WASHC4 (WASH complex subunit 4)

Gene

• Entrez ID: 23325
• Gene name: WASH complex subunit 4
• Gene symbol: WASHC4
• Synonyms (NCBI Gene): KIAA1033, MRT43, SWIP
• Chromosome: 12
• Chromosome location: 12q23.3
• 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 multipl

SNPs

SNP ID	Visualize variation	Clinical significance	Consequence
rs35267264	G>A	Conflicting-interpretations-of-pathogenicity, uncertain-significance	Missense variant, non coding transcript variant, coding sequence variant
rs201428088	A>G,T	Likely-pathogenic	Missense variant, non coding transcript variant, coding sequence variant
rs587777411	C>G	Pathogenic	Coding sequence variant, missense variant, non coding transcript variant, genic downstream transcript variant
rs748436953	A>G	Likely-pathogenic	Coding sequence variant, missense variant, non coding transcript variant, genic downstream transcript variant
rs1064797173	->A	Likely-pathogenic	Non coding transcript variant, stop gained, coding sequence variant

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0005515	Function	Protein binding	IPI	32353859, 33060197, 36217030
GO:0005654	Component	Nucleoplasm	IDA
GO:0005768	Component	Endosome	IBA
GO:0005768	Component	Endosome	IDA	20923837
GO:0005768	Component	Endosome	IEA
GO:0005769	Component	Early endosome	IEA
GO:0007032	Process	Endosome organization	IBA
GO:0007032	Process	Endosome organization	IMP	23676666
GO:0015031	Process	Protein transport	IEA
GO:0016197	Process	Endosomal transport	IBA
GO:0016197	Process	Endosomal transport	IEA
GO:0016197	Process	Endosomal transport	IMP	20923837
GO:0016197	Process	Endosomal transport	ISS
GO:0016197	Process	Endosomal transport	NAS	19922875
GO:0031083	Component	BLOC-1 complex	IDA	23676666
GO:0031901	Component	Early endosome membrane	NAS	19922874
GO:0034315	Process	Regulation of Arp2/3 complex-mediated actin nucleation	NAS	19922875
GO:0050890	Process	Cognition	IEA
GO:0050905	Process	Neuromuscular process	IEA
GO:0061635	Process	Regulation of protein complex stability	IEA
GO:0071203	Component	WASH complex	IBA
GO:0071203	Component	WASH complex	IDA	19922875
GO:0071203	Component	WASH complex	IEA
GO:0071203	Component	WASH complex	NAS	19922875
GO:0140591	Process	Nuclear envelope budding	ISS
GO:0140894	Process	Endolysosomal toll-like receptor signaling pathway	IEA

Other IDs

• MIM: 615748
• HGNC: 29174
• e!Ensembl: ENSG00000136051

Protein

• UniProt ID: Q2M389
• Protein name: WASH complex subunit 4 (Strumpellin and WASH-interacting protein) (SWIP) (WASH complex subunit SWIP)
• Protein function: Acts as a component of the WASH core complex that functions as a nucleation-promoting factor (NPF) at the surface of endosomes, where it recruits and activates the Arp2/3 complex to induce actin polymerization, playing a key role in the fission
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF14745	WASH-7_N	32 → 604	WASH complex subunit 7, N-terminal	Family
  PF14744	WASH-7_mid	605 → 949	WASH complex subunit 7	Family
  PF14746	WASH-7_C	966 → 1135	WASH complex subunit 7, C-terminal	Family

• Sequence:

