WFS1 Gene: Wolframin ER Transmembrane Glycoprotein
Comprehensive genomic and clinical resource for WFS1, associated with Wolfram syndrome and non-syndromic hearing loss.
Gene Information Card
| Symbol | WFS1 |
|---|---|
| Full Name | Wolframin ER transmembrane glycoprotein |
| Gene Type | Protein coding |
| Chromosomal Location | 4p16.1 |
| NCBI Gene ID | 7466 ncbi.nlm.nih.gov/gene/7466 |
| Ensembl ID | ENSG00000109501 |
| UniProt ID | O76024 |
| OMIM ID | 606201 |
| HGNC ID | 12762 |
| Aliases | WFRS, WFSL, DFNA6, DFNA14, DFNA38, DIDMOAD |
Description
WFS1 encodes wolframin, a transmembrane glycoprotein localized to the endoplasmic reticulum (ER). It is involved in ER calcium homeostasis, unfolded protein response, and cell survival. Loss-of-function mutations cause Wolfram syndrome (DIDMOAD: diabetes insipidus, diabetes mellitus, optic atrophy, deafness) and autosomal dominant non-syndromic hearing loss (DFNA6/14/38).
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Wolfram syndrome (DIDMOAD) | Loss of wolframin function leads to ER stress, impaired calcium regulation, and apoptosis of pancreatic beta cells and neurons. | OMIM #222300; ClinVar |
| Non-syndromic hearing loss (DFNA6/14/38) | Dominant missense mutations disrupt ER homeostasis in cochlear hair cells. | OMIM #600965; ClinVar |
| Autosomal dominant diabetes mellitus type 6 | WFS1 variants impair insulin secretion via ER stress. | OMIM #606176; ClinVar |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Pancreas | 23.4 | High |
| Brain | 12.1 | Medium |
| Inner ear (cochlea) | 8.5 | Medium |
| Heart | 5.2 | Low |
| Liver | 3.8 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK293 | 18.7 | High expression in kidney-derived cells |
| SH-SY5Y | 14.2 | Neuronal cell line |
| MIN6 | 22.1 | Pancreatic beta-cell line |
| HeLa | 9.3 | Cervical cancer cell line |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.2649delC (p.Phe884Serfs*28) | Frameshift | Common in Wolfram syndrome | Loss of function |
| c.1230_1233delGCTG (p.Leu411Phefs*13) | Frameshift | Reported in Wolfram syndrome | Loss of function |
| c.2590G>A (p.Glu864Lys) | Missense | Dominant hearing loss | Gain of toxic function / dominant negative |
| c.2002C>T (p.Arg668Cys) | Missense | Dominant hearing loss | Altered ER calcium handling |
Mutation functional classification
Loss of Function (LOF)
Biallelic loss-of-function mutations (nonsense, frameshift, large deletions) cause Wolfram syndrome via ER stress and apoptosis.
Gain of Function (GOF)
Not clearly established; some dominant missense variants may have toxic gain-of-function effects in cochlear cells.
Dominant Negative (DN)
Dominant missense mutations in the C-terminal domain (e.g., p.Glu864Lys) interfere with wild-type wolframin function, leading to hearing loss.
View complete mutation data：
Gene Ontology (GO)
| • GO:0005783 – endoplasmic reticulum | • GO:0005509 – calcium ion binding |
| • GO:0034976 – response to endoplasmic reticulum stress | • GO:0006915 – apoptotic process |
| • GO:0031018 – endoplasmic reticulum calcium ion homeostasis |
Pathways
• Unfolded Protein Response (UPR)
• ER Calcium Homeostasis
• Apoptosis signaling in response to ER stress
Protein Summary
Wolframin is a 890-amino acid transmembrane glycoprotein with nine transmembrane domains, localized to the ER. It regulates calcium flux from the ER to the cytosol and modulates the unfolded protein response. Loss of wolframin increases ER stress and sensitizes cells to apoptosis, particularly in pancreatic beta cells and neurons.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| WFS1 Knockout HEK293 Cell Line | EDC07862 | Human | 7466 | Details Get a Quote |
| WFS1 Knockout A-549 Cell Line | EDJ-KQ29625 | Human | 7466 | Details Get a Quote |
| WFS1 Knockout HCT 116 Cell Line | EDJ-KQ29626 | Human | 7466 | Details Get a Quote |
| WFS1 Knockout HeLa Cell Line | EDJ-KQ29627 | Human | 7466 | Details Get a Quote |
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