PPP2R1A Gene

HGNC Family	Protein phosphatase 2 regulatory subunits (PPP2R)
Name	protein phosphatase 2, regulatory subunit A, alpha
Description	This gene encodes a constant regulatory subunit of protein phosphatase 2. Protein phosphatase 2 is one of the four major Ser/Thr phosphatases, and it is implicated in the negative control of cell growth and division. It consists of a common heteromeric core enzyme, which is composed of a catalytic subunit and a constant regulatory subunit, that associates with a variety of regulatory subunits. The constant regulatory subunit A serves as a scaffolding molecule to coordinate the assembly of the catalytic subunit and a variable regulatory B subunit. This gene encodes an alpha isoform of the constant regulatory subunit A. Alternatively spliced transcript variants have been described. [provided by RefSeq, Apr 2010]
Summary	{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nPPP2R1A encodes the primary scaffolding Aα subunit of protein phosphatase 2A (PP2A), a major serine/threonine phosphatase that regulates diverse cellular processes including cell cycle progression, mitotic exit, apoptosis, and DNA repair. As the central organizer of the PP2A holoenzyme, PPP2R1A coordinates the binding of both the catalytic C and various regulatory B subunits to determine substrate specificity and ensure proper dephosphorylation of key signaling proteins. This orchestration is critical in T‐cell receptor signaling (via dephosphorylating Carma1) and in protecting anti‐apoptotic factors such as BCL‑2, thereby maintaining cellular homeostasis."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "3"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nMutations and altered expression of PPP2R1A have been implicated in the pathogenesis of several cancers. Hotspot missense variants have been detected in ovarian clear cell carcinoma, high‐grade serous endometrial tumors, and certain uterine, ovarian, and gastrointestinal stromal tumors. These mutations generally impair the assembly of specific PP2A holoenzymes—either by reducing binding to select B subunits or by enabling aberrant, dominant‑negative interactions with PP2A inhibitors—thereby compromising the phosphatase’s tumor suppressor function. As a consequence, key oncogenic pathways (including Akt, MAPK, and mTOR signaling) become hyperactivated, leading to enhanced cell proliferation, migration, and chemoresistance."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "4", "end_ref": "11"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn addition to its role in cancer, alterations in PPP2R1A—including de novo missense variants and regulatory promoter polymorphisms—have been linked to neurodevelopmental disorders and congenital anomalies, underscoring its importance in proper developmental processes. Such genetic changes can disrupt PP2A holoenzyme formation or modify its activity, thereby perturbing signaling pathways central to neuronal differentiation and synaptic function. Importantly, these findings have spurred investigation into targeted therapeutic strategies, such as exploiting synthetic lethality with ribonucleotide reductase inhibitors, to correct the downstream effects of aberrant PPP2R1A function."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "12", "end_ref": "14"}]}, {"type": "t", "text": ""}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Siân Jones, Tian-Li Wang, Ie-Ming Shih, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Frequent mutations of chromatin remodeling gene ARID1A in ovarian clear cell carcinoma."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Science (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1126/science.1196333"}], "href": "https://doi.org/10.1126/science.1196333"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20826764"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20826764"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Andrea C Eitelhuber, Sebastian Warth, Gisela Schimmack, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Dephosphorylation of Carma1 by PP2A negatively regulates T-cell activation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "EMBO J (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/emboj.2010.331"}], "href": "https://doi.org/10.1038/emboj.2010.331"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21157432"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21157432"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Stephen S Lin, Michael C Bassik, Heikyung Suh, et al. "}, {"type": "b", "children": [{"type": "t", "text": "PP2A regulates BCL-2 phosphorylation and proteasome-mediated degradation at the endoplasmic reticulum."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2006)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M602648200"}], "href": "https://doi.org/10.1074/jbc.M602648200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16717086"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16717086"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Melissa K McConechy, Michael S Anglesio, Steve E Kalloger, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Subtype-specific mutation of PPP2R1A in endometrial and ovarian carcinomas."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Pathol (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/path.2848"}], "href": "https://doi.org/10.1002/path.2848"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21381030"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21381030"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Dorien Haesen, Layka Abbasi Asbagh, Rita Derua, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Recurrent PPP2R1A Mutations in Uterine Cancer Act through a Dominant-Negative Mechanism to Promote Malignant Cell Growth."