PPP2R1A
PPP2R1A is a gene that drives cell growth when it is altered. The public catalogues list it as a drug target, an oncogene driver, a tumour suppressor and a biomarker, and clinical evidence ties its variants to diagnosis, prognosis or drug response.
Overview
The PR65 subunit of protein phosphatase 2A serves as a scaffolding molecule to coordinate the assembly of the catalytic subunit and a variable regulatory B subunit. Upon interaction with GNA12 promotes dephosphorylation of microtubule associated protein TAU/MAPT. Required for proper chromosome segregation and for centromeric localisation of SGO1 in mitosis.
CIViC holds 2 clinical evidence items and 0 assertions across 2 variants, naming Ipilimumab/Nivolumab Regimen and Durvalumab/Tremelimumab Regimen. Open Targets scores its association with cancer at 0.81 (direct and indirect evidence; datatypes affected pathway 0.89, literature 0.89, genetic association 0.00, somatic mutation 0.97, animal model 0.69). IntOGen calls it a driver in 11 cohorts (10 activating, 1 loss-of-function), covering Adenoid Cystic Carcinoma, Colorectal Adenocarcinoma, Ovarian Epithelial Tumour, Small Cell Lung Cancer, Endometrial Carcinoma, Uterine Carcinosarcoma/Uterine Malignant Mixed Mullerian Tumour and others.
- Target · the protein and the cell it sits on
- Drug · antibody, small molecule, cell or radioligand
- Effect · signal, damage or kill
In plain words · PPP2R1A is a gene that drives cell growth when it is altered. The public catalogues list it as a drug target, an oncogene driver, a tumour suppressor and a biomarker, and clinical evidence ties its variants to diagnosis, prognosis or drug response.
- 1 · What it is
PPP2R1A is a gene that drives cell growth when it is altered. The public catalogues list it as a drug target, an oncogene driver, a tumour suppressor and a biomarker, and clinical evidence ties its variants to diagnosis, prognosis or drug response.
- 2 · What goes wrong in cancer
The PR65 subunit of protein phosphatase 2A serves as a scaffolding molecule to coordinate the assembly of the catalytic subunit and a variable regulatory B subunit.
- 3 · How drugs use it
No product in this corpus aims at PPP2R1A yet. Drugs fit a pocket that exists only in one shape of the mutant protein and hold it there, off.
External identifiers
Sources: HGNC HGNC:9302 (approved symbol, name, aliases, locus and cross-references (hgnc_complete_set.txt)); UniProt P30153 (protein name, function text, keywords and locations (REST API)); CIViC gene PPP2R1A (2 evidence items, 0 assertions, 2 variants; diseases: Ovarian Clear Cell Carcinoma (GraphQL API, CC0)); Open Targets ENSG00000105568 (association with cancer (MONDO_0004992) 0.81; per-cancer scores at or above 0.5: colorectal cancer 0.54, gastric cancer 0.50, ovarian cancer 0.51, endometrial cancer 0.68, melanoma 0.55, skin cancer 0.55 (GraphQL API, CC0)); IntOGen PPP2R1A (driver in 11 cohorts (Act 10, LoF 1); Compendium_Cancer_Genes.tsv release 20240920, CC0 1.0)
Biology
The PR65 subunit of protein phosphatase 2A serves as a scaffolding molecule to coordinate the assembly of the catalytic subunit and a variable regulatory B subunit. Upon interaction with GNA12 promotes dephosphorylation of microtubule associated protein TAU/MAPT. Required for proper chromosome segregation and for centromeric localisation of SGO1 in mitosis. Together with RACK1 adapter, mediates dephosphorylation of AKT1 at 'Ser-473', preventing AKT1 activation and AKT-mTOR signalling pathway. Dephosphorylation of AKT1 is essential for regulatory T-cells (Treg) homeostasis and stability. Part of the striatin-interacting phosphatase and kinase (STRIPAK) complexes. Location: Cytoplasm; Nucleus; Chromosome; Chromosome, centromere (UniProt). Locus 19q13.41 (HGNC).
- Endometrial cancer: Open Targets association 0.68 with endometrial cancer (MONDO_0011962); IntOGen driver in 4 cohorts (UCEC)
- Colorectal cancer: Open Targets association 0.54 with colorectal cancer (MONDO_0005575); IntOGen driver in 1 cohort (COADREAD)
- Ovarian cancer: Open Targets association 0.51 with ovarian cancer (MONDO_0008170); IntOGen driver in 1 cohort (OVT)
- Salivary gland cancers: IntOGen driver in 1 cohort (ACYC)
- Thyroid cancer: IntOGen driver in 1 cohort (WDTC)
- Lung cancer: Open Targets association 0.56 with lung cancer (MONDO_0008903)
Notes
top- Written by scripts/fetch-cancer-genes.ts from CIViC, Open Targets, IntOGen, HGNC and UniProt; the function text is UniProt's, condensed and in UK spelling. Roles: CIViC lists 2 therapies; IntOGen calls it an activating (Act) driver in 10 cohorts; IntOGen calls it a loss-of-function (LoF) driver in 1 cohort; CIViC holds 2 clinical evidence items on its variants. Evidence tier "clinical-evidence" is the strongest of those signals.
- Prevalence not recorded: none of the sources gives a positivity rate.
- Diseases the sources name that have no OnCo cancer page yet, so they are not linked: Ovarian Clear Cell Carcinoma.
Latest papers
topQuery for this target: (TITLE:"PPP2R1A" OR ABSTRACT:"PPP2R1A" OR TITLE:"protein phosphatase 2 scaffold subunit Aalpha" OR ABSTRACT:"protein phosphatase 2 scaffold subunit Aalpha" OR TITLE:"Serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A alpha isoform" OR ABSTRACT:"Serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A alpha isoform" OR TITLE:"PR65A" OR ABSTRACT:"PR65A" OR TITLE:"PP2A-Aalpha" OR ABSTRACT:"PP2A-Aalpha" OR TITLE:"PP2AA" OR ABSTRACT:"PP2AA") AND (cancer OR tumor OR tumour OR oncology OR carcinoma OR lymphoma OR leukemia OR leukaemia OR myeloma OR sarcoma OR melanoma OR glioma). Results are unfiltered search hits about PPP2R1A, not a curated reading list.
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