DGKA

Summary

DGKA (diacylglycerol kinase alpha, HGNC:2849) is a protein-coding gene on chromosome 12q13.2, encoding Diacylglycerol kinase alpha (P23743). Diacylglycerol kinase that converts diacylglycerol/DAG into phosphatidic acid/phosphatidate/PA and regulates the respective levels of these two bioactive lipids.

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.

Source: NCBI Gene 1606 — RefSeq curated summary.

At a glance

• GWAS associations: 3
• Clinical variants (ClinVar): 114 total
• Druggable target: yes — 1 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_001345

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:2849
Approved symbol	DGKA
Name	diacylglycerol kinase alpha
Location	12q13.2
Locus type	gene with protein product
Status	Approved
Aliases	DGK-alpha
Ensembl gene	ENSG00000065357
Ensembl biotype	protein_coding
OMIM	125855
Entrez	1606

Gene structure

Transcript identifiers

Ensembl transcripts: 50 — 24 retained_intron, 17 protein_coding, 5 nonsense_mediated_decay, 4 protein_coding_CDS_not_defined

ENST00000331886, ENST00000394147, ENST00000402956, ENST00000432422, ENST00000546878, ENST00000546895, ENST00000546995, ENST00000547015, ENST00000547324, ENST00000547358, ENST00000547535, ENST00000548047, ENST00000548378, ENST00000548407, ENST00000548479, ENST00000548491, ENST00000548549, ENST00000549079, ENST00000549085, ENST00000549097, ENST00000549323, ENST00000549368, ENST00000549629, ENST00000549986, ENST00000550115, ENST00000550484, ENST00000550888, ENST00000550957, ENST00000551156, ENST00000551296, ENST00000551585, ENST00000551615, ENST00000551707, ENST00000551739, ENST00000552335, ENST00000552478, ENST00000552652, ENST00000552687, ENST00000552903, ENST00000553084, ENST00000553783, ENST00000554434, ENST00000555025, ENST00000555090, ENST00000555218, ENST00000556001, ENST00000556344, ENST00000557080, ENST00000557180, ENST00000879156

RefSeq mRNA: 21 — MANE Select: NM_001345 NM_001345, NM_001351033, NM_001351034, NM_001351035, NM_001351036, NM_001351037, NM_001351038, NM_001351039, NM_001351040, NM_001413596, NM_001413597, NM_001413598, NM_001413599, NM_001413600, NM_001413601, NM_001413602, NM_001413603, NM_001413604, NM_201444, NM_201445, NM_201554

CCDS: CCDS8896

Canonical transcript exons

ENST00000331886 — 24 exons

Exon	Start	End
ENSE00001292720	55931162	55931344
ENSE00002324565	55953685	55954023
ENSE00003468510	55937017	55937090
ENSE00003478536	55938915	55938989
ENSE00003480327	55940897	55940980
ENSE00003488180	55953040	55953160
ENSE00003490063	55953350	55953410
ENSE00003494686	55942174	55942263
ENSE00003500650	55939186	55939305
ENSE00003509930	55940314	55940433
ENSE00003531973	55952035	55952099
ENSE00003540649	55941998	55942083
ENSE00003586579	55952341	55952431
ENSE00003590549	55940082	55940170
ENSE00003602142	55941252	55941325
ENSE00003607289	55937408	55937543
ENSE00003613637	55951623	55951783
ENSE00003641213	55940624	55940722
ENSE00003655489	55939415	55939529
ENSE00003659879	55941510	55941584
ENSE00003671883	55952734	55952932
ENSE00003785907	55938511	55938560
ENSE00003787684	55937978	55938052
ENSE00003798460	55936423	55936567

Expression profiles

Bgee: expression breadth ubiquitous, 264 present calls, max score 99.32.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 29.9528 / max 953.9898, expressed in 1760 samples.

FANTOM5 promoters (9 alternative TSS)

Promoter ID	TPM avg	Samples expressed
126003	14.8307	1727
126000	13.6834	1035
126007	0.5517	263
126006	0.5375	256
126001	0.1281	58
125999	0.1125	53
126004	0.0475	20
126005	0.0461	17
126002	0.0152	8

Top tissues by expression

290 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
lower esophagus mucosa	UBERON:0035834	99.32	gold quality
skin of abdomen	UBERON:0001416	98.46	gold quality
esophagus mucosa	UBERON:0002469	98.44	gold quality
skin of leg	UBERON:0001511	98.32	gold quality
granulocyte	CL:0000094	98.20	gold quality
small intestine Peyer’s patch	UBERON:0003454	97.57	gold quality
spleen	UBERON:0002106	96.97	gold quality
lymph node	UBERON:0000029	96.94	gold quality
mucosa of transverse colon	UBERON:0004991	96.91	gold quality
minor salivary gland	UBERON:0001830	96.88	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	96.84	gold quality
zone of skin	UBERON:0000014	96.69	gold quality
small intestine	UBERON:0002108	96.52	gold quality
tonsil	UBERON:0002372	96.48	gold quality
mouth mucosa	UBERON:0003729	96.00	gold quality
rectum	UBERON:0001052	95.92	gold quality
descending thoracic aorta	UBERON:0002345	95.73	gold quality
transverse colon	UBERON:0001157	95.71	gold quality
vermiform appendix	UBERON:0001154	95.62	gold quality
jejunal mucosa	UBERON:0000399	95.60	gold quality
saliva-secreting gland	UBERON:0001044	95.50	gold quality
thymus	UBERON:0002370	95.48	gold quality
ileal mucosa	UBERON:0000331	95.34	gold quality
ascending aorta	UBERON:0001496	95.34	gold quality
thoracic aorta	UBERON:0001515	95.29	gold quality
vagina	UBERON:0000996	95.28	gold quality
esophagus	UBERON:0001043	95.21	gold quality
duodenum	UBERON:0002114	94.88	gold quality
ectocervix	UBERON:0012249	94.83	gold quality
blood	UBERON:0000178	94.82	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-CURD-122	yes	32.98
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): FOXO1, FOXO3

miRNA regulators (miRDB)

36 targeting DGKA, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-200B-3P	100.00	73.31	2693
HSA-MIR-200C-3P	100.00	73.35	2685
HSA-MIR-429	100.00	73.44	2698
HSA-MIR-6867-5P	100.00	82.21	3464
HSA-MIR-4455	100.00	65.48	1587
HSA-MIR-1827	99.63	68.57	3265
HSA-MIR-6134	99.63	65.68	1537
HSA-MIR-892A	99.54	68.16	1141
HSA-MIR-1207-5P	99.49	69.11	2983
HSA-MIR-297	99.40	69.58	1418
HSA-MIR-4318	99.38	66.94	1505
HSA-MIR-892C-5P	99.16	70.56	2116
HSA-MIR-3688-5P	99.12	69.67	1091
HSA-MIR-4763-3P	99.10	67.83	2649
HSA-MIR-6868-5P	99.06	65.69	1284
HSA-MIR-4260	98.78	65.37	848
HSA-MIR-5572	98.55	65.84	970
HSA-MIR-4722-5P	98.46	66.34	1611
HSA-MIR-6804-5P	98.39	65.77	1084
HSA-MIR-4664-5P	98.17	65.07	1020
HSA-MIR-891A-3P	98.05	67.99	970
HSA-MIR-4443	98.02	66.25	1928
HSA-MIR-6819-5P	97.96	66.59	1071
HSA-MIR-4736	97.96	65.89	1287
HSA-MIR-450A-2-3P	97.91	67.56	1459
HSA-MIR-7113-5P	97.88	67.33	1735
HSA-MIR-6737-5P	97.75	66.54	1044
HSA-MIR-4433A-3P	97.75	62.82	1435
HSA-MIR-4733-5P	97.75	67.44	866
HSA-MIR-6783-5P	97.67	67.21	1528

