Wolframin ER Transmembrane Glycoprotein

Alternative Names

WFS1
Wolframin

Length

33,417 bases

No. of Exons

No. of isoforms

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 Name	Country	Genomic Location	Clinvar Clinical Significance	CTGA Clinical Significance	Condition(s)	HGVS Expressions	dbSNP	Clinvar
NM_006005.3:c.1382C>G	Lebanon	chr4:6301177	Likely Benign, Likely Pathogenic	Pathogenic	Wolfram Syndrome 1	NG_011700.1:g.36328C>G; NM_006005.3:c.1382C>G; NP_005996.2:p.Thr461Ser	71530925	229636
NM_006005.3:c.1441_1447dup	Saudi Arabia	chr4:6301236-6301242	Pathogenic	Pathogenic	Wolfram Syndrome 1	NG_011700.1:g.36387_36393dup; NM_006005.3:c.1441_1447dup; NP_005996.2:p.Val483fs	727503745	166564
NM_006005.3:c.1582T>G	Lebanon	chr4:6301377		Likely Pathogenic	Wolfram Syndrome 1	NG_011700.1:g.36528T>G; NM_006005.3:c.1582T>G; NP_005996.2:p.Tyr528Asp	761976067
NM_006005.3:c.1936_1943del	Lebanon	NC_000004.12:g.6301731_6301738del	Pathogenic	Likely Pathogenic, Pathogenic	Wolfram Syndrome 1; Type 2 Diabetes Mellitus	NG_011700.1:g.36882_36889del; NM_006005.3:c.1936_1943del; NP_005996.2:p.Phe646fs	71524374	30553
NM_006005.3:c.2068T>G	Lebanon	chr4:6301863		Likely Pathogenic	Wolfram Syndrome 1	NG_011700.1:g.37014T>G; NM_006005.3:c.2068T>G; NP_005996.2:p.Cys690Gly	754373473
NM_006005.3:c.2119G>A	Lebanon	NC_000004.12:g.6301914G>A	Likely Benign, Uncertain Significance	Likely Benign	Wolfram Syndrome 1; Type 2 Diabetes Mellitus	NG_011700.1:g.37065G>A; NM_006005.3:c.2119G>A; NP_005996.2:p.Val707Ile	71524377	215367
NM_006005.3:c.2467_2469delATC	Lebanon	chr4:6302262:6302264		Likely Pathogenic	Wolfram Syndrome 1	NG_011700.1:g.37413_37415delATC; NM_006005.3:c.2467_2469delATC; NP_005996.2:p.823Iledel
NM_006005.3:c.2524C>T	Lebanon	NC_000004.12:g.6302319C>T	Uncertain Significance	Pathogenic	Wolfram Syndrome 1	NG_011700.1:g.37470C>T; NM_006005.3:c.2524C>T; NP_005996.2:p.Leu842Phe	71530915	1518006
NM_006005.3:c.2649del	Lebanon	chr4:6302444		Likely Pathogenic	Wolfram Syndrome 1; Type 2 Diabetes Mellitus	NG_011700.1:g.37595del; NM_006005.3:c.2649del; NP_005996.2:p.Phe884fs	71524394
NM_006005.3:c.320G>A	Lebanon	chr4:6288991	Likely Pathogenic	Likely Pathogenic	Wolfram Syndrome 1	NG_011700.1:g.24142G>A; NM_006005.3:c.320G>A; NP_005996.2:p.Gly107Glu	71530914	982858
NM_006005.3:c.461-9A>G	Lebanon	NC_000004.12:g.6291188A>G	Benign	Benign		NG_011700.1:g.26339A>G; NM_006005.3:c.461-9A>G; NP_005996.2:p.?	10010131	4527

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Other Reports

Jordan

[See: Syria > El-Shanti et al., 2000; Ajlouni et al., 2002].

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.

External Links

http://ghr.nlm.nih.gov/gene=wfs1 http://www.genecards.org/cgi-bin/carddisp.pl?gene=WFS1&search=neurodegenerative+or+senile http://www.khri.med.umich.edu/research/lesperance_lab/low_freq.php

Contributors

Pratibha Nair: 13.04.2020
Tasneem Obeid: 10.05.2011
Ghazi O. Tadmouri: 12.03.2009
Tasneem Obeid: 11.03.2009
Pratibha Nair: 04.03.2009

Edit History

Sami Bizzari: 11.03.2021
Pratibha Nair: 14.04.2020
Pratibha Nair: 13.04.2020
Pratibha Nair: 12.05.2011
Shirine Gallala: 17.05.2009
Tasneem Obeid: 26.03.2009
Sarah Al-Haj Ali: 20.11.2004
Sarah Al-Haj Ali: 10.11.2004

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