ADK Gene

Name	adenosine kinase
Description	This gene an enzyme which catalyzes the transfer of the gamma-phosphate from ATP to adenosine, thereby serving as a regulator of concentrations of both extracellular adenosine and intracellular adenine nucleotides. Adenosine has widespread effects on the cardiovascular, nervous, respiratory, and immune systems and inhibitors of the enzyme could play an important pharmacological role in increasing intravascular adenosine concentrations and acting as anti-inflammatory agents. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jan 2011]
Summary	{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n Adenosine kinase (ADK) is emerging as a pivotal enzyme that shapes cellular and extracellular adenosine levels, thereby influencing a wide range of physiological and pathological processes. In the brain, astrocyte‐expressed ADK governs the inhibitory tone of adenosine, and its upregulation has been directly linked to astrogliosis‐induced neuronal hyperexcitability and epileptogenesis, as demonstrated by focal overexpression leading to spontaneous seizures"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": "and confirmed by findings in temporal lobe epilepsy models."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": " Moreover, genetic variations reducing ADK activity have been associated with altered seizure susceptibility following traumatic brain injury"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": ", while experimental modulation of ADK levels in the ischemic brain predicts infarct size, with overexpression exacerbating injury and knockdown affording neuroprotection."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": " Complementary work has implicated glial ADK as a key modulator of sleep homeostasis, linking glial energy metabolism to the buildup and resolution of sleep drive."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Outside the central nervous system, ADK facilitates critical metabolic processes. In the liver, ADK is essential for maintaining adenine nucleotide levels and for sustaining S‐adenosylmethionine–dependent transmethylation; deficiency in ADK leads to neonatal hepatic steatosis with profound metabolic consequences."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": " In the vasculature, hypoxia‐induced repression of endothelial ADK elevates extracellular adenosine, thereby enhancing adenosine–dependent barrier responses and protecting against vascular leakage and inflammation"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": ", whereas increased endothelial ADK correlates with proinflammatory activation and atherosclerotic risk."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "8"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Pharmacologically, selective inhibition of ADK has been shown to exert cell type–specific benefits. In pancreatic islets, ADK inhibitors selectively promote β‐cell replication without affecting other cell populations, highlighting a promising therapeutic strategy for diabetes."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "9"}]}, {"type": "t", "text": " Similarly, by elevating endogenous adenosine, ADK inhibition produces potent analgesic effects through activation of A3 adenosine receptors, offering a novel target for chronic pain management."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "10"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n On the molecular level, ADK exists in distinct isoforms with differential subcellular localizations. The long isoform, which harbors an N‐terminal nuclear localization signal, is predominantly nuclear and is thought to be instrumental in sustaining methylation reactions, thereby influencing gene regulation."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "11"}]}, {"type": "t", "text": " Furthermore, ADK critically modulates extracellular adenosine tone, which in turn regulates synaptic transmission, plasticity, and BDNF–dependent synaptic actions in the hippocampus."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "12"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n In summary, ADK’s multifaceted roles across the brain and peripheral tissues place it at the nexus of adenosine homeostasis. By dictating adenosine availability, ADK influences neuronal excitability and epileptogenesis, neuroprotection in stroke, sleep regulation, metabolic processes in the liver, vascular inflammation, pancreatic β‐cell replication, and nociception. This central position makes ADK a highly attractive therapeutic target in epilepsy, stroke, diabetes, and chronic pain."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}, {"type": "fg_f", "ref": "12"}, {"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": "\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Tianfu Li, Gaoying Ren, Theresa Lusardi, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Adenosine kinase is a target for the prediction and prevention of epileptogenesis 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/JCI33737"}], "href": "https://doi.org/10.1172/JCI33737"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18172552"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18172552"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Eleonora Aronica, Emanuele Zurolo, Anand Iyer, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Upregulation of adenosine kinase in astrocytes in experimental and human temporal lobe epilepsy."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Epilepsia (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1111/j.1528-1167.2011.03115.x"}], "href": "https://doi.org/10.1111/j.1528-1167.2011.03115.x"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21635241"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21635241"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Mark Nellist, Rutger W W Brouwer, Christel E M Kockx, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Targeted Next Generation Sequencing reveals previously unidentified TSC1 and TSC2 mutations."