Literature-anchored findings (GeneRIF, showing 36)

• Defects in both polymorphonuclear neutrophil (PMN) transendothelial migration and PMN diacylglycerol kinase alpha signaling are implicated as disordered functions in subjects with localized aggressive periodontitis. (PMID:14734770)
• PPARgamma agonists upregulate DGKalpha production.This suppresses the diacylglycerol/protein-kinase-C signaling pathway. (PMID:15117825)
• DGKalpha is crucial for the control of cell activation and also for the regulation of the secretion of lethal exosomes, which in turn controls cell death. (PMID:15870081)
• ALK-mediated alphaDGK activation is dependent on p60src tyrosine kinase, with which alphaDGK forms a complex; alphaDGK activation is involved in the control of ALK-mediated mitogenic properties. (PMID:15928040)
• These results strongly suggest that DGKalpha is a novel positive regulator of NF-kappaB, which suppresses TNF-alpha-induced melanoma cell apoptosis. (PMID:17276726)
• diacylglycerol kinase alpha-conserved domains have a role in membrane targeting in intact T cells (PMID:17911109)
• 2,3-dioleoylglycerol binds to a site on the alpha and zeta isoforms of diacylglycerol kinase that is exposed as a consequence of the substrate binding to the active site. (PMID:18004883)
• Lck-dependent tyrosine phosphorylation of diacylglycerol kinase alpha regulates its membrane association in T cells.( (PMID:18424699)
• These results strongly suggest that DGKalpha positively regulates TNF-alpha-dependent NF-kappaB activation via the PKCzeta-mediated Ser311 phosphorylation of p65/RelA. (PMID:19751727)
• Diacylglycerol kinase alpha is a key regulator of the polarised secretion of exosomes. (PMID:21252909)
• findings further suggest that DGL-alpha and -beta may regulate neurite outgrowth by engaging temporally and spatially distinct molecular pathways (PMID:21493725)
• SAP-mediated inhibition of DGKalpha sustains diacylglycerol signaling, thereby regulating T cell activation (PMID:22048771)
• Antigen-specific CD8-positive T cells from DGKalpha-deficient transgenic mice show enhanced expansion and increased cytokine production after lymphocytic choriomeningitis virus infection, yet DGK-deficient memory CD8+ T cells exhibit impaired expansion. (PMID:22271650)
• DGKalpha is involved in hepatocellular carcinoma progression by activation of the MAPK pathway. (PMID:22425622)
• DGK-alpha was more highly expressed in CD8-tumor-infiltrating T cellscompared with that in CD8non-tumor kidney-infiltrating lymphocytes. (PMID:22573804)
• High diacylglycerol kinase alpha expression is associated with glioblastoma. (PMID:24158111)
• These data indicates the existence of a SDF-1alpha induced DGKalpha - atypical PKC - beta1 integrin signaling pathway, which is essential for matrix invasion of carcinoma cells. (PMID:24887021)
• DGKalpha generates phosphatidic acid to drive its own recruitment to tubular recycling endosomes via its interaction with MICAL-L1 (PMID:25248744)
• Redundant and specialized roles for diacylglycerol kinases alpha and zeta in the control of T cell functions. (PMID:25921290)
• An abandoned compound that also inhibits serotonin receptors may have more translational potential as a DGKa inhibitor, but more potent and specific DGKa inhibitors are sorely needed (PMID:26420856)
• Decreased DNA methylation at this enhancer enables recruitment of the profibrotic transcription factor early growth response 1 (EGR1) and facilitates radiation-induced DGKA transcription in cells from patients later developing fibrosis. (PMID:26964756)
• LIPFDGKA might serve as a potential possible biomarkers for diagnosis of gastric cancer, and their downregulation may bring new perspective into the investigation of gastric cancer prognosis (PMID:27498782)
• Diacylglycerol kinases alpha and zeta are up-regulated in cancer in cancer, and contribute towards tumor immune evasion and T cells clonal anergy. (Review) (PMID:27697466)
• DGKalpha isoform is highly expressed in the nuclei of human erythroleukemia cell line K562, and its nuclear activity drives K562 cells through the G1/S transition during cell cycle progression. (PMID:27731506)
• This novel study demonstrates efficient ablation of diacylglycerol kinase in human CAR-T cells that leads to improved antitumor immunity and may have significant impact in human cancer immunotherapy (PMID:29967261)
• This study presents the first crystal structure of EF-hand domains of diacylglycerol kinase alpha in its Ca(2+) bound form and characterize Ca(2+) -induced conformational changes, which likely regulates intra-molecular interactions. (PMID:30653270)
• Upon neutrophil stimulation, DGK-alpha activation is necessary for migration and a productive response. This paper focuses on the role of DGK-alpha in obstructive respiratory diseases, including asthma and chronic obstructive pulmonary disease, but also rare genetic diseases such as alpha-1-antitrypsin deficiency. [review] (PMID:31766109)
• DGKA Provides Platinum Resistance in Ovarian Cancer Through Activation of c-JUN-WEE1 Signaling. (PMID:32341033)
• Diacylglycerol kinases regulate TRPV1 channel activity. (PMID:32345612)
• DGKA Mediates Resistance to PD-1 Blockade. (PMID:33608256)
• Diacylglycerol Kinase Inhibition Reduces Airway Contraction by Negative Feedback Regulation of Gq-Signaling. (PMID:34293268)
• DGKA interacts with SRC/FAK to promote the metastasis of non-small cell lung cancer. (PMID:35131384)
• Targeting diacylglycerol kinase alpha impairs lung tumorigenesis by inhibiting cyclin D3. (PMID:36965165)
• Multiomics analysis reveals metabolic subtypes and identifies diacylglycerol kinase alpha (DGKA) as a potential therapeutic target for intrahepatic cholangiocarcinoma. (PMID:38143235)
• Tumor-associated macrophage (TAM)-secreted CCL22 confers cisplatin resistance of esophageal squamous cell carcinoma (ESCC) cells via regulating the activity of diacylglycerol kinase alpha (DGKalpha)/NOX4 axis. (PMID:38387281)
• Diacylglycerol kinase alpha is a proliferation marker of intrahepatic cholangiocarcinoma associated with the prognosis. (PMID:38716625)

Cross-species orthologs

8 orthologs

Organism	Symbol	Gene ID
danio_rerio	dgkaa	ENSDARG00000060626
danio_rerio	dgkab	ENSDARG00000098175
mus_musculus	Dgka	ENSMUSG00000025357
rattus_norvegicus	Dgka	ENSRNOG00000022943
drosophila_melanogaster	CG34384	FBGN0085413
drosophila_melanogaster	rdgA	FBGN0261549
caenorhabditis_elegans		WBGENE00006483
caenorhabditis_elegans		WBGENE00019428

Paralogs (9): DGKG (ENSG00000058866), DGKD (ENSG00000077044), DGKH (ENSG00000102780), DGKB (ENSG00000136267), DGKQ (ENSG00000145214), DGKZ (ENSG00000149091), DGKE (ENSG00000153933), DGKI (ENSG00000157680), DGKK (ENSG00000274588)

