PPP3R1 Gene

HGNC Family	EF-hand domain containing
Name	protein phosphatase 3, regulatory subunit B, alpha
Description	Enables phosphatase binding activity and protein domain specific binding activity. Involved in calcineurin-NFAT signaling cascade and positive regulation of transcription by RNA polymerase II. Part of calcineurin complex. Implicated in Alzheimer's disease and dilated cardiomyopathy. [provided by Alliance of Genome Resources, Mar 2025]
Summary	{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nPPP3R1 encodes the regulatory B subunit of calcineurin, a Ca²⁺/calmodulin‐dependent phosphatase that modulates key signaling pathways in neural and sensory cells. Several studies have implicated PPP3R1 variants in neurodegenerative processes. For example, single‐nucleotide polymorphisms in PPP3R1 have been associated with increased cerebrospinal fluid phosphorylated-tau levels and a faster clinical decline in Alzheimer’s disease, underscoring its role in tau dephosphorylation and disease progression. In parallel, mutations affecting the structure or expression of PPP3R1—as seen in familial duplications that include its first exon—have been linked to sensorineural hearing loss, while altered expression levels in peripheral blood were observed in patients with schizophrenia, suggesting that this regulatory subunit contributes to both cognitive and sensory functions."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "5"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn the realm of cardiovascular and skeletal muscle physiology, genetic polymorphisms in PPP3R1 are emerging as determinants of performance and structural remodeling. Variants—such as those in promoter regions or insertion/deletion polymorphisms—have been linked to differences in muscle fiber composition, strength training responsiveness, and endurance athlete status, presumably by fine-tuning calcineurin-dependent signaling that regulates slow myosin heavy chain expression and metabolic adaptation. Moreover, alterations in PPP3R1 genotype correlate with features of cardiac hypertrophy and elevated serum calcineurin levels that may predispose to coronary inflammation and dilated cardiomyopathy, highlighting its importance in both exercise performance and cardiovascular remodeling."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "6", "end_ref": "11"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond its classical role in calcium signaling, PPP3R1 contributes to diverse cellular processes such as the regulation of gene transcription via NFAT, modulation of inflammatory cytokine production, and even the control of cell fate decisions. Notably, recent evidence indicates that overexpression or gain of function of PPP3R1 accelerates mesenchymal stem cell senescence by altering membrane polarization, promoting Ca²⁺ influx and activating downstream NFAT/ATF3/p53 signaling. These emerging functions suggest that PPP3R1 not only sustains calcineurin phosphatase activity but also serves as a nodal regulator in processes critical for cell proliferation, differentiation, and aging."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "12"}]}, {"type": "t", "text": ""}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Masahiko Murata, Masahiko Tsunoda, Tomiki Sumiyoshi, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Calcineurin A gamma and B gene expressions in the whole blood in Japanese patients with schizophrenia."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Prog Neuropsychopharmacol Biol Psychiatry (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.pnpbp.2008.01.013"}], "href": "https://doi.org/10.1016/j.pnpbp.2008.01.013"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18343007"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18343007"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Carlos Cruchaga, John S K Kauwe, Kevin Mayo, et al. "}, {"type": "b", "children": [{"type": "t", "text": "SNPs associated with cerebrospinal fluid phospho-tau levels influence rate of decline in Alzheimer's disease."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "PLoS Genet (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1371/journal.pgen.1001101"}], "href": "https://doi.org/10.1371/journal.pgen.1001101"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20862329"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20862329"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Jinbo Cheng, Wei Tang, Zhenyi Su, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Mutation of calcineurin subunit B M118 influences the activities of NF-AT and p53, but not calcineurin expression level."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochem Biophys Res Commun (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.bbrc.2011.08.126"}], "href": "https://doi.org/10.1016/j.bbrc.2011.08.126"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21910968"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21910968"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "David Peterson, Caitlin Munger, Jared Crowley, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Variants in PPP3R1 and MAPT are associated with more rapid functional decline in Alzheimer's disease: the Cache County Dementia Progression Study."