WFS1

WFS1
Identifiers
Aliases	WFS1, CTRCT41, WFRS, WFS, WFSL, wolframin ER transmembrane glycoprotein
External IDs	OMIM: 606201; MGI: 1328355; HomoloGene: 4380; GeneCards: WFS1; OMA:WFS1 - orthologs
Gene location (Human) Chr. Chromosome 4 (human) Band 4p16.1 Start 6,269,849 bp End 6,303,265 bp
Gene location (Mouse) Chr. Chromosome 5 (mouse) Band 5|5 B3 Start 37,123,448 bp End 37,146,549 bp
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in right ovary left ovary body of uterus nucleus accumbens stromal cell of endometrium popliteal artery tibial arteries ascending aorta right lung gastric mucosa Top expressed in olfactory tubercle nucleus accumbens Region I of hippocampus proper extraocular muscle digastric muscle thalamic reticular nucleus plantaris muscle aortic valve superior frontal gyrus sternocleidomastoid muscle More reference expression data BioGPS More reference expression data
Gene ontology Molecular function ATPase binding protein binding ubiquitin protein ligase binding calcium-dependent protein binding calmodulin binding proteasome binding Cellular component integral component of membrane endoplasmic reticulum membrane membrane integral component of endoplasmic reticulum membrane dendrite endoplasmic reticulum proteasome complex endoplasmic reticulum lumen integral component of synaptic vesicle membrane Biological process negative regulation of neuron apoptotic process negative regulation of endoplasmic reticulum stress-induced intrinsic apoptotic signaling pathway calcium ion homeostasis glucose homeostasis kidney development protein stabilization nervous system process positive regulation of growth negative regulation of transcription by RNA polymerase II hearing endoplasmic reticulum calcium ion homeostasis protein maturation by protein folding negative regulation of ATF6-mediated unfolded protein response negative regulation of DNA-binding transcription factor activity response to endoplasmic reticulum stress ER overload response IRE1-mediated unfolded protein response ubiquitin-dependent ERAD pathway renal water homeostasis negative regulation of programmed cell death positive regulation of protein ubiquitination negative regulation of type B pancreatic cell apoptotic process visual perception positive regulation of calcium ion transport pancreas development endoplasmic reticulum unfolded protein response olfactory behavior post-translational protein modification Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 7466 22393 Ensembl ENSG00000109501 ENSMUSG00000039474 UniProt O76024 P56695 RefSeq (mRNA) NM_006005 NM_001145853 NM_011716 RefSeq (protein) NP_001139325 NP_005996 NP_035846 Location (UCSC) Chr 4: 6.27 – 6.3 Mb Chr 5: 37.12 – 37.15 Mb PubMed search
Wikidata
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Wolframin is a protein that in humans is encoded by the WFS1 gene.

Function

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.

Clinical significance

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.

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. S2CID 2944382.
• 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. S2CID 39815754.
• 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. S2CID 31662957.
• 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/endo.142.3.8046. 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. S2CID 45109749.
• 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. PMC 6198816. 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.