WWOX

Chr 16

WW domain containing oxidoreductase

Also known as: D16S432E, DEE28, EIEE28, FOR, FRA16D, HHCMA56, PRO0128, SCAR12

NCBI Gene: 51741 ENSG00000186153 UniProt: Q9NZC7

The WWOX protein is an oxidoreductase that functions as a tumor suppressor by inducing apoptosis and inhibiting Wnt signaling. Biallelic mutations cause autosomal recessive developmental and epileptic encephalopathy 28 and spinocerebellar ataxia 12. The gene shows very low constraint against loss-of-function variants, consistent with the recessive inheritance pattern where heterozygous carriers are typically unaffected.

GeneReviews ResearchSummary from RefSeq, OMIM, UniProt, Mechanism

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]

GeneReviews ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

UniProtEsophageal cancer

UniProtSpinocerebellar ataxia, autosomal recessive, 12

UniProtDevelopmental and epileptic encephalopathy 28

Clinical highlights

Gene-disease validity (ClinGen)

genetic developmental and epileptic encephalopathy · ARDefinitivesufficient evidence for diagnostic panels

Interpreting a novel variant

Loss of function is the established mechanism, though the gene is not strongly LoF-constrained in the population — weigh truncating variants against that tolerance.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

Pubs (1 yr)

—

P/LP submissions

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P/LP missense

1.53

LOEUF

LOF

Mechanism· annotated

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GeneReview available — WWOX