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cancer Res (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1158/0008-5472.CAN-15-3342"}], "href": "https://doi.org/10.1158/0008-5472.CAN-15-3342"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27485451"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27485451"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Ie-Ming Shih, Pradeep K Panuganti, Kuan-Tin Kuo, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Somatic mutations of PPP2R1A in ovarian and uterine carcinomas."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Am J Pathol (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.ajpath.2011.01.009"}], "href": "https://doi.org/10.1016/j.ajpath.2011.01.009"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21435433"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21435433"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Deepak C Nagendra, James Burke, G Larry Maxwell, et al. "}, {"type": "b", "children": [{"type": "t", "text": "PPP2R1A mutations are common in the serous type of endometrial cancer."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Carcinog (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/mc.20850"}], "href": "https://doi.org/10.1002/mc.20850"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21882256"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21882256"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Midori Toda-Ishii, Keisuke Akaike, Yoshiyuki Suehara, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Clinicopathological effects of protein phosphatase 2, regulatory subunit A, alpha mutations in gastrointestinal stromal tumors."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mod Pathol (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/modpathol.2016.138"}], "href": "https://doi.org/10.1038/modpathol.2016.138"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27469332"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27469332"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "Justin Miron, Cynthia Picard, Anne Labonté, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Association of PPP2R1A with Alzheimer's disease and specific cognitive domains."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Neurobiol Aging (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.neurobiolaging.2019.06.008"}], "href": "https://doi.org/10.1016/j.neurobiolaging.2019.06.008"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31349112"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31349112"}]}, {"type": "r", "ref": 10, "children": [{"type": "t", "text": "Feng Wang, Yang Zou, Fa-Ying Liu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Infrequent mutations of the PPP2R1A and PPP2R1B genes in patients with ovarian cancer."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Med Rep (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.3892/mmr.2013.1416"}], "href": "https://doi.org/10.3892/mmr.2013.1416"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23588898"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23588898"}]}, {"type": "r", "ref": 11, "children": [{"type": "t", "text": "Caitlin M O'Connor, Sarah E Taylor, Kathryn M Miller, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Targeting Ribonucleotide Reductase Induces Synthetic Lethality in PP2A-Deficient Uterine Serous Carcinoma."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cancer Res (2022)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1158/0008-5472.CAN-21-1987"}], "href": "https://doi.org/10.1158/0008-5472.CAN-21-1987"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "34921012"}], "href": "https://pubmed.ncbi.nlm.nih.gov/34921012"}]}, {"type": "r", "ref": 12, "children": [{"type": "t", "text": "Elizabeth K Baker, Beulah Solivio, Ben Pode-Shakked, et al. "}, {"type": "b", "children": [{"type": "t", "text": "PPP2R1A neurodevelopmental disorder is associated with congenital heart defects."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Am J Med Genet A (2022)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/ajmg.a.62946"}], "href": "https://doi.org/10.1002/ajmg.a.62946"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "36209351"}], "href": "https://pubmed.ncbi.nlm.nih.gov/36209351"}]}, {"type": "r", "ref": 13, "children": [{"type": "t", "text": "Yanyan Qian, Yinmo Jiang, Ji Wang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Novel Variants of PPP2R1A in Catalytic Subunit Binding Domain and Genotype-Phenotype Analysis in Neurodevelopmentally Delayed Patients."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Genes (Basel) (2023)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.3390/genes14091750"}], "href": "https://doi.org/10.3390/genes14091750"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "37761890"}], "href": "https://pubmed.ncbi.nlm.nih.gov/37761890"}]}, {"type": "r", "ref": 14, "children": [{"type": "t", "text": "Michiel Remmerie, Rüveyda Dok, Zhigang Wang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The PPP2R1A cancer hotspot mutant p.R183W increases clofarabine resistance in uterine serous carcinoma cells by a gain-of-function mechanism."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Oncol (Dordr) (2024)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s13402-024-00963-5"}], "href": "https://doi.org/10.1007/s13402-024-00963-5"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "38888850"}], "href": "https://pubmed.ncbi.nlm.nih.gov/38888850"}]}]}]}
Synonyms	MRD36, PP2AAALPHA, PP2AA, PP2A-AALPHA, PR65A
Proteins	2AAA_HUMAN
NCBI Gene ID	5518
API
Download Associations
Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

