ADORA2B Gene

HGNC Family	G protein-coupled receptors
Name	adenosine A2b receptor
Description	This gene encodes an adenosine receptor that is a member of the G protein-coupled receptor superfamily. This integral membrane protein stimulates adenylate cyclase activity in the presence of adenosine. This protein also interacts with netrin-1, which is involved in axon elongation. The gene is located near the Smith-Magenis syndrome region on chromosome 17. [provided by RefSeq, Jul 2008]
Summary	{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n The adenosine A<sub>2B</sub> receptor (ADORA2B) is emerging as a key mediator in diverse tissue‐protective and immunomodulatory pathways. In hypoxic settings, ADORA2B expression is robustly induced via a hypoxia‐inducible factor (HIF)–responsive promoter element, which enhances endothelial barrier function and limits vascular leak during low oxygen conditions."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "3"}]}, {"type": "t", "text": "\n In the cardiovascular system, ADORA2B signaling plays a critical role in cardioprotection during ischemic preconditioning and myocardial ischemia by promoting metabolic adaptation—mediated in part through stabilization of regulators such as Period2 and HIF‐1α—that improves glycolytic flux and limits infarct size."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n In pulmonary tissues, activation of ADORA2B attenuates ventilator‐induced lung injury by enhancing alveolar fluid clearance and reducing inflammatory edema."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": " In the tumor microenvironment, ADORA2B contributes to immunosuppressive and protumorigenic mechanisms. Its activity can modulate the tumor stroma—by, for example, suppressing NF‐κB signaling in tumor cells—and cooperate with other adenosine receptor subtypes to support metastasis, even though blockade of ADORA2B may not affect all aspects of natural killer cell cytotoxicity."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n In addition, ADORA2B signaling in mast cells drives the secretion of angiogenic factors such as vascular endothelial growth factor (VEGF) and interleukin-8, thereby contributing to angiogenesis in inflamed or remodeled tissues."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "9"}]}, {"type": "t", "text": " Within innate immunity, although ADORA2B plays a relatively minor role compared to other adenosine receptors in modulating cytokine responses from macrophages challenged with bacterial stimuli"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "10"}]}, {"type": "t", "text": ", it has been implicated in the activation of the NLRP3 inflammasome in response to nanoparticle exposure via complex purinergic feedback loops."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "11"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n ADORA2B is also upregulated in chronic inflammatory conditions; for instance, in models of IL-13–driven lung remodeling, augmented ADORA2B expression contributes to tissue inflammation and fibrosis."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "12"}]}, {"type": "t", "text": " Finally, interactions at the immune synapse—such as those involving adenosine deaminase tethered to cell-surface proteins—highlight that ADORA2B not only participates in paracrine signaling but also fine tunes costimulatory signals during T cell activation."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "13"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Collectively, these studies reveal that ADORA2B functions as a versatile sensor of metabolic and hypoxic stress that, by modulating vascular permeability, myocardial metabolism, lung fluid balance, angiogenesis, tumor immunity, and inflammatory signaling, constitutes an attractive therapeutic target in cardiovascular, pulmonary, oncologic, and inflammatory diseases.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Holger K Eltzschig, Juan C Ibla, Glenn T Furuta, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Coordinated adenine nucleotide phosphohydrolysis and nucleoside signaling in posthypoxic endothelium: role of ectonucleotidases and adenosine A2B receptors."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Exp Med (2003)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1084/jem.20030891"}], "href": "https://doi.org/10.1084/jem.20030891"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12939345"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12939345"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Tianqing Kong, Karen A Westerman, Marion Faigle, et al. "}, {"type": "b", "children": [{"type": "t", "text": "HIF-dependent induction of adenosine A2B receptor in hypoxia."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "FASEB J (2006)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1096/fj.06-6419com"}], "href": "https://doi.org/10.1096/fj.06-6419com"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17077301"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17077301"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Tobias Eckle, Marion Faigle, Almut Grenz, et al. "}, {"type": "b", "children": [{"type": "t", "text": "A2B adenosine receptor dampens hypoxia-induced vascular leak."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Blood (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1182/blood-2007-10-117044"}], "href": "https://doi.org/10.1182/blood-2007-10-117044"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18056839"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18056839"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Tobias Eckle, Thomas Krahn, Almut Grenz, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Cardioprotection by ecto-5'-nucleotidase (CD73) and A2B adenosine receptors."