The Function of WWOX
Putative oxidoreductase. Acts as a tumor suppressor and plays a role in apoptosis. Required for normal bone development (By similarity). May function synergistically with p53/TP53 to control genotoxic stress-induced cell death. Plays a role in TGFB1 signaling and TGFB1-mediated cell death. May also play a role in tumor necrosis factor (TNF)-mediated cell death. Inhibits Wnt signaling, probably by sequestering DVL2 in the cytoplasm.
Protein names
Recommended name:
WW domain-containing oxidoreductaseAlternative name(s):
Fragile site FRA16D oxidoreductaseShort chain dehydrogenase/reductase family 41C member 1
- RS1079572 (WWOX) ??
- RS1079635 (WWOX) ??
- RS11150078 (WWOX) ??
- RS113496184 (WWOX) ??
- RS11642282 (WWOX) ??
- RS12716850 (WWOX) ??
- RS12716852 (WWOX) ??
- RS12918952 (WWOX) ??
- RS17706989 (WWOX) ??
- RS17713676 (WWOX) ??
- RS2059238 (WWOX) ??
- RS2288033 (WWOX) ??
- RS2288034 (WWOX) ??
- RS2548861 (WWOX) ??
- RS2656620 (WWOX) ??
- RS2859631 (WWOX) ??
- RS383362 (WWOX) ??
- RS78867184 (WWOX) ??
- RS8050187 (WWOX) ??
- RS8056446 (WWOX) ??
- RS9923451 (WWOX) ??
- RS9940536 (WWOX) ??
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Top Gene-Substance Interactions
WWOX Interacts with These Diseases
Disease | Score |
Substances That Increase WWOX
Substances | Interaction | Organism | Category |
Substances That Decrease WWOX
Substances | Interaction | Organism | Category |
Advanced Summary
From NCBI Gene: Spinocerebellar ataxia, autosomal recessive 12Epileptic encephalopathy, early infantile, 28From UniProt: Spinocerebellar ataxia, autosomal recessive, 12 (SCAR12): Spinocerebellar ataxia is a clinically and genetically heterogeneous group of cerebellar disorders. Patients show progressive incoordination of gait and often poor coordination of hands, speech and eye movements, due to degeneration of the cerebellum with variable involvement of the brainstem and spinal cord. SCAR12 is additionally characterized by onset of generalized seizures in infancy, and delayed psychomotor development with mental retardation. Some patients may also show spasticity. [MIM:614322] Epileptic encephalopathy, early infantile, 28 (EIEE28): A form of epileptic encephalopathy, a heterogeneous group of severe childhood onset epilepsies characterized by refractory seizures, neurodevelopmental impairment, and poor prognosis. Development is normal prior to seizure onset, after which cognitive and motor delays become apparent. [MIM:616211] Defects in WWOX may be involved in several cancer types. The gene spans the second most common chromosomal fragile site (FRA16D) which is frequently altered in cancers (PubMed:10861292). Alteration of the expression and expression of some isoforms is associated with cancers. However, it is still unclear if alteration of WWOX is directly implicated in cancerogenesis or if it corresponds to a secondary effect (PubMed:10861292, PubMed:11572989, PubMed:15266310, PubMed:15073125, PubMed:15131042). Esophageal cancer (ESCR): A malignancy of the esophagus. The most common types are esophageal squamous cell carcinoma and adenocarcinoma. Cancer of the esophagus remains a devastating disease because it is usually not detected until it has progressed to an advanced incurable stage. [MIM:133239]
From NCBI Gene: This gene encodes a member of the short-chain dehydrogenases/reductases (SDR) protein family. This gene spans the FRA16D common chromosomal fragile site and appears to function as a tumor suppressor gene. Expression of the encoded protein is able to induce apoptosis, while defects in this gene are associated with multiple types of cancer. Disruption of this gene is also associated with autosomal recessive spinocerebellar ataxia 12. Disruption of a similar gene in mouse results in impaired steroidogenesis, additionally suggesting a metabolic function for the protein. Alternative splicing results in multiple transcript variants. [provided by RefSeq, May 2014] From UniProt: Putative oxidoreductase. Acts as a tumor suppressor and plays a role in apoptosis. Required for normal bone development (By similarity). May function synergistically with p53/TP53 to control genotoxic stress-induced cell death. Plays a role in TGFB1 signaling and TGFB1-mediated cell death. May also play a role in tumor necrosis factor (TNF)-mediated cell death. Inhibits Wnt signaling, probably by sequestering DVL2 in the cytoplasm.
Conditions with Increased Gene Activity
Condition | Change (log2fold) | Comparison | Species | Experimental variables | Experiment name |
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Conditions with Decreased Gene Activity
Condition | Change (log2fold) | Comparison | Species | Experimental variables | Experiment name |
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Technical
The following transcription factors affect gene expression:
Tissue specificity:
Widely expressed. Strongly expressed in testis, prostate, and ovary. Overexpressed in cancer cell lines. Isoform 5 and isoform 6 may only be expressed in tumor cell lines.
Gene Pathways:
Molecular Function:
- Coenzyme Binding
- Cofactor Binding
- Enzyme Binding
- Oxidoreductase Activity
- Protein Dimerization Activity
- Rna Polymerase Ii Transcription Coactivator Activity
Biological Processes:
- Cellular Response To Transforming Growth Factor Beta Stimulus
- Extrinsic Apoptotic Signaling Pathway
- Intrinsic Apoptotic Signaling Pathway By P53 Class Mediator
- Negative Regulation Of Wnt Signaling Pathway
- Osteoblast Differentiation
- Oxidation-Reduction Process
- Positive Regulation Of Extrinsic Apoptotic Signaling Pathway
- Positive Regulation Of Extrinsic Apoptotic Signaling Pathway In Absence Of Ligand
- Positive Regulation Of Transcription From Rna Polymerase Ii Promoter
- Skeletal System Morphogenesis
- Steroid Metabolic Process
- Wnt Signaling Pathway