DGKI

Summary

DGKI (diacylglycerol kinase iota, HGNC:2855) is a protein-coding gene on chromosome 7q33, encoding Diacylglycerol kinase iota (O75912). Diacylglycerol kinase that converts diacylglycerol/DAG into phosphatidic acid/phosphatidate/PA and regulates the respective levels of these two bioactive lipids.

This gene is a member of the type IV diacylglycerol kinase subfamily. Diacylglycerol kinases regulate the intracellular concentration of diacylglycerol through its phosphorylation, producing phosphatidic acid. The specific role of the enzyme encoded by this gene is undetermined, however, it may play a crucial role in the production of phosphatidic acid in the retina or in recessive forms of retinal degeneration.

Source: NCBI Gene 9162 — RefSeq curated summary.

At a glance

• GWAS associations: 17
• Clinical variants (ClinVar): 164 total
• Druggable target: yes
• MANE Select transcript: NM_001321708

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:2855
Approved symbol	DGKI
Name	diacylglycerol kinase iota
Location	7q33
Locus type	gene with protein product
Status	Approved
Aliases	DGK-IOTA
Ensembl gene	ENSG00000157680
Ensembl biotype	protein_coding
OMIM	604072
Entrez	9162

Gene structure

Transcript identifiers

Ensembl transcripts: 14 — 7 protein_coding_CDS_not_defined, 6 protein_coding, 1 retained_intron

ENST00000288490, ENST00000424189, ENST00000446122, ENST00000453654, ENST00000460662, ENST00000470895, ENST00000475388, ENST00000477835, ENST00000483619, ENST00000486153, ENST00000494390, ENST00000497321, ENST00000614521, ENST00000706929

RefSeq mRNA: 5 — MANE Select: NM_001321708 NM_001321708, NM_001321709, NM_001321710, NM_001388092, NM_004717

CCDS: CCDS5845, CCDS83227, CCDS94212, CCDS94213

Canonical transcript exons

ENST00000614521 — 33 exons

Exon	Start	End
ENSE00001034359	137608966	137609064
ENSE00001034368	137485374	137485418
ENSE00001034376	137609535	137609609
ENSE00001034386	137585209	137585346
ENSE00001140177	137587097	137587210
ENSE00001140184	137597847	137597907
ENSE00001140192	137599823	137599905
ENSE00003459695	137407875	137407995
ENSE00003461997	137689894	137690002
ENSE00003464478	137572765	137572838
ENSE00003470242	137577222	137577284
ENSE00003479009	137469550	137469619
ENSE00003511205	137656466	137656540
ENSE00003516006	137578270	137578325
ENSE00003526565	137397377	137397413
ENSE00003530141	137412170	137412207
ENSE00003536630	137521866	137521966
ENSE00003568444	137645472	137645537
ENSE00003569916	137654732	137654788
ENSE00003578949	137466902	137466942
ENSE00003585535	137552369	137552568
ENSE00003588269	137678557	137678652
ENSE00003592843	137581850	137581928
ENSE00003606063	137619824	137619940
ENSE00003614583	137463489	137463611
ENSE00003617607	137623483	137623554
ENSE00003627282	137465908	137466035
ENSE00003633531	137487610	137487689
ENSE00003653160	137444077	137444102
ENSE00003657431	137571175	137571286
ENSE00003681133	137381037	137391336
ENSE00003682189	137395598	137395697
ENSE00003913405	137846462	137846974

Expression profiles

Bgee: expression breadth ubiquitous, 185 present calls, max score 86.68.

FANTOM5 (CAGE): breadth broad, TPM avg 3.1279 / max 115.6828, expressed in 595 samples.

