WFS1

Wolfram syndrome 1 (wolframin)
Identifiers
Symbols	WFS1 ; CTRCT41; WFRS; WFS; WFSL
External IDs	OMIM: 606201 MGI: 1328355 HomoloGene: 4380 GeneCards: WFS1 Gene
Gene ontology Molecular function • transporter activity • ubiquitin protein ligase binding • activating transcription factor binding • ATPase binding Cellular component • endoplasmic reticulum • endoplasmic reticulum membrane • integral component of endoplasmic reticulum membrane • dendrite Biological process • negative regulation of transcription from RNA polymerase II promoter • kidney development • renal water homeostasis • ER overload response • visual perception • sensory perception of sound • protein maturation by protein folding • ER-associated ubiquitin-dependent protein catabolic process • endoplasmic reticulum unfolded protein response • positive regulation of protein ubiquitination • endoplasmic reticulum calcium ion homeostasis • response to endoplasmic reticulum stress • IRE1-mediated unfolded protein response • glucose homeostasis • negative regulation of programmed cell death • negative regulation of sequence-specific DNA binding transcription factor activity • negative regulation of neuron apoptotic process • cellular protein metabolic process • positive regulation of adenylate cyclase activity • positive regulation of proteolysis • positive regulation of growth • protein stabilization • neurological system process • positive regulation of protein metabolic process • positive regulation of calcium ion transport • calcium ion homeostasis • polyubiquitinated misfolded protein transport • negative regulation of endoplasmic reticulum stress-induced intrinsic apoptotic signaling pathway • negative regulation of ATF6-mediated unfolded protein response • negative regulation of type B pancreatic cell apoptotic process Sources: Amigo / QuickGO
RNA expression pattern
More reference expression data
Orthologs
Species	Human	Mouse
Entrez	7466	22393
Ensembl	ENSG00000109501	ENSMUSG00000039474
UniProt	O76024	P56695
RefSeq (mRNA)	NM_001145853	NM_011716
RefSeq (protein)	NP_001139325	NP_035846
Location (UCSC)	Chr 4: 6.27 – 6.3 Mb	Chr 5: 36.97 – 36.99 Mb
PubMed search

Wolframin is a protein that in humans is encoded by the WFS1 gene.^[1][2][3]

Function

Wolframin is a transmembrane protein.^[3] Wolframin appears to function as a cation-selective ion channel.^[4]

Clinical significance

Mutations in this gene are associated with an autosomal recessive syndrome characterized by 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.^[3]

Mutations in this gene have also been associated with congenital cataracts.^[5]

References

1. Polymeropoulos MH, Swift RG, Swift M (Jan 1995). "Linkage of the gene for Wolfram syndrome to markers on the short arm of chromosome 4". Nat Genet 8 (1): 95–7. doi:10.1038/ng0994-95. PMID 7987399.
2. Inoue H, Tanizawa Y, Wasson J, Behn P, Kalidas K, Bernal-Mizrachi E, Mueckler M, Marshall H, Donis-Keller H, Crock P, Rogers D, Mikuni M, Kumashiro H, Higashi K, Sobue G, Oka Y, Permutt MA (Oct 1998). "A gene encoding a transmembrane protein is mutated in patients with diabetes mellitus and optic atrophy (Wolfram syndrome)". Nat Genet 20 (2): 143–8. doi:10.1038/2441. PMID 9771706.
3. "Entrez Gene: WFS1 Wolfram syndrome 1 (wolframin)".
4. Osman AA, Saito M, Makepeace C, Permutt MA, Schlesinger P, Mueckler M (December 2003). "Wolframin expression induces novel ion channel activity in endoplasmic reticulum membranes and increases intracellular calcium". J. Biol. Chem. 278 (52): 52755–62. doi:10.1074/jbc.M310331200. PMID 14527944.
5. Berry V, Gregory-Evans C, Emmett W, Waseem N, Raby J, Prescott D, Moore AT, Bhattacharya SS (March 2013). "Wolfram gene (WFS1) mutation causes autosomal dominant congenital nuclear cataract in humans". Eur. J. Hum. Genet. 21 (12): 1356–60. doi:10.1038/ejhg.2013.52. PMID 23531866.

