WFS1

Protein identityUniProt · HPA

UniProt accession

O76024

Gene

WFS1

Ensembl

ENSG00000109501

Chromosome

4

Canonical length

890 aa

Protein class

Disease related genes, Human disease related genes, Plasma proteins, Potential drug targets, Predicted intracellular proteins, Predicted membrane proteins, Transporters

OverviewNCBI Gene

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. 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 affects the brain and central nervous system. Mutations in this gene can also cause autosomal dominant deafness 6 (DFNA6), also known as DFNA14 or DFNA38. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Mar 2009]

Canonical amino-acid sequenceUniProt

890 residues, UniProt reviewed canonical sequence.

>O76024|WFS1
     1  MDSNTAPLGP SCPQPPPAPQ PQARSRLNAT ASLEQERSER PRAPGPQAGP GPGVRDAAAP
    61  AEPQAQHTRS RERADGTGPT KGDMEIPFEE VLERAKAGDP KAQTEVGKHY LQLAGDTDEE
   121  LNSCTAVDWL VLAAKQGRRE AVKLLRRCLA DRRGITSENE REVRQLSSET DLERAVRKAA
   181  LVMYWKLNPK KKKQVAVAEL LENVGQVNEH DGGAQPGPVP KSLQKQRRML ERLVSSESKN
   241  YIALDDFVEI TKKYAKGVIP SSLFLQDDED DDELAGKSPE DLPLRLKVVK YPLHAIMEIK
   301  EYLIDMASRA GMHWLSTIIP THHINALIFF FIVSNLTIDF FAFFIPLVIF YLSFISMVIC
   361  TLKVFQDSKA WENFRTLTDL LLRFEPNLDV EQAEVNFGWN HLEPYAHFLL SVFFVIFSFP
   421  IASKDCIPCS ELAVITGFFT VTSYLSLSTH AEPYTRRALA TEVTAGLLSL LPSMPLNWPY
   481  LKVLGQTFIT VPVGHLVVLN VSVPCLLYVY LLYLFFRMAQ LRNFKGTYCY LVPYLVCFMW
   541  CELSVVILLE STGLGLLRAS IGYFLFLFAL PILVAGLALV GVLQFARWFT SLELTKIAVT
   601  VAVCSVPLLL RWWTKASFSV VGMVKSLTRS SMVKLILVWL TAIVLFCWFY VYRSEGMKVY
   661  NSTLTWQQYG ALCGPRAWKE TNMARTQILC SHLEGHRVTW TGRFKYVRVT DIDNSAESAI
   721  NMLPFFIGDW MRCLYGEAYP ACSPGNTSTA EEELCRLKLL AKHPCHIKKF DRYKFEITVG
   781  MPFSSGADGS RSREEDDVTK DIVLRASSEF KSVLLSLRQG SLIEFSTILE GRLGSKWPVF
   841  ELKAISCLNC MAQLSPTRRH VKIEHDWRST VHGAVKFAFD FFFFPFLSAA

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against WFS1 can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability

Other membrane

Secreted

No

Transmembrane segments

11

Mean surface accessibility (rSASA)

0.38

Highest tissue expression

71 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about WFS1.

Disease | AllUniProt

Conditions WFS1 is implicated in, by any mechanism.

• Wolfram syndrome 1 (WFS1) MIM:222300
• Deafness, autosomal dominant, 6 (DFNA6) MIM:600965
• Wolfram-like syndrome autosomal dominant (WFSL) MIM:614296
• Cataract 41 (CTRCT41) MIM:116400

Disease | GeneticClinVar

238 pathogenic / likely-pathogenic of 2,146 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Wolfram syndrome 1
• Autosomal dominant nonsyndromic hearing loss 6
• Wolfram-like syndrome
• Type 2 diabetes mellitus
• Cataract 41

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance)

1.93

gnomAD pLI

0

gnomAD missense Z

-4.71

DepMap mean gene effect

0.18

DepMap dependency class

none

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 3% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• calcium ion homeostasis
• endoplasmic reticulum calcium ion homeostasis
• endoplasmic reticulum unfolded protein response
• ER overload response
• ERAD pathway
• glucose homeostasis
• intrinsic apoptotic signaling pathway
• kidney development
• negative regulation of apoptotic process
• negative regulation of ATF6-mediated unfolded protein response
• negative regulation of endoplasmic reticulum stress-induced intrinsic apoptotic signaling pathway
• negative regulation of neuron apoptotic process
• negative regulation of programmed cell death
• negative regulation of response to endoplasmic reticulum stress
• negative regulation of transcription by RNA polymerase II
• negative regulation of translation
• negative regulation of type B pancreatic cell apoptotic process
• nervous system process
• olfactory behavior
• pancreas development
• positive regulation of calcium ion transport
• positive regulation of ERAD pathway
• positive regulation of growth
• positive regulation of protein metabolic process
• positive regulation of protein ubiquitination
• protein stabilization
• renal water homeostasis
• response to endoplasmic reticulum stress
• sensory perception of sound
• visual perception

Molecular functions

• ATPase binding
• calcium-dependent protein binding
• calmodulin binding
• DNA-binding transcription factor binding
• proteasome binding
• protein carrier chaperone
• ubiquitin protein ligase binding

Cellular components

• dendrite
• endoplasmic reticulum
• endoplasmic reticulum lumen
• endoplasmic reticulum membrane
• secretory granule
• synaptic vesicle membrane

Protein domainsUniProt · Pfam · InterPro

• Tetratricopeptide-like helical domain superfamily
• Wolframin
• Wolframin family
• Wolframin, cysteine-rich domain
• Wolframin, Sel1-like repeat
• Wolframin, EF-hand domain
• Wolframin, OB-fold domain
• Wolframin C-terminal OB-fold domain
• Wolframin EF-hand domain
• Wolframin Sel1-like repeat
• Wolframin cysteine-rich domain

KeywordsUniProt

• Acetylation
• Cataract
• Cytoplasmic vesicle
• Deafness
• Diabetes insipidus
• Diabetes mellitus
• Endoplasmic reticulum
• Glycoprotein
• Membrane
• Non-syndromic deafness
• Phosphoprotein
• Transmembrane
• Transmembrane helix

InteractionsUniProt · HPA

Protein binding partners of WFS1 in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

• ATP6V1A