ESR2 Gene

HGNC Family	Zinc fingers
Name	estrogen receptor 2 (ER beta)
Description	This gene encodes a member of the family of estrogen receptors and superfamily of nuclear receptor transcription factors. The gene product contains an N-terminal DNA binding domain and C-terminal ligand binding domain and is localized to the nucleus, cytoplasm, and mitochondria. Upon binding to 17beta-estradiol or related ligands, the encoded protein forms homo- or hetero-dimers that interact with specific DNA sequences to activate transcription. Some isoforms dominantly inhibit the activity of other estrogen receptor family members. Several alternatively spliced transcript variants of this gene have been described, but the full-length nature of some of these variants has not been fully characterized. [provided by RefSeq, Jul 2008]
Summary	{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n Estrogen receptor beta (ERβ, also known as ESR2) functions as a key modulator of estrogen signaling in diverse tissues by often opposing the classical actions mediated by estrogen receptor alpha (ERα). In the brain, ERβ displays a region‐selective nuclear and extranuclear distribution that is consistent with roles in modulating neural circuits and behavior."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": " In breast cancer cells, the activation of ERβ can counteract the proliferative, tumor‐promoting effects of ERα by repressing genes involved in cell cycle progression—such as c‑myc, cyclin D1, and cyclin A—and by upregulating cell cycle inhibitors, thereby inducing cell cycle arrest and suppressing tumorigenesis."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "2", "end_ref": "4"}]}, {"type": "t", "text": " In the vascular system, ERβ plays an indispensable role in modulating vascular tone; for instance, its deficiency in vascular smooth muscle cells leads to abnormal ion channel function, enhanced vasoconstriction, and the development of sustained hypertension."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": " In bone, ERβ acts as a physiological “brake” on ERα‐mediated gene transcription and thus modulates estrogen-regulated functions by attenuating the stimulatory effects of ERα on target gene expression, an interaction that underscores the yin–yang relationship between the two receptors in skeletal homeostasis."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": " Furthermore, studies of ERβ isoforms reveal that although only the full-length ERβ1 is fully active, other isoforms can heterodimerize with ERβ1 to enhance its transactivation in a ligand-dependent manner, suggesting that the overall activity of ERβ is finely tuned by the relative expression of its variants."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Collectively, these findings indicate that ERβ/ESR2 serves as an inhibitory or modulatory counterpart to ERα in various estrogen-responsive tissues, thereby contributing to the fine regulation of cell proliferation, vascular function, bone metabolism, and neural signaling. The ability of ERβ-selective ligands to harness these distinct actions has considerable therapeutic implications in conditions such as breast cancer, cardiovascular disorders, and osteoporosis.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Sudha Warrier Mitra, Elena Hoskin, Joel Yudkovitz, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Immunolocalization of estrogen receptor beta in the mouse brain: comparison with estrogen receptor alpha."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Endocrinology (2003)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1210/en.2002-221069"}], "href": "https://doi.org/10.1210/en.2002-221069"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12697714"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12697714"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Sreenivasan Paruthiyil, Hema Parmar, Vaishali Kerekatte, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Estrogen receptor beta inhibits human breast cancer cell proliferation and tumor formation by causing a G2 cell cycle arrest."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cancer Res (2004)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1158/0008-5472.can-03-2446"}], "href": "https://doi.org/10.1158/0008-5472.can-03-2446"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "14729654"}], "href": "https://pubmed.ncbi.nlm.nih.gov/14729654"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Anders Ström, Johan Hartman, James S Foster, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Estrogen receptor beta inhibits 17beta-estradiol-stimulated proliferation of the breast cancer cell line T47D."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Proc Natl Acad Sci U S A (2004)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1073/pnas.0308319100"}], "href": "https://doi.org/10.1073/pnas.0308319100"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "14745018"}], "href": "https://pubmed.ncbi.nlm.nih.gov/14745018"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Meng-Min Liu, Chris Albanese, Carol M Anderson, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Opposing action of estrogen receptors alpha and beta on cyclin D1 gene expression."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2002)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M201829200"}], "href": "https://doi.org/10.1074/jbc.M201829200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "11986316"}], "href": "https://pubmed.ncbi.nlm.nih.gov/11986316"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Yan Zhu, Zhao Bian, Ping Lu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Abnormal vascular function and hypertension in mice deficient in estrogen receptor beta."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Science (2002)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1126/science.1065250"}], "href": "https://doi.org/10.1126/science.1065250"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "11799247"}], "href": "https://pubmed.ncbi.nlm.nih.gov/11799247"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Marie K Lindberg, Sofia Movérare, Stanko Skrtic, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Estrogen receptor (ER)-beta reduces ERalpha-regulated gene transcription, supporting a \"ying yang\" relationship between ERalpha and ERbeta in mice."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Endocrinol (2003)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1210/me.2002-0206"}], "href": "https://doi.org/10.1210/me.2002-0206"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12554748"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12554748"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Yuet-Kin Leung, Paul Mak, Sazzad Hassan, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Estrogen receptor (ER)-beta isoforms: a key to understanding ER-beta signaling."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Proc Natl Acad Sci U S A (2006)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1073/pnas.0605676103"}], "href": "https://doi.org/10.1073/pnas.0605676103"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16938840"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16938840"}]}]}]}
Synonyms	ESTRB, ESR-BETA, ER-BETA, ERB, NR3A2, ESRB
Proteins	ESR2_HUMAN
NCBI Gene ID	2100
API
Download Associations
Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

