RGS3 Gene

HGNC Family	C2 domain containing, Regulators of G-protein signaling (RGS)
Name	regulator of G-protein signaling 3
Description	This gene encodes a member of the regulator of G-protein signaling (RGS) family. This protein is a GTPase-activating protein that inhibits G-protein-mediated signal transduction. Alternative splicing and the use of alternative promoters results in multiple transcript variants encoding different isoforms. Long isoforms are largely cytosolic and plasma membrane-associated with a function in Wnt signaling and in the epithelial mesenchymal transition, while shorter N-terminally-truncated isoforms can be nuclear. [provided by RefSeq, Jan 2013]
Summary	{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nRGS3 is a multifunctional regulator of G‐protein signaling that accelerates GTP hydrolysis by binding to activated Gα subunits, thereby terminating receptor–effector signaling. In its canonical role, RGS3 modulates the amplitude and kinetics of GPCR‐mediated responses—inhibition of inositol trisphosphate generation and Ca2+ mobilization in response to receptor activation has been demonstrated. Moreover, its GAP function is regulated by phosphorylation‐dependent binding of 14–3–3 proteins, which induces conformational changes that limit its availability for interacting with Gα subunits. These mechanisms are highlighted by structural and biochemical studies showing how the RGS domain is altered to modulate signaling efficacy."}, {"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": "\nBeyond its classical GAP activity, RGS3 participates in non‐canonical signaling pathways by interacting with proteins outside the realm of heterotrimeric G-protein cascades. Different isoforms, including PDZ-containing variants, localize predominantly in the cytosol and integrate with developmental and differentiation pathways. For example, RGS3 and its longer isoform (RGS3L) function as molecular switches in neural progenitor cells—affecting the balance between Rac1 and RhoA activation and associating with partners such as KIF20A to influence the mode of cell division. In addition, RGS3 can bind to Smad transcription factors, thereby interfering with TGFβ-induced gene transcription and myofibroblast differentiation, and modulate Wnt/β-catenin signaling through interactions that impinge on GSK3β activity. Such interactions not only underscore its role as a signal integrator but also support its emerging status as a marker in non-embryonic tissues, including in follicular cells that predict oocyte competence."}, {"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": "\nIn disease contexts, aberrant expression or regulation of RGS3 has been linked to cancer, cardiovascular remodeling, and therapeutic responsiveness. In tumorigenesis, RGS3 has been implicated as a mediator of apoptosis—for instance, overexpression in certain leukemic cells promotes cell death via downregulation of ERK signaling. Conversely, oncogenic microRNAs such as miR-126-3p or miR-25 target RGS3 in triple-negative breast cancer and non-small-cell lung cancer, respectively, thereby influencing tumor cell proliferation, migration, invasion, and resistance to apoptosis. In addition, dysregulated levels of RGS3 have been associated with gastric and hepatocellular cancers via ceRNA networks, and its modulation affects KRAS GTPase activity—a finding that may explain sensitivity to novel KRAS inhibitors. Finally, genetic variants in RGS3 have been linked to changes in cardiac structure and function and overexpression in the heart attenuates hypertrophic remodeling by inhibiting MEK-ERK signaling."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "12", "end_ref": "19"}]}, {"type": "t", "text": ""}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Jiaxin Niu, Astrid Scheschonka, Kirk M Druey, et al. "}, {"type": "b", "children": [{"type": "t", "text": "RGS3 interacts with 14-3-3 via the N-terminal region distinct from the RGS (regulator of G-protein signalling) domain."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochem J (2002)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1042/BJ20020390"}], "href": "https://doi.org/10.1042/BJ20020390"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "11985497"}], "href": "https://pubmed.ncbi.nlm.nih.gov/11985497"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Stephen C Tovey, Gary B Willars "}, {"type": "b", "children": [{"type": "t", "text": "Single-cell imaging of intracellular Ca2+ and phospholipase C activity reveals that RGS 2, 3, and 4 differentially regulate signaling via the Galphaq/11-linked muscarinic M3 receptor."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Pharmacol (2004)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1124/mol.104.005827"}], "href": "https://doi.org/10.1124/mol.104.005827"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15383626"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15383626"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Carmen Toro-Castillo, Ashish Thapliyal, Hector Gonzalez-Ochoa, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Muscarinic modulation of Cav2.3 (R-type) calcium channels is antagonized by RGS3 and RGS3T."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Am J Physiol Cell Physiol (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1152/ajpcell.00219.2006"}], "href": "https://doi.org/10.1152/ajpcell.00219.2006"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16855219"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16855219"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Lenka Rezabkova, Evzen Boura, Petr Herman, et al. "}, {"type": "b", "children": [{"type": "t", "text": "14-3-3 protein interacts with and affects the structure of RGS domain of regulator of G protein signaling 3 (RGS3)."