DGKG

Summary

DGKG (diacylglycerol kinase gamma, HGNC:2853) is a protein-coding gene on chromosome 3q27.2-q27.3, encoding Diacylglycerol kinase gamma (P49619). Diacylglycerol kinase that converts diacylglycerol/DAG into phosphatidic acid/phosphatidate/PA and regulates the respective levels of these two bioactive lipids.

This gene encodes an enzyme that is a member of the type I subfamily of diacylglycerol kinases, which are involved in lipid metabolism. These enzymes generate phosphatidic acid by catalyzing the phosphorylation of diacylglycerol, a fundamental lipid second messenger that activates numerous proteins, including protein kinase C isoforms, Ras guanyl nucleotide-releasing proteins and some transient receptor potential channels. Diacylglycerol kinase gamma has been implicated in cell cycle regulation and in the negative regulation of macrophage differentiation in leukemia cells. Multiple transcript variants encoding different isoforms have been found for this gene.

Source: NCBI Gene 1608 — RefSeq curated summary.

At a glance

• GWAS associations: 29
• Clinical variants (ClinVar): 157 total — 1 pathogenic
• Druggable target: yes
• MANE Select transcript: NM_001346

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:2853
Approved symbol	DGKG
Name	diacylglycerol kinase gamma
Location	3q27.2-q27.3
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000058866
Ensembl biotype	protein_coding
OMIM	601854
Entrez	1608

Gene structure

Transcript identifiers

Ensembl transcripts: 15 — 8 protein_coding, 6 retained_intron, 1 protein_coding_CDS_not_defined

ENST00000265022, ENST00000344484, ENST00000382164, ENST00000437018, ENST00000447054, ENST00000466466, ENST00000472506, ENST00000480809, ENST00000480933, ENST00000482566, ENST00000490452, ENST00000851915, ENST00000851916, ENST00000851917, ENST00000964900

RefSeq mRNA: 3 — MANE Select: NM_001346 NM_001080744, NM_001080745, NM_001346

CCDS: CCDS3274, CCDS43181, CCDS43182

Canonical transcript exons

ENST00000265022 — 25 exons

Exon	Start	End
ENSE00000781444	186268801	186268917
ENSE00001140798	186147201	186150188
ENSE00001177976	186361946	186362234
ENSE00003460418	186272255	186272343
ENSE00003465310	186253093	186253182
ENSE00003471336	186279851	186279973
ENSE00003475070	186275547	186275664
ENSE00003485588	186260439	186260513
ENSE00003490658	186164898	186165018
ENSE00003511931	186188202	186188379
ENSE00003521000	186297421	186297483
ENSE00003524966	186242504	186242568
ENSE00003529136	186284660	186284709
ENSE00003541028	186280670	186280744
ENSE00003568971	186211795	186211885
ENSE00003571614	186298064	186298229
ENSE00003592390	186261699	186261778
ENSE00003598897	186306901	186306977
ENSE00003607396	186320393	186320707
ENSE00003613263	186257854	186257939
ENSE00003636317	186265247	186265306
ENSE00003674269	186288710	186288880
ENSE00003674589	186251759	186251919
ENSE00003680316	186161603	186161663
ENSE00003787015	186267685	186267777

Expression profiles

Bgee: expression breadth ubiquitous, 177 present calls, max score 91.11.

FANTOM5 (CAGE): breadth broad, TPM avg 7.2274 / max 538.2601, expressed in 859 samples.

FANTOM5 promoters (8 alternative TSS)

Promoter ID	TPM avg	Samples expressed
45967	5.4171	450
45964	0.9310	376
45968	0.2154	104
45969	0.1914	83
45966	0.1812	79
45963	0.1627	72
45970	0.1106	52
45961	0.0180	5

