DGKB

Summary

DGKB (diacylglycerol kinase beta, HGNC:2850) is a protein-coding gene on chromosome 7p21.2, encoding Diacylglycerol kinase beta (Q9Y6T7). Diacylglycerol kinase that converts diacylglycerol/DAG into phosphatidic acid/phosphatidate/PA and regulates the respective levels of these two bioactive lipids.

Diacylglycerol kinases (DGKs) are regulators of the intracellular concentration of the second messenger diacylglycerol (DAG) and thus play a key role in cellular processes. Nine mammalian isotypes have been identified, which are encoded by separate genes. Mammalian DGK isozymes contain a conserved catalytic (kinase) domain and a cysteine-rich domain (CRD). The protein encoded by this gene is a diacylglycerol kinase, beta isotype. Several alternatively spliced transcript variants encoding different isoforms have been found for this gene.

Source: NCBI Gene 1607 — RefSeq curated summary.

At a glance

• GWAS associations: 56
• Clinical variants (ClinVar): 95 total
• Druggable target: yes
• MANE Select transcript: NM_001350709

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:2850
Approved symbol	DGKB
Name	diacylglycerol kinase beta
Location	7p21.2
Locus type	gene with protein product
Status	Approved
Aliases	KIAA0718, DGK, DGK-BETA
Ensembl gene	ENSG00000136267
Ensembl biotype	protein_coding
OMIM	604070
Entrez	1607

Gene structure

Transcript identifiers

Ensembl transcripts: 26 — 19 protein_coding, 5 protein_coding_CDS_not_defined, 2 retained_intron

ENST00000399322, ENST00000402815, ENST00000403951, ENST00000403963, ENST00000406247, ENST00000407950, ENST00000437998, ENST00000463981, ENST00000464065, ENST00000467449, ENST00000471732, ENST00000477401, ENST00000493142, ENST00000910828, ENST00000910829, ENST00000910830, ENST00000910831, ENST00000910832, ENST00000910833, ENST00000910834, ENST00000932238, ENST00000932239, ENST00000967726, ENST00000967727, ENST00000967728, ENST00000967729

RefSeq mRNA: 19 — MANE Select: NM_001350709 NM_001350705, NM_001350706, NM_001350707, NM_001350708, NM_001350709, NM_001350711, NM_001350712, NM_001350714, NM_001350715, NM_001350716, NM_001350717, NM_001350718, NM_001350719, NM_001350720, NM_001350721, NM_001350722, NM_001350723, NM_001350724, NM_145695

CCDS: CCDS47547, CCDS47548, CCDS87480, CCDS87481

Canonical transcript exons

ENST00000402815 — 26 exons

Exon	Start	End
ENSE00001546951	14902592	14902751
ENSE00001551315	14145049	14149238
ENSE00003472080	14682753	14682841
ENSE00003494343	14694075	14694194
ENSE00003496486	14736041	14736194
ENSE00003499152	14757655	14757731
ENSE00003500197	14682553	14682669
ENSE00003504227	14178031	14178151
ENSE00003523792	14753928	14753948
ENSE00003526496	14841194	14841450
ENSE00003549325	14718542	14718685
ENSE00003565221	14574212	14574372
ENSE00003565654	14698095	14698169
ENSE00003577245	14613340	14613413
ENSE00003611138	14338515	14338710
ENSE00003613592	14701681	14701730
ENSE00003617838	14607434	14607508
ENSE00003643797	14621378	14621494
ENSE00003657009	14630236	14630268
ENSE00003665795	14478161	14478225
ENSE00003669591	14580862	14580951
ENSE00003672494	14685245	14685362
ENSE00003681142	14672929	14673027
ENSE00003683474	14176839	14176899
ENSE00003692196	14345301	14345391
ENSE00003694123	14583052	14583137

Expression profiles

Bgee: expression breadth ubiquitous, 177 present calls, max score 88.73.

FANTOM5 (CAGE): breadth broad, TPM avg 4.2305 / max 588.4982, expressed in 267 samples.

