VPS26A
VPS26 retromer complex component A
Basic information
Region (hg38): 10:69123512-69174412
Previous symbols: [ "VPS26" ]
Links
Phenotypes
GenCC
Source:
No genCC data.
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 VPS26A 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 | 0 | |||||
| missense | 14 | 14 | ||||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| inframe indel | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| splice region | 0 | |||||
| non coding | 0 | |||||
| Total | 0 | 0 | 14 | 0 | 0 |
Variants in VPS26A
This is a list of pathogenic ClinVar variants found in the VPS26A region.
You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.
| Position | Type | Phenotype | Significance | ClinVar |
|---|---|---|---|---|
| 10-69132943-G-A | not specified | Uncertain significance (Feb 21, 2024) | ||
| 10-69133012-T-C | not specified | Uncertain significance (Feb 28, 2024) | ||
| 10-69133036-G-A | not specified | Uncertain significance (Nov 07, 2023) | ||
| 10-69155883-A-C | not specified | Uncertain significance (Jan 22, 2024) | ||
| 10-69157040-T-A | not specified | Uncertain significance (Nov 01, 2022) | ||
| 10-69157112-T-C | not specified | Uncertain significance (Nov 20, 2023) | ||
| 10-69157141-A-T | not specified | Uncertain significance (Oct 21, 2021) | ||
| 10-69157156-C-T | not specified | Uncertain significance (Apr 18, 2023) | ||
| 10-69158058-A-C | not specified | Uncertain significance (Apr 14, 2022) | ||
| 10-69158067-T-C | not specified | Uncertain significance (Dec 16, 2022) | ||
| 10-69158097-A-C | not specified | Uncertain significance (Jan 30, 2024) | ||
| 10-69162413-T-A | not specified | Uncertain significance (May 03, 2023) | ||
| 10-69162473-A-G | not specified | Uncertain significance (May 31, 2023) | ||
| 10-69166071-A-G | not specified | Uncertain significance (Mar 28, 2024) | ||
| 10-69166074-G-A | not specified | Uncertain significance (Feb 10, 2023) | ||
| 10-69168546-G-A | not specified | Uncertain significance (Jun 07, 2024) | ||
| 10-69171178-C-T | not specified | Uncertain significance (Jun 07, 2024) |
GnomAD
Source:
| Gene | Type | Bio Type | Transcript | Coding Exons | Length |
|---|---|---|---|---|---|
| VPS26A | protein_coding | protein_coding | ENST00000373382 | 9 | 49350 |
| pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
|---|---|---|---|---|---|---|
| 0.614 | 0.386 | 125730 | 0 | 11 | 125741 | 0.0000437 |
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
|---|---|---|---|---|---|---|
| Missense | 1.56 | 108 | 164 | 0.658 | 0.00000786 | 2160 |
| Missense in Polyphen | 15 | 44.959 | 0.33364 | 588 | ||
| Synonymous | 1.60 | 40 | 55.2 | 0.725 | 0.00000276 | 572 |
| Loss of Function | 3.01 | 3 | 16.0 | 0.187 | 6.71e-7 | 244 |
LoF frequencies by population
| Ethnicity | Sum of pLOFs | p |
|---|---|---|
| African & African-American | 0.0000683 | 0.0000683 |
| Ashkenazi Jewish | 0.00 | 0.00 |
| East Asian | 0.0000544 | 0.0000544 |
| Finnish | 0.0000924 | 0.0000924 |
| European (Non-Finnish) | 0.0000534 | 0.0000527 |
| Middle Eastern | 0.0000544 | 0.0000544 |
| South Asian | 0.00 | 0.00 |
| Other | 0.00 | 0.00 |
dbNSFP
Source:
- Function
- FUNCTION: Acts as component of the retromer cargo-selective complex (CSC). The CSC is believed to be the core functional component of retromer or respective retromer complex variants acting to prevent missorting of selected transmembrane cargo proteins into the lysosomal degradation pathway. The recruitment of the CSC to the endosomal membrane involves RAB7A and SNX3. The SNX-BAR retromer mediates retrograde transport of cargo proteins from endosomes to the trans-Golgi network (TGN) and is involved in endosome-to-plasma membrane transport for cargo protein recycling. The SNX3-retromer mediates the retrograde endosome-to-TGN transport of WLS distinct from the SNX-BAR retromer pathway. The SNX27-retromer is believed to be involved in endosome-to-plasma membrane trafficking and recycling of a broad spectrum of cargo proteins (Probable). The CSC seems to act as recruitment hub for other proteins, such as the WASH complex and TBC1D5 (Probable). Required for retrograde transport of lysosomal enzyme receptor IGF2R (PubMed:15078902, PubMed:15078903). Required to regulate transcytosis of the polymeric immunoglobulin receptor (pIgR-pIgA) (PubMed:15247922). Required for the endosomal localization of WASHC2A (indicative for the WASH complex) (PubMed:22070227). Required for the endosomal localization of TBC1D5 (PubMed:20923837). Mediates retromer cargo recognition of SORL1 and is involved in trafficking of SORL1 implicated in sorting and processing of APP (PubMed:22279231). Involved in retromer- independent lysosomal sorting of F2R (PubMed:16407403). Involved in recycling of ADRB2 (PubMed:21602791). Enhances the affinity of SNX27 for PDZ-binding motifs in cargo proteins (By similarity). {ECO:0000250|UniProtKB:P40336, ECO:0000269|PubMed:15078902, ECO:0000269|PubMed:15078903, ECO:0000269|PubMed:15247922, ECO:0000269|PubMed:16407403, ECO:0000269|PubMed:22070227, ECO:0000269|PubMed:22279231, ECO:0000303|PubMed:20923837, ECO:0000303|PubMed:21602791, ECO:0000303|PubMed:21725319, ECO:0000303|PubMed:23563491, ECO:0000305}.;
- Pathway
- Endocytosis - Homo sapiens (human);Signaling by WNT;Signal Transduction;WNT ligand biogenesis and trafficking
(Consensus)
Recessive Scores
- pRec
- 0.136
Intolerance Scores
- loftool
- 0.279
- rvis_EVS
- -0.25
- rvis_percentile_EVS
- 35.42
Haploinsufficiency Scores
- pHI
- 0.146
- hipred
- Y
- hipred_score
- 0.749
- ghis
- 0.678
Essentials
- essential_gene_CRISPR
- N
- essential_gene_CRISPR2
- N
- essential_gene_gene_trap
- gene_indispensability_pred
- E
- gene_indispensability_score
- 0.949
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |
Mouse Genome Informatics
- Gene name
- Vps26a
- Phenotype
- cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); 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); normal phenotype; embryo phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); craniofacial phenotype; growth/size/body region phenotype;
Gene ontology
- Biological process
- intracellular protein transport;Wnt signaling pathway;regulation of macroautophagy;retrograde transport, endosome to Golgi;retrograde transport, endosome to plasma membrane
- Cellular component
- lysosome;endosome;early endosome;cytosol;endosome membrane;retromer complex;retromer, cargo-selective complex;vesicle;tubular endosome
- Molecular function
- protein binding;protein transporter activity