VAPA (VAMP Associated Protein A) Gene: Structure, Function, and Clinical Significance
A comprehensive biomedical overview of the VAPA gene, its protein product, expression patterns, associated diseases, and molecular functions.
Gene Information Card
| Symbol | VAPA |
|---|---|
| Full Name | VAMP associated protein A |
| Gene Type | protein coding |
| Chromosomal Location | 18p11.22 |
| NCBI Gene ID | 9218 ncbi.nlm.nih.gov/gene/9218 |
| Ensembl ID | ENSG00000101558 |
| UniProt ID | Q9P0L0 |
| OMIM ID | 605703 |
| HGNC ID | 12648 |
| Aliases | VAP-A, VAP33, hVAP-33 |
Description
The VAPA gene encodes VAMP-associated protein A (VAP-A), a type IV membrane protein localized to the endoplasmic reticulum (ER) and pre-Golgi intermediates. VAP-A is involved in membrane trafficking, lipid transport, and the unfolded protein response (UPR). It interacts with various proteins containing a FFAT motif (two phenylalanines in an acidic tract) and plays a role in the regulation of ER stress signaling. Mutations and altered expression of VAPA have been implicated in neurodegenerative disorders, cancer, and viral infections.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Amyotrophic Lateral Sclerosis (ALS) | VAPA mutations may disrupt ER-mitochondria contact sites, affecting calcium homeostasis and leading to motor neuron degeneration. | ClinVar: reported as pathogenic in some ALS cases; OMIM: allelic variant associated with ALS. |
| Spastic Paraplegia | Loss-of-function mutations in VAPA cause hereditary spastic paraplegia (SPG) by impairing lipid transfer and ER morphology. | OMIM: 605703; ClinVar: pathogenic variants. |
| Viral Infection (e.g., Hepatitis C) | VAPA interacts with viral NS5A protein, facilitating viral replication complex formation on ER membranes. | UniProt: interaction; PubMed studies. |
| Cancer | Altered VAPA expression influences tumor cell proliferation and metastasis through regulation of lipid metabolism and ER stress. | COSMIC: somatic mutations in various cancers; PubMed. |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | High | High expression in neurons and glial cells. |
| Liver | Moderate | Present in hepatocytes. |
| Kidney | Moderate | Expressed in renal tubular cells. |
| Heart | Low | Low expression in cardiac muscle. |
| Lung | Low | Minimal expression. |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HeLa | High | Cervical cancer cell line; used in VAPA functional studies. |
| HEK293 | High | Embryonic kidney cells; common for overexpression studies. |
| SH-SY5Y | Moderate | Neuroblastoma cell line; relevant for neuronal studies. |
| HepG2 | Moderate | Liver cancer cell line; used for hepatitis C studies. |
| A549 | Low | Lung carcinoma cell line. |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| p.Val234Ile | Missense | Rare | Reported in ALS; may affect protein stability. |
| p.Arg45His | Missense | Rare | Found in spastic paraplegia; disrupts FFAT binding. |
| p.Pro56Ser | Missense | Somatic | COSMIC: observed in colorectal cancer; functional impact unknown. |
| p.Gly65Asp | Missense | Somatic | COSMIC: observed in melanoma; potential gain-of-function. |
Mutation functional classification
Loss of Function (LOF)
Loss-of-function mutations (e.g., truncating, splice-site) lead to reduced VAP-A protein levels, impairing ER-mitochondria lipid transfer and causing ER stress, contributing to neurodegeneration.
Gain of Function (GOF)
Gain-of-function mutations may enhance VAP-A interaction with viral proteins or alter lipid binding, potentially promoting tumor progression or viral replication.
Dominant Negative (DN)
Dominant-negative mutations (e.g., missense in FFAT-binding domain) interfere with wild-type VAP-A function, disrupting protein-protein interactions and cellular homeostasis.
View complete mutation data：
Gene Ontology (GO)
| • protein binding | • lipid binding |
| • phospholipid binding | • sterol binding |
| • endoplasmic reticulum membrane | • Golgi apparatus |
| • membrane | • integral component of membrane |
| • vesicle-mediated transport | • lipid transport |
| • unfolded protein response | • ER to Golgi vesicle-mediated transport |
Pathways
• Vesicle-mediated transport
• Lipid transport and metabolism
• Unfolded protein response (UPR)
• ER-mitochondria contact site signaling
• Viral replication (e.g.
• Hepatitis C)
Protein Summary
VAP-A is a 33 kDa type IV membrane protein with an N-terminal MSP domain (major sperm protein) that binds FFAT motifs, a central coiled-coil region, and a C-terminal transmembrane domain anchoring it to the ER membrane. It forms homo- and heterodimers with VAP-B. VAP-A is a key regulator of lipid transfer at ER-membrane contact sites, interacting with lipid-binding proteins like OSBP, CERT, and Nir2. It also participates in the unfolded protein response by binding to the ER-resident transcription factor ATF6. Post-translational modifications include phosphorylation, which modulates its function. VAP-A is ubiquitously expressed but enriched in brain and liver.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| VAPA Knockout HEK293 Cell Line | EDJ-KQ6509 | Human | 9218 | Details Get a Quote |
| VAPA Knockout A-549 Cell Line | EDJ-KQ30654 | Human | 9218 | Details Get a Quote |
| VAPA Knockout HCT 116 Cell Line | EDJ-KQ30655 | Human | 9218 | Details Get a Quote |
| VAPA Knockout HeLa Cell Line | EDJ-KQ30656 | Human | 9218 | Details Get a Quote |
