NR1H2 Gene

HGNC Family	Zinc fingers
Name	nuclear receptor subfamily 1, group H, member 2
Description	The liver X receptors, LXRA (NR1H3; MIM 602423) and LXRB, form a subfamily of the nuclear receptor superfamily and are key regulators of macrophage function, controlling transcriptional programs involved in lipid homeostasis and inflammation. The inducible LXRA is highly expressed in liver, adrenal gland, intestine, adipose tissue, macrophages, lung, and kidney, whereas LXRB is ubiquitously expressed. Ligand-activated LXRs form obligate heterodimers with retinoid X receptors (RXRs; see MIM 180245) and regulate expression of target genes containing LXR response elements (summary by Korf et al., 2009 [PubMed 19436111]).[supplied by OMIM, Jan 2010]
Summary	{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nNR1H2, which encodes liver X receptor beta (LXRβ), functions as a key cholesterol sensor that, upon binding endogenous oxysterols, forms heterodimers with retinoid X receptors to drive the transcription of genes essential for cholesterol homeostasis, lipogenesis, and anti‐inflammatory responses. Structural studies have elucidated a unique ligand‐binding domain—with a characteristic histidine–tryptophan switch—that stabilizes LXRβ in its active conformation."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": " In addition, expression profiling distinguishes LXRβ from its LXRα counterpart, highlighting its distinct regulatory contributions."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond its canonical role as a nuclear transcription factor, LXRβ activity is finely tuned by post‐translational modifications. For example, O‑GlcNAcylation modulates its target gene specificity"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": ", while ligand–dependent sumoylation and cofactor recruitment underlie anti‐inflammatory pathways."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": " Moreover, LXRβ can exert rapid, non‐genomic control over cholesterol efflux by directly interacting with proteins such as ABCA1."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": " In specialized cell types, it also influences cell fate decisions; for instance, in melanocytes, LXRβ activation suppresses melanogenesis"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": ", and in vascular endothelial cells, its extranuclear actions—mediated via crosstalk with estrogen receptor α in caveolae—promote nitric oxide production and protect against senescence."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIntriguingly, under certain pathological contexts, LXRβ localizes to the cytoplasm where it partners with pannexin 1 to trigger caspase‑1–dependent pyroptosis in colon cancer cells, revealing a non‐canonical, tumor‐suppressive function."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "9"}]}, {"type": "t", "text": " Its versatility is further underscored by regulatory interactions with co-regulators such as TIPARP, which, through ADP‑ribosylation, modulate LXRβ signaling across both genomic and non‑genomic pathways."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "10"}]}, {"type": "t", "text": " Collectively, these studies underscore the multifaceted roles of NR1H2/LXRβ in orchestrating lipid metabolism, inflammation, cellular differentiation, and stress responses across diverse tissue contexts."}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Shawn Williams, Randy K Bledsoe, Jon L Collins, et al. "}, {"type": "b", "children": [{"type": "t", "text": "X-ray crystal structure of the liver X receptor beta ligand binding domain: regulation by a histidine-tryptophan switch."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2003)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M302260200"}], "href": "https://doi.org/10.1074/jbc.M302260200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12736258"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12736258"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Chunyan Zhao, Karin Dahlman-Wright "}, {"type": "b", "children": [{"type": "t", "text": "Liver X receptor in cholesterol metabolism."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Endocrinol (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1677/JOE-09-0271"}], "href": "https://doi.org/10.1677/JOE-09-0271"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19837721"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19837721"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Elin Holter Anthonisen, Lise Berven, Sverre Holm, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Nuclear receptor liver X receptor is O-GlcNAc-modified in response to glucose."}]}, {"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.M109.082685"}], "href": "https://doi.org/10.1074/jbc.M109.082685"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19933273"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19933273"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Nicolas Venteclef, Tomas Jakobsson, Anna Ehrlund, et al. "}, {"type": "b", "children": [{"type": "t", "text": "GPS2-dependent corepressor/SUMO pathways govern anti-inflammatory actions of LRH-1 and LXRbeta in the hepatic acute phase response."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Genes Dev (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1101/gad.545110"}], "href": "https://doi.org/10.1101/gad.545110"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20159957"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20159957"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Masako Hozoji-Inada, Youichi Munehira, Kohjiro Nagao, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Liver X receptor beta (LXRbeta) interacts directly with ATP-binding cassette A1 (ABCA1) to promote high density lipoprotein formation during acute cholesterol accumulation."}]}, {"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.M111.235846"}], "href": "https://doi.org/10.1074/jbc.M111.235846"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21507939"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21507939"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Chang Seok Lee, Miyoung Park, Jiwon Han, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Liver X receptor activation inhibits melanogenesis through the acceleration of ERK-mediated MITF degradation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Invest Dermatol (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/jid.2012.409"}], "href": "https://doi.org/10.1038/jid.2012.409"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23223141"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23223141"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Tomonori Ishikawa, Ivan S Yuhanna, Junko Umetani, et al. "}, {"type": "b", "children": [{"type": "t", "text": "LXRβ/estrogen receptor-α signaling in lipid rafts preserves endothelial integrity."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Clin Invest (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1172/JCI66533"}], "href": "https://doi.org/10.1172/JCI66533"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23867501"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23867501"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Toshio Hayashi, Hitoshi Kotani, Tomoe Yamaguchi, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Endothelial cellular senescence is inhibited by liver X receptor activation with an additional mechanism for its atheroprotection in diabetes."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Proc Natl Acad Sci U S A (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1073/pnas.1322153111"}], "href": "https://doi.org/10.1073/pnas.1322153111"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24398515"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24398515"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "V Derangère, A Chevriaux, F Courtaut, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Liver X receptor β activation induces pyroptosis of human and murine colon cancer cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Death Differ (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/cdd.2014.117"}], "href": "https://doi.org/10.1038/cdd.2014.117"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25124554"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25124554"}]}, {"type": "r", "ref": 10, "children": [{"type": "t", "text": "Christian Bindesbøll, Susanna Tan, Debbie Bott, et al. "}, {"type": "b", "children": [{"type": "t", "text": "TCDD-inducible poly-ADP-ribose polymerase (TIPARP/PARP7) mono-ADP-ribosylates and co-activates liver X receptors."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochem J (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1042/BJ20151077"}], "href": "https://doi.org/10.1042/BJ20151077"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26814197"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26814197"}]}]}]}
Synonyms	LXRB, RIP15, LXR-B, NER-I, NER
Proteins	NR1H2_HUMAN
NCBI Gene ID	7376
API
Download Associations
Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