FANTOM5 promoters (9 alternative TSS)

Promoter ID	TPM avg	Samples expressed
86415	1.3662	293
86416	0.8538	198
86407	0.2961	84
86413	0.2420	94
86412	0.1386	54
86405	0.1130	43
86404	0.0443	18
86406	0.0380	16
86414	0.0359	13

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
cortical plate	UBERON:0005343	86.68	gold quality
lateral nuclear group of thalamus	UBERON:0002736	82.43	gold quality
calcaneal tendon	UBERON:0003701	81.12	gold quality
stromal cell of endometrium	CL:0002255	80.15	gold quality
thyroid gland	UBERON:0002046	78.94	gold quality
prefrontal cortex	UBERON:0000451	78.68	gold quality
left lobe of thyroid gland	UBERON:0001120	78.64	gold quality
Brodmann (1909) area 23	UBERON:0013554	78.56	gold quality
primary visual cortex	UBERON:0002436	78.05	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	77.28	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	76.96	gold quality
corpus callosum	UBERON:0002336	76.94	gold quality
right lobe of thyroid gland	UBERON:0001119	76.50	gold quality
putamen	UBERON:0001874	76.50	gold quality
nucleus accumbens	UBERON:0001882	76.39	gold quality
occipital lobe	UBERON:0002021	76.15	gold quality
frontal cortex	UBERON:0001870	76.12	gold quality
caudate nucleus	UBERON:0001873	75.47	gold quality
neocortex	UBERON:0001950	75.46	gold quality
ganglionic eminence	UBERON:0004023	75.22	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	75.06	gold quality
entorhinal cortex	UBERON:0002728	74.71	gold quality
superior frontal gyrus	UBERON:0002661	74.28	gold quality
parietal lobe	UBERON:0001872	74.24	gold quality
postcentral gyrus	UBERON:0002581	74.24	gold quality
ventricular zone	UBERON:0003053	74.12	gold quality
telencephalon	UBERON:0001893	74.08	gold quality
cerebral cortex	UBERON:0000956	74.04	gold quality
Brodmann (1909) area 9	UBERON:0013540	74.02	gold quality
middle temporal gyrus	UBERON:0002771	73.84	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-HCAD-35	yes	61.47
E-CURD-119	yes	27.41
E-CURD-114	yes	11.88
E-ANND-3	yes	7.73

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): E2F1

miRNA regulators (miRDB)

145 targeting DGKI, 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-126-5P	100.00	72.71	3180
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-656-3P	100.00	72.15	2788
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-4668-3P	100.00	68.74	2635
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-4795-3P	100.00	74.62	4024
HSA-MIR-6873-3P	100.00	71.42	2626
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-4482-3P	99.98	72.50	3147
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-493-5P	99.96	72.47	2382
HSA-MIR-1250-3P	99.96	70.04	4038
HSA-LET-7C-3P	99.95	73.42	2862
HSA-MIR-144-3P	99.94	73.98	2698
HSA-MIR-101-3P	99.94	75.03	2230
HSA-MIR-9983-3P	99.94	71.48	3631
HSA-MIR-6835-3P	99.93	70.49	2904
HSA-MIR-338-5P	99.92	72.34	2951
HSA-MIR-5680	99.91	69.83	3421
HSA-MIR-10527-5P	99.91	72.28	3754
HSA-MIR-153-5P	99.89	73.86	6317
HSA-MIR-129-5P	99.88	70.26	3273
HSA-LET-7A-2-3P	99.87	70.53	1921
HSA-LET-7G-3P	99.85	70.43	1929
HSA-MIR-4728-5P	99.85	69.39	4718
HSA-MIR-4698	99.84	71.41	4303
HSA-MIR-6079	99.84	68.54	1170
HSA-MIR-6785-5P	99.82	68.68	4428

Literature-anchored findings (GeneRIF, showing 3)

• Here, we report results from a fine-mapping approach involving linkage and association analysis in Finnish and German dyslexic cohorts. We restrict a candidate region to 0.3 Mb on chromosome 7q33. (PMID:21203819)
• the DGKI methylation status identified 22% of poorly responding patients in the low-risk group (PMID:25233099)
• Key molecules associated with thyroid carcinoma prognosis: A study based on transcriptome sequencing and GEO datasets. (PMID:36059514)

Cross-species orthologs

7 orthologs

Organism	Symbol	Gene ID
danio_rerio	DGKI	ENSDARG00000063578
mus_musculus	Dgki	ENSMUSG00000038665
rattus_norvegicus	Dgki	ENSRNOG00000026705
drosophila_melanogaster	CG34384	FBGN0085413
drosophila_melanogaster	rdgA	FBGN0261549
caenorhabditis_elegans		WBGENE00006483
caenorhabditis_elegans		WBGENE00019428

