CAPN3 Gene: Calpain 3
Key regulator of muscle structure and function; mutations cause limb-girdle muscular dystrophy type 2A (LGMD2A)
Gene Information Card
| Symbol | CAPN3 |
|---|---|
| Full Name | calpain 3 |
| Gene Type | protein-coding |
| Chromosomal Location | 15q15.1 |
| NCBI Gene ID | 825 ncbi.nlm.nih.gov/gene/825 |
| Ensembl ID | ENSG00000142319 |
| UniProt ID | P20807 |
| OMIM ID | 114240 |
| HGNC ID | 1479 |
| Aliases | CANP3, LGMD2A, nCL-1, p94 |
Description
The CAPN3 gene encodes calpain 3, a muscle-specific calcium-dependent cysteine protease. It is a member of the calpain family and plays a critical role in sarcomere remodeling, myofibril stability, and muscle cell survival. Mutations in CAPN3 are the primary cause of limb-girdle muscular dystrophy type 2A (LGMD2A), also known as calpainopathy. The protein undergoes rapid autolysis and is localized to the titin N2A region, where it regulates proteolysis and signaling pathways essential for muscle maintenance.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Limb-girdle muscular dystrophy type 2A (LGMD2A) | Loss-of-function mutations in CAPN3 impair calpain 3 proteolytic activity, leading to defective sarcomere remodeling, increased apoptosis, and progressive muscle fiber degeneration. | ClinVar, OMIM |
| Muscular dystrophy, limb-girdle, autosomal recessive 1 (LGMDR1) | Same as LGMD2A; biallelic pathogenic variants cause recessive calpainopathy. | ClinVar, OMIM |
| Sporadic inclusion body myositis (sIBM) | Reduced CAPN3 expression and altered autolytic activity observed in muscle biopsies; potential role in protein aggregation. | NCBI Gene, PubMed |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Skeletal muscle | 78.5 | High |
| Heart | 2.3 | Low |
| Brain | 0.4 | Not detected |
| Liver | 0.1 | Not detected |
| Kidney | 0.2 | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| Skeletal muscle myotubes | 85.2 | Differentiated primary cells |
| Rhabdomyosarcoma (RD) | 12.4 | Cancer cell line |
| Fibroblasts (normal) | 0.3 | Low expression |
| HEK293 | 0.1 | Not detected |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.550delA | Frameshift | Common in European populations | Loss of function |
| c.598_612del | In-frame deletion | Rare | Loss of function |
| c.2362AG>TCATCT | Missense | Found in LGMD2A families | Loss of function |
| c.1746-20C>G | Splice site | Pathogenic | Loss of function |
Mutation functional classification
Loss of Function (LOF)
Most CAPN3 mutations are recessive loss-of-function, leading to absent or severely reduced proteolytic activity and LGMD2A.
Gain of Function (GOF)
No confirmed gain-of-function mutations reported in CAPN3.
Dominant Negative (DN)
Rare dominant-negative effects have been suggested in some missense variants, but evidence is limited; primarily recessive.
View complete mutation data：
Gene Ontology (GO)
Pathways
• Calpain proteolysis pathway (Reactome: R-HSA-5625740)
• Muscle contraction (Reactome: R-HSA-397014)
• Titin/calpain signaling (Reactome: R-HSA-390522)
Protein Summary
Calpain 3 (p94) is a 94 kDa muscle-specific protease that contains four domains: a catalytic cysteine protease domain (CysPc), a calpain-type beta-sandwich domain (CBSW), and two C-terminal EF-hand domains. It binds to titin at the N2A region and undergoes rapid autolysis. The protein is essential for sarcomere integrity, myofibril turnover, and protection against apoptosis. Loss of calpain 3 activity leads to progressive muscle weakness and dystrophy.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| CAPN3 Knockout HEK293 Cell Line | EDJ-KQ3508 | Human | 825 | Details Get a Quote |
| CAPN3 Knockout A-549 Cell Line | EDJ-KQ26641 | Human | 825 | Details Get a Quote |
| CAPN3 Knockout HCT 116 Cell Line | EDJ-KQ26643 | Human | 825 | Details Get a Quote |
| CAPN3 Knockout HeLa Cell Line | EDJ-KQ26644 | Human | 825 | Details Get a Quote |
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