PPP3CB: Calcineurin Subunit B Type 2
A regulatory subunit of the calcium/calmodulin-dependent protein phosphatase calcineurin, involved in immune response, cardiac function, and neuronal signaling.
Gene Information Card
| Symbol | PPP3CB |
|---|---|
| Full Name | Protein Phosphatase 3 Catalytic Subunit Beta |
| Gene Type | protein-coding |
| Chromosomal Location | 10q22.2 |
| NCBI Gene ID | 5532 ncbi.nlm.nih.gov/gene/5532 |
| Ensembl ID | ENSG00000107758 |
| UniProt ID | P16298 |
| OMIM ID | 114106 |
| HGNC ID | 9315 |
| Aliases | CALNB2, CNA2, PP2Bbeta, calcineurin A beta |
Description
PPP3CB encodes the beta isoform of the catalytic subunit of calcineurin, a calcium/calmodulin-dependent serine/threonine phosphatase. Calcineurin is a heterodimer composed of a catalytic A subunit (encoded by PPP3CA, PPP3CB, or PPP3CC) and a regulatory B subunit (encoded by PPP3R1). PPP3CB is widely expressed and plays a critical role in T-cell activation, cardiac hypertrophy, synaptic plasticity, and muscle differentiation. It dephosphorylates NFAT transcription factors, enabling their nuclear translocation and target gene expression.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Cardiac hypertrophy | Dephosphorylation of NFAT leads to hypertrophic gene expression; PPP3CB overexpression induces hypertrophy in cardiomyocytes. | PMID: 10679433, 15123618 |
| Alzheimer disease | Calcineurin activity dysregulation linked to tau hyperphosphorylation and synaptic dysfunction; PPP3CB variants associated with altered risk. | PMID: 21738471, 28430825 |
| T-cell acute lymphoblastic leukemia (T-ALL) | Gain-of-function mutations in PPP3CB (e.g., E71K) enhance calcineurin activity, promoting NFAT activation and leukemogenesis. | COSMIC, PMID: 23563267 |
| Immunodeficiency | Loss-of-function mutations impair T-cell receptor signaling and NFAT activation, leading to combined immunodeficiency. | ClinVar, PMID: 23374273 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 12.5 | Medium |
| Heart | 9.8 | Medium |
| Skeletal Muscle | 8.2 | Medium |
| Lung | 6.4 | Low |
| Liver | 4.1 | Low |
| Kidney | 7.3 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK293 | 10.1 | High expression in kidney-derived line |
| Jurkat | 8.5 | T-cell line; relevant for immune function |
| SH-SY5Y | 9.2 | Neuroblastoma; used in neuronal studies |
| HeLa | 7.8 | Cervical carcinoma; moderate expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| E71K | Missense | 0.02% (COSMIC) | Gain-of-function; increases phosphatase activity; associated with T-ALL |
| R269Q | Missense | <0.01% (ClinVar) | Loss-of-function; reduces calcineurin activity; linked to immunodeficiency |
| G160S | Missense | 0.01% (COSMIC) | Unknown functional effect; reported in colorectal cancer |
| c.1003-1G>A | Splice acceptor | <0.01% (ClinVar) | Loss-of-function; causes exon skipping; associated with severe combined immunodeficiency |
Mutation functional classification
Loss of Function (LOF)
Mutations such as R269Q and splice-site variants reduce or abolish calcineurin phosphatase activity, impairing NFAT dephosphorylation and T-cell activation, leading to immunodeficiency.
Gain of Function (GOF)
Mutations such as E71K enhance calcineurin activity, increasing NFAT nuclear translocation and promoting oncogenic signaling in T-ALL.
Dominant Negative (DN)
No well-characterized dominant-negative mutations reported for PPP3CB.
View complete mutation data：
Gene Ontology (GO)
| • calcium-dependent protein serine/threonine phosphatase activity | • calmodulin binding |
| • protein phosphatase 2B binding | • NFAT protein binding |
| • signal transduction | • T cell receptor signaling pathway |
| • cardiac muscle cell differentiation | • positive regulation of transcription by RNA polymerase II |
Pathways
• Calcineurin-NFAT signaling pathway
• T cell receptor signaling pathway
• Cardiac hypertrophy signaling
• Calcium signaling pathway
• Neurotrophin signaling pathway
Protein Summary
PPP3CB encodes the catalytic A beta subunit of calcineurin, a calcium/calmodulin-dependent phosphatase. The protein contains a catalytic domain, a calmodulin-binding domain, and an autoinhibitory domain. Upon calcium influx, calmodulin binds and relieves autoinhibition, allowing dephosphorylation of substrates such as NFAT, MEF2, and CREB. PPP3CB is essential for immune activation, cardiac growth, and neuronal plasticity. Dysregulation contributes to cardiac hypertrophy, Alzheimer disease, and leukemia.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| PPP3CB Knockout HEK293 Cell Line | EDJ-KQ734 | Human | 5532 | Details Get a Quote |
| PPP3CB Knockout A-549 Cell Line | EDJ-KQ18196 | Human | 5532 | Details Get a Quote |
| PPP3CB Knockout HCT 116 Cell Line | EDJ-KQ19363 | Human | 5532 | Details Get a Quote |
| PPP3CB Knockout HeLa Cell Line | EDJ-KQ19364 | Human | 5532 | Details Get a Quote |
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