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Alzheimers Dement (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.jalz.2013.02.010"}], "href": "https://doi.org/10.1016/j.jalz.2013.02.010"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23727081"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23727081"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Xintong Zhao, Ronghua Li, Meng Qiao, et al. "}, {"type": "b", "children": [{"type": "t", "text": "MiR-548a-3p Promotes Keratinocyte Proliferation Targeting PPP3R1 after Being Induced by IL-22."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Inflammation (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s10753-017-0705-3"}], "href": "https://doi.org/10.1007/s10753-017-0705-3"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "29181737"}], "href": "https://pubmed.ncbi.nlm.nih.gov/29181737"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Brian D Hand, Matthew C Kostek, Robert E Ferrell, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Influence of promoter region variants of insulin-like growth factor pathway genes on the strength-training response of muscle phenotypes in older adults."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Appl Physiol (1985) (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1152/japplphysiol.00420.2007"}], "href": "https://doi.org/10.1152/japplphysiol.00420.2007"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17761791"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17761791"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Ildus I Ahmetov, Alun G Williams, Daniil V Popov, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The combined impact of metabolic gene polymorphisms on elite endurance athlete status and related phenotypes."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Hum Genet (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s00439-009-0728-4"}], "href": "https://doi.org/10.1007/s00439-009-0728-4"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19653005"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19653005"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Zi-Hong He, Yang Hu, Hai-Yan Wang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Are calcineurin genes associated with endurance phenotype traits?"}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Eur J Appl Physiol (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s00421-010-1361-6"}], "href": "https://doi.org/10.1007/s00421-010-1361-6"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20107831"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20107831"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "Zi-Hong He, Yang Hu, Yan-Chun Li, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Polymorphisms in the calcineurin genes are associated with the training responsiveness of cardiac phenotypes in Chinese young adults."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Eur J Appl Physiol (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s00421-010-1558-8"}], "href": "https://doi.org/10.1007/s00421-010-1558-8"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20593291"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20593291"}]}, {"type": "r", "ref": 10, "children": [{"type": "t", "text": "Sailaja Maddhuri, Srinivas Bandaru, Chaitanya Bhukya, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Association of CnB 5I/5D promoter gene polymorphism and serum calcineurin levels in early onset of coronary artery disease of south Indian cohort."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Gene (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.gene.2017.08.002"}], "href": "https://doi.org/10.1016/j.gene.2017.08.002"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "28827117"}], "href": "https://pubmed.ncbi.nlm.nih.gov/28827117"}]}, {"type": "r", "ref": 11, "children": [{"type": "t", "text": "M D Jinqiang Zhuang, M D Ruijun Yuan, M D Yizeng, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The CnB1 p.D102A variant is linked to dilated cardiomyopathy via impaired Calcineurin activity."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Mol Cell Cardiol (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.yjmcc.2020.08.012"}], "href": "https://doi.org/10.1016/j.yjmcc.2020.08.012"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "32882262"}], "href": "https://pubmed.ncbi.nlm.nih.gov/32882262"}]}, {"type": "r", "ref": 12, "children": [{"type": "t", "text": "Molin Li, Weimin Gong, Jie Chen, et al. "}, {"type": "b", "children": [{"type": "a", "children": [{"type": "t", "text": "i"}], "href": "i"}, {"type": "t", "text": "PPP3R1"}, {"type": "a", "children": [{"type": "t", "text": "/i"}], "href": "/i"}, {"type": "t", "text": " Promotes MSCs Senescence by Inducing Plasma Membrane Depolarization and Increasing Ca"}, {"type": "a", "children": [{"type": "t", "text": "sup"}], "href": "sup"}, {"type": "t", "text": "2+"}, {"type": "a", "children": [{"type": "t", "text": "/sup"}], "href": "/sup"}, {"type": "t", "text": " Influx."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Int J Mol Sci (2023)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.3390/ijms24054421"}], "href": "https://doi.org/10.3390/ijms24054421"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "36901851"}], "href": "https://pubmed.ncbi.nlm.nih.gov/36901851"}]}]}]}
Synonyms	CNB1, CALNB1, CNB
Proteins	CANB1_HUMAN
NCBI Gene ID	5534
API
Download Associations
Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