Further reading

• Khanim F, Kirk J, Latif F, Barrett TG (2001). "WFS1/wolframin mutations, Wolfram syndrome, and associated diseases.". Hum. Mutat. 17 (5): 357–67. doi:10.1002/humu.1110. PMID 11317350.
• Cryns K, Sivakumaran TA, Van den Ouweland JM, et al. (2004). "Mutational spectrum of the WFS1 gene in Wolfram syndrome, nonsyndromic hearing impairment, diabetes mellitus, and psychiatric disease.". Hum. Mutat. 22 (4): 275–87. doi:10.1002/humu.10258. PMID 12955714.
• McHugh RK, Friedman RA (2006). "Genetics of hearing loss: Allelism and modifier genes produce a phenotypic continuum.". The Anatomical Record Part A: Discoveries in Molecular, Cellular, and Evolutionary Biology 288 (4): 370–81. doi:10.1002/ar.a.20297. PMID 16550584.
• Lesperance MM, Hall JW, Bess FH, et al. (1996). "A gene for autosomal dominant nonsyndromic hereditary hearing impairment maps to 4p16.3.". Hum. Mol. Genet. 4 (10): 1967–72. doi:10.1093/hmg/4.10.1967. PMID 8595423.
• Strom TM, Hörtnagel K, Hofmann S, et al. (1999). "Diabetes insipidus, diabetes mellitus, optic atrophy and deafness (DIDMOAD) caused by mutations in a novel gene (wolframin) coding for a predicted transmembrane protein.". Hum. Mol. Genet. 7 (13): 2021–8. doi:10.1093/hmg/7.13.2021. PMID 9817917.
• Van Camp G, Kunst H, Flothmann K, et al. (1999). "A gene for autosomal dominant hearing impairment (DFNA14) maps to a region on chromosome 4p16.3 that does not overlap the DFNA6 locus.". J. Med. Genet. 36 (7): 532–6. doi:10.1136/jmg.36.7.532. PMC 1734405. PMID 10424813.
• Hardy C, Khanim F, Torres R, et al. (1999). "Clinical and molecular genetic analysis of 19 Wolfram syndrome kindreds demonstrating a wide spectrum of mutations in WFS1.". Am. J. Hum. Genet. 65 (5): 1279–90. doi:10.1086/302609. PMC 1288280. PMID 10521293.
• Furlong RA, Ho LW, Rubinsztein JS, et al. (2000). "A rare coding variant within the wolframin gene in bipolar and unipolar affective disorder cases.". Neurosci. Lett. 277 (2): 123–6. doi:10.1016/S0304-3940(99)00865-4. PMID 10624825.
• Awata T, Inoue K, Kurihara S, et al. (2000). "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.". Biochem. Biophys. Res. Commun. 268 (2): 612–6. doi:10.1006/bbrc.2000.2169. PMID 10679252.
• Ohtsuki T, Ishiguro H, Yoshikawa T, Arinami T (2000). "WFS1 gene mutation search in depressive patients: detection of five missense polymorphisms but no association with depression or bipolar affective disorder.". Journal of Affective Disorders 58 (1): 11–7. doi:10.1016/S0165-0327(99)00099-3. PMID 10760554.
• Gómez-Zaera M, Strom TM, Rodríguez B, et al. (2001). "Presence of a major WFS1 mutation in Spanish Wolfram syndrome pedigrees.". Mol. Genet. Metab. 72 (1): 72–81. doi:10.1006/mgme.2000.3107. PMID 11161832.
• Kaytor EN, Zhu JL, Pao CI, Phillips LS (2001). "Physiological concentrations of insulin promote binding of nuclear proteins to the insulin-like growth factor I gene.". Endocrinology 142 (3): 1041–9. doi:10.1210/en.142.3.1041. PMID 11181517.
• Takeda K, Inoue H, Tanizawa Y, et al. (2001). "WFS1 (Wolfram syndrome 1) gene product: predominant subcellular localization to endoplasmic reticulum in cultured cells and neuronal expression in rat brain.". Hum. Mol. Genet. 10 (5): 477–84. doi:10.1093/hmg/10.5.477. PMID 11181571.
• Tessa A, Carbone I, Matteoli MC, et al. (2001). "Identification of novel WFS1 mutations in Italian children with Wolfram syndrome.". Hum. Mutat. 17 (4): 348–9. doi:10.1002/humu.32. PMID 11295831.
• Bespalova IN, Van Camp G, Bom SJ, et al. (2002). "Mutations in the Wolfram syndrome 1 gene (WFS1) are a common cause of low frequency sensorineural hearing loss.". Hum. Mol. Genet. 10 (22): 2501–8. doi:10.1093/hmg/10.22.2501. PMID 11709537.
• Young TL, Ives E, Lynch E, et al. (2002). "Non-syndromic progressive hearing loss DFNA38 is caused by heterozygous missense mutation in the Wolfram syndrome gene WFS1.". Hum. Mol. Genet. 10 (22): 2509–14. doi:10.1093/hmg/10.22.2509. PMID 11709538.
• Crawford J, Zielinski MA, Fisher LJ, et al. (2002). "Is there a relationship between Wolfram syndrome carrier status and suicide?". Am. J. Med. Genet. 114 (3): 343–6. doi:10.1002/ajmg.10256. PMID 11920861.

External links

• GeneReviews/NCBI/NIH/UW entry on WFS1-Related Disorders

This article incorporates text from the United States National Library of Medicine, which is in the public domain.