:Region MONARCH:.well-known/genid/OMIM106180ref58 biolink:NamedThing Angiotensin-I converting enzyme gene is on chromosome 17. (Abstract) omim.nt IAO:0000310 PMID:10099885 biolink:NamedThing omim.nt IAO:0000013 PMID:10193250 biolink:NamedThing omim.nt IAO:0000013 PMID:10636736 biolink:NamedThing omim.nt IAO:0000013 PMID:10643899 biolink:NamedThing omim.nt IAO:0000013 PMID:10688186 biolink:NamedThing omim.nt IAO:0000013 PMID:10841123 biolink:NamedThing omim.nt IAO:0000013 PMID:10882751 biolink:NamedThing omim.nt IAO:0000013 PMID:11001581 biolink:NamedThing omim.nt IAO:0000013 PMID:11076943 biolink:NamedThing omim.nt IAO:0000013 PMID:11274151 biolink:NamedThing omim.nt IAO:0000013 PMID:11283791 biolink:NamedThing omim.nt IAO:0000013 PMID:11333991 biolink:NamedThing omim.nt IAO:0000013 PMID:11344227 biolink:NamedThing omim.nt IAO:0000013 PMID:11551873 biolink:NamedThing omim.nt IAO:0000013 PMID:11604391 biolink:NamedThing omim.nt IAO:0000013 PMID:11687636 biolink:NamedThing omim.nt IAO:0000013 PMID:11956052 biolink:NamedThing omim.nt IAO:0000013 PMID:12099691 biolink:NamedThing omim.nt IAO:0000013 PMID:12220450 biolink:NamedThing omim.nt IAO:0000013 PMID:12372063 biolink:NamedThing omim.nt IAO:0000013 PMID:12459472 biolink:NamedThing omim.nt IAO:0000013 PMID:12540854 biolink:NamedThing omim.nt IAO:0000013 PMID:12630962 biolink:NamedThing omim.nt IAO:0000013 PMID:12666117 biolink:NamedThing omim.nt IAO:0000013 PMID:12668609 biolink:NamedThing omim.nt IAO:0000013 PMID:12777443 biolink:NamedThing omim.nt IAO:0000013 PMID:1313972 biolink:NamedThing omim.nt IAO:0000013 PMID:1319114 biolink:NamedThing omim.nt IAO:0000013 PMID:1328887 biolink:NamedThing omim.nt IAO:0000013 PMID:1328889 biolink:NamedThing omim.nt IAO:0000013 PMID:1338766 biolink:NamedThing omim.nt IAO:0000013 PMID:1386652 biolink:NamedThing omim.nt IAO:0000013 PMID:14657821 biolink:NamedThing omim.nt IAO:0000013 PMID:14694062 biolink:NamedThing omim.nt IAO:0000013 PMID:14755464 biolink:NamedThing omim.nt IAO:0000013 PMID:14986105 biolink:NamedThing omim.nt IAO:0000013 PMID:15110771 biolink:NamedThing omim.nt IAO:0000013 PMID:15128700 biolink:NamedThing omim.nt IAO:0000013 PMID:15164285 biolink:NamedThing omim.nt IAO:0000013 PMID:15277638 biolink:NamedThing omim.nt IAO:0000013 PMID:15326315 biolink:NamedThing omim.nt IAO:0000013 PMID:15367486 biolink:NamedThing omim.nt IAO:0000013 PMID:15381116 biolink:NamedThing omim.nt IAO:0000013 PMID:15531537 biolink:NamedThing omim.nt IAO:0000013 PMID:15534175 biolink:NamedThing omim.nt IAO:0000013 PMID:15635071 biolink:NamedThing omim.nt IAO:0000013 PMID:15665832 biolink:NamedThing omim.nt IAO:0000013 PMID:16002416 biolink:NamedThing omim.nt IAO:0000013 PMID:16642441 biolink:NamedThing omim.nt IAO:0000013 PMID:16760444 biolink:NamedThing omim.nt IAO:0000013 PMID:18443281 biolink:NamedThing omim.nt IAO:0000013 PMID:19221299 biolink:NamedThing omim.nt IAO:0000013 PMID:1976655 biolink:NamedThing omim.nt IAO:0000013 PMID:2164636 biolink:NamedThing omim.nt IAO:0000013 PMID:2554286 biolink:NamedThing omim.nt IAO:0000013 PMID:2847529 biolink:NamedThing omim.nt IAO:0000013 PMID:2849100 biolink:NamedThing omim.nt IAO:0000013 PMID:2989970 biolink:NamedThing omim.nt IAO:0000013 PMID:7593601 biolink:NamedThing omim.nt IAO:0000013 PMID:7729604 biolink:NamedThing omim.nt IAO:0000013 PMID:7753170 biolink:NamedThing omim.nt IAO:0000013 PMID:7783416 biolink:NamedThing omim.nt IAO:0000013 PMID:7854377 biolink:NamedThing omim.nt IAO:0000013 PMID:7909524 biolink:NamedThing omim.nt IAO:0000013 PMID:8062433 biolink:NamedThing omim.nt IAO:0000013 PMID:8131299 biolink:NamedThing omim.nt IAO:0000013 PMID:8131300 biolink:NamedThing omim.nt IAO:0000013 PMID:8136829 biolink:NamedThing omim.nt IAO:0000013 PMID:8170965 biolink:NamedThing omim.nt IAO:0000013 PMID:8177269 biolink:NamedThing omim.nt IAO:0000013 PMID:8208911 biolink:NamedThing omim.nt IAO:0000013 PMID:8298638 biolink:NamedThing omim.nt IAO:0000013 PMID:8314010 biolink:NamedThing omim.nt IAO:0000013 PMID:8541160 biolink:NamedThing omim.nt IAO:0000013 PMID:8598840 biolink:NamedThing omim.nt IAO:0000013 PMID:8640851 biolink:NamedThing omim.nt IAO:0000013 PMID:8644984 biolink:NamedThing omim.nt IAO:0000013 PMID:8675669 biolink:NamedThing omim.nt IAO:0000013 PMID:8689816 biolink:NamedThing omim.nt IAO:0000013 PMID:8759058 biolink:NamedThing omim.nt IAO:0000013 PMID:8873661 biolink:NamedThing omim.nt IAO:0000013 PMID:9153279 biolink:NamedThing omim.nt IAO:0000013 PMID:9236417 biolink:NamedThing omim.nt IAO:0000013 PMID:9264477 biolink:NamedThing omim.nt IAO:0000013 PMID:9328471 biolink:NamedThing omim.nt IAO:0000013 PMID:9482924 biolink:NamedThing omim.nt IAO:0000013 PMID:9607758 biolink:NamedThing omim.nt IAO:0000013 PMID:9664078 biolink:NamedThing omim.nt IAO:0000013 PMID:9699903 biolink:NamedThing omim.nt IAO:0000013 PMID:9737775 biolink:NamedThing omim.nt IAO:0000013 PMID:9916793 biolink:NamedThing omim.nt IAO:0000013 http://omim.org/entry/612624 biolink:NamedThing|biolink:Disease Microvascular Complications of Diabetes, Susceptibility To, 3 Microvascular Complications of Diabetes, Susceptibility To, 3 omim.nt MICROVASCULAR COMPLICATIONS OF DIABETES, SUSCEPTIBILITY TO, 3; MVCD3|End-Stage Renal Disease, Diabetic, Susceptibility to|Nephropathy, Diabetic, Susceptibility to owl:Class http://omim.org/entry/614519 biolink:NamedThing|biolink:Disease Hemorrhage, Intracerebral, Susceptibility to Hemorrhage, Intracerebral, Susceptibility to omim.nt HEMORRHAGE, INTRACEREBRAL, SUSCEPTIBILITY TO; ICH|Stroke, Hemorrhagic, Susceptibility to owl:Class OBO:CHR_9606chr17q23 biolink:NamedThing omim.nt owl:Class http://www.omim.org/phenotypicSeries/PS603933 biolink:NamedThing|biolink:Disease Microvascular complications of diabetes omim.nt owl:Class UMLS:C1413931 biolink:NamedThing omim.nt owl:Class UMLS:C1862873 biolink:NamedThing omim.nt owl:Class UMLS:C1862874 biolink:NamedThing omim.nt owl:Class https://www.ncbi.nlm.nih.gov/gene/1636 biolink:NamedThing omim.nt http://omim.org/entry/106190 biolink:NamedThing|biolink:Disease Anhidrosis, Isolated, With Normal Sweat Glands Anhidrosis, Isolated, With Normal Sweat Glands omim.nt ANHIDROSIS, ISOLATED, WITH NORMAL SWEAT GLANDS; ANHD|Dann-Epstein-Sohar Syndrome owl:Class PMID:2401610 biolink:NamedThing omim.nt IAO:0000013 PMID:2401613 biolink:NamedThing omim.nt IAO:0000013 PMID:25329695 biolink:NamedThing omim.nt IAO:0000013 UMLS:C1862871 biolink:NamedThing omim.nt owl:Class ORPHA:468666 biolink:NamedThing|biolink:Disease omim.nt owl:Class http://omim.org/entry/106195 biolink:NamedThing|biolink:Gene SLC4A3 Solute Carrier Family 4 (Anion Exchanger), Member 3 omim.nt SOLUTE CARRIER FAMILY 4 (ANION EXCHANGER), MEMBER 3; SLC4A3|Anion Exchanger 3|Anion Exchanger, Neuronal|Slc2C owl:Class MONARCH:.well-known/genid/ba1a0f382f201eb58b26 biolink:NamedThing GRCh38chr2-219627629-219641979-Region omim.nt MONARCH:.well-known/genid/b4d5864c23eb1b2a6d72 faldo:Region MONARCH:.well-known/genid/OMIM106195ref3 biolink:NamedThing Personal Communication. omim.nt IAO:0000310 PMID:18779325 biolink:NamedThing omim.nt IAO:0000013 PMID:2686841 biolink:NamedThing omim.nt IAO:0000013 PMID:7894173 biolink:NamedThing omim.nt IAO:0000013 PMID:8001971 biolink:NamedThing omim.nt IAO:0000013 OBO:CHR_9606chr2q36 biolink:NamedThing omim.nt owl:Class UMLS:C1420195 biolink:NamedThing omim.nt owl:Class https://www.ncbi.nlm.nih.gov/gene/6508 biolink:NamedThing omim.nt http://omim.org/entry/106200 biolink:NamedThing omim.nt True owl:Class http://omim.org/entry/106210 biolink:NamedThing|biolink:Disease Aniridia 1 Aniridia 1 omim.nt ANIRIDIA 1; AN1|An|Aniridia Ii, Formerly|Cataract, Congenital, With Late-Onset Corneal Dystrophy owl:Class MONARCH:.well-known/genid/OMIM106210ref20 biolink:NamedThing Aniridia 1 update of linkage to ACP. (Abstract) omim.nt IAO:0000310 MONARCH:.well-known/genid/OMIM106210ref27 biolink:NamedThing A family study of aniridia. omim.nt IAO:0000310 MONARCH:.well-known/genid/OMIM106210ref39 biolink:NamedThing Personal Communication. omim.nt IAO:0000310 MONARCH:.well-known/genid/OMIM106210ref4 biolink:NamedThing Aniridie, une famille a degre de penetrance faible. omim.nt IAO:0000310 MONARCH:.well-known/genid/OMIM106210ref58 biolink:NamedThing On the evolution of photoreceptors and eyes. In: Hecht, M. K.; Steere, W.; Wallace, B. (eds.): Evolutionary Biology. Vol. 10. omim.nt IAO:0000310 MONARCH:.well-known/genid/OMIM106210ref61 biolink:NamedThing A separate gene for aniridia at 11p13. (Abstract) omim.nt IAO:0000310 PMID:10857836 biolink:NamedThing omim.nt IAO:0000013 PMID:11087823 biolink:NamedThing omim.nt IAO:0000013 PMID:11431688 biolink:NamedThing omim.nt IAO:0000013 PMID:11479730 biolink:NamedThing omim.nt IAO:0000013 PMID:11481423 biolink:NamedThing omim.nt IAO:0000013 PMID:11553050 biolink:NamedThing omim.nt IAO:0000013 PMID:11826019 biolink:NamedThing omim.nt IAO:0000013 PMID:12386836 biolink:NamedThing omim.nt IAO:0000013 PMID:12427081 biolink:NamedThing omim.nt IAO:0000013 PMID:1247409 biolink:NamedThing