DGKD

Summary

DGKD (diacylglycerol kinase delta, HGNC:2851) is a protein-coding gene on chromosome 2q37.1, encoding Diacylglycerol kinase delta (Q16760). Diacylglycerol kinase that converts diacylglycerol/DAG into phosphatidic acid/phosphatidate/PA and regulates the respective levels of these two bioactive lipids.

This gene encodes a cytoplasmic enzyme that phosphorylates diacylglycerol to produce phosphatidic acid. Diacylglycerol and phosphatidic acid are two lipids that act as second messengers in signaling cascades. Their cellular concentrations are regulated by the encoded protein, and so it is thought to play an important role in cellular signal transduction. Alternative splicing results in two transcript variants encoding different isoforms.

Source: NCBI Gene 8527 — RefSeq curated summary.

At a glance

• GWAS associations: 21
• Clinical variants (ClinVar): 224 total
• Phenotypes (HPO): 1
• Druggable target: yes
• MANE Select transcript: NM_152879

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:2851
Approved symbol	DGKD
Name	diacylglycerol kinase delta
Location	2q37.1
Locus type	gene with protein product
Status	Approved
Aliases	KIAA0145, DGKdelta
Ensembl gene	ENSG00000077044
Ensembl biotype	protein_coding
OMIM	601826
Entrez	8527

Gene structure

Transcript identifiers

Ensembl transcripts: 23 — 14 protein_coding, 6 retained_intron, 2 protein_coding_CDS_not_defined, 1 nonsense_mediated_decay

ENST00000264057, ENST00000409813, ENST00000427930, ENST00000430834, ENST00000442524, ENST00000447484, ENST00000465569, ENST00000471764, ENST00000472732, ENST00000474488, ENST00000480535, ENST00000489613, ENST00000490764, ENST00000495901, ENST00000877255, ENST00000916439, ENST00000916440, ENST00000963806, ENST00000963807, ENST00000963808, ENST00000963809, ENST00000963810, ENST00000963811

RefSeq mRNA: 3 — MANE Select: NM_152879 NM_001377259, NM_003648, NM_152879

CCDS: CCDS2504, CCDS46546

Canonical transcript exons

ENST00000264057 — 30 exons

Exon	Start	End
ENSE00001123844	233354494	233354674
ENSE00001923484	233469371	233472098
ENSE00003460976	233467086	233467203
ENSE00003471846	233451964	233452060
ENSE00003477743	233436316	233436441
ENSE00003489928	233437377	233437479
ENSE00003490200	233450922	233451050
ENSE00003491367	233435818	233435924
ENSE00003493654	233438217	233438379
ENSE00003502975	233449103	233449376
ENSE00003509358	233446712	233446796
ENSE00003532606	233460194	233460345
ENSE00003545485	233458284	233458397
ENSE00003550088	233456899	233456995
ENSE00003552222	233434769	233434901
ENSE00003555974	233462643	233462735
ENSE00003567500	233434380	233434484
ENSE00003589381	233468423	233468553
ENSE00003603897	233457221	233457328
ENSE00003604862	233459757	233459891
ENSE00003614353	233454763	233454873
ENSE00003616468	233445623	233445762
ENSE00003618699	233448087	233448181
ENSE00003628430	233462348	233462459
ENSE00003636958	233464164	233464283
ENSE00003643477	233448276	233448375
ENSE00003651675	233441887	233441995
ENSE00003670395	233449982	233450131
ENSE00003755602	233390403	233390483
ENSE00003759155	233388257	233388367

Expression profiles

Bgee: expression breadth ubiquitous, 141 present calls, max score 97.15.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 13.6572 / max 215.3484, expressed in 1717 samples.

