DGKK

Summary

DGKK (diacylglycerol kinase kappa, HGNC:32395) is a protein-coding gene on chromosome Xp11.22, encoding Diacylglycerol kinase kappa (Q5KSL6). Diacylglycerol kinase that converts diacylglycerol/DAG into phosphatidic acid/phosphatidate/PA and regulates the respective levels of these two bioactive lipids.

The protein encoded by this gene is an enzyme that phosphorylates diacylglycerol, converting it to phosphatidic acid. The encoded protein is a membrane protein and is inhibited by hydrogen peroxide. Variations in this gene have been associated with hypospadias.

Source: NCBI Gene 139189 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 126 total
• Druggable target: yes
• MANE Select transcript: NM_001013742

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:32395
Approved symbol	DGKK
Name	diacylglycerol kinase kappa
Location	Xp11.22
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000274588
Ensembl biotype	protein_coding
OMIM	300837
Entrez	139189

Gene structure

Transcript identifiers

Ensembl transcripts: 2 — 2 protein_coding

ENST00000611977, ENST00000924126

RefSeq mRNA: 1 — MANE Select: NM_001013742 NM_001013742

CCDS: CCDS75980

Canonical transcript exons

ENST00000611977 — 28 exons

Exon	Start	End
ENSE00003058338	50403061	50403183
ENSE00003168486	50470034	50470825
ENSE00003178041	50422446	50422526
ENSE00003206519	50392341	50392449
ENSE00003712763	50403491	50403597
ENSE00003712876	50404049	50404184
ENSE00003713376	50384720	50384824
ENSE00003719885	50376024	50376165
ENSE00003726282	50386358	50386586
ENSE00003726602	50376758	50376918
ENSE00003727020	50378098	50378232
ENSE00003728315	50379981	50380077
ENSE00003733207	50387554	50387653
ENSE00003733621	50401037	50401139
ENSE00003734272	50388527	50388618
ENSE00003734977	50370426	50370549
ENSE00003735330	50379627	50379734
ENSE00003736274	50382496	50382603
ENSE00003736819	50420403	50420507
ENSE00003737344	50424248	50424358
ENSE00003739503	50390328	50390409
ENSE00003739949	50393152	50393335
ENSE00003742232	50384168	50384264
ENSE00003744004	50374971	50375057
ENSE00003747398	50378578	50378691
ENSE00003752808	50391437	50391576
ENSE00003754104	50371724	50371834
ENSE00003754452	50365409	50369019

Expression profiles

Bgee: expression breadth broad, 45 present calls, max score 83.46.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.3933 / max 96.9394, expressed in 129 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
199292	0.3371	120
199291	0.0562	25

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
cardiac muscle of right atrium	UBERON:0003379	83.46	gold quality
left ventricle myocardium	UBERON:0006566	82.93	gold quality
kidney epithelium	UBERON:0004819	81.26	gold quality
epithelial cell of pancreas	CL:0000083	79.90	gold quality
myocardium	UBERON:0002349	76.05	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	74.53	gold quality
ventricular zone	UBERON:0003053	73.82	gold quality
adenohypophysis	UBERON:0002196	73.16	gold quality
upper arm skin	UBERON:0004263	72.38	gold quality
pituitary gland	UBERON:0000007	72.33	gold quality
nasal cavity epithelium	UBERON:0005384	70.26	gold quality
sperm	CL:0000019	68.51	gold quality
vastus lateralis	UBERON:0001379	67.37	gold quality
nucleus accumbens	UBERON:0001882	67.09	gold quality
quadriceps femoris	UBERON:0001377	66.99	gold quality
granulocyte	CL:0000094	66.39	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	65.92	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	65.71	gold quality
endothelial cell	CL:0000115	65.49	gold quality
cauda epididymis	UBERON:0004360	61.43	gold quality
mucosa of paranasal sinus	UBERON:0005030	61.08	gold quality
superficial temporal artery	UBERON:0001614	60.39	gold quality
cerebellar vermis	UBERON:0004720	59.63	gold quality
cartilage tissue	UBERON:0002418	58.92	gold quality
cardia of stomach	UBERON:0001162	58.56	gold quality
lower lobe of lung	UBERON:0008949	58.38	silver quality
epithelium of nasopharynx	UBERON:0001951	57.53	gold quality
hypothalamus	UBERON:0001898	57.30	gold quality
heart right ventricle	UBERON:0002080	56.67	gold quality
tibialis anterior	UBERON:0001385	56.06	silver quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	5.56