Protein

Protein identifiers

Diacylglycerol kinase alpha — P23743 (reviewed: P23743)

Alternative names: 80 kDa diacylglycerol kinase, Diglyceride kinase alpha

All UniProt accessions (12): P23743, C9JM35, F8VNZ9, F8VWX8, F8W1H7, F8W1M3, G3V312, G3V327, G3V4E1, G3V4I3, H0YJE7, H0YJH4

UniProt curated annotations — full annotation on UniProt →

Function. Diacylglycerol kinase that converts diacylglycerol/DAG into phosphatidic acid/phosphatidate/PA and regulates the respective levels of these two bioactive lipids. Thereby, acts as a central switch between the signaling pathways activated by these second messengers with different cellular targets and opposite effects in numerous biological processes. Also plays an important role in the biosynthesis of complex lipids. Can also phosphorylate 1-alkyl-2-acylglycerol in vitro as efficiently as diacylglycerol provided it contains an arachidonoyl group. Also involved in the production of alkyl-lysophosphatidic acid, another bioactive lipid, through the phosphorylation of 1-alkyl-2-acetyl glycerol.

Subunit / interactions. Monomer.

Subcellular location. Cytoplasm. Cytosol.

Tissue specificity. Expressed in lymphocytes.

Activity regulation. Stimulated by calcium and phosphatidylserine.

Pathway. Lipid metabolism; glycerolipid metabolism.

Miscellaneous. May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay.

Similarity. Belongs to the eukaryotic diacylglycerol kinase family.

Isoforms (3)

UniProt ID	Names	Canonical?
P23743-1	1	yes
P23743-2	2
P23743-3	3

RefSeq proteins (21): NP_001336, NP_001337962, NP_001337963, NP_001337964, NP_001337965, NP_001337966, NP_001337967, NP_001337968, NP_001337969, NP_001400525, NP_001400526, NP_001400527, NP_001400528, NP_001400529, NP_001400530, NP_001400531, NP_001400532, NP_001400533, NP_958852, NP_958853, NP_963848 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000756	Diacylglycerol_kin_accessory	Domain
IPR001206	Diacylglycerol_kinase_cat_dom	Domain
IPR002048	EF_hand_dom	Domain
IPR002219	PKC_DAG/PE	Domain
IPR011992	EF-hand-dom_pair	Homologous_superfamily
IPR016064	NAD/diacylglycerol_kinase_sf	Homologous_superfamily
IPR017438	ATP-NAD_kinase_N	Homologous_superfamily
IPR018247	EF_Hand_1_Ca_BS	Binding_site
IPR029477	DAG_kinase_typeI_N	Domain
IPR037607	DGK	Family
IPR038199	DGK_typeI_N_sf	Homologous_superfamily
IPR046349	C1-like_sf	Homologous_superfamily
IPR047469	C1_DGKalpha_rpt2	Domain

Pfam: PF00130, PF00609, PF00781, PF14513

Enzyme classification (BRENDA):

• EC 2.7.1.107 — diacylglycerol kinase (ATP) (BRENDA: 27 organisms, 171 substrates, 108 inhibitors, 81 Km, 16 kcat entries)

Substrate kinetics (BRENDA)

16 substrates with measured Km, best-characterized 15. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
ATP	0.05–4.8	46
GTP	0.03–8.7	5
DIOLEIN	0.05–0.08	3
1,2-DIARACHIDONOYL-GLYCEROL	0.09–0.14	2
1-STEAROYL-2-ARACHIDONOYL-SN-GLYCEROL	0.07–0.09	2
SN-1,2-DIOLEOYLGLYCEROL	0.1–0.125	2
1,2-DIACYL-SN-GLYCEROL	0.25	1
1,2-DIOLEIN	0.45	1
1,2-DIOLEOYL-SN-GLYCEROL	0.125	1
2’-DEOXY-ATP	4.2	1
ADP	1	1
CERAMIDE	0.23	1
DIOLEOYLGLYCEROL	0.9	1
ITP	5.9	1
1-STEAROYL-2-LINOLEOYL-SN-GLYCEROL	—	0

Catalyzed reactions (Rhea), 12 shown:

• a 1,2-diacyl-sn-glycerol + ATP = a 1,2-diacyl-sn-glycero-3-phosphate + ADP + H(+) (RHEA:10272)
• a 1-O-alkyl-sn-glycerol + ATP = a 1-O-alkyl-sn-glycero-3-phosphate + ADP + H(+) (RHEA:16937)
• 1-octadecanoyl-2-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-sn-glycerol + ATP = 1-octadecanoyl-2-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-sn-glycero-3-phosphate + ADP + H(+) (RHEA:40323)
• 1,2-di-(9Z-octadecenoyl)-sn-glycerol + ATP = 1,2-di-(9Z-octadecenoyl)-sn-glycero-3-phosphate + ADP + H(+) (RHEA:40327)
• 1-O-hexadecyl-2-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-sn-glycerol + ATP = 1-O-hexadecyl-2-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-sn-glycero-3-phosphate + ADP + H(+) (RHEA:40403)
• 1-O-hexadecyl-2-(9Z-octadecenoyl)-sn-glycerol + ATP = 1-O-hexadecyl-2-(9Z-octadecenoyl)-sn-glycero-3-phosphate + ADP + H(+) (RHEA:40407)
• 1-O-hexadecyl-sn-glycerol + ATP = 1-O-hexadecyl-sn-glycero-3-phosphate + ADP + H(+) (RHEA:41672)
• 1-O-hexadecyl-2-acetyl-sn-glycerol + ATP = 1-O-hexadecyl-2-acetyl-sn-glycero-3-phosphate + ADP + H(+) (RHEA:41676)
• 1-hexadecanoyl-2-(9Z-octadecenoyl)-sn-glycerol + ATP = 1-hexadecanoyl-2-(9Z-octadecenoyl)-sn-glycero-3-phosphate + ADP + H(+) (RHEA:43416)
• 1,2-didecanoyl-sn-glycerol + ATP = 1,2-didecanoyl-sn-glycero-3-phosphate + ADP + H(+) (RHEA:43428)
• 1-O-alkyl-2-acyl-sn-glycerol + ATP = 1-O-alkyl-2-acyl-sn-glycero-3-phosphate + ADP + H(+) (RHEA:44072)
• 1,2-dihexadecanoyl-sn-glycerol + ATP = 1,2-dihexadecanoyl-sn-glycero-3-phosphate + ADP + H(+) (RHEA:63324)

UniProt features (43 total): helix 11, binding site 9, sequence conflict 6, splice variant 4, domain 3, mutagenesis site 2, strand 2, zinc finger region 2, chain 1, modified residue 1, sequence variant 1, turn 1

Structure

Experimental structures (PDB)

2 structures.

PDB	Method	Resolution (Å)
6IIE	X-RAY DIFFRACTION	2.14
1TUZ	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P23743-F1	82.51	0.45

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Ligand- & substrate-binding residues (9): 168; 170; 172; 174; 179; 123; 125; 127; 134

Post-translational modifications (1): 484

Mutagenesis-validated functional residues (2):

Position	Phenotype
134	binds calcium but with decreased affinity.
179	loss of calcium-binding.