omim.nt IAO:0000013 PMID:12511357 biolink:NamedThing omim.nt IAO:0000013 PMID:1251879 biolink:NamedThing omim.nt IAO:0000013 PMID:12566018 biolink:NamedThing omim.nt IAO:0000013 PMID:12714618 biolink:NamedThing omim.nt IAO:0000013 PMID:12731001 biolink:NamedThing omim.nt IAO:0000013 PMID:1302030 biolink:NamedThing omim.nt IAO:0000013 PMID:1334370 biolink:NamedThing omim.nt IAO:0000013 PMID:14962429 biolink:NamedThing omim.nt IAO:0000013 PMID:1505982 biolink:NamedThing omim.nt IAO:0000013 PMID:15846561 biolink:NamedThing omim.nt IAO:0000013 PMID:16493447 biolink:NamedThing omim.nt IAO:0000013 PMID:16543198 biolink:NamedThing omim.nt IAO:0000013 PMID:16638998 biolink:NamedThing omim.nt IAO:0000013 PMID:1684639 biolink:NamedThing omim.nt IAO:0000013 PMID:1684738 biolink:NamedThing omim.nt IAO:0000013 PMID:17148041 biolink:NamedThing omim.nt IAO:0000013 PMID:17406642 biolink:NamedThing omim.nt IAO:0000013 PMID:17591901 biolink:NamedThing omim.nt IAO:0000013 PMID:17595013 biolink:NamedThing omim.nt IAO:0000013 PMID:17948455 biolink:NamedThing omim.nt IAO:0000013 PMID:18322702 biolink:NamedThing omim.nt IAO:0000013 PMID:19876904 biolink:NamedThing omim.nt IAO:0000013 PMID:21321669 biolink:NamedThing omim.nt IAO:0000013 PMID:2173141 biolink:NamedThing omim.nt IAO:0000013 PMID:2347591 biolink:NamedThing omim.nt IAO:0000013 PMID:2544995 biolink:NamedThing omim.nt IAO:0000013 PMID:2575483 biolink:NamedThing omim.nt IAO:0000013 PMID:2817003 biolink:NamedThing omim.nt IAO:0000013 PMID:2841760 biolink:NamedThing omim.nt IAO:0000013 PMID:3427001 biolink:NamedThing omim.nt IAO:0000013 PMID:3754537 biolink:NamedThing omim.nt IAO:0000013 PMID:3941902 biolink:NamedThing omim.nt IAO:0000013 PMID:4782857 biolink:NamedThing omim.nt IAO:0000013 PMID:6092262 biolink:NamedThing omim.nt IAO:0000013 PMID:6301974 biolink:NamedThing omim.nt IAO:0000013 PMID:6325323 biolink:NamedThing omim.nt IAO:0000013 PMID:6929510 biolink:NamedThing omim.nt IAO:0000013 PMID:6988567 biolink:NamedThing omim.nt IAO:0000013 PMID:7369316 biolink:NamedThing omim.nt IAO:0000013 PMID:7550230 biolink:NamedThing omim.nt IAO:0000013 PMID:7795596 biolink:NamedThing omim.nt IAO:0000013 PMID:7914031 biolink:NamedThing omim.nt IAO:0000013 PMID:7951315 biolink:NamedThing omim.nt IAO:0000013 PMID:7981749 biolink:NamedThing omim.nt IAO:0000013 PMID:8032206 biolink:NamedThing omim.nt IAO:0000013 PMID:8047881 biolink:NamedThing omim.nt IAO:0000013 PMID:8364574 biolink:NamedThing omim.nt IAO:0000013 PMID:8478003 biolink:NamedThing omim.nt IAO:0000013 PMID:848489 biolink:NamedThing omim.nt IAO:0000013 PMID:8689689 biolink:NamedThing omim.nt IAO:0000013 PMID:868970 biolink:NamedThing omim.nt IAO:0000013 PMID:8825052 biolink:NamedThing omim.nt IAO:0000013 PMID:9138149 biolink:NamedThing omim.nt IAO:0000013 PMID:9482572 biolink:NamedThing omim.nt IAO:0000013 UMLS:C0003076 biolink:NamedThing omim.nt owl:Class UMLS:C3805349 biolink:NamedThing omim.nt owl:Class ORPHA:250923 biolink:NamedThing|biolink:Disease omim.nt owl:Class http://www.omim.org/phenotypicSeries/PS106210 biolink:NamedThing|biolink:Disease Aniridia omim.nt owl:Class http://omim.org/entry/106220 biolink:NamedThing|biolink:Disease Aniridia and Absent Patella omim.nt ANIRIDIA AND ABSENT PATELLA owl:Class MONARCH:.well-known/genid/OMIM106220ref1 biolink:NamedThing A familial syndrome of aniridia and absence of the patella. omim.nt IAO:0000310 UMLS:C1862868 biolink:NamedThing omim.nt owl:Class ORPHA:1069 biolink:NamedThing|biolink:Disease omim.nt owl:Class http://omim.org/entry/106230 biolink:NamedThing Aniridia, Microcornea, and Spontaneously Reabsorbed Cataract omim.nt ANIRIDIA, MICROCORNEA, AND SPONTANEOUSLY REABSORBED CATARACT owl:Class PMID:3355417 biolink:NamedThing omim.nt IAO:0000013 UMLS:C1862867 biolink:NamedThing omim.nt owl:Class http://omim.org/entry/106240 biolink:NamedThing Anisocoria omim.nt ANISOCORIA owl:Class PMID:2330952 biolink:NamedThing omim.nt IAO:0000013 UMLS:C0003079 biolink:NamedThing omim.nt owl:Class http://omim.org/entry/106250 biolink:NamedThing|biolink:Disease Ankyloblepharon Filiforme Adnatum and Cleft Palate omim.nt ANKYLOBLEPHARON FILIFORME ADNATUM AND CLEFT PALATE; AFA owl:Class MONARCH:.well-known/genid/OMIM106250ref4 biolink:NamedThing Personal Communication. omim.nt IAO:0000310 MONARCH:.well-known/genid/OMIM106250ref7 biolink:NamedThing Ankyloblepharon filiforme et membraniforme adnatum. omim.nt IAO:0000310 PMID:13411166 biolink:NamedThing omim.nt IAO:0000013 PMID:218608 biolink:NamedThing omim.nt IAO:0000013 PMID:2277391 biolink:NamedThing omim.nt IAO:0000013 PMID:4473200 biolink:NamedThing omim.nt IAO:0000013 PMID:5536004 biolink:NamedThing omim.nt IAO:0000013 UMLS:C1862866 biolink:NamedThing omim.nt owl:Class ORPHA:1072 biolink:NamedThing|biolink:Disease omim.nt owl:Class http://omim.org/entry/106260 biolink:NamedThing|biolink:Disease Ankyloblepharon-Ectodermal Defects-Cleft Lip/Palate Ankyloblepharon-Ectodermal Defects-Cleft Lip/Palate omim.nt ANKYLOBLEPHARON-ECTODERMAL DEFECTS-CLEFT LIP/PALATE; AEC|Aec Syndrome|Hay-Wells Syndrome owl:Class MONARCH:.well-known/genid/OMIM106260ref14 biolink:NamedThing AEC syndrome: ankyloblepharon, ectodermal defects, and cleft lip and palate. omim.nt IAO:0000310 PMID:10535733 biolink:NamedThing omim.nt IAO:0000013 PMID:10886756 biolink:NamedThing omim.nt IAO:0000013 PMID:11159940 biolink:NamedThing omim.nt IAO:0000013 PMID:14684701 biolink:NamedThing omim.nt IAO:0000013 PMID:15200513 biolink:NamedThing omim.nt IAO:0000013 PMID:1536181 biolink:NamedThing omim.nt IAO:0000013 PMID:19239083 biolink:NamedThing omim.nt IAO:0000013 PMID:19353643 biolink:NamedThing omim.nt IAO:0000013 PMID:19676059 biolink:NamedThing omim.nt IAO:0000013 PMID:19681108 biolink:NamedThing omim.nt IAO:0000013 PMID:19697429 biolink:NamedThing omim.nt IAO:0000013 PMID:19697430 biolink:NamedThing omim.nt IAO:0000013 PMID:3605196 biolink:NamedThing omim.nt IAO:0000013 PMID:8411079 biolink:NamedThing omim.nt IAO:0000013 PMID:946410 biolink:NamedThing omim.nt IAO:0000013 UMLS:C0406709 biolink:NamedThing omim.nt owl:Class ORPHA:1071 biolink:NamedThing|biolink:Disease omim.nt owl:Class http://omim.org/entry/106280 biolink:NamedThing Ankyloglossia With or Without Tooth Anomalies omim.nt ANKYLOGLOSSIA WITH OR WITHOUT TOOTH ANOMALIES; ANKG|Ankyloglossia|'Tongue-Tie' owl:Class PMID:13013390 biolink:NamedThing omim.nt IAO:0000013 PMID:17588677 biolink:NamedThing omim.nt IAO:0000013 PMID:18983637 biolink:NamedThing omim.nt IAO:0000013 PMID:20042737 biolink:NamedThing omim.nt IAO:0000013 PMID:28384993 biolink:NamedThing omim.nt IAO:0000013 PMID:29704302 biolink:NamedThing omim.nt IAO:0000013 UMLS:C4759698 biolink:NamedThing omim.nt owl:Class http://omim.org/entry/106300 biolink:NamedThing|biolink:Disease Spondyloarthropathy, Susceptibility To, 1 Spondyloarthropathy, Susceptibility To, 1 omim.nt SPONDYLOARTHROPATHY, SUSCEPTIBILITY TO, 1; SPDA1|Ankylosing Spondylitis, Susceptibility to|Bechterew Syndrome|Marie-Strumpell Spondylitis owl:Class MONARCH:.well-known/genid/OMIM106300ref35 biolink:NamedThing Linkage studies of class I MHC region genes in ankylosing spondylitis. (Abstract) omim.nt IAO:0000310 MONARCH:.well-known/genid/OMIM106300ref36 biolink:NamedThing Prevalence of ankylosing spondylitis. omim.nt IAO:0000310 PMID:107868 biolink:NamedThing omim.nt IAO:0000013 PMID:10857795 biolink:NamedThing omim.nt IAO:0000013 PMID:10861282 biolink:NamedThing omim.nt IAO:0000013 PMID:1130424 biolink:NamedThing omim.nt IAO:0000013 PMID:11762681 biolink:NamedThing omim.nt IAO:0000013 PMID:1185744 biolink:NamedThing omim.nt IAO:0000013 PMID:126380 biolink:NamedThing omim.nt IAO:0000013 PMID:12905477 biolink:NamedThing omim.nt IAO:0000013 PMID:13650428 biolink:NamedThing omim.nt IAO:0000013 PMID:13869952 biolink:NamedThing omim.nt IAO:0000013 PMID:14411096 biolink:NamedThing omim.nt IAO:0000013 PMID:14454080 biolink:NamedThing omim.nt IAO:0000013 PMID:14783304 biolink:NamedThing omim.nt IAO:0000013 PMID:15051216 biolink:NamedThing omim.nt IAO:0000013 PMID:15234954 biolink:NamedThing omim.nt IAO:0000013 PMID:15388324 biolink:NamedThing omim.nt IAO:0000013 PMID:17448825 biolink:NamedThing omim.nt IAO:0000013 PMID:17952073 biolink:NamedThing omim.nt IAO:0000013 PMID:19416804 biolink:NamedThing omim.nt IAO:0000013 PMID:1999831 biolink:NamedThing omim.nt IAO:0000013 PMID:20062062 biolink:NamedThing omim.nt IAO:0000013 PMID:21743469 biolink:NamedThing omim.nt IAO:0000013 PMID:2300126 biolink:NamedThing omim.nt IAO:0000013 PMID:2912465 biolink:NamedThing omim.nt IAO:0000013 PMID:2927470 biolink:NamedThing omim.nt IAO:0000013 PMID:3190783 biolink:NamedThing omim.nt IAO:0000013 PMID:3485286 biolink:NamedThing omim.nt IAO:0000013 PMID:4123836 biolink:NamedThing omim.nt IAO:0000013 PMID:4688372 biolink:NamedThing omim.nt IAO:0000013 PMID:4694299 biolink:NamedThing omim.nt IAO:0000013 PMID:6082899 biolink:NamedThing omim.nt IAO:0000013 PMID:6332689 biolink:NamedThing omim.nt IAO:0000013 PMID:657578 biolink:NamedThing omim.nt IAO:0000013 