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

178 targeting DGKK, 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-4747-5P	100.00	67.90	2681
HSA-MIR-5196-5P	100.00	67.98	2761
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-29A-3P	100.00	73.11	1835
HSA-MIR-29B-3P	100.00	73.18	1833
HSA-MIR-29C-3P	100.00	73.15	1833
HSA-MIR-4481	100.00	66.42	1669
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-574-5P	100.00	66.01	989
HSA-MIR-196A-1-3P	99.99	72.15	2772
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-8068	99.98	73.85	2376
HSA-MIR-3692-3P	99.98	70.27	2139
HSA-MIR-103A-3P	99.98	69.14	1595
HSA-MIR-107	99.98	69.14	1595
HSA-MIR-8075	99.97	67.20	962
HSA-MIR-4725-3P	99.96	69.53	2520
HSA-MIR-6780B-5P	99.96	69.60	2562
HSA-MIR-146A-5P	99.96	68.93	988
HSA-MIR-146B-5P	99.96	69.13	977
HSA-MIR-96-5P	99.95	72.80	2140
HSA-MIR-767-5P	99.95	70.85	993
HSA-MIR-7153-5P	99.94	68.89	1006
HSA-MIR-3143	99.93	71.96	3104
HSA-MIR-539-5P	99.93	70.30	2855
HSA-MIR-12133	99.92	71.82	2006
HSA-MIR-1271-5P	99.91	71.99	1972
HSA-MIR-6809-3P	99.91	71.45	3814

Literature-anchored findings (GeneRIF, showing 8)

• DGK kappa is a novel human type II diacylglycerol kinase (PMID:16210324)
• Common variants in DGKK are strongly associated with risk of hypospadias (PMID:21113153)
• Studied the relationship between DGKK single nucleotide polymorphisms (SNPs) and hypospadias risk in the Han Chinese population. (PMID:25327554)
• Dgkk appears to be a marker or mediator of squamous cell differentiation in development of mouse external genitalia. No association exists between Dgkk expression and formation of preputial cleft in the genital tubercle of diethylsilbestrol treated mice. (PMID:26162297)
• FMRP is mostly associated diacylglycerol kinase kappa (Dgkkappa), a master regulator that controls the switch between diacylglycerol and phosphatidic acid signaling pathways. (PMID:27233938)
• This study successfully implicated DGKK variants in hypospadias risk among a Han Chinese population, especially for mild/moderate cases. Severe forms of hypospadias are likely due to other genetic factors (PMID:28597849)
• Our study provides strong evidence of an association between DGKK nucleotide variants, haplotypes and hypospadias susceptibility. (PMID:29464676)
• Five DGKK variants previously reported as associated with hypospadias were identified in the genotype data. None of the variants were associated with second- or third-degree hypospadias (range of odds ratios = 0.7-0.9, all p > .05). None of the variants were associated with second- or third-degree hypospadias (range of odds ratios = 0.7-0.9, all p > .05). (PMID:31102501)

Cross-species orthologs

10 orthologs

Organism	Symbol	Gene ID
mus_musculus	Dgkk	ENSMUSG00000062393
rattus_norvegicus	Dgkk	ENSRNOG00000039323
drosophila_melanogaster	Dgkepsilon	FBGN0020930
drosophila_melanogaster	Dgk	FBGN0085390
drosophila_melanogaster	CG34384	FBGN0085413
drosophila_melanogaster	rdgA	FBGN0261549
caenorhabditis_elegans		WBGENE00000959
caenorhabditis_elegans		WBGENE00000960
caenorhabditis_elegans		WBGENE00006483
caenorhabditis_elegans		WBGENE00019428

Paralogs (9): DGKG (ENSG00000058866), DGKA (ENSG00000065357), DGKD (ENSG00000077044), DGKH (ENSG00000102780), DGKB (ENSG00000136267), DGKQ (ENSG00000145214), DGKZ (ENSG00000149091), DGKE (ENSG00000153933), DGKI (ENSG00000157680)

Protein

Protein identifiers

Diacylglycerol kinase kappa — Q5KSL6 (reviewed: Q5KSL6)

Alternative names: 142 kDa diacylglycerol kinase, Diglyceride kinase kappa

All UniProt accessions (1): Q5KSL6

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.

