WASHC1

Chr 9

WASH complex subunit 1

Also known as: FAM39E, WASH, WASH1

NCBI Gene: 100287171 ENSG00000181404 UniProt: A8K0Z3 OMIM: 613632

The WASHC1 protein is a component of the WASH complex that activates actin polymerization at endosome surfaces, regulating endosomal trafficking and receptor recycling. Mutations cause Ritscher-Schinzel syndrome, a rare autosomal recessive disorder characterized by intellectual disability, cerebellar hypoplasia, and craniofacial anomalies. This gene shows high constraint against loss-of-function variants, indicating that biallelic mutations are required for disease manifestation.

OMIM ResearchSummary from RefSeq, UniProt

Enables alpha-tubulin binding activity and ubiquitin protein ligase binding activity. Involved in several processes, including Arp2/3 complex-mediated actin nucleation; endosomal transport; and positive regulation of pseudopodium assembly. Located in several cellular components, including endosome; exocyst; and lamellipodium. Part of WASH complex. [provided by Alliance of Genome Resources, Jul 2025]

OMIM ResearchGenerating clinical summary…

Active trials

Pubs (1 yr)

—

P/LP submissions

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P/LP missense

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LOEUF

Mechanism· predicted

Population Genetics & Constraint

gnomAD

Constraint data not available from gnomAD.

Background carrier burden — how many people carry a rare variant somewhere in WASHC1?

gnomAD v4 · ~697k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 72

157 rare PASS variants

Rare truncating (LoF)

1 in 270

42 rare PASS variants

Rare synonymous (reference)

1 in 150

60 rare PASS variants

Rare missense and truncating variants are carried at similar rates in WASHC1; 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)	~533k	1 in 100	1 in 900
South Asian	~42k	1 in 110	1 in 7,200
Remaining (unassigned)	~29k	1 in 75	1 in 350
European (Finnish)	~25k	1 in 340	1 in 4,100
Admixed American	~22k	1 in 81	1 in 200
African / African American	~20k	1 in 78	1 in 800
East Asian	~20k	1 in 98	1 in 360
Ashkenazi Jewish	~12k	1 in 400	none seen
Middle Eastern	~1,965	1 in 200	≈ 1 in 600

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): 0 of 10 coding exons well covered in gnomAD exomes; exons 2, 3, 4, 5, 6 and 2 more poorly covered; exons 7, 9, 11 marginal. Genomes: 0 of 10 (exons 2, 3, 4, 5, 6 and 5 more below).? see exons ↓