PMID:6604602 biolink:NamedThing omim.nt IAO:0000013 PMID:6606431 biolink:NamedThing omim.nt IAO:0000013 PMID:68310 biolink:NamedThing omim.nt IAO:0000013 PMID:7276519 biolink:NamedThing omim.nt IAO:0000013 PMID:7562959 biolink:NamedThing omim.nt IAO:0000013 PMID:7702399 biolink:NamedThing omim.nt IAO:0000013 PMID:7791441 biolink:NamedThing omim.nt IAO:0000013 PMID:782462 biolink:NamedThing omim.nt IAO:0000013 PMID:8053961 biolink:NamedThing omim.nt IAO:0000013 PMID:8415702 biolink:NamedThing omim.nt IAO:0000013 PMID:9336417 biolink:NamedThing omim.nt IAO:0000013 PMID:9519942 biolink:NamedThing omim.nt IAO:0000013 UMLS:C1862852 biolink:NamedThing omim.nt owl:Class http://www.omim.org/phenotypicSeries/PS106300 biolink:NamedThing|biolink:Disease Spondyloarthropathy, susceptibility to omim.nt owl:Class http://omim.org/entry/106400 biolink:NamedThing|biolink:Disease Ankylosing Vertebral Hyperostosis With Tylosis omim.nt ANKYLOSING VERTEBRAL HYPEROSTOSIS WITH TYLOSIS|Diffuse Idiopathic Skeletal Hyperostosis owl:Class MONARCH:.well-known/genid/OMIM106400ref2 biolink:NamedThing Personal Communication. omim.nt IAO:0000310 PMID:1129458 biolink:NamedThing omim.nt IAO:0000013 PMID:14800245 biolink:NamedThing omim.nt IAO:0000013 PMID:2322769 biolink:NamedThing omim.nt IAO:0000013 PMID:3899489 biolink:NamedThing omim.nt IAO:0000013 PMID:5346342 biolink:NamedThing omim.nt IAO:0000013 UMLS:C0020498 biolink:NamedThing omim.nt owl:Class ORPHA:2206 biolink:NamedThing|biolink:Disease omim.nt owl:Class http://omim.org/entry/106410.0001 biolink:NamedThing ANK2, GLU1425GLY In a large French kindred with autosomal dominant type 4 long QT syndrome ({600919}), {3:Mohler et al. (2003)} demonstrated that the underlying defect is a glu1425-to-gly (E1425G) missense mutation in ankyrin-B. The amino acid substitution was the result of an A-to-G transition at nucleotide position 4274 in exon 36 of the ANK2 gene. Further studies reported by {4:Mohler et al. (2004)} expanded the phenotype associated with this mutation (see {600919}). In a screening of 664 patients for mutations in the ANK2 gene, a Caucasian female was found to carry the E1425G mutation. She was clinically unaffected and, in contrast to previously identified E1425G patients ({3:Mohler et al., 2003}), had a normal QTc of 410 msec with a heart rate of 60 beats per minute. The proband's 67-year-old mother was a carrier of the E1425G variant with slightly elevated QTc (430-450 msec) and moderately low heart rate (63 beats per minute). Three sibs of the proband died young of sudden death at 25, 17, and 15 years of age. The 25-year-old died while winning a prize. The 17-year-old died in the shower and had previously experienced syncopal episodes associated with athletics. The 15-year-old died getting out of the pool after swimming. The E1425G mutation was not observed in 550 control individuals. It was the only SSCP variant identified within the ankyrin-B spectrin-binding domain (exons 24-36). omim.nt GENO:0000002 http://omim.org/entry/106410 biolink:NamedThing|biolink:Gene ANK2 Ankyrin 2 omim.nt ANKYRIN 2; ANK2|Ankyrin-B|Ankyrin, Brain|Ankyrin, Neuronal|Ankyrin, Nonerythroid owl:Class ClinVar:RCV000019672 biolink:NamedThing omim.nt ClinVar:RCV000019673 biolink:NamedThing omim.nt ClinVar:RCV000058356 biolink:NamedThing omim.nt ClinVar:RCV000170702 biolink:NamedThing omim.nt ClinVar:RCV000171737 biolink:NamedThing omim.nt ClinVar:RCV000244762 biolink:NamedThing omim.nt ClinVar:RCV000845369 biolink:NamedThing omim.nt ClinVar:RCV001002092 biolink:NamedThing omim.nt dbSNP:rs72544141 biolink:NamedThing omim.nt owl:NamedIndividual http://omim.org/entry/106410#0001 biolink:NamedThing omim.nt http://omim.org/entry/106410.0002 biolink:NamedThing ANK2, THR1626ASN In 2 unrelated Caucasian probands from the United States with marginally elevated QTc and arrhythmia ({600919}), {4:Mohler et al. (2004)} identified a 4877C-A transversion in exon 42 of the ANK2 gene, resulting in a thr1626-to-asn (T1626N) substitution. One proband was a 46-year-old female who had a QTc of 450 msec and had experienced syncope, but had a normal resting heart rate of 72 beats per minute. Her daughter was also heterozygous for the T1626N mutation and died of sudden death at age 19 years with no previous cardiac symptoms; QTc and heart rate data were not available. Two sibs, 2 sons, and the mother of the proband were also carriers of the mutation and had resting QTc in the normal range. At the time of report, these carriers were asymptomatic. The second proband was a 51-year-old male who displayed mildly elevated QTc (450 msec) with sinus arrhythmia (heart rate varying from 50 to 110 beats per minute). Two of his sibs with normal QTc were heterozygous for the T1626N mutation but asymptomatic at the time of report. The T1626N mutation was not observed in 550 control individuals. omim.nt GENO:0000002 ClinVar:RCV000019674 biolink:NamedThing omim.nt ClinVar:RCV000058347 biolink:NamedThing omim.nt ClinVar:RCV000171749 biolink:NamedThing omim.nt ClinVar:RCV000204635 biolink:NamedThing omim.nt ClinVar:RCV000223796 biolink:NamedThing omim.nt ClinVar:RCV000618056 biolink:NamedThing omim.nt ClinVar:RCV000723633 biolink:NamedThing omim.nt dbSNP:rs121912705 biolink:NamedThing omim.nt owl:NamedIndividual http://omim.org/entry/106410#0002 biolink:NamedThing omim.nt http://omim.org/entry/106410.0003 biolink:NamedThing ANK2, LEU1622ILE In a European Caucasian female with ventricular tachycardia and ventricular fibrillation ({600919}), {4:Mohler et al. (2004)} identified a 4864C-A transversion in exon 42 of the ANK2 gene, resulting in a leu1622-to-ile (L1622I) substitution. The proband had a normal QTc and a resting heart rate of 63 beats per minute. The proband's mother, sister, and brother were carriers of the mutation, but at the time of report all had been asymptomatic with normal resting QTc and normal heart rates. The L1622I mutation was not observed in control individuals. omim.nt GENO:0000002 ClinVar:RCV000019675 biolink:NamedThing omim.nt ClinVar:RCV000058346 biolink:NamedThing omim.nt ClinVar:RCV000171797 biolink:NamedThing omim.nt ClinVar:RCV000227575 biolink:NamedThing omim.nt ClinVar:RCV000242138 biolink:NamedThing omim.nt ClinVar:RCV000852981 biolink:NamedThing omim.nt ClinVar:RCV000999933 biolink:NamedThing omim.nt dbSNP:rs35530544 biolink:NamedThing omim.nt owl:NamedIndividual http://omim.org/entry/106410#0003 biolink:NamedThing omim.nt http://omim.org/entry/106410.0004 biolink:NamedThing ANK2, ARG1788TRP In 2 unrelated probands with long QT syndrome (LQT4; {600919}), {4:Mohler et al. (2004)} identified a 5336C-T transition in exon 45 of the ANK2 gene, resulting in an arg1788-to-trp (R1788W) substitution. One proband was a 37-year-old Caucasian female from the United States. She presented with syncope (originally treated as a seizure) at age 12 years. This woman subsequently had multiple episodes of syncope associated with sleep, and torsades de pointes ventricular tachycardia was documented. Beta-blocker therapy failed to eliminate symptoms and she was treated with an implantable cardiac defibrillator. ECGs revealed a heart rate of 60 beats per minute, prominent T-U waves, and prolongation of the QT interval with a QTc of 530 msec. The proband's son had also been diagnosed with long QT syndrome. The second proband, heterozygous for the R1788W mutation, was a Caucasian female from Europe with multiple episodes of exercise-associated syncope. She presented with supraventricular and ventricular tachycardias that were reproducibly elicited by exercise tests. The patient had normal QTc at rest (430 msec), but prolongation of 470 msec was observed after a syncopal episode. The woman was successfully treated with beta blockers; however, exercise-induced nonsustained supraventricular and ventricular arrhythmias persisted. The father of the proband carried the mutation with QTc of 430 msec and a heart rate of 67 beats per minute. The R1788W mutation was not identified in 280 DNA samples obtained from individuals with normal ECG. omim.nt GENO:0000002 ClinVar:RCV000019676 biolink:NamedThing omim.nt ClinVar:RCV000058351 biolink:NamedThing omim.nt ClinVar:RCV000171750 biolink:NamedThing omim.nt ClinVar:RCV000211890 biolink:NamedThing omim.nt ClinVar:RCV000234999 biolink:NamedThing omim.nt ClinVar:RCV000474063 biolink:NamedThing omim.nt ClinVar:RCV000620379 biolink:NamedThing omim.nt ClinVar:RCV000852983 biolink:NamedThing omim.nt ClinVar:RCV001082560 biolink:NamedThing omim.nt ClinVar:RCV001145853 biolink:NamedThing omim.nt dbSNP:rs121912706 biolink:NamedThing omim.nt owl:NamedIndividual http://omim.org/entry/106410#0004 biolink:NamedThing omim.nt http://omim.org/entry/106410.0005 biolink:NamedThing ANK2, GLU1813LYS This variant, formerly titled CARDIAC ARRHYTHMIA, ANKYRIN-B-RELATED, has been reclassified because its contribution to the phenotype has not been confirmed. In 2 unrelated probands with cardiac arrhythmia and ventricular fibrillation, respectively ({600919}), {4:Mohler et al. (2004)} identified a 5437G-A transition in exon 45 of the ANK2 gene, resulting in a glu1813-to-lys (E1813K) substitution. One proband was a 24-year-old Caucasian female from Europe diagnosed with recurring arrhythmia and documented torsades de pointes ventricular tachycardia. She presented with an elevated resting QTc of 490 msec and mild brachycardia (62 beats per minute). The second proband was a 60-year-old Caucasian male from the United States who displayed idiopathic ventricular fibrillation ({6:Priori et al., 2001}) with a normal QTc (395 msec), a normal resting ECG, and a heart rate of 64 beats per minute. The E1813K mutation was found in 5 DNA samples obtained from individuals with normal ECGs. omim.nt GENO:0000002 ClinVar:RCV000019677 biolink:NamedThing omim.nt ClinVar:RCV000058352 biolink:NamedThing omim.nt ClinVar:RCV000123649 biolink:NamedThing omim.nt ClinVar:RCV000171798 biolink:NamedThing omim.nt ClinVar:RCV000420423 biolink:NamedThing omim.nt ClinVar:RCV000617748 biolink:NamedThing omim.nt ClinVar:RCV000852984 biolink:NamedThing omim.nt ClinVar:RCV001084983 biolink:NamedThing omim.nt dbSNP:rs45454496 biolink:NamedThing omim.nt owl:NamedIndividual http://omim.org/entry/106410#0005 biolink:NamedThing omim.nt MONARCH:.well-known/genid/bc7c1ce103981e80f329 biolink:NamedThing GRCh38chr4-112705621-113383735-Region omim.nt MONARCH:.well-known/genid/b82c8f76aea01aed14e6 faldo:Region PMID:10579720 biolink:NamedThing omim.nt IAO:0000013 PMID:11334825 biolink:NamedThing omim.nt IAO:0000013 PMID:12571597 biolink:NamedThing omim.nt IAO:0000013 PMID:15178757 biolink:NamedThing omim.nt IAO:0000013 PMID:17242276 biolink:NamedThing omim.nt IAO:0000013 PMID:1830053 biolink:NamedThing omim.nt IAO:0000013 PMID:1833308 biolink:NamedThing omim.nt IAO:0000013 PMID:20543825 biolink:NamedThing omim.nt IAO:0000013 PMID:7485162 biolink:NamedThing omim.nt IAO:0000013 OBO:CHR_9606chr4q25 biolink:NamedThing omim.nt owl:Class http://omim.org/entry/600919 biolink:NamedThing|biolink:Disease Cardiac Arrhythmia, Ankyrin-B-Related Cardiac Arrhythmia, Ankyrin-B-Related omim.nt CARDIAC ARRHYTHMIA, ANKYRIN-B-RELATED|Ankyrin-B Syndrome|Long Qt Syndrome 4 owl:Class http://www.omim.org/phenotypicSeries/PS192500 biolink:NamedThing|biolink:Disease Long QT syndrome omim.nt owl:Class UMLS:C1412403 biolink:NamedThing omim.nt owl:Class https://www.ncbi.nlm.nih.gov/gene/287 biolink:NamedThing omim.nt http://omim.org/entry/106490 biolink:NamedThing|biolink:Gene ANXA3 Annexin A3 omim.nt ANNEXIN A3; ANXA3|Annexin 3|Lipocortin 3 owl:Class MONARCH:.well-known/genid/b6293a9829815c0e5810 biolink:NamedThing GRCh38chr4-78551760-78610446-Region omim.nt MONARCH:.well-known/genid/b3908d7a1dbc12812f42 faldo:Region PMID:1830024 biolink:NamedThing omim.nt IAO:0000013 PMID:2968983 biolink:NamedThing omim.nt IAO:0000013 PMID:2975506 biolink:NamedThing omim.nt IAO:0000013 PMID:8276419 biolink:NamedThing omim.nt IAO:0000013 UMLS:C1412424 biolink:NamedThing omim.nt owl:Class https://www.ncbi.nlm.nih.gov/gene/306 biolink:NamedThing omim.nt http://omim.org/entry/106491 biolink:NamedThing|biolink:Gene ANXA4 Annexin A4 omim.nt ANNEXIN A4; ANXA4|Annexin 4|Placental Anticoagulant Protein 2|Zymogen Granule Membrane-Associated Protein, 36-Kd owl:Class MONARCH:.well-known/genid/b73fc0cebad3d876db56 biolink:NamedThing GRCh38chr2-69643807-69827111-Region omim.nt MONARCH:.well-known/genid/b5e89b511a439b0d8a26 faldo:Region MONARCH:.well-known/genid/OMIM106491ref3 biolink:NamedThing Isolation and expression of cDNA coding for a new member of the phospholipase A2 inhibitor family. omim.nt IAO:0000310 PMID:12020832 biolink:NamedThing omim.nt IAO:0000013 PMID:1346776 biolink:NamedThing omim.nt IAO:0000013 PMID:2530088 biolink:NamedThing omim.nt IAO:0000013 PMID:8188273 biolink:NamedThing omim.nt IAO:0000013 OBO:CHR_9606chr2p13 biolink:NamedThing omim.nt owl:Class UMLS:C1412425 biolink:NamedThing omim.nt owl:Class https://www.ncbi.nlm.nih.gov/gene/307 biolink:NamedThing omim.nt http://omim.org/entry/106500 biolink:NamedThing Annular Erythema omim.nt ANNULAR ERYTHEMA owl:Class PMID:5908098 biolink:NamedThing omim.nt IAO:0000013 UMLS:C0234906 biolink:NamedThing omim.nt owl:Class http://omim.org/entry/106600 biolink:NamedThing|biolink:Disease Tooth Agenesis, Selective, 1 Tooth Agenesis, Selective, 1 omim.nt TOOTH AGENESIS, SELECTIVE, 1; STHAG1|Hypodontia/Oligodontia 1|Hypodontia/Oligodontia With Orofacial Cleft|Second Premolars and Third Molars, Absence of|Tooth Agenesis, Familial|Tooth Agenesis, Selective, With Orofacial Cleft owl:Class MONARCH:.well-known/genid/OMIM106600ref3 biolink:NamedThing Syndromes of the Head and Neck. omim.nt IAO:0000310 MONARCH:.well-known/genid/OMIM106600ref4 biolink:NamedThing Personal Communication. omim.nt IAO:0000310 MONARCH:.well-known/genid/OMIM106600ref5 biolink:NamedThing Two independent inherited tooth anomalies in one family. omim.nt IAO:0000310 MONARCH:.well-known/genid/OMIM106600ref8 biolink:NamedThing Personal Communication. omim.nt IAO:0000310 PMID:10742093 biolink:NamedThing omim.nt IAO:0000013 PMID:12097313 biolink:NamedThing omim.nt IAO:0000013 PMID:15264286 biolink:NamedThing omim.nt IAO:0000013 PMID:16498076 biolink:NamedThing omim.nt IAO:0000013 PMID:18137065 biolink:NamedThing omim.nt IAO:0000013 PMID:22581971 biolink:NamedThing omim.nt IAO:0000013 PMID:27321946 biolink:NamedThing omim.nt IAO:0000013 PMID:8696335 biolink:NamedThing omim.nt IAO:0000013 UMLS:C1970117 biolink:NamedThing omim.nt owl:Class UMLS:C1970118 biolink:NamedThing omim.nt owl:Class UMLS:C3489529 biolink:NamedThing omim.nt owl:Class ORPHA:99798 biolink:NamedThing|biolink:Disease omim.nt owl:Class http://www.omim.org/phenotypicSeries/PS106600 biolink:NamedThing|biolink:Disease Tooth agenesis, selective omim.nt owl:Class http://omim.org/entry/106700 biolink:NamedThing|biolink:Disease Total Anomalous Pulmonary Venous Return 1 Total Anomalous Pulmonary Venous Return 1 omim.nt TOTAL ANOMALOUS PULMONARY VENOUS RETURN 1; TAPVR1|Anomalous Pulmonary Venous Return|Scimitar Anomaly|Scimitar Syndrome owl:Class MONARCH:.well-known/genid/OMIM106700ref1 biolink:NamedThing Familial total anomalous pulmonary venous return: characterization of a large Utah family. (Abstract) omim.nt IAO:0000310 MONARCH:.well-known/genid/OMIM106700ref13 biolink:NamedThing Retour veineux pulmonaire anormal total infra-diaphragmatique familiale. omim.nt IAO:0000310 MONARCH:.well-known/genid/OMIM106700ref14 biolink:NamedThing Personal Communication. omim.nt IAO:0000310 MONARCH:.well-known/genid/OMIM106700ref3 biolink:NamedThing A gene for total anomalous pulmonary venous return (TAPVR-1) maps to the centromere of chromosome 4. (Abstract) omim.nt IAO:0000310 MONARCH:.well-known/genid/OMIM106700ref8 biolink:NamedThing Family studies in congenital heart disease. III. Total anomalous venous connection in two sisters and their female maternal first cousin. omim.nt IAO:0000310 PMID:13878593 biolink:NamedThing omim.nt IAO:0000013 PMID:14426379 biolink:NamedThing omim.nt IAO:0000013 PMID:17036341 biolink:NamedThing omim.nt IAO:0000013 PMID:1887837 biolink:NamedThing omim.nt IAO:0000013 PMID:20071345 biolink:NamedThing omim.nt IAO:0000013 PMID:3564987 biolink:NamedThing omim.nt IAO:0000013 PMID:5097138 biolink:NamedThing omim.nt IAO:0000013 PMID:7747759 biolink:NamedThing omim.nt IAO:0000013 PMID:7847375 biolink:NamedThing omim.nt IAO:0000013 UMLS:C4551904 biolink:NamedThing omim.nt owl:Class UMLS:C4551905 biolink:NamedThing omim.nt owl:Class ORPHA:99125 biolink:NamedThing|biolink:Disease omim.nt owl:Class http://omim.org/entry/106750 biolink:NamedThing|biolink:Disease Anonychia With Flexural Pigmentation omim.nt ANONYCHIA WITH FLEXURAL PIGMENTATION owl:Class PMID:1156563 biolink:NamedThing omim.nt IAO:0000013 UMLS:C1862844 biolink:NamedThing omim.nt owl:Class ORPHA:69125 biolink:NamedThing|biolink:Disease omim.nt owl:Class http://omim.org/entry/106900 biolink:NamedThing Anonychia-Ectrodactyly omim.nt ANONYCHIA-ECTRODACTYLY owl:Class PMID:13488188 biolink:NamedThing omim.nt IAO:0000013 UMLS:C1862843 biolink:NamedThing omim.nt owl:Class http://omim.org/entry/106990 biolink:NamedThing|biolink:Disease Anonychia-Onychodystrophy With Brachydactyly Type B and Ectrodactyly omim.nt ANONYCHIA-ONYCHODYSTROPHY WITH BRACHYDACTYLY TYPE B AND ECTRODACTYLY owl:Class PMID:17163524 biolink:NamedThing omim.nt IAO:0000013 PMID:3780038 biolink:NamedThing omim.nt IAO:0000013 UMLS:C1862842 biolink:NamedThing omim.nt owl:Class ORPHA:2355 biolink:NamedThing|biolink:Disease omim.nt owl:Class http://omim.org/entry/106995 biolink:NamedThing|biolink:Disease Anonychia-Onychodystrophy With Hypoplasia or Absence of Distal Phalanges Anonychia-Onychodystrophy With Hypoplasia or Absence of Distal Phalanges omim.nt ANONYCHIA-ONYCHODYSTROPHY WITH HYPOPLASIA OR ABSENCE OF DISTAL PHALANGES|Cooks Syndrome owl:Class PMID:10327250 biolink:NamedThing omim.nt IAO:0000013 PMID:19639023 biolink:NamedThing omim.nt IAO:0000013 PMID:20145678 biolink:NamedThing