FANTOM5 promoters (12 alternative TSS)

Promoter ID	TPM avg	Samples expressed
26047	11.8800	1704
26058	0.3307	173
26055	0.2588	72
26062	0.2391	112
26060	0.1651	93
26054	0.1493	57
26050	0.1467	53
26057	0.1327	64
26056	0.1277	64
26059	0.1160	53

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
body of stomach	UBERON:0001161	97.15	gold quality
cerebellar hemisphere	UBERON:0002245	96.94	gold quality
cerebellum	UBERON:0002037	96.88	gold quality
cerebellar cortex	UBERON:0002129	96.87	gold quality
right hemisphere of cerebellum	UBERON:0014890	96.80	gold quality
stomach	UBERON:0000945	96.58	gold quality
granulocyte	CL:0000094	96.28	gold quality
gastrocnemius	UBERON:0001388	96.12	gold quality
bone marrow	UBERON:0002371	95.78	gold quality
bone element	UBERON:0001474	95.77	gold quality
muscle of leg	UBERON:0001383	95.55	gold quality
skeletal muscle organ	UBERON:0014892	95.55	gold quality
skeletal muscle tissue	UBERON:0001134	95.54	gold quality
blood	UBERON:0000178	95.51	gold quality
fundus of stomach	UBERON:0001160	95.14	gold quality
bone marrow cell	CL:0002092	94.82	gold quality
cortical plate	UBERON:0005343	94.75	gold quality
apex of heart	UBERON:0002098	94.66	gold quality
small intestine Peyer’s patch	UBERON:0003454	93.99	gold quality
mucosa of stomach	UBERON:0001199	93.96	gold quality
spleen	UBERON:0002106	93.49	gold quality
lymph node	UBERON:0000029	93.45	gold quality
upper lobe of left lung	UBERON:0008952	93.44	gold quality
small intestine	UBERON:0002108	93.41	gold quality
right lung	UBERON:0002167	93.33	gold quality
monocyte	CL:0000576	93.21	gold quality
tibial artery	UBERON:0007610	93.10	gold quality
popliteal artery	UBERON:0002250	93.09	gold quality
muscle tissue	UBERON:0002385	93.09	gold quality
leukocyte	CL:0000738	93.05	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	10.61

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

107 targeting DGKD, 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-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-30A-5P	100.00	76.31	3233
HSA-MIR-30B-5P	100.00	76.29	3248
HSA-MIR-30C-5P	100.00	76.29	3248
HSA-MIR-30D-5P	100.00	76.32	3233
HSA-MIR-30E-5P	100.00	76.32	3242
HSA-MIR-5193	100.00	67.26	1744
HSA-LET-7A-3P	100.00	74.03	3932
HSA-LET-7B-3P	100.00	74.08	3913
HSA-LET-7F-1-3P	100.00	74.02	3928
HSA-MIR-98-3P	100.00	74.08	3907
HSA-MIR-4481	100.00	66.42	1669
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-3667-3P	99.99	67.17	1636
HSA-MIR-1184	99.99	68.19	1458
HSA-MIR-4789-5P	99.98	70.76	2721
HSA-LET-7F-2-3P	99.98	70.98	2588
HSA-MIR-1185-1-3P	99.98	71.04	2593
HSA-MIR-1185-2-3P	99.98	71.04	2593
HSA-MIR-4745-5P	99.98	65.95	1028
HSA-MIR-3065-5P	99.97	71.56	3281
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-493-5P	99.96	72.47	2382
HSA-MIR-4487	99.96	64.58	1252
HSA-MIR-767-5P	99.95	70.85	993
HSA-MIR-6721-5P	99.93	68.92	2981
HSA-MIR-381-3P	99.93	71.87	2854
HSA-MIR-515-5P	99.92	69.82	2343

Literature-anchored findings (GeneRIF, showing 11)

