PPP2R1A
Protein Phosphatase 2 Regulatory Subunit A Alpha
Gene Information Card
| Symbol | PPP2R1A |
|---|---|
| Full Name | Protein Phosphatase 2 Regulatory Subunit A Alpha |
| Gene Type | Protein coding |
| Chromosomal Location | 19q13.41 |
| NCBI Gene ID | 5518 ncbi.nlm.nih.gov/gene/5518 |
| Ensembl ID | ENSG00000105568 |
| UniProt ID | P30153 |
| OMIM ID | 605983 |
| HGNC ID | 9302 |
| Aliases | PP2A-Aalpha, PR65A, MGC786, PP2A-A, PP2AA |
Description
PPP2R1A (Protein Phosphatase 2 Regulatory Subunit A Alpha) is a protein-coding gene that encodes the A alpha regulatory subunit of protein phosphatase 2 (PP2A). PP2A is one of the major serine/threonine phosphatases in eukaryotic cells, regulating diverse cellular processes including cell cycle progression, DNA replication, transcription, translation, and signal transduction. The A subunit serves as a scaffold that binds the catalytic C subunit and various regulatory B subunits, determining substrate specificity and subcellular localization. Mutations in PPP2R1A are frequently observed in several cancers, particularly endometrial and ovarian carcinomas, and are associated with altered PP2A activity and tumorigenesis.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Endometrial carcinoma | Somatic mutations (e.g., R183W, S256F) disrupt PP2A complex assembly and activity, promoting cell proliferation and tumor growth. | ClinVar, COSMIC |
| Ovarian carcinoma | Recurrent missense mutations (e.g., R183W) impair PP2A function, contributing to serous ovarian cancer development. | ClinVar, COSMIC |
| Lung adenocarcinoma | PPP2R1A mutations (e.g., R183W) identified in lung cancer, potentially affecting PP2A-mediated tumor suppression. | COSMIC |
| Breast cancer | Somatic alterations reported, though less frequent; may influence PP2A signaling in breast tumorigenesis. | COSMIC |
| Colorectal cancer | Rare mutations observed; functional impact on PP2A activity and cell growth control. | COSMIC |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 38.2 | High |
| Ovary | 25.1 | Medium |
| Endometrium | 22.8 | Medium |
| Lung | 19.5 | Medium |
| Breast | 17.3 | Medium |
| Colon | 15.6 | Medium |
| Liver | 12.4 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HeLa (cervical) | 32.5 | High expression |
| A549 (lung) | 28.1 | High expression |
| MCF7 (breast) | 24.3 | Medium expression |
| OVCAR3 (ovarian) | 22.0 | Medium expression |
| HCT116 (colon) | 18.7 | Medium expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| R183W | Missense | ~5-10% in endometrial cancer | Disrupts A subunit scaffold function, reduces PP2A activity, promotes cell proliferation |
| S256F | Missense | ~2-5% in endometrial cancer | Alters B subunit binding, impairs PP2A complex formation |
| R183Q | Missense | <1% in ovarian cancer | Similar to R183W, affects PP2A assembly |
| P179R | Missense | <1% in lung cancer | Potential loss of PP2A function |
| E64D | Missense | Rare | Unknown functional impact |
Mutation functional classification
Loss of Function (LOF)
Most PPP2R1A mutations (e.g., R183W, S256F) are loss-of-function, impairing PP2A holoenzyme assembly and reducing phosphatase activity, leading to unchecked cell growth.
Gain of Function (GOF)
No clear gain-of-function mutations reported; alterations primarily disrupt normal PP2A function.
Dominant Negative (DN)
Mutations such as R183W may act in a dominant-negative manner by incorporating into PP2A complexes and impairing their activity, even in the presence of wild-type allele.
View complete mutation data：
Gene Ontology (GO)
Pathways
• hsa04110 - Cell cycle
• hsa04115 - p53 signaling pathway
• hsa04010 - MAPK signaling pathway
• hsa04120 - Ubiquitin mediated proteolysis
• hsa05200 - Pathways in cancer
Protein Summary
The PPP2R1A gene encodes the A alpha regulatory subunit (PR65A) of protein phosphatase 2 (PP2A), a heterotrimeric serine/threonine phosphatase. The A subunit acts as a scaffold, binding the catalytic C subunit and variable regulatory B subunits to form the active PP2A holoenzyme. PP2A regulates numerous cellular processes including cell cycle progression, DNA replication, transcription, translation, and signal transduction by dephosphorylating key substrates such as AKT, ERK, and p53. Mutations in PPP2R1A, particularly recurrent missense changes like R183W and S256F, are oncogenic and commonly found in endometrial and ovarian cancers. These mutations disrupt PP2A complex assembly and activity, leading to increased cell proliferation and tumorigenesis. PPP2R1A is considered a tumor suppressor gene, and its alterations contribute to cancer development through loss of PP2A-mediated growth control.
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