ESR2 has 13,297 functional associations with biological entities spanning 9 categories (molecular profile, organism, chemical, disease, phenotype or trait, functional term, phrase or reference, structural feature, cell line, cell type or tissue, gene, protein or microRNA, sequence feature) extracted from 130 datasets.

Click the + buttons to view associations for ESR2 from the datasets below.

If available, associations are ranked by standardized value

Harmonizome 3.0

ESR2 Gene

Functional Associations

Please acknowledge the Harmonizome in your publications by citing the following reference(s):

	Dataset	Summary
	Allen Brain Atlas Adult Mouse Brain Tissue Gene Expression Profiles	tissues with high or low expression of ESR2 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 ESR2 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 ESR2 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 ESR2 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 ESR2 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 ESR2 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 ESR2 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 ESR2 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 ESR2 gene from the Carcinogenome Chemical Perturbation Carcinogenicity Signatures dataset.
	CCLE Cell Line Gene CNV Profiles	cell lines with high or low copy number of ESR2 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 ESR2 gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
	CCLE Cell Line Gene Mutation Profiles	cell lines with ESR2 gene mutations from the CCLE Cell Line Gene Mutation Profiles dataset.
	CellMarker Gene-Cell Type Associations	cell types associated with ESR2 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 ESR2 gene from the CHEA Transcription Factor Binding Site Profiles dataset.
	ChEA Transcription Factor Targets	transcription factors binding the promoter of ESR2 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 ESR2 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 ESR2 gene from the curated ClinVar Gene-Phenotype Associations 2025 dataset.
	CMAP Signatures of Differentially Expressed Genes for Small Molecules	small molecule perturbations changing expression of ESR2 gene from the CMAP Signatures of Differentially Expressed Genes for Small Molecules dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores	cellular components containing ESR2 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores 2025	cellular components containing ESR2 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores 2025 dataset.
	COMPARTMENTS Experimental Protein Localization Evidence Scores	cellular components containing ESR2 protein in low- or high-throughput protein localization assays from the COMPARTMENTS Experimental Protein Localization Evidence Scores dataset.
	COMPARTMENTS Experimental Protein Localization Evidence Scores 2025	cellular components containing ESR2 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 ESR2 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 ESR2 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 ESR2 gene relative to other cell lines from the COSMIC Cell Line Gene CNV Profiles dataset.
	COSMIC Cell Line Gene Mutation Profiles	cell lines with ESR2 gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
	CTD Gene-Chemical Interactions	chemicals interacting with ESR2 gene/protein from the curated CTD Gene-Chemical Interactions dataset.
	CTD Gene-Disease Associations	diseases associated with ESR2 gene/protein from the curated CTD Gene-Disease Associations dataset.
	dbGAP Gene-Trait Associations	traits associated with ESR2 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 ESR2 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 ESR2 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 ESR2 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 ESR2 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 ESR2 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.
	DisGeNET Gene-Phenotype Associations	phenotypes associated with ESR2 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Phenoptype Associations dataset.
	DrugBank Drug Targets	interacting drugs for ESR2 protein from the curated DrugBank Drug Targets dataset.
	ENCODE Histone Modification Site Profiles	histone modification site profiles with high histone modification abundance at ESR2 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 ESR2 gene from the ENCODE Transcription Factor Binding Site Profiles dataset.
	ENCODE Transcription Factor Targets	transcription factors binding the promoter of ESR2 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 ESR2 from the ESCAPE Omics Signatures of Genes and Proteins for Stem Cells dataset.