PPP2R1A has 10,254 functional associations with biological entities spanning 9 categories (molecular profile, organism, chemical, disease, phenotype or trait, functional term, phrase or reference, structural feature, cell line, cell type or tissue, gene, protein or microRNA, sequence feature) extracted from 134 datasets.

Click the + buttons to view associations for PPP2R1A from the datasets below.

If available, associations are ranked by standardized value

Harmonizome 3.0

PPP2R1A Gene

Functional Associations

Please acknowledge the Harmonizome in your publications by citing the following reference(s):

	Dataset	Summary
	Allen Brain Atlas Adult Human Brain Tissue Gene Expression Profiles	tissues with high or low expression of PPP2R1A gene relative to other tissues from the Allen Brain Atlas Adult Human Brain Tissue Gene Expression Profiles dataset.
	Allen Brain Atlas Adult Mouse Brain Tissue Gene Expression Profiles	tissues with high or low expression of PPP2R1A gene relative to other tissues from the Allen Brain Atlas Adult Mouse Brain Tissue Gene Expression Profiles dataset.
	Allen Brain Atlas Aging Dementia and Traumatic Brain Injury Tissue Sample Gene Expression Profiles	tissue samples with high or low expression of PPP2R1A gene relative to other tissue samples from the Allen Brain Atlas Aging Dementia and Traumatic Brain Injury Tissue Sample Gene Expression Profiles dataset.
	Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by Microarray	tissue samples with high or low expression of PPP2R1A gene relative to other tissue samples from the Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by Microarray dataset.
	Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by RNA-seq	tissue samples with high or low expression of PPP2R1A gene relative to other tissue samples from the Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by RNA-seq dataset.
	Allen Brain Atlas Prenatal Human Brain Tissue Gene Expression Profiles	tissues with high or low expression of PPP2R1A gene relative to other tissues from the Allen Brain Atlas Prenatal Human Brain Tissue Gene Expression Profiles dataset.
	BioGPS Cell Line Gene Expression Profiles	cell lines with high or low expression of PPP2R1A gene relative to other cell lines from the BioGPS Cell Line Gene Expression Profiles dataset.
	BioGPS Human Cell Type and Tissue Gene Expression Profiles	cell types and tissues with high or low expression of PPP2R1A gene relative to other cell types and tissues from the BioGPS Human Cell Type and Tissue Gene Expression Profiles dataset.
	BioGPS Mouse Cell Type and Tissue Gene Expression Profiles	cell types and tissues with high or low expression of PPP2R1A gene relative to other cell types and tissues from the BioGPS Mouse Cell Type and Tissue Gene Expression Profiles dataset.
	Carcinogenome Chemical Perturbation Carcinogenicity Signatures	small molecule perturbations changing expression of PPP2R1A gene from the Carcinogenome Chemical Perturbation Carcinogenicity Signatures dataset.
	CCLE Cell Line Gene CNV Profiles	cell lines with high or low copy number of PPP2R1A gene relative to other cell lines from the CCLE Cell Line Gene CNV Profiles dataset.
	CCLE Cell Line Gene Expression Profiles	cell lines with high or low expression of PPP2R1A gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
	CCLE Cell Line Proteomics	Cell lines associated with PPP2R1A protein from the CCLE Cell Line Proteomics dataset.
	ChEA Transcription Factor Binding Site Profiles	transcription factor binding site profiles with transcription factor binding evidence at the promoter of PPP2R1A gene from the CHEA Transcription Factor Binding Site Profiles dataset.
	ChEA Transcription Factor Targets	transcription factors binding the promoter of PPP2R1A gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets dataset.
	ChEA Transcription Factor Targets 2022	transcription factors binding the promoter of PPP2R1A gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets 2022 dataset.
	ClinVar Gene-Phenotype Associations 2025	phenotypes associated with PPP2R1A gene from the curated ClinVar Gene-Phenotype Associations 2025 dataset.
