RGS12 Gene

HGNC Family	Regulators of G-protein signaling (RGS)
Name	regulator of G-protein signaling 12
Description	This gene encodes a member of the 'regulator of G protein signaling' (RGS) gene family. The encoded protein may function as a guanosine triphosphatase (GTPase)-activating protein as well as a transcriptional repressor. This protein may play a role in tumorigenesis. Multiple transcript variants encoding distinct isoforms have been identified for this gene. Other alternative splice variants have been described but their biological nature has not been determined. [provided by RefSeq, Jul 2008]
Summary	{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nRGS12, a member of the regulators of G protein signaling family, was first cloned from rat and human tissues and is distinguished by its unusually large size and complex modular structure. Its predicted polypeptide contains not only a conserved RGS domain but also additional regions—including coiled‐coil and rhophilin‐like domains—that are likely to mediate interactions with ras‐like G-proteins and other signaling molecules, consistent with its tissue‐selective high expression in brain and lung."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nRGS12 plays a critical role in bone remodeling and inflammatory processes. It is essential for RANKL-induced intracellular Ca²⁺ oscillations that drive osteoclast differentiation—a key step in bone resorption—and, in models of periodontitis, deletion of RGS12 in hematopoietic cells markedly reduces osteoclast formation, inflammatory cytokine production, and subsequent alveolar bone loss."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn diverse cancer contexts, RGS12 exhibits potent tumor suppressor functions. In prostate cancer, reduced RGS12 expression correlates with increased tumor aggressiveness, likely through its negative regulation of AKT signaling and the oncogene MNX1. Similarly, in osteosarcoma, loss of RGS12 promotes tumor progression and metastasis via the GNA12/13-RhoA-YAP-TEAD1 axis that upregulates the osteosarcoma marker Ezrin. In oral squamous cell carcinoma, RGS12 associates with PTEN via its PDZ domain, promoting PTEN phosphorylation and SUMOylation to inactivate the AKT/mTOR pathway and thereby restrain cell proliferation and migration. Beyond cancer cell–intrinsic effects, RGS12 in tumor-associated macrophages enhances antitumor immunity by driving these cells toward an M1 phenotype through MYCBP2-mediated degradation of the cilia protein KIF2A."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "4", "end_ref": "7"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nRGS12 additionally fine-tunes receptor-mediated signal transduction. It regulates the activity and desensitization of TRPC4 channels through the combined actions of its RGS and GoLoco domains, highlighting its role in modulating Gi/o protein-dependent signaling events. In the kidney, a carboxy-terminal splice variant of RGS12 interacts with the PDZ scaffold protein NHERF1 to modulate the hormone-sensitive NPT2A-mediated phosphate uptake, thereby contributing to the homeostatic regulation of serum phosphate levels."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "8"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "B E Snow, L Antonio, S Suggs, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Molecular cloning and expression analysis of rat Rgs12 and Rgs14."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochem Biophys Res Commun (1997)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1006/bbrc.1997.6537"}], "href": "https://doi.org/10.1006/bbrc.1997.6537"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "9168931"}], "href": "https://pubmed.ncbi.nlm.nih.gov/9168931"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Shuying Yang, Yi-Ping Li "}, {"type": "b", "children": [{"type": "t", "text": "RGS12 is essential for RANKL-evoked signaling for terminal differentiation of osteoclasts in vitro."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Bone Miner Res (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1359/jbmr.061007"}], "href": "https://doi.org/10.1359/jbmr.061007"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17042716"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17042716"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "G Yuan, C Fu, S T Yang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "RGS12 Drives Macrophage Activation and Osteoclastogenesis in Periodontitis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Dent Res (2022)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1177/00220345211045303"}], "href": "https://doi.org/10.1177/00220345211045303"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "34796776"}], "href": "https://pubmed.ncbi.nlm.nih.gov/34796776"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Yongquan Wang, Jianghua Wang, Li Zhang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "RGS12 Is a Novel Tumor-Suppressor Gene in African American Prostate Cancer That Represses AKT and MNX1 Expression."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cancer Res (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1158/0008-5472.CAN-17-0669"}], "href": "https://doi.org/10.1158/0008-5472.CAN-17-0669"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "28611045"}], "href": "https://pubmed.ncbi.nlm.nih.gov/28611045"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Yang Li, Min Liu, Shuting Yang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "RGS12 is a novel tumor suppressor in osteosarcoma that inhibits YAP-TEAD1-Ezrin signaling."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Oncogene (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s41388-020-01599-z"}], "href": "https://doi.org/10.1038/s41388-020-01599-z"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "33686240"}], "href": "https://pubmed.ncbi.nlm.nih.gov/33686240"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "C Fu, G Yuan, S T Yang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "RGS12 Represses Oral Cancer via the Phosphorylation and SUMOylation of PTEN."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Dent Res (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1177/0022034520972095"}], "href": "https://doi.org/10.1177/0022034520972095"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "33198557"}], "href": "https://pubmed.ncbi.nlm.nih.gov/33198557"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Gongsheng Yuan, Shuting Yang, Shuying Yang "}, {"type": "b", "children": [{"type": "t", "text": "RGS12 represses oral squamous cell carcinoma by driving M1 polarization of tumor-associated macrophages via controlling ciliary MYCBP2/KIF2A signaling."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Int J Oral Sci (2023)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s41368-023-00216-5"}], "href": "https://doi.org/10.1038/s41368-023-00216-5"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "36797232"}], "href": "https://pubmed.ncbi.nlm.nih.gov/36797232"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Jae-Pyo Jeon, Dhananjay P Thakur, Jin-Bin Tian, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Regulator of G-protein signalling and GoLoco proteins suppress TRPC4 channel function via acting at Gαi/o."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochem J (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1042/BCJ20160214"}], "href": "https://doi.org/10.1042/BCJ20160214"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26987813"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26987813"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "W Bruce Sneddon, Suneela Ramineni, G Emme Van Doorn, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Distinct and overlapping RGS14 and RGS12 actions regulate NPT2A-mediated phosphate transport."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochem Biophys Res Commun (2024)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.bbrc.2024.150700"}], "href": "https://doi.org/10.1016/j.bbrc.2024.150700"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "39293332"}], "href": "https://pubmed.ncbi.nlm.nih.gov/39293332"}]}]}]}
Proteins	RGS12_HUMAN
NCBI Gene ID	6002
API
Download Associations
Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