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Struct Biol (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.jsb.2010.03.009"}], "href": "https://doi.org/10.1016/j.jsb.2010.03.009"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20347994"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20347994"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Lenka Rezabkova, Petr Man, Petr Novak, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Structural basis for the 14-3-3 protein-dependent inhibition of the regulator of G protein signaling 3 (RGS3) function."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M111.273573"}], "href": "https://doi.org/10.1074/jbc.M111.273573"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22027839"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22027839"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Andreas Vogt, Susanne Lutz, Ulrich Rümenapp, et al. 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"}, {"type": "b", "children": [{"type": "t", "text": "C2PA is a nuclear protein implicated in the heat shock response."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Cell Biochem (2002)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/jcb.10279"}], "href": "https://doi.org/10.1002/jcb.10279"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12210723"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12210723"}]}, {"type": "r", "ref": 12, "children": [{"type": "t", "text": "Hiroshi Nishiura, Hideo Nonaka, Ivette S Revollo, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Pro- and anti-apoptotic dual functions of the C5a receptor: involvement of regulator of G protein signaling 3 and extracellular signal-regulated kinase."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Lab Invest (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/labinvest.2009.27"}], "href": "https://doi.org/10.1038/labinvest.2009.27"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19333232"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19333232"}]}, {"type": "r", "ref": 13, "children": [{"type": "t", "text": "Zhize Chen, Yang Wu, Qingtao Meng, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Elevated microRNA-25 inhibits cell apoptosis in lung cancer by targeting RGS3."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "In Vitro Cell Dev Biol Anim (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s11626-015-9947-2"}], "href": "https://doi.org/10.1007/s11626-015-9947-2"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26416661"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26416661"}]}, {"type": "r", "ref": 14, "children": [{"type": "t", "text": "Junqing Wang, Yunyun Zhou, Xiaochun Fei, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Regulator of G-protein signaling 3 targeted by miR-126 correlates with poor prognosis in gastric cancer patients."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Anticancer Drugs (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1097/CAD.0000000000000446"}], "href": "https://doi.org/10.1097/CAD.0000000000000446"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27754994"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27754994"}]}, {"type": "r", "ref": 15, "children": [{"type": "t", "text": "Zhipeng Hong, Chengye Hong, Bo Ma, et al. "}, {"type": "b", "children": [{"type": "t", "text": "MicroRNA‑126‑3p inhibits the proliferation, migration, invasion, and angiogenesis of triple‑negative breast cancer cells by targeting RGS3."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Oncol Rep (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.3892/or.2019.7251"}], "href": "https://doi.org/10.3892/or.2019.7251"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31364749"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31364749"}]}, {"type": "r", "ref": 16, "children": [{"type": "t", "text": "Akram Yazdani, Azam Yazdani, Raúl Méndez Giráldez, et al. 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"}, {"type": "b", "children": [{"type": "t", "text": "Pseudogene UBE2MP1 derived transcript enhances "}, {"type": "a", "children": [{"type": "t", "text": "i"}], "href": "i"}, {"type": "t", "text": "in vitro"}, {"type": "a", "children": [{"type": "t", "text": "/i"}], "href": "/i"}, {"type": "t", "text": " cell proliferation and apoptosis resistance of hepatocellular carcinoma cells through miR-145-5p/RGS3 axis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Aging (Albany NY) (2022)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.18632/aging.204319"}], "href": "https://doi.org/10.18632/aging.204319"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "36214767"}], "href": "https://pubmed.ncbi.nlm.nih.gov/36214767"}]}, {"type": "r", "ref": 19, "children": [{"type": "t", "text": "Wei Li, Xianke Si, Jiahua Yang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Regulator of G-protein signalling 3 and its regulator microRNA-133a mediate cell proliferation in gastric cancer."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Arab J Gastroenterol (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.ajg.2020.07.011"}], "href": "https://doi.org/10.1016/j.ajg.2020.07.011"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "32928707"}], "href": "https://pubmed.ncbi.nlm.nih.gov/32928707"}]}]}]}
Synonyms	C2PA
Proteins	RGS3_HUMAN
NCBI Gene ID	5998
API
Download Associations
Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

