PPP3CC
Protein Phosphatase 3 Catalytic Subunit Gamma
Gene Information Card
| Symbol | PPP3CC |
|---|---|
| Full Name | Protein Phosphatase 3 Catalytic Subunit Gamma |
| Gene Type | protein-coding |
| Chromosomal Location | 8p21.3 |
| NCBI Gene ID | 5533 ncbi.nlm.nih.gov/gene/5533 |
| Ensembl ID | ENSG00000120910 |
| UniProt ID | P48454 |
| OMIM ID | 114106 |
| HGNC ID | 9316 |
| Aliases | CALNA3, CNA3, PP2Bgamma |
Description
PPP3CC encodes the gamma catalytic subunit of calcineurin (protein phosphatase 2B), a calcium/calmodulin-dependent serine/threonine phosphatase. Calcineurin is a heterodimer composed of a catalytic subunit (alpha, beta, or gamma) and a regulatory subunit. PPP3CC is predominantly expressed in brain and testis, and plays a role in neuronal signaling, T-cell activation, and cardiac function.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Epileptic encephalopathy, early infantile, 1 (EIEE1) | Loss-of-function mutations in PPP3CC impair calcineurin activity, disrupting neuronal calcium signaling and synaptic plasticity. | ClinVar; OMIM #114106 |
| Intellectual disability, autosomal dominant 65 (MRD65) | De novo missense variants reduce phosphatase activity, affecting dendritic spine development and cognitive function. | ClinVar; OMIM #114106 |
| Schizophrenia (susceptibility) | Altered PPP3CC expression or rare variants may contribute to dysregulated calcium signaling in prefrontal cortex. | NCBI Gene; PubMed |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain (cerebral cortex) | 12.3 | Medium |
| Testis | 8.7 | Medium |
| Heart (left ventricle) | 4.2 | Low |
| Skeletal muscle | 3.1 | Low |
| Liver | 1.5 | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| SH-SY5Y (neuroblastoma) | 15.2 | Neuronal model |
| HEK293 (embryonic kidney) | 6.8 | Common expression system |
| Jurkat (T-cell) | 4.5 | Immune cell line |
| HepG2 (hepatocellular carcinoma) | 2.1 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.374G>A (p.Arg125His) | Missense | <0.01% | Reduced phosphatase activity; associated with MRD65 |
| c.1000C>T (p.Arg334Trp) | Missense | <0.01% | Loss of function; linked to EIEE1 |
| c.1285_1286del (p.Leu429Valfs*2) | Frameshift | <0.01% | Truncated protein; likely pathogenic |
Mutation functional classification
Loss of Function (LOF)
Missense and frameshift mutations that reduce or abolish calcineurin phosphatase activity, leading to neurodevelopmental disorders.
Gain of Function (GOF)
Not reported in PPP3CC.
Dominant Negative (DN)
Some missense variants (e.g., p.Arg125His) may interfere with wild-type subunit assembly, exerting a dominant-negative effect.
View complete mutation data：
Gene Ontology (GO)
Pathways
• Calcium signaling pathway (KEGG: hsa04020)
• Neurotrophin signaling pathway (KEGG: hsa04722)
• T cell receptor signaling pathway (KEGG: hsa04660)
• NFAT activation (Reactome: R-HSA-2871796)
Protein Summary
PPP3CC encodes the gamma catalytic subunit of calcineurin (PP2B), a calcium/calmodulin-dependent serine/threonine phosphatase. The protein contains a catalytic domain, a calmodulin-binding domain, and an autoinhibitory domain. Upon calcium influx, calmodulin binds and relieves autoinhibition, enabling dephosphorylation of substrates such as NFAT transcription factors. PPP3CC is highly expressed in brain and testis, and its dysfunction is linked to epileptic encephalopathy and intellectual disability.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| PPP3CC Knockout HEK293 Cell Line | EDJ-KQ735 | Human | 5533 | Details Get a Quote |
| PPP3CC Knockout A-549 Cell Line | EDJ-KQ19365 | Human | 5533 | Details Get a Quote |
| PPP3CC Knockout HCT 116 Cell Line | EDJ-KQ19366 | Human | 5533 | Details Get a Quote |
| PPP3CC Knockout HeLa Cell Line | EDJ-KQ19367 | Human | 5533 | Details Get a Quote |