omim.nt IAO:0000013 PMID:3978841 biolink:NamedThing omim.nt IAO:0000013 PMID:7315521 biolink:NamedThing omim.nt IAO:0000013 PMID:7473658 biolink:NamedThing omim.nt IAO:0000013 PMID:7981857 biolink:NamedThing omim.nt IAO:0000013 UMLS:C1862841 biolink:NamedThing omim.nt owl:Class ORPHA:1487 biolink:NamedThing|biolink:Disease omim.nt owl:Class http://omim.org/entry/107000 biolink:NamedThing|biolink:Disease Nail Disorder, Nonsyndromic Congenital, 6 Nail Disorder, Nonsyndromic Congenital, 6 omim.nt NAIL DISORDER, NONSYNDROMIC CONGENITAL, 6; NDNC6|Anonychia/Hyponychia and Onychodystrophy|Anonychia, Partial owl:Class MONARCH:.well-known/genid/OMIM107000ref1 biolink:NamedThing Congenital hip dislocation and onychodystrophy in a family. omim.nt IAO:0000310 MONARCH:.well-known/genid/OMIM107000ref3 biolink:NamedThing Hereditary onychial dysplasia. omim.nt IAO:0000310 MONARCH:.well-known/genid/OMIM107000ref4 biolink:NamedThing Nagel und Skelettanomalian. omim.nt IAO:0000310 MONARCH:.well-known/genid/OMIM107000ref5 biolink:NamedThing Personal Communication. omim.nt IAO:0000310 MONARCH:.well-known/genid/OMIM107000ref6 biolink:NamedThing Inheritance of absence of thumb nails. omim.nt IAO:0000310 MONARCH:.well-known/genid/OMIM107000ref8 biolink:NamedThing Anonychia congenita. In: Becker, P. E. (ed.): Humangenetik. Vol. 4. omim.nt IAO:0000310 PMID:30435097 biolink:NamedThing omim.nt IAO:0000013 PMID:5771215 biolink:NamedThing omim.nt IAO:0000013 UMLS:C3275544 biolink:NamedThing omim.nt owl:Class ORPHA:79143 biolink:NamedThing|biolink:Disease omim.nt owl:Class ORPHA:90390 biolink:NamedThing|biolink:Disease omim.nt owl:Class http://omim.org/entry/107100 biolink:NamedThing|biolink:Disease Anorectal Anomalies Anorectal Anomalies omim.nt ANORECTAL ANOMALIES owl:Class MONARCH:.well-known/genid/OMIM107100ref1 biolink:NamedThing Familial incidence of congenital anorectal anomalies. omim.nt IAO:0000310 MONARCH:.well-known/genid/OMIM107100ref5 biolink:NamedThing Familial anorectal anomalies. omim.nt IAO:0000310 PMID:13424267 biolink:NamedThing omim.nt IAO:0000013 PMID:6627722 biolink:NamedThing omim.nt IAO:0000013 PMID:9268096 biolink:NamedThing omim.nt IAO:0000013 UMLS:C3495676 biolink:NamedThing omim.nt owl:Class ORPHA:557 biolink:NamedThing|biolink:Disease omim.nt owl:Class http://omim.org/entry/107200 biolink:NamedThing|biolink:Disease Anosmia, Isolated Congenital Anosmia, Isolated Congenital omim.nt ANOSMIA, ISOLATED CONGENITAL; ANIC|Anosmia, Congenital owl:Class MONARCH:.well-known/genid/OMIM107200ref10 biolink:NamedThing A family showing smell disturbance and tremor. omim.nt IAO:0000310 MONARCH:.well-known/genid/OMIM107200ref6 biolink:NamedThing Absence of olfactory sensation. omim.nt IAO:0000310 PMID:13965019 biolink:NamedThing omim.nt IAO:0000013 PMID:15060109 biolink:NamedThing omim.nt IAO:0000013 PMID:16606836 biolink:NamedThing omim.nt IAO:0000013 PMID:18869064 biolink:NamedThing omim.nt IAO:0000013 PMID:5399208 biolink:NamedThing omim.nt IAO:0000013 PMID:5409599 biolink:NamedThing omim.nt IAO:0000013 PMID:5919183 biolink:NamedThing omim.nt IAO:0000013 PMID:9568760 biolink:NamedThing omim.nt IAO:0000013 UMLS:C0393778 biolink:NamedThing omim.nt owl:Class ORPHA:88620 biolink:NamedThing|biolink:Disease omim.nt owl:Class http://omim.org/entry/107240 biolink:NamedThing omim.nt True owl:Class http://omim.org/entry/116930 biolink:NamedThing|biolink:Gene NCAM1 Cell Adhesion Molecule, Neural, 1|defective in "staggerer" in mice omim.nt CELL ADHESION MOLECULE, NEURAL, 1; NCAM1|Antigen Msk39 Identified by Monoclonal Antibody 5.1H11|Cd56 owl:Class http://omim.org/entry/107250 biolink:NamedThing|biolink:Disease Anterior Segment Dysgenesis 1 Anterior Segment Dysgenesis 1 omim.nt ANTERIOR SEGMENT DYSGENESIS 1; ASGD1|Anterior Segment Mesenchymal Dysgenesis|Anterior Segment Ocular Dysgenesis owl:Class MONARCH:.well-known/genid/OMIM107250ref3 biolink:NamedThing Hereditary microcornea and cataract in 5 generations. omim.nt IAO:0000310 MONARCH:.well-known/genid/OMIM107250ref5 biolink:NamedThing Autosomal dominant anterior segment dysgenesis with variable expressivity: probable linkage to MNS blood group on chromosome 4. (Abstract) omim.nt IAO:0000310 PMID:10361984 biolink:NamedThing omim.nt IAO:0000013 PMID:12015278 biolink:NamedThing omim.nt IAO:0000013 PMID:18989383 biolink:NamedThing omim.nt IAO:0000013 PMID:27839872 biolink:NamedThing omim.nt IAO:0000013 PMID:3355418 biolink:NamedThing omim.nt IAO:0000013 PMID:4028500 biolink:NamedThing omim.nt IAO:0000013 PMID:550913 biolink:NamedThing omim.nt IAO:0000013 PMID:6801987 biolink:NamedThing omim.nt IAO:0000013 PMID:6978612 biolink:NamedThing omim.nt IAO:0000013 PMID:9620774 biolink:NamedThing omim.nt IAO:0000013 UMLS:C1862839 biolink:NamedThing omim.nt owl:Class UMLS:C4551992 biolink:NamedThing omim.nt owl:Class ORPHA:88632 biolink:NamedThing|biolink:Disease omim.nt owl:Class http://www.omim.org/phenotypicSeries/PS107250 biolink:NamedThing|biolink:Disease Anterior segment dysgenesis omim.nt owl:Class http://omim.org/entry/107254 biolink:NamedThing Antigen Identified by Monoclonal Antibody 30.2A8 omim.nt ANTIGEN IDENTIFIED BY MONOCLONAL ANTIBODY 30.2A8; MIC12|Leukocyte Antigen Mic12 owl:Class PMID:3979119 biolink:NamedThing omim.nt IAO:0000013 UMLS:C1417155 biolink:NamedThing omim.nt owl:Class http://omim.org/entry/107257 biolink:NamedThing omim.nt True owl:Class http://omim.org/entry/143030 biolink:NamedThing|biolink:Gene CD9 Cd9 Antigen omim.nt CD9 ANTIGEN; CD9|Antigen Defined by Monoclonal Antibody 602-29|Leukocyte Antigen Mic3 owl:Class http://omim.org/entry/107260 biolink:NamedThing Antigen Msk41 Identified by Monoclonal Antibody E3 omim.nt ANTIGEN MSK41 IDENTIFIED BY MONOCLONAL ANTIBODY E3; MSK41 owl:Class MONARCH:.well-known/genid/OMIM107260ref1 biolink:NamedThing Chromosome assignment of the human 5.1H11 and E3 cell surface antigens. (Abstract) omim.nt IAO:0000310 UMLS:C1862836 biolink:NamedThing omim.nt owl:Class http://omim.org/entry/107265.0001 biolink:NamedThing CD19, 1-BP INS, 972A In a Turkish girl, born of consanguineous parents, who had common variable immunodeficiency-3 (CVID3; {613493}), {12:van Zelm et al. (2006)} identified homozygosity for an insertion of an adenine in exon 6 of the CD19 gene. This insertion caused a frameshift, resulting in a premature stop codon at the intracellular amino acid 328. The patient had a history of recurrent bronchiolitis and bronchopneumonia starting at 1 year of age and meningitis starting at 8 years of age. A diagnosis of postinfectious glomerulonephritis was made at the age of 10 years, at which time she was found to have hypogammaglobulinemia. omim.nt GENO:0000002 http://omim.org/entry/107265 biolink:NamedThing|biolink:Gene CD19 Cd19 Antigen omim.nt CD19 ANTIGEN; CD19|B-Lymphocyte Antigen Cd19 owl:Class ClinVar:RCV000019670 biolink:NamedThing omim.nt http://omim.org/entry/107265#0001 biolink:NamedThing omim.nt http://omim.org/entry/107265.0002 biolink:NamedThing CD19, 2-BP DEL, 1384GA In 3 sibs, offspring of unrelated parents of Colombian descent, examined at ages 35, 33, and 49 years of age, respectively, for common variable immunodeficiency-3 (CVID3; {613493}), {12:van Zelm et al. (2006)} identified homozygosity for a dinucleotide deletion of guanine and adenine in exon 11 of the CD19 gene, resulting in a premature stop codon at the intracellular amino acid 465. The parents and several members of the family were heterozygous for the mutation but had no clinical features of immunodeficiency. All 3 sibs had had otitis media, sinusitis, and pharyngitis during childhood. In addition, 1 had had 4 bouts of pneumonia between the ages of 18 and 35 years; he had received diagnoses of bacterial conjunctivitis and chronic gastritis (Helicobacter pylori infection). The study showed that the disruption of CD19 signaling results in a primary antibody deficiency, mainly characterized by a poor antigen-specific response. Normal levels of CD19 transcripts were found in B cells from all patients. omim.nt GENO:0000002 ClinVar:RCV000019671 biolink:NamedThing omim.nt http://omim.org/entry/107265#0002 biolink:NamedThing omim.nt http://omim.org/entry/107265.0003 biolink:NamedThing CD19, IVS6AS, G-T, -1 In a Japanese boy with common variable immunodeficiency-3 (CVID3; {613493}), {6:Kanegane et al. (2007)} identified compound heterozygous genetic alterations resulting in disruption of the CD19 gene. One allele, inherited from the unaffected mother, carried a heterozygous G-to-T transversion in intron 6, resulting in the skipping of exon 6, a frameshift, and premature termination. The other allele carried a 68.5-kb deletion including the ATP2A1 ({108730}), CD19, and NFATC2IP ({614525}) genes. Paternal DNA was not available to determine whether the large deletion was inherited or occurred de novo. omim.nt GENO:0000002 ClinVar:RCV000240815 biolink:NamedThing omim.nt dbSNP:rs1567506566 biolink:NamedThing omim.nt owl:NamedIndividual http://omim.org/entry/107265#0003 biolink:NamedThing omim.nt