PPP3R1
Protein Phosphatase 3 Regulatory Subunit B, Alpha
Gene Information Card
| Symbol | PPP3R1 |
|---|---|
| Full Name | Protein Phosphatase 3 Regulatory Subunit B, Alpha |
| Gene Type | Protein coding |
| Chromosomal Location | 2p14 |
| NCBI Gene ID | 5534 ncbi.nlm.nih.gov/gene/5534 |
| Ensembl ID | ENSG00000115977 |
| UniProt ID | P63098 |
| OMIM ID | 601302 |
| HGNC ID | 9317 |
| Aliases | CNB1, CALNB1, PPP3RL |
Description
PPP3R1 encodes the regulatory subunit B (calcineurin B) of protein phosphatase 3 (calcineurin), a calcium/calmodulin-dependent serine/threonine phosphatase. Calcineurin B binds calcium and is essential for the activation of the catalytic subunit (PPP3CA/PPP3CB). The heterodimer dephosphorylates nuclear factor of activated T-cells (NFAT) transcription factors, regulating immune response, cardiac hypertrophy, and neuronal plasticity. PPP3R1 is ubiquitously expressed with highest levels in brain, heart, and skeletal muscle.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Epileptic encephalopathy, early infantile, 1 (EIEE1) | Missense mutations in PPP3R1 impair calcineurin activity, disrupting neuronal calcium signaling and synaptic function. | ClinVar, OMIM |
| Intellectual disability, autosomal dominant 65 (MRD65) | De novo loss-of-function variants reduce calcineurin phosphatase activity, affecting NFAT-dependent gene expression in neurons. | ClinVar, OMIM |
| Cardiac hypertrophy (susceptibility) | Altered calcineurin signaling via PPP3R1 variants may enhance NFAT nuclear translocation, promoting pathological hypertrophy. | NCBI Gene, PubMed |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain cortex | 42.3 | High |
| Heart | 38.1 | High |
| Skeletal muscle | 35.7 | High |
| Liver | 12.4 | Medium |
| Lung | 8.9 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| SH-SY5Y (neuroblastoma) | 45.2 | High expression |
| HEK293 (embryonic kidney) | 30.1 | Moderate expression |
| HepG2 (hepatocellular carcinoma) | 15.8 | Low expression |
| K562 (leukemia) | 22.4 | Moderate expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.143G>A (p.Arg48His) | Missense | Rare | Reduces calcium binding affinity; associated with EIEE1 |
| c.364C>T (p.Arg122Trp) | Missense | Rare | Impairs calcineurin heterodimer stability; linked to MRD65 |
| c.1A>G (p.Met1?) | Start loss | Very rare | Loss of protein expression; likely pathogenic |
Mutation functional classification
Loss of Function (LOF)
Missense variants (e.g., p.Arg48His, p.Arg122Trp) reduce calcium binding or disrupt subunit interaction, leading to decreased calcineurin phosphatase activity.
Gain of Function (GOF)
No gain-of-function mutations reported in PPP3R1.
Dominant Negative (DN)
Heterozygous missense mutations may act dominant-negative by forming inactive calcineurin complexes, as observed in EIEE1.
View complete mutation data：
Gene Ontology (GO)
| • calcium ion binding (GO:0005509) | • calmodulin binding (GO:0005516) |
| • protein phosphatase regulator activity (GO:0019888) | • calcineurin complex (GO:0005955) |
| • regulation of NFAT protein import into nucleus (GO:0051532) |
Pathways
• Calcineurin-NFAT signaling pathway (Reactome: R-HSA-202424)
• Calcium signaling pathway (KEGG: hsa04020)
• T cell receptor signaling pathway (KEGG: hsa04660)
Protein Summary
PPP3R1 (calcineurin B, alpha) is a 170-amino acid calcium-binding regulatory subunit of calcineurin. It contains four EF-hand motifs that bind calcium ions, inducing a conformational change required for catalytic subunit activation. The protein is highly conserved and essential for calcineurin-mediated dephosphorylation of NFAT transcription factors. Mutations in PPP3R1 cause neurodevelopmental disorders due to disrupted calcium-dependent signaling.
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