VPS16

VPS16 core subunit of CORVET and HOPS complexes, the group of CORVET complex|HOPS complex

Basic information

Region (hg38): 20:2840703-2866732

Links

ENSG00000215305 ∙ NCBI:64601 ∙ OMIM:608550 ∙ HGNC:14584 ∙ Uniprot:Q9H269 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• isolated dystonia (Limited), mode of inheritance: AR
• dystonia 30 (Strong), mode of inheritance: AD
• dystonia 30 (Limited), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Dystonia 30	AD/AR	Neurologic	Response to deep brain stimulation has been described	Neurologic	27174565; 32808683; 33482438

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the VPS16 gene.

• not provided (2 variants)
• Dystonia 30 (2 variants)
• VPS16-associated disorder (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the VPS16 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				7	4	11
missense			73	3	1	77
nonsense	2	1	1			4
start loss						0
frameshift	1	1	3			5
inframe indel						0
splice donor/acceptor (+/-2bp)		2	1			3
splice region			1	1		2
non coding		1	2		10	13
Total	3	5	80	10	15

Highest pathogenic variant AF is 0.00000657

Variants in VPS16

This is a list of pathogenic ClinVar variants found in the VPS16 region.

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

Position	Type	Phenotype	Significance	ClinVar
20-2840754-C-T			Benign (May 17, 2021)
20-2840769-C-G			Uncertain significance (Mar 01, 2023)
20-2840779-A-G		Inborn genetic diseases	Uncertain significance (Oct 26, 2021)
20-2840825-C-G			Uncertain significance (Oct 01, 2022)
20-2840882-C-T			Benign (May 26, 2021)
20-2840955-C-T			Benign (May 17, 2021)
20-2859715-G-A			Likely benign (Mar 01, 2022)
20-2859795-G-A		Dystonia 30	Uncertain significance (-)
20-2859801-C-T		Inborn genetic diseases	Uncertain significance (Oct 10, 2023)
20-2860052-A-T		Dystonia 30	Likely pathogenic (-)
20-2860067-C-A		Dystonia 30	Pathogenic (Apr 30, 2021)
20-2860109-C-G			Likely benign (Feb 01, 2023)
20-2860110-G-A		Inborn genetic diseases	Uncertain significance (Nov 08, 2022)
20-2860117-A-C		Inborn genetic diseases	Uncertain significance (Jun 18, 2021)
20-2860127-C-T			Benign (May 05, 2021)
20-2860144-G-T		Inborn genetic diseases	Uncertain significance (Feb 26, 2024)
20-2860242-AAGAGTGGACCCGTGG-GAGAGC		Dystonia 30	Pathogenic (Oct 20, 2021)
20-2860283-G-A			Benign (May 05, 2021)
20-2860284-G-A		Inborn genetic diseases	Uncertain significance (Jan 01, 2023)
20-2860320-G-A			Uncertain significance (Dec 28, 2023)
20-2860365-A-C		Inborn genetic diseases	Uncertain significance (Jul 06, 2021)
20-2860366-A-G		Inborn genetic diseases	Uncertain significance (May 02, 2024)
20-2860454-G-A			Likely benign (Aug 01, 2024)
20-2860486-T-C		Inborn genetic diseases	Uncertain significance (Nov 30, 2022)
20-2860490-C-T			Likely benign (Mar 01, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
VPS16	protein_coding	protein_coding	ENST00000380445	24	26030

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
2.27e-15	0.988	125697	0	51	125748	0.000203

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.823	458	510	0.897	0.0000321	5454
Missense in Polyphen		158	193.89	0.81488		1979
Synonymous	0.861	184	199	0.922	0.0000120	1654
Loss of Function	2.62	32	52.5	0.609	0.00000298	555

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000384	0.000384
Ashkenazi Jewish	0.0000993	0.0000992
East Asian	0.000217	0.000217
Finnish	0.000139	0.000139
European (Non-Finnish)	0.000274	0.000264
Middle Eastern	0.000217	0.000217
South Asian	0.0000653	0.0000653
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Plays a role in vesicle-mediated protein trafficking to lysosomal compartments including the endocytic membrane transport and autophagic pathways. Believed to act as a core component of the putative HOPS and CORVET endosomal tethering complexes which are 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 HOPS complex is proposed to be recruited to Rab7 on the late endosomal membrane and to regulate late endocytic, phagocytic and autophagic traffic towards lysosomes. The CORVET complex is proposed to function as a Rab5 effector to mediate early endosome fusion probably in specific endosome subpopulations (PubMed:11382755, PubMed:23351085, PubMed:24554770, PubMed:25266290, PubMed:25783203). Required for recruitment of VPS33A to the HOPS complex (PubMed:23901104). Required for fusion of endosomes and autophagosomes with lysosomes; the function is dependent on its association with VPS33A but not VPS33B (PubMed:25783203). The function in autophagosome-lysosome fusion implicates STX17 but not UVRAG (PubMed:24554770). {ECO:0000269|PubMed:23901104, ECO:0000269|PubMed:24554770, ECO:0000269|PubMed:25783203, ECO:0000305|PubMed:11382755, ECO:0000305|PubMed:23351085, ECO:0000305|PubMed:25266290, ECO:0000305|PubMed:25783203}.
• Pathway: Ebola Virus Pathway on Host;Ebola Virus Pathway on Host (Consensus)

Recessive Scores

• pRec: 0.111

Intolerance Scores

• loftool: 0.817
• rvis_EVS: -0.9
• rvis_percentile_EVS: 10.14

Haploinsufficiency Scores

• pHI: 0.303
• hipred: N
• hipred_score: 0.415
• ghis: 0.565

Essentials

• essential_gene_CRISPR: E
• essential_gene_CRISPR2: S
• essential_gene_gene_trap: K
• gene_indispensability_pred: E
• gene_indispensability_score: 0.890

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Vps16
• Phenotype: behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); muscle phenotype

Gene ontology

• Biological process: intracellular protein transport;vacuole organization;endosome to lysosome transport;endosomal transport;regulation of vacuole fusion, non-autophagic;regulation of SNARE complex assembly;autophagosome maturation
• Cellular component: lysosome;lysosomal membrane;endosome;early endosome;late endosome;autophagosome;clathrin-coated vesicle;axon;HOPS complex;late endosome membrane;neuronal cell body;recycling endosome
• Molecular function: actin binding;protein binding;actin filament binding