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
cerebellar cortex	UBERON:0002129	91.11	gold quality
cerebellar hemisphere	UBERON:0002245	91.10	gold quality
right hemisphere of cerebellum	UBERON:0014890	90.85	gold quality
lower esophagus muscularis layer	UBERON:0035833	90.13	gold quality
lower esophagus	UBERON:0013473	90.01	gold quality
cerebellum	UBERON:0002037	89.81	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	88.30	gold quality
buccal mucosa cell	CL:0002336	88.06	gold quality
mucosa of stomach	UBERON:0001199	86.42	gold quality
monocyte	CL:0000576	84.42	gold quality
mononuclear cell	CL:0000842	84.10	gold quality
leukocyte	CL:0000738	83.38	gold quality
cingulate cortex	UBERON:0003027	81.77	gold quality
heart left ventricle	UBERON:0002084	81.73	gold quality
anterior cingulate cortex	UBERON:0009835	81.73	gold quality
apex of heart	UBERON:0002098	81.69	gold quality
right frontal lobe	UBERON:0002810	81.30	gold quality
cardiac ventricle	UBERON:0002082	81.07	gold quality
adrenal tissue	UBERON:0018303	80.94	gold quality
adenohypophysis	UBERON:0002196	80.92	gold quality
right lung	UBERON:0002167	80.41	gold quality
postcentral gyrus	UBERON:0002581	80.32	gold quality
popliteal artery	UBERON:0002250	80.30	gold quality
tibial artery	UBERON:0007610	80.30	gold quality
prefrontal cortex	UBERON:0000451	80.04	gold quality
right adrenal gland cortex	UBERON:0035827	79.77	gold quality
Ammon’s horn	UBERON:0001954	79.68	gold quality
right atrium auricular region	UBERON:0006631	79.64	gold quality
left adrenal gland	UBERON:0001234	79.53	gold quality
left adrenal gland cortex	UBERON:0035825	79.10	gold quality

Single-cell (SCXA)

Detected in 4 experiment(s), a significant marker in 4.

Experiment	Marker?	Max mean expression
E-HCAD-35	yes	72.92
E-HCAD-25	yes	23.85
E-CURD-119	yes	17.21
E-ANND-3	yes	6.29

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): CREB5

miRNA regulators (miRDB)

160 targeting DGKG, 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-5011-5P	100.00	83.46	5820
HSA-MIR-6867-5P	100.00	82.21	3464
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-574-5P	100.00	66.01	989
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-6833-3P	100.00	70.63	3197
HSA-MIR-4768-5P	100.00	69.49	2861
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-6873-3P	100.00	71.42	2626
HSA-MIR-196A-1-3P	99.99	72.15	2772
HSA-MIR-10401-5P	99.99	65.79	948
HSA-MIR-6870-5P	99.99	68.55	2115
HSA-MIR-27A-3P	99.98	72.13	2955
HSA-MIR-27B-3P	99.98	72.13	2955
HSA-MIR-9985	99.98	72.11	2939
HSA-MIR-19A-3P	99.98	75.33	2762
HSA-MIR-19B-3P	99.98	75.44	2754
HSA-MIR-4723-5P	99.97	68.70	2034
HSA-MIR-5698	99.97	68.49	2029
HSA-MIR-7111-5P	99.97	68.48	2062
HSA-MIR-1229-3P	99.97	66.49	906
HSA-MIR-1-3P	99.93	72.35	1914
HSA-MIR-206	99.93	72.50	1893
HSA-MIR-3119	99.92	71.34	2390
HSA-MIR-10527-5P	99.91	72.28	3754
HSA-MIR-613	99.91	71.50	1710
HSA-MIR-4648	99.91	67.00	710
HSA-MIR-3686	99.90	70.53	2432
HSA-MIR-627-3P	99.90	71.42	3316

Literature-anchored findings (GeneRIF, showing 7)

• diacylglycerol kinase gamma regulates macrophage differentiation. (PMID:12732202)
• the interaction of diacylglycerol kinase gamma with the Src homology 2 and C1 domains of beta2-chimaerin is induced synergistically by Phorbol ester and hydrogen peroxide (PMID:17803461)
• these results indicate that DGKG is an anionic phospholipid binding protein that preferably interacts with a small highly charged head group that is very close to the glycerol or sphingosine backbone. (PMID:24486543)
• Epigenetic silencing of DGKG expression is associated with skin cancer. (PMID:28218473)
• Decreased expression of DGKgamma in hepatocellular carcinoma tissues was an independent risk factor for a poor prognosis. (PMID:30399372)
• Characterization of alpha-synuclein N-terminal domain as a novel cellular phosphatidic acid sensor. (PMID:31722116)
• Endothelial DGKG promotes tumor angiogenesis and immune evasion in hepatocellular carcinoma. (PMID:37838036)