Paralogs (9): DGKG (ENSG00000058866), DGKA (ENSG00000065357), DGKD (ENSG00000077044), DGKH (ENSG00000102780), DGKB (ENSG00000136267), DGKQ (ENSG00000145214), DGKZ (ENSG00000149091), DGKE (ENSG00000153933), DGKK (ENSG00000274588)

Protein

Protein identifiers

Diacylglycerol kinase iota — O75912 (reviewed: O75912)

All UniProt accessions (5): A0A9L9PXR3, E7EM72, O75912, E7EWQ4, E9PFX6

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 probably no preference for any of the diacylglycerols in terms of the acyl chain composition, especially for the acyl chain at the sn-2 position. By controlling the diacylglycerol/DAG-mediated activation of RASGRP3, negatively regulates the Rap1 signaling pathway. May play a role in presynaptic diacylglycerol/DAG signaling and control neurotransmitter release during metabotropic glutamate receptor-dependent long-term depression.

Subunit / interactions. Interacts (via PDZ-binding motif) with DLG4; controls the localization of DGKI to the synapse. Interacts (via PDZ-binding motif) with DLG1. Interacts (via PDZ-binding motif) with DLG2. Interacts (via PDZ-binding motif) with DLG3. May interact with RASGRP3; involved in the regulation of RASGRP3 activity.

Subcellular location. Cell projection. Axon. Dendrite. Presynapse. Postsynapse. Postsynaptic density. Synaptic cell membrane. Cytoplasmic vesicle. Secretory vesicle. Synaptic vesicle membrane. Cytoplasm. Cytosol. Nucleus.

Tissue specificity. Specifically expressed in brain and retina. In brain, highly expressed in hippocampus, caudate nucleus, occipital pole, cerebral cortex, and cerebellum. Also detected in kidney.

Pathway. Lipid metabolism; glycerolipid metabolism.

Similarity. Belongs to the eukaryotic diacylglycerol kinase family.

Isoforms (2)

UniProt ID	Names	Canonical?
O75912-2	2	yes
O75912-1	1

RefSeq proteins (5): NP_001308637, NP_001308638, NP_001308639, NP_001375021, NP_004708 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000756	Diacylglycerol_kin_accessory	Domain
IPR001206	Diacylglycerol_kinase_cat_dom	Domain
IPR002110	Ankyrin_rpt	Repeat
IPR002219	PKC_DAG/PE	Domain
IPR016064	NAD/diacylglycerol_kinase_sf	Homologous_superfamily
IPR017438	ATP-NAD_kinase_N	Homologous_superfamily
IPR036770	Ankyrin_rpt-contain_sf	Homologous_superfamily
IPR037607	DGK	Family
IPR047486	C1_DGKiota_rpt1	Domain
IPR047487	C1_DGKiota_rpt2	Domain
IPR056383	DGKI-like_dom	Domain

Pfam: PF00130, PF00609, PF00781, PF12796, PF23578

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), 4 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)

UniProt features (15 total): compositionally biased region 3, region of interest 3, splice variant 2, repeat 2, chain 1, domain 1, sequence variant 1, sequence conflict 1, short sequence motif 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O75912-F1	73.59	0.37

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-114508	Effects of PIP2 hydrolysis

MSigDB gene sets: 205 (showing top): GOBP_LIPID_MODIFICATION, GOBP_PHOSPHOLIPID_METABOLIC_PROCESS, BENPORATH_ES_WITH_H3K27ME3, REACTOME_PLATELET_ACTIVATION_SIGNALING_AND_AGGREGATION, GOBP_PLATELET_ACTIVATION, ROVERSI_GLIOMA_COPY_NUMBER_UP, GOBP_ORGANOPHOSPHATE_METABOLIC_PROCESS, TGACCTY_ERR1_Q2, MEF2_02, GOBP_ORGANOPHOSPHATE_BIOSYNTHETIC_PROCESS, GOBP_PHOSPHOLIPID_BIOSYNTHETIC_PROCESS, GOBP_GLYCEROLIPID_METABOLIC_PROCESS, GOBP_WOUND_HEALING, REACTOME_EFFECTS_OF_PIP2_HYDROLYSIS, MODULE_289

