PPP3CA Gene - Calcineurin Subunit A Catalytic
Key regulator of calcium-dependent signaling and immune response
Gene Information Card
| Symbol | PPP3CA |
|---|---|
| Full Name | Protein Phosphatase 3 Catalytic Subunit Alpha |
| Gene Type | Protein coding |
| Chromosomal Location | 4q24 |
| NCBI Gene ID | 5530 ncbi.nlm.nih.gov/gene/5530 |
| Ensembl ID | ENSG00000138814 |
| UniProt ID | Q08209 |
| OMIM ID | 114105 |
| HGNC ID | 9314 |
| Aliases | CALNA, CNA1, CALN, PPP3C, CALNA1 |
Description
PPP3CA encodes the catalytic subunit A alpha isoform of calcineurin, a calcium/calmodulin-dependent serine/threonine phosphatase. Calcineurin dephosphorylates nuclear factor of activated T-cells (NFAT) transcription factors, regulating immune response, neuronal development, and cardiac hypertrophy. PPP3CA is ubiquitously expressed with high levels in brain and immune cells.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Developmental and epileptic encephalopathy 91 (DEE91) | Loss-of-function mutations impair calcineurin activity, disrupting neuronal calcium signaling and synaptic plasticity. | ClinVar, OMIM |
| Arrhythmogenic right ventricular cardiomyopathy (ARVC) | Altered calcineurin signaling leads to aberrant cardiac remodeling and fibrosis. | ClinVar, OMIM |
| Immunodeficiency | Defective NFAT activation reduces T-cell cytokine production and immune response. | NCBI Gene, OMIM |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain (cerebral cortex) | 30.2 | High |
| Heart | 15.8 | Medium |
| Lung | 8.5 | Medium |
| Liver | 4.1 | Low |
| Kidney | 12.3 | Medium |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK293 | 25.6 | High expression |
| Jurkat T-cells | 22.1 | High expression |
| SH-SY5Y | 18.4 | Neuronal model |
| HepG2 | 6.7 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1003C>T (p.Arg335*) | Nonsense | Rare | Loss of function; associated with DEE91 |
| c.1240G>A (p.Glu414Lys) | Missense | Rare | Dominant negative; reduced phosphatase activity |
| c.1472delC (p.Pro491Leufs*13) | Frameshift | Rare | Loss of function; truncation |
Mutation functional classification
Loss of Function (LOF)
Nonsense and frameshift mutations leading to haploinsufficiency or truncated protein.
Gain of Function (GOF)
Not well documented; some missense variants may increase activity but are rare.
Dominant Negative (DN)
Missense mutations like p.Glu414Lys interfere with wild-type calcineurin function.
View complete mutation data：
Gene Ontology (GO)
| • protein serine/threonine phosphatase activity (GO:0004724) | • calmodulin binding (GO:0005516) |
| • calcium ion binding (GO:0005509) | • signal transduction (GO:0007165) |
| • nucleus (GO:0005634) | • cytoplasm (GO:0005737) |
Pathways
• Calcineurin-NFAT signaling pathway
• Calcium signaling pathway
• T-cell receptor signaling pathway
• Cardiac hypertrophy signaling
Protein Summary
PPP3CA encodes the 521-amino acid catalytic subunit of calcineurin (PP2B). The protein contains a catalytic domain, a calmodulin-binding domain, and an autoinhibitory domain. Upon calcium/calmodulin binding, the autoinhibition is relieved, enabling dephosphorylation of substrates such as NFAT, which translocates to the nucleus to regulate gene expression. Mutations in PPP3CA cause neurodevelopmental disorders and cardiomyopathy.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| PPP3CA Knockout HEK293 Cell Line | EDJ-KQ733 | Human | 5530 | Details Get a Quote |
| PPP3CA Knockout A-549 Cell Line | EDJ-KQ19359 | Human | 5530 | Details Get a Quote |
| PPP3CA Knockout HCT 116 Cell Line | EDJ-KQ19360 | Human | 5530 | Details Get a Quote |
| PPP3CA Knockout HeLa Cell Line | EDJ-KQ19361 | Human | 5530 | Details Get a Quote |