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Circulation (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1161/CIRCULATIONAHA.106.669697"}], "href": "https://doi.org/10.1161/CIRCULATIONAHA.106.669697"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17353435"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17353435"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Tobias Eckle, Katherine Hartmann, Stephanie Bonney, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Adora2b-elicited Per2 stabilization promotes a HIF-dependent metabolic switch crucial for myocardial adaptation to ischemia."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Med (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/nm.2728"}], "href": "https://doi.org/10.1038/nm.2728"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22504483"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22504483"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Tobias Eckle, Almut Grenz, Stefanie Laucher, et al. "}, {"type": "b", "children": [{"type": "t", "text": "A2B adenosine receptor signaling attenuates acute lung injury by enhancing alveolar fluid clearance in mice."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Clin Invest (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1172/JCI34203"}], "href": "https://doi.org/10.1172/JCI34203"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18787641"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18787641"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Paul A Beavis, Upulie Divisekera, Christophe Paget, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Blockade of A2A receptors potently suppresses the metastasis of CD73+ tumors."}]}, {"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.1308209110"}], "href": "https://doi.org/10.1073/pnas.1308209110"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23964122"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23964122"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Caglar Cekic, Duygu Sag, Yuesheng Li, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Adenosine A2B receptor blockade slows growth of bladder and breast tumors."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Immunol (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.4049/jimmunol.1101845"}], "href": "https://doi.org/10.4049/jimmunol.1101845"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22116822"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22116822"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "Igor Feoktistov, Sergey Ryzhov, Anna E Goldstein, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Mast cell-mediated stimulation of angiogenesis: cooperative interaction between A2B and A3 adenosine receptors."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Circ Res (2003)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1161/01.RES.0000061572.10929.2D"}], "href": "https://doi.org/10.1161/01.RES.0000061572.10929.2D"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12600879"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12600879"}]}, {"type": "r", "ref": 10, "children": [{"type": "t", "text": "Balázs Csóka, Zoltán H Németh, László Virág, et al. "}, {"type": "b", "children": [{"type": "t", "text": "A2A adenosine receptors and C/EBPbeta are crucially required for IL-10 production by macrophages exposed to Escherichia coli."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Blood (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1182/blood-2007-01-065870"}], "href": "https://doi.org/10.1182/blood-2007-01-065870"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17525287"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17525287"}]}, {"type": "r", "ref": 11, "children": [{"type": "t", "text": "L Baron, A Gombault, M Fanny, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The NLRP3 inflammasome is activated by nanoparticles through ATP, ADP and adenosine."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Death Dis (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/cddis.2014.576"}], "href": "https://doi.org/10.1038/cddis.2014.576"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25654762"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25654762"}]}, {"type": "r", "ref": 12, "children": [{"type": "t", "text": "Michael R Blackburn, Chun G Lee, Hays W J Young, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Adenosine mediates IL-13-induced inflammation and remodeling in the lung and interacts in an IL-13-adenosine amplification pathway."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Clin Invest (2003)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1172/JCI16815"}], "href": "https://doi.org/10.1172/JCI16815"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12897202"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12897202"}]}, {"type": "r", "ref": 13, "children": [{"type": "t", "text": "R Pacheco, J M Martinez-Navio, M Lejeune, et al. "}, {"type": "b", "children": [{"type": "t", "text": "CD26, adenosine deaminase, and adenosine receptors mediate costimulatory signals in the immunological synapse."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Proc Natl Acad Sci U S A (2005)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1073/pnas.0501050102"}], "href": "https://doi.org/10.1073/pnas.0501050102"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15983379"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15983379"}]}]}]}
Synonyms	ADORA2
Proteins	AA2BR_HUMAN
NCBI Gene ID	136
API
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Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

ADORA2B has 8,229 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 117 datasets.

