WFS1

This gene encodes a transmembrane protein, which is located primarily in the endoplasmic reticulum and ubiquitously expressed with highest levels in brain, pancreas, heart, and insulinoma beta-cell lines. Wolframin appears to function as a cation-selective ion channel.{{cite journal | vauthors = Osman AA, Saito M, Makepeace C, Permutt MA, Schlesinger P, Mueckler M | title = Wolframin expression induces novel ion channel activity in endoplasmic reticulum membranes and increases intracellular calcium | journal = J. Biol. Chem. | volume = 278 | issue = 52 | pages = 52755–62 |date=December 2003 | pmid = 14527944 | doi = 10.1074/jbc.M310331200 | doi-access = free }}

Mutations in this gene are associated with Wolfram syndrome, also called DIDMOAD (Diabetes Insipidus, Diabetes Mellitus, Optic Atrophy, and Deafness), an autosomal recessive disorder. The disease is characterized by non-immune insulin-dependent diabetes mellitus and bilateral progressive optic atrophy, usually presenting in childhood or early adult life. Diverse neurologic symptoms, including a predisposition to psychiatric illness, may also be associated with this disorder. A large number and variety of mutations in this gene, particularly in exon 8, can be associated with this syndrome. Mutations in this gene can also cause autosomal dominant deafness 6 (DFNA6), also known as DFNA14 or DFNA38.

Mutations in this gene have also been associated with congenital cataracts.{{cite journal | vauthors = Berry V, Gregory-Evans C, Emmett W, Waseem N, Raby J, Prescott D, Moore AT, Bhattacharya SS | title = Wolfram gene (WFS1) mutation causes autosomal dominant congenital nuclear cataract in humans | journal = Eur. J. Hum. Genet. | volume = 21| issue = 12| pages = 1356–60|date=March 2013 | pmid = 23531866 | doi = 10.1038/ejhg.2013.52 | pmc=3831071}}