  MAVETLSPDWEFDRVDDGSQKIHAEVQLKNYGKFLEEYTSQLRRIEDALDDSIGDVWDFN
  LDPIALKLLPYEQSSLLELIKTENKVLNKVITVYAALCCEIKKLKYEAETKFYNGLLFYG
  EGATDASMVEGDCQIQMGRFISFLQELSCFVTRCYEVVMNVVHQLAALYISNKIAPKIIE
  TTGVHFQTMYEHLGELLTVLLTLDEIIDNHITLKDHWTMYKRLLKSVHHNPSKFGIQEEK
  LKPFEKFLLKLEGQLLDGMIFQACIEQQFDSLNGGVSVSKNSTFAEEFAHSIRSIFANVE
  AKLGEPSEIDQRDKYVGICGLFVLHFQIFRTIDKKFYKSLLDICKKVPAITLTANIIWFP
  DNFLIQKIPAAAKLLDRKSLQAIKIHRDTFLQQKAQSLTKDVQSYYVFVSSWMMKMESIL
  SKEQRMDKFAEDLTNRCNVFIQGFLYAYSISTIIKTTMNLYMSMQKPMTKTSVKALCRLV
  ELLKAIEHMFYRRSMVVADSVSHITQHLQHQALHSISVAKKRVISDKKYSEQRLDVLSAL
  VLAENTLNGPSTKQRRLIVSLALSVGTQMKTFKDEELFPLQVVMKKLDLISELRERVQTQ
  CDCCFLYWHRAVFPIYLDDVYENAVDAARLHYMFSALRDCVPAMMHARHLESYEILLDCY
  DKEIMEILNEHLLDKLCKEIEKDLRLSVHTHLKLDDRNPFKVGMKDLALFFSLNPIRFFN
  RFIDIRAYVTHYLDKTFYNLTTVALHDWATYSEMRNLATQRYGLVMTEAHLPSQTLEQGL
  DVLEIMRNIHIFVSRYLYNLNNQIFIERTSNNKHLNTINIRHIANSIRTHGTGIMNTTVN
  FTYQFLKKKFYIFSQFMYDEHIKSRLIKDIRFFREIKDQNDHKYPFDRAEKFNRGIRKLG
  VTPEGQSYLDQFRQLISQIGNAMGYVRMIRSGGLHCSSNAIRFVPDLEDIVNFEELVKEE
  GLAEETLKAARHLDSVLSDHTRNSAEGTEYFKMLVDVFAPEFRRPKNIHLRNFYIIVPPL
  TLNFVEHSISCKEKLNKKNKIGAAFTDDGFAMGVAYILKLLDQYREFDSLHWFQSVREKY
  LKEIRAVAKQQNVQSASQDEKLLQTMNLTQKRLDVYLQEFELLYFSLSSARIFFRADKTA
  AEENQEKKEKEEETKTSNGDLSDSTVSADPVVK

• Sequence length: 1173

Pathways

KEGG:

Endocytosis

Associated diseases

Evidence Score:

• ★☆☆☆☆  Gene-disease association found in Text Mining only
• ★★☆☆☆  Found in Text Mining and Unknown/Other Associations
• ★★★☆☆  Reported in Unknown/Other Associations across ≥2 Sources
• ★★★★☆  ClinVar: Pathogenic/Likely Pathogenic (<5 Variants)
• ★★★★★  ClinVar: Pathogenic/Likely Pathogenic (≥5 Variants)

Causal
Phenotype Name	Clinical Significance	dbSNP ID	RCV Accession	Evidence Score
Intellectual disability, autosomal recessive 43	Pathogenic; Likely pathogenic	rs587777411, rs2135773055, rs1212552985, rs2502632564, rs2502685643, rs748436953, rs1881282106	RCV000119809 RCV002267714 RCV002267715 RCV002470164 RCV002510342 RCV000857314 RCV001291735	★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)

Unknown / Other Associations
Phenotype Name	Clinical Significance	Source	Evidence Score
Acute myeloid leukemia	Uncertain significance	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
AUTOSOMAL RECESSIVE NON-SYNDROMIC INTELLECTUAL DISABILITY	—	Disgenet, Orphanet Disgenet, Orphanet Disgenet, Orphanet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Cervical cancer	Likely benign; Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Clear cell carcinoma of kidney	Likely benign; Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Familial cancer of breast	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
INTELLECTUAL DEVELOPMENTAL DISORDER, AUTOSOMAL RECESSIVE 43	—	CTD, Disgenet, HPO CTD, Disgenet, HPO CTD, Disgenet, HPO	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Intellectual disability	Conflicting classifications of pathogenicity	ClinVar Disgenet	★★★☆☆ Reported in Unknown/Other Associations (≥2 sources)
Malignant lymphoma, large B-cell, diffuse	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Malignant tumor of esophagus	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Ovarian serous cystadenocarcinoma	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Sarcoma	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
SCHIZOPHRENIA	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Thymoma	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Thyroid cancer, nonmedullary, 1	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
WASHC4-related disorder	Uncertain significance; Conflicting classifications of pathogenicity; Likely benign; Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations

Associations from Text Mining
Disease Name	Disease (Merged)	Source	PMID	Relationship Type	Evidence Score
Absence of septum pellucidum	Absence Of Septum Pellucidum	HPO_DG			★☆☆☆☆ Found in Text Mining only
Alzheimer Disease	Alzheimer disease	Pubtator	22673115	Associate	★☆☆☆☆ Found in Text Mining only
Autistic behavior	Autism	HPO_DG			★☆☆☆☆ Found in Text Mining only
Autosomal recessive non-syndromic intellectual disability	Non-Syndromic Intellectual Disability	Orphanet			★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Central visual impairment	Central Visual Impairment	HPO_DG			★☆☆☆☆ Found in Text Mining only
Cerebral atrophy	Cerebral Atrophy	HPO_DG			★☆☆☆☆ Found in Text Mining only
Clumsiness - motor delay	Motor delay	HPO_DG			★☆☆☆☆ Found in Text Mining only
Cortical Dysplasia	Cortical Dysplasia	HPO_DG			★☆☆☆☆ Found in Text Mining only
Depressive disorder	Mental Depression	HPO_DG			★☆☆☆☆ Found in Text Mining only
Dwarfism	Dwarfism	HPO_DG			★☆☆☆☆ Found in Text Mining only
Dyskinetic syndrome	Dyskinetic Syndrome	HPO_DG			★☆☆☆☆ Found in Text Mining only
Dyssomnias	Dyssomnia	HPO_DG			★☆☆☆☆ Found in Text Mining only
Generalized seizures	Seizure	HPO_DG			★☆☆☆☆ Found in Text Mining only
Global developmental delay	Developmental Delay	HPO_DG			★☆☆☆☆ Found in Text Mining only
Hypoplasia of corpus callosum	Hypoplasia Of Corpus Callosum	HPO_DG			★☆☆☆☆ Found in Text Mining only
Intellectual Disability	Mental retardation	BEFREE	21498477		★★★☆☆ Reported in Unknown/Other Associations (≥2 sources)
Intellectual Disability	Mental retardation	HPO_DG			★★★☆☆ Reported in Unknown/Other Associations (≥2 sources)
MENTAL RETARDATION, AUTOSOMAL RECESSIVE 43	Mental retardation	UNIPROT_DG	21498477		★☆☆☆☆ Found in Text Mining only
MENTAL RETARDATION, AUTOSOMAL RECESSIVE 43	Mental retardation	CLINVAR_DG			★☆☆☆☆ Found in Text Mining only
MENTAL RETARDATION, AUTOSOMAL RECESSIVE 43	Mental retardation	CTD_human_DG			★☆☆☆☆ Found in Text Mining only
Microcephaly	Microcephaly	HPO_DG			★☆☆☆☆ Found in Text Mining only
Mild Mental Retardation	Mental retardation	HPO_DG			★☆☆☆☆ Found in Text Mining only
Moderate intellectual disability	Mental retardation	HPO_DG			★☆☆☆☆ Found in Text Mining only
Myopathy	Myopathy	BEFREE	30010465		★☆☆☆☆ Found in Text Mining only
Penile Neoplasms	Penile neoplasm	Pubtator	23341933	Associate	★☆☆☆☆ Found in Text Mining only
Polymicrogyria	Polymicrogyria	HPO_DG			★☆☆☆☆ Found in Text Mining only
Salaam Seizures	Salaam Seizures	HPO_DG			★☆☆☆☆ Found in Text Mining only
Severe intellectual disability	Mental retardation	HPO_DG			★☆☆☆☆ Found in Text Mining only
Sleep Disorders	Sleep Disorders	HPO_DG			★☆☆☆☆ Found in Text Mining only
Stereotyped Behavior	Stereotyped Behavior	HPO_DG			★☆☆☆☆ Found in Text Mining only