http://omim.org/entry/107265.0004 biolink:NamedThing CD19, TRP52CYS In a 6-year-old Moroccan boy, born of consanguineous parents, with common variable immunodeficiency-3 (CVID3; {613493}), {13:van Zelm et al. (2011)} identified a homozygous c.156G-C transversion ({VAR c.156G-C, NM_001770.5}) in exon 2 of the CD19 gene, resulting in a trp52-to-cys (W52C) substitution at a conserved residue in the D1 extracellular immunoglobulin superfamily constant domain. Each unaffected parent was heterozygous for the mutation. Flow cytometry showed absence of CD19 expression on the patient's B cells; heterozygous carriers had decreased CD19 expression compared to controls. Western blot analysis of patient cells showed decreased amounts of intracellular protein compared to controls, and the mutant protein was smaller, suggesting abnormal processing and immature glycosylation. Patient B cells showed defective antibody production in response to vaccination, as well as delayed calcium influx from the endoplasmic reticulum to the cytoplasm upon stimulation, consistent with a signaling defect. The few remaining memory B cells from the patient showed greatly reduced somatic hypermutation compared to controls. Expression of wildtype CD19 in patient cells restored the expression of CD19 on the surface of B cells. The findings indicated that the W52 residue is critical for proper folding and stability of the immunoglobulin superfamily domain. omim.nt GENO:0000002 ClinVar:RCV000240828 biolink:NamedThing omim.nt dbSNP:rs886037920 biolink:NamedThing omim.nt owl:NamedIndividual http://omim.org/entry/107265#0004 biolink:NamedThing omim.nt http://omim.org/entry/107265.0005 biolink:NamedThing CD19, 1-BP DEL, 1464C In a 11-year-old girl of Kurdish descent (patient A) with common variable immunodeficiency-3 (CVID3; {613493}), {15:Vince et al. (2011)} identified a homozygous 1-bp deletion (c.1464delC) in the CD19 gene, resulting in a frameshift and premature termination (Pro488ProfsTer15) in the intracytoplasmic domain. The patient's unaffected parents and sibling were heterozygous for the mutation. omim.nt GENO:0000002 ClinVar:RCV000240806 biolink:NamedThing omim.nt dbSNP:rs886037921 biolink:NamedThing omim.nt owl:NamedIndividual http://omim.org/entry/107265#0005 biolink:NamedThing omim.nt http://omim.org/entry/107265.0006 biolink:NamedThing CD19, 28-BP DEL/23-BP INS In a 31-year-old woman (Patient B), born of consanguineous Moroccan parents, with common variable immunodeficiency-3 (CVID3; {613493}), {15:Vince et al. (2011)} identified a homozygous complex insertion in the CD19 gene (c.1653_1671+9del28bpins23bp) that was predicted to disrupt the wildtype stop codon (Gly551GlyfsTer25) and affect the intracytoplasmic domain. The patient had a somewhat unusual phenotype in that she had protective levels of antibodies to vaccinations, had selective IgG1 deficiency, normal levels of IgD-CD27+ switched memory B cells. She had clinical evidence of immunodeficiency, but the major complication was progressive IgA nephropathy and glomerulonephritis resulting in end-stage renal disease. omim.nt GENO:0000002 ClinVar:RCV000240820 biolink:NamedThing omim.nt http://omim.org/entry/107265#0006 biolink:NamedThing omim.nt MONARCH:.well-known/genid/b7fb187f58c72c491d69 biolink:NamedThing GRCh38chr16-28931734-28939346-Region omim.nt MONARCH:.well-known/genid/bde8347150f8b4ba966a faldo:Region PMID:10933394 biolink:NamedThing omim.nt IAO:0000013 PMID:11086109 biolink:NamedThing omim.nt IAO:0000013 PMID:11509585 biolink:NamedThing omim.nt IAO:0000013 PMID:12045259 biolink:NamedThing omim.nt IAO:0000013 PMID:12563260 biolink:NamedThing omim.nt IAO:0000013 PMID:1373518 biolink:NamedThing omim.nt IAO:0000013 PMID:16672701 biolink:NamedThing omim.nt IAO:0000013 PMID:17882224 biolink:NamedThing omim.nt IAO:0000013 PMID:19494255 biolink:NamedThing omim.nt IAO:0000013 PMID:19706534 biolink:NamedThing omim.nt IAO:0000013 PMID:21159371 biolink:NamedThing omim.nt IAO:0000013 PMID:21330302 biolink:NamedThing omim.nt IAO:0000013 PMID:24418477 biolink:NamedThing omim.nt IAO:0000013 PMID:2472450 biolink:NamedThing omim.nt IAO:0000013 PMID:28562582 biolink:NamedThing omim.nt IAO:0000013 PMID:7513297 biolink:NamedThing omim.nt IAO:0000013 http://omim.org/entry/613493 biolink:NamedThing|biolink:Disease Immunodeficiency, Common Variable, 3 Immunodeficiency, Common Variable, 3 omim.nt IMMUNODEFICIENCY, COMMON VARIABLE, 3; CVID3|Antibody Deficiency Due to Cd19 Defect owl:Class http://www.omim.org/phenotypicSeries/PS607594 biolink:NamedThing|biolink:Disease Immunodeficiency, common variable omim.nt owl:Class UMLS:C1413206 biolink:NamedThing omim.nt owl:Class https://www.ncbi.nlm.nih.gov/gene/930 biolink:NamedThing omim.nt http://omim.org/entry/107266 biolink:NamedThing|biolink:Gene CD22 Cd22 Antigen omim.nt CD22 ANTIGEN; CD22|B-Cell Antigen Cd22|Sialic Acid-Binding Immunoglobulin-Like Lectin 2 owl:Class MONARCH:.well-known/genid/b66f7ade972036988e44 biolink:NamedThing GRCh38chr19-35329186-35347360-Region omim.nt MONARCH:.well-known/genid/b2f5504573bd736579f9 faldo:Region PMID:10722703 biolink:NamedThing omim.nt IAO:0000013 PMID:11021804 biolink:NamedThing omim.nt IAO:0000013 PMID:12493916 biolink:NamedThing omim.nt IAO:0000013 PMID:12646615 biolink:NamedThing omim.nt IAO:0000013 PMID:15133509 biolink:NamedThing omim.nt IAO:0000013 PMID:1985119 biolink:NamedThing omim.nt IAO:0000013 PMID:30944478 biolink:NamedThing omim.nt IAO:0000013 PMID:8496602 biolink:NamedThing omim.nt IAO:0000013 PMID:8864124 biolink:NamedThing omim.nt IAO:0000013 OBO:CHR_9606chr19q13.1 biolink:NamedThing omim.nt owl:Class UMLS:C1332708 biolink:NamedThing omim.nt owl:Class https://www.ncbi.nlm.nih.gov/gene/933 biolink:NamedThing omim.nt http://omim.org/entry/107269.0001 biolink:NamedThing CD44, ARG46PRO ({dbSNP rs369473842}) The Indian blood group ({609027}) comprises 2 antigens, In(a) and In(b), which reside on CD44. By RT-PCR analysis of cDNA extracted from In(a+b-)-transformed B lymphocytes, {33:Telen et al. (1996)} identified the CD44 polymorphism that causes the In(b-) phenotype. The G-to-C change at nucleotide 252 results in an arg46-to-pro change (R46P), removing the basically charged amino acid at the C terminus of the hyaluronan (HA)-binding motif of CD44. In previous studies using chimeric proteins, arg46 was shown to be crucial for HA binding by CD44 ({39:Yang et al., 1994}). However, {33:Telen et al. (1996)} demonstrated that the R46P change does not reduce HA binding to CD44. The SNP for the Indian blood group polymorphism is {dbSNP rs369473842} ({8:Gassner et al., 2018}). omim.nt GENO:0000002 http://omim.org/entry/107269 biolink:NamedThing|biolink:Gene CD44 Cd44 Antigen omim.nt CD44 ANTIGEN; CD44|Hermes Antigen|Inlu-Related P80 Glycoprotein|Mdu3|Pgp1 owl:Class ClinVar:RCV000019669 biolink:NamedThing omim.nt dbSNP:rs121909545 biolink:NamedThing omim.nt owl:NamedIndividual dbSNP:rs369473842 biolink:NamedThing omim.nt owl:NamedIndividual http://omim.org/entry/107269#0001 biolink:NamedThing omim.nt MONARCH:.well-known/genid/b5f303ccc23df0e84f9c biolink:NamedThing GRCh38chr11-35139167-35232401-Region omim.nt MONARCH:.well-known/genid/b92146c4c97ee5d1fa9d faldo:Region MONARCH:.well-known/genid/OMIM107269ref1 biolink:NamedThing Mapping of gene for human lymphocyte homing receptor to the short arm of chromosome 11. (Abstract) omim.nt IAO:0000310 MONARCH:.well-known/genid/OMIM107269ref11 biolink:NamedThing Personal Communication. omim.nt IAO:0000310 MONARCH:.well-known/genid/OMIM107269ref25 biolink:NamedThing Personal Communication. omim.nt IAO:0000310 MONARCH:.well-known/genid/OMIM107269ref34 biolink:NamedThing Personal Communication. omim.nt IAO:0000310 PMID:11740562 biolink:NamedThing omim.nt IAO:0000013 PMID:11935029 biolink:NamedThing omim.nt IAO:0000013 PMID:12618522 biolink:NamedThing omim.nt IAO:0000013 PMID:12697740 biolink:NamedThing omim.nt IAO:0000013 PMID:1357452 biolink:NamedThing omim.nt IAO:0000013 PMID:1399141 biolink:NamedThing omim.nt IAO:0000013 PMID:1465456 biolink:NamedThing omim.nt IAO:0000013 PMID:15023889 biolink:NamedThing omim.nt IAO:0000013 PMID:15781582 biolink:NamedThing omim.nt IAO:0000013 PMID:1694723 biolink:NamedThing omim.nt IAO:0000013 PMID:16998483 biolink:NamedThing omim.nt IAO:0000013 PMID:16998484 biolink:NamedThing omim.nt IAO:0000013 PMID:18193036 biolink:NamedThing omim.nt IAO:0000013 PMID:1830244 biolink:NamedThing omim.nt IAO:0000013 PMID:18614011 biolink:NamedThing omim.nt IAO:0000013 PMID:21364036 biolink:NamedThing omim.nt IAO:0000013 PMID:24378538 biolink:NamedThing omim.nt IAO:0000013 PMID:2466575 biolink:NamedThing omim.nt IAO:0000013 PMID:2467821 biolink:NamedThing omim.nt IAO:0000013 PMID:25767277 biolink:NamedThing omim.nt IAO:0000013 PMID:2659502 biolink:NamedThing omim.nt IAO:0000013 PMID:2659503 biolink:NamedThing omim.nt IAO:0000013 PMID:27974793 biolink:NamedThing omim.nt IAO:0000013 PMID:30283273 biolink:NamedThing omim.nt IAO:0000013 PMID:3286493 biolink:NamedThing omim.nt IAO:0000013 