WWC2
Chr 4WW and C2 domain containing 2
Also known as: BOMB
The protein regulates the Hippo signaling pathway by enhancing phosphorylation of LATS1 and YAP1, thereby suppressing cell proliferation and organ growth through inhibition of YAP1 transcriptional activity. Mutations cause autosomal recessive intellectual disability with microcephaly and seizures, typically presenting in early childhood. The gene shows minimal constraint against loss-of-function variants, consistent with its recessive inheritance pattern.
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
More LoF-intolerant than ~75% of genes
Mild missense constraint
The highest-scoring mechanism for this gene is dominant-negative.
Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.
Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.
ClinVar Variant Classifications
343 submitted variants in ClinVar
Classification Summary
Curated Variants Distribution
Classified variants from ClinVar · 5 ACMG categories
| Classification | LoF | Missense + Inframe | Non-coding | Synonymous | Total |
|---|---|---|---|---|---|
Pathogenic | 0 | 0 | 91 | 0 | 91 |
Likely Pathogenic | 0 | 0 | 8 | 0 | 8 |
VUS | 0 | 189 | 12 | 0 | 201 |
Likely Benign | 0 | 10 | 1 | 2 | 13 |
Benign | 0 | 0 | 1 | 2 | 3 |
| Total | 0 | 199 | 113 | 4 | 316 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
WWC2 · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
External Resources
Links to major genomics databases and tools
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
No active trials found for this gene.
Search ClinicalTrials.gov →External Resources
Links to major genomics databases and tools