VPS11

VPS11 core subunit of CORVET and HOPS complexes, the group of HOPS complex|CORVET complex|Ring finger proteins

Basic information

Region (hg38): 11:119067818-119081972

Links

ENSG00000160695 ∙ NCBI:55823 ∙ OMIM:608549 ∙ HGNC:14583 ∙ Uniprot:Q9H270 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• hypomyelinating leukodystrophy 12 (Supportive), mode of inheritance: AR
• hypomyelinating leukodystrophy 12 (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Dystonia 32; Leukodystrophy, hypomyelinating 12	AR	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Neurologic	26307567; 33452836

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the VPS11 gene.

• not_provided (504 variants)
• Inborn_genetic_diseases (37 variants)
• Hypomyelinating_leukodystrophy_12 (15 variants)
• VPS11-related_disorder (4 variants)
• Dystonia_32 (3 variants)
• not_specified (2 variants)
• Leukoencephalopathy (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the VPS11 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000021729.6. 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	251	9	263
missense	1	1	110	7	5	124
nonsense			2			2
start loss						0
frameshift					2	2
splice donor/acceptor (+/-2bp)						0
Total	1	1	115	258	16

Highest pathogenic variant AF is 0.00005266693

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
VPS11	protein_coding	protein_coding	ENST00000300793	17	14286

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.0000189	1.00	70	123218	1410	124698	0.976

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	2.30	384	534	0.720	0.0000307	6185
Missense in Polyphen		108	178.73	0.60425		2209
Synonymous	-0.777	225	211	1.07	0.0000121	1771
Loss of Function	4.09	17	47.4	0.358	0.00000262	511

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	2.00	1.93
Ashkenazi Jewish	1.00	1.00
East Asian	1.00	0.989
Finnish	1.00	0.978
European (Non-Finnish)	1.00	0.979
Middle Eastern	1.00	0.989
South Asian	1.00	1.00
Other	1.00	0.956

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 fusion of endosomes and autophagosomes with lysosomes (PubMed:25783203). Involved in cargo transport from early to late endosomes and required for the transition from early to late endosomes (PubMed:21148287). Involved in the retrograde Shiga toxin transport (PubMed:23593995). {ECO:0000269|PubMed:21148287, ECO:0000269|PubMed:23593995, ECO:0000269|PubMed:25783203, ECO:0000305|PubMed:11382755, ECO:0000305|PubMed:23351085, ECO:0000305|PubMed:24554770, ECO:0000305|PubMed:25266290, ECO:0000305|PubMed:25783203}.
• Pathway: Ebola Virus Pathway on Host;Ebola Virus Pathway on Host (Consensus)

Recessive Scores

• pRec: 0.221

Haploinsufficiency Scores

• pHI: 0.292
• hipred: Y
• hipred_score: 0.575

Essentials

• gene_indispensability_pred: E
• gene_indispensability_score: 0.873

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Vps11

Zebrafish Information Network

• Gene name: vps11
• Affected structure: Muller cell
• Phenotype tag: abnormal
• Phenotype quality: hypertrophic

Gene ontology

• Biological process: intracellular protein transport;vesicle docking involved in exocytosis;autophagy;endosome organization;vacuole organization;endosome to lysosome transport;regulation of protein stability;endosomal vesicle fusion;regulation of SNARE complex assembly;regulation of organelle assembly;positive regulation of cellular protein catabolic process;positive regulation of protein targeting to mitochondrion;positive regulation of early endosome to late endosome transport
• Cellular component: lysosome;lysosomal membrane;endosome;early endosome;late endosome;autophagosome;clathrin-coated vesicle;endocytic vesicle;HOPS complex;late endosome membrane
• Molecular function: nucleotide binding;protein binding;protein domain specific binding;syntaxin binding;protein binding, bridging;metal ion binding