VAPA
protein-codingVAMP associated protein A
Gene summary
The protein encoded by this gene is a type IV membrane protein. It is present in the plasma membrane and intracellular vesicles. It may also be associated with the cytoskeleton. This protein may function in vesicle trafficking, membrane fusion, protein complex assembly and cell motility. Alternative splicing occurs at this locus and two transcript variants encoding distinct isoforms have been identified. [provided by RefSeq, Jul 2008]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~46.0 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 VAPA variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_194434.3. 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 | 0 | |||||
| missense | 27 | 1 | 28 | |||
| nonsense | 1 | 1 | ||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 3 | 3 | ||||
| Total | 0 | 1 | 30 | 1 | 0 | 32 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_919415.2 | 6 | MANE Select | |
| Ensembl | ENSP00000382880.3 | 6 | MANE Select | |
| RefSeq | NP_003565.4 | 7 | Standard | |
| Ensembl | ENSP00000345656.4 | 7 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Cholesterol metabolism - Homo sapiens (human)
- Exercise-induced Circadian Regulation
- Neutrophil degranulation
- Metabolism of lipids
- Innate Immune System
Biological Process
- endoplasmic reticulum to Golgi vesicle-mediated transport
- endoplasmic reticulum organization
- cell death
- sphingolipid biosynthetic process
- neuron projection development
Molecular Function
- protein binding
- microtubule binding
- protein domain specific binding
- FFAT motif binding
- cadherin binding
Cellular Component
- Golgi membrane
- endoplasmic reticulum
- endoplasmic reticulum membrane
- plasma membrane
- bicellular tight junction
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000340541
- Coding exons
- 7
- Length
- 46020
- Individuals with no LoFs
- 124766
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 8
- Defined
- 124774
- p
- 0.0000321
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.953 | 125 | 159 | 0.787 | 0.00000776 | 1929 |
| Missense (PolyPhen) | 8 | 25.502 | 0.31371 | 358 | ||
| Synonymous | 0.544 | 53 | 58.3 | 0.909 | 0.00000307 | 555 |
| Loss of Function | 2.60 | 3 | 13.2 | 0.228 | 6.37e-7 | 172 |
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 | 0.00022 | 0.00022 | rare |
| Finnish | 0.000048 | 0.000046 | rare |
| European (Non-Finnish) | 0.000032 | 0.000026 | rare |
| South Asian | 0 | 0.0 | absent |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Binds to OSBPL3, which mediates recruitment of VAPA to plasma membrane sites (PubMed:25447204). The ORP3-VAPA complex stimulates RRAS signaling which in turn attenuates integrin beta-1 (ITGB1) activation at the cell surface (PubMed:25447204). With OSBPL3, may regulate ER morphology (PubMed:16143324). May play a role in vesicle trafficking (PubMed:11511104, PubMed:19289470). {ECO:0000269|PubMed:11511104, ECO:0000269|PubMed:16143324, ECO:0000269|PubMed:19289470, ECO:0000269|PubMed:25447204}.;
Recessive Scores
- pRec
- 0.154
Intolerance Scores
- LoFtool
- 0.691
- RVIS EVS
- 0.42
- RVIS percentile EVS
- 76.96
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- K
- Indispensability pred.
- E
- Indispensability score
- 0.935
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |