WASHC4

protein-coding

WASH complex subunit 4, the group of WASH complex

Gene summary

This gene encodes a component of the WASH complex, which functions in the intracellular transport of endosomes. Mutations in this gene have been detected in individuals with autosomal recessive cognitive disability. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jun 2014]

Previous symbols:

KIAA1033

MANE transcript

NM_015275.3

Inheritance

ClinVar variants

P:18U:181B:48

Top phenotype

Intellectual developmental disorder, autosomal recessive 43

gnomAD constraint

pLI —, LoF o/e 0.32

Max pathogenic AF

—

Genomic locus

chr12:105,107,324-105,169,130

External References & Databases

Ensembl (ENSG00000136051)

Transcript & Mutation Effects

hg38 • Region Span ~61.8 kb

Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

intellectual disability, autosomal recessive 43LIMITED

Inheritance Pattern: AR

Disease ID:MONDO:0014354

Submitter: Ambry Genetics

autosomal recessive non-syndromic intellectual disabilitySUPPORTIVE

Inheritance Pattern: AR

Disease ID:MONDO:0019502

Submitter: Orphanet

intellectual disability, autosomal recessive 43STRONG

Inheritance Pattern: AR

Disease ID:MONDO:0014354

Submitter: PanelApp Australia

schizophreniaNO_KNOWN

Inheritance Pattern: Unknown

Disease ID:MONDO:0005090

Submitter: Labcorp Genetics (formerly Invitae)

Clinical Genomic Database (CGD)

Intellectual developmental disorder, autosomal recessive 43AR

Manifestation: Neurologic

Intervention: General

Rationale: 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

Refs: 21498477

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to WASHC4 variants in ClinVar

7 Conditions Cataloged

not specifiedTotal: 163

not providedTotal: 82

Intellectual disability, autosomal recessive 43Total: 28

WASHC4-related disorderTotal: 13

See casesTotal: 2

Intellectual disabilityTotal: 1

Inborn genetic diseasesTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_015275.3. 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			3 clinvar	30 clinvar	5 clinvar	38
missense	2 clinvar	3 clinvar	163 clinvar	11 clinvar	2 clinvar	181
nonsense	1 clinvar	6 clinvar	3 clinvar			10
start loss						0
frameshift		5 clinvar	4 clinvar			9
splice donor/acceptor (+/-2bp)		1 clinvar	8 clinvar			9
Total	3	15	181	41	7	247

Highest pathogenic variant AF is 0.00044489224

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 46 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_015275.3	RefSeq	NP_056090.1	33	MANE Select
ENST00000332180.10	Ensembl	ENSP00000328062.6	33	MANE Select
NM_001293640.2	RefSeq	NP_001280569.1	33	Standard
ENST00000547404.1	Ensembl	ENSP00000473263.1	4	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Endocytosis - Homo sapiens (human)

Biological Process

endosome organization
protein transport
endosomal transport

Cellular Component

nucleoplasm
endosome
early endosome
BLOC-1 complex
WASH complex

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000332180
Coding exons: 33
Length: 61811
Individuals with no LoFs: 124661
Homozygous LoFs: 0
Heterozygous LoFs: 132
Defined: 124793
p: 0.000529

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.981	541	609	0.888	0.0000298	7809
Missense (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

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00026	0.00026	rare
Latino/Admixed American	0.0018	0.0018	notable
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00017	0.00017	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.00033	0.00033	rare
South Asian	0.00026	0.00026	rare
Other	0.0028	0.0028	notable

dbNSFP Gene Annotations

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.;

Recessive Scores

pRec: 0.0984

Intolerance Scores

RVIS EVS: 0.21
RVIS percentile EVS: 67.5

Essentials

Essential (gene trap): N