Subunit / interactions. Does not form homooligomers.

Subcellular location. Cell membrane.

Tissue specificity. Expressed in testis, and to a lesser extent in placenta.

Post-translational modifications. Phosphorylated at Tyr-78 by some member of the SRC family in response to H(2)O(2).

Activity regulation. Inhibited in response to H(2)O(2).

Pathway. Lipid metabolism; glycerolipid metabolism.

Similarity. Belongs to the eukaryotic diacylglycerol kinase family.

RefSeq proteins (1): NP_001013764* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000756	Diacylglycerol_kin_accessory	Domain
IPR001206	Diacylglycerol_kinase_cat_dom	Domain
IPR001849	PH_domain	Domain
IPR002219	PKC_DAG/PE	Domain
IPR011993	PH-like_dom_sf	Homologous_superfamily
IPR016064	NAD/diacylglycerol_kinase_sf	Homologous_superfamily
IPR017438	ATP-NAD_kinase_N	Homologous_superfamily
IPR037607	DGK	Family
IPR046349	C1-like_sf	Homologous_superfamily
IPR054474	DGKD_4H	Domain

Pfam: PF00130, PF00169, PF00609, PF00781, PF22944

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), 2 shown:

• a 1,2-diacyl-sn-glycerol + ATP = a 1,2-diacyl-sn-glycero-3-phosphate + ADP + H(+) (RHEA:10272)
• 1,2-di-(9Z-octadecenoyl)-sn-glycerol + ATP = 1,2-di-(9Z-octadecenoyl)-sn-glycero-3-phosphate + ADP + H(+) (RHEA:40327)

UniProt features (53 total): repeat 33, region of interest 6, compositionally biased region 5, domain 2, zinc finger region 2, mutagenesis site 2, chain 1, modified residue 1, sequence variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q5KSL6-F1	66.68	0.19

Functional residue map

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

Post-translational modifications (1): 78

Mutagenesis-validated functional residues (2):

Position	Phenotype
78	induces a strong reduction in phosphorylation but is still sensitive to h(2)o(2).
1075	does not affect phosphorylation.

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-114508	Effects of PIP2 hydrolysis

MSigDB gene sets: 84 (showing top): GSE45365_NK_CELL_VS_CD8A_DC_DN, GOBP_PHOSPHOLIPID_METABOLIC_PROCESS, REACTOME_PLATELET_ACTIVATION_SIGNALING_AND_AGGREGATION, GOBP_PLATELET_ACTIVATION, GOBP_ORGANOPHOSPHATE_METABOLIC_PROCESS, GOBP_ORGANOPHOSPHATE_BIOSYNTHETIC_PROCESS, GOBP_PHOSPHOLIPID_BIOSYNTHETIC_PROCESS, GOBP_GLYCEROLIPID_METABOLIC_PROCESS, GOBP_WOUND_HEALING, REACTOME_EFFECTS_OF_PIP2_HYDROLYSIS, GOBP_GLYCEROLIPID_BIOSYNTHETIC_PROCESS, GOBP_GLYCEROPHOSPHOLIPID_METABOLIC_PROCESS, GOBP_LIPID_METABOLIC_PROCESS, GOBP_NEUTRAL_LIPID_METABOLIC_PROCESS, GOBP_LIPID_BIOSYNTHETIC_PROCESS

GO Biological Process (9): phosphatidic acid biosynthetic process (GO:0006654), response to oxidative stress (GO:0006979), 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 metabolic process (GO:0006629), signal transduction (GO:0007165), glycerolipid metabolic process (GO:0046486)