Cross-species orthologs

7 orthologs

Organism	Symbol	Gene ID
danio_rerio	dgkg	ENSDARG00000062696
mus_musculus	Dgkg	ENSMUSG00000022861
rattus_norvegicus	Dgkg	ENSRNOG00000001796
drosophila_melanogaster	CG34384	FBGN0085413
drosophila_melanogaster	rdgA	FBGN0261549
caenorhabditis_elegans		WBGENE00006483
caenorhabditis_elegans		WBGENE00019428

Paralogs (9): DGKA (ENSG00000065357), DGKD (ENSG00000077044), DGKH (ENSG00000102780), DGKB (ENSG00000136267), DGKQ (ENSG00000145214), DGKZ (ENSG00000149091), DGKE (ENSG00000153933), DGKI (ENSG00000157680), DGKK (ENSG00000274588)

Protein

Protein identifiers

Diacylglycerol kinase gamma — P49619 (reviewed: P49619)

Alternative names: Diglyceride kinase gamma

All UniProt accessions (2): P49619, H7C0L0

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 no apparent specificity with regard to the acyl compositions of diacylglycerol. Specifically expressed in the cerebellum where it controls the level of diacylglycerol which in turn regulates the activity of protein kinase C gamma. Through protein kinase C gamma, indirectly regulates the dendritic development of Purkinje cells, cerebellar long term depression and ultimately cerebellar motor coordination.

Subcellular location. Membrane. Cytoplasm. Cytosol. Cytoskeleton.

Tissue specificity. Predominantly expressed in retina and in a much lesser extent in the brain. Other tissues contain extremely low levels of DGK-gamma.

Activity regulation. The activity is calcium-dependent. Requires phosphatidylserine for maximal activity.

Pathway. Lipid metabolism; glycerolipid metabolism.

Miscellaneous. May be inactive.

Similarity. Belongs to the eukaryotic diacylglycerol kinase family.

Isoforms (3)

UniProt ID	Names	Canonical?
P49619-1	1, Long	yes
P49619-2	2, Short
P49619-3	3

RefSeq proteins (3): NP_001074213, NP_001074214, NP_001337* (*=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
IPR047475	C1_DGKgamma_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), 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 8, sequence variant 4, domain 3, region of interest 3, compositionally biased region 2, splice variant 2, zinc finger region 2, chain 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P49619-F1	77.53	0.39

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 (8): 188; 190; 192; 199; 233; 235; 237; 244

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-114508	Effects of PIP2 hydrolysis

MSigDB gene sets: 213 (showing top): GOBP_DENDRITE_DEVELOPMENT, GOBP_LIPID_MODIFICATION, MULLIGHAN_NPM1_SIGNATURE_3_UP, GOBP_PHOSPHOLIPID_METABOLIC_PROCESS, BENPORATH_ES_WITH_H3K27ME3, REACTOME_PLATELET_ACTIVATION_SIGNALING_AND_AGGREGATION, GOBP_PLATELET_ACTIVATION, GOBP_NEUROGENESIS, GOBP_ORGANOPHOSPHATE_METABOLIC_PROCESS, GOBP_ORGANOPHOSPHATE_BIOSYNTHETIC_PROCESS, SRF_Q5_01, GOBP_NEGATIVE_REGULATION_OF_INTRACELLULAR_SIGNAL_TRANSDUCTION, GOBP_PHOSPHOLIPID_BIOSYNTHETIC_PROCESS, GOBP_GLYCEROLIPID_METABOLIC_PROCESS, GOBP_WOUND_HEALING

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), regulation of dendrite development (GO:0050773), negative regulation of phospholipase C/protein kinase C signal transduction (GO:0160195), lipid metabolic process (GO:0006629), signal transduction (GO:0007165)

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 (5): cytosol (GO:0005829), cytoskeleton (GO:0005856), 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
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
regulation of neuron projection development	1
dendrite development	1
regulation of developmental process	1
phospholipase C/protein kinase C signal transduction	1
negative regulation of intracellular signal transduction	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
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
cytoplasm	1
intracellular membraneless organelle	1
membrane	1
cell periphery	1

