WASHC4

Chr 12AR

WASH complex subunit 4

Also known as: KIAA1033, MRT43, SWIP

The protein acts as a component of the WASH core complex that recruits and activates the Arp2/3 complex to induce actin polymerization at endosome surfaces, playing a key role in endosome sorting and tubule fission during intracellular transport. Mutations cause autosomal recessive intellectual developmental disorder. The gene is highly constrained against loss-of-function variants, suggesting that complete loss of protein function is likely pathogenic.

OMIMResearchSummary from RefSeq, OMIM, UniProt
ARLOEUF 0.451 OMIM phenotype
Clinical SummaryWASHC4
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.32) despite low pLI — interpret in context.
📋
ClinVar Variants
21 unique Pathogenic / Likely Pathogenic· 167 VUS of 271 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Moderate LoF intolerance
LoF Constraint
0.45LOEUF
pLI 0.000
Z-score 5.53
OE 0.32 (0.230.45)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint
0.98Z-score
OE missense 0.89 (0.830.95)
541 obs / 609.1 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.32 (0.230.45)
00.351.4
Missense OE0.89 (0.830.95)
00.61.4
Synonymous OE0.92
01.21.6
LoF obs/exp: 25 / 77.6Missense obs/exp: 541 / 609.1Syn Z: 0.88

ClinVar Variant Classifications

271 submitted variants in ClinVar

Classification Summary

Pathogenic10
Likely Pathogenic11
VUS167
Likely Benign38
Benign10
Conflicting9
10
Pathogenic
11
Likely Pathogenic
167
VUS
38
Likely Benign
10
Benign
9
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
1
2
7
0
10
Likely Pathogenic
9
1
1
0
11
VUS
5
152
8
2
167
Likely Benign
0
4
9
25
38
Benign
0
3
1
6
10
Conflicting
9
Total151622633245

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

View in ClinVar →

Protein Context — Lollipop Plot

WASHC4 · 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.

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Clinical Literature
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