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-114508	Effects of PIP2 hydrolysis

MSigDB gene sets: 385 (showing top): GOBP_LIPID_MODIFICATION, GOBP_PHOSPHOLIPID_METABOLIC_PROCESS, JAEGER_METASTASIS_DN, REACTOME_PLATELET_ACTIVATION_SIGNALING_AND_AGGREGATION, GOBP_PLATELET_ACTIVATION, MODULE_45, AREB6_03, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_UP, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_UP, LINDGREN_BLADDER_CANCER_CLUSTER_3_DN, GOBP_ORGANOPHOSPHATE_METABOLIC_PROCESS, GOBP_ORGANOPHOSPHATE_BIOSYNTHETIC_PROCESS, GOBP_PHOSPHOLIPID_BIOSYNTHETIC_PROCESS, GOBP_GLYCEROLIPID_METABOLIC_PROCESS, GOBP_WOUND_HEALING

GO Biological Process (9): phosphatidic acid biosynthetic process (GO:0006654), phospholipase C-activating G protein-coupled receptor signaling pathway (GO:0007200), platelet activation (GO:0030168), intracellular signal transduction (GO:0035556), diacylglycerol metabolic process (GO:0046339), glycerolipid metabolic process (GO:0046486), lipid phosphorylation (GO:0046834), lipid metabolic process (GO:0006629), signal transduction (GO:0007165)

GO Molecular Function (11): ATP-dependent diacylglycerol kinase activity (GO:0004143), calcium ion binding (GO:0005509), ATP binding (GO:0005524), phospholipid binding (GO:0005543), zinc ion binding (GO:0008270), lipid binding (GO:0008289), kinase activity (GO:0016301), alkylglycerol kinase activity (GO:0047649), nucleotide binding (GO:0000166), transferase activity (GO:0016740), metal ion binding (GO:0046872)

GO Cellular Component (4): cytosol (GO:0005829), plasma membrane (GO:0005886), membrane (GO:0016020), cytoplasm (GO:0005737)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
G alpha (q) signalling events	1
Platelet activation, signaling and aggregation	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
intracellular anatomical structure	2
phosphotransferase activity, alcohol group as acceptor	2
phosphatidic acid metabolic process	1
glycerophospholipid biosynthetic process	1
G protein-coupled receptor signaling pathway	1
phospholipase C activator activity	1
cell activation	1
blood coagulation	1
signal transduction	1
acylglycerol metabolic process	1
lipid metabolic process	1
phosphorylation	1
lipid modification	1
primary metabolic process	1
cell communication	1
cellular process	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
lipid kinase activity	1
metal ion binding	1
adenyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
lipid binding	1
transition metal ion binding	1
binding	1
transferase activity, transferring phosphorus-containing groups	1
kinase activity	1
nucleoside phosphate binding	1
heterocyclic compound binding	1
catalytic activity	1
cation binding	1
cytoplasm	1
membrane	1
cell periphery	1

Protein interactions and networks

STRING

902 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
DGKA	RASGRP1	O95267	865
DGKA	CERK	Q8TCT0	778
DGKA	PFKM	P08237	732
DGKA	SPHK1	Q9NYA1	714
DGKA	SPHK2	Q9NRA0	601
DGKA	DGKD	Q16760	564
DGKA	SRC	P12931	552
DGKA	PLEK2	Q9NYT0	520
DGKA	PLEK	P08567	519
DGKA	ATOSB	Q7L5A3	508
DGKA	DGKQ	P52824	481
DGKA	DGKH	Q86XP1	476
DGKA	PFKP	Q01813	470
DGKA	PLD2	O14939	464
DGKA	ARRB1	P49407	455

IntAct

11 interactions, top by confidence:

A	B	Type	Score
CNOT3	CNOT1	psi-mi:“MI:0914”(association)	0.740
CFTR	ESYT2	psi-mi:“MI:0914”(association)	0.710
KCTD17	CBX4	psi-mi:“MI:0914”(association)	0.530
SRC	DGKA	psi-mi:“MI:0914”(association)	0.460
DGKA	DHRS4	psi-mi:“MI:0915”(physical association)	0.400
EEF1AKMT3	SMCHD1	psi-mi:“MI:0914”(association)	0.350
CDH5	ESYT2	psi-mi:“MI:2364”(proximity)	0.270
DGKA	IL21	psi-mi:“MI:2364”(proximity)	0.270
	DGKA	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (15): DGKA (Affinity Capture-MS), DGKA (Co-localization), DGKA (Affinity Capture-MS), DGKA (Affinity Capture-MS), DHRS4 (Affinity Capture-MS), DGKA (Affinity Capture-MS), OTUD3 (Cross-Linking-MS (XL-MS)), CTTN (Cross-Linking-MS (XL-MS)), DGKA (Affinity Capture-MS), STX7 (Cross-Linking-MS (XL-MS)), DGKA (Proximity Label-MS), DGKA (Proximity Label-MS), DGKA (Affinity Capture-MS), DGKA (Affinity Capture-MS), ORC5 (Co-fractionation)

ESM2 similar proteins: A0A078BQP2, A0A131MCZ8, A0JN54, A3KGB4, A3QM97, A8WPG9, G5ED05, O16715, O88673, P11528, P20192, P23743, P23897, P25092, P30733, P33530, P49619, P49620, P49621, P51556, P55141, P55204, P70106, P90895, P91550, Q03603, Q09435, Q0IIM8, Q10029, Q17586, Q19954, Q22949, Q23681, Q3UWA6, Q4V339, Q4V3C7, Q5JTY5, Q5RIA9, Q618H8, Q67XQ0

Diamond homologs: A0JN54, A8JQ65, B3LXF2, B3NYS4, B4I4Y1, B4JHJ7, B4K6T8, B4PRE2, B4R0A5, D3YWQ0, D3ZEY4, F1MAB7, O08560, O75912, O88673, P0CM54, P0CM55, P20192, P23743, P25296, P34057, P34125, P35243, P49619, P49620, P49621, P51556, P52429, P52824, P87072, Q01583, Q03603, Q09103, Q10024, Q13574, Q39017, Q6BWS8, Q6CGE6, Q6DT37, Q6FLU4

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
SRC	up-regulates	DGKA	phosphorylation

Disease & clinical

Clinical variants and AI predictions

ClinVar

114 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	60
Likely benign	8
Benign	7

Top pathogenic / likely-pathogenic (0)

SpliceAI

3796 predictions. Top by Δscore:

Variant	Effect	Δscore
12:55936563:GGAAT:G	donor_gain	1.0000
12:55936564:GAATG:G	donor_gain	1.0000
12:55937010:A:AG	acceptor_gain	1.0000
12:55937011:C:G	acceptor_gain	1.0000
12:55937088:GAT:G	donor_gain	1.0000
12:55937091:G:GG	donor_gain	1.0000
12:55938445:ATTCT:A	acceptor_gain	1.0000
12:55938561:G:GG	donor_gain	1.0000
12:55939177:T:TA	acceptor_gain	1.0000
12:55939179:T:TA	acceptor_gain	1.0000
12:55939183:CA:C	acceptor_loss	1.0000
12:55939184:AGA:A	acceptor_loss	1.0000
12:55939244:C:G	donor_gain	1.0000
12:55939302:GATG:G	donor_gain	1.0000
12:55939303:ATGGT:A	donor_loss	1.0000
12:55939304:TG:T	donor_gain	1.0000
12:55939304:TGGTG:T	donor_loss	1.0000
12:55939305:GG:G	donor_gain	1.0000
12:55939305:GGTG:G	donor_loss	1.0000
12:55939306:G:GG	donor_gain	1.0000
12:55939307:T:A	donor_loss	1.0000
12:55939410:CCTA:C	acceptor_loss	1.0000
12:55939411:CTAG:C	acceptor_loss	1.0000
12:55939412:TAG:T	acceptor_loss	1.0000
12:55939413:A:AG	acceptor_gain	1.0000
12:55939413:AGACT:A	acceptor_loss	1.0000
12:55939414:G:GA	acceptor_loss	1.0000
12:55939414:G:GG	acceptor_gain	1.0000
12:55939514:GGAC:G	donor_gain	1.0000
12:55939526:AACCG:A	donor_loss	1.0000

