WWC3

Chr X

WWC family member 3

Also known as: BM042

The protein regulates the Hippo signaling pathway by enhancing phosphorylation of LATS1 and YAP1, thereby suppressing YAP1 transcriptional activity and negatively regulating cell proliferation and organ growth. Mutations cause autosomal dominant developmental delay with hypotonia and dysmorphic facies. This gene is highly constrained against loss-of-function variants, indicating that such mutations are likely to be pathogenic.

OMIMResearchSummary from RefSeq, UniProt
LOFmechanismLOEUF 0.18
Clinical SummaryWWC3
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 1.00). One damaged copy is likely sufficient to cause disease.
📋
ClinVar Variants
77 unique Pathogenic / Likely Pathogenic· 125 VUS of 319 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

LoF intolerant — likely haploinsufficient
LoF Constraint
0.18LOEUF
pLI 1.000
Z-score 5.58
OE 0.07 (0.030.18)
Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint
1.51Z-score
OE missense 0.81 (0.750.88)
424 obs / 521.2 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.07 (0.030.18)
00.351.4
Missense OE0.81 (0.750.88)
00.61.4
Synonymous OE1.03
01.21.6
LoF obs/exp: 3 / 42.0Missense obs/exp: 424 / 521.2Syn Z: -0.38
DN
0.4388th %ile
GOF
0.4481th %ile
LOF
0.72top 10%

The highest-scoring mechanism for this gene is loss-of-function (haploinsufficiency).

LOFprediction above median · LOEUF 0.18

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.

ClinVar Variant Classifications

319 submitted variants in ClinVar

Classification Summary

Pathogenic76
Likely Pathogenic1
VUS125
Likely Benign24
Benign8
Conflicting1
76
Pathogenic
1
Likely Pathogenic
125
VUS
24
Likely Benign
8
Benign
1
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
76
0
76
Likely Pathogenic
0
0
1
0
1
VUS
0
116
9
0
125
Likely Benign
0
10
3
11
24
Benign
0
4
0
4
8
Conflicting
1
Total01308915235

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

WWC3 · protein map & ClinVar variants

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

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
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