• Alternative splicing of the gene generates two isoforms differing in their expression patterns and in regulatory functions (PMID:12200442)
• Phosphorylation is involved in the control of subcellular localization of DGKdelta1. (PMID:15228384)
• Disruption of diacylglycerol kinase delta (DGKD) is associated with seizures in humans and mice. (PMID:17357084)
• Study identified reduced diacylglycerol kinase delta (DGKdelta) expression and DGK activity in skeletal muscle from type 2 diabetic patients. (PMID:18267070)
• Polymerization of DGK delta regulates the activity of the enzyme by sequestering DGK delta in an inactive cellular location. (PMID:18334213)
• Data indicate a novel mechanism where diacylglycerol kinase delta and protein kinase Calpha modulate the levels of ubiquitinated epidermal growth factor receptors through Akt and ubiquitin-specific protease 8. (PMID:20064931)
• Zinc site mutations impair DGKdelta localization to cytoplasmic puncta and enhance localization the plasma membrane. (PMID:20857926)
• This study demonistrated that the lack of association of DGKD SNPs with PD in the Han Chinese population. (PMID:22406787)
• Diacylglycerol signaling limits Akt activation through diacylglycerol kinase delta and PHLPP2. (PMID:23184957)
• purification and characterization of DGKepsilon’s enzymatic and conformational properties (PMID:28199087)
• Diacylglycerol kinase delta and sphingomyelin synthase-related protein functionally interact via their sterile alpha motif domains. (PMID:31980461)

Cross-species orthologs

7 orthologs

Organism	Symbol	Gene ID
danio_rerio	DGKD	ENSDARG00000113111
mus_musculus	Dgkd	ENSMUSG00000070738
rattus_norvegicus	Dgkd	ENSRNOG00000023238
drosophila_melanogaster	CG34384	FBGN0085413
drosophila_melanogaster	rdgA	FBGN0261549
caenorhabditis_elegans		WBGENE00006483
caenorhabditis_elegans		WBGENE00019428

Paralogs (9): DGKG (ENSG00000058866), DGKA (ENSG00000065357), DGKH (ENSG00000102780), DGKB (ENSG00000136267), DGKQ (ENSG00000145214), DGKZ (ENSG00000149091), DGKE (ENSG00000153933), DGKI (ENSG00000157680), DGKK (ENSG00000274588)

Protein

Protein identifiers

Diacylglycerol kinase delta — Q16760 (reviewed: Q16760)

Alternative names: 130 kDa diacylglycerol kinase, Diglyceride kinase delta

All UniProt accessions (5): Q16760, A0A096LNI6, C9JY42, H7BZR7, H7C0L1

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. By controlling the levels of diacylglycerol, regulates for instance the PKC and EGF receptor signaling pathways and plays a crucial role during development. May also regulate clathrin-dependent endocytosis.

Subunit / interactions. Homooligomer. Monomer. Interacts with AP2A2; regulates clathrin-dependent endocytosis.

Subcellular location. Membrane. Clathrin-coated pit. Cytoplasm Cell membrane. Cytoplasm.

Tissue specificity. Widely expressed. Only detected in ovary, and to a lesser extent in spleen.

Post-translational modifications. Phosphorylated. Phosphorylation by PKC induced by phorbol esters prevents homooligomerization and promotes association with membranes.

Domain organisation. The SAM domain mediates homooligomerization. The PH domain mediates association with membranes.

Induction. Up-regulated by phorbol esters and EGF. Down-regulated by phorbol esters.

Pathway. Lipid metabolism; glycerolipid metabolism.

Similarity. Belongs to the eukaryotic diacylglycerol kinase family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q16760-1	2, DGKdelta2	yes
Q16760-2	1, DGKdelta1

RefSeq proteins (3): NP_001364188, NP_003639, NP_690618* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000756	Diacylglycerol_kin_accessory	Domain
IPR001206	Diacylglycerol_kinase_cat_dom	Domain
IPR001660	SAM	Domain
IPR001849	PH_domain	Domain
IPR002219	PKC_DAG/PE	Domain
IPR011993	PH-like_dom_sf	Homologous_superfamily
IPR013761	SAM/pointed_sf	Homologous_superfamily
IPR016064	NAD/diacylglycerol_kinase_sf	Homologous_superfamily
IPR017438	ATP-NAD_kinase_N	Homologous_superfamily
IPR037606	DGK-delta_SAM	Domain
IPR037607	DGK	Family
IPR046349	C1-like_sf	Homologous_superfamily
IPR047477	C1_DGKdelta_rpt2	Domain
IPR047478	C1_DGKdelta_rpt1	Domain
IPR054474	DGKD_4H	Domain

Pfam: PF00130, PF00169, PF00609, PF00781, PF07647, 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), 3 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)

UniProt features (32 total): helix 8, mutagenesis site 4, sequence conflict 4, region of interest 4, domain 3, strand 3, zinc finger region 2, chain 1, compositionally biased region 1, splice variant 1, turn 1

Structure

Experimental structures (PDB)

2 structures.

