WWOX Gene: WW Domain Containing Oxidoreductase
A tumor suppressor gene involved in cancer, neurological disorders, and metabolic disease
Gene Information Card
| Symbol | WWOX |
|---|---|
| Full Name | WW domain containing oxidoreductase |
| Gene Type | Protein coding |
| Chromosomal Location | 16q23.1 |
| NCBI Gene ID | 51741 ncbi.nlm.nih.gov/gene/51741 |
| Ensembl ID | ENSG00000186153 |
| UniProt ID | Q9NZC7 |
| OMIM ID | 605131 |
| HGNC ID | 12799 |
| Aliases | FOR, WOX1, D16S432E, EIEE28, SDR41C1, FRA16D |
Description
The WWOX gene encodes a protein containing two N-terminal WW domains and a C-terminal short-chain dehydrogenase/reductase (SDR) domain. It functions as a tumor suppressor, regulating apoptosis, cell cycle, and DNA damage response. WWOX spans the common fragile site FRA16D, making it prone to genomic alterations in cancer. Loss of WWOX expression is implicated in various cancers, neurological disorders (e.g., epileptic encephalopathy), and metabolic syndrome.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Cancer (breast, prostate, lung, ovarian, etc.) | Loss of WWOX expression due to genomic deletions or epigenetic silencing promotes tumorigenesis by impairing apoptosis and cell cycle control. | Multiple studies in NCBI PubMed; COSMIC somatic mutation data. |
| Epileptic encephalopathy, early infantile, 28 (EIEE28) | Biallelic loss-of-function mutations in WWOX cause severe neurodevelopmental disorder with early-onset seizures. | ClinVar; OMIM #616211. |
| Metabolic syndrome | WWOX deficiency alters lipid metabolism and glucose homeostasis, contributing to obesity and insulin resistance. | NCBI Gene; UniProt. |
| Spinocerebellar ataxia, autosomal recessive 12 (SCAR12) | Homozygous mutations in WWOX lead to progressive cerebellar ataxia and intellectual disability. | OMIM #614322; ClinVar. |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Testis | 35.2 | High |
| Prostate | 20.1 | Medium |
| Breast | 15.8 | Medium |
| Brain (cerebellum) | 12.4 | Medium |
| Liver | 8.5 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| MCF7 (breast cancer) | 18.3 | Moderate expression |
| HeLa (cervical cancer) | 14.7 | Moderate expression |
| A549 (lung cancer) | 11.2 | Low expression |
| HEK293 (embryonic kidney) | 22.1 | High expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1007G>A (p.Arg336Gln) | Missense | Rare | Loss of SDR domain function; associated with EIEE28 |
| c.681_682del (p.Glu228fs) | Frameshift | Rare | Loss of function; truncation |
| c.1A>G (p.Met1Val) | Start loss | Rare | No protein production |
| Whole gene deletion | Copy number loss | Frequent in cancer | Tumor suppressor inactivation |
Mutation functional classification
Loss of Function (LOF)
Most WWOX mutations in cancer and neurological disorders are loss-of-function, including deletions, frameshifts, and missense variants that disrupt WW domains or SDR activity.
Gain of Function (GOF)
No well-characterized gain-of-function mutations reported for WWOX.
Dominant Negative (DN)
Some missense mutations in the WW domains may exert dominant-negative effects by interfering with wild-type WWOX protein interactions, though evidence is limited.
View complete mutation data：
Gene Ontology (GO)
| • apoptotic process (GO:0006915) | • cytoplasm (GO:0005737) |
| • protein binding (GO:0005515) | • oxidoreductase activity (GO:0016491) |
| • cell cycle (GO:0007049) | • DNA damage response (GO:0006974) |
Pathways
• Apoptosis (KEGG hsa04210)
• p53 signaling pathway (KEGG hsa04115)
• TNF signaling pathway (KEGG hsa04668)
Protein Summary
The WWOX protein (UniProt Q9NZC7) is a 414-amino acid oxidoreductase with two N-terminal WW domains that mediate protein-protein interactions and a C-terminal SDR domain with predicted dehydrogenase activity. It localizes to the cytoplasm and mitochondria, and translocates to the nucleus upon stress. WWOX interacts with p53, AP-2γ, and other partners to promote apoptosis and suppress tumor growth. Loss of WWOX is a hallmark of many cancers and is linked to poor prognosis.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| WWOX Knockout HEK293 Cell Line | EDJ-KQ15369 | Human | 51741 | Details Get a Quote |
| WWOX Knockout A-549 Cell Line | EDJ-KQ47340 | Human | 51741 | Details Get a Quote |
| WWOX Knockout HCT 116 Cell Line | EDJ-KQ47342 | Human | 51741 | Details Get a Quote |
| WWOX Knockout HeLa Cell Line | EDJ-KQ47343 | Human | 51741 | Details Get a Quote |
| WWOX Knockout iPSC Cell Line | EDJ-KZ81 | Human | 51741 | Details Get a Quote |