PPP3R1 has 7,904 functional associations with biological entities spanning 9 categories (molecular profile, organism, chemical, functional term, phrase or reference, disease, phenotype or trait, structural feature, cell line, cell type or tissue, gene, protein or microRNA, sequence feature) extracted from 133 datasets.

Click the + buttons to view associations for PPP3R1 from the datasets below.

If available, associations are ranked by standardized value

Harmonizome 3.0

PPP3R1 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 PPP3R1 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 PPP3R1 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 PPP3R1 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 RNA-seq	tissue samples with high or low expression of PPP3R1 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 PPP3R1 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 PPP3R1 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 PPP3R1 gene relative to other cell types and tissues from the BioGPS Human Cell Type and Tissue Gene Expression Profiles dataset.
	Carcinogenome Chemical Perturbation Carcinogenicity Signatures	small molecule perturbations changing expression of PPP3R1 gene from the Carcinogenome Chemical Perturbation Carcinogenicity Signatures dataset.
	CCLE Cell Line Gene CNV Profiles	cell lines with high or low copy number of PPP3R1 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 PPP3R1 gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
	CCLE Cell Line Gene Mutation Profiles	cell lines with PPP3R1 gene mutations from the CCLE Cell Line Gene Mutation Profiles dataset.
	CCLE Cell Line Proteomics	Cell lines associated with PPP3R1 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 PPP3R1 gene from the CHEA Transcription Factor Binding Site Profiles dataset.
	ChEA Transcription Factor Targets	transcription factors binding the promoter of PPP3R1 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 PPP3R1 gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets 2022 dataset.
	CM4AI KOLF21J CRISPRi Gene Perturbation Atlas	gene perturbations changing expression of PPP3R1 gene from the CM4AI KOLF21J CRISPRi Gene Perturbation Atlas dataset.
	CM4AI U2OS Cell Map Protein Localization Assemblies	assemblies containing PPP3R1 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 PPP3R1 gene from the CMAP Signatures of Differentially Expressed Genes for Small Molecules dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores	cellular components containing PPP3R1 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores 2025	cellular components containing PPP3R1 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores 2025 dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores	cellular components co-occuring with PPP3R1 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 PPP3R1 protein in abstracts of biomedical publications from the COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025 dataset.
	COSMIC Cell Line Gene CNV Profiles	cell lines with high or low copy number of PPP3R1 gene relative to other cell lines from the COSMIC Cell Line Gene CNV Profiles dataset.
	COSMIC Cell Line Gene Mutation Profiles	cell lines with PPP3R1 gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
	CTD Gene-Chemical Interactions	chemicals interacting with PPP3R1 gene/protein from the curated CTD Gene-Chemical Interactions dataset.
	CTD Gene-Disease Associations	diseases associated with PPP3R1 gene/protein from the curated CTD Gene-Disease Associations dataset.
	DeepCoverMOA Drug Mechanisms of Action	small molecule perturbations with high or low expression of PPP3R1 protein relative to other small molecule perturbations from the DeepCoverMOA Drug Mechanisms of Action dataset.
	DepMap CRISPR Gene Dependency	cell lines with fitness changed by PPP3R1 gene knockdown relative to other cell lines from the DepMap CRISPR Gene Dependency dataset.
	DGIdb Drug Targets 2026	interacting drugs for PPP3R1 protein from the DGIdb Drug Targets 2026 dataset.
	DISEASES Experimental Gene-Disease Association Evidence Scores 2025	diseases associated with PPP3R1 gene in GWAS datasets from the DISEASES Experimental Gene-Disease Assocation Evidence Scores 2025 dataset.
	DISEASES Text-mining Gene-Disease Association Evidence Scores	diseases co-occuring with PPP3R1 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 PPP3R1 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 PPP3R1 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.
	DisGeNET Gene-Phenotype Associations	phenotypes associated with PPP3R1 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Phenoptype Associations dataset.
	DrugBank Drug Targets	interacting drugs for PPP3R1 protein from the curated DrugBank Drug Targets dataset.
	ENCODE Histone Modification Site Profiles	histone modification site profiles with high histone modification abundance at PPP3R1 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 PPP3R1 gene from the ENCODE Transcription Factor Binding Site Profiles dataset.
	ENCODE Transcription Factor Targets	transcription factors binding the promoter of PPP3R1 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 PPP3R1 from the ESCAPE Omics Signatures of Genes and Proteins for Stem Cells dataset.
	GAD Gene-Disease Associations	diseases associated with PPP3R1 gene in GWAS and other genetic association datasets from the GAD Gene-Disease Associations dataset.