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "BMC Med Genet (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1186/s12881-015-0155-4"}], "href": "https://doi.org/10.1186/s12881-015-0155-4"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25927202"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25927202"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Hai-Ying Shen, Theresa A Lusardi, Rebecca L Williams-Karnesky, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Adenosine kinase determines the degree of brain injury after ischemic stroke in mice."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Cereb Blood Flow Metab (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/jcbfm.2011.30"}], "href": "https://doi.org/10.1038/jcbfm.2011.30"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21427729"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21427729"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Theresa E Bjorness, Nicholas Dale, Gabriel Mettlach, et al. "}, {"type": "b", "children": [{"type": "t", "text": "An Adenosine-Mediated Glial-Neuronal Circuit for Homeostatic Sleep."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Neurosci (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1523/JNEUROSCI.3906-15.2016"}], "href": "https://doi.org/10.1523/JNEUROSCI.3906-15.2016"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27030757"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27030757"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Detlev Boison, Louis Scheurer, Valérie Zumsteg, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Neonatal hepatic steatosis by disruption of the adenosine kinase gene."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Proc Natl Acad Sci U S A (2002)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1073/pnas.092642899"}], "href": "https://doi.org/10.1073/pnas.092642899"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "11997462"}], "href": "https://pubmed.ncbi.nlm.nih.gov/11997462"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Julio C Morote-Garcia, Peter Rosenberger, Johannes Kuhlicke, et al. "}, {"type": "b", "children": [{"type": "t", "text": "HIF-1-dependent repression of adenosine kinase attenuates 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-2007-11-126763"}], "href": "https://doi.org/10.1182/blood-2007-11-126763"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18309031"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18309031"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Yiming Xu, Yong Wang, Siyuan Yan, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Regulation of endothelial intracellular adenosine via adenosine kinase epigenetically modulates vascular inflammation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Commun (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s41467-017-00986-7"}], "href": "https://doi.org/10.1038/s41467-017-00986-7"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "29038540"}], "href": "https://pubmed.ncbi.nlm.nih.gov/29038540"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "Justin P Annes, Jennifer Hyoje Ryu, Kelvin Lam, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Adenosine kinase inhibition selectively promotes rodent and porcine islet β-cell replication."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Proc Natl Acad Sci U S A (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1073/pnas.1201149109"}], "href": "https://doi.org/10.1073/pnas.1201149109"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22345561"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22345561"}]}, {"type": "r", "ref": 10, "children": [{"type": "t", "text": "Joshua W Little, Amanda Ford, Ashley M Symons-Liguori, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Endogenous adenosine A3 receptor activation selectively alleviates persistent pain states."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Brain (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1093/brain/awu330"}], "href": "https://doi.org/10.1093/brain/awu330"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25414036"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25414036"}]}, {"type": "r", "ref": 11, "children": [{"type": "t", "text": "Xianying Amy Cui, Bhag Singh, Jae Park, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Subcellular localization of adenosine kinase in mammalian cells: The long isoform of AdK is localized in the nucleus."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochem Biophys Res Commun (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.bbrc.2009.07.106"}], "href": "https://doi.org/10.1016/j.bbrc.2009.07.106"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19635462"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19635462"}]}, {"type": "r", "ref": 12, "children": [{"type": "t", "text": "Maria José Diógenes, Raquel Neves-Tomé, Sergio Fucile, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Homeostatic control of synaptic activity by endogenous adenosine is mediated by adenosine kinase."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cereb Cortex (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1093/cercor/bhs284"}], "href": "https://doi.org/10.1093/cercor/bhs284"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22997174"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22997174"}]}]}]}
Synonyms	AK
Proteins	ADK_HUMAN
NCBI Gene ID	132
API
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Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

ADK has 7,467 functional associations with biological entities spanning 8 categories (molecular profile, organism, disease, phenotype or trait, chemical, functional term, phrase or reference, structural feature, cell line, cell type or tissue, gene, protein or microRNA) extracted from 116 datasets.