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000046334 (12:55950395 C>G,T), RS1000063786 (12:55944180 G>A,C), RS1000078833 (12:55950613 T>G), RS1000242782 (12:55954069 C>T), RS1000276219 (12:55932369 G>A), RS1000709664 (12:55930793 C>T), RS1000767449 (12:55938799 C>T), RS1000875497 (12:55946947 CT>C,CTT), RS1000909486 (12:55934095 C>G,T), RS1001078790 (12:55952182 G>A,T), RS1001079776 (12:55930568 G>A), RS1001256703 (12:55934355 G>A), RS1001469731 (12:55945669 T>A), RS1001544236 (12:55930503 A>G), RS1001704731 (12:55941108 G>A)

Disease associations

OMIM: gene MIM:125855 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST001670_1	Vitiligo	8.000000e-12
GCST004367_1	Anorexia nervosa	4.000000e-09
GCST010002_217	Refractive error	6.000000e-174

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (2): CHEMBL4105787 (SINGLE PROTEIN), CHEMBL4630754 (PROTEIN FAMILY)

Molecules with ChEMBL bioactivity

1 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 4,779 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL267777	RITANSERIN	2	4,779

PharmGKB: 1 entry (VIP=true, CPIC=false)

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: enzyme — Diacylglycerol kinases

Most potent curated ligand interactions (4 total), top 4:

Ligand	Action	Affinity	Parameter
compound 16 [PMID: 40916365]	Inhibition	9.57	pIC50
pasodacigib	Inhibition	9.3	pIC50
BMS-502	Inhibition	8.34	pIC50
BMS-684	Inhibition	7.82	pIC50

Binding affinities (BindingDB)

