NR2C1 Gene

HGNC Family	Zinc fingers
Name	nuclear receptor subfamily 2, group C, member 1
Description	This gene encodes a nuclear hormone receptor characterized by a highly conserved DNA binding domain (DBD), a variable hinge region, and a carboxy-terminal ligand binding domain (LBD) that is typical for all members of the steroid/thyroid hormone receptor superfamily. This protein also belongs to a large family of ligand-inducible transcription factors that regulate gene expression by binding to specific DNA sequences within promoters of target genes. Multiple alternatively spliced transcript variants have been described, but the full-length nature of some of these variants has not been determined. [provided by RefSeq, Jul 2008]
Summary	{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nNR2C1, also known as the orphan nuclear receptor TR2, functions primarily as a transcriptional regulator with context‐dependent repressive activity. In definitive erythroid cells, NR2C1 forms heterodimers with related receptors (TR4) and binds with high affinity to DR1 elements in the promoters of embryonic and fetal globin genes, where it represses their transcription and thereby helps to ensure the proper developmental silencing of these genes."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn addition to its erythroid function, NR2C1 modulates hormonal signaling in other tissues. In estrogen‐responsive breast cancer cells, NR2C1 interacts directly with the estrogen receptor to interrupt receptor homodimerization and DNA binding, leading to the suppression of estrogen‐induced transcription and consequent inhibition of cell proliferation and cell cycle progression. This repressor activity has been demonstrated using interaction blockers and antisense approaches, highlighting the pivotal role of NR2C1 in fine tuning hormone‐mediated transcriptional responses."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nNR2C1 is also expressed in prostate tissue and prostate cancer cell lines, where it appears to engage in cross talk with androgen receptor signaling; however, its precise functional contributions in this context remain to be fully elucidated."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nRegulation of NR2C1 gene transcription has been further characterized by the identification of cis‐regulatory elements. For example, the promoter activating cis-element (PACE) in the minimal promoter region is bound by transcription factors such as NF1-A, which potently activates NR2C1 expression. This mechanism suggests an additional layer of control over NR2C1 function in tissues where its activity is critical."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn pancreatic cancer, recent evidence has uncovered a novel oncogenic role for NR2C1. Here, enhancer activation by miR-492 leads to the upregulation of NR2C1 (alongside neighboring genes), which in turn promotes cell proliferation, migration, and invasion. This upregulation activates the TGF-β/Smad3 signaling pathway, driving epithelial-mesenchymal transition and thereby contributing to the aggressive behavior of pancreatic cancer cells."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Osamu Tanabe, Fumiki Katsuoka, Andrew D Campbell, et al. "}, {"type": "b", "children": [{"type": "t", "text": "An embryonic/fetal beta-type globin gene repressor contains a nuclear receptor TR2/TR4 heterodimer."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "EMBO J (2002)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1093/emboj/cdf340"}], "href": "https://doi.org/10.1093/emboj/cdf340"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12093744"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12093744"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Yueh-Chiang Hu, Chih-Rong Shyr, Wenyi Che, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Suppression of estrogen receptor-mediated transcription and cell growth by interaction with TR2 orphan receptor."}]}, {"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.M203531200"}], "href": "https://doi.org/10.1074/jbc.M203531200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12093804"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12093804"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Shigeki Inui, Yi-Fen Lee, Eugene Chang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Differential and bi-directional regulation between TR2/TR4 orphan nuclear receptors and a specific ligand mediated-peroxisome proliferator-activated receptor alpha in human HaCaT keratinocytes."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Dermatol Sci (2003)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/s0923-1811(02)00152-4"}], "href": "https://doi.org/10.1016/s0923-1811(02"}, {"type": "t", "text": "00152-4) PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12615366"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12615366"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Xiaomin Mu, Chawnshang Chang "}, {"type": "b", "children": [{"type": "t", "text": "TR2 orphan receptor functions as negative modulator for androgen receptor in prostate cancer cells PC-3."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Prostate (2003)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/pros.10282"}], "href": "https://doi.org/10.1002/pros.10282"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12949936"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12949936"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Yun-Lu Lin, Ya-Hui Wang, Han-Jung Lee "}, {"type": "b", "children": [{"type": "t", "text": "Transcriptional regulation of the human TR2 orphan receptor gene by nuclear factor 1-A."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochem Biophys Res Commun (2006)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.bbrc.2006.09.061"}], "href": "https://doi.org/10.1016/j.bbrc.2006.09.061"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17010934"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17010934"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Shanshan Liu, Xiaomeng He, Yang Di, et al. "}, {"type": "b", "children": [{"type": "t", "text": "NamiRNA-enhancer network of miR-492 activates the NR2C1-TGF-β/Smad3 pathway to promote epithelial-mesenchymal transition of pancreatic cancer."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Carcinogenesis (2023)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1093/carcin/bgac102"}], "href": "https://doi.org/10.1093/carcin/bgac102"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "36591938"}], "href": "https://pubmed.ncbi.nlm.nih.gov/36591938"}]}]}]}
Synonyms	TR2
Proteins	NR2C1_HUMAN
NCBI Gene ID	7181
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Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

