VPS11
Basic information
Region (hg38): 11:119067818-119081972
Links
Phenotypes
GenCC
Source:
- hypomyelinating leukodystrophy 12 (Supportive), mode of inheritance: AR
- hypomyelinating leukodystrophy 12 (Strong), mode of inheritance: AR
Clinical Genomic Database
Source:
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
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.
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 | 228 | 10 | 241 | |||
missense | 83 | 95 | ||||
nonsense | 1 | |||||
start loss | 0 | |||||
frameshift | 2 | |||||
inframe indel | 3 | |||||
splice donor/acceptor (+/-2bp) | 0 | |||||
splice region | 3 | 36 | 6 | 45 | ||
non coding | 96 | 10 | 110 | |||
Total | 0 | 1 | 94 | 329 | 28 |
Variants in VPS11
This is a list of pathogenic ClinVar variants found in the VPS11 region.
You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.
Position | Type | Phenotype | Significance | ClinVar |
---|---|---|---|---|
11-119067829-G-A | Likely benign (Nov 28, 2023) | |||
11-119067829-G-C | Likely benign (May 15, 2023) | |||
11-119067832-C-T | Likely benign (Jan 24, 2024) | |||
11-119067833-T-C | Uncertain significance (Dec 15, 2021) | |||
11-119067836-C-T | Likely benign (Oct 13, 2023) | |||
11-119067838-G-A | Likely benign (Dec 22, 2023) | |||
11-119067847-G-A | Likely benign (Dec 22, 2023) | |||
11-119067847-G-C | Likely benign (Jan 29, 2024) | |||
11-119067850-C-T | Likely benign (Oct 30, 2023) | |||
11-119067853-C-A | Uncertain significance (Nov 27, 2023) | |||
11-119067853-C-T | Likely benign (Nov 29, 2023) | |||
11-119067859-C-T | Likely benign (Mar 12, 2023) | |||
11-119067862-C-T | Likely benign (Jun 17, 2023) | |||
11-119067863-G-C | Inborn genetic diseases | Uncertain significance (Jan 17, 2024) | ||
11-119067868-G-A | Likely benign (Jul 13, 2023) | |||
11-119067871-G-A | Likely benign (Nov 29, 2023) | |||
11-119067875-G-A | Inborn genetic diseases | Uncertain significance (Jan 23, 2024) | ||
11-119067875-G-C | Uncertain significance (Mar 16, 2022) | |||
11-119067876-T-G | Inborn genetic diseases | Uncertain significance (May 13, 2024) | ||
11-119067883-G-A | Likely benign (Jul 06, 2023) | |||
11-119067895-T-C | Likely benign (Oct 04, 2023) | |||
11-119067902-G-C | Inborn genetic diseases | Uncertain significance (Jan 09, 2024) | ||
11-119067904-C-T | Likely benign (Apr 07, 2023) | |||
11-119067905-G-A | Inborn genetic diseases | Uncertain significance (Jun 12, 2023) | ||
11-119067907-T-C | Likely benign (Jun 04, 2023) |
GnomAD
Source:
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:
- 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
- ghis
Essentials
- essential_gene_CRISPR
- essential_gene_CRISPR2
- essential_gene_gene_trap
- 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
- Phenotype
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