FANTOM5 promoters (18 alternative TSS)

Promoter ID	TPM avg	Samples expressed
82845	0.9962	139
82839	0.7951	116
82848	0.5605	83
82843	0.5085	142
82841	0.3346	96
82844	0.2702	94
82842	0.1583	63
82836	0.1146	61
82838	0.0935	35
82837	0.0858	30

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
buccal mucosa cell	CL:0002336	88.73	gold quality
putamen	UBERON:0001874	85.98	gold quality
caudate nucleus	UBERON:0001873	85.59	gold quality
prefrontal cortex	UBERON:0000451	84.91	gold quality
nucleus accumbens	UBERON:0001882	84.40	gold quality
orbitofrontal cortex	UBERON:0004167	83.46	gold quality
superior frontal gyrus	UBERON:0002661	81.54	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	81.40	gold quality
Brodmann (1909) area 9	UBERON:0013540	81.14	gold quality
frontal cortex	UBERON:0001870	81.08	gold quality
Brodmann (1909) area 46	UBERON:0006483	79.84	gold quality
neocortex	UBERON:0001950	79.76	gold quality
telencephalon	UBERON:0001893	79.61	gold quality
middle temporal gyrus	UBERON:0002771	78.74	gold quality
cingulate cortex	UBERON:0003027	78.57	gold quality
cerebral cortex	UBERON:0000956	78.53	gold quality
anterior cingulate cortex	UBERON:0009835	78.39	gold quality
postcentral gyrus	UBERON:0002581	78.13	gold quality
frontal pole	UBERON:0002795	77.40	gold quality
Brodmann (1909) area 10	UBERON:0013541	77.13	gold quality
entorhinal cortex	UBERON:0002728	77.05	gold quality
Brodmann (1909) area 23	UBERON:0013554	77.03	gold quality
right frontal lobe	UBERON:0002810	76.65	gold quality
forebrain	UBERON:0001890	76.52	gold quality
parietal lobe	UBERON:0001872	75.80	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	74.65	silver quality
oocyte	CL:0000023	74.58	gold quality
corpus callosum	UBERON:0002336	74.43	gold quality
Ammon’s horn	UBERON:0001954	74.33	gold quality
primary visual cortex	UBERON:0002436	74.23	gold quality

Single-cell (SCXA)

Detected in 6 experiment(s), a significant marker in 6.

Experiment	Marker?	Max mean expression
E-HCAD-35	yes	5286.23
E-ANND-2	yes	3661.85
E-HCAD-30	yes	1800.22
E-HCAD-25	yes	1194.49
E-GEOD-93593	yes	7.65
E-ANND-3	yes	6.97

Regulation

Is transcription factor: no

Literature-anchored findings (GeneRIF, showing 10)

• human diacylglycerol kinase beta gene can generate several enzyme isoforms, which can display different expression levels and subcellular localization but similar enzymatic activities in vitro. (PMID:11719522)
• Indicates that this protein can interact with keratin 31 and with protocadherin beta 5. (PMID:17353931)
• findings further suggest that DGL-alpha and -beta may regulate neurite outgrowth by engaging temporally and spatially distinct molecular pathways (PMID:21493725)
• forced expression of diacylglycerol kinase beta abrogated DAG accumulation at the phagosome, leading to impaired respiratory burst. (PMID:23814057)
• in addition to kinase activity, plasma membrane localization via the C1 domain and basic amino acids at the C-terminus were indispensable for neurite induction by DGKbeta (PMID:24695318)
• Association with the efficiency of hematopoietic stem cells (HSC) mobilization to PB were found in the SNPs of the DGKB gene involved in cell transport and SDF-1-induced migration ability and of the VCAM1 gene which is essential for HSC homing, suggesting that SNPs involved in cell migration ability might be partly involved in HSC mobilization to peripheral blood. (PMID:27839966)
• RNA interference-mediated knockdown of the Drosophila ortholog of DGKB in insulin-producing cells, a model for mammalian beta cells, conferred increased insulin output. (PMID:30242153)
• RalA, PLD and mTORC1 Are Required for Kinase-Independent Pathways in DGKbeta-Induced Neurite Outgrowth. (PMID:34944458)
• DGKB mediates radioresistance by regulating DGAT1-dependent lipotoxicity in glioblastoma. (PMID:36603576)
• Includes the identification and expression profile of this gene (named as KIAA0718). (PMID:9872452)

Cross-species orthologs

9 orthologs

Organism	Symbol	Gene ID
danio_rerio	dgkb	ENSDARG00000027724
mus_musculus	Dgkb	ENSMUSG00000036095
rattus_norvegicus	Dgkb	ENSRNOG00000030771
drosophila_melanogaster	Dgkepsilon	FBGN0020930
drosophila_melanogaster	CG34384	FBGN0085413
drosophila_melanogaster	rdgA	FBGN0261549
caenorhabditis_elegans		WBGENE00000959
caenorhabditis_elegans		WBGENE00006483
caenorhabditis_elegans		WBGENE00019428