NR2C1 has 5,737 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 NR2C1 from the datasets below.

If available, associations are ranked by standardized value

Harmonizome 3.0

NR2C1 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 NR2C1 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 NR2C1 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 NR2C1 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 NR2C1 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 NR2C1 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 NR2C1 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 NR2C1 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 NR2C1 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 NR2C1 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 NR2C1 gene from the Carcinogenome Chemical Perturbation Carcinogenicity Signatures dataset.
	CCLE Cell Line Gene CNV Profiles	cell lines with high or low copy number of NR2C1 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 NR2C1 gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
	CCLE Cell Line Proteomics	Cell lines associated with NR2C1 protein from the CCLE Cell Line Proteomics dataset.
	CellMarker Gene-Cell Type Associations	cell types associated with NR2C1 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 NR2C1 gene from the CHEA Transcription Factor Binding Site Profiles dataset.
	ChEA Transcription Factor Targets	transcription factors binding the promoter of NR2C1 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 NR2C1 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 NR2C1 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 NR2C1 gene from the CMAP Signatures of Differentially Expressed Genes for Small Molecules dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores	cellular components containing NR2C1 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores 2025	cellular components containing NR2C1 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores 2025 dataset.
	COMPARTMENTS Experimental Protein Localization Evidence Scores 2025	cellular components containing NR2C1 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 NR2C1 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 NR2C1 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 NR2C1 gene relative to other cell lines from the COSMIC Cell Line Gene CNV Profiles dataset.
	COSMIC Cell Line Gene Mutation Profiles	cell lines with NR2C1 gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
	CTD Gene-Chemical Interactions	chemicals interacting with NR2C1 gene/protein from the curated CTD Gene-Chemical Interactions dataset.
	CTD Gene-Disease Associations	diseases associated with NR2C1 gene/protein from the curated CTD Gene-Disease Associations dataset.
	DeepCoverMOA Drug Mechanisms of Action	small molecule perturbations with high or low expression of NR2C1 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 NR2C1 gene knockdown relative to other cell lines from the DepMap CRISPR Gene Dependency dataset.
	DGIdb Drug Targets 2026	interacting drugs for NR2C1 protein from the DGIdb Drug Targets 2026 dataset.
	DISEASES Experimental Gene-Disease Association Evidence Scores 2025	diseases associated with NR2C1 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 NR2C1 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 NR2C1 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 NR2C1 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.
	ENCODE Histone Modification Site Profiles	histone modification site profiles with high histone modification abundance at NR2C1 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 NR2C1 gene from the ENCODE Transcription Factor Binding Site Profiles dataset.
	ENCODE Transcription Factor Targets	transcription factors binding the promoter of NR2C1 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 NR2C1 from the ESCAPE Omics Signatures of Genes and Proteins for Stem Cells dataset.
	GAD Gene-Disease Associations	diseases associated with NR2C1 gene in GWAS and other genetic association datasets from the GAD Gene-Disease Associations dataset.