PMID:6190235 biolink:NamedThing omim.nt IAO:0000013 PMID:6466869 biolink:NamedThing omim.nt IAO:0000013 PMID:6863545 biolink:NamedThing omim.nt IAO:0000013 PMID:7508860 biolink:NamedThing omim.nt IAO:0000013 PMID:7692200 biolink:NamedThing omim.nt IAO:0000013 PMID:7909665 biolink:NamedThing omim.nt IAO:0000013 PMID:8560266 biolink:NamedThing omim.nt IAO:0000013 PMID:8636151 biolink:NamedThing omim.nt IAO:0000013 PMID:9310473 biolink:NamedThing omim.nt IAO:0000013 PMID:9531542 biolink:NamedThing omim.nt IAO:0000013 http://omim.org/entry/609027 biolink:NamedThing|biolink:Disease Blood Group, Indian System Blood Group, Indian System omim.nt BLOOD GROUP, INDIAN SYSTEM; IN|Indian Blood Group System owl:Class UMLS:C1332712 biolink:NamedThing omim.nt owl:Class https://www.ncbi.nlm.nih.gov/gene/960 biolink:NamedThing omim.nt http://omim.org/entry/107270 biolink:NamedThing|biolink:Gene CD38 Cd38 Antigen omim.nt CD38 ANTIGEN; CD38|Adp-Ribosyl Cyclase/Cyclic Adp-Ribose Hydrolase|Ecto-Nicotinamide Adenine Dinucleotide Glycohydrolase owl:Class MONARCH:.well-known/genid/bd3ef8ad92dcedcf0bd4 biolink:NamedThing GRCh38chr4-15778327-15853231-Region omim.nt MONARCH:.well-known/genid/bda1d0692e4e61c551c2 faldo:Region PMID:10369916 biolink:NamedThing omim.nt IAO:0000013 PMID:11001947 biolink:NamedThing omim.nt IAO:0000013 PMID:17287729 biolink:NamedThing omim.nt IAO:0000013 PMID:2319135 biolink:NamedThing omim.nt IAO:0000013 PMID:6198179 biolink:NamedThing omim.nt IAO:0000013 PMID:7835083 biolink:NamedThing omim.nt IAO:0000013 PMID:8202488 biolink:NamedThing omim.nt IAO:0000013 PMID:8253715 biolink:NamedThing omim.nt IAO:0000013 PMID:8420005 biolink:NamedThing omim.nt IAO:0000013 PMID:9378973 biolink:NamedThing omim.nt IAO:0000013 PMID:9694721 biolink:NamedThing omim.nt IAO:0000013 OBO:CHR_9606chr4p15 biolink:NamedThing omim.nt owl:Class UMLS:C1413221 biolink:NamedThing omim.nt owl:Class https://www.ncbi.nlm.nih.gov/gene/952 biolink:NamedThing omim.nt http://omim.org/entry/107271.0001 biolink:NamedThing CD59, 1-BP DEL, CODON 16 In a 23-year-old Japanese male with complete deficiency of CD59 (HACD59; {612300}), {19:Motoyama et al. (1992)} identified single-nucleotide deletions in codon 16 (GCC to GC) and codon 96 (GCA to CA). The homozygous deletion in codon 16 resulted in a frameshift and introduced a stop codon at position 54. The parents, who were cousins, were heterozygous for the mutation. One sister was also heterozygous; a brother was homozygous normal. Presumably it was the deletion in codon 16 that was responsible for the effects on the protein resulting in CD59 deficiency. The patient presented with paroxysmal nocturnal hemoglobinuria with onset in adolescence. He had no involvement of the peripheral nervous system at age 22 years ({20:Nevo et al., 2013}). omim.nt GENO:0000002 http://omim.org/entry/107271 biolink:NamedThing|biolink:Gene CD59 Cd59 Antigen|in mouse Ly-6 = multigene complex omim.nt CD59 ANTIGEN; CD59|Human Leukocyte Antigen Mic11|Protectin|Surface Antigen Recognized by Monoclonal Antibody 16.3A5 owl:Class ClinVar:RCV000019668 biolink:NamedThing omim.nt http://omim.org/entry/107271#0001 biolink:NamedThing omim.nt http://omim.org/entry/107271.0002 biolink:NamedThing CD59, CYS89TYR In 5 patients from 4 unrelated families of North African Jewish descent with CD59-mediated hemolytic anemia and immune-mediated polyneuropathy (HACD59; {612300}), {20:Nevo et al. (2013)} identified a homozygous c.266G-A transition in exon 3 of the CD59 gene, resulting in a cys89-to-tyr (C89Y) substitution at a highly conserved residue that participates in the formation of a disulfide bond. The mutation was found by whole-exome sequencing in 2 affected sibs, segregated with the disorder in all families, and was not found in the dbSNP or the Exome Variant Server database. Haplotype analysis indicated a founder effect, and the mutation was found in heterozygous state in 3 of 197 ethnically matched individuals (carrier rate of 1 in 66 in this community). Red blood cells derived from the patients showed lack of CD59 expression, and sural nerve biopsy of 1 patient showed no CD59 expression. Western blot analysis detected reduced amounts of the protein, suggesting that it is synthesized but fails to reach cell membranes. Because C89Y disrupts a disulfide bond, the tertiary structure of the mutant protein may be affected. {20:Nevo et al. (2013)} suggested that improper activation of the complement system due to lack of CD59 expression may cause damage to red cell membranes and result in myelin and axonal damage. omim.nt GENO:0000002 ClinVar:RCV000054836 biolink:NamedThing omim.nt dbSNP:rs397514767 biolink:NamedThing omim.nt owl:NamedIndividual http://omim.org/entry/107271#0002 biolink:NamedThing omim.nt http://omim.org/entry/107271.0003 biolink:NamedThing CD59, 1-BP DEL, 146A In a girl with CD59 deficiency (HACD59; {612300}), progressive neurologic dysfunction, and hemolytic anemia, {8:Hochsmann et al. (2014)} identified a homozygous 1-bp deletion (c.146delA) in exon 5 of the CD59 gene, resulting in a frameshift and premature termination (Asp49ValfsTer31). Her unaffected parents were heterozygous for the mutation. The patient first presented at age 7 months with generalized hypotonia, bulbar symptoms, and areflexia. During later febrile episodes, she developed hemolytic anemia with progressive neurologic deterioration, including T2-weighted hyperintense lesions on brain MRI, seizures, and visual impairment. Flow cytometric analysis of patient peripheral blood cells showed isolated CD59 deficiency. Treatment with eculizumab, an inhibitor of the complement membrane-attack complex, resulted in neurologic improvement about 6 months later. At age 5.5 years, the patient could eat and swallow normally, could walk short distances with support, and had improved cognitive and speech production. omim.nt GENO:0000002 ClinVar:RCV000087130 biolink:NamedThing omim.nt dbSNP:rs587777149 biolink:NamedThing omim.nt owl:NamedIndividual http://omim.org/entry/107271#0003 biolink:NamedThing omim.nt MONARCH:.well-known/genid/b554413433ee42dd46d8 biolink:NamedThing GRCh38chr11-33703009-33736478-Region omim.nt MONARCH:.well-known/genid/b69d818bbd4947efb818 faldo:Region MONARCH:.well-known/genid/OMIM107271ref18 biolink:NamedThing The newt ortholog of CD59 is implicated in proximodistal identity during amphibian limb regeneration. omim.nt IAO:0000310 PMID:10568747 biolink:NamedThing omim.nt IAO:0000013 PMID:10805801 biolink:NamedThing omim.nt IAO:0000013 PMID:10965140 biolink:NamedThing omim.nt IAO:0000013 PMID:11435315 biolink:NamedThing omim.nt IAO:0000013 PMID:1282740 biolink:NamedThing omim.nt IAO:0000013 PMID:1381503 biolink:NamedThing omim.nt IAO:0000013 PMID:1382994 biolink:NamedThing omim.nt IAO:0000013 PMID:1383553 biolink:NamedThing omim.nt IAO:0000013 PMID:16567644 biolink:NamedThing omim.nt IAO:0000013 PMID:1694224 biolink:NamedThing omim.nt IAO:0000013 PMID:1698710 biolink:NamedThing omim.nt IAO:0000013 PMID:1733867 biolink:NamedThing omim.nt IAO:0000013 PMID:17975060 biolink:NamedThing omim.nt IAO:0000013 PMID:2307842 biolink:NamedThing omim.nt IAO:0000013 PMID:23149847 biolink:NamedThing omim.nt IAO:0000013 PMID:24382084 biolink:NamedThing omim.nt IAO:0000013 PMID:2475570 biolink:NamedThing omim.nt IAO:0000013 PMID:2476389 biolink:NamedThing omim.nt IAO:0000013 PMID:2487685 biolink:NamedThing omim.nt IAO:0000013 PMID:2882510 biolink:NamedThing omim.nt IAO:0000013 PMID:2892786 biolink:NamedThing omim.nt IAO:0000013 PMID:6382636 biolink:NamedThing omim.nt IAO:0000013 PMID:7522635 biolink:NamedThing omim.nt IAO:0000013 PMID:7683594 biolink:NamedThing omim.nt IAO:0000013 PMID:7691713 biolink:NamedThing omim.nt IAO:0000013 PMID:8650192 biolink:NamedThing omim.nt IAO:0000013 OBO:CHR_9606chr11p13 biolink:NamedThing omim.nt owl:Class http://omim.org/entry/612300 biolink:NamedThing|biolink:Disease Hemolytic Anemia, Cd59-Mediated, With or Without Immune-Mediated Polyneuropathy Hemolytic Anemia, Cd59-Mediated, With or Without Immune-Mediated Polyneuropathy omim.nt HEMOLYTIC ANEMIA, CD59-MEDIATED, WITH OR WITHOUT IMMUNE-MEDIATED POLYNEUROPATHY; HACD59|Cd59 Deficiency owl:Class UMLS:C1413230 biolink:NamedThing omim.nt owl:Class https://www.ncbi.nlm.nih.gov/gene/966 biolink:NamedThing omim.nt http://omim.org/entry/107272 biolink:NamedThing|biolink:Gene CD72 Cd72 Antigen omim.nt CD72 ANTIGEN; CD72|Lyb2, Mouse, Homolog of owl:Class MONARCH:.well-known/genid/b499eb4992c0e938bf06 biolink:NamedThing GRCh38chr9-35609980-35618426-Region omim.nt MONARCH:.well-known/genid/b3fce5705f9619940090 faldo:Region PMID:11114375 biolink:NamedThing omim.nt IAO:0000013 PMID:15459183 biolink:NamedThing omim.nt IAO:0000013 PMID:2044654 biolink:NamedThing omim.nt IAO:0000013 OBO:CHR_9606chr9p biolink:NamedThing omim.nt owl:Class UMLS:C1332716 biolink:NamedThing omim.nt owl:Class https://www.ncbi.nlm.nih.gov/gene/971 biolink:NamedThing omim.nt http://omim.org/entry/107273 biolink:NamedThing|biolink:Gene CD69 Cd69 Antigen