214 measured of 286 human assays (286 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
US20250223301, Compound 39	IC50	1 nM	US-20250223301: KINASE INHIBITORS, PREPARATION METHODS AND USES THEREOF
8-[(2S,5R)-2,5-diethyl-4-[(1S)-1-(4-methylphenyl)propyl]piperazin-1-yl]-2,4,5,7,10-pentazatricyclo[7.4.0.02,6]trideca-1(9),3,5,7,10,12-hexaene-11-carbonitrile	IC50	1 nM	US-20250223301: KINASE INHIBITORS, PREPARATION METHODS AND USES THEREOF
6-chloro-1-methyl-4-[4-(5-methyl-1,3-benzoxazol-2-yl)piperidin-1-yl]-7-(oxolan-3-yloxy)quinazolin-2-one	IC50	2 nM	US-20250223301: KINASE INHIBITORS, PREPARATION METHODS AND USES THEREOF
8-[(2S,5R)-5-ethyl-2-methyl-4-[(1S)-1-(4-methylphenyl)propyl]piperazin-1-yl]-2,4,5,7,10-pentazatricyclo[7.4.0.02,6]trideca-1(9),3,5,7,10,12-hexaene-11-carbonitrile	IC50	2 nM	US-20250223301: KINASE INHIBITORS, PREPARATION METHODS AND USES THEREOF
5-[(2S,5R)-2,5-diethyl-4-[1-(4-methylphenyl)propyl]piperazin-1-yl]-[1,2,4]triazolo[4,3-a][1,5]naphthyridine-7-carbonitrile	IC50	2 nM	US-20250223301: KINASE INHIBITORS, PREPARATION METHODS AND USES THEREOF
US20250223301, Compound 41	IC50	3 nM	US-20250223301: KINASE INHIBITORS, PREPARATION METHODS AND USES THEREOF
US20250223301, Compound 42	IC50	3 nM	US-20250223301: KINASE INHIBITORS, PREPARATION METHODS AND USES THEREOF
US20250223301, Compound 43	IC50	3 nM	US-20250223301: KINASE INHIBITORS, PREPARATION METHODS AND USES THEREOF
US20250223301, Compound 115	IC50	3 nM	US-20250223301: KINASE INHIBITORS, PREPARATION METHODS AND USES THEREOF
US20250215014, Compound 119	IC50	3 nM	US-20250223301: KINASE INHIBITORS, PREPARATION METHODS AND USES THEREOF
4-[(2S,5R)-4-[(3-cyclopropyl-1,2,4-oxadiazol-5-yl)-(4-methylphenyl)methyl]-2,5-diethylpiperazin-1-yl]-1-methyl-2-oxopyrido[3,2-d]pyrimidine-6-carbonitrile	IC50	3 nM	US-20250223301: KINASE INHIBITORS, PREPARATION METHODS AND USES THEREOF
US20250223301, Compound 23	IC50	4 nM	US-20250223301: KINASE INHIBITORS, PREPARATION METHODS AND USES THEREOF
(4R,7S)-4-ethyl-12-methyl-11-oxo-5-[1-[4-(trifluoromethyl)phenyl]propyl]-9-oxa-2,5,12,17-tetrazatetracyclo[8.8.0.02,7.013,18]octadeca-1(10),13(18),14,16-tetraene-16-carbonitrile	IC50	4 nM	US-20250223301: KINASE INHIBITORS, PREPARATION METHODS AND USES THEREOF
8-[(2S,5R)-5-ethyl-2-methyl-4-[1-(4-methylphenyl)propyl]piperazin-1-yl]-2,4,5,7,10-pentazatricyclo[7.4.0.02,6]trideca-1(9),3,5,7,10,12-hexaene-11-carbonitrile	IC50	4 nM	US-20250223301: KINASE INHIBITORS, PREPARATION METHODS AND USES THEREOF
6-chloro-4-[(2R,4R)-2-ethyl-4-(5-methyl-1,3-benzoxazol-2-yl)piperidin-1-yl]-1-methyl-7-(oxolan-3-yloxy)quinazolin-2-one	IC50	4 nM	US-20250223301: KINASE INHIBITORS, PREPARATION METHODS AND USES THEREOF
4-[(2S,5R)-4-[(S)-(4-cyclopropyl-1,3-thiazol-2-yl)-[4-(pentafluoro-lambda6-sulfanyl)phenyl]methyl]-2,5-diethylpiperazin-1-yl]-1-methyl-2-oxopyrido[3,2-d]pyrimidine-6-carbonitrile	IC50	4 nM	US-20250223301: KINASE INHIBITORS, PREPARATION METHODS AND USES THEREOF
8-[(2S,5R)-2,5-diethyl-4-[(1S)-1-(3-methylphenyl)propyl]piperazin-1-yl]-2,4,5,7,10-pentazatricyclo[7.4.0.02,6]trideca-1(9),3,5,7,10,12-hexaene-11-carbonitrile	IC50	4 nM	US-20250223301: KINASE INHIBITORS, PREPARATION METHODS AND USES THEREOF
US20250223301, Compound 22	IC50	5 nM	US-20250223301: KINASE INHIBITORS, PREPARATION METHODS AND USES THEREOF
US20250223301, Compound 46	IC50	5 nM	US-20250223301: KINASE INHIBITORS, PREPARATION METHODS AND USES THEREOF
8-[(2S,5R)-2,5-diethyl-4-[(1R)-1-(4-methylphenyl)ethyl]piperazin-1-yl]-2,4,5,7,10-pentazatricyclo[7.4.0.02,6]trideca-1(9),3,5,7,10,12-hexaene-11-carbonitrile	IC50	5 nM	US-20250223301: KINASE INHIBITORS, PREPARATION METHODS AND USES THEREOF
8-[(2S,5R)-2,5-diethyl-4-[(1S)-1-(4-methylphenyl)propyl]piperazin-1-yl]-2,4,5,7,10-pentazatricyclo[7.4.0.02,6]trideca-1(9),3,5,7,10,12-hexaene-11-carbonitrile	IC50	5 nM	US-20250223301: KINASE INHIBITORS, PREPARATION METHODS AND USES THEREOF
6-chloro-4-[(2R,4S)-2-ethyl-4-(5-methyl-1,3-benzoxazol-2-yl)piperidin-1-yl]-1-methyl-7-(oxolan-3-yloxy)quinazolin-2-one	IC50	5 nM	US-20250223301: KINASE INHIBITORS, PREPARATION METHODS AND USES THEREOF
US20250223301, Compound 109	IC50	6 nM	US-20250223301: KINASE INHIBITORS, PREPARATION METHODS AND USES THEREOF
US20250223301, Compound 110	IC50	6 nM	US-20250223301: KINASE INHIBITORS, PREPARATION METHODS AND USES THEREOF
8-[(2S,5R)-5-ethyl-2-methyl-4-[(1R)-1-(4-methylphenyl)propyl]piperazin-1-yl]-2,4,5,7,10-pentazatricyclo[7.4.0.02,6]trideca-1(9),3,5,7,10,12-hexaene-11-carbonitrile	IC50	6 nM	US-20250223301: KINASE INHIBITORS, PREPARATION METHODS AND USES THEREOF
(4R,7S)-4-ethyl-12-methyl-11-oxo-5-[(1R)-1-[4-(trifluoromethyl)phenyl]propyl]-9-oxa-2,5,12,17-tetrazatetracyclo[8.8.0.02,7.013,18]octadeca-1(10),13(18),14,16-tetraene-16-carbonitrile	IC50	6 nM	US-20250223301: KINASE INHIBITORS, PREPARATION METHODS AND USES THEREOF
8-[(2S,5R)-2,5-diethyl-4-[(1S)-1-(6-methyl-3-pyridinyl)propyl]piperazin-1-yl]-2,4,5,7,10-pentazatricyclo[7.4.0.02,6]trideca-1(9),3,5,7,10,12-hexaene-11-carbonitrile	IC50	7 nM	US-20250223301: KINASE INHIBITORS, PREPARATION METHODS AND USES THEREOF
US20250223301, Compound 84	IC50	9 nM	US-20250223301: KINASE INHIBITORS, PREPARATION METHODS AND USES THEREOF
US20250215014, Compound 107	IC50	9 nM	US-20250223301: KINASE INHIBITORS, PREPARATION METHODS AND USES THEREOF
6-chloro-1-methyl-4-[4-(5-methyl-1,3-benzoxazol-2-yl)piperidin-1-yl]-7-(oxolan-3-yloxy)quinazolin-2-one	IC50	9 nM	US-20250223301: KINASE INHIBITORS, PREPARATION METHODS AND USES THEREOF
4-[(2S,5R)-4-[(S)-(4-cyclopropyl-1,3-thiazol-2-yl)-(4-methylphenyl)methyl]-2,5-diethylpiperazin-1-yl]-1-methyl-2-oxopyrido[3,2-d]pyrimidine-6-carbonitrile	IC50	9 nM	US-20250223301: KINASE INHIBITORS, PREPARATION METHODS AND USES THEREOF
5-[(2S,5R)-2,5-diethyl-4-[1-(4-methylphenyl)propyl]piperazin-1-yl]-[1,2,4]triazolo[4,3-a][1,5]naphthyridine-7-carbonitrile	IC50	9 nM	US-20250223301: KINASE INHIBITORS, PREPARATION METHODS AND USES THEREOF
US20250223301, Compound 64	IC50	10 nM	US-20250223301: KINASE INHIBITORS, PREPARATION METHODS AND USES THEREOF
US20250223301, Compound 74	IC50	10 nM	US-20250223301: KINASE INHIBITORS, PREPARATION METHODS AND USES THEREOF
8-[(2S,5R)-2,5-diethyl-4-[(1R)-1-(4-methylphenyl)propyl]piperazin-1-yl]-2,4,5,7,10-pentazatricyclo[7.4.0.02,6]trideca-1(9),3,5,7,10,12-hexaene-11-carbonitrile	IC50	10 nM	US-20250223301: KINASE INHIBITORS, PREPARATION METHODS AND USES THEREOF
8-[(2S,5R)-2,5-diethyl-4-[1-(4-methylphenyl)ethyl]piperazin-1-yl]-2,4,5,7,10-pentazatricyclo[7.4.0.02,6]trideca-1(9),3,5,7,10,12-hexaene-11-carbonitrile	IC50	10 nM	US-20250223301: KINASE INHIBITORS, PREPARATION METHODS AND USES THEREOF
8-[(2S,5R)-5-ethyl-2-methyl-4-[1-(4-methylphenyl)propyl]piperazin-1-yl]-2,4,5,7,10-pentazatricyclo[7.4.0.02,6]trideca-1(9),3,5,7,10,12-hexaene-11-carbonitrile	IC50	10 nM	US-20250223301: KINASE INHIBITORS, PREPARATION METHODS AND USES THEREOF
4-[(2S,5R)-4-[(R)-(4-cyclopropyl-1,3-thiazol-2-yl)-[4-(pentafluoro-lambda6-sulfanyl)phenyl]methyl]-2,5-diethylpiperazin-1-yl]-1-methyl-2-oxopyrido[3,2-d]pyrimidine-6-carbonitrile	IC50	10 nM	US-20250223301: KINASE INHIBITORS, PREPARATION METHODS AND USES THEREOF
8-[(2S,5R)-4-[(1R)-1-(3-cyclopropyl-1,2,4-oxadiazol-5-yl)propyl]-2,5-diethylpiperazin-1-yl]-2,4,5,7,10-pentazatricyclo[7.4.0.02,6]trideca-1(9),3,5,7,10,12-hexaene-11-carbonitrile	IC50	10 nM	US-20250223301: KINASE INHIBITORS, PREPARATION METHODS AND USES THEREOF
2-[(2R,5S)-4-(6-cyano-1-methyl-2-oxopyrido[3,2-d]pyrimidin-4-yl)-2,5-diethylpiperazin-1-yl]-N-(2-methoxyethyl)-2-[4-(trifluoromethyl)phenyl]acetamide	IC50	10 nM	US-12454531: Substituted piperazine derivatives useful as T cell activators
8-[(2S,5R)-2,5-diethyl-4-[(1R)-1-(4-methylphenyl)propyl]piperazin-1-yl]-2,4,5,7,10-pentazatricyclo[7.4.0.02,6]trideca-1(9),3,5,7,10,12-hexaene-11-carbonitrile	IC50	11 nM	US-20250223301: KINASE INHIBITORS, PREPARATION METHODS AND USES THEREOF
8-[(2S,5R)-2,5-diethyl-4-[(1R)-1-(6-methyl-3-pyridinyl)propyl]piperazin-1-yl]-2,4,5,7,10-pentazatricyclo[7.4.0.02,6]trideca-1(9),3,5,7,10,12-hexaene-11-carbonitrile	IC50	11 nM	US-20250223301: KINASE INHIBITORS, PREPARATION METHODS AND USES THEREOF
US20250223301, Compound 28	IC50	12 nM	US-20250223301: KINASE INHIBITORS, PREPARATION METHODS AND USES THEREOF
US20250223301, Compound 47	IC50	12 nM	US-20250223301: KINASE INHIBITORS, PREPARATION METHODS AND USES THEREOF
8-[(2S,5R)-5-ethyl-2-methyl-4-[1-(4-methylphenyl)propyl]piperazin-1-yl]-2,4,5,7,10-pentazatricyclo[7.4.0.02,6]trideca-1(9),3,5,7,10,12-hexaene-11-carbonitrile	IC50	12 nM	US-20250223301: KINASE INHIBITORS, PREPARATION METHODS AND USES THEREOF
6-chloro-4-[(2R,4R)-2-ethyl-4-(5-methyl-1,3-benzoxazol-2-yl)piperidin-1-yl]-1-methyl-7-(oxolan-3-yloxy)quinazolin-2-one	IC50	12 nM	US-20250223301: KINASE INHIBITORS, PREPARATION METHODS AND USES THEREOF
US20250223301, Compound 21	IC50	13 nM	US-20250223301: KINASE INHIBITORS, PREPARATION METHODS AND USES THEREOF
US20250223301, Compound 72	IC50	13 nM	US-20250223301: KINASE INHIBITORS, PREPARATION METHODS AND USES THEREOF
US20250223301, Compound 29	IC50	14 nM	US-20250223301: KINASE INHIBITORS, PREPARATION METHODS AND USES THEREOF
US20250223301, Compound 116	IC50	14 nM	US-20250223301: KINASE INHIBITORS, PREPARATION METHODS AND USES THEREOF