	CM4AI U2OS Cell Map Protein Localization Assemblies	assemblies containing PPP2R1A protein from integrated AP-MS and IF data from the CM4AI U2OS Cell Map Protein Localization Assemblies dataset.
	CMAP Signatures of Differentially Expressed Genes for Small Molecules	small molecule perturbations changing expression of PPP2R1A gene from the CMAP Signatures of Differentially Expressed Genes for Small Molecules dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores	cellular components containing PPP2R1A protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores 2025	cellular components containing PPP2R1A protein from the COMPARTMENTS Curated Protein Localization Evidence Scores 2025 dataset.
	COMPARTMENTS Experimental Protein Localization Evidence Scores	cellular components containing PPP2R1A protein in low- or high-throughput protein localization assays from the COMPARTMENTS Experimental Protein Localization Evidence Scores dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores	cellular components co-occuring with PPP2R1A protein in abstracts of biomedical publications from the COMPARTMENTS Text-mining Protein Localization Evidence Scores dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025	cellular components co-occuring with PPP2R1A protein in abstracts of biomedical publications from the COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025 dataset.
	CORUM Protein Complexes	protein complexs containing PPP2R1A protein from the CORUM Protein Complexes dataset.
	COSMIC Cell Line Gene CNV Profiles	cell lines with high or low copy number of PPP2R1A gene relative to other cell lines from the COSMIC Cell Line Gene CNV Profiles dataset.
	COSMIC Cell Line Gene Mutation Profiles	cell lines with PPP2R1A gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
	CTD Gene-Chemical Interactions	chemicals interacting with PPP2R1A gene/protein from the curated CTD Gene-Chemical Interactions dataset.
	CTD Gene-Disease Associations	diseases associated with PPP2R1A gene/protein from the curated CTD Gene-Disease Associations dataset.
	DeepCoverMOA Drug Mechanisms of Action	small molecule perturbations with high or low expression of PPP2R1A protein relative to other small molecule perturbations from the DeepCoverMOA Drug Mechanisms of Action dataset.
	DISEASES Text-mining Gene-Disease Association Evidence Scores	diseases co-occuring with PPP2R1A gene in abstracts of biomedical publications from the DISEASES Text-mining Gene-Disease Assocation Evidence Scores dataset.
	DISEASES Text-mining Gene-Disease Association Evidence Scores 2025	diseases co-occuring with PPP2R1A gene in abstracts of biomedical publications from the DISEASES Text-mining Gene-Disease Assocation Evidence Scores 2025 dataset.
	DisGeNET Gene-Disease Associations	diseases associated with PPP2R1A gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.
	DisGeNET Gene-Phenotype Associations	phenotypes associated with PPP2R1A gene in GWAS and other genetic association datasets from the DisGeNET Gene-Phenoptype Associations dataset.
	DrugBank Drug Targets	interacting drugs for PPP2R1A protein from the curated DrugBank Drug Targets dataset.
	ENCODE Histone Modification Site Profiles	histone modification site profiles with high histone modification abundance at PPP2R1A gene from the ENCODE Histone Modification Site Profiles dataset.
	ENCODE Transcription Factor Binding Site Profiles	transcription factor binding site profiles with transcription factor binding evidence at the promoter of PPP2R1A gene from the ENCODE Transcription Factor Binding Site Profiles dataset.
	ENCODE Transcription Factor Targets	transcription factors binding the promoter of PPP2R1A gene in ChIP-seq datasets from the ENCODE Transcription Factor Targets dataset.
	ESCAPE Omics Signatures of Genes and Proteins for Stem Cells	PubMedIDs of publications reporting gene signatures containing PPP2R1A from the ESCAPE Omics Signatures of Genes and Proteins for Stem Cells dataset.
	GAD Gene-Disease Associations	diseases associated with PPP2R1A gene in GWAS and other genetic association datasets from the GAD Gene-Disease Associations dataset.