CAV3 Gene (Caveolin-3): Function, Mutations, and Associated Diseases
A comprehensive biomedical overview of the CAV3 gene, its protein product caveolin-3, tissue expression, mutations, and clinical significance.
Gene Information Card
| Symbol | CAV3 |
|---|---|
| Full Name | Caveolin 3 |
| Gene Type | protein-coding |
| Chromosomal Location | 3p25.3 |
| NCBI Gene ID | 859 ncbi.nlm.nih.gov/gene/859 |
| Ensembl ID | ENSG00000182533 |
| UniProt ID | P56539 |
| OMIM ID | 601253 |
| HGNC ID | 1529 |
| Aliases | LGMD1C, VIP-21, M-caveolin, CSN3 |
Description
The CAV3 gene encodes caveolin-3, a muscle-specific member of the caveolin family. Caveolin-3 is a structural component of caveolae, small invaginations of the plasma membrane, and plays critical roles in signal transduction, membrane trafficking, and lipid regulation. Mutations in CAV3 are associated with several muscle disorders and cardiac conditions, including limb-girdle muscular dystrophy type 1C (LGMD1C), rippling muscle disease, hyperCKemia, and long QT syndrome. The protein is predominantly expressed in striated muscle (skeletal and cardiac) and smooth muscle.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Limb-girdle muscular dystrophy type 1C (LGMD1C) | Missense mutations (e.g., p.Pro104Leu) disrupt caveolin-3 oligomerization and membrane localization, leading to reduced caveolae formation and impaired muscle membrane integrity. | ClinVar; OMIM #607801 |
| Rippling muscle disease (RMD) | Mutations such as p.Arg26Gln cause abnormal muscle hyperexcitability and mechanical stress-induced muscle contractions, likely due to altered caveolin-3 function in T-tubules. | ClinVar; OMIM #606072 |
| HyperCKemia | Heterozygous mutations (e.g., p.Arg26Gln, p.Pro104Leu) lead to elevated serum creatine kinase levels without overt muscle weakness, indicating subclinical muscle membrane instability. | ClinVar; OMIM #123320 |
| Long QT syndrome (LQTS) | Mutations (e.g., p.Thr78Met) affect cardiac ion channel regulation, particularly sodium and potassium channels, prolonging ventricular repolarization. | ClinVar; OMIM #611818 |
| Sudden infant death syndrome (SIDS) | A rare CAV3 variant (p.Thr78Met) has been identified in some SIDS cases, suggesting a potential link to cardiac arrhythmias. | ClinVar; PMID: 21715716 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Skeletal muscle | High | High |
| Heart | High | High |
| Smooth muscle | Medium | Medium |
| Brain | Low | Low |
| Liver | Not detected | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| Skeletal muscle cells (myotubes) | High | Caveolin-3 is a marker for differentiated muscle cells. |
| Cardiomyocytes | High | Essential for cardiac T-tubule organization. |
| Smooth muscle cells (e.g., aortic) | Medium | Present in caveolae of smooth muscle. |
| Fibroblasts | Low | Minimal expression; not a typical marker. |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| p.Arg26Gln (c.77G>A) | Missense | Rare (found in RMD and hyperCKemia) | Disrupts caveolin-3 membrane scaffolding, leading to muscle hyperexcitability. |
| p.Pro104Leu (c.311C>T) | Missense | Rare (LGMD1C) | Impairs oligomerization and caveolae formation, causing muscle degeneration. |
| p.Thr78Met (c.233C>T) | Missense | Rare (LQTS and SIDS) | Alters cardiac ion channel regulation, prolonging QT interval. |
| p.Ael27Val (c.80A>T) | Missense | Rare (hyperCKemia) | Reduces caveolin-3 protein stability and membrane localization. |
Mutation functional classification
Loss of Function (LOF)
Many CAV3 mutations lead to loss of caveolin-3 function, reducing caveolae formation and impairing membrane integrity, as seen in LGMD1C and hyperCKemia.
Gain of Function (GOF)
Some mutations, particularly those associated with LQTS, may cause a gain-of-function effect on ion channels (e.g., increased late sodium current), leading to prolonged action potential.
Dominant Negative (DN)
Most CAV3 mutations act in a dominant-negative manner, as the mutant protein interferes with wild-type caveolin-3 oligomerization, disrupting normal caveolae formation.
View complete mutation data：
Gene Ontology (GO)
| • caveola | • plasma membrane |
| • signal transduction | • lipid binding |
| • protein homodimerization activity | • membrane raft |
| • muscle contraction | • T-tubule organization |
Pathways
• Caveolin-mediated endocytosis
• Muscle contraction (calcium signaling)
• Cardiac conduction (ion channel regulation)
• Insulin signaling (GLUT4 translocation)
Protein Summary
Caveolin-3 is a 151-amino acid protein with a molecular weight of ~17 kDa. It is a scaffolding protein that forms caveolae in muscle cells. It contains a conserved caveolin signature domain (residues 54-73) that mediates oligomerization and membrane attachment. Caveolin-3 interacts with various signaling molecules, including G-proteins, Src-family kinases, and ion channels, modulating their activity. Mutations in CAV3 lead to a spectrum of muscle and cardiac diseases, highlighting its critical role in muscle physiology.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| Cav3.2 Overexpression HEK293 Stable Cell Line | EDJ-GQ58 | Human | Details Get a Quote | |
| CAV3 Knockout HEK293 Cell Line | EDJ-KQ4196 | Human | 859 | Details Get a Quote |
| CAV3 Knockout HeLa Cell Line | EDJ-KQ52793 | Human | 859 | Details Get a Quote |
| CAV3 Knockout A-549 Cell Line | EDJ-KQ61263 | Human | 859 | Details Get a Quote |
| CAV3 Knockout HCT 116 Cell Line | EDJ-KQ69759 | Human | 859 | Details Get a Quote |
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