NR1H2 has 8,042 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 115 datasets.

Click the + buttons to view associations for NR1H2 from the datasets below.

If available, associations are ranked by standardized value

Harmonizome 3.0

NR1H2 Gene

Functional Associations

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

	Dataset	Summary
	Achilles Cell Line Gene Essentiality Profiles	cell lines with fitness changed by NR1H2 gene knockdown relative to other cell lines from the Achilles Cell Line Gene Essentiality Profiles dataset.
	Allen Brain Atlas Adult Human Brain Tissue Gene Expression Profiles	tissues with high or low expression of NR1H2 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 NR1H2 gene relative to other tissues from the Allen Brain Atlas Adult Mouse Brain Tissue Gene Expression Profiles dataset.
	Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by Microarray	tissue samples with high or low expression of NR1H2 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 NR1H2 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 NR1H2 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 NR1H2 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 NR1H2 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 NR1H2 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 NR1H2 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 NR1H2 gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
	CCLE Cell Line Gene Mutation Profiles	cell lines with NR1H2 gene mutations from the CCLE Cell Line Gene Mutation Profiles dataset.
	CellMarker Gene-Cell Type Associations	cell types associated with NR1H2 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 NR1H2 gene from the CHEA Transcription Factor Binding Site Profiles dataset.
	ChEA Transcription Factor Targets	transcription factors binding the promoter of NR1H2 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 NR1H2 gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets 2022 dataset.
	CMAP Signatures of Differentially Expressed Genes for Small Molecules	small molecule perturbations changing expression of NR1H2 gene from the CMAP Signatures of Differentially Expressed Genes for Small Molecules dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores	cellular components containing NR1H2 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores 2025	cellular components containing NR1H2 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores 2025 dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores	cellular components co-occuring with NR1H2 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 NR1H2 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 NR1H2 gene relative to other cell lines from the COSMIC Cell Line Gene CNV Profiles dataset.
	COSMIC Cell Line Gene Mutation Profiles	cell lines with NR1H2 gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
	CTD Gene-Chemical Interactions	chemicals interacting with NR1H2 gene/protein from the curated CTD Gene-Chemical Interactions dataset.
	CTD Gene-Disease Associations	diseases associated with NR1H2 gene/protein from the curated CTD Gene-Disease Associations dataset.
	DeepCoverMOA Drug Mechanisms of Action	small molecule perturbations with high or low expression of NR1H2 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 NR1H2 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 NR1H2 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 NR1H2 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 NR1H2 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 NR1H2 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.
	DisGeNET Gene-Phenotype Associations	phenotypes associated with NR1H2 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Phenoptype Associations dataset.
	DrugBank Drug Targets	interacting drugs for NR1H2 protein from the curated DrugBank Drug Targets dataset.
	ENCODE Histone Modification Site Profiles	histone modification site profiles with high histone modification abundance at NR1H2 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 NR1H2 gene from the ENCODE Transcription Factor Binding Site Profiles dataset.
	ENCODE Transcription Factor Targets	transcription factors binding the promoter of NR1H2 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 NR1H2 from the ESCAPE Omics Signatures of Genes and Proteins for Stem Cells dataset.
	GAD Gene-Disease Associations	diseases associated with NR1H2 gene in GWAS and other genetic association datasets from the GAD Gene-Disease Associations dataset.
	GAD High Level Gene-Disease Associations	diseases associated with NR1H2 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 NR1H2 gene relative to other cell lines from the GDSC Cell Line Gene Expression Profiles dataset.