RGS12 has 5,516 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 120 datasets.

Click the + buttons to view associations for RGS12 from the datasets below.

If available, associations are ranked by standardized value

Harmonizome 3.0

RGS12 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 RGS12 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 RGS12 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 RGS12 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 RGS12 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 RGS12 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 RGS12 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 RGS12 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 RGS12 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 RGS12 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 RGS12 gene from the Carcinogenome Chemical Perturbation Carcinogenicity Signatures dataset.
	CCLE Cell Line Gene CNV Profiles	cell lines with high or low copy number of RGS12 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 RGS12 gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
	CellMarker Gene-Cell Type Associations	cell types associated with RGS12 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 RGS12 gene from the CHEA Transcription Factor Binding Site Profiles dataset.
	ChEA Transcription Factor Targets	transcription factors binding the promoter of RGS12 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 RGS12 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 RGS12 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 RGS12 gene from the CMAP Signatures of Differentially Expressed Genes for Small Molecules dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores	cellular components containing RGS12 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores 2025	cellular components containing RGS12 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores 2025 dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores	cellular components co-occuring with RGS12 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 RGS12 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 RGS12 gene relative to other cell lines from the COSMIC Cell Line Gene CNV Profiles dataset.
	COSMIC Cell Line Gene Mutation Profiles	cell lines with RGS12 gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
	CTD Gene-Chemical Interactions	chemicals interacting with RGS12 gene/protein from the curated CTD Gene-Chemical Interactions dataset.
	CTD Gene-Disease Associations	diseases associated with RGS12 gene/protein from the curated CTD Gene-Disease Associations dataset.
	dbGAP Gene-Trait Associations	traits associated with RGS12 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 RGS12 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 RGS12 gene knockdown relative to other cell lines from the DepMap CRISPR Gene Dependency dataset.
	DISEASES Experimental Gene-Disease Association Evidence Scores 2025	diseases associated with RGS12 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 RGS12 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 RGS12 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 RGS12 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.
	DisGeNET Gene-Phenotype Associations	phenotypes associated with RGS12 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 RGS12 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 RGS12 gene from the ENCODE Transcription Factor Binding Site Profiles dataset.
	ENCODE Transcription Factor Targets	transcription factors binding the promoter of RGS12 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 RGS12 from the ESCAPE Omics Signatures of Genes and Proteins for Stem Cells dataset.
	GAD Gene-Disease Associations	diseases associated with RGS12 gene in GWAS and other genetic association datasets from the GAD Gene-Disease Associations dataset.
	GAD High Level Gene-Disease Associations	diseases associated with RGS12 gene in GWAS and other genetic association datasets from the GAD High Level Gene-Disease Associations dataset.