WWOX

Chr 16AR

WW domain containing oxidoreductase

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

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.

OMIMResearchSummary from RefSeq, OMIM, UniProt, Mechanism
LOFmechanismARLOEUF 1.533 OMIM phenotypes
Clinical SummaryWWOX
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Gene-Disease Validity (ClinGen)
developmental and epileptic encephalopathy · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
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Clinical Trials
2 active or recruiting trials — potential therapeutic options may be available

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
1.53LOEUF
pLI 0.000
Z-score -0.31
OE 1.07 (0.771.53)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
-4.44Z-score
OE missense 1.81 (1.671.94)
435 obs / 241.0 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios
LoF OE1.07 (0.771.53)
00.351.4
Missense OE1.81 (1.671.94)
00.61.4
Synonymous OE1.82
01.21.6
LoF obs/exp: 22 / 20.5Missense obs/exp: 435 / 241.0Syn Z: -6.24
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
strongWWOX-related epileptic encephalopathy, early infantileLOFAR
strongWWOX-related spinocerebellar ataxiaOTHERAR
Mechanism Note (expert annotation)
LOF

Biallelic LOF causes WOREE syndrome (DEE28) or SCAR12 (spinocerebellar ataxia). This is an autosomal recessive LOF gene; the GOF prediction does not apply.

References:PMID:25644381

Predictions shown for reference only — model trained on dominant genes, not applicable to AR conditions.

DN
0.6647th %ile
GOF
0.6639th %ile
LOF
0.3260th %ile

The Badonyi & Marsh prediction model was trained exclusively on dominant disease genes. Predictions are not reliable for genes with autosomal recessive inheritance and are shown at reduced opacity for reference only.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

WWOX · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

3D Protein StructureAlphaFold
Clinical Literature
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Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