WBP4

Chr 13AR

WW domain binding protein 4

Also known as: FBP21, NEDHFDB

NCBI Gene: 11193 ENSG00000120688 UniProt: O75554 OMIM: 604981

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.

OMIM ResearchSummary from RefSeq, OMIM, UniProt

This gene encodes WW domain-containing binding protein 4. The WW domain represents a small and compact globular structure that interacts with proline-rich ligands. This encoded protein is a general spliceosomal protein that may play a role in cross-intron bridging of U1 and U2 snRNPs in the spliceosomal complex A. [provided by RefSeq, Jul 2008]

OMIM ResearchGenerating clinical summary…

LOFmechanismARLOEUF 1.021 OMIM phenotype

Clinical Summary— WBP4

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Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

6 unique Pathogenic / Likely Pathogenic· 55 VUS of 85 total submissions

Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.02LOEUF

pLI 0.000

Z-score 1.50

OE 0.66 (0.44–1.02)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

0.24Z-score

OE missense 0.95 (0.84–1.08)

171 obs / 180.0 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.66 (0.44–1.02)

0≤0.351.4

Missense OE?0.95 (0.84–1.08)

0≤0.61.4

Synonymous OE?1.08

0≤1.21.6

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

This gene — mechanism propensity

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

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. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.

ClinVar Variant Classifications

85 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic1

Likely Pathogenic5

VUS55

Likely Benign7

Benign1

Conflicting1

Pathogenic

Likely Pathogenic

VUS

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	1	0	0	0	1
Likely Pathogenic	4	0	1	0	5
VUS	0	54	0	1	55
Likely Benign	0	2	2	3	7
Benign	0	0	0	1	1
Conflicting	—				1
Total	5	56	3	5	70

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

View in ClinVar →

47 pathogenic / likely-pathogenic (of 53) ClinVar copy-number / structural variants overlap WBP4 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →