WASF3

Chr 13

WASP family member 3

Also known as: Brush-1, SCAR3, WAVE3

NCBI Gene: 10810 ENSG00000132970 UniProt: Q9UPY6

The WASF3 protein is a downstream effector that transmits signals from tyrosine kinase receptors and small GTPases to the actin cytoskeleton, regulating cell morphology and cytoskeletal organization. Mutations cause autosomal dominant intellectual disability with macrocephaly, seizures, and speech delay. The gene shows moderate constraint against loss-of-function variants (LOEUF 0.467), consistent with its role in essential cellular processes.

ResearchSummary from RefSeq, UniProt

This gene encodes a member of the Wiskott-Aldrich syndrome protein family. The gene product is a protein that forms a multiprotein complex that links receptor kinases and actin. Binding to actin occurs through a C-terminal verprolin homology domain in all family members. The multiprotein complex serves to tranduce signals that involve changes in cell shape, motility or function. A pseudogene of this gene have been defined on chromosome 6. Alternative splicing results in multiple transcript variants [provided by RefSeq, May 2014]

ResearchGenerating clinical summary…

Clinical highlights

Interpreting a novel variant

This gene is strongly intolerant of loss-of-function variation in the population, so LoF variants warrant close attention. No curated mechanism annotation is available — see the mechanism card for the computational prediction and its caveats.Based on population constraint only.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.47

LOEUF

—

Mechanism

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Moderate LoF intolerance

LoF Constraint?

0.47LOEUF

pLI 0.540

Z-score 3.27

OE 0.20 (0.10–0.47)

Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?

1.29Z-score

OE missense 0.80 (0.72–0.88)

257 obs / 322.2 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.20 (0.10–0.47)

0≤0.351.4

Missense OE?0.80 (0.72–0.88)

0≤0.61.4

Synonymous OE?1.03

0≤1.21.6

LoF obs/exp: 4 / 19.6Missense obs/exp: 257 / 322.2Syn Z: -0.30

Background carrier burden — how many people carry a rare variant somewhere in WASF3?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 77

675 rare PASS variants

Rare truncating (LoF)

1 in 1,800

64 rare PASS variants

Rare synonymous (reference)

1 in 130

282 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for WASF3. 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 120	1 in 2,900
South Asian	~43k	1 in 95	1 in 1,400
Remaining (unassigned)	~30k	1 in 84	1 in 2,000
European (Finnish)	~27k	1 in 210	1 in 1,900
Admixed American	~22k	1 in 73	1 in 1,700
African / African American	~21k	1 in 61	1 in 2,500
East Asian	~20k	1 in 70	1 in 1,300
Ashkenazi Jewish	~13k	1 in 450	1 in 1,900
Middle Eastern	~2,884	1 in 110	none seen

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): All 8 coding exons well covered in gnomAD exomes and genomes.? see exons ↓