ESRRG Gene

HGNC Family	Zinc fingers
Name	estrogen-related receptor gamma
Description	This gene encodes a member of the estrogen receptor-related receptor (ESRR) family, which belongs to the nuclear hormone receptor superfamily. All members of the ESRR family share an almost identical DNA binding domain, which is composed of two C4-type zinc finger motifs. The ESRR members are orphan nuclear receptors; they bind to the estrogen response element and steroidogenic factor 1 response element, and activate genes controlled by both response elements in the absence of any ligands. The ESRR family is closely related to the estrogen receptor (ER) family. They share target genes, co-regulators and promoters, and by targeting the same set of genes, the ESRRs seem to interfere with the ER-mediated estrogen response in various ways. It has been reported that the family member encoded by this gene functions as a transcriptional activator of DNA cytosine-5-methyltransferases 1 (Dnmt1) expression by direct binding to its response elements in the DNMT1 promoters, modulates cell proliferation and estrogen signaling in breast cancer, and negatively regulates bone morphogenetic protein 2-induced osteoblast differentiation and bone formation. Multiple alternatively spliced transcript variants have been identified, which mainly differ at the 5' end and some of which encode protein isoforms differing in the N-terminal region. [provided by RefSeq, Aug 2011]
Summary	{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n Estrogen‐related receptor gamma (ESRRG) is emerging as a multifaceted, constitutively active nuclear receptor whose intrinsic activity is largely “hard‐wired” into its structure. Structural analyses have shown that its ligand‐binding domain adopts an active conformation even in the absence of a conventional ligand, thereby enabling robust coactivator recruitment and transcriptional activation."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": " In parallel, ESRRG is a sensitive target for endocrine-disrupting chemicals: for instance, bisphenol A binds with high affinity to ESRRG, preserving its constitutive activity and potentially contributing to alterations in developmental epigenetic programming in the brain."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": " Beyond its structural and ligand‐interaction properties, ESRRG plays a central role in metabolic regulation. In the heart, it governs the perinatal transition to oxidative metabolism that is vital for proper myocardial function"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": ", while in pancreatic β cells, ESRRG drives the transcriptional network that supports mitochondrial oxidative phosphorylation and ATP production necessary for glucose-responsive insulin secretion and β cell maturation."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": " In addition, transient induction of ESRRG is implicated in the early metabolic reprogramming required during induced pluripotent stem cell generation."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": " Collectively, these findings define ESRRG as a pivotal mediator linking ligand-independent transcriptional activation with the control of energy metabolism, neurodevelopment, and cell-fate transitions—highlighting its potential as a therapeutic target in metabolic diseases and in mitigating the adverse effects of endocrine disruptors.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Holger Greschik, Jean-Marie Wurtz, Sarah Sanglier, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Structural and functional evidence for ligand-independent transcriptional activation by the estrogen-related receptor 3."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Cell (2002)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/s1097-2765(02)00444-6"}], "href": "https://doi.org/10.1016/s1097-2765(02"}, {"type": "t", "text": "00444-6) PMID: "}, {"type": "a", "children": [{"type": "t", "text": "11864604"}], "href": "https://pubmed.ncbi.nlm.nih.gov/11864604"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Holger Greschik, Ralf Flaig, Jean-Paul Renaud, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Structural basis for the deactivation of the estrogen-related receptor gamma by diethylstilbestrol or 4-hydroxytamoxifen and determinants of selectivity."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2004)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M402195200"}], "href": "https://doi.org/10.1074/jbc.M402195200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15161930"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15161930"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Ayami Matsushima, Yoshimitsu Kakuta, Takamasa Teramoto, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Structural evidence for endocrine disruptor bisphenol A binding to human nuclear receptor ERR gamma."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biochem (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1093/jb/mvm158"}], "href": "https://doi.org/10.1093/jb/mvm158"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17761695"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17761695"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Marija Kundakovic, Kathryn Gudsnuk, Becca Franks, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Sex-specific epigenetic disruption and behavioral changes following low-dose in utero bisphenol A exposure."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Proc Natl Acad Sci U S A (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1073/pnas.1214056110"}], "href": "https://doi.org/10.1073/pnas.1214056110"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23716699"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23716699"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Shamina M Rangwala, Xiaomei Wang, Jennifer A Calvo, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Estrogen-related receptor gamma is a key regulator of muscle mitochondrial activity and oxidative capacity."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M110.125401"}], "href": "https://doi.org/10.1074/jbc.M110.125401"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20418374"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20418374"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Eiji Yoshihara, Zong Wei, Chun Shi Lin, et al. "}, {"type": "b", "children": [{"type": "t", "text": "ERRγ Is Required for the Metabolic Maturation of Therapeutically Functional Glucose-Responsive β Cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Metab (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.cmet.2016.03.005"}], "href": "https://doi.org/10.1016/j.cmet.2016.03.005"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27076077"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27076077"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Yasuyuki S Kida, Teruhisa Kawamura, Zong Wei, et al. "}, {"type": "b", "children": [{"type": "t", "text": "ERRs Mediate a Metabolic Switch Required for Somatic Cell Reprogramming to Pluripotency."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Stem Cell (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.stem.2015.03.001"}], "href": "https://doi.org/10.1016/j.stem.2015.03.001"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25865501"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25865501"}]}]}]}
Synonyms	ERR3, NR3B3, ERRg, ERRGAMMA, ERR-gamma
Proteins	ERR3_HUMAN
NCBI Gene ID	2104
API
Download Associations
Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

ESRRG has 6,245 functional associations with biological entities spanning 8 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) extracted from 121 datasets.

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

If available, associations are ranked by standardized value

Harmonizome 3.0

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