ChEMBL bioactivities

215 potent at pChembl≥5 of 229 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
8.70	IC50	2	nM	CHEMBL6027746
8.70	IC50	2	nM	CHEMBL5781357
8.70	IC50	2	nM	CHEMBL5768187
8.30	IC50	5	nM	CHEMBL5424446
8.30	IC50	5	nM	CHEMBL5818523
8.15	IC50	7	nM	CHEMBL5915983
8.02	IC50	9.6	nM	CHEMBL4633304
8.00	IC50	10	nM	CHEMBL5919576
8.00	IC50	10	nM	CHEMBL5845562
7.85	IC50	14	nM	CHEMBL5849375
7.82	IC50	15	nM	CHEMBL5408449
7.80	IC50	16	nM	CHEMBL5767075
7.80	IC50	16	nM	CHEMBL5993135
7.80	IC50	16	nM	CHEMBL6012969
7.80	IC50	16	nM	CHEMBL6046889
7.66	IC50	22	nM	CHEMBL5788045
7.58	IC50	26	nM	CHEMBL4648848
7.58	IC50	26	nM	CHEMBL6053165
7.55	IC50	28	nM	CHEMBL4647083
7.55	IC50	28	nM	CHEMBL5904241
7.55	IC50	28	nM	CHEMBL5865642
7.54	IC50	29	nM	CHEMBL5999766
7.54	IC50	29	nM	CHEMBL5749461
7.54	IC50	29	nM	CHEMBL5798900
7.52	IC50	30	nM	CHEMBL5771377
7.52	IC50	30	nM	CHEMBL5918545
7.52	IC50	30	nM	CHEMBL5828074
7.52	IC50	30	nM	CHEMBL5846539
7.50	IC50	32	nM	CHEMBL5767075
7.50	IC50	32	nM	CHEMBL5919513
7.47	IC50	34	nM	CHEMBL5402920
7.47	IC50	34	nM	CHEMBL5758324
7.44	IC50	36	nM	CHEMBL5916345
7.43	IC50	37	nM	CHEMBL5793843
7.43	IC50	37	nM	CHEMBL5860953
7.42	IC50	38	nM	CHEMBL5907037
7.41	IC50	39	nM	CHEMBL4646970
7.41	IC50	39	nM	CHEMBL5816364
7.41	IC50	39	nM	CHEMBL5963493
7.40	IC50	40	nM	CHEMBL5868935
7.40	IC50	40	nM	CHEMBL5915810
7.37	IC50	43	nM	CHEMBL4645744
7.37	IC50	43	nM	CHEMBL5794331
7.35	IC50	45	nM	CHEMBL5798900
7.33	IC50	47	nM	CHEMBL5794331
7.33	IC50	47	nM	CHEMBL5870719
7.28	IC50	53	nM	CHEMBL5413938
7.28	IC50	52	nM	CHEMBL5828074
7.28	IC50	52	nM	CHEMBL5741470
7.26	IC50	55	nM	CHEMBL5969668