Paralogs (9): DGKG (ENSG00000058866), DGKA (ENSG00000065357), DGKD (ENSG00000077044), DGKH (ENSG00000102780), DGKQ (ENSG00000145214), DGKZ (ENSG00000149091), DGKE (ENSG00000153933), DGKI (ENSG00000157680), DGKK (ENSG00000274588)

Protein

Protein identifiers

Diacylglycerol kinase beta — Q9Y6T7 (reviewed: Q9Y6T7)

Alternative names: 90 kDa diacylglycerol kinase, Diglyceride kinase beta

All UniProt accessions (4): B5MBY2, B5MCD5, Q9Y6T7, C9JA18

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. Has a higher activity with long-chain diacylglycerols like 1,2-di-(9Z-octadecenoyl)-sn-glycerol compared to 1,2-didecanoyl-sn-glycerol. Specifically expressed in brain, it regulates neuron-specific morphological changes including neurite branching and neurite spine formation. Does not associate with membranes but has a diacylglycerol kinase activity.

Subcellular location. Postsynaptic cell membrane. Cell membrane. Cytoplasm Cytoplasm.

Tissue specificity. Specifically expressed in brain but also detected in uterus. In adult brain, expressed in the amygdala, caudate nucleus, and hippocampus. More ubiquitously expressed but at lower level compared to isoform 1.

Activity regulation. Activated by calcium.

Pathway. Lipid metabolism; glycerolipid metabolism.

Similarity. Belongs to the eukaryotic diacylglycerol kinase family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q9Y6T7-1	1, STD	yes
Q9Y6T7-2	2, SV3'

RefSeq proteins (19): NP_001337634, NP_001337635, NP_001337636, NP_001337637, NP_001337638, NP_001337640, NP_001337641, NP_001337643, NP_001337644, NP_001337645, NP_001337646, NP_001337647, NP_001337648, NP_001337649, NP_001337650, NP_001337651, NP_001337652, NP_001337653, NP_663733 (=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
IPR047470	C1_DGKbeta_rpt2	Domain
IPR047471	C1_DGKbeta-like_rpt1	Domain

Pfam: PF00130, PF00609, PF00781, PF13499, 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), 5 shown:

• a 1,2-diacyl-sn-glycerol + ATP = a 1,2-diacyl-sn-glycero-3-phosphate + ADP + H(+) (RHEA:10272)
• 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-octadecanoyl-2-(9Z,12Z)-octadecadienoyl-sn-glycerol + ATP = 1-octadecanoyl-2-(9Z,12Z-octadecadienoyl)-sn-glycero-3-phosphate + ADP + H(+) (RHEA:40339)
• 1,2-didecanoyl-sn-glycerol + ATP = 1,2-didecanoyl-sn-glycero-3-phosphate + ADP + H(+) (RHEA:43428)

UniProt features (26 total): binding site 9, domain 3, modified residue 3, region of interest 3, compositionally biased region 2, splice variant 2, zinc finger region 2, chain 1, sequence variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9Y6T7-F1	78.02	0.43

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): 162; 164; 166; 173; 207; 209; 211; 213; 218

Post-translational modifications (3): 117, 420, 793

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-114508	Effects of PIP2 hydrolysis

MSigDB gene sets: 100 (showing top): GOBP_LIPID_MODIFICATION, GOBP_PHOSPHOLIPID_METABOLIC_PROCESS, YAGI_AML_WITH_INV_16_TRANSLOCATION, REACTOME_PLATELET_ACTIVATION_SIGNALING_AND_AGGREGATION, GOBP_PLATELET_ACTIVATION, GOBP_ORGANOPHOSPHATE_METABOLIC_PROCESS, AAAYRNCTG_UNKNOWN, GOBP_ORGANOPHOSPHATE_BIOSYNTHETIC_PROCESS, GOBP_PHOSPHOLIPID_BIOSYNTHETIC_PROCESS, GOBP_GLYCEROLIPID_METABOLIC_PROCESS, GOBP_WOUND_HEALING, REACTOME_EFFECTS_OF_PIP2_HYDROLYSIS, CATTTCA_MIR203, GOBP_GLYCEROLIPID_BIOSYNTHETIC_PROCESS, TGANTCA_AP1_C

