DCK Gene

Name	deoxycytidine kinase
Description	Deoxycytidine kinase (DCK) is required for the phosphorylation of several deoxyribonucleosides and their nucleoside analogs. Deficiency of DCK is associated with resistance to antiviral and anticancer chemotherapeutic agents. Conversely, increased deoxycytidine kinase activity is associated with increased activation of these compounds to cytotoxic nucleoside triphosphate derivatives. DCK is clinically important because of its relationship to drug resistance and sensitivity. [provided by RefSeq, Jul 2008]
Summary	{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n Deoxycytidine kinase (dCK) is a pivotal, rate‐limiting enzyme in the deoxyribonucleoside salvage pathway that phosphorylates deoxycytidine as well as structurally related nucleoside analog prodrugs (such as cytarabine and gemcitabine) to generate their active metabolites. This activation is essential for the antitumor effects of these agents, and elevated dCK expression or activity is associated with improved clinical responses and longer survival in cancers such as pancreatic ductal adenocarcinoma and acute myeloid leukemia."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "4"}]}, {"type": "t", "text": " \n In contrast, genetic alterations in dCK—including inactivating mutations, alternative splicing that yields inactive isoforms, and impaired post‐translational modifications (for example, loss of phosphorylation at Ser‐74)—are linked to reduced enzymatic activity and consequent chemoresistance."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "5", "end_ref": "11"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Moreover, oncogenic mutations—for instance, those in mutant p53—can impose a dependency on the nucleoside salvage pathway via dCK to maintain balanced deoxynucleotide pools necessary for proliferation."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "12"}]}, {"type": "t", "text": " Transcriptional regulation of dCK is mediated by factors including Sp1 and USF that bind GC‐ and E‐box motifs in its promoter"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "13"}]}, {"type": "t", "text": ", while its overall activity is also subject to modulation by additional factors such as co‐expressed metabolic enzymes and post‐translational modifications."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "14"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n\n "}, {"type": "p", "children": [{"type": "t", "text": "\n In addition to its central role in activating nucleoside analogs used in chemotherapy, dCK is crucial for normal cellular physiology. For example, studies in knockout mice have demonstrated that loss of dCK profoundly disrupts T- and B-lymphocyte development, underscoring a fundamental role in lymphopoiesis."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "15"}]}, {"type": "t", "text": " Furthermore, dCK expression levels are part of a predictive biomarker panel—often in combination with membrane transporters such as hENT1—to forecast treatment outcomes in patients receiving nucleoside analog–based therapies."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "16", "end_ref": "18"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Overall, dCK serves not only as the essential mediator for the activation of several potent chemotherapeutic agents but also as a potential therapeutic target and biomarker to optimize treatment strategies across multiple cancer types."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "19"}]}, {"type": "t", "text": "\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Raphaël Maréchal, Jean-Baptiste Bachet, John R Mackey, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Levels of gemcitabine transport and metabolism proteins predict survival times of patients treated with gemcitabine for pancreatic adenocarcinoma."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Gastroenterology (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1053/j.gastro.2012.06.006"}], "href": "https://doi.org/10.1053/j.gastro.2012.06.006"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22705007"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22705007"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Hayato Fujita, Kenoki Ohuchida, Kazuhiro Mizumoto, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Gene expression levels as predictive markers of outcome in pancreatic cancer after gemcitabine-based adjuvant chemotherapy."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Neoplasia (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1593/neo.10458"}], "href": "https://doi.org/10.1593/neo.10458"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20927319"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20927319"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "N Skrypek, B Duchêne, M Hebbar, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The MUC4 mucin mediates gemcitabine resistance of human pancreatic cancer cells via the Concentrative Nucleoside Transporter family."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Oncogene (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/onc.2012.179"}], "href": "https://doi.org/10.1038/onc.2012.179"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22580602"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22580602"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "I Hubeek, R W Stam, G J Peters, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The human equilibrative nucleoside transporter 1 mediates in vitro cytarabine sensitivity in childhood acute myeloid leukaemia."