Protein interactions and networks

STRING

842 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
DGKG	CHN1	P15882	670
DGKG	CHN2	P52757	650
DGKG	DGKK	Q5KSL6	489
DGKG	GNPDA2	Q8TDQ7	486
DGKG	PLCE1	Q9P212	477
DGKG	RASA1	P20936	438
DGKG	MTCH2	Q9Y6C9	433
DGKG	SEC16B	Q96JE7	432
DGKG	KCTD15	Q96SI1	432
DGKG	CDKAL1	Q5VV42	422
DGKG	CDC123	O75794	420
DGKG	ARRB1	P49407	411
DGKG	ARRB2	P32121	408
DGKG	DGKD	Q16760	406
DGKG	NEGR1	Q7Z3B1	404

IntAct

9 interactions, top by confidence:

A	B	Type	Score
ECE1	DGKG	psi-mi:“MI:0915”(physical association)	0.370
ALB	CNOT1	psi-mi:“MI:0914”(association)	0.350
ARRB1		psi-mi:“MI:0914”(association)	0.350
SDHA	HMGB3	psi-mi:“MI:0914”(association)	0.350
SDHA	NME2P1	psi-mi:“MI:0914”(association)	0.350
DGKG	SMCHD1	psi-mi:“MI:0914”(association)	0.350

BioGRID (43): DGKG (Affinity Capture-MS), FBXW8 (Affinity Capture-MS), ZC2HC1A (Affinity Capture-MS), DGKH (Affinity Capture-MS), TBL1X (Affinity Capture-MS), VCPIP1 (Affinity Capture-MS), SMCHD1 (Affinity Capture-MS), USP15 (Affinity Capture-MS), DHTKD1 (Affinity Capture-MS), TPP1 (Affinity Capture-MS), NCOR2 (Affinity Capture-MS), NCOR1 (Affinity Capture-MS), TBL1XR1 (Affinity Capture-MS), NOP14 (Affinity Capture-MS), CUL7 (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

2 interactions.

A	Effect	B	Mechanism
CREB5	“up-regulates quantity by expression”	DGKG	“transcriptional regulation”
CREB5	“down-regulates quantity by repression”	DGKG	“transcriptional regulation”

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	129
Likely benign	4
Benign	2

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
4070971	NM_001346.3(DGKG):c.546_547del (p.Met183fs)	Pathogenic

SpliceAI

4690 predictions. Top by Δscore:

Variant	Effect	Δscore
3:186105710:TTT:T	acceptor_gain	1.0000
3:186105711:TT:T	acceptor_gain	1.0000
3:186105711:TTCT:T	acceptor_loss	1.0000
3:186105712:TCTGA:T	acceptor_loss	1.0000
3:186105713:C:CC	acceptor_gain	1.0000
3:186105713:CTGAA:C	acceptor_loss	1.0000
3:186105714:T:C	acceptor_loss	1.0000
3:186108934:CCTCA:C	donor_loss	1.0000
3:186108935:CTCA:C	donor_loss	1.0000
3:186108936:TCA:T	donor_loss	1.0000
3:186108937:CACCT:C	donor_loss	1.0000
3:186108939:C:CG	donor_loss	1.0000
3:186161672:C:CT	acceptor_gain	1.0000
3:186161672:C:T	acceptor_gain	1.0000
3:186161673:A:T	acceptor_gain	1.0000
3:186170867:T:TA	donor_gain	1.0000
3:186188197:CTTA:C	donor_loss	1.0000
3:186188198:TTAC:T	donor_loss	1.0000
3:186188199:TACCT:T	donor_loss	1.0000
3:186188200:A:AG	donor_loss	1.0000
3:186188378:CA:C	acceptor_gain	1.0000
3:186211790:CTTA:C	donor_loss	1.0000
3:186211791:TTA:T	donor_loss	1.0000
3:186211792:TA:T	donor_loss	1.0000
3:186211794:C:G	donor_loss	1.0000
3:186211892:C:CT	acceptor_gain	1.0000
3:186242498:GCTTA:G	donor_loss	1.0000
3:186242499:CTTA:C	donor_loss	1.0000
3:186242500:TTA:T	donor_loss	1.0000
3:186242501:TA:T	donor_loss	1.0000