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

GO Molecular Function (6): ATP-dependent diacylglycerol kinase activity (GO:0004143), ATP binding (GO:0005524), nucleotide binding (GO:0000166), protein binding (GO:0005515), kinase activity (GO:0016301), transferase activity (GO:0016740)

GO Cellular Component (18): nucleus (GO:0005634), cytoplasm (GO:0005737), cytosol (GO:0005829), plasma membrane (GO:0005886), postsynaptic density (GO:0014069), axon (GO:0030424), synaptic vesicle membrane (GO:0030672), protein-containing complex (GO:0032991), dendritic spine (GO:0043197), synapse (GO:0045202), synaptic membrane (GO:0097060), glutamatergic synapse (GO:0098978), membrane (GO:0016020), dendrite (GO:0030425), cytoplasmic vesicle (GO:0031410), cell projection (GO:0042995), presynapse (GO:0098793), postsynapse (GO:0098794)

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	6
synapse	4
intracellular anatomical structure	2
cytoplasm	2
neuron projection	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
phosphorylation	1
lipid modification	1
primary metabolic process	1
cell communication	1
cellular process	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
lipid metabolic process	1
lipid kinase activity	1
phosphotransferase activity, alcohol group as acceptor	1
adenyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
nucleoside phosphate binding	1
heterocyclic compound binding	1
binding	1
transferase activity, transferring phosphorus-containing groups	1
catalytic activity	1
intracellular membrane-bounded organelle	1
membrane	1
cell periphery	1
asymmetric synapse	1
postsynaptic specialization	1
synaptic vesicle	1
exocytic vesicle membrane	1
cellular_component	1
dendrite	1

Protein interactions and networks

STRING

1116 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
DGKI	RASGRP3	Q8IV61	806
DGKI	MARCKS	P29966	755
DGKI	DLG4	P78352	687
DGKI	PRKCA	P17252	550
DGKI	ANK3	Q12955	548
DGKI	ANK1	P16157	546
DGKI	PLCB2	Q00722	451
DGKI	BTBD9	Q96Q07	406
DGKI	DGKH	Q86XP1	373
DGKI	DGKD	Q16760	371
DGKI	ARL6IP4	Q66PJ3	367
DGKI	TMEM178B	H3BS89	351
DGKI	DGKK	Q5KSL6	342
DGKI	TTC7B	Q86TV6	341
DGKI	KIF26B	Q2KJY2	340

IntAct

124 interactions, top by confidence:

A	B	Type	Score
VHL	DGKI	psi-mi:“MI:0915”(physical association)	0.510
DGKI	VHL	psi-mi:“MI:0915”(physical association)	0.510
DGKI	SNX27	psi-mi:“MI:0407”(direct interaction)	0.440
DGKI	MAST2	psi-mi:“MI:0407”(direct interaction)	0.440
SNTG1	DGKI	psi-mi:“MI:0407”(direct interaction)	0.440
DGKI	PDZD2	psi-mi:“MI:0407”(direct interaction)	0.440
SYNJ2BP	DGKI	psi-mi:“MI:0407”(direct interaction)	0.440
DGKI	FRMPD2	psi-mi:“MI:0407”(direct interaction)	0.440
DGKI	SNTA1	psi-mi:“MI:0407”(direct interaction)	0.440
DGKI	DLG1	psi-mi:“MI:0407”(direct interaction)	0.440
DGKI	SNTB1	psi-mi:“MI:0407”(direct interaction)	0.440
DGKI	PTPN3	psi-mi:“MI:0407”(direct interaction)	0.440
DLG4	DGKI	psi-mi:“MI:0407”(direct interaction)	0.440
DGKI	SCRIB	psi-mi:“MI:0407”(direct interaction)	0.440
DGKI	MAST1	psi-mi:“MI:0407”(direct interaction)	0.440
MAGI2	DGKI	psi-mi:“MI:0407”(direct interaction)	0.440
DLG3	DGKI	psi-mi:“MI:0407”(direct interaction)	0.440
DGKI	SNTG2	psi-mi:“MI:0407”(direct interaction)	0.440
DGKI	WHRN	psi-mi:“MI:0407”(direct interaction)	0.440
DGKI	RHPN1	psi-mi:“MI:0407”(direct interaction)	0.440
DGKI	PDZRN3	psi-mi:“MI:0407”(direct interaction)	0.440
DGKI	PDZK1	psi-mi:“MI:0407”(direct interaction)	0.440
DGKI	DLG2	psi-mi:“MI:0407”(direct interaction)	0.440
DGKI	PDZRN4	psi-mi:“MI:0407”(direct interaction)	0.440
DGKI	DLG4	psi-mi:“MI:0407”(direct interaction)	0.440
DGKI	MAGI2	psi-mi:“MI:0407”(direct interaction)	0.440
DGKI	PDZD7	psi-mi:“MI:0407”(direct interaction)	0.440