RGS3 has 6,368 functional associations with biological entities spanning 9 categories (molecular profile, organism, functional term, phrase or reference, chemical, disease, phenotype or trait, structural feature, cell line, cell type or tissue, gene, protein or microRNA, sequence feature) extracted from 125 datasets.

Click the + buttons to view associations for RGS3 from the datasets below.

If available, associations are ranked by standardized value

Harmonizome 3.0

RGS3 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 RGS3 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 RGS3 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 RGS3 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 RGS3 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 RGS3 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 RGS3 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 RGS3 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 RGS3 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 RGS3 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 RGS3 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 RGS3 gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
	CCLE Cell Line Proteomics	Cell lines associated with RGS3 protein from the CCLE Cell Line Proteomics dataset.
	CellMarker Gene-Cell Type Associations	cell types associated with RGS3 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 RGS3 gene from the CHEA Transcription Factor Binding Site Profiles dataset.
	ChEA Transcription Factor Targets	transcription factors binding the promoter of RGS3 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 RGS3 gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets 2022 dataset.
	CM4AI U2OS Cell Map Protein Localization Assemblies	assemblies containing RGS3 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 RGS3 gene from the CMAP Signatures of Differentially Expressed Genes for Small Molecules dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores	cellular components containing RGS3 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset.
	COMPARTMENTS Experimental Protein Localization Evidence Scores 2025	cellular components containing RGS3 protein in low- or high-throughput protein localization assays from the COMPARTMENTS Experimental Protein Localization Evidence Scores 2025 dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores	cellular components co-occuring with RGS3 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 RGS3 protein in abstracts of biomedical publications from the COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025 dataset.
	COSMIC Cell Line Gene Mutation Profiles	cell lines with RGS3 gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
	CTD Gene-Chemical Interactions	chemicals interacting with RGS3 gene/protein from the curated CTD Gene-Chemical Interactions dataset.
	CTD Gene-Disease Associations	diseases associated with RGS3 gene/protein from the curated CTD Gene-Disease Associations dataset.
	DeepCoverMOA Drug Mechanisms of Action	small molecule perturbations with high or low expression of RGS3 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 RGS3 gene knockdown relative to other cell lines from the DepMap CRISPR Gene Dependency dataset.
	DISEASES Experimental Gene-Disease Association Evidence Scores	diseases associated with RGS3 gene in GWAS datasets from the DISEASES Experimental Gene-Disease Assocation Evidence Scores dataset.
	DISEASES Text-mining Gene-Disease Association Evidence Scores	diseases co-occuring with RGS3 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 RGS3 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 RGS3 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.
	DisGeNET Gene-Phenotype Associations	phenotypes associated with RGS3 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 RGS3 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 RGS3 gene from the ENCODE Transcription Factor Binding Site Profiles dataset.
	ENCODE Transcription Factor Targets	transcription factors binding the promoter of RGS3 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 RGS3 from the ESCAPE Omics Signatures of Genes and Proteins for Stem Cells dataset.
	GAD Gene-Disease Associations	diseases associated with RGS3 gene in GWAS and other genetic association datasets from the GAD Gene-Disease Associations dataset.
	GAD High Level Gene-Disease Associations	diseases associated with RGS3 gene in GWAS and other genetic association datasets from the GAD High Level Gene-Disease Associations dataset.
	GDSC Cell Line Gene Expression Profiles	cell lines with high or low expression of RGS3 gene relative to other cell lines from the GDSC Cell Line Gene Expression Profiles dataset.
	GeneRIF Biological Term Annotations	biological terms co-occuring with RGS3 gene in literature-supported statements describing functions of genes from the GeneRIF Biological Term Annotations dataset.