GO Molecular Function (7): ATP-dependent diacylglycerol kinase activity (GO:0004143), ATP binding (GO:0005524), zinc ion binding (GO:0008270), nucleotide binding (GO:0000166), kinase activity (GO:0016301), transferase activity (GO:0016740), metal ion binding (GO:0046872)

GO Cellular Component (2): plasma membrane (GO:0005886), membrane (GO:0016020)

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
phosphatidic acid metabolic process	1
glycerophospholipid biosynthetic process	1
response to stress	1
G protein-coupled receptor signaling pathway	1
phospholipase C activator activity	1
cell activation	1
blood coagulation	1
intracellular anatomical structure	1
signal transduction	1
acylglycerol metabolic process	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
transition metal ion binding	1
nucleoside phosphate binding	1
heterocyclic compound binding	1
transferase activity, transferring phosphorus-containing groups	1
catalytic activity	1
cation binding	1
membrane	1
cell periphery	1
cellular anatomical structure	1

Protein interactions and networks

STRING

814 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
DGKK	MAMLD1	Q13495	586
DGKK	FMR1	Q06787	538
DGKK	RSBN1L	Q6PCB5	526
DGKK	DGKG	P49619	489
DGKK	DGKQ	P52824	464
DGKK	SRD5A2	P31213	449
DGKK	BNC2	Q6ZN30	429
DGKK	HSD17B3	P37058	428
DGKK	MTHFR	P42898	426
DGKK	DGKD	Q16760	424
DGKK	HOXA4	Q00056	421
DGKK	DGKH	Q86XP1	419
DGKK	HOXB6	P09068	408
DGKK	SHROOM4	Q9ULL8	390
DGKK	FXR2	P51116	375

IntAct

254 interactions, top by confidence:

A	B	Type	Score
DGKK	APBA3	psi-mi:“MI:0407”(direct interaction)	0.440
DGKK	PTPN13	psi-mi:“MI:0407”(direct interaction)	0.440
DGKK	MAST2	psi-mi:“MI:0407”(direct interaction)	0.440
DGKK	LIMK1	psi-mi:“MI:0407”(direct interaction)	0.440
DGKK	CNKSR1	psi-mi:“MI:0407”(direct interaction)	0.440
DGKK	GORASP2	psi-mi:“MI:0407”(direct interaction)	0.440
DGKK	TAMALIN	psi-mi:“MI:0407”(direct interaction)	0.440
DGKK	MAST1	psi-mi:“MI:0407”(direct interaction)	0.440
DVL2	DGKK	psi-mi:“MI:0407”(direct interaction)	0.440
DGKK	SHANK1	psi-mi:“MI:0407”(direct interaction)	0.440
DGKK	PDZRN3	psi-mi:“MI:0407”(direct interaction)	0.440
GRID2IP	DGKK	psi-mi:“MI:0407”(direct interaction)	0.440
DGKK	PDZRN4	psi-mi:“MI:0407”(direct interaction)	0.440
DGKK	DLG1	psi-mi:“MI:0407”(direct interaction)	0.440
APBA3	DGKK	psi-mi:“MI:0407”(direct interaction)	0.440
DGKK	CARD11	psi-mi:“MI:0407”(direct interaction)	0.440
DGKK	WHRN	psi-mi:“MI:0407”(direct interaction)	0.440
TAX1BP3	DGKK	psi-mi:“MI:0407”(direct interaction)	0.440
DGKK	PDZD7	psi-mi:“MI:0407”(direct interaction)	0.440
DGKK	PATJ	psi-mi:“MI:0407”(direct interaction)	0.440
DGKK	LNX1	psi-mi:“MI:0407”(direct interaction)	0.440
DGKK	APBA2	psi-mi:“MI:0407”(direct interaction)	0.440
DGKK	SCRIB	psi-mi:“MI:0407”(direct interaction)	0.440
DGKK	AHNAK	psi-mi:“MI:0407”(direct interaction)	0.440
DGKK	ARHGAP21	psi-mi:“MI:0407”(direct interaction)	0.440
DGKK	ARHGEF11	psi-mi:“MI:0407”(direct interaction)	0.440