GO Biological Process (12): 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), response to bacterium (GO:0009617), modulation of chemical synaptic transmission (GO:0050804), regulation of postsynapse organization (GO:0099175)

GO Molecular Function (9): ATP-dependent diacylglycerol kinase activity (GO:0004143), calcium ion binding (GO:0005509), ATP binding (GO:0005524), zinc ion binding (GO:0008270), lipid binding (GO:0008289), nucleotide binding (GO:0000166), kinase activity (GO:0016301), transferase activity (GO:0016740), metal ion binding (GO:0046872)

GO Cellular Component (10): nucleoplasm (GO:0005654), cytoplasm (GO:0005737), cytosol (GO:0005829), plasma membrane (GO:0005886), nuclear speck (GO:0016607), postsynaptic membrane (GO:0045211), membrane (GO:0016020), synapse (GO:0045202), Schaffer collateral - CA1 synapse (GO:0098685), glutamatergic synapse (GO:0098978)

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	4
intracellular anatomical structure	2
synapse	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
response to other organism	1
chemical synaptic transmission	1
regulation of trans-synaptic signaling	1
regulation of synapse organization	1
postsynapse organization	1
lipid kinase activity	1
phosphotransferase activity, alcohol group as acceptor	1
metal ion binding	1
adenyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
transition metal ion binding	1
binding	1
nucleoside phosphate binding	1
heterocyclic compound binding	1
transferase activity, transferring phosphorus-containing groups	1
catalytic activity	1
cation binding	1
nuclear lumen	1
cytoplasm	1
membrane	1

Protein interactions and networks

STRING

1094 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
DGKB	ADCY5	O95622	925
DGKB	MTNR1B	P49286	884
DGKB	G6PC2	Q9NQR9	757
DGKB	GCKR	Q14397	743
DGKB	AGMO	Q6ZNB7	720
DGKB	C2CD4B	A6NLJ0	669
DGKB	GCK	P35557	629
DGKB	SLC30A8	Q8IWU4	605
DGKB	GLIS3	Q8NEA6	581
DGKB	CDKAL1	Q5VV42	544
DGKB	INS	P01308	535
DGKB	ZBED3	Q96IU2	523
DGKB	TCF7L2	Q9NQB0	516
DGKB	ADRA2A	P08913	507
DGKB	C2CD4A	Q8NCU7	507
DGKB	PROX1	Q92786	507
DGKB	ARAP1	Q96P48	507

IntAct

2 interactions, top by confidence:

A	B	Type	Score
DGKB	PCDHB5	psi-mi:“MI:0915”(physical association)	0.000
DGKB	KRT31	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (5): KRT31 (Affinity Capture-MS), PCDHB5 (Affinity Capture-MS), DGKE (Negative Genetic), DGKB (Cross-Linking-MS (XL-MS)), DGKB (Affinity Capture-MS)

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

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	62
Likely benign	9
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

4997 predictions. Top by Δscore:

Variant	Effect	Δscore
7:14178028:TACCT:T	donor_loss	1.0000
7:14178029:A:AT	donor_loss	1.0000
7:14178032:TGATG:T	donor_gain	1.0000
7:14178149:GAT:G	acceptor_gain	1.0000
7:14178152:C:CC	acceptor_gain	1.0000
7:14178152:C:G	acceptor_loss	1.0000
7:14338510:CTGA:C	donor_loss	1.0000
7:14338511:TGA:T	donor_loss	1.0000
7:14338512:GAC:G	donor_loss	1.0000
7:14338513:A:AG	donor_loss	1.0000
7:14338514:C:A	donor_loss	1.0000
7:14338709:CA:C	acceptor_gain	1.0000
7:14338711:C:CC	acceptor_gain	1.0000
7:14338716:CGG:C	acceptor_gain	1.0000
7:14338717:G:T	acceptor_gain	1.0000
7:14338718:G:C	acceptor_gain	1.0000
7:14338718:G:GC	acceptor_gain	1.0000
7:14345299:A:AC	donor_gain	1.0000
7:14345300:C:CC	donor_gain	1.0000
7:14345300:CTT:C	donor_gain	1.0000
7:14345300:CTTCT:C	donor_gain	1.0000
7:14345302:T:TA	donor_gain	1.0000
7:14345388:CATT:C	acceptor_gain	1.0000
7:14345390:TT:T	acceptor_gain	1.0000
7:14345391:TCTGA:T	acceptor_loss	1.0000
7:14345392:C:CC	acceptor_gain	1.0000
7:14345392:CT:C	acceptor_loss	1.0000
7:14345393:T:G	acceptor_loss	1.0000
7:14574207:CTTA:C	donor_loss	1.0000
7:14574209:TAC:T	donor_loss	1.0000

