WASHC4

WASH complex subunit 4, the group of WASH complex

Basic information

Region (hg38): 12:105107324-105169130

Previous symbols: [ "KIAA1033" ]

Links

ENSG00000136051 ∙ NCBI:23325 ∙ OMIM:615748 ∙ HGNC:29174 ∙ Uniprot:Q2M389 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• schizophrenia (No Known Disease Relationship), mode of inheritance: Unknown
• autosomal recessive non-syndromic intellectual disability (Supportive), mode of inheritance: AR
• intellectual disability, autosomal recessive 43 (Limited), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Intellectual developmental disorder, autosomal recessive 43	AR	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Neurologic	21498477

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the WASHC4 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the WASHC4 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			2	19	6	27
missense		1	72	4	4	81
nonsense		1	1			2
start loss						0
frameshift		2	2			4
inframe indel			1			1
splice donor/acceptor (+/-2bp)		1				1
splice region			2	8	1	11
non coding			1	1		2
Total	0	5	79	24	10

Variants in WASHC4

This is a list of pathogenic ClinVar variants found in the WASHC4 region.

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

Position	Type	Phenotype	Significance	ClinVar
12-105107796-G-C		WASHC4-related disorder	Likely benign (Sep 06, 2019)
12-105107798-G-T		not specified	Uncertain significance (Feb 22, 2016)
12-105107805-C-T		not specified	Uncertain significance (May 20, 2024)
12-105107849-G-A		Intellectual disability, autosomal recessive 43 • WASHC4-related disorder	Conflicting classifications of pathogenicity (Dec 31, 2019)
12-105107851-C-G		not specified	Uncertain significance (Aug 12, 2021)
12-105111175-T-C		WASHC4-related disorder	Benign (Sep 05, 2019)
12-105111180-C-G		WASHC4-related disorder	Benign (Jun 08, 2018)
12-105111204-C-T		not specified	Likely benign (Dec 19, 2016)
12-105111217-T-G		Intellectual disability, autosomal recessive 43	Uncertain significance (Jun 19, 2020)
12-105111221-T-C		not specified	Uncertain significance (Dec 06, 2021)
12-105111242-A-G			Likely benign (Dec 31, 2019)
12-105111272-T-G			Benign (Dec 31, 2019)
12-105114390-C-G		not specified	Uncertain significance (Oct 22, 2021)
12-105115218-A-G		not specified	Uncertain significance (Feb 23, 2023)
12-105115658-C-T		not specified	Uncertain significance (Dec 15, 2016)
12-105115677-G-T			Benign (Apr 01, 2023)
12-105115709-G-A		not specified	Uncertain significance (Aug 22, 2016)
12-105115725-A-G		not specified	Benign/Likely benign (Dec 31, 2019)
12-105118453-C-G		Intellectual disability, autosomal recessive 43	Uncertain significance (Jan 01, 2018)
12-105118490-C-T		not specified	Uncertain significance (Sep 29, 2015)
12-105120548-A-G			Likely benign (Dec 31, 2019)
12-105121180-A-G		Intellectual disability, autosomal recessive 43 • not specified	Uncertain significance (Dec 06, 2022)
12-105122121-A-G			Likely benign (Apr 01, 2023)
12-105122126-A-G		not specified	Uncertain significance (Feb 21, 2024)
12-105122201-A-G		not specified	Uncertain significance (Oct 04, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
WASHC4	protein_coding	protein_coding	ENST00000332180	33	61811

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.00000279	1.00	124661	0	132	124793	0.000529

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.981	541	609	0.888	0.0000298	7809
Missense in Polyphen		131	193.09	0.67843		2609
Synonymous	0.880	188	204	0.922	0.00000998	2065
Loss of Function	5.53	25	77.6	0.322	0.00000452	876

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00209	0.00208
Ashkenazi Jewish	0.00	0.00
East Asian	0.000167	0.000167
Finnish	0.00	0.00
European (Non-Finnish)	0.000333	0.000327
Middle Eastern	0.000167	0.000167
South Asian	0.000264	0.000261
Other	0.00281	0.00281

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Acts at least in part as component of the WASH core complex whose assembly at the surface of endosomes seems to inhibit WASH nucleation-promoting factor (NPF) activity in recruiting and activating the Arp2/3 complex to induce actin polymerization, and which is involved in the regulation of the fission of tubules that serve as transport intermediates during endosome sorting (PubMed:19922875, PubMed:20498093). {ECO:0000250|UniProtKB:Q3UMB9, ECO:0000303|PubMed:21498477, ECO:0000305|PubMed:19922875, ECO:0000305|PubMed:20498093}.
• Disease: DISEASE: Mental retardation, autosomal recessive 43 (MRT43) [MIM:615817]: A disorder characterized by significantly below average general intellectual functioning associated with impairments in adaptive behavior and manifested during the developmental period. {ECO:0000269|PubMed:21498477}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Endocytosis - Homo sapiens (human) (Consensus)

Recessive Scores

• pRec: 0.0984

Intolerance Scores

• rvis_EVS: 0.21
• rvis_percentile_EVS: 67.5

Haploinsufficiency Scores

• pHI: 0.205
• hipred: N
• hipred_score: 0.426
• ghis: 0.571

Essentials

• essential_gene_gene_trap: N

Mouse Genome Informatics

• Gene name: Washc4

Gene ontology

• Biological process: endosome organization;protein transport;endosomal transport
• Cellular component: nucleoplasm;endosome;early endosome;BLOC-1 complex;WASH complex