WASHC2C
protein-codingWASH complex subunit 2C, the group of WASH complex
Gene summary
Enables phosphatidylinositol phosphate binding activity; phosphatidylinositol-3,4-bisphosphate binding activity; and retromer complex binding activity. Involved in several processes, including endosomal transport; negative regulation of barbed-end actin filament capping; and regulation of substrate adhesion-dependent cell spreading. Located in early endosome. Part of WASH complex. [provided by Alliance of Genome Resources, Jun 2026]
- FAM21C
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~65.8 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
No GenCC data available for this gene.
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to WASHC2C variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_001330074.2. Only rare variants are included.
We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.
Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 1 | 4 | 5 | |||
| missense | 158 | 14 | 172 | |||
| nonsense | 0 | |||||
| start loss | 1 | 1 | ||||
| frameshift | 1 | 1 | ||||
| splice donor/acceptor (+/-2bp) | 1 | 1 | ||||
| Total | 0 | 0 | 162 | 18 | 0 | 180 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_001317003.1 | 31 | MANE Select | |
| Ensembl | ENSP00000485513.1 | 31 | MANE Select | |
| RefSeq | NP_001162577.1 | 29 | Standard | |
| RefSeq | NP_001162578.1 | 28 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Endocytosis - Homo sapiens (human)
Biological Process
- protein transport
- retrograde transport, endosome to Golgi
- regulation of substrate adhesion-dependent cell spreading
- retrograde transport, endosome to plasma membrane
- negative regulation of barbed-end actin filament capping
Molecular Function
- protein binding
- phosphatidylinositol-4,5-bisphosphate binding
- phosphatidylinositol-3,4,5-trisphosphate binding
- phosphatidylinositol-5-phosphate binding
- phosphatidylinositol-3-phosphate binding
Cellular Component
- nucleolus
- endosome
- early endosome
- cytosol
- plasma membrane
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000374362
- Coding exons
- 30
- Length
- 65762
- Individuals with no LoFs
- 124685
- Homozygous LoFs
- 1
- Heterozygous LoFs
- 110
- Defined
- 124796
- p
- 0.000445
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | -0.00909 | 408 | 407 | 1.00 | 0.0000207 | 8660 |
| Missense (PolyPhen) | 128 | 140.24 | 0.9127 | 3021 | ||
| Synonymous | 0.189 | 157 | 160 | 0.981 | 0.00000916 | 2471 |
| Loss of Function | 2.30 | 26 | 42.1 | 0.617 | 0.00000190 | 824 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00054 | 0.00052 | rare |
| Latino/Admixed American | 0.00078 | 0.00070 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.00012 | 0.00011 | rare |
| Finnish | 0.000093 | 0.000093 | rare |
| European (Non-Finnish) | 0.00033 | 0.00033 | rare |
| South Asian | 0.0012 | 0.0012 | notable |
| Other | 0.00017 | 0.00016 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Acts at least in part as component of the WASH core complex whose assembly at the surface of endosomes inhibits WASH nucleation-promoting factor (NPF) activity in recruiting and activating the Arp2/3 complex to induce actin polymerization and is involved in the fission of tubules that serve as transport intermediates during endosome sorting. Mediates the recruitment of the WASH core complex to endosome membranes via binding to phospholipids and VPS35 of the retromer CSC. Mediates the recruitment of the F-actin-capping protein dimer to the WASH core complex probably promoting localized F-actin polymerization needed for vesicle scission (PubMed:19922874, PubMed:20498093, PubMed:22513087, PubMed:23331060). Via its C-terminus binds various phospholipids, most strongly phosphatidylinositol 4- phosphate (PtdIns-(4)P), phosphatidylinositol 5-phosphate (PtdIns- (5)P) and phosphatidylinositol 3,5-bisphosphate (PtdIns-(3,5)P2). Involved in the endosome-to-plasma membrane trafficking and recycling of SNX27-retromer-dependent cargo proteins, such as GLUT1 (PubMed:25278552). Required for the association of DNAJC13, ENTR1, ANKRD50 with retromer CSC subunit VPS35 (PubMed:24980502). Required for the endosomal recruitment of CCC complex subunits COMMD1, CCDC93 AND C16orf62 (PubMed:25355947). Plays a role in fluid-phase endocytosis, a process exploited by vaccinia intracellular mature virus (IMV) to enter cells. As a result, may facilitate the penetration of IMV into cells (PubMed:18550675). {ECO:0000269|PubMed:18550675, ECO:0000269|PubMed:19922874, ECO:0000269|PubMed:20498093, ECO:0000269|PubMed:22513087, ECO:0000269|PubMed:23331060, ECO:0000269|PubMed:24980502, ECO:0000269|PubMed:25278552, ECO:0000269|PubMed:25355947}.;
Recessive Scores
- pRec
- 0.0828
Essentials
- Essential (gene trap)
- N