AlphaMissense

5331 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
7:14176859:A:G	W763R	1.000
7:14176859:A:T	W763R	1.000
7:14176867:C:A	G760V	1.000
7:14176867:C:T	G760E	1.000
7:14176868:C:A	G760W	1.000
7:14176870:T:A	D759V	1.000
7:14176875:T:A	Q757H	1.000
7:14176875:T:G	Q757H	1.000
7:14176876:T:G	Q757P	1.000
7:14338620:A:G	W674R	1.000
7:14338620:A:T	W674R	1.000
7:14338661:G:T	A660D	1.000
7:14338668:C:G	G658R	1.000
7:14338668:C:T	G658R	1.000
7:14345359:C:T	G624D	1.000
7:14345371:T:C	Y620C	1.000
7:14345372:A:G	Y620H	1.000
7:14345381:T:C	K617E	1.000
7:14345382:G:C	N616K	1.000
7:14345382:G:T	N616K	1.000
7:14478169:G:C	F610L	1.000
7:14478169:G:T	F610L	1.000
7:14478170:A:G	F610S	1.000
7:14478171:A:G	F610L	1.000
7:14478190:T:A	R603S	1.000
7:14478190:T:G	R603S	1.000
7:14478191:C:A	R603I	1.000
7:14478191:C:G	R603T	1.000
7:14478201:G:C	H600D	1.000
7:14478202:G:C	F599L	1.000

dbSNP variants (sampled 300 via entrez): RS1000000978 (7:14662785 T>A), RS1000001893 (7:14209091 T>C), RS1000004682 (7:14665213 C>A,G,T), RS1000004703 (7:14183036 A>G,T), RS1000005180 (7:14480008 G>A), RS1000006002 (7:14564153 T>C), RS1000006747 (7:14853605 G>A), RS1000010722 (7:14294265 C>A,T), RS1000011011 (7:14605907 G>C), RS1000015434 (7:14730786 C>G,T), RS1000017162 (7:14445202 G>A,C), RS1000019254 (7:14298188 A>G), RS1000019721 (7:14547615 G>T), RS1000022485 (7:14679966 G>A), RS1000024290 (7:14896244 T>C)

Disease associations

OMIM: gene MIM:604070 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

56 associations (top):

Study	Trait	p-value
GCST000323_6	Response to treatment for acute lymphoblastic leukemia	3.000000e-06
GCST000568_7	Fasting blood glucose	3.000000e-44
GCST001436_13	Metabolic syndrome	1.000000e-13
GCST001527_18	Fasting blood glucose (BMI interaction)	3.000000e-21
GCST002074_10	Paclitaxel-induced neuropathy	7.000000e-06
GCST002352_13	Type 2 diabetes	3.000000e-07
GCST002586_8	Fasting plasma glucose	3.000000e-11
GCST002701_12	Verbal declarative memory	3.000000e-06
GCST003430_3	Incident myocardial infarction	2.000000e-06
GCST004070_16	Cerebrospinal P-tau181p levels	7.000000e-07
GCST004075_34	Vertical cup-disc ratio	2.000000e-08
GCST004075_35	Vertical cup-disc ratio	5.000000e-08
GCST004894_138	Type 2 diabetes	1.000000e-12
GCST004894_139	Type 2 diabetes	1.000000e-09
GCST004894_61	Type 2 diabetes	2.000000e-12
GCST004894_62	Type 2 diabetes	1.000000e-06
GCST005047_1	Type 2 diabetes	3.000000e-07
GCST005047_49	Type 2 diabetes	6.000000e-11
GCST005047_93	Type 2 diabetes	7.000000e-13
GCST005180_8	Homeostasis model assessment of beta-cell function	3.000000e-17
GCST005186_19	Fasting blood glucose	2.000000e-20
GCST005231_5	Major depressive disorder	4.000000e-06
GCST005414_13	Type 2 diabetes	2.000000e-06
GCST005759_9	Dimensional psychopathology (Social)	4.000000e-07
GCST005790_1	Rosacea symptom severity	2.000000e-06
GCST006002_9	Blood sugar levels	5.000000e-13
GCST006061_89	Atrial fibrillation	7.000000e-10
GCST006061_90	Atrial fibrillation	1.000000e-10
GCST006414_121	Atrial fibrillation	2.000000e-12
GCST006627_25	Diastolic blood pressure	4.000000e-10

