PPP2R3C Gene

HGNC Family	Protein phosphatase 2 regulatory subunits (PPP2R)
Name	protein phosphatase 2, regulatory subunit B'', gamma
Description	This gene encodes a regulatory subunit of the serine/threonine phosphatase, protein phosphatase 2. This protein is localized to both nuclear and cytoplasmic regions depending on cell cycle phase. Homozygous conditional knockout mice for this gene exhibit reduced numbers and impaired proliferation of immune system B cells. This protein may regulate the expression of the P-glycoprotein ATP-binding cassette transporter through its phosphatase activity. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Feb 2015]
Summary	{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nPPP2R3C functions as a regulatory subunit of serine/threonine phosphatases, and one study referring to its isoform known as G5PR shows that it is upregulated in activated B cells. In this context, G5PR suppresses late‐phase JNK phosphorylation, thereby rescuing B cells—particularly the B-1a subset—from activation-induced cell death and influencing both affinity maturation and the selection of self-reactive B cell clones."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn cancer cells, PPP2R3C (in complex with PP5) has been demonstrated to dephosphorylate key sites on the multidrug resistance protein P-glycoprotein (P-gp/ABCB1). This dephosphorylation leads to a downregulation of P-gp expression and function, resulting in increased sensitivity to chemotherapeutics such as vincristine and doxorubicin."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nGenetic studies have revealed that PPP2R3C is crucial for proper gonadal development. Homozygous variants in this gene cause a syndromic form of 46,XY complete gonadal dysgenesis characterized by impaired testis formation, decreased SOX9-phosphorylation, and extragonadal anomalies, while heterozygous variants are associated with abnormal sperm morphology and reduced fertility. These findings underscore its essential role in the early signaling cascades governing sex determination and spermatogenesis."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "3", "end_ref": "5"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond its roles in cell survival and gonadal development, PPP2R3C localizes to distal centrioles where it forms functional partnerships with centriolar proteins such as CEP350 and FOP. In this centrosomal compartment, PPP2R3C acts to counterbalance the kinase activity of MAP3K1, thereby modulating basal and stress-induced JNK signaling. Disruption of this kinase–phosphatase equilibrium has been implicated in the pathophysiology of congenital disorders, including those affecting gonadal development."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Masahiro Kitabatake, Teppei Toda, Kazuhiko Kuwahara, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Transgenic overexpression of G5PR that is normally augmented in centrocytes impairs the enrichment of high-affinity antigen-specific B cells, increases peritoneal B-1a cells, and induces autoimmunity in aged female mice."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Immunol (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.4049/jimmunol.1102774"}], "href": "https://doi.org/10.4049/jimmunol.1102774"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22753944"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22753944"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Kazuhiro Katayama, Miho Yamaguchi, Kohji Noguchi, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Protein phosphatase complex PP5/PPP2R3C dephosphorylates P-glycoprotein/ABCB1 and down-regulates the expression and function."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cancer Lett (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.canlet.2013.12.007"}], "href": "https://doi.org/10.1016/j.canlet.2013.12.007"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24333728"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24333728"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Tulay Guran, Gozde Yesil, Serap Turan, et al. "}, {"type": "b", "children": [{"type": "t", "text": "PPP2R3C gene variants cause syndromic 46,XY gonadal dysgenesis and impaired spermatogenesis in humans."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Eur J Endocrinol (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1530/EJE-19-0067"}], "href": "https://doi.org/10.1530/EJE-19-0067"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "30893644"}], "href": "https://pubmed.ncbi.nlm.nih.gov/30893644"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Dilek Cicek, Nick Warr, Gozde Yesil, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Broad-spectrum XX and XY gonadal dysgenesis in patients with a homozygous L193S variant in PPP2R3C."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Eur J Endocrinol (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1530/EJE-21-0910"}], "href": "https://doi.org/10.1530/EJE-21-0910"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "34714774"}], "href": "https://pubmed.ncbi.nlm.nih.gov/34714774"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Umut Altunoglu, Esra Börklü, Anju Shukla, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Expanding the spectrum of syndromic PPP2R3C-related XY gonadal dysgenesis to XX gonadal dysgenesis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Clin Genet (2022)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1111/cge.14086"}], "href": "https://doi.org/10.1111/cge.14086"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "34750818"}], "href": "https://pubmed.ncbi.nlm.nih.gov/34750818"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Anil Kumar Ganga, Lauren K Sweeney, Armando Rubio Ramos, et al. "}, {"type": "b", "children": [{"type": "t", "text": "A disease-associated PPP2R3C-MAP3K1 phospho-regulatory module controls centrosome function."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Curr Biol (2024)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.cub.2024.08.058"}], "href": "https://doi.org/10.1016/j.cub.2024.08.058"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "39317195"}], "href": "https://pubmed.ncbi.nlm.nih.gov/39317195"}]}]}]}
Synonyms	G4-1, G5PR, C14ORF10
Proteins	P2R3C_HUMAN
NCBI Gene ID	55012
API
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Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

PPP2R3C has 6,082 functional associations with biological entities spanning 9 categories (molecular profile, organism, disease, phenotype or trait, functional term, phrase or reference, chemical, structural feature, cell line, cell type or tissue, gene, protein or microRNA, sequence feature) extracted from 109 datasets.

