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 (top 2% of genes corpus-wide)
• Clinical variants (ClinVar): 95 total
• Expression (HPA): Tissue enriched — highest in putamen, caudate putamen, basal ganglia
• GTEx eGene: eQTL in 24 tissues, sQTL in 0 (q < 0.05)
• Constraint (gnomAD): pLI 0.00 (LoF-tolerant), LOEUF 0.76 (unconstrained)
• MANE Select transcript: NM_001350709
• Notable: 95 clinical variants but no curated precision-oncology (CIViC) evidence yet

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: 27 — 20 protein_coding, 5 protein_coding_CDS_not_defined, 2 retained_intron

MANE Select: ENST00000402815

Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 1: 1, TSL 3: 1, TSL 4: 5, TSL 5: 6

ENST00000402815, ENST00000399322, ENST00000403951, ENST00000403963, ENST00000406247, ENST00000407950, ENST00000437998, ENST00000463981, ENST00000464065, ENST00000467449, ENST00000471732, ENST00000477401, ENST00000493142, ENST00000910828, ENST00000910829, ENST00000910830, ENST00000910831, ENST00000910832, ENST00000910833, ENST00000910834, ENST00000932238, ENST00000932239, ENST00000967726, ENST00000967727, ENST00000967728, ENST00000967729, ENST00001138016

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.

Highest expression (Bgee): buccal mucosa cell, putamen, caudate nucleus, prefrontal cortex, nucleus accumbens.

Genetic regulation across tissues (GTEx eQTL / sQTL)

DGKB is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 24 tissues and its splicing (sQTL) in 0 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

showing 20 of 24 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Cells Cultured fibroblasts	eqtl	1.9e-100	+0.94	7:14834814:A:G
Muscle Skeletal	eqtl	5.4e-29	+0.60	7:14835742:A:C
Artery Tibial	eqtl	3.7e-15	+0.45	7:14773790:T:A
Brain Cerebellar Hemisphere	eqtl	1.7e-08	-0.49	7:14771441:C:T
Brain Cerebellum	eqtl	1.1e-04	-0.37	7:14804386:T:A
Nerve Tibial	eqtl	3.6e-04	-0.31	7:14756156:C:A
Brain Cortex	eqtl	7.3e-04	+0.11	7:14891423:A:G
Brain Frontal Cortex BA9	eqtl	8.3e-04	-0.26	7:14703239:T:C
Esophagus Mucosa	eqtl	1.4e-03	+0.24	7:14791537:TA:T
Brain Amygdala	eqtl	2.5e-03	-0.19	7:14901931:C:T
Heart Atrial Appendage	eqtl	2.8e-03	+0.40	7:14834606:T:A
Esophagus Muscularis	eqtl	3.3e-03	+0.19	7:14800779:T:C
Brain Substantia nigra	eqtl	4.9e-03	+0.31	7:14863120:G:GTAGTT
Brain Spinal cord cervical c-1	eqtl	6.0e-03	-0.22	7:14888306:G:C
Brain Anterior cingulate cortex BA24	eqtl	1.8e-02	+0.39	7:14835462:T:C
Adipose Visceral Omentum	eqtl	2.2e-02	+0.26	7:14076211:A:G
Esophagus Gastroesophageal Junction	eqtl	2.3e-02	+0.21	7:14844112:A:G
Brain Hypothalamus	eqtl	2.6e-02	+0.29	7:14874234:G:A
Pituitary	eqtl	3.0e-02	+0.29	7:14965384:G:C
Brain Putamen basal ganglia	eqtl	3.5e-02	+0.18	7:14871499:G:A

