DGKA Gene

HGNC Family	EF-hand domain containing
Name	diacylglycerol kinase, alpha 80kDa
Description	The protein encoded by this gene belongs to the eukaryotic diacylglycerol kinase family. It acts as a modulator that competes with protein kinase C for the second messenger diacylglycerol in intracellular signaling pathways. It also plays an important role in the resynthesis of phosphatidylinositols and phosphorylating diacylglycerol to phosphatidic acid. Several transcript variants encoding different isoforms have been identified for this gene. [provided by RefSeq, Apr 2017]
Summary	{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n Diacylglycerol kinase α (DGKα) is emerging as a central regulator in cellular signaling by metabolizing diacylglycerol (DAG) to phosphatidic acid (PA), thereby tempering the strength and duration of signals emanating from receptors such as the T‐cell receptor (TCR). In T lymphocytes, DGKα activity attenuates key pathways—including Ras/ERK, NF‐κB, and signals mediated by RasGRP—that are essential for full T cell activation. Increased DGKα expression or activity in T cells contributes to the induction and maintenance of anergy, a hyporesponsive state observed when T cells encounter self antigens, chronic infections, or the immunosuppressive tumor microenvironment."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "3"}]}, {"type": "t", "text": " Conversely, inhibition or genetic deletion of DGKα can restore downstream DAG‐mediated signaling—including improved Ras/ERK activation and interleukin‐2 production—and boosts effector functions, as exemplified in studies using chimeric antigen receptor T cells."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": " Furthermore, DGKα regulates intracellular vesicle dynamics by localizing to multivesicular bodies (MVBs) where its activity controls the maturation and polarized trafficking of exosomes that carry pro‐apoptotic Fas ligand, thus influencing activation‐induced cell death."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": " Beyond immune cell regulation, DGKα is implicated in tumor progression. In hepatocellular carcinoma and melanoma, for example, DGKα activity promotes malignant behaviors by modulating the MAPK pathway and activating NF‐κB, thereby enhancing proliferation, survival, invasive potential, and resistance to apoptosis."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": " Collectively, these studies illustrate that DGKα functions as a critical checkpoint that limits DAG‐based signals: in T cells, its activity underlies anergy and immune dysfunction—a state that tumors may exploit to evade immune surveillance—while in cancer cells, DGKα supports oncogenic pathways. Thus, modulation of DGKα activity represents an attractive strategy to enhance T cell responses in adoptive cell therapies and to counteract tumor cell proliferation."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "9", "end_ref": "12"}]}, {"type": "t", "text": "\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Benjamin A Olenchock, Rishu Guo, Jeffery H Carpenter, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Disruption of diacylglycerol metabolism impairs the induction of T cell anergy."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Immunol (2006)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/ni1400"}], "href": "https://doi.org/10.1038/ni1400"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17028587"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17028587"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Yuanyuan Zha, Reinhard Marks, Allen W Ho, et al. "}, {"type": "b", "children": [{"type": "t", "text": "T cell anergy is reversed by active Ras and is regulated by diacylglycerol kinase-alpha."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Immunol (2006)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/ni1394"}], "href": "https://doi.org/10.1038/ni1394"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17028589"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17028589"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Miguel A Sanjuán, Bérengère Pradet-Balade, David R Jones, et al. "}, {"type": "b", "children": [{"type": "t", "text": "T cell activation in vivo targets diacylglycerol kinase alpha to the membrane: a novel mechanism for Ras attenuation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Immunol (2003)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.4049/jimmunol.170.6.2877"}], "href": "https://doi.org/10.4049/jimmunol.170.6.2877"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12626538"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12626538"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Matthew J Riese, Liang-Chuan S Wang, Edmund K Moon, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Enhanced effector responses in activated CD8+ T cells deficient in diacylglycerol kinases."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cancer Res (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1158/0008-5472.CAN-12-3874"}], "href": "https://doi.org/10.1158/0008-5472.CAN-12-3874"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23576561"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23576561"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "R Alonso, C Mazzeo, M C Rodriguez, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Diacylglycerol kinase α regulates the formation and polarisation of mature multivesicular bodies involved in the secretion of Fas ligand-containing exosomes in T lymphocytes."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Death Differ (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/cdd.2010.184"}], "href": "https://doi.org/10.1038/cdd.2010.184"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21252909"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21252909"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Roberto Alonso, M Carmen Rodríguez, Jose Pindado, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Diacylglycerol kinase alpha regulates the secretion of lethal exosomes bearing Fas ligand during activation-induced cell death of T lymphocytes."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2005)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M501112200"}], "href": "https://doi.org/10.1074/jbc.M501112200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15870081"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15870081"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Kazuki Takeishi, Akinobu Taketomi, Ken Shirabe, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Diacylglycerol kinase alpha enhances hepatocellular carcinoma progression by activation of Ras-Raf-MEK-ERK pathway."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Hepatol (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.jhep.2012.02.026"}], "href": "https://doi.org/10.1016/j.jhep.2012.02.026"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22425622"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22425622"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Kenji Yanagisawa, Satoshi Yasuda, Masahiro Kai, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Diacylglycerol kinase alpha suppresses tumor necrosis factor-alpha-induced apoptosis of human melanoma cells through NF-kappaB activation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochim Biophys Acta (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.bbalip.2006.12.008"}], "href": "https://doi.org/10.1016/j.bbalip.2006.12.008"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17276726"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17276726"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "Isabel Mérida, Elena Andrada, Severine I Gharbi, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Redundant and specialized roles for diacylglycerol kinases α and ζ in the control of T cell functions."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Sci Signal (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1126/scisignal.aaa0974"}], "href": "https://doi.org/10.1126/scisignal.aaa0974"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25921290"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25921290"}]}, {"type": "r", "ref": 10, "children": [{"type": "t", "text": "Isabel Mérida, Pedro Torres-Ayuso, Antonia Ávila-Flores, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Diacylglycerol kinases in cancer."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Adv Biol Regul (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.jbior.2016.09.005"}], "href": "https://doi.org/10.1016/j.jbior.2016.09.005"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27697466"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27697466"}]}, {"type": "r", "ref": 11, "children": [{"type": "t", "text": "Gianluca Baldanzi, Andrea Pighini, Valentina Bettio, et al. "}, {"type": "b", "children": [{"type": "t", "text": "SAP-mediated inhibition of diacylglycerol kinase α regulates TCR-induced diacylglycerol signaling."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Immunol (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.4049/jimmunol.1002476"}], "href": "https://doi.org/10.4049/jimmunol.1002476"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22048771"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22048771"}]}, {"type": "r", "ref": 12, "children": [{"type": "t", "text": "Benjamin Kefas, Desiree H Floyd, Laurey Comeau, et al. "}, {"type": "b", "children": [{"type": "t", "text": "A miR-297/hypoxia/DGK-α axis regulating glioblastoma survival."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Neuro Oncol (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1093/neuonc/not118"}], "href": "https://doi.org/10.1093/neuonc/not118"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24158111"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24158111"}]}]}]}
Synonyms	DGK-ALPHA, DAGK1, DAGK
Proteins	DGKA_HUMAN
NCBI Gene ID	1606
API
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Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