BioGRID (7): HIST1H2BH (Proximity Label-MS), DGKK (Affinity Capture-MS), DGKK (Negative Genetic), DGKK (Cross-Linking-MS (XL-MS)), DGKK (Cross-Linking-MS (XL-MS)), DGKK (Affinity Capture-MS), DGKK (Cross-Linking-MS (XL-MS))

ESM2 similar proteins: A0A8M3B525, A2AHJ4, A5PJP6, B0KWU8, B2RYM5, B5X8M4, E1C3P4, E9Q4Z2, O00763, O42611, O94967, O95630, P46736, P46737, P48553, Q15386, Q15542, Q3TLI0, Q4VA72, Q5KSL6, Q5R558, Q5R9L6, Q5RAQ5, Q5VVJ2, Q641K1, Q66GV6, Q66H62, Q69Z66, Q6RI45, Q6WKZ8, Q76N33, Q7M757, Q80U95, Q8BPM2, Q8CGF6, Q8IVH8, Q8QFR2, Q8TAT6, Q8VDD9, Q8W206

Diamond homologs: A0JN54, A8JQ65, B3LXF2, B3NYS4, B4I4Y1, B4JHJ7, B4K6T8, B4PRE2, B4R0A5, D3YWQ0, D3YXJ0, D3YZU1, D3ZEY4, E9PUQ8, F1MAB7, F4JKI3, F4JQ95, G9CGD6, O08560, O75912, O88673, P09216, P10830, P16054, P20192, P23298, P23743, P34885, P49619, P49620, P49621, P51556, P52429, P52824, P90980, Q01583, Q02156, Q03603, Q05655, Q09103

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 115 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	39.1×	9e-06
Unblocking of NMDA receptors, glutamate binding and activation	5	37.2×	9e-06
Negative regulation of NMDA receptor-mediated neuronal transmission	5	37.2×	9e-06
Long-term potentiation	5	32.6×	1e-05
Assembly and cell surface presentation of NMDA receptors	9	31.3×	1e-09
Tight junction interactions	6	30.3×	4e-06
Neurexins and neuroligins	11	29.7×	2e-11
Protein-protein interactions at synapses	6	21.8×	1e-05

GO biological processes:

GO term	Partners	Fold	FDR
establishment or maintenance of epithelial cell apical/basal polarity	14	74.6×	5e-21
protein localization to synapse	7	49.2×	1e-08
receptor clustering	8	45.8×	1e-09
neurotransmitter secretion	5	32.2×	2e-05
regulation of postsynaptic membrane neurotransmitter receptor levels	6	27.3×	6e-06
establishment or maintenance of cell polarity	6	22.1×	1e-05
bicellular tight junction assembly	5	15.2×	6e-04
protein-containing complex assembly	10	10.4×	4e-06

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	95
Likely benign	13
Benign	9

Top pathogenic / likely-pathogenic (0)

SpliceAI

3146 predictions. Top by Δscore:

Variant	Effect	Δscore
X:50370559:C:CT	acceptor_gain	1.0000
X:50371720:GCA:G	donor_loss	1.0000
X:50371721:CA:C	donor_loss	1.0000
X:50371723:CCT:C	donor_gain	1.0000
X:50371830:CTCAG:C	acceptor_gain	1.0000
X:50371831:TCAG:T	acceptor_gain	1.0000
X:50371831:TCAGC:T	acceptor_loss	1.0000
X:50371832:CAG:C	acceptor_gain	1.0000
X:50371832:CAGC:C	acceptor_gain	1.0000
X:50371833:AG:A	acceptor_gain	1.0000
X:50371834:GC:G	acceptor_loss	1.0000
X:50371835:C:CA	acceptor_loss	1.0000
X:50371835:C:CC	acceptor_gain	1.0000
X:50371838:G:C	acceptor_gain	1.0000
X:50371838:G:GC	acceptor_gain	1.0000
X:50371841:C:CT	acceptor_gain	1.0000
X:50371845:C:CT	acceptor_gain	1.0000
X:50371846:A:T	acceptor_gain	1.0000
X:50374964:CACT:C	donor_loss	1.0000
X:50374965:ACTC:A	donor_loss	1.0000
X:50374966:CTCA:C	donor_loss	1.0000
X:50374967:T:TA	donor_loss	1.0000
X:50374968:CA:C	donor_loss	1.0000
X:50374969:A:AC	donor_gain	1.0000
X:50374969:ACC:A	donor_loss	1.0000
X:50374969:ACCAG:A	donor_gain	1.0000
X:50374970:C:CC	donor_gain	1.0000
X:50374970:CCA:C	donor_gain	1.0000
X:50374970:CCAG:C	donor_gain	1.0000
X:50374970:CCAGC:C	donor_gain	1.0000