BioGRID (11): AP2M1 (Co-fractionation), PHB2 (Proximity Label-MS), HIST1H1A (Proximity Label-MS), DGKI (Affinity Capture-MS), GAPDH (Cross-Linking-MS (XL-MS)), HNRNPA2B1 (Cross-Linking-MS (XL-MS)), DGKI (Two-hybrid), VHL (Two-hybrid), DGKI (Affinity Capture-Western), RASGRP3 (Affinity Capture-Western), RAP1A (Affinity Capture-Western)

ESM2 similar proteins: A0JMQ9, A1L1R5, A5PF44, A6QP16, B1H2Q2, B4HWV2, B4JE52, B4KKN5, B4LS82, B5E0H4, D3YWQ0, E7FEV0, F1MAB7, G5E8P1, M9PD06, O46080, O75912, O95696, O96838, P59438, Q10024, Q1L8G6, Q2NKQ1, Q3UGY8, Q3V0G7, Q4G017, Q5TH69, Q5U595, Q5VUJ5, Q5VVW2, Q5VW22, Q6NUB7, Q6P5D3, Q7M760, Q7ZUL9, Q80TM9, Q80U12, Q8AXQ3, Q8BPQ7, Q8K3Y6

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.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 80 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Ras activation upon Ca2+ influx through NMDA receptor	5	52.9×	1e-06
Unblocking of NMDA receptors, glutamate binding and activation	5	50.4×	1e-06
Negative regulation of NMDA receptor-mediated neuronal transmission	5	50.4×	1e-06
Assembly and cell surface presentation of NMDA receptors	10	47.0×	7e-13
Dopamine Neurotransmitter Release Cycle	5	46.0×	2e-06
Long-term potentiation	5	44.1×	2e-06
Neurexins and neuroligins	11	40.1×	4e-13
Protein-protein interactions at synapses	7	34.4×	7e-08

GO biological processes:

GO term	Partners	Fold	FDR
establishment or maintenance of epithelial cell apical/basal polarity	10	74.5×	2e-14
protein localization to synapse	6	58.9×	8e-08
receptor clustering	7	56.0×	8e-09
regulation of postsynaptic membrane neurotransmitter receptor levels	7	44.5×	3e-08
cell-cell adhesion	10	13.0×	4e-07
protein-containing complex assembly	8	11.7×	2e-05
chemical synaptic transmission	7	6.9×	2e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	127
Likely benign	2
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

7840 predictions. Top by Δscore:

