WBP4

Chr 13

WW domain binding protein 4

Also known as: FBP21, NEDHFDB

NCBI Gene: 11193 ENSG00000120688 UniProt: O75554

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.

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]

ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

UniProtNeurodevelopmental disorder with hypotonia, feeding difficulties, facial dysmorphism, and brain abnormalities

Clinical highlights

Interpreting a novel variant

Loss of function is the curated mechanism (Gene2Phenotype), though the gene is not strongly LoF-constrained in the population — weigh truncating variants against that tolerance.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.02

LOEUF

LOF

Mechanism· G2P

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

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

Background carrier burden — how many people carry a rare variant somewhere in WBP4?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 120

421 rare PASS variants

Rare truncating (LoF)

1 in 570

132 rare PASS variants

Rare synonymous (reference)

1 in 340

150 rare PASS variants

Rare missense and truncating variants are carried at similar rates in WBP4; this gene does not show strong loss-of-function constraint by this measure. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 230	1 in 640
South Asian	~43k	1 in 140	1 in 270
Remaining (unassigned)	~30k	1 in 200	1 in 600
European (Finnish)	~27k	1 in 630	1 in 520
Admixed American	~22k	1 in 180	1 in 510
African / African American	~21k	1 in 120	1 in 400
East Asian	~20k	1 in 170	1 in 800
Ashkenazi Jewish	~13k	1 in 1,000	1 in 350
Middle Eastern	~2,884	1 in 190	≈ 1 in 1,700

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): 10 of 10 coding exons well covered in gnomAD exomes. Genomes: 9 of 10 (exon 4 below).? see exons ↓