AlphaMissense

5275 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
3:186161623:A:G	W753R	1.000
3:186161623:A:T	W753R	1.000
3:186161625:G:T	P752H	1.000
3:186161631:C:A	G750V	1.000
3:186161631:C:T	G750E	1.000
3:186161632:C:G	G750R	1.000
3:186161632:C:T	G750R	1.000
3:186188289:A:G	W670R	1.000
3:186188289:A:T	W670R	1.000
3:186188303:C:T	G665E	1.000
3:186188320:G:C	N659K	1.000
3:186188320:G:T	N659K	1.000
3:186188330:G:T	A656D	1.000
3:186188337:C:G	G654R	1.000
3:186211853:C:T	G620D	1.000
3:186211866:A:G	Y616H	1.000
3:186211873:C:A	K613N	1.000
3:186211873:C:G	K613N	1.000
3:186211875:T:C	K613E	1.000
3:186211876:G:C	N612K	1.000
3:186211876:G:T	N612K	1.000
3:186211877:T:A	N612I	1.000
3:186211878:T:C	N612D	1.000
3:186211885:C:A	R609S	1.000
3:186211885:C:G	R609S	1.000
3:186242504:C:A	R609M	1.000
3:186242512:G:C	F606L	1.000
3:186242512:G:T	F606L	1.000
3:186242513:A:G	F606S	1.000
3:186242514:A:G	F606L	1.000

dbSNP variants (sampled 300 via entrez): RS1000012822 (3:186225800 T>G), RS1000032259 (3:186262647 C>G), RS1000038827 (3:186179943 C>T), RS1000049783 (3:186284159 G>C), RS1000072573 (3:186249701 A>G), RS1000090409 (3:186293494 C>T), RS1000105630 (3:186201418 C>T), RS1000116763 (3:186363732 G>C), RS1000124343 (3:186216708 G>A,C), RS1000127601 (3:186220078 A>C,T), RS1000151436 (3:186283702 T>C), RS1000183392 (3:186293289 C>T), RS1000193592 (3:186173160 A>G), RS1000204632 (3:186347677 G>A), RS1000220862 (3:186336138 G>T)

Disease associations

OMIM: gene MIM:601854 | disease phenotypes: MIM:143890

GenCC curated gene-disease

Mondo (1): hypercholesterolemia, familial, 1 (MONDO:0007750)

Orphanet (1): Homozygous familial hypercholesterolemia (Orphanet:391665)

HPO phenotypes

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

GWAS associations

29 associations (top):

Study	Trait	p-value
GCST000296_14	Body mass index	7.000000e-11
GCST000299_16	Weight	4.000000e-09
GCST003811_1	Response to citalopram or escitalopram and depression	1.000000e-06
GCST003854_26	Gut microbiota (functional units)	5.000000e-08
GCST004136_11	Methadone dose in opioid dependence	7.000000e-06
GCST004557_47	Body mass index	3.000000e-17
GCST004557_89	Body mass index	6.000000e-15
GCST004558_213	Body mass index (joint analysis main effects and physical activity interaction)	2.000000e-14
GCST004560_16	Body mass index in physically inactive individuals	2.000000e-06
GCST004560_8	Body mass index in physically inactive individuals	7.000000e-06
GCST005170_51	Intraocular pressure	3.000000e-15
GCST005580_122	Intraocular pressure	2.000000e-28
GCST006394_38	Intraocular pressure	3.000000e-43
GCST006395_43	Glaucoma	4.000000e-11
GCST006412_39	Intraocular pressure	9.000000e-52
GCST006611_154	HDL cholesterol	2.000000e-10
GCST006979_313	Heel bone mineral density	5.000000e-17
GCST007565_137	Morning person	6.000000e-16
GCST007576_28	Chronotype	6.000000e-16
GCST007576_413	Chronotype	4.000000e-12
GCST007672_5	3-month functional outcome in ischaemic stroke (modified Rankin score)	9.000000e-06
GCST008152_25	Weight	7.000000e-08
GCST010241_333	Apolipoprotein A1 levels	3.000000e-08
GCST010241_86	Apolipoprotein A1 levels	4.000000e-13
GCST010242_11	HDL cholesterol levels	3.000000e-17
GCST010242_312	HDL cholesterol levels	4.000000e-14
GCST90002398_437	Neutrophil count	2.000000e-09
GCST90002407_419	White blood cell count	4.000000e-09
GCST90011766_10	Glaucoma (primary open-angle)	4.000000e-19