FANTOM5 promoters

showing 10 of 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

showing 100 of 282 tissues 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
temporal lobe	UBERON:0001871	74.18	gold quality
endothelial cell	CL:0000115	73.73	silver quality
brain	UBERON:0000955	73.49	gold quality
secondary oocyte	CL:0000655	73.47	gold quality
CA1 field of hippocampus	UBERON:0003881	73.33	gold quality
central nervous system	UBERON:0001017	73.15	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	72.65	gold quality
islet of Langerhans	UBERON:0000006	72.65	gold quality
amygdala	UBERON:0001876	72.43	gold quality
occipital lobe	UBERON:0002021	71.39	gold quality
ventricular zone	UBERON:0003053	70.59	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	70.17	gold quality
hypothalamus	UBERON:0001898	69.97	gold quality
lower esophagus muscularis layer	UBERON:0035833	69.51	gold quality
lower esophagus	UBERON:0013473	69.38	gold quality
lateral globus pallidus	UBERON:0002476	67.25	gold quality
middle frontal gyrus	UBERON:0002702	67.13	gold quality
colonic epithelium	UBERON:0000397	66.54	gold quality
ganglionic eminence	UBERON:0004023	65.85	gold quality
medial globus pallidus	UBERON:0002477	65.81	gold quality
smooth muscle tissue	UBERON:0001135	65.60	gold quality
mucosa of stomach	UBERON:0001199	65.47	gold quality
pons	UBERON:0000988	64.90	gold quality
cranial nerve II	UBERON:0000941	64.80	gold quality
globus pallidus	UBERON:0001875	64.28	gold quality
diaphragm	UBERON:0001103	63.88	gold quality
left uterine tube	UBERON:0001303	63.40	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	63.40	gold quality
spinal cord	UBERON:0002240	62.41	gold quality
substantia nigra	UBERON:0002038	62.19	gold quality
muscle layer of sigmoid colon	UBERON:0035805	61.73	gold quality
sural nerve	UBERON:0015488	61.50	silver quality
calcaneal tendon	UBERON:0003701	61.24	gold quality
adrenal tissue	UBERON:0018303	61.19	gold quality
midbrain	UBERON:0001891	60.73	gold quality
body of uterus	UBERON:0009853	60.43	gold quality
endocervix	UBERON:0000458	60.14	gold quality
cortical plate	UBERON:0005343	60.09	gold quality
paraflocculus	UBERON:0005351	59.79	gold quality
cerebellar vermis	UBERON:0004720	59.50	gold quality
right hemisphere of cerebellum	UBERON:0014890	59.21	gold quality
embryo	UBERON:0000922	58.79	gold quality
cerebellar cortex	UBERON:0002129	58.68	gold quality
cerebellar hemisphere	UBERON:0002245	58.42	gold quality
cerebellum	UBERON:0002037	58.28	gold quality
sigmoid colon	UBERON:0001159	57.78	gold quality
lower lobe of lung	UBERON:0008949	56.13	silver quality
uterine cervix	UBERON:0000002	55.21	gold quality
esophagus	UBERON:0001043	54.38	gold quality
vermiform appendix	UBERON:0001154	54.25	gold quality
urinary bladder	UBERON:0001255	53.83	gold quality
tibialis anterior	UBERON:0001385	53.77	silver quality
gall bladder	UBERON:0002110	53.38	gold quality
tendon	UBERON:0000043	53.26	gold quality
uterus	UBERON:0000995	53.20	gold quality
pancreas	UBERON:0001264	53.10	gold quality
hindlimb stylopod muscle	UBERON:0004252	53.02	gold quality
fallopian tube	UBERON:0003889	53.01	gold quality
myometrium	UBERON:0001296	52.95	gold quality
colon	UBERON:0001155	52.74	gold quality
caecum	UBERON:0001153	52.33	gold quality
large intestine	UBERON:0000059	52.32	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	52.22	gold quality
ectocervix	UBERON:0012249	52.20	gold quality
rectum	UBERON:0001052	51.80	gold quality
pituitary gland	UBERON:0000007	51.74	gold quality
adult mammalian kidney	UBERON:0000082	51.68	gold quality
ventral tegmental area	UBERON:0002691	51.58	silver quality
adenohypophysis	UBERON:0002196	51.19	gold quality
fundus of stomach	UBERON:0001160	51.14	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

