WASF1

Chr 6AD

WASP family member 1

Also known as: NEDALVS, SCAR1, WAVE, WAVE-1, WAVE1

NCBI Gene: 8936ENSG00000112290UniProt: Q92558OMIM: 605035

This protein regulates actin cytoskeleton dynamics by promoting actin filament formation as part of the WAVE complex and is involved in BDNF-NTRK2 endocytic trafficking and mitochondrial dynamics. Mutations cause neurodevelopmental disorder with absent language and variable seizures with autosomal dominant inheritance. The gene is highly constrained against loss-of-function variants (pLI 0.998, LOEUF 0.215), indicating intolerance to protein disruption.

OMIMResearchSummary from RefSeq, OMIM, UniProt
LOFmechanismADLOEUF 0.211 OMIM phenotype
Clinical Summary— WASF1
⚡
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.
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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
LoF intolerant — likely haploinsufficient
LoF Constraint
0.21LOEUF
pLI 0.998
Z-score 4.15
OE 0.05 (0.01–0.21)
Highly constrained

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

Missense Constraint
2.55Z-score
OE missense 0.59 (0.52–0.66)
175 obs / 298.9 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios
LoF OE0.05 (0.01–0.21)
0≤0.351.4
Missense OE0.59 (0.52–0.66)
0≤0.61.4
Synonymous OE0.84
0≤1.21.6
LoF obs/exp: 1 / 22.1Missense obs/exp: 175 / 298.9Syn Z: 1.32
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
limitedWASF1-related neurodevelopmental disorderLOFAD
moderateWASF1-related intellectual disability with seizuresLOFAD
DN
0.2598th %ile
GOF
0.4183th %ile
LOF
0.78top 5%

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

LOFprediction above median · LOEUF 0.21

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

0 submitted variants in ClinVar

ClinVar

Protein Context — Lollipop Plot

WASF1 · 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

ClinicalTrials.gov

No active trials found for this gene.

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Clinical Literature
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Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
[Report of a Chinese pedigree affected with Neurodevelopmental disorder with absent language and variable seizures due to variant of WASF1 gene and a literature review].
Xiu Y et al.·Zhonghua Yi Xue Yi Chuan Xue Za Zhi
2025Review
The recurrent WASF1 nonsense variant identified in two unaffected Chinese families with neurodevelopmental disorder: case report and review of the literatures.
Tang X et al.·BMC Med Genomics
2023Open AccessReview
Recurrent de novo pathogenic variant of WASF1 in a Japanese patient with neurodevelopmental disorder with absent language and variable seizures.
Shimojima Yamamoto K et al.·Hum Genome Var
2021Open Access
Trio exome sequencing identified a novel de novo WASF1 missense variant leading to recurrent site substitution in a Chinese patient with developmental delay, microcephaly, and early-onset seizures: A mutational hotspot p.Trp161 and literature review.
Zhao A et al.·Clin Chim Acta
2021Review
Expansion of the Genotypic and Phenotypic Spectrum of WASF1-Related Neurodevelopmental Disorder.
Srivastava S et al.·Brain Sci
2021Open Access
Top 5 resultsSearch Europe PMC ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients