WASHC5

WASH complex subunit 5, the group of WASH complex

Basic information

Region (hg38): 8:125024260-125091819

Previous symbols: [ "SPG8", "KIAA0196" ]

Links

ENSG00000164961 ∙ NCBI:9897 ∙ OMIM:610657 ∙ HGNC:28984 ∙ Uniprot:Q12768 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• Ritscher-Schinzel syndrome 1 (Strong), mode of inheritance: AR
• Ritscher-Schinzel syndrome (Supportive), mode of inheritance: AR
• hereditary spastic paraplegia 8 (Supportive), mode of inheritance: AD
• Ritscher-Schinzel syndrome 1 (Strong), mode of inheritance: AR
• Ritscher-Schinzel syndrome 1 (Strong), mode of inheritance: AR
• hereditary spastic paraplegia 8 (Moderate), mode of inheritance: AD
• Ritscher-Schinzel syndrome 1 (Limited), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Ritscher-Schinzel syndrome 1 (3C syndrome)	AR	Cardiovascular	The condition may involve congenital heart anomalies, some of which may require surgical and other interventions, and awareness may allow early diagnosis and management	Cardiovascular; Craniofacial; Neurologic; Ophthalmologic	7604842; 10797436; 17160902; 20301727; 23455931; 24065355

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the WASHC5 gene.

• Hereditary_spastic_paraplegia_8 (402 variants)
• Ritscher-Schinzel_syndrome (362 variants)
• not_provided (185 variants)
• not_specified (46 variants)
• Hereditary_spastic_paraplegia (41 variants)
• Ritscher-Schinzel_syndrome_1 (28 variants)
• WASHC5-related_disorder (26 variants)
• Inborn_genetic_diseases (22 variants)
• Spastic_paraplegia,_autosomal_dominant (2 variants)
• Spastic_paraplegia (2 variants)
• See_cases (2 variants)
• Muscle_weakness (2 variants)
• Incidental_Discovery (1 variants)
• Stress_urinary_incontinence (1 variants)
• Headache (1 variants)
• Spasticity (1 variants)
• Hereditary_spastic_paraplegia_47 (1 variants)
• Spastic_gait (1 variants)
• Intellectual_disability (1 variants)
• Equinovarus_deformity (1 variants)
• Loss_of_ambulation (1 variants)
• Lower_limb_spasticity (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the WASHC5 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000014846.4. Only rare variants are included in the table.

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.

Effect	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			11	97	3	111
missense	5	12	236	12	3	268
nonsense	6	6	5	1		18
start loss			1			1
frameshift	6	6	4			16
splice donor/acceptor (+/-2bp)		7	1			8
Total	17	31	258	110	6

Highest pathogenic variant AF is 0.000017969585

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
WASHC5	protein_coding	protein_coding	ENST00000318410	28	67581

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
8.27e-18	0.999	125635	0	113	125748	0.000449

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.30	527	618	0.853	0.0000334	7654
Missense in Polyphen		188	239.56	0.78478		2978
Synonymous	-0.464	235	226	1.04	0.0000127	2169
Loss of Function	3.29	39	68.3	0.571	0.00000372	790

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000898	0.000897
Ashkenazi Jewish	0.0000993	0.0000992
East Asian	0.000218	0.000217
Finnish	0.000279	0.000277
European (Non-Finnish)	0.000565	0.000563
Middle Eastern	0.000218	0.000217
South Asian	0.000425	0.000425
Other	0.000490	0.000489

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 regulation of the fission of tubules that serve as transport intermediates during endosome sorting (PubMed:19922875, PubMed:20498093). May be involved in axonal outgrowth. Involved in cellular localization of ADRB2 (PubMed:23085491). Involved in cellular trafficking of BLOC-1 complex cargos such as ATP7A and VAMP7 (PubMed:23676666). {ECO:0000269|PubMed:19922875, ECO:0000269|PubMed:20833645, ECO:0000269|PubMed:23085491, ECO:0000269|PubMed:23676666}.
• Disease: DISEASE: Ritscher-Schinzel syndrome 1 (RTSC1) [MIM:220210]: A developmental malformation syndrome characterized by craniofacial abnormalities, congenital heart defects, and cerebellar brain malformations. Facial features include prominent occiput, prominent forehead, low-set ears, downslanting palpebral fissures, depressed nasal bridge, and micrognathia. Cardiac defects can include septal defects and aortic stenosis, among others, and brain imaging shows Dandy-Walker malformation, cerebellar vermis hypoplasia, posterior fossa cysts, and ventricular dilatation. Affected individuals have severe developmental delay. {ECO:0000269|PubMed:24065355}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Endocytosis - Homo sapiens (human) (Consensus)

Recessive Scores

• pRec: 0.120

Intolerance Scores

• rvis_EVS: -1.3
• rvis_percentile_EVS: 4.93

Haploinsufficiency Scores

• pHI: 0.384
• hipred: N
• hipred_score: 0.414
• ghis: 0.585

Essentials

• essential_gene_gene_trap: N

Mouse Genome Informatics

• Gene name: Washc5
• Phenotype: growth/size/body region phenotype; pigmentation phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); hematopoietic system phenotype

Zebrafish Information Network

• Gene name: washc5
• Affected structure: motor neuron
• Phenotype tag: abnormal
• Phenotype quality: absent

Gene ontology

• Biological process: oocyte maturation;positive regulation of neuron projection development;protein transport;endosomal transport;polar body extrusion after meiotic divisions;spindle assembly involved in meiosis
• Cellular component: nucleoplasm;early endosome;endoplasmic reticulum;cytosol;neuron projection;neuronal cell body;WASH complex
• Molecular function: protein binding