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• {{cite journal | vauthors=Khanim F, Kirk J, Latif F, Barrett TG |title=WFS1/wolframin mutations, Wolfram syndrome, and associated diseases. |journal=Hum. Mutat. |volume=17 |issue= 5 |pages= 357–67 |year= 2001 |pmid= 11317350 |doi= 10.1002/humu.1110 |s2cid=2944382 |doi-access=free }}
• {{cite journal |vauthors=Cryns K, Sivakumaran TA, Van den Ouweland JM, etal |title=Mutational spectrum of the WFS1 gene in Wolfram syndrome, nonsyndromic hearing impairment, diabetes mellitus, and psychiatric disease. |journal=Hum. Mutat. |volume=22 |issue= 4 |pages= 275–87 |year= 2004 |pmid= 12955714 |doi= 10.1002/humu.10258 |s2cid=39815754 |doi-access=free }}
• {{cite journal | vauthors=McHugh RK, Friedman RA |title=Genetics of hearing loss: Allelism and modifier genes produce a phenotypic continuum. |journal=The Anatomical Record Part A: Discoveries in Molecular, Cellular, and Evolutionary Biology |volume=288 |issue= 4 |pages= 370–81 |year= 2006 |pmid= 16550584 |doi= 10.1002/ar.a.20297 |doi-access= free }}
• {{cite journal |vauthors=Lesperance MM, Hall JW, Bess FH, etal |title=A gene for autosomal dominant nonsyndromic hereditary hearing impairment maps to 4p16.3. |journal=Hum. Mol. Genet. |volume=4 |issue= 10 |pages= 1967–72 |year= 1996 |pmid= 8595423 |doi=10.1093/hmg/4.10.1967 |url=https://zenodo.org/record/1234323 }}
• {{cite journal |vauthors=Strom TM, Hörtnagel K, Hofmann S, etal |title=Diabetes insipidus, diabetes mellitus, optic atrophy and deafness (DIDMOAD) caused by mutations in a novel gene (wolframin) coding for a predicted transmembrane protein. |journal=Hum. Mol. Genet. |volume=7 |issue= 13 |pages= 2021–8 |year= 1999 |pmid= 9817917 |doi=10.1093/hmg/7.13.2021 |doi-access=free }}
• {{cite journal |vauthors=Van Camp G, Kunst H, Flothmann K, etal |title=A gene for autosomal dominant hearing impairment (DFNA14) maps to a region on chromosome 4p16.3 that does not overlap the DFNA6 locus. |journal=J. Med. Genet. |volume=36 |issue= 7 |pages= 532–6 |year= 1999 |pmid= 10424813 |doi= 10.1136/jmg.36.7.532 | pmc=1734405 }}
• {{cite journal |vauthors=Hardy C, Khanim F, Torres R, etal |title=Clinical and molecular genetic analysis of 19 Wolfram syndrome kindreds demonstrating a wide spectrum of mutations in WFS1. |journal=Am. J. Hum. Genet. |volume=65 |issue= 5 |pages= 1279–90 |year= 1999 |pmid= 10521293 |doi=10.1086/302609 | pmc=1288280 }}
• {{cite journal |vauthors=Furlong RA, Ho LW, Rubinsztein JS, etal |title=A rare coding variant within the wolframin gene in bipolar and unipolar affective disorder cases. |journal=Neurosci. Lett. |volume=277 |issue= 2 |pages= 123–6 |year= 2000 |pmid= 10624825 |doi=10.1016/S0304-3940(99)00865-4 |s2cid=31662957 }}
• {{cite journal |vauthors=Awata T, Inoue K, Kurihara S, etal |title=Missense variations of the gene responsible for Wolfram syndrome (WFS1/wolframin) in Japanese: possible contribution of the Arg456His mutation to type 1 diabetes as a nonautoimmune genetic basis. |journal=Biochem. Biophys. Res. Commun. |volume=268 |issue= 2 |pages= 612–6 |year= 2000 |pmid= 10679252 |doi= 10.1006/bbrc.2000.2169 }}
• {{cite journal | vauthors=Ohtsuki T, Ishiguro H, Yoshikawa T, Arinami T |title=WFS1 gene mutation search in depressive patients: detection of five missense polymorphisms but no association with depression or bipolar affective disorder. |journal=Journal of Affective Disorders |volume=58 |issue= 1 |pages= 11–7 |year= 2000 |pmid= 10760554 |doi=10.1016/S0165-0327(99)00099-3 }}
• {{cite journal |vauthors=Gómez-Zaera M, Strom TM, Rodríguez B, etal |title=Presence of a major WFS1 mutation in Spanish Wolfram syndrome pedigrees. |journal=Mol. Genet. Metab. |volume=72 |issue= 1 |pages= 72–81 |year= 2001 |pmid= 11161832 |doi= 10.1006/mgme.2000.3107 }}
• {{cite journal | vauthors=Kaytor EN, Zhu JL, Pao CI, Phillips LS |title=Physiological concentrations of insulin promote binding of nuclear proteins to the insulin-like growth factor I gene. |journal=Endocrinology |volume=142 |issue= 3 |pages= 1041–9 |year= 2001 |pmid= 11181517 |doi=10.1210/endo.142.3.8046 |doi-access=free }}
• {{cite journal |vauthors=Takeda K, Inoue H, Tanizawa Y, etal |title=WFS1 (Wolfram syndrome 1) gene product: predominant subcellular localization to endoplasmic reticulum in cultured cells and neuronal expression in rat brain. |journal=Hum. Mol. Genet. |volume=10 |issue= 5 |pages= 477–84 |year= 2001 |pmid= 11181571 |doi=10.1093/hmg/10.5.477 |doi-access=free }}
• {{cite journal |vauthors=Tessa A, Carbone I, Matteoli MC, etal |title=Identification of novel WFS1 mutations in Italian children with Wolfram syndrome. |journal=Hum. Mutat. |volume=17 |issue= 4 |pages= 348–9 |year= 2001 |pmid= 11295831 |doi= 10.1002/humu.32 |s2cid=45109749 |doi-access= }}
• {{cite journal |vauthors=Bespalova IN, Van Camp G, Bom SJ, etal |title=Mutations in the Wolfram syndrome 1 gene (WFS1) are a common cause of low frequency sensorineural hearing loss. |journal=Hum. Mol. Genet. |volume=10 |issue= 22 |pages= 2501–8 |year= 2002 |pmid= 11709537 |pmc=6198816 |doi=10.1093/hmg/10.22.2501 }}
• {{cite journal |vauthors=Young TL, Ives E, Lynch E, etal |title=Non-syndromic progressive hearing loss DFNA38 is caused by heterozygous missense mutation in the Wolfram syndrome gene WFS1. |journal=Hum. Mol. Genet. |volume=10 |issue= 22 |pages= 2509–14 |year= 2002 |pmid= 11709538 |doi=10.1093/hmg/10.22.2509 |doi-access=free }}
• {{cite journal |vauthors=Crawford J, Zielinski MA, Fisher LJ, etal |title=Is there a relationship between Wolfram syndrome carrier status and suicide? |journal=Am. J. Med. Genet. |volume=114 |issue= 3 |pages= 343–6 |year= 2002 |pmid= 11920861 |doi=10.1002/ajmg.10256 }}

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• [https://www.ncbi.nlm.nih.gov/bookshelf/br.fcgi?book=gene&part=wfs GeneReviews/NCBI/NIH/UW entry on WFS1-Related Disorders]

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