VAPB Gene: Vesicle-Associated Membrane Protein-Associated Protein B
Key regulator of endoplasmic reticulum dynamics and unfolded protein response; implicated in ALS and related motor neuron diseases.
Gene Information Card
| Symbol | VAPB |
|---|---|
| Full Name | Vesicle-associated membrane protein-associated protein B/C |
| Gene Type | Protein coding |
| Chromosomal Location | 20q13.32 |
| NCBI Gene ID | 9217 ncbi.nlm.nih.gov/gene/9217 |
| Ensembl ID | ENSG00000124164 |
| UniProt ID | O95292 |
| OMIM ID | 605704 |
| HGNC ID | 12649 |
| Aliases | ALS8, VAMP-B, VAP-B, VAPC |
Description
The VAPB gene encodes vesicle-associated membrane protein-associated protein B, a type II transmembrane protein localized to the endoplasmic reticulum (ER) and pre-Golgi intermediates. VAPB is involved in ER membrane tethering, lipid transport, and the unfolded protein response (UPR). Mutations in VAPB cause a dominantly inherited form of amyotrophic lateral sclerosis (ALS8) and may contribute to other neurodegenerative disorders.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Amyotrophic lateral sclerosis 8 (ALS8) | Dominant-negative or gain-of-toxic-function mutations (e.g., P56S) disrupt ER structure and UPR, leading to motor neuron degeneration. | OMIM #608627; ClinVar; multiple case reports |
| Spinal muscular atrophy (SMA) variant | VAPB mutations have been reported in patients with late-onset SMA, suggesting phenotypic overlap with ALS. | OMIM; literature review |
| Frontotemporal dementia (FTD) | Rare VAPB variants identified in FTD cohorts, though mechanism unclear. | ClinVar; limited evidence |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 12.5 | Medium |
| Spinal cord | 15.2 | Medium |
| Heart | 8.3 | Low |
| Liver | 6.1 | Low |
| Skeletal muscle | 10.7 | Medium |
| Pancreas | 5.4 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| SH-SY5Y (neuroblastoma) | 18.3 | Neuronal model |
| HeLa (cervical carcinoma) | 14.1 | Epithelial |
| HEK293 (embryonic kidney) | 12.8 | Common expression system |
| U-87 MG (glioblastoma) | 16.5 | Glial model |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| P56S | Missense | ~50% of ALS8 families | Dominant-negative; disrupts ER localization and induces aggregation |
| T46I | Missense | Rare | Impaired VAPB–VAPA interaction; reduced ER tethering |
| S160Δ | Deletion | Rare | Frameshift; loss of C-terminal domain, likely loss of function |
Mutation functional classification
Loss of Function (LOF)
Not clearly established; heterozygous loss may contribute but haploinsufficiency is not sufficient for disease.
Gain of Function (GOF)
Proposed for P56S: toxic aggregates and ER stress.
Dominant Negative (DN)
P56S and T46I act via dominant-negative interference with wild-type VAPB and VAPA.
View complete mutation data：
Gene Ontology (GO)
| • endoplasmic reticulum (GO:0005783) | • Golgi apparatus (GO:0005794) |
| • protein binding (GO:0005515) | • response to unfolded protein (GO:0006986) |
| • integral component of membrane (GO:0016021) | • cellular response to insulin stimulus (GO:0032869) |
| • protein N-terminus binding (GO:0047485) |
Pathways
• Unfolded protein response (UPR) – Reactome R-HSA-381119
• ER to Golgi vesicle-mediated transport – Reactome R-HSA-199977
• Lipid transport at ER membrane – Reactome R-HSA-1483206
Protein Summary
VAPB is a 243-amino acid transmembrane protein with an N-terminal MSP domain, a coiled-coil region, and a C-terminal transmembrane anchor. It forms homodimers and heterodimers with VAPA, tethering the ER to other organelles. The MSP domain interacts with lipid-transfer proteins and FFAT-motif-containing partners. Mutant VAPB (e.g., P56S) misfolds, aggregates, and disrupts ER homeostasis, leading to motor neuron death.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| VAPB Knockout HEK293 Cell Line | EDJ-KQ2736 | Human | 9217 | Details Get a Quote |
| VAPB Knockout A-549 Cell Line | EDJ-KQ23603 | Human | 9217 | Details Get a Quote |
| VAPB Knockout HCT 116 Cell Line | EDJ-KQ23604 | Human | 9217 | Details Get a Quote |
| VAPB Knockout HeLa Cell Line | EDJ-KQ23605 | Human | 9217 | Details Get a Quote |
