CAST: Calpastatin Gene
Endogenous inhibitor of calpain proteases
Gene Information Card
| Symbol | CAST |
|---|---|
| Full Name | Calpastatin |
| Gene Type | Protein coding |
| Chromosomal Location | 5q15.3 |
| NCBI Gene ID | 8310 ncbi.nlm.nih.gov/gene/8310 |
| Ensembl ID | ENSG00000153113 |
| UniProt ID | P20810 |
| OMIM ID | 114090 |
| HGNC ID | 1515 |
| Aliases | BS-17, PLACK, calpastatin |
Description
The CAST gene encodes calpastatin, an endogenous inhibitor of calpain proteases (calpain-1 and calpain-2). Calpastatin specifically inhibits calpain activity by binding to the calpain catalytic domain, regulating calcium-dependent proteolysis involved in cell signaling, cytoskeletal remodeling, and apoptosis. Dysregulation of the calpain-calpastatin system is implicated in muscle wasting, cancer progression, neurodegenerative disorders, and cardiovascular diseases.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Muscle wasting (cachexia, muscular dystrophy) | Reduced calpastatin leads to uncontrolled calpain-mediated proteolysis of myofibrillar proteins | PMID: 23442217 |
| Cancer (e.g., breast, colorectal) | Altered calpastatin expression modulates calpain-dependent cell migration and invasion | PMID: 25605244 |
| Neurodegeneration (Alzheimer disease, Parkinson disease) | Imbalance in calpain/calpastatin contributes to tau cleavage and synaptic dysfunction | PMID: 21576235 |
| Cardiovascular disease (cardiac hypertrophy, ischemia-reperfusion injury) | Calpastatin deficiency exacerbates calpain-mediated cardiomyocyte death | PMID: 20089855 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Skeletal muscle | 12.5 | Medium |
| Heart | 10.2 | Medium |
| Brain | 8.9 | Medium |
| Liver | 3.1 | Low |
| Kidney | 6.4 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HeLa | 15.3 | Cervical cancer cell line |
| HEK293 | 11.8 | Embryonic kidney cells |
| SH-SY5Y | 9.2 | Neuroblastoma cells |
| MCF7 | 7.5 | Breast cancer cells |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.646C>T (p.Arg216*) | Nonsense | <0.01% | Loss of function; associated with PLACK syndrome |
| c.1123G>A (p.Gly375Arg) | Missense | <0.01% | Reduced calpain inhibition |
| c.1780C>T (p.Arg594Trp) | Missense | <0.01% | Unknown |
Mutation functional classification
Loss of Function (LOF)
Nonsense mutations (e.g., p.Arg216*) lead to truncated calpastatin with reduced inhibitory capacity, increasing calpain activity.
Gain of Function (GOF)
Not described for CAST.
Dominant Negative (DN)
Not described for CAST.
View complete mutation data：
Gene Ontology (GO)
| • cysteine-type endopeptidase inhibitor activity (GO:0004869) | • identical protein binding (GO:0042802) |
| • cytoplasm (GO:0005737) | • cytosol (GO:0005829) |
| • ubiquitin-dependent ERAD pathway (GO:0030433) |
Pathways
• Calpain proteolysis pathway (Reactome: R-HSA-5625886)
• Apoptosis (KEGG: hsa04210)
• Alzheimer disease (KEGG: hsa05010)
Protein Summary
Calpastatin is a 708-amino-acid protein (UniProt P20810) that contains four inhibitory domains (domains 1–4), each capable of inhibiting calpain. It is predominantly cytosolic and is expressed in multiple tissues, especially skeletal muscle and heart. Calpastatin is cleaved by calpain itself, allowing fine-tuned regulation of proteolytic activity. Alternative splicing generates multiple isoforms with varying inhibitory potencies.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| CASTOR1 Knockout HEK293 Cell Line | EDJ-KQ1158 | Human | 652968 | Details Get a Quote |
| CASTOR2 Knockout HEK293 Cell Line | EDJ-KQ1159 | Human | 729438 | Details Get a Quote |
| CAST Knockout HEK293 Cell Line | EDJ-KQ2271 | Human | 831 | Details Get a Quote |
| CASTOR2 Knockout HCT 116 Cell Line | EDJ-KQ19057 | Human | 729438 | Details Get a Quote |
| CASTOR1 Knockout A-549 Cell Line | EDJ-KQ20399 | Human | 652968 | Details Get a Quote |
| CASTOR1 Knockout HCT 116 Cell Line | EDJ-KQ20400 | Human | 652968 | Details Get a Quote |
| CASTOR1 Knockout HeLa Cell Line | EDJ-KQ20401 | Human | 652968 | Details Get a Quote |
| CASTOR2 Knockout A-549 Cell Line | EDJ-KQ20402 | Human | 729438 | Details Get a Quote |
| CASTOR2 Knockout HeLa Cell Line | EDJ-KQ20404 | Human | 729438 | Details Get a Quote |
| CAST Knockout HCT 116 Cell Line | EDJ-KQ21287 | Human | 831 | Details Get a Quote |
| CAST Knockout A-549 Cell Line | EDJ-KQ22613 | Human | 831 | Details Get a Quote |
| CAST Knockout HeLa Cell Line | EDJ-KQ22614 | Human | 831 | Details Get a Quote |