Variant	Effect	Δscore
7:137391335:CC:C	acceptor_gain	1.0000
7:137391336:CC:C	acceptor_gain	1.0000
7:137397375:A:AC	donor_gain	1.0000
7:137397376:C:CC	donor_gain	1.0000
7:137407871:TTAC:T	donor_loss	1.0000
7:137407872:T:TG	donor_loss	1.0000
7:137412210:G:C	acceptor_gain	1.0000
7:137444075:A:AC	donor_gain	1.0000
7:137444076:C:CC	donor_gain	1.0000
7:137463487:A:AC	donor_gain	1.0000
7:137463488:C:CT	donor_gain	1.0000
7:137463489:TGTAG:T	donor_gain	1.0000
7:137465901:CACT:C	donor_loss	1.0000
7:137465902:ACTC:A	donor_loss	1.0000
7:137465903:CTCA:C	donor_loss	1.0000
7:137465904:TCA:T	donor_loss	1.0000
7:137465905:CA:C	donor_loss	1.0000
7:137465906:AC:A	donor_gain	1.0000
7:137465906:ACC:A	donor_gain	1.0000
7:137465907:CC:C	donor_gain	1.0000
7:137465907:CCC:C	donor_gain	1.0000
7:137466036:C:CC	acceptor_gain	1.0000
7:137466036:CTA:C	acceptor_loss	1.0000
7:137466037:T:A	acceptor_loss	1.0000
7:137466943:C:CC	acceptor_gain	1.0000
7:137521856:T:TA	donor_gain	1.0000
7:137521864:A:AC	donor_gain	1.0000
7:137521865:C:CC	donor_gain	1.0000
7:137521865:CAAG:C	donor_gain	1.0000
7:137521962:GGGGA:G	acceptor_gain	1.0000

AlphaMissense

7034 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
7:137469558:A:G	F830S	1.000
7:137469565:A:G	W828R	1.000
7:137469565:A:T	W828R	1.000
7:137487635:C:G	R786P	1.000
7:137552475:C:A	G681W	1.000
7:137552543:C:T	G658E	1.000
7:137552561:A:G	L652P	1.000
7:137571191:A:G	F644S	1.000
7:137571194:C:T	G643E	1.000
7:137571195:C:G	G643R	1.000
7:137571195:C:T	G643R	1.000
7:137571262:C:A	W620C	1.000
7:137571262:C:G	W620C	1.000
7:137571264:A:G	W620R	1.000
7:137571264:A:T	W620R	1.000
7:137572788:A:C	C604W	1.000
7:137572790:A:G	C604R	1.000
7:137577232:A:T	V584D	1.000
7:137578279:G:C	F563L	1.000
7:137578279:G:T	F563L	1.000
7:137578281:A:G	F563L	1.000
7:137578285:T:A	K561N	1.000
7:137578285:T:G	K561N	1.000
7:137578286:T:A	K561I	1.000
7:137578287:T:C	K561E	1.000
7:137578288:A:C	N560K	1.000
7:137578288:A:T	N560K	1.000
7:137578289:T:A	N560I	1.000
7:137578306:G:C	F554L	1.000
7:137578306:G:T	F554L	1.000

dbSNP variants (sampled 300 via entrez): RS1000000103 (7:137718388 C>A,T), RS1000003986 (7:137847996 T>C), RS1000004617 (7:137548900 G>T), RS1000019290 (7:137668191 T>C), RS1000023042 (7:137411974 G>A), RS1000029933 (7:137627391 G>T), RS1000037357 (7:137718032 G>A), RS1000047161 (7:137423698 C>T), RS1000047258 (7:137381245 A>G), RS1000048350 (7:137763786 T>A,C), RS1000049799 (7:137590073 A>C), RS1000053128 (7:137759431 T>G), RS1000053471 (7:137462019 G>A), RS1000054007 (7:137596838 T>C), RS1000054905 (7:137500661 T>C)

Disease associations

OMIM: gene MIM:604072 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

17 associations (top):