DGKA has 8,028 functional associations with biological entities spanning 9 categories (molecular profile, organism, functional term, phrase or reference, chemical, disease, phenotype or trait, structural feature, cell line, cell type or tissue, gene, protein or microRNA, sequence feature) extracted from 121 datasets.

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

If available, associations are ranked by standardized value

Harmonizome 3.0

DGKA 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 DGKA 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 DGKA 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 DGKA 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 DGKA 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 DGKA 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 DGKA 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 DGKA 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 DGKA 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 DGKA 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 DGKA 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 DGKA 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 DGKA gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
	CCLE Cell Line Proteomics	Cell lines associated with DGKA protein from the CCLE Cell Line Proteomics dataset.
	CellMarker Gene-Cell Type Associations	cell types associated with DGKA 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 DGKA gene from the CHEA Transcription Factor Binding Site Profiles dataset.
	ChEA Transcription Factor Targets	transcription factors binding the promoter of DGKA 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 DGKA gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets 2022 dataset.
	CM4AI U2OS Cell Map Protein Localization Assemblies	assemblies containing DGKA protein from integrated AP-MS and IF data from the CM4AI U2OS Cell Map Protein Localization Assemblies dataset.
	CMAP Signatures of Differentially Expressed Genes for Small Molecules	small molecule perturbations changing expression of DGKA gene from the CMAP Signatures of Differentially Expressed Genes for Small Molecules dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores	cellular components containing DGKA protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores 2025	cellular components containing DGKA protein from the COMPARTMENTS Curated Protein Localization Evidence Scores 2025 dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores	cellular components co-occuring with DGKA 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 DGKA 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 DGKA gene relative to other cell lines from the COSMIC Cell Line Gene CNV Profiles dataset.
	COSMIC Cell Line Gene Mutation Profiles	cell lines with DGKA gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
	CTD Gene-Chemical Interactions	chemicals interacting with DGKA gene/protein from the curated CTD Gene-Chemical Interactions dataset.
	CTD Gene-Disease Associations	diseases associated with DGKA gene/protein from the curated CTD Gene-Disease Associations dataset.
	DeepCoverMOA Drug Mechanisms of Action	small molecule perturbations with high or low expression of DGKA 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 DGKA 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 DGKA 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 DGKA 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 DGKA 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 DGKA gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.
	DisGeNET Gene-Phenotype Associations	phenotypes associated with DGKA gene in GWAS and other genetic association datasets from the DisGeNET Gene-Phenoptype Associations dataset.
	DrugBank Drug Targets	interacting drugs for DGKA protein from the curated DrugBank Drug Targets dataset.
	ENCODE Histone Modification Site Profiles	histone modification site profiles with high histone modification abundance at DGKA 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 DGKA gene from the ENCODE Transcription Factor Binding Site Profiles dataset.
	ENCODE Transcription Factor Targets	transcription factors binding the promoter of DGKA 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 DGKA from the ESCAPE Omics Signatures of Genes and Proteins for Stem Cells dataset.
	GDSC Cell Line Gene Expression Profiles	cell lines with high or low expression of DGKA gene relative to other cell lines from the GDSC Cell Line Gene Expression Profiles dataset.