NADK Gene

Name	NAD kinase
Description	NADK catalyzes the transfer of a phosphate group from ATP to NAD to generate NADP, which in its reduced form acts as an electron donor for biosynthetic reactions (Lerner et al., 2001 [PubMed 11594753]).[supplied by OMIM, Mar 2008]
Summary	{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nNAD kinase (NADK) is the sole enzyme that phosphorylates NAD⁺ to generate NADP⁺, thereby establishing the NADP(H) pool indispensable for reductive biosynthesis and antioxidant defenses in mammalian cells. Functional perturbation of NADK—as shown by loss‐ and gain‐of‐function studies—results in marked changes in cellular NADPH levels and redox balance, with reduced enzyme expression leading to heightened sensitivity to oxidative stress. Biochemical investigations have revealed that human NADK exhibits sigmoidal kinetics toward ATP and is subject to feedback inhibition by NADPH and NADH. In addition, studies on mitochondrial NADK have demonstrated that phosphorylation at conserved serine residues (for example, at a critical Ser188) downregulates its catalytic activity, while growth factor signaling via Akt phosphorylates NADK on specific amino‐terminal serines to relieve an autoinhibitory mechanism and stimulate NADP⁺ production."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "4"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond its central role in normal cellular metabolism, NADK has emerged as a critical mediator of cancer cell survival and tumor progression. Genome‐wide screens in mutant KRAS–driven cancers have identified NADK as a targetable metabolic enzyme, with gain‐of‐function mutants—aided by mutant forms that lower reactive oxygen species—promoting pancreatic ductal adenocarcinoma. Oncogenic signals, including protein kinase C–mediated phosphorylation, further hyperactivate NADK to sustain high NADPH levels necessary for coping with oxidative stress. Moreover, in gastric cancer models, enhanced NADK activity through reduced ubiquitination and increased phosphorylation driven by the G‐protein–coupled estrogen receptor contributes to peritoneal metastasis; and in lung cancer, NADK (by supplying NADPH essential for redox defense) may underlie resistance to ferroptotic cell death."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "5", "end_ref": "9"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Nadine Pollak, Marc Niere, Mathias Ziegler "}, {"type": "b", "children": [{"type": "t", "text": "NAD kinase levels control the NADPH concentration in human cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M704442200"}], "href": "https://doi.org/10.1074/jbc.M704442200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17855339"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17855339"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Kazuto Ohashi, Shigeyuki Kawai, Mari Koshimizu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "NADPH regulates human NAD kinase, a NADP⁺-biosynthetic enzyme."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Cell Biochem (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s11010-011-0838-x"}], "href": "https://doi.org/10.1007/s11010-011-0838-x"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21526340"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21526340"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Yutaka Kawabata, Kousaku Murata, Shigeyuki Kawai "}, {"type": "b", "children": [{"type": "t", "text": "Significance of Ser-188 in human mitochondrial NAD kinase as determined by phosphomimetic and phosphoresistant amino-acid substitutions."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochem Biophys Res Commun (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.bbrc.2015.11.017"}], "href": "https://doi.org/10.1016/j.bbrc.2015.11.017"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26577408"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26577408"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Gerta Hoxhaj, Issam Ben-Sahra, Sophie E Lockwood, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Direct stimulation of NADP"}, {"type": "a", "children": [{"type": "t", "text": "sup"}], "href": "sup"}, {"type": "t", "text": "+"}, {"type": "a", "children": [{"type": "t", "text": "/sup"}], "href": "/sup"}, {"type": "t", "text": " synthesis through Akt-mediated phosphorylation of NAD kinase."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Science (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1126/science.aau3903"}], "href": "https://doi.org/10.1126/science.aau3903"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "30846598"}], "href": "https://pubmed.ncbi.nlm.nih.gov/30846598"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Yiu Huen Tsang, Turgut Dogruluk, Philip M Tedeschi, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Functional annotation of rare gene aberration drivers of pancreatic cancer."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Commun (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/ncomms10500"}], "href": "https://doi.org/10.1038/ncomms10500"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26806015"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26806015"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Edwin H Yau, Indrasena Reddy Kummetha, Gianluigi Lichinchi, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Genome-Wide CRISPR Screen for Essential Cell Growth Mediators in Mutant KRAS Colorectal Cancers."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cancer Res (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1158/0008-5472.CAN-17-2043"}], "href": "https://doi.org/10.1158/0008-5472.CAN-17-2043"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "28954733"}], "href": "https://pubmed.ncbi.nlm.nih.gov/28954733"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Tanya Schild, Melanie R McReynolds, Christie Shea, et al. "}, {"type": "b", "children": [{"type": "t", "text": "NADK is activated by oncogenic signaling to sustain pancreatic ductal adenocarcinoma."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Rep (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.celrep.2021.109238"}], "href": "https://doi.org/10.1016/j.celrep.2021.109238"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "34133937"}], "href": "https://pubmed.ncbi.nlm.nih.gov/34133937"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Teng Wu, Ke Ding, Chun Wang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "G-protein-coupled estrogen receptor 1 promotes peritoneal metastasis of gastric cancer through nicotinamide adenine dinucleotide kinase 1-mediated redox modulation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "FASEB J (2024)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1096/fj.202301172RRRR"}], "href": "https://doi.org/10.1096/fj.202301172RRRR"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "38315451"}], "href": "https://pubmed.ncbi.nlm.nih.gov/38315451"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "Xiangpeng Meng, Fang Peng, Shijie Yu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Knockdown of NADK promotes LUAD ferroptosis via NADPH/FSP1 axis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Cancer Res Clin Oncol (2024)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s00432-024-05752-z"}], "href": "https://doi.org/10.1007/s00432-024-05752-z"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "38700533"}], "href": "https://pubmed.ncbi.nlm.nih.gov/38700533"}]}]}]}
Synonyms	DJ283E3.1
Proteins	NADK_HUMAN
NCBI Gene ID	65220
API
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Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