Study	Trait	p-value
GCST001060_3	AIDS progression	6.000000e-07
GCST002320_9	Cognitive decline (age-related)	6.000000e-06
GCST002539_70	Schizophrenia	3.000000e-09
GCST003248_1	Body mass index	2.000000e-06
GCST004521_256	Autism spectrum disorder or schizophrenia	6.000000e-10
GCST004946_3	Schizophrenia	4.000000e-12
GCST005272_3	Testosterone levels in polycystic ovary syndrome	6.000000e-06
GCST006803_103	Schizophrenia	7.000000e-11
GCST007201_425	Schizophrenia	3.000000e-08
GCST007201_79	Schizophrenia	1.000000e-09
GCST007324_70	Adventurousness	7.000000e-14
GCST007325_271	General risk tolerance (MTAG)	1.000000e-13
GCST008153_25	Lean body mass	5.000000e-06
GCST009600_77	Anorexia nervosa, attention-deficit/hyperactivity disorder, autism spectrum disorder, bipolar disorder, major depression, obsessive-compulsive disorder, schizophrenia, or Tourette syndrome (pleiotropy)	3.000000e-08
GCST010702_3	Subcortical volume (MOSTest)	3.000000e-08
GCST010703_300	Brain morphology (MOSTest)	6.000000e-10
GCST010988_172	Adult body size	2.000000e-08

EFO canonical traits (5, from GWAS)

EFO ID	Trait name
EFO:0004340	body mass index
EFO:0004908	testosterone measurement
EFO:0008579	risk-taking behaviour
EFO:0004995	lean body mass
EFO:0004346	neuroimaging measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL5465280 (SINGLE PROTEIN)

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

PharmGKB variants

1 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs73728712	DGKI		0.00	0

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
8.52	IC50	3	nM	CHEMBL5424446
6.00	IC50	1000	nM	CHEMBL5413938
5.21	IC50	6200	nM	CHEMBL5402920

PubChem BioAssay actives

3 with measured affinity, of 6 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	2010065: Inhibition of human DGK iota using 1, 2-Dilauroyl-sn-glycerol as substrate by ADP-Glo kinase assay	ic50	0.0030	uM
4-[4-[bis(4-fluorophenyl)methyl]piperazin-1-yl]-1-methyl-3-nitro-1,5-naphthyridin-2-one	2010065: Inhibition of human DGK iota using 1, 2-Dilauroyl-sn-glycerol as substrate by ADP-Glo kinase assay	ic50	1.0000	uM
4-[4-[bis(4-fluorophenyl)methyl]piperazin-1-yl]-1-methyl-3-nitro-2-oxoquinoline-6-carbonitrile	2010065: Inhibition of human DGK iota using 1, 2-Dilauroyl-sn-glycerol as substrate by ADP-Glo kinase assay	ic50	6.2000	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, increases expression	3
sodium arsenite	decreases expression, increases expression	2
mercuric bromide	decreases expression, affects cotreatment	2
Benzo(a)pyrene	affects methylation, decreases expression	2
Phenylmercuric Acetate	affects cotreatment, decreases expression	2
Tretinoin	decreases expression, increases expression	2
Aflatoxin B1	affects methylation, decreases methylation	2
p-Chloromercuribenzoic Acid	affects cotreatment, decreases expression	2
aristolochic acid I	decreases expression	1
lead acetate	increases expression	1
ethyl-p-hydroxybenzoate	decreases expression	1
trichostatin A	decreases expression, increases expression	1
arsenite	affects expression	1
mono-(2-ethylhexyl)phthalate	increases expression	1
benzo(e)pyrene	increases methylation	1
potassium chromate(VI)	decreases expression	1
aflatoxin B2	increases methylation	1
nickel sulfate	decreases expression	1
S-(1,2-dichlorovinyl)cysteine	affects response to substance, increases expression, affects cotreatment	1
CGP 52608	affects binding, increases reaction	1
2-palmitoylglycerol	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
2,2’,4,4’,5-brominated diphenyl ether	decreases expression	1
belinostat	affects cotreatment, decreases expression	1
abrine	increases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
Temozolomide	decreases expression	1
Sunitinib	decreases expression	1
Arsenic Trioxide	increases expression	1
Doxorubicin	decreases expression	1

ChEMBL screening assays

1 unique, capped per target: 1 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5363633	Binding	Inhibition of human DGK iota using 1, 2-Dilauroyl-sn-glycerol as substrate by ADP-Glo kinase assay	Discovery of Potent, Dual-Inhibitors of Diacylglycerol Kinases Alpha and Zeta Guided by Phenotypic Optimization. — ACS Med Chem Lett

Clinical trials (associated diseases)

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