Click the + buttons to view associations for ADORA2B from the datasets below.

If available, associations are ranked by standardized value

Harmonizome 3.0

ADORA2B 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 ADORA2B 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 ADORA2B 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 ADORA2B 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 ADORA2B 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 ADORA2B 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 ADORA2B 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 ADORA2B 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 ADORA2B 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 ADORA2B 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 ADORA2B gene from the Carcinogenome Chemical Perturbation Carcinogenicity Signatures dataset.
	CCLE Cell Line Gene CNV Profiles	cell lines with high or low copy number of ADORA2B 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 ADORA2B gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
	CellMarker Gene-Cell Type Associations	cell types associated with ADORA2B 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 ADORA2B gene from the CHEA Transcription Factor Binding Site Profiles dataset.
	ChEA Transcription Factor Targets	transcription factors binding the promoter of ADORA2B 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 ADORA2B 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 ADORA2B gene from the CMAP Signatures of Differentially Expressed Genes for Small Molecules dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores	cellular components containing ADORA2B protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores	cellular components co-occuring with ADORA2B 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 ADORA2B 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 ADORA2B gene relative to other cell lines from the COSMIC Cell Line Gene CNV Profiles dataset.
	COSMIC Cell Line Gene Mutation Profiles	cell lines with ADORA2B gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
	CTD Gene-Chemical Interactions	chemicals interacting with ADORA2B gene/protein from the curated CTD Gene-Chemical Interactions dataset.
	CTD Gene-Disease Associations	diseases associated with ADORA2B gene/protein from the curated CTD Gene-Disease Associations dataset.
	DepMap CRISPR Gene Dependency	cell lines with fitness changed by ADORA2B gene knockdown relative to other cell lines from the DepMap CRISPR Gene Dependency dataset.
	DISEASES Text-mining Gene-Disease Association Evidence Scores	diseases co-occuring with ADORA2B 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 ADORA2B 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 ADORA2B gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.
	DisGeNET Gene-Phenotype Associations	phenotypes associated with ADORA2B gene in GWAS and other genetic association datasets from the DisGeNET Gene-Phenoptype Associations dataset.
	DrugBank Drug Targets	interacting drugs for ADORA2B protein from the curated DrugBank Drug Targets dataset.
	ENCODE Histone Modification Site Profiles	histone modification site profiles with high histone modification abundance at ADORA2B 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 ADORA2B gene from the ENCODE Transcription Factor Binding Site Profiles dataset.
	ENCODE Transcription Factor Targets	transcription factors binding the promoter of ADORA2B 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 ADORA2B from the ESCAPE Omics Signatures of Genes and Proteins for Stem Cells dataset.
	GAD Gene-Disease Associations	diseases associated with ADORA2B gene in GWAS and other genetic association datasets from the GAD Gene-Disease Associations dataset.
	GAD High Level Gene-Disease Associations	diseases associated with ADORA2B 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 ADORA2B gene relative to other cell lines from the GDSC Cell Line Gene Expression Profiles dataset.
	GeneRIF Biological Term Annotations	biological terms co-occuring with ADORA2B gene in literature-supported statements describing functions of genes from the GeneRIF Biological Term Annotations dataset.
	GeneSigDB Published Gene Signatures	PubMedIDs of publications reporting gene signatures containing ADORA2B from the GeneSigDB Published Gene Signatures dataset.
	GEO Signatures of Differentially Expressed Genes for Diseases	disease perturbations changing expression of ADORA2B gene from the GEO Signatures of Differentially Expressed Genes for Diseases dataset.