NADK has 6,686 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 115 datasets.

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

If available, associations are ranked by standardized value

Harmonizome 3.0

NADK 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 NADK 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 NADK 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 NADK 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 NADK 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 NADK 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 NADK 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 NADK 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 NADK 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 NADK 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 NADK gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
	CCLE Cell Line Proteomics	Cell lines associated with NADK protein from the CCLE Cell Line Proteomics dataset.
	CellMarker Gene-Cell Type Associations	cell types associated with NADK 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 NADK gene from the CHEA Transcription Factor Binding Site Profiles dataset.
	ChEA Transcription Factor Targets	transcription factors binding the promoter of NADK 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 NADK 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 NADK gene from the CMAP Signatures of Differentially Expressed Genes for Small Molecules dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores	cellular components containing NADK protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores 2025	cellular components containing NADK protein from the COMPARTMENTS Curated Protein Localization Evidence Scores 2025 dataset.
	COMPARTMENTS Experimental Protein Localization Evidence Scores	cellular components containing NADK protein in low- or high-throughput protein localization assays from the COMPARTMENTS Experimental Protein Localization Evidence Scores dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores	cellular components co-occuring with NADK 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 NADK 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 NADK gene relative to other cell lines from the COSMIC Cell Line Gene CNV Profiles dataset.
	COSMIC Cell Line Gene Mutation Profiles	cell lines with NADK gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
	CTD Gene-Chemical Interactions	chemicals interacting with NADK gene/protein from the curated CTD Gene-Chemical Interactions dataset.
	CTD Gene-Disease Associations	diseases associated with NADK gene/protein from the curated CTD Gene-Disease Associations dataset.
	DeepCoverMOA Drug Mechanisms of Action	small molecule perturbations with high or low expression of NADK 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 NADK 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 NADK 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 NADK 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 NADK gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.
	DisGeNET Gene-Phenotype Associations	phenotypes associated with NADK gene in GWAS and other genetic association datasets from the DisGeNET Gene-Phenoptype Associations dataset.
	ENCODE Histone Modification Site Profiles	histone modification site profiles with high histone modification abundance at NADK 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 NADK gene from the ENCODE Transcription Factor Binding Site Profiles dataset.
	ENCODE Transcription Factor Targets	transcription factors binding the promoter of NADK 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 NADK from the ESCAPE Omics Signatures of Genes and Proteins for Stem Cells dataset.
	GAD Gene-Disease Associations	diseases associated with NADK gene in GWAS and other genetic association datasets from the GAD Gene-Disease Associations dataset.
	GDSC Cell Line Gene Expression Profiles	cell lines with high or low expression of NADK gene relative to other cell lines from the GDSC Cell Line Gene Expression Profiles dataset.
	GeneRIF Biological Term Annotations	biological terms co-occuring with NADK 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 NADK from the GeneSigDB Published Gene Signatures dataset.
	GEO Signatures of Differentially Expressed Genes for Diseases	disease perturbations changing expression of NADK gene from the GEO Signatures of Differentially Expressed Genes for Diseases dataset.