Wolframin ER Transmembrane Glycoprotein

Alternative Names

  • WFS1
  • Wolframin
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OMIM Number

606201

NCBI Gene ID

7466

Uniprot ID

O76024

Length

33,417 bases

No. of Exons

10

No. of isoforms

1

Protein Name

Wolframin

Molecular Mass

100292 Da

Amino Acid Count

890

Genomic Location

chr4:6,269,849-6,303,265

Gene Map Locus
4p16.1

Description

The WFS1 gene codes for a protein called wolframin, defect in whose function have been found to lead to a variety of diseases. The most complex of these disorders is Wolfram Syndrome, which is characterized by diabetes insipidus, childhood onset diabetes mellitus, optic atrophy, and deafness. Mutations in this gene are also involved in imparting a genetic disposition to mood disorders, as well as non syndromic sensorineural hearing loss, specifically a type known as DFNA6.

The exact function of the wolframin protein is not known. However, it is known that the protein localizes to the endoplasmic reticulum with the cells. This fact has led researchers to speculate that the protein may actually mediate proper protein folding as well as maintain intracellular levels of calcium ions. In this respect, it is clear to see how defects in the protein may lead to diabetes by causing improper folding of the proinsulin protein, and to deafness by causing disequilibrium in the ion channels.

Epidemiology in the Arab World

View Map
Variant NameCountryGenomic LocationClinvar Clinical SignificanceCTGA Clinical Significance Condition(s)HGVS ExpressionsdbSNPClinvar
NM_006005.3:c.1382C>GLebanonchr4:6301177Likely Benign, Likely PathogenicPathogenicWolfram Syndrome 1NG_011700.1:g.36328C>G; NM_006005.3:c.1382C>G; NP_005996.2:p.Thr461Ser71530925229636
NM_006005.3:c.1441_1447dupSaudi Arabiachr4:6301236-6301242PathogenicPathogenicWolfram Syndrome 1NG_011700.1:g.36387_36393dup; NM_006005.3:c.1441_1447dup; NP_005996.2:p.Val483fs727503745166564
NM_006005.3:c.1582T>GLebanonchr4:6301377Likely PathogenicWolfram Syndrome 1NG_011700.1:g.36528T>G; NM_006005.3:c.1582T>G; NP_005996.2:p.Tyr528Asp761976067
NM_006005.3:c.1936_1943delLebanonNC_000004.12:g.6301731_6301738delPathogenicLikely Pathogenic, PathogenicWolfram Syndrome 1; Type 2 Diabetes MellitusNG_011700.1:g.36882_36889del; NM_006005.3:c.1936_1943del; NP_005996.2:p.Phe646fs7152437430553
NM_006005.3:c.2068T>GLebanonchr4:6301863Likely PathogenicWolfram Syndrome 1NG_011700.1:g.37014T>G; NM_006005.3:c.2068T>G; NP_005996.2:p.Cys690Gly754373473
NM_006005.3:c.2119G>ALebanonNC_000004.12:g.6301914G>ALikely Benign, Uncertain SignificanceLikely BenignWolfram Syndrome 1; Type 2 Diabetes MellitusNG_011700.1:g.37065G>A; NM_006005.3:c.2119G>A; NP_005996.2:p.Val707Ile71524377215367
NM_006005.3:c.2467_2469delATCLebanonchr4:6302262:6302264Likely PathogenicWolfram Syndrome 1NG_011700.1:g.37413_37415delATC; NM_006005.3:c.2467_2469delATC; NP_005996.2:p.823Iledel
NM_006005.3:c.2524C>TLebanonNC_000004.12:g.6302319C>TUncertain SignificancePathogenicWolfram Syndrome 1NG_011700.1:g.37470C>T; NM_006005.3:c.2524C>T; NP_005996.2:p.Leu842Phe715309151518006
NM_006005.3:c.2649delLebanonchr4:6302444Likely PathogenicWolfram Syndrome 1; Type 2 Diabetes MellitusNG_011700.1:g.37595del; NM_006005.3:c.2649del; NP_005996.2:p.Phe884fs71524394
NM_006005.3:c.320G>ALebanonchr4:6288991Likely PathogenicLikely PathogenicWolfram Syndrome 1NG_011700.1:g.24142G>A; NM_006005.3:c.320G>A; NP_005996.2:p.Gly107Glu71530914982858
NM_006005.3:c.461-9A>GLebanonNC_000004.12:g.6291188A>GBenignBenignNG_011700.1:g.26339A>G; NM_006005.3:c.461-9A>G; NP_005996.2:p.?100101314527

Other Reports

Jordan
Syria

El-Shanti et al. (2000) and Ajlouni et al. (2002) reported on a Jordanian family of Syrian origin, in which two children, born to consanguineous parents, were affected with Wolfram Syndrome. Homozygosity analysis revealed that both patients were homozygous for markers D4S432, D4S3023, D4S2366, and D4S2639. Maximum LOD score with a two-point linkage analysis was 1.28, whereas that with a multi-point linkage analysis was 1.87 near D4S3023. El-Shanti et al. (2000) and Ajlouni et al. (2002) were, thus, able to show that the condition in these patients is linked to the WSF1 locus.

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