VPS8
protein-codingVPS8 subunit of CORVET complex, the group of CORVET complex|Ring finger proteins
Gene summary
Predicted to enable protein-membrane adaptor activity. Involved in endosomal vesicle fusion. Located in early endosome. [provided by Alliance of Genome Resources, Jun 2026]
- KIAA0804
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~240.5 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
Inheritance Pattern: Unknown
Disease ID:MONDO:0015168
Submitter: ClinGen
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to VPS8 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_001009921.3. 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 | 1 | 3 | 2 | 6 | ||
| missense | 195 | 8 | 2 | 205 | ||
| nonsense | 3 | 3 | ||||
| start loss | 0 | |||||
| frameshift | 1 | 1 | ||||
| splice donor/acceptor (+/-2bp) | 12 | 12 | ||||
| Total | 0 | 0 | 212 | 11 | 4 | 227 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_001009921.1 | 47 | MANE Select | |
| Ensembl | ENSP00000487164.1 | 47 | MANE Select | |
| RefSeq | NP_001336221.1 | 47 | Standard | |
| RefSeq | NP_001336222.1 | 47 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Biological Process
- protein transport
- endosomal vesicle fusion
Molecular Function
- protein binding
- metal ion binding
Cellular Component
- early endosome
- CORVET complex
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000437079
- Coding exons
- 47
- Length
- 240472
- Individuals with no LoFs
- 124489
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 149
- Defined
- 124638
- p
- 0.000598
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 1.36 | 594 | 695 | 0.855 | 0.0000346 | 9347 |
| Missense (PolyPhen) | 135 | 193.58 | 0.69738 | 2693 | ||
| Synonymous | 0.565 | 230 | 241 | 0.954 | 0.0000121 | 2557 |
| Loss of Function | 5.79 | 30 | 88.9 | 0.337 | 0.00000456 | 1160 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00041 | 0.00039 | rare |
| Latino/Admixed American | 0.000095 | 0.000087 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.00040 | 0.00039 | rare |
| Finnish | 0.00051 | 0.00051 | rare |
| European (Non-Finnish) | 0.0010 | 0.00095 | notable |
| South Asian | 0.00033 | 0.00033 | rare |
| Other | 0.00085 | 0.00083 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Plays a role in vesicle-mediated protein trafficking of the endocytic membrane transport pathway. Believed to act as a component of the putative CORVET endosomal tethering complexes which is 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 CORVET complex is proposed to function as a Rab5 effector to mediate early endosome fusion probably in specific endosome subpopulations (PubMed:25266290). Functions predominantly in APPL1-containing endosomes (PubMed:25266290). {ECO:0000269|PubMed:25266290, ECO:0000305|PubMed:25266290}.;
Recessive Scores
- pRec
- 0.111
Intolerance Scores
- LoFtool
- 0.909
- RVIS EVS
- -0.37
- RVIS percentile EVS
- 28.31
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- N
- Indispensability score
- 0.407
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | High |
| Cancer | Medium | Medium | Medium |