HPA expression

RNA tissue specificity: Tissue enriched

showing 60 of 63 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM
Putamen	tissue	252.7
Caudate putamen	tissue	205.9
Basal ganglia	tissue	197.9
Ventral forebrain	tissue	108.8
Olfactory bulb	tissue	92.9
Nucleus accumbens	tissue	79.0
Septum	tissue	71.5
Prefrontal cortex	tissue	59.8
Cerebral cortex	tissue	59.8
Frontal cortex	tissue	59.2
Temporal cortex	tissue	56.5
Hippocampal formation	tissue	55.3
Entorhinal cortex	tissue	55.3
Motor cortex	tissue	54.0
Postcentral gyrus	tissue	51.4
Retrosplenial and cingulate cortex	tissue	50.8
Occipital cortex	tissue	50.8
Insular cortex	tissue	50.0
Retrosplenial cortex	tissue	48.1
Somatosensory cortex	tissue	47.8
Amygdala	tissue	44.0
Spinal cord	tissue	41.7
Hypothalamus	tissue	33.9
Pons	tissue	32.3
Hippocampus	tissue	31.4
Medulla oblongata	tissue	29.9
Midbrain	tissue	29.6
Substantia nigra	tissue	28.4
Periaqueductal gray	tissue	23.2
Thalamus	tissue	22.3
Locus coeruleus	tissue	19.3
Superior colliculi	tissue	18.7
Corpus callosum	tissue	14.5
Cerebellum	tissue	13.7
Choroid plexus	tissue	5.1
Endometrium 1	tissue	3.0
Adrenal gland	tissue	2.5
Cervix	tissue	2.2
Retina	tissue	1.8
Smooth muscle	tissue	1.3
Tongue	tissue	1.3
Fallopian tube	tissue	1.1
Kidney	tissue	1.0
Pituitary gland	tissue	0.6
Esophagus	tissue	0.5
Rectum	tissue	0.5
Colon	tissue	0.4
Urinary bladder	tissue	0.4
Heart muscle	tissue	0.3
Vagina	tissue	0.3
Skeletal muscle	tissue	0.3
Gallbladder	tissue	0.3
Adipose tissue	tissue	0.2
Liver	tissue	0.2
Small intestine	tissue	0.2
Prostate	tissue	0.2
Appendix	tissue	0.2
Testis	tissue	0.1
Ovary	tissue	0.1
Seminal vesicle	tissue	0.1

Brain sub-regions (HPA Brain Atlas): detected in 189; highest nTPM — Caudate nucleus (88.4), Temporal pole (67.5), Arcuate nucleus (62.9), Perirhinal gyrus (55.8), Superior temporal gyrus (55.3).

Regulation

Is transcription factor: no

Functional genomics

gnomAD constraint: pLI 0.000158, LOEUF 0.755, missense Z 0.96 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD)

ENST00000402815 splits into 3 regions with different missense tolerance; 0 are missense-constrained. Missense variants in a constrained region (low observed/expected) are more likely to be pathogenic. gnomAD

Region (GRCh38)	Missense obs / exp	o/e	Constrained
7:14,149,134–14,176,857	58 / 52.5	1.10	no
7:14,176,858–14,178,137	35 / 66.0	0.53	no
7:14,178,138–14,841,263	814 / 856.6	0.95	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)

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:2442474) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 13 distinct phenotype terms.

Mouse phenotype (MP)	Records
hyperactivity	1
reduced long-term potentiation	1
abnormal lipid level	1
increased vertical activity	1
abnormal response to novel object	1
decreased heart rate	1
abnormal spatial working memory	1
abnormal long-term spatial reference memory	1
abnormal synapse morphology	1
impaired behavioral response to xenobiotic	1
abnormal hippocampus neuron morphology	1
prolonged RR interval	1
increased locomotor activity	1

Additional cross-species homologs

Sequence homologs in species beyond Ensembl Compara’s model organisms, by Diamond local protein alignment (% sequence identity; best hit per species). Lower-identity rows are more distant homologs. The matched accessions’ gene symbols aren’t in biobtree yet, so each row shows the UniProt accession.

Organism	UniProt	Identity	Method
Drosophila sechellia	B4I4Y1	98.1%	Diamond
Drosophila simulans	B4R0A5	98.1%	Diamond
Drosophila yakuba	B4PRE2	97.6%	Diamond
Bos taurus	A0JN54	97.1%	Diamond
Drosophila erecta	B3NYS4	97.1%	Diamond
Sus scrofa	P20192	97.1%	Diamond
Ovis aries	C7A278	95.7%	Diamond
Drosophila ananassae	B3LXF2	90.2%	Diamond
Arabidopsis thaliana	O81445	89.7%	Diamond
Drosophila grimshawi	B4JHJ7	87.6%	Diamond
Drosophila mojavensis	B4K6T8	87.6%	Diamond
Lithobates pipiens	O73762	85.9%	Diamond
Gallus gallus	P79881	85.9%	Diamond
Oryza sativa Japonica Group	Q3HRN7	66.3%	Diamond
Dictyostelium discoideum	Q86A72	50.0%	Diamond

Genomic neighbors (locus context)

Genes flanking this one on the chromosome (NCBI/Entrez gene neighborhood). Positional context only — some neighbors share regulatory elements (bidirectional promoters, antisense/overlapping transcripts), but chromosomal adjacency is not itself a functional relationship (see Interactions for that).