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Br J Cancer (2005)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/sj.bjc.6602881"}], "href": "https://doi.org/10.1038/sj.bjc.6602881"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16333246"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16333246"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Yuriko Saiki, Yuki Yoshino, Hiroko Fujimura, et al. "}, {"type": "b", "children": [{"type": "t", "text": "DCK is frequently inactivated in acquired gemcitabine-resistant human cancer cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochem Biophys Res Commun (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.bbrc.2012.03.122"}], "href": "https://doi.org/10.1016/j.bbrc.2012.03.122"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22490663"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22490663"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Taro Okazaki, Milind Javle, Motofumi Tanaka, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Single nucleotide polymorphisms of gemcitabine metabolic genes and pancreatic cancer survival and drug toxicity."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Clin Cancer Res (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1158/1078-0432.CCR-09-1555"}], "href": "https://doi.org/10.1158/1078-0432.CCR-09-1555"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20028759"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20028759"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Jatinder K Lamba, Kristine Crews, Stanley Pounds, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Pharmacogenetics of deoxycytidine kinase: identification and characterization of novel genetic variants."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Pharmacol Exp Ther (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1124/jpet.107.128595"}], "href": "https://doi.org/10.1124/jpet.107.128595"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17855478"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17855478"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Soukaina Réjiba, Christelle Bigand, Céline Parmentier, et al. 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Role of Ser-74 in the control of enzyme activity."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2006)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M512129200"}], "href": "https://doi.org/10.1074/jbc.M512129200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16361699"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16361699"}]}, {"type": "r", "ref": 10, "children": [{"type": "t", "text": "Marjan J T Veuger, Mirjam H M Heemskerk, M Willy Honders, et al. 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"}, {"type": "b", "children": [{"type": "t", "text": "Intracellular cytarabine triphosphate production correlates to deoxycytidine kinase/cytosolic 5'-nucleotidase II expression ratio in primary acute myeloid leukemia cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochem Pharmacol (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.bcp.2009.03.011"}], "href": "https://doi.org/10.1016/j.bcp.2009.03.011"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19428333"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19428333"}]}, {"type": "r", "ref": 12, "children": [{"type": "t", "text": "Madhusudhan Kollareddy, Elizabeth Dimitrova, Krishna C Vallabhaneni, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Regulation of nucleotide metabolism by mutant p53 contributes to its gain-of-function activities."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Commun (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/ncomms8389"}], "href": "https://doi.org/10.1038/ncomms8389"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26067754"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26067754"}]}, {"type": "r", "ref": 13, "children": [{"type": "t", "text": "Yubin Ge, Tanya L Jensen, Larry H Matherly, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Physical and functional interactions between USF and Sp1 proteins regulate human deoxycytidine kinase promoter activity."}]}, {"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.M305085200"}], "href": "https://doi.org/10.1074/jbc.M305085200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "14514691"}], "href": "https://pubmed.ncbi.nlm.nih.gov/14514691"}]}, {"type": "r", "ref": 14, "children": [{"type": "t", "text": "Emiko Sugiyama, Nahoko Kaniwa, Su-Ryang Kim, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Population pharmacokinetics of gemcitabine and its metabolite in Japanese cancer patients: impact of genetic polymorphisms."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Clin Pharmacokinet (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.2165/11532970-000000000-00000"}], "href": "https://doi.org/10.2165/11532970-000000000-00000"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20608756"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20608756"}]}, {"type": "r", "ref": 15, "children": [{"type": "t", "text": "Gerald Toy, Wayne R Austin, Hsiang-I Liao, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Requirement for deoxycytidine kinase in T and B lymphocyte development."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Proc Natl Acad Sci U S A (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1073/pnas.0913900107"}], "href": "https://doi.org/10.1073/pnas.0913900107"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20080663"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20080663"}]}, {"type": "r", "ref": 16, "children": [{"type": "t", "text": "PMID:25358007"}]}, {"type": "r", "ref": 17, "children": [{"type": "t", "text": "Gabriella Ferrandina, Valentina Mey, Sara Nannizzi, et al. 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"}, {"type": "b", "children": [{"type": "t", "text": "SAMHD1 protects cancer cells from various nucleoside-based antimetabolites."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Cycle (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1080/15384101.2017.1314407"}], "href": "https://doi.org/10.1080/15384101.2017.1314407"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "28436707"}], "href": "https://pubmed.ncbi.nlm.nih.gov/28436707"}]}]}]}
Proteins	DCK_HUMAN
NCBI Gene ID	1633
API
Download Associations
Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

DCK has 10,702 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 129 datasets.

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

If available, associations are ranked by standardized value

Harmonizome 3.0

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