VPS29
protein-codingVPS29 retromer complex component, the group of Retriever complex
Gene summary
This gene belongs to a group of vacuolar protein sorting (VPS) genes that, when functionally impaired, disrupt the efficient delivery of vacuolar hydrolases. The protein encoded by this gene is a component of a large multimeric complex, termed the retromer complex, which is involved in retrograde transport of proteins from endosomes to the trans-Golgi network. This VPS protein may be involved in the formation of the inner shell of the retromer coat for retrograde vesicles leaving the prevacuolar compartment. Alternative splice variants encoding different isoforms and representing non-protein coding transcripts have been found for this gene. [provided by RefSeq, Aug 2013]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~11.0 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
No GenCC data available for this gene.
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to VPS29 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_016226.5. Only rare variants are included.
We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.
Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 0 | |||||
| missense | 11 | 11 | ||||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 1 | 1 | ||||
| Total | 0 | 0 | 12 | 0 | 0 | 12 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_057310.1 | 4 | MANE Select | |
| Ensembl | ENSP00000447058.1 | 4 | MANE Select | |
| RefSeq | NP_001269079.1 | 5 | Standard | |
| RefSeq | NP_001269080.1 | 3 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Endocytosis - Homo sapiens (human)
- Signaling by WNT
- Signal Transduction
- serine biosynthesis (phosphorylated route)
- serine and glycine biosynthesis
Biological Process
- intracellular protein transport
- regulation of autophagy
- viral process
- Wnt signaling pathway
- retrograde transport, endosome to Golgi
Molecular Function
- protein binding
- protein transporter activity
- metal ion binding
Cellular Component
- endosome
- early endosome
- late endosome
- cytosol
- endosome membrane
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000360579
- Coding exons
- 5
- Length
- 11021
- Individuals with no LoFs
- 124732
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 2
- Defined
- 124734
- p
- 0.00000802
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 1.70 | 49 | 95.9 | 0.511 | 0.00000460 | 1219 |
| Missense (PolyPhen) | 6 | 24.001 | 0.24999 | 350 | ||
| Synonymous | 0.445 | 33 | 36.4 | 0.906 | 0.00000178 | 351 |
| Loss of Function | 2.45 | 1 | 8.88 | 0.113 | 4.59e-7 | 116 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0 | 0.0 | absent |
| Latino/Admixed American | 0 | 0.0 | absent |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0 | 0.0 | absent |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.0000090 | 0.0000088 | rare |
| South Asian | 0 | 0.0 | absent |
| Other | 0.00017 | 0.00017 | rare |
dbNSFP Gene Annotations
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. The CSC seems to act as recruitment hub for other proteins, such as the WASH complex and TBC1D5. Required to regulate transcytosis of the polymeric immunoglobulin receptor (pIgR-pIgA) (Probable). Involved in GLUT1 endosome-to-plasma membrane trafficking; the function is dependent of association with ANKRD27 (PubMed:24856514). {ECO:0000250|UniProtKB:Q9QZ88, ECO:0000269|PubMed:16737443, ECO:0000269|PubMed:24856514, ECO:0000303|PubMed:15247922, ECO:0000303|PubMed:21725319, ECO:0000303|PubMed:23563491}.;
Recessive Scores
- pRec
- 0.103
Intolerance Scores
- LoFtool
- 0.242
- RVIS EVS
- 0.08
- RVIS percentile EVS
- 59.43
Essentials
- Essential (CRISPR)
- E
- Essential (CRISPR2)
- S
- Essential (gene trap)
- E
- Indispensability pred.
- E
- Indispensability score
- 0.781
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Low | Medium |
| Primary Immunodeficiency | Medium | Low | Medium |
| Cancer | Medium | Medium | Medium |