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.

• Ritscher-Schinzel syndrome;Hereditary spastic paraplegia 8 (5 variants)
• Hereditary spastic paraplegia 8;Ritscher-Schinzel syndrome (5 variants)
• Hereditary spastic paraplegia 8 (3 variants)
• Ritscher-Schinzel syndrome 1 (2 variants)
• Inborn genetic diseases (2 variants)
• Combined oxidative phosphorylation defect type 7 (1 variants)
• Ritscher-Schinzel syndrome 1;Hereditary spastic paraplegia 8 (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.

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			9	81	5	95
missense	3	6	199	4	2	214
nonsense	7	2	4			13
start loss			1			1
frameshift	6	1	2			9
inframe indel			2			2
splice donor/acceptor (+/-2bp)		5	1			6
splice region			17	20	4	41
non coding			20	60	144	224
Total	16	14	238	145	151

Highest pathogenic variant AF is 0.0000131

Variants in WASHC5

This is a list of pathogenic ClinVar variants found in the WASHC5 region.

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

Position	Type	Phenotype	Significance	ClinVar
8-125024280-T-C		Hereditary spastic paraplegia 8	Uncertain significance (Jan 13, 2018)
8-125024346-AAC-A		Spastic paraplegia, autosomal dominant	Likely benign (Jun 14, 2016)
8-125024399-A-G		Hereditary spastic paraplegia 8	Benign (Jan 13, 2018)
8-125024427-G-A		Hereditary spastic paraplegia 8	Uncertain significance (Jan 13, 2018)
8-125024440-T-G		Hereditary spastic paraplegia 8	Uncertain significance (Jan 13, 2018)
8-125024492-T-C		Hereditary spastic paraplegia	Uncertain significance (Dec 20, 2016)
8-125024493-T-G		Hereditary spastic paraplegia 8	Uncertain significance (Jan 13, 2018)
8-125024539-T-C		Hereditary spastic paraplegia 8	Benign (Jan 13, 2018)
8-125024576-AT-A		Spastic paraplegia, autosomal dominant	Likely benign (Jun 14, 2016)
8-125024613-AC-A		Spastic paraplegia • not specified	Benign/Likely benign (Oct 19, 2020)
8-125024627-G-A		Hereditary spastic paraplegia	Uncertain significance (Dec 12, 2016)
8-125024635-C-A		WASHC5-related disorder	Uncertain significance (Mar 11, 2024)
8-125024647-G-C		Hereditary spastic paraplegia 8;Ritscher-Schinzel syndrome	Uncertain significance (Jul 24, 2022)
8-125024656-C-T		Hereditary spastic paraplegia 8	Uncertain significance (Jan 13, 2018)
8-125024658-C-T		Inborn genetic diseases	Uncertain significance (Aug 17, 2022)
8-125024659-A-G		Hereditary spastic paraplegia 8	Uncertain significance (Jan 13, 2018)
8-125024674-C-A		Hereditary spastic paraplegia 8	Likely pathogenic (Jun 28, 2019)
8-125024687-GAATTA-G		Hereditary spastic paraplegia 8;Ritscher-Schinzel syndrome	Likely benign (Jan 22, 2024)
8-125024791-A-G			Benign (Jun 26, 2018)
8-125028331-C-T			Benign (Jun 16, 2018)
8-125028383-G-A			Benign (Jun 26, 2018)
8-125028604-ACTAT-A		Spastic paraplegia, autosomal dominant	Uncertain significance (Jun 14, 2016)
8-125028643-G-A		Hereditary spastic paraplegia 8;Ritscher-Schinzel syndrome	Uncertain significance (Sep 17, 2022)
8-125028668-G-A		Ritscher-Schinzel syndrome;Hereditary spastic paraplegia 8	Likely benign (Oct 07, 2020)
8-125028687-G-C		Ritscher-Schinzel syndrome;Hereditary spastic paraplegia 8 • Inborn genetic diseases	Uncertain significance (Sep 04, 2023)

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