Symbol	Type	Entrez
AGMO	protein-coding	392636
ETV1	protein-coding	2115
MEOX2	protein-coding	4223
LINC02587	ncRNA	101927524

Protein

Protein identifiers

Diacylglycerol kinase beta — Q9Y6T7 (reviewed: Q9Y6T7)

Alternative names: 90 kDa diacylglycerol kinase, Diglyceride kinase beta

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

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)

• 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

Predicted structure (AlphaFold)

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

Human Protein Atlas

Protein class: Enzymes, ENZYME proteins, Transferases, Metabolic proteins, Predicted intracellular proteins, Plasma proteins

Protein evidence: Evidence at protein level

Subcellular location (HPA, imaging): plasma membrane; nuclear speckles; nucleoplasm

Antibody reliability (HPA): IF approved

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)

Position	Role
162	Ca(2+)
164	Ca(2+)
166	Ca(2+)
173	Ca(2+)
207	Ca(2+)
209	Ca(2+)
211	Ca(2+)
213	Ca(2+)
218	Ca(2+)

Post-translational modifications (3)

Type	Positions
Phosphothreonine	117
Phosphoserine	420, 793

Function

Pathways and Gene Ontology

Reactome pathways

1 curated (TAS) of 7; 0 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

7 pathways:

ID	Pathway	Evidence
R-HSA-114508	Effects of PIP2 hydrolysis	curated
R-HSA-416476	G alpha (q) signalling events	—
R-HSA-388396	GPCR downstream signalling	—
R-HSA-109582	Hemostasis	—
R-HSA-76002	Platelet activation, signaling and aggregation	—
R-HSA-162582	Signal Transduction	—
R-HSA-372790	Signaling by GPCR	—

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 (11): 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), 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 (6): cytoplasm (GO:0005737), cytosol (GO:0005829), plasma membrane (GO:0005886), postsynaptic membrane (GO:0045211), Schaffer collateral - CA1 synapse (GO:0098685), glutamatergic synapse (GO:0098978)

Reactome top-level categories

6 top-level categories:

Category	Pathways
G alpha (q) signalling events	1
Platelet activation, signaling and aggregation	1
Signal Transduction	1
Signaling by GPCR	1
GPCR downstream signalling	1
Hemostasis	1

GO top-level categories

42 GO namespaces:

Category	Terms
intracellular anatomical structure	2
cellular 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
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
anion 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
cytoplasm	1
membrane	1
cell periphery	1
synaptic membrane	1
postsynapse	1

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 6 of 26 annotations. The rest are phylogenetic / computational / electronic (IEA).

6 experimentally-supported GO terms:

GO term	NS	Evidence
glycerolipid metabolic process	BP	direct assay
lipid phosphorylation	BP	direct assay
cytosol	CC	direct assay
plasma membrane	CC	direct assay
ATP-dependent diacylglycerol kinase activity	MF	direct assay
lipid binding	MF	direct assay

Protein interactions and networks

STRING

showing 15 of 786 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
DGKB	ADCY5	O95622	876
DGKB	MTNR1B	P49286	868
DGKB	G6PC2	Q9NQR9	748
DGKB	GCKR	Q14397	738
DGKB	AGMO	Q6ZNB7	703
DGKB	C2CD4B	A6NLJ0	652
DGKB	GCK	P35557	616
DGKB	SLC30A8	Q8IWU4	577
DGKB	CDKAL1	Q5VV42	547
DGKB	GLIS3	Q8NEA6	547
DGKB	INS	P01308	522
DGKB	TCF7L2	Q9NQB0	494
DGKB	ZBED3	Q96IU2	493
DGKB	ARAP1	Q96P48	470
DGKB	ADRA2A	P08913	469

IntAct

Human interaction partners of DGKB in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

2 partners by confidence:

Partner	Interaction type	MIscore	Records
KRT31	physical association	0.000	1
PCDHB5	physical association	0.000	1

BioGRID (8 interactions; top human partners by supporting records): DGKE (Negative Genetic), KRT31 (Affinity Capture-MS), PARP12 (Proximity Label-MS), PARP8 (Proximity Label-MS), PCDHB5 (Affinity Capture-MS), PRNP (Affinity Capture-MS), STMN1 (Cross-Linking-MS (XL-MS)), WTAP (Affinity Capture-MS)

Disease & clinical

Genetic variants

Variant evidence for DGKB: 95 ClinVar records (0 pathogenic / likely pathogenic); 1 PharmGKB clinical annotation; 56 GWAS associations.