EFO canonical traits (12, from GWAS)

EFO ID	Trait name
EFO:0004340	body mass index
EFO:0004338	body weight
EFO:0007874	gut microbiome measurement
EFO:0007907	methadone dose measurement
EFO:0008002	physical activity measurement
EFO:0004695	intraocular pressure measurement
EFO:0004612	high density lipoprotein cholesterol measurement
EFO:0009270	heel bone mineral density
EFO:0008328	chronotype measurement
EFO:0009603	stroke outcome severity measurement
EFO:0004614	apolipoprotein A 1 measurement
EFO:0004833	neutrophil count

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL1075157 (SINGLE PROTEIN)

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

ChEMBL bioactivities

3 potent at pChembl≥5 of 3 total, top 3 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
6.17	IC50	680	nM	CHEMBL5424446
5.72	IC50	1900	nM	CHEMBL5408449
5.47	IC50	3400	nM	DIACYLGLYCEROL KINASE INHIBITOR II

PubChem BioAssay actives

3 with measured affinity, of 9 total; 3 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	2010062: Inhibition of human DGK gamma using 1, 2-Dilauroyl-sn-glycerol as substrate by ADP-Glo assay	ic50	0.6800	uM
4-(4-benzhydrylpiperazin-1-yl)-1-methyl-3-nitroquinolin-2-one	2010062: Inhibition of human DGK gamma using 1, 2-Dilauroyl-sn-glycerol as substrate by ADP-Glo assay	ic50	1.9000	uM
3-[2-[4-[bis(4-fluorophenyl)methylidene]piperidin-1-yl]ethyl]-2-sulfanylidene-1H-quinazolin-4-one	2010062: Inhibition of human DGK gamma using 1, 2-Dilauroyl-sn-glycerol as substrate by ADP-Glo assay	ic50	3.4000	uM

CTD chemical–gene interactions

29 total (human), top 29 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	affects methylation, decreases methylation, increases expression, increases methylation	3
sodium arsenite	increases expression	2
Vanadium	increases abundance, increases methylation, decreases expression	2
bisphenol A	decreases methylation	1
9,10-dihydro-9,10-dihydroxybenzo(a)pyrene	increases expression	1
3,4,5,3’,4’-pentachlorobiphenyl	increases expression	1
benzo(e)pyrene	increases methylation	1
aflatoxin B2	increases methylation	1
S-(1,2-dichlorovinyl)cysteine	decreases expression, decreases reaction	1
CGP 52608	affects binding, increases reaction	1
abrine	decreases expression	1
perfluorobutanesulfonic acid	decreases expression	1
jinfukang	affects cotreatment, increases expression	1
(+)-JQ1 compound	decreases expression	1
Cisplatin	affects cotreatment, increases expression	1
Doxorubicin	decreases expression	1
Endosulfan	decreases expression	1
Lipopolysaccharides	decreases expression, decreases reaction	1
Methapyrilene	increases methylation	1
Silver	increases expression	1
Smoke	increases expression	1
Thiram	increases expression	1
Tobacco Smoke Pollution	increases expression	1
Triclosan	decreases expression	1
Urethane	decreases expression	1
Metals, Heavy	increases abundance, increases methylation	1
Okadaic Acid	increases expression	1
Copper Sulfate	increases expression	1
Coal Ash	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
CHEMBL1109754	Binding	Inhibition of DAGgamma up to 100 uM	Discovery, biological evaluation, and structure-activity relationship of amidine based sphingosine kinase inhibitors. — J Med Chem

Cellosaurus cell lines

2 cell lines: 1 induced pluripotent stem cell, 1 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_C0IG	LZUSHI001-A	Induced pluripotent stem cell	Male
CVCL_D7NL	Ubigene A-549 DGKG KO	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT06231459	PHASE4	COMPLETED	Expression of Pro- and Anti-inflammatory Cytokines During Anti-PCSK9 in Familial Hypercholesterolemia
NCT00000594	PHASE3	COMPLETED	NHLBI Type II Coronary Intervention Study
NCT00092833	PHASE3	TERMINATED	Investigational Drug in Patients With Hypercholesterolemia or in Patients With Sitosterolemia (0653-026)(COMPLETED)
NCT00134485	PHASE3	COMPLETED	Study To Evaluate The Safety And Efficacy Of Torcetrapib/Atorvastatin In Subjects With Familial Hypercholerolemia
NCT00134511	PHASE3	COMPLETED	Study To Evaluate The Effect Of Torcetrapib/Atorvastatin In Patients With Genetic High Cholesterol Disorder
NCT00136981	PHASE3	COMPLETED	Carotid B-Mode Ultrasound Study to Compare Anti-Atherosclerotic Effect of Torcetrpib/Atorvastatin to Atorvastatin Alone.
NCT00384293	PHASE3	TERMINATED	Carotid IMT (Intima Media Thickening) Study (0524A-041)(TERMINATED)
NCT01524289	PHASE3	COMPLETED	Study to Assess the Tolerability and Efficacy of Anacetrapib (MK-0859) Co-Administered With Statin in Participants With Heterozygous Familial Hypercholesterolemia (MK-0859-020)
NCT00280995	PHASE2	COMPLETED	Dose-escalating Safety Study of ISIS 301012 in Homozygous Familial Hypercholesterolemia Subjects on Lipid Lowering Therapy
NCT00281008	PHASE2	COMPLETED	Study of ISIS 301012 (Mipomersen) in Heterozygous Familial Hypercholesterolemia Subjects on Lipid Lowering Therapy
NCT01375751	PHASE2	COMPLETED	Reduction of Low-Density Lipoprotein Cholesterol (LDL-C) With PCSK9 Inhibition in Heterozygous Familial Hypercholesterolemia Disorder Study
NCT00515307	PHASE1	COMPLETED	Bone Marrow Stem Cells as a Source of Allogenic Hepatocyte Transplantation in Homozygous Familial Hypercholesterolemia
NCT01583647	PHASE1	TERMINATED	A Study of Extended-release (ER) Niacin/Laropiprant in Adolescents With Heterozygous Familial Hypercholesterolemia (MK-0524A-158)
NCT00005168	Not specified	COMPLETED	Hyperapo B and Coronary Heart Disease
NCT01753232	Not specified	COMPLETED	Safety and Efficacy of the DALI LDL-adsorber and MONET Lipoprotein Filter
NCT03018678	Not specified	COMPLETED	Screening Protocol for a Gene Therapy Trial in Subjects With Homozygous Familial Hypercholesterolemia
NCT03110432	Not specified	COMPLETED	Prospective German Very High Cardiovascular Risk Patients Dyslipidemia Treatment Indication Registry
NCT03795038	Not specified	COMPLETED	Comparison of the Plasma Lipoprotein Apheresis Systems DIAMED and MONET vs. the Whole Blood Apheresis System DALI
NCT03989167	Not specified	RECRUITING	Clinical Decision Support for Familial Hypercholesterolemia
NCT04073797	Not specified	RECRUITING	PET Imaging of Inflammation and Lipid Lowering Study
NCT04118348	Not specified	COMPLETED	Evaluating the Efficacy of Pediatric Lipid Screening Alerts
NCT04313270	Not specified	UNKNOWN	Subclinical Atherosclerosis in Patients With Familial Hypercholesterolemia Treated With Evolocumab®
NCT04526457	Not specified	COMPLETED	Is Family Screening Improved by Genetic Testing of Familial Hypercholesterolemia
NCT04656028	Not specified	ACTIVE_NOT_RECRUITING	Genetic Testing and Motivational Counseling for FH
NCT04722068	Not specified	COMPLETED	Regeneron 1331 Kinetics Sub-Study HoFH
NCT04837638	Not specified	UNKNOWN	Diet Quality and Coronary Artery Calcification in Adults With Heterozygous Familial Hypercholesterolemia
NCT06555120	Not specified	RECRUITING	Screening for Familial Hypercholesterolemia in Children
NCT07543731	Not specified	NOT_YET_RECRUITING	A Real-World Study of Long-Term Adherence and Persistence to Inclisiran, Evolocumab, and Alirocumab