Click the + buttons to view associations for PPP2R3C from the datasets below.

If available, associations are ranked by standardized value

Harmonizome 3.0

PPP2R3C 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 PPP2R3C 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 PPP2R3C 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 PPP2R3C 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 PPP2R3C 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 PPP2R3C 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 PPP2R3C 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 PPP2R3C 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 PPP2R3C 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 PPP2R3C gene relative to other cell types and tissues from the BioGPS Mouse Cell Type and Tissue Gene Expression Profiles dataset.
	CCLE Cell Line Gene CNV Profiles	cell lines with high or low copy number of PPP2R3C 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 PPP2R3C gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
	CCLE Cell Line Proteomics	Cell lines associated with PPP2R3C protein from the CCLE Cell Line Proteomics dataset.
	CellMarker Gene-Cell Type Associations	cell types associated with PPP2R3C gene from the CellMarker Gene-Cell Type Associations dataset.
	ChEA Transcription Factor Binding Site Profiles	transcription factor binding site profiles with transcription factor binding evidence at the promoter of PPP2R3C gene from the CHEA Transcription Factor Binding Site Profiles dataset.
	ChEA Transcription Factor Targets	transcription factors binding the promoter of PPP2R3C 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 PPP2R3C 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 PPP2R3C gene from the curated ClinVar Gene-Phenotype Associations 2025 dataset.
	CM4AI U2OS Cell Map Protein Localization Assemblies	assemblies containing PPP2R3C 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 PPP2R3C gene from the CMAP Signatures of Differentially Expressed Genes for Small Molecules dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores	cellular components containing PPP2R3C protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores 2025	cellular components containing PPP2R3C protein from the COMPARTMENTS Curated Protein Localization Evidence Scores 2025 dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores	cellular components co-occuring with PPP2R3C 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 PPP2R3C 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 PPP2R3C gene relative to other cell lines from the COSMIC Cell Line Gene CNV Profiles dataset.
	COSMIC Cell Line Gene Mutation Profiles	cell lines with PPP2R3C gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
	CTD Gene-Disease Associations	diseases associated with PPP2R3C gene/protein from the curated CTD Gene-Disease Associations dataset.
	dbGAP Gene-Trait Associations	traits associated with PPP2R3C gene in GWAS and other genetic association datasets from the dbGAP Gene-Trait Associations dataset.
	DeepCoverMOA Drug Mechanisms of Action	small molecule perturbations with high or low expression of PPP2R3C protein relative to other small molecule perturbations from the DeepCoverMOA Drug Mechanisms of Action dataset.
	DISEASES Curated Gene-Disease Association Evidence Scores 2025	diseases involving PPP2R3C gene from the DISEASES Curated Gene-Disease Association Evidence Scores 2025 dataset.
	DISEASES Experimental Gene-Disease Association Evidence Scores 2025	diseases associated with PPP2R3C gene in GWAS datasets from the DISEASES Experimental Gene-Disease Assocation Evidence Scores 2025 dataset.
	DISEASES Text-mining Gene-Disease Association Evidence Scores 2025	diseases co-occuring with PPP2R3C 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 PPP2R3C gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.
	DisGeNET Gene-Phenotype Associations	phenotypes associated with PPP2R3C gene in GWAS and other genetic association datasets from the DisGeNET Gene-Phenoptype Associations dataset.
	ENCODE Histone Modification Site Profiles	histone modification site profiles with high histone modification abundance at PPP2R3C 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 PPP2R3C gene from the ENCODE Transcription Factor Binding Site Profiles dataset.
	ENCODE Transcription Factor Targets	transcription factors binding the promoter of PPP2R3C 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 PPP2R3C from the ESCAPE Omics Signatures of Genes and Proteins for Stem Cells dataset.
	GAD Gene-Disease Associations	diseases associated with PPP2R3C gene in GWAS and other genetic association datasets from the GAD Gene-Disease Associations dataset.
	GeneRIF Biological Term Annotations	biological terms co-occuring with PPP2R3C gene in literature-supported statements describing functions of genes from the GeneRIF Biological Term Annotations dataset.
	GeneSigDB Published Gene Signatures	PubMedIDs of publications reporting gene signatures containing PPP2R3C from the GeneSigDB Published Gene Signatures dataset.