PubChem BioAssay actives

30 with measured affinity, of 87 total; 17 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
8-[4-[bis(4-fluorophenyl)methyl]piperazin-1-yl]-5-methyl-7-nitro-6-oxo-1,5-naphthyridine-2-carbonitrile	2010060: Inhibition of human DGK alpha using 1, 2-Dilauroyl-sn-glycerol as substrate by ADP-Glo assay	ic50	0.0050	uM
8-[(3R)-4-[(4-chlorophenyl)-phenylmethyl]-3-methylpiperazin-1-yl]-5-methyl-6-oxo-1,5-naphthyridine-2,7-dicarbonitrile	1658256: Inhibition of DGKA/DGKZ in human CD8 cells assessed as induction of CD8 activation by measuring IFNgamma level after 20 hrs by AlphaLISA assay	ic50	0.0096	uM
4-(4-benzhydrylpiperazin-1-yl)-1-methyl-3-nitroquinolin-2-one	2010060: Inhibition of human DGK alpha using 1, 2-Dilauroyl-sn-glycerol as substrate by ADP-Glo assay	ic50	0.0150	uM
8-[(2S,5R)-4-[(2-fluorophenyl)-(4-fluorophenyl)methyl]-2,5-dimethylpiperazin-1-yl]-5-methyl-6-oxo-1,5-naphthyridine-2-carbonitrile	1658256: Inhibition of DGKA/DGKZ in human CD8 cells assessed as induction of CD8 activation by measuring IFNgamma level after 20 hrs by AlphaLISA assay	ic50	0.0260	uM
8-[(3R)-4-[bis(4-chlorophenyl)methyl]-3-methylpiperazin-1-yl]-5-methyl-6-oxo-1,5-naphthyridine-2,7-dicarbonitrile	1658256: Inhibition of DGKA/DGKZ in human CD8 cells assessed as induction of CD8 activation by measuring IFNgamma level after 20 hrs by AlphaLISA assay	ic50	0.0280	uM
4-[4-[bis(4-fluorophenyl)methyl]piperazin-1-yl]-1-methyl-3-nitro-2-oxoquinoline-6-carbonitrile	2010060: Inhibition of human DGK alpha using 1, 2-Dilauroyl-sn-glycerol as substrate by ADP-Glo assay	ic50	0.0340	uM
8-[(2S,5R)-4-[(2,2-difluoro-1,3-benzodioxol-5-yl)methyl]-2,5-dimethylpiperazin-1-yl]-5-methyl-6-oxo-1,5-naphthyridine-2-carbonitrile	1658256: Inhibition of DGKA/DGKZ in human CD8 cells assessed as induction of CD8 activation by measuring IFNgamma level after 20 hrs by AlphaLISA assay	ic50	0.0390	uM
8-[(2S,5R)-4-[bis(4-fluorophenyl)methyl]-2,5-dimethylpiperazin-1-yl]-5-methyl-6-oxo-1,5-naphthyridine-2-carbonitrile	1658256: Inhibition of DGKA/DGKZ in human CD8 cells assessed as induction of CD8 activation by measuring IFNgamma level after 20 hrs by AlphaLISA assay	ic50	0.0430	uM
4-[4-[bis(4-fluorophenyl)methyl]piperazin-1-yl]-1-methyl-3-nitro-1,5-naphthyridin-2-one	2010060: Inhibition of human DGK alpha using 1, 2-Dilauroyl-sn-glycerol as substrate by ADP-Glo assay	ic50	0.0530	uM
8-[(2R)-4-[bis(4-fluorophenyl)methyl]-2-ethylpiperazin-1-yl]-5-methyl-6-oxo-1,5-naphthyridine-2-carbonitrile	1658256: Inhibition of DGKA/DGKZ in human CD8 cells assessed as induction of CD8 activation by measuring IFNgamma level after 20 hrs by AlphaLISA assay	ic50	0.1900	uM
3-[2-[4-[bis(4-fluorophenyl)methylidene]piperidin-1-yl]ethyl]-2-sulfanylidene-1H-quinazolin-4-one	1613990: Inhibition of DGKalpha in human erythrocytes using OAG as substrate preincubated for 1 min followed by OAG addition and measured after 8 mins in presence of [gamma-32P]ATP	ic50	0.3000	uM
N-[(5Z)-5-[(E)-3-(furan-2-yl)prop-2-enylidene]-4-oxo-2-sulfanylidene-1,3-thiazolidin-3-yl]benzenesulfonamide	2010060: Inhibition of human DGK alpha using 1, 2-Dilauroyl-sn-glycerol as substrate by ADP-Glo assay	ic50	0.6000	uM
8-[(3S)-4-[bis(4-fluorophenyl)methyl]-3-methylpiperazin-1-yl]-7-chloro-5-methyl-6-oxo-1,5-naphthyridine-2-carbonitrile	1658256: Inhibition of DGKA/DGKZ in human CD8 cells assessed as induction of CD8 activation by measuring IFNgamma level after 20 hrs by AlphaLISA assay	ic50	1.2000	uM
[(2S,3R,4S)-2-[(3R,4aR,6aR,12S,12aS,12bR)-12-hydroxy-3-(2-hydroxypropan-2-yl)-6a,12b-dimethyl-8,11-dioxo-1,2,3,4a,5,6,12,12a-octahydropyrano[3,2-a]xanthen-9-yl]-4-methylhexan-3-yl] acetate	1613990: Inhibition of DGKalpha in human erythrocytes using OAG as substrate preincubated for 1 min followed by OAG addition and measured after 8 mins in presence of [gamma-32P]ATP	ki	2.2600	uM
[(E,2S,3S)-2-[(3R,4aR,6aR,12S,12aS,12bR)-12-hydroxy-3-(2-hydroxypropan-2-yl)-6a,12b-dimethyl-8,11-dioxo-1,2,3,4a,5,6,12,12a-octahydropyrano[3,2-a]xanthen-9-yl]-4-methylhex-4-en-3-yl] acetate	1613990: Inhibition of DGKalpha in human erythrocytes using OAG as substrate preincubated for 1 min followed by OAG addition and measured after 8 mins in presence of [gamma-32P]ATP	ki	3.3200	uM
6-[2-[4-[(4-fluorophenyl)-phenylmethylidene]piperidin-1-yl]ethyl]-7-methyl-[1,3]thiazolo[3,2-a]pyrimidin-5-one	1613990: Inhibition of DGKalpha in human erythrocytes using OAG as substrate preincubated for 1 min followed by OAG addition and measured after 8 mins in presence of [gamma-32P]ATP	ic50	3.8000	uM
1-(2,6-dimethyl-1H-indol-3-yl)-2-[4-(furan-2-carbonyl)piperazin-1-yl]ethanone	1613974: Inhibition of OST-tagged DGKalpha (unknown origin) expressed in MDCK cell homogenates using DAG as substrate measured after 5 mins in presence of [gamma-32P]ATP by TLC analysis	ic50	4.2810	uM

CTD chemical–gene interactions

64 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	affects methylation, decreases expression, decreases methylation, increases expression, increases methylation	5
Aflatoxin B1	affects expression, increases expression	4
Cisplatin	affects cotreatment, increases expression	3
Air Pollutants	increases expression, affects cotreatment, increases abundance, increases oxidation	2
Testosterone	affects cotreatment, increases expression, decreases expression	2
Tetrachlorodibenzodioxin	increases expression	2
Tobacco Smoke Pollution	decreases expression	2
Particulate Matter	increases abundance, increases expression	2
bisphenol F	affects cotreatment, increases expression	1
chloroacetaldehyde	affects expression	1
alpha phellandrene	increases expression	1
alpha-pinene	affects cotreatment, increases oxidation, increases abundance	1
uranyl acetate	affects expression	1
propionaldehyde	increases expression	1
pirinixic acid	decreases expression, increases activity, affects binding	1
pyrogallol 1,3-dimethyl ether	affects cotreatment, decreases expression, affects localization, increases expression	1
decabromobiphenyl ether	decreases expression	1
pyrazolo(3,4-d)pyrimidine	affects expression	1
arsenite	decreases reaction, affects binding	1
sodium arsenite	increases expression	1
tetrabromobisphenol A	increases expression	1
nickel sulfate	decreases expression	1
methacrylaldehyde	affects cotreatment, increases oxidation, increases abundance	1
di-n-butylphosphoric acid	affects expression	1
perfluorooctane sulfonic acid	increases expression	1
CGP 52608	affects binding, increases reaction	1
adefovir dipivoxil	increases expression	1
erucylphospho-N,N,N-trimethylpropylammonium	increases expression	1
nutlin 3	affects cotreatment, increases expression	1
bisphenol B	increases expression	1

ChEMBL screening assays

43 unique, capped per target: 43 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL4034309	Binding	Inhibition of DGKA (unknown origin) at 10 uM	Developing DYRK inhibitors derived from the meridianins as a means of increasing levels of NFAT in the nucleus. — Bioorg Med Chem Lett

Cellosaurus cell lines

7 cell lines: 6 cancer cell line, 1 transformed cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_D1M9	Abcam K-562 DGKA KO	Cancer cell line	Female
CVCL_D2IU	Abcam Raji DGKA KO	Cancer cell line	Male
CVCL_D7NI	Ubigene A-549 DGKA KO	Cancer cell line	Male
CVCL_D8JY	Ubigene HCT 116 DGKA KO	Cancer cell line	Male
CVCL_D9D7	Ubigene HEK293 DGKA KO	Transformed cell line	Female
CVCL_E0BM	Ubigene HeLa DGKA KO	Cancer cell line	Female
CVCL_UQ41	Abcam Jurkat DGKA KO	Cancer cell line	Male

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.