omim.nt CD69 ANTIGEN; CD69|Early T-Cell Activation Antigen P60 owl:Class MONARCH:.well-known/genid/b5cad6cf7c2a29e62b9a biolink:NamedThing GRCh38chr12-9752485-9760900-Region omim.nt MONARCH:.well-known/genid/b642da29f86592482b8f faldo:Region PMID:12732655 biolink:NamedThing omim.nt IAO:0000013 PMID:12975472 biolink:NamedThing omim.nt IAO:0000013 PMID:1612643 biolink:NamedThing omim.nt IAO:0000013 PMID:16525420 biolink:NamedThing omim.nt IAO:0000013 PMID:8340758 biolink:NamedThing omim.nt IAO:0000013 UMLS:C1413235 biolink:NamedThing omim.nt owl:Class https://www.ncbi.nlm.nih.gov/gene/969 biolink:NamedThing omim.nt http://omim.org/entry/107280.0001 biolink:NamedThing SERPINA3, MET389VAL By PCR-single strand conformation polymorphism (SSCP) analysis, {23:Tsuda et al. (1992)} identified a point mutation in exon 5 of the AACT gene resulting in substitution of met by val at codon 389. The mutation, an A-to-G transition at basepair 1252, was found in heterozygous state in 6 patients; 4 of the 6 (aged 38, 43, 69, and 80 years) had occlusive cerebrovascular disease. In 35 individuals with non-AD dementia (primarily vascular) and 100 with Alzheimer-type dementia, {4:Gilfix and Briones (1997)} found none that carried the met389-to-val polymorphism. The polymorphism was also not found in 59 North American controls. {21:Tachikawa et al. (2001)} found that the frequency of the met389-to-val variant of AACT was higher in a group with ischemic cerebrovascular disease than in a control group, which appeared to be independent of known risk factors. They subdivided the cerebrovascular disease group into lacunar and atherothrombotic subgroups. Atherothrombotic infarction occurs with atherosclerosis involving selected sites in extracranial and major intracranial arteries. The term lacunar-type infarction is used to refer to small lesions that result from the involvement of deep, small, penetrating arteries. Further analysis by subtype showed association of the mutation particularly with lacunar infarction. omim.nt GENO:0000002 http://omim.org/entry/107280 biolink:NamedThing|biolink:Gene SERPINA3 220kb from PI|Serpin Peptidase Inhibitor, Clade A, Member 3 omim.nt SERPIN PEPTIDASE INHIBITOR, CLADE A, MEMBER 3; SERPINA3|Alpha-1-Antichymotrypsin|Antichymotrypsin, Alpha-1 owl:Class ClinVar:RCV000019663 biolink:NamedThing omim.nt ClinVar:RCV000490276 biolink:NamedThing omim.nt dbSNP:rs116929575 biolink:NamedThing omim.nt owl:NamedIndividual http://omim.org/entry/107280#0001 biolink:NamedThing omim.nt http://omim.org/entry/107280.0002 biolink:NamedThing SERPINA3, 2-BP DEL {22:Tsuda et al. (1992)} used PCR-SCCP and direct sequencing to demonstrate a variant AACT: deletion of 2 bases (AA) from codon 391 (AAA for lys) led to a frameshift, a change in the amino acid sequence downstream of the deletion, and elongation of the peptide chain by 10 amino acids. The subject was a 26-year-old asymptomatic male. The concentration of serum AACT was about 40% of the normal level, suggesting that the variant molecule is not secreted from the liver or is rapidly degraded. omim.nt GENO:0000002 ClinVar:RCV000019664 biolink:NamedThing omim.nt http://omim.org/entry/107280#0002 biolink:NamedThing omim.nt http://omim.org/entry/107280.0003 biolink:NamedThing SERPINA3, LEU55PRO Using denaturing gradient gel electrophoresis and direct sequencing of amplified genomic DNA, {15:Poller et al. (1993)} identified 2 defective mutants of the human AACT gene associated with chronic obstructive pulmonary disease (COPD). A CTG (leu) to CCG (pro) transition in codon 55 was found in affected members in 3 successive generations. omim.nt GENO:0000002 ClinVar:RCV000019665 biolink:NamedThing omim.nt dbSNP:rs1800463 biolink:NamedThing omim.nt owl:NamedIndividual http://omim.org/entry/107280#0003 biolink:NamedThing omim.nt http://omim.org/entry/107280.0004 biolink:NamedThing SERPINA3, PRO229ALA In 4 patients with COPD and a positive family history for COPD, {15:Poller et al. (1993)} observed a CCT (pro)-to-GCT (ala) transversion in codon 229. ({14:Poller et al. (1992)} referred to this mutation as PRO227ALA.) {18:Samilchuk and Chuchalin (1993)} failed to find this mutation among 102 COPD patients treated in Moscow hospitals. omim.nt GENO:0000002 ClinVar:RCV000019666 biolink:NamedThing omim.nt ClinVar:RCV000485718 biolink:NamedThing omim.nt dbSNP:rs17473 biolink:NamedThing omim.nt owl:NamedIndividual http://omim.org/entry/107280#0004 biolink:NamedThing omim.nt http://omim.org/entry/107280.0005 biolink:NamedThing SERPINA3, ALA-15THR The polymorphism discussed by {8:Kamboh et al. (1995)} results in the presence of either an alanine (the A allele, symbolized ACT*A by them) or threonine (the T allele, symbolized ACT*T by them) at residue -15 of the AACT signal peptide; their 'AA' genotype is biallelic for ACT*A, while genotypes 'AT' and 'TT' have 1 and no ACT*A alleles, respectively. The frequency of the 2 alleles ACT*A and ACT*T was approximately equal in the control population and 0.57 and 0.43, respectively, in a group of Alzheimer disease patients. The combination of AA homozygosity with homozygosity of APOE4 ({107741.0016}) had a frequency of 1/17 in the AD group compared to 1/313 in the general population control. Possible mechanisms for the apparent dependent effect of APOE4 on the AACT signal peptide polymorphism were proposed by {8:Kamboh et al. (1995)}: the ACT*A allele in the signal peptide may be in strong linkage disequilibrium with a functional mutation affecting an amino acid substitution in the mature AACT protein which possibly enhances the binding of the AACT protein to amyloid beta protein or interacts with APOE to alter binding to microtubular elements. Alternatively, amino acid changes in a signal peptide could affect hydrophobicity and alter the posttranslational protein structure. {5:Haines et al. (1996)} were, however, unable to confirm any effect of the AA/TT polymorphism, either alone or in combination with the APOE4 allele, in a large set of Alzheimer disease families and sporadic Alzheimer cases. {7:Kamboh et al. (1997)} felt that the data of {5:Haines et al. (1996)} were at least not inconsistent with their own as reported in {8:Kamboh et al. (1995)}. {6:Haines et al. (1997)} retorted and pointed out that 3 additional reports had failed to confirm the findings of {8:Kamboh et al. (1995)}. {6:Haines et al. (1997)} concluded that, in toto, the results suggest that any effect of the ACT signal peptide polymorphism on AD, if it exists at all, is very small. omim.nt GENO:0000002 ClinVar:RCV000019667 biolink:NamedThing omim.nt ClinVar:RCV000455742 biolink:NamedThing omim.nt dbSNP:rs4934 biolink:NamedThing omim.nt owl:NamedIndividual http://omim.org/entry/107280#0005 biolink:NamedThing omim.nt MONARCH:.well-known/genid/b58249d100ed1bcfbf89 biolink:NamedThing GRCh38chr14-94612390-94624052-Region omim.nt MONARCH:.well-known/genid/b3a49344de9fea0085f5 faldo:Region MONARCH:.well-known/genid/OMIM107280ref16 biolink:NamedThing Human alpha-1-antichymotrypsin and alpha-1-antitrypsin (PI) genes map to the same region on chromosome 14. (Abstract) omim.nt IAO:0000310 MONARCH:.well-known/genid/OMIM107280ref19 biolink:NamedThing Physical linkage of the genes PI and AACT. (Abstract) omim.nt IAO:0000310 MONARCH:.well-known/genid/OMIM107280ref6 biolink:NamedThing Reply to 'Genetic effect of alpha-1-antichymotrypsin on the risk of Alzheimer disease.' (Letter) omim.nt IAO:0000310 PMID:11289720 biolink:NamedThing omim.nt IAO:0000013 PMID:11702211 biolink:NamedThing omim.nt IAO:0000013 PMID:11941486 biolink:NamedThing omim.nt IAO:0000013 PMID:1339400 biolink:NamedThing omim.nt IAO:0000013 PMID:1351206 biolink:NamedThing omim.nt IAO:0000013 PMID:14668352 biolink:NamedThing omim.nt IAO:0000013 PMID:1618300 biolink:NamedThing omim.nt IAO:0000013 PMID:16278826 biolink:NamedThing omim.nt IAO:0000013 PMID:1973140 biolink:NamedThing omim.nt IAO:0000013 PMID:3260956 biolink:NamedThing omim.nt IAO:0000013 PMID:3485824 biolink:NamedThing omim.nt IAO:0000013 PMID:3492865 biolink:NamedThing omim.nt IAO:0000013 PMID:6606438 biolink:NamedThing omim.nt IAO:0000013 PMID:7670501 biolink:NamedThing omim.nt IAO:0000013 PMID:8102759 biolink:NamedThing omim.nt IAO:0000013 PMID:8244391 biolink:NamedThing omim.nt IAO:0000013 PMID:8617509 biolink:NamedThing omim.nt IAO:0000013 PMID:9003488 biolink:NamedThing omim.nt IAO:0000013 PMID:9040504 biolink:NamedThing omim.nt IAO:0000013 PMID:9119413 biolink:NamedThing omim.nt IAO:0000013 PMID:9219874 biolink:NamedThing omim.nt IAO:0000013 PMID:9932947 biolink:NamedThing omim.nt IAO:0000013 OBO:CHR_9606chr14q32.1 biolink:NamedThing omim.nt owl:Class UMLS:C1412050 biolink:NamedThing omim.nt owl:Class https://www.ncbi.nlm.nih.gov/gene/12 biolink:NamedThing omim.nt http://omim.org/entry/107285 biolink:NamedThing|biolink:Gene SLPI Secretory Leukocyte Protease Inhibitor omim.nt SECRETORY LEUKOCYTE PROTEASE INHIBITOR; SLPI|Antileukoprotease|Human Seminal Proteinase Inhibitor owl:Class MONARCH:.well-kno