WASHC2C

WASH complex subunit 2C, the group of WASH complex

Basic information

Region (hg38): 10:45727200-45792964

Previous symbols: [ "FAM21C" ]

Links

ENSG00000172661 ∙ NCBI:253725 ∙ OMIM:613631 ∙ HGNC:23414 ∙ Uniprot:Q9Y4E1 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the WASHC2C gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the WASHC2C gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous				3		3
missense			55	8		63
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding						0
Total	0	0	55	11	0

Variants in WASHC2C

This is a list of pathogenic ClinVar variants found in the WASHC2C region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
10-45727419-G-A		not specified	Uncertain significance (Aug 17, 2022)
10-45727424-G-C		not specified	Uncertain significance (Aug 17, 2022)
10-45727434-C-G			Likely benign (Jul 01, 2022)
10-45727439-A-C		not specified	Uncertain significance (Dec 11, 2023)
10-45727465-G-T		not specified	Uncertain significance (Dec 02, 2021)
10-45727486-G-A		not specified	Uncertain significance (Jan 22, 2024)
10-45727509-C-A		not specified	Uncertain significance (Dec 02, 2022)
10-45727531-G-A		not specified	Uncertain significance (Oct 01, 2024)
10-45728877-C-A		not specified	Uncertain significance (May 29, 2024)
10-45728918-C-G		not specified	Uncertain significance (Oct 14, 2023)
10-45728935-G-A		not specified	Uncertain significance (Feb 22, 2024)
10-45728943-C-T		not specified	Uncertain significance (Dec 16, 2021)
10-45737984-G-A		not specified	Uncertain significance (May 23, 2024)
10-45737989-T-C		not specified	Uncertain significance (Sep 03, 2024)
10-45743424-T-C		not specified	Uncertain significance (Jun 18, 2021)
10-45743441-A-T		not specified	Uncertain significance (Apr 23, 2024)
10-45743443-G-A		not specified	Uncertain significance (Feb 16, 2023)
10-45743444-G-A		not specified	Uncertain significance (May 13, 2024)
10-45743454-A-G		not specified	Uncertain significance (Oct 05, 2021)
10-45746604-C-T		not specified	Uncertain significance (Jun 10, 2024)
10-45750100-C-T		not specified	Uncertain significance (Jun 26, 2023)
10-45750103-C-T		not specified	Uncertain significance (Sep 16, 2021)
10-45750127-A-T		not specified	Uncertain significance (Sep 25, 2023)
10-45750171-G-A		not specified	Uncertain significance (Jun 22, 2023)
10-45750174-G-T		not specified	Uncertain significance (Sep 13, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
WASHC2C	protein_coding	protein_coding	ENST00000374362	30	65762

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
9.03e-13	0.968	124685	1	110	124796	0.000445

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.00909	408	407	1.00	0.0000207	8660
Missense in 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

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00132	0.00130
Ashkenazi Jewish	0.00	0.00
East Asian	0.000116	0.000111
Finnish	0.0000928	0.0000928
European (Non-Finnish)	0.000332	0.000327
Middle Eastern	0.000116	0.000111
South Asian	0.00121	0.00121
Other	0.000165	0.000165

dbNSFP

Source: dbNSFP

• 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}.
• Pathway: Endocytosis - Homo sapiens (human) (Consensus)

Recessive Scores

• pRec: 0.0828

Haploinsufficiency Scores

• ghis: 0.532

Essentials

• essential_gene_gene_trap: N

Mouse Genome Informatics

• Gene name: Washc2

Gene ontology

• 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
• Cellular component: nucleolus;endosome;early endosome;cytosol;plasma membrane;early endosome membrane;intracellular membrane-bounded organelle;WASH complex
• Molecular function: protein binding;phosphatidylinositol-4,5-bisphosphate binding;phosphatidylinositol-3,4,5-trisphosphate binding;phosphatidylinositol-5-phosphate binding;phosphatidylinositol-3-phosphate binding;phosphatidylinositol-3,4-bisphosphate binding;phosphatidylinositol-4-phosphate binding;phosphatidylinositol-3,5-bisphosphate binding;retromer complex binding