VCP Gene (Valosin Containing Protein)
Key regulator of protein homeostasis and cellular stress responses
Gene Information Card
| Symbol | VCP |
|---|---|
| Full Name | Valosin Containing Protein |
| Gene Type | Protein coding |
| Chromosomal Location | 9p13.3 |
| NCBI Gene ID | 7415 ncbi.nlm.nih.gov/gene/7415 |
| Ensembl ID | ENSG00000165280 |
| UniProt ID | P55072 |
| OMIM ID | 601023 |
| HGNC ID | 12666 |
| Aliases | p97, CDC48, TERA, ALS14, IBMPFD1 |
Description
The VCP gene encodes valosin-containing protein (p97), a member of the AAA ATPase family. This protein is essential for ubiquitin-dependent protein degradation, endoplasmic reticulum-associated degradation (ERAD), membrane fusion, and autophagy. Mutations in VCP cause multisystem proteinopathy (MSP), including inclusion body myopathy with Paget disease of bone and frontotemporal dementia (IBMPFD), and amyotrophic lateral sclerosis (ALS).
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Inclusion Body Myopathy with Paget Disease and Frontotemporal Dementia (IBMPFD) | Dominant-negative mutations impair autophagic clearance, leading to protein aggregation in muscle, bone, and brain | ClinVar, OMIM |
| Amyotrophic Lateral Sclerosis (ALS) | Gain-of-function or dominant-negative effects disrupt proteostasis and cause motor neuron degeneration | ClinVar, OMIM |
| Charcot-Marie-Tooth Disease Type 2Y | Missense mutations alter axonal transport and protein degradation | ClinVar |
| Hereditary Spastic Paraplegia | Loss of VCP function affects ERAD and mitochondrial dynamics | ClinVar |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Liver | 18.5 | High |
| Skeletal Muscle | 15.2 | High |
| Brain (cerebellum) | 12.8 | High |
| Heart | 11.3 | High |
| Pancreas | 9.7 | Medium |
| Lung | 8.4 | Medium |
| Kidney | 7.9 | Medium |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HeLa | 22.1 | High expression |
| HEK293 | 19.6 | High expression |
| K562 | 15.3 | High expression |
| HepG2 | 14.8 | High expression |
| A549 | 12.5 | High expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| p.Arg155His | Missense | Common in IBMPFD | Dominant-negative; impairs ATPase activity and autophagy |
| p.Arg159His | Missense | Common in IBMPFD/ALS | Disrupts cofactor binding and ERAD |
| p.Gly97Glu | Missense | Rare | Gain-of-function; increases ATPase activity |
| p.Ala232Glu | Missense | Rare | Dominant-negative; reduces protein stability |
| p.Arg191Gln | Missense | Rare | Loss of function; impairs ubiquitin binding |
Mutation functional classification
Loss of Function (LOF)
Rare; some missense mutations reduce ATPase activity or ubiquitin binding, impairing ERAD and autophagy.
Gain of Function (GOF)
Rare; mutations like p.Gly97Glu increase ATPase activity, potentially causing hyperactive degradation.
Dominant Negative (DN)
Most common mechanism; mutations (e.g., p.Arg155His, p.Arg159His) disrupt hexamer assembly or cofactor interaction, leading to protein aggregation.
View complete mutation data：
Gene Ontology (GO)
| • ATP binding | • ATP hydrolysis activity |
| • ubiquitin protein ligase binding | • protein homodimerization activity |
| • endoplasmic reticulum | • cytoplasm |
| • nucleus | • autophagy |
| • ERAD pathway | • protein ubiquitination |
Pathways
• Endoplasmic reticulum-associated degradation (ERAD)
• Ubiquitin-proteasome system
• Autophagy
• Valosin-containing protein (VCP) mediated degradation
• p97-mediated protein degradation
Protein Summary
Valosin-containing protein (VCP/p97) is a 97 kDa AAA ATPase that forms a homohexameric ring structure. It functions as a segregase, extracting ubiquitinated proteins from membranes or complexes for degradation by the proteasome or autophagy. VCP interacts with multiple cofactors (e.g., UFD1, NPL4, p47) to regulate diverse cellular processes including ERAD, mitochondrial quality control, and cell cycle progression. Mutations in VCP cause multisystem proteinopathy through impaired protein homeostasis.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| VCPIP1 Knockout HEK293 Cell Line | EDJ-KQ3520 | Human | 80124 | Details Get a Quote |
| VCPKMT Knockout HEK293 Cell Line | EDJ-KQ16094 | Human | 79609 | Details Get a Quote |
| VCPIP1 Knockout A-549 Cell Line | EDJ-KQ23971 | Human | 80124 | Details Get a Quote |
| VCPIP1 Knockout HCT 116 Cell Line | EDJ-KQ25349 | Human | 80124 | Details Get a Quote |
| VCPIP1 Knockout HeLa Cell Line | EDJ-KQ25350 | Human | 80124 | Details Get a Quote |
| VCPKMT Knockout A-549 Cell Line | EDJ-KQ47241 | Human | 79609 | Details Get a Quote |
| VCPKMT Knockout HCT 116 Cell Line | EDJ-KQ47242 | Human | 79609 | Details Get a Quote |
| VCPKMT Knockout HeLa Cell Line | EDJ-KQ47243 | Human | 79609 | Details Get a Quote |
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