AlphaMissense

8392 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
X:50390408:A:G	W616R	0.999
X:50390408:A:T	W616R	0.999
X:50392389:G:C	S552R	0.998
X:50392389:G:T	S552R	0.998
X:50392391:T:G	S552R	0.998
X:50382531:G:C	F874L	0.997
X:50382531:G:T	F874L	0.997
X:50382533:A:G	F874L	0.997
X:50382559:C:T	G865E	0.997
X:50382532:A:G	F874S	0.996
X:50391519:A:G	W588R	0.996
X:50391519:A:T	W588R	0.996
X:50392396:T:A	D550V	0.996
X:50393234:C:A	G505W	0.996
X:50420447:A:G	W300R	0.996
X:50420447:A:T	W300R	0.996
X:50378186:A:T	V1008E	0.995
X:50379698:C:G	G931R	0.995
X:50379985:A:G	L917S	0.995
X:50382519:T:A	R878S	0.995
X:50382519:T:G	R878S	0.995
X:50390406:C:A	W616C	0.995
X:50390406:C:G	W616C	0.995
X:50393247:A:C	S500R	0.995
X:50393247:A:T	S500R	0.995
X:50393249:T:G	S500R	0.995
X:50378230:G:C	C993W	0.994
X:50378657:A:G	L966P	0.994
X:50382560:C:G	G865R	0.994
X:50382560:C:T	G865R	0.994

dbSNP variants (sampled 300 via entrez): RS1000088844 (X:50406574 A>G), RS1000138952 (X:50414581 G>A,C), RS1000291715 (X:50464935 C>T), RS1000368108 (X:50388475 C>G), RS1000486939 (X:50454864 T>C), RS1000517030 (X:50458009 G>A,C), RS1000533259 (X:50417349 G>T), RS1000578023 (X:50447163 G>A), RS1000627514 (X:50467051 A>G), RS1000661203 (X:50381428 A>G), RS1000704578 (X:50391033 T>C), RS1000787969 (X:50427183 C>T), RS1000797300 (X:50398535 A>G), RS1000925341 (X:50427648 A>G), RS1000928720 (X:50380983 C>T)

Disease associations

OMIM: gene MIM:300837 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST000888_1	Hypospadias	3.000000e-21
GCST002563_19	Hypospadias	1.000000e-93

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL5465316 (SINGLE PROTEIN)

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

ChEMBL bioactivities

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

pChembl	Type	Value	Unit	Molecule
5.34	IC50	4600	nM	CHEMBL5424446

PubChem BioAssay actives

1 with measured affinity, of 3 total; 1 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	2010063: Inhibition of human DGK kappa using 1, 2-Dilauroyl-sn-glycerol as substrate by ADP-Glo kinase assay	ic50	4.6000	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression	3
entinostat	affects cotreatment, increases expression	2
Aflatoxin B1	decreases methylation, increases methylation	2
GSK-J4	decreases expression	1
FR900359	decreases phosphorylation	1
bisphenol A	affects expression	1
thallium sulfate	decreases expression	1
CGP 52608	affects binding, increases reaction	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
dorsomorphin	affects cotreatment, increases expression	1
bisphenol S	increases methylation	1
Sunitinib	decreases expression	1
Microplastics	decreases expression, increases abundance	1
Benzo(a)pyrene	increases methylation	1
Caffeine	increases phosphorylation	1
Nitrogen Dioxide	increases expression	1
Ozone	increases expression	1
Pesticides	affects response to substance	1
Polyethylene Terephthalates	decreases expression, increases abundance	1
Urethane	decreases expression	1

ChEMBL screening assays

2 unique, capped per target: 2 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5363631	Binding	Inhibition of human DGK kappa 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.