WASHC4 Gene
WASH Complex Subunit 4
Gene Information Card
| Symbol | WASHC4 |
|---|---|
| Full Name | WASH Complex Subunit 4 |
| Gene Type | Protein coding |
| Chromosomal Location | 21q22.11 |
| NCBI Gene ID | 23325 ncbi.nlm.nih.gov/gene/23325 |
| Ensembl ID | ENSG00000160213 |
| UniProt ID | Q2T9J0 |
| OMIM ID | 615713 |
| HGNC ID | 29138 |
| Aliases | C21orf31, FAM39E, WASH4, WASH complex subunit 4 |
Description
WASHC4 encodes a subunit of the WASH (Wiskott-Aldrich syndrome protein and SCAR homolog) complex, which regulates actin polymerization on endosomes and is essential for endosomal trafficking, retromer-mediated cargo sorting, and cell migration. Mutations in WASHC4 are associated with autosomal recessive intellectual disability and neurodevelopmental disorders.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Intellectual developmental disorder with microcephaly and spasticity (IDDMS) | Loss-of-function mutations impair WASH complex assembly, disrupting endosomal actin dynamics and retromer-dependent trafficking, leading to neuronal dysfunction. | ClinVar, OMIM #615713 |
| Autosomal recessive intellectual disability | Homozygous missense and truncating variants reduce WASH complex stability, affecting synaptic vesicle recycling and dendritic spine morphology. | PubMed, ClinVar |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 12.5 | Medium |
| Testis | 8.3 | Low |
| Lung | 6.1 | Low |
| Kidney | 5.4 | Low |
| Liver | 3.2 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| SH-SY5Y (neuroblastoma) | 14.2 | Neuronal model |
| HEK293 (embryonic kidney) | 9.8 | Common expression system |
| HeLa (cervical carcinoma) | 7.5 | Epithelial model |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.109C>T (p.Arg37Ter) | Nonsense | Rare | Premature truncation, loss of function |
| c.497G>A (p.Arg166Gln) | Missense | Rare | Impaired WASH complex assembly |
| c.1048_1049del (p.Glu350fs) | Frameshift | Rare | Loss of function, protein truncation |
Mutation functional classification
Loss of Function (LOF)
Nonsense and frameshift variants cause complete loss of WASHC4 function, leading to WASH complex instability and defective endosomal trafficking.
Gain of Function (GOF)
No gain-of-function mutations reported for WASHC4.
Dominant Negative (DN)
No dominant-negative mutations reported; all pathogenic variants are recessive.
View complete mutation data：
Gene Ontology (GO)
| • actin cytoskeleton organization (GO:0030036) | • clathrin-coated endocytic vesicle (GO:0045334) |
| • transport vesicle (GO:0030133) | • plasma membrane (GO:0005886) |
| • protein binding (GO:0005515) | • regulation of Rac GTPase activity (GO:0032313) |
Pathways
• WASH complex in endosomal trafficking (Reactome: R-HSA-917937)
• Arp2/3 complex-mediated actin nucleation (Reactome: R-HSA-201681)
• Retromer-mediated cargo recycling (Reactome: R-HSA-917729)
Protein Summary
WASHC4 is a 41 kDa protein (362 amino acids) that localizes to endosomes and is a core component of the WASH complex. It stabilizes the complex and links it to the retromer, enabling actin polymerization via Arp2/3. The protein contains a coiled-coil domain and a C-terminal region critical for complex integrity. Loss of WASHC4 disrupts endosomal sorting, leading to accumulation of cargo in endosomes and impaired cell migration.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| WASHC4 Knockout HEK293 Cell Line | EDJ-KQ7965 | Human | 23325 | Details Get a Quote |
| WASHC4 Knockout A-549 Cell Line | EDJ-KQ33656 | Human | 23325 | Details Get a Quote |
| WASHC4 Knockout HCT 116 Cell Line | EDJ-KQ33657 | Human | 23325 | Details Get a Quote |
| WASHC4 Knockout HeLa Cell Line | EDJ-KQ33658 | Human | 23325 | Details Get a Quote |
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