WBP4

Chr 13AR

WW domain binding protein 4

Also known as: FBP21, NEDHFDB

The protein functions as a component of the spliceosome involved in pre-mRNA splicing and may facilitate cross-intron bridging of U1 and U2 snRNPs in the spliceosomal A complex. Mutations cause a neurodevelopmental disorder with hypotonia, feeding difficulties, facial dysmorphism, and brain abnormalities with autosomal recessive inheritance. The gene shows extreme intolerance to loss-of-function variants (pLI near zero), indicating it is highly constrained in the population.

OMIMResearchSummary from RefSeq, OMIM, UniProt
LOFmechanismARLOEUF 1.021 OMIM phenotype
Clinical SummaryWBP4
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
33 unique Pathogenic / Likely Pathogenic· 2 VUS of 37 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
1.02LOEUF
pLI 0.000
Z-score 1.50
OE 0.66 (0.441.02)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
0.24Z-score
OE missense 0.95 (0.841.08)
171 obs / 180.0 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.66 (0.441.02)
00.351.4
Missense OE0.95 (0.841.08)
00.61.4
Synonymous OE1.08
01.21.6
LoF obs/exp: 15 / 22.7Missense obs/exp: 171 / 180.0Syn Z: -0.47
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
moderateWBP4-related neurodevelopmental disorder with hypotonia, feeding difficulties, facial dysmorphism, and brain abnormalitiesLOFAR

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

DN
0.6161th %ile
GOF
0.5955th %ile
LOF
0.4134th %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

37 submitted variants in ClinVar

Classification Summary

Pathogenic33
VUS2
Likely Benign1
Benign1
33
Pathogenic
2
VUS
1
Likely Benign
1
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories· variant type breakdown unavailable

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
33
Likely Pathogenic
0
VUS
2
Likely Benign
1
Benign
1
Total37

Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

WBP4 · 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
Open Research Assistant →
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC

No open access results found