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

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 44 predictions of 3,664):

Position(s)	Effect	Δscore	Sites
7:14178029–14178030	donor_loss	1.0000	5
7:14178152–14178153	acceptor_loss	1.0000	6
7:14338513–14338514	donor_loss	1.0000	5
7:14338717–14338718	acceptor_gain	1.0000	2
7:14345392–14345393	acceptor_loss	1.0000	5
7:14574210–14574211	donor_loss	1.0000	6
7:14574373–14574374	acceptor_loss	1.0000	4
7:14621376–14621377	donor_loss	1.0000	4
7:14621495–14621496	acceptor_loss	1.0000	6
7:14621497	acceptor_gain	1.0000

AlphaMissense

2,748 missense substitutions predicted likely pathogenic (of 5,331 scored), across 572 residues. Top 20 hotspot residues, ranked by the number of likely-pathogenic substitutions (of those reachable by a single-nucleotide change), then by mean score:

Residue	Likely-pathogenic substitutions	Mean am_pathogenicity	Max am_pathogenicity
M181	9	0.987	0.999
M202	9	0.936	0.996
M726	9	0.935	0.997
D528	8	1.000	1.000
D592	8	0.999	0.999
N616	8	0.999	1.000
H283	8	0.998	0.999
H347	8	0.998	0.999
D497	8	0.998	1.000
H600	8	0.998	1.000
D759	8	0.998	1.000
H245	8	0.997	0.999
N527	8	0.997	1.000
D162	8	0.996	0.999
F599	8	0.994	1.000
F610	8	0.993	1.000
D207	8	0.991	0.997
H310	8	0.991	0.998
S447	8	0.988	0.999
D560	8	0.988	0.997

HPA cancer prognostics

RNA cancer specificity: Cancer enriched (Glioblastoma Multiforme)

Disease associations

OMIM: gene MIM:604070 | disease phenotypes:

GWAS associations

showing 30 of 56 associations:

Study	Trait	p-value
GCST000568_7	Fasting blood glucose	3e-44
GCST009379_288	Type 2 diabetes	1e-28
GCST010118_12	Type 2 diabetes	8e-22
GCST001527_22	Fasting blood glucose (BMI interaction)	3e-21
GCST005186_7	Fasting blood glucose	2e-20
GCST009379_287	Type 2 diabetes	2e-17
GCST005180_3	Homeostasis model assessment of beta-cell function	3e-17
GCST010321_204	PR interval	1e-16
GCST010320_33	PR interval	2e-16
GCST006867_56	Type 2 diabetes	2e-15
GCST009724_33	Vertical cup-disc ratio (multi-trait analysis)	3e-14
GCST011587_9	Fasting blood glucose	9e-14
GCST001436_13	Metabolic syndrome	1e-13
GCST006002_9	Blood sugar levels	5e-13
GCST005047_58	Type 2 diabetes	7e-13
GCST004894_138	Type 2 diabetes	1e-12
GCST004894_11	Type 2 diabetes	2e-12
GCST006414_85	Atrial fibrillation	2e-12
GCST007847_40	Type 2 diabetes	2e-12
GCST007899_6	Fasting blood glucose	4e-12
GCST008674_5	Glycemic traits (pleiotropy)	2e-11
GCST002586_8	Fasting plasma glucose	3e-11
GCST006979_98	Heel bone mineral density	3e-11
GCST005047_88	Type 2 diabetes	6e-11
GCST007847_57	Type 2 diabetes	8e-11
GCST006061_140	Atrial fibrillation	1e-10
GCST006627_40	Diastolic blood pressure	4e-10
GCST006061_139	Atrial fibrillation	7e-10
GCST004894_139	Type 2 diabetes	1e-9
GCST011587_8	Fasting blood glucose	4e-9

EFO canonical traits (from GWAS)

27 canonical traits:

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 (CPIC guideline: no)

PharmGKB clinical annotations

1 annotation by evidence level (1 strongest → 4):

Variant	Association	Level	Drugs	Phenotypes
rs1525085	Toxicity	3	antipsychotics	Weight gain

PharmGKB variants

1 variant:

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

Binding affinities (BindingDB)

4 measured of 5 human assays (5 total across all organisms); most potent 4 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value
8-(4-(bis(4-fluorophenyl)methyl)piperazin-1-yl)-5-methyl-7-nitro-6-oxo-5,6-dihydro-1,5-naphthyridine-2-carbonitrile	IC50	5 nM
CHEMBL5408449	IC50	15 nM
cid_5074	KI	2920 nM
SMR000058550	IC50	10600 nM

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)

Via MONDO — disease-level, not drug-specific.

Predicted chemistry — Sugi Predict

The predicted patent-compound landscape for DGKB across ~30M SureChEMBL compounds — explore on Sugi Predict.