VPS8

VPS8 subunit of CORVET complex, the group of CORVET complex|Ring finger proteins

Basic information

Region (hg38): 3:184812143-185052614

Previous symbols: [ "KIAA0804" ]

Links

ENSG00000156931 ∙ NCBI:23355 ∙ OMIM:618366 ∙ HGNC:29122 ∙ Uniprot:Q8N3P4 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• arthrogryposis multiplex congenita (Limited), mode of inheritance: AR

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the VPS8 gene.

• not_specified (170 variants)
• not_provided (9 variants)
• VPS8-related_disorder (3 variants)
• Flexion_contracture (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the VPS8 gene is commonly pathogenic or not. These statistics are base on transcript: NM_001009921.3. 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				3	2	5
missense			166	7	2	175
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)						0
Total	0	0	166	10	4

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
VPS8	protein_coding	protein_coding	ENST00000437079	47	240472

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
5.11e-8	1.00	124489	0	149	124638	0.000598

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.36	594	695	0.855	0.0000346	9347
Missense in Polyphen		135	193.58	0.69738		2693
Synonymous	0.565	230	241	0.954	0.0000121	2557
Loss of Function	5.79	30	88.9	0.337	0.00000456	1160

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000505	0.000483
Ashkenazi Jewish	0.00	0.00
East Asian	0.000402	0.000389
Finnish	0.000514	0.000511
European (Non-Finnish)	0.00104	0.000947
Middle Eastern	0.000402	0.000389
South Asian	0.000331	0.000327
Other	0.000851	0.000826

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Plays a role in vesicle-mediated protein trafficking of the endocytic membrane transport pathway. Believed to act as a component of the putative CORVET endosomal tethering complexes which is proposed to be involved in the Rab5-to-Rab7 endosome conversion probably implicating MON1A/B, and via binding SNAREs and SNARE complexes to mediate tethering and docking events during SNARE-mediated membrane fusion. The CORVET complex is proposed to function as a Rab5 effector to mediate early endosome fusion probably in specific endosome subpopulations (PubMed:25266290). Functions predominantly in APPL1-containing endosomes (PubMed:25266290). {ECO:0000269|PubMed:25266290, ECO:0000305|PubMed:25266290}.

Recessive Scores

• pRec: 0.111

Intolerance Scores

• loftool: 0.909
• rvis_EVS: -0.37
• rvis_percentile_EVS: 28.31

Haploinsufficiency Scores

• pHI: 0.134
• hipred: N
• hipred_score: 0.478
• ghis: 0.499

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.407

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	High
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Vps8

Gene ontology

• Biological process: protein transport;endosomal vesicle fusion
• Cellular component: early endosome;CORVET complex
• Molecular function: protein binding;metal ion binding