EFO canonical traits (27, from GWAS)

EFO ID	Trait name
EFO:0000195	metabolic syndrome
EFO:0004340	body mass index
EFO:0004874	memory performance
EFO:0006805	word list delayed recall measurement
EFO:0004763	p-tau measurement
EFO:0006939	cup-to-disc ratio measurement
EFO:0004469	HOMA-B
EFO:0009100	social domain measurement
EFO:0009180	rosacea severity measurement
EFO:0004468	glucose measurement
EFO:0006336	diastolic blood pressure
EFO:0009270	heel bone mineral density
EFO:0006876	seasonality measurement
EFO:0008328	chronotype measurement
EFO:0004541	HbA1c measurement
EFO:0004695	intraocular pressure measurement
EFO:0007789	BMI-adjusted waist circumference
EFO:0008344	response to placebo
EFO:0010339	FVC change measurement
EFO:0004567	antipsychotic drug related weight gain
EFO:0007621	bone mineral content measurement
EFO:0010478	fructose-1-phosphate measurement
EFO:0010479	fructose-6-phosphate measurement
EFO:0010484	glucose-1-phosphate measurement
EFO:0010485	glucose-6-phosphate measurement
EFO:0004462	PR interval
EFO:0007874	gut microbiome measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4105755 (SINGLE PROTEIN)

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

PharmGKB clinical annotations

1 annotations.

Variant	Type	Level	Drugs	Phenotypes
rs1525085	Toxicity	3	antipsychotics	Weight gain

PharmGKB variants

1 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs1525085	DGKB	3	0.00	1	antipsychotics

ChEMBL bioactivities

2 potent at pChembl≥5 of 2 total, top 2 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
6.00	IC50	1000	nM	CHEMBL5424446
5.60	IC50	2500	nM	CHEMBL5408449

PubChem BioAssay actives

2 with measured affinity, of 7 total; 2 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	2010061: Inhibition of human DGK beta using 1, 2-Dilauroyl-sn-glycerol as substrate by ADP-Glo assay	ic50	1.0000	uM
4-(4-benzhydrylpiperazin-1-yl)-1-methyl-3-nitroquinolin-2-one	2010061: Inhibition of human DGK beta using 1, 2-Dilauroyl-sn-glycerol as substrate by ADP-Glo assay	ic50	2.5000	uM

CTD chemical–gene interactions

20 total (human), top 20 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	affects methylation, increases expression	2
GSK-J4	increases expression	1
bisphenol A	increases methylation	1
trichostatin A	decreases expression	1
aflatoxin B2	decreases methylation	1
S-(1,2-dichlorovinyl)cysteine	affects cotreatment, increases expression	1
perfluoro-n-nonanoic acid	increases expression	1
perfluorohexanesulfonic acid	increases expression	1
bisphenol S	increases methylation	1
theaflavin-3,3’-digallate	affects expression	1
Acetaminophen	increases expression	1
Benzo(a)pyrene	decreases methylation	1
Lipopolysaccharides	affects cotreatment, increases expression	1
Niclosamide	increases expression	1
Progesterone	decreases expression	1
Valproic Acid	increases expression	1
Vanadium	increases expression	1
8-Bromo Cyclic Adenosine Monophosphate	increases expression	1
Aflatoxin B1	increases methylation	1
Okadaic Acid	decreases expression	1

ChEMBL screening assays

5 unique, capped per target: 5 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL4015088	Binding	Inhibition of human DGKbeta (1 to 804 residues) by ADP Glo HTS assay	Discovery of a series of 8-(1-phenylpyrrolidin-2-yl)-6-carboxamide-2-morpholino-4H-chromen-4-one as PI3Kβ/δ inhibitors for the treatment of PTEN-deficient tumours. — Bioorg Med Chem Lett

Clinical trials (associated diseases)

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