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

If available, associations are ranked by standardized value

Harmonizome 3.0

ADK 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 ADK 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 ADK gene relative to other tissues from the Allen Brain Atlas Adult Human 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 ADK 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 ADK 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 ADK 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 ADK 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 ADK 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 ADK 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 ADK 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 ADK gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
	CCLE Cell Line Gene Mutation Profiles	cell lines with ADK gene mutations from the CCLE Cell Line Gene Mutation Profiles dataset.
	CCLE Cell Line Proteomics	Cell lines associated with ADK protein from the CCLE Cell Line Proteomics dataset.
	CellMarker Gene-Cell Type Associations	cell types associated with ADK 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 ADK gene from the CHEA Transcription Factor Binding Site Profiles dataset.
	ChEA Transcription Factor Targets	transcription factors binding the promoter of ADK 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 ADK gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets 2022 dataset.
	ClinVar Gene-Phenotype Associations	phenotypes associated with ADK gene from the curated ClinVar Gene-Phenotype Associations dataset.
	CMAP Signatures of Differentially Expressed Genes for Small Molecules	small molecule perturbations changing expression of ADK gene from the CMAP Signatures of Differentially Expressed Genes for Small Molecules dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores	cellular components containing ADK protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores	cellular components co-occuring with ADK protein in abstracts of biomedical publications from the COMPARTMENTS Text-mining Protein Localization Evidence Scores dataset.
	COSMIC Cell Line Gene CNV Profiles	cell lines with high or low copy number of ADK gene relative to other cell lines from the COSMIC Cell Line Gene CNV Profiles dataset.
	COSMIC Cell Line Gene Mutation Profiles	cell lines with ADK gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
	CTD Gene-Chemical Interactions	chemicals interacting with ADK gene/protein from the curated CTD Gene-Chemical Interactions dataset.
	CTD Gene-Disease Associations	diseases associated with ADK gene/protein from the curated CTD Gene-Disease Associations dataset.
	dbGAP Gene-Trait Associations	traits associated with ADK gene in GWAS and other genetic association datasets from the dbGAP Gene-Trait Associations dataset.
	DeepCoverMOA Drug Mechanisms of Action	small molecule perturbations with high or low expression of ADK 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 ADK 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 ADK 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 ADK 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 ADK gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.
	DisGeNET Gene-Phenotype Associations	phenotypes associated with ADK gene in GWAS and other genetic association datasets from the DisGeNET Gene-Phenoptype Associations dataset.
	DrugBank Drug Targets	interacting drugs for ADK protein from the curated DrugBank Drug Targets dataset.
	ENCODE Histone Modification Site Profiles	histone modification site profiles with high histone modification abundance at ADK 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 ADK gene from the ENCODE Transcription Factor Binding Site Profiles dataset.
	ENCODE Transcription Factor Targets	transcription factors binding the promoter of ADK 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 ADK from the ESCAPE Omics Signatures of Genes and Proteins for Stem Cells dataset.
	GAD Gene-Disease Associations	diseases associated with ADK gene in GWAS and other genetic association datasets from the GAD Gene-Disease Associations dataset.
	GAD High Level Gene-Disease Associations	diseases associated with ADK 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 ADK gene relative to other cell lines from the GDSC Cell Line Gene Expression Profiles dataset.
	GeneRIF Biological Term Annotations	biological terms co-occuring with ADK gene in literature-supported statements describing functions of genes from the GeneRIF Biological Term Annotations dataset.