PDB	Method	Resolution (Å)
3BQ7	X-RAY DIFFRACTION	2.9
1R79	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q16760-F1	72.02	0.28

Functional residue map

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

Mutagenesis-validated functional residues (4):

Position	Phenotype
369	decreased interaction with ap2a2; when associated with a-372.
372	decreased interaction with ap2a2; when associated with a-369.
748	decreased interaction with ap2a2.
1145	loss of homooligomerization.

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-114508	Effects of PIP2 hydrolysis

MSigDB gene sets: 260 (showing top): TGGTGCT_MIR29A_MIR29B_MIR29C, GOBP_LIPID_MODIFICATION, GOBP_PHOSPHOLIPID_METABOLIC_PROCESS, GOBP_POSITIVE_REGULATION_OF_ENDOCYTOSIS, YAGI_AML_WITH_INV_16_TRANSLOCATION, GOBP_REGULATION_OF_ERBB_SIGNALING_PATHWAY, REACTOME_PLATELET_ACTIVATION_SIGNALING_AND_AGGREGATION, GOBP_PLATELET_ACTIVATION, MORF_SNRP70, GOZGIT_ESR1_TARGETS_DN, GOBP_ORGANOPHOSPHATE_METABOLIC_PROCESS, GOBP_VESICLE_MEDIATED_TRANSPORT, GOBP_POSITIVE_REGULATION_OF_RECEPTOR_MEDIATED_ENDOCYTOSIS, GOBP_ORGANOPHOSPHATE_BIOSYNTHETIC_PROCESS, RODRIGUES_NTN1_TARGETS_DN

GO Biological Process (16): phosphatidic acid biosynthetic process (GO:0006654), endocytosis (GO:0006897), signal transduction (GO:0007165), phospholipase C-activating G protein-coupled receptor signaling pathway (GO:0007200), protein transport (GO:0015031), platelet activation (GO:0030168), intracellular signal transduction (GO:0035556), positive regulation of epidermal growth factor receptor signaling pathway (GO:0045742), diacylglycerol metabolic process (GO:0046339), diacylglycerol catabolic process (GO:0046340), lipid phosphorylation (GO:0046834), negative regulation of phospholipase C/protein kinase C signal transduction (GO:0160195), positive regulation of clathrin-dependent endocytosis (GO:2000370), lipid metabolic process (GO:0006629), phosphatidic acid metabolic process (GO:0046473), glycerolipid metabolic process (GO:0046486)

GO Molecular Function (13): ATP-dependent diacylglycerol kinase activity (GO:0004143), ATP binding (GO:0005524), zinc ion binding (GO:0008270), kinase binding (GO:0019900), diacylglycerol binding (GO:0019992), identical protein binding (GO:0042802), protein homodimerization activity (GO:0042803), protein heterodimerization activity (GO:0046982), nucleotide binding (GO:0000166), protein binding (GO:0005515), kinase activity (GO:0016301), transferase activity (GO:0016740), metal ion binding (GO:0046872)

GO Cellular Component (7): nucleus (GO:0005634), cytoplasm (GO:0005737), cytosol (GO:0005829), plasma membrane (GO:0005886), clathrin-coated pit (GO:0005905), cytoplasmic vesicle (GO:0031410), 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
cellular anatomical structure	3
intracellular anatomical structure	2
protein dimerization activity	2
cytoplasm	2
membrane	2
phosphatidic acid metabolic process	1
glycerophospholipid biosynthetic process	1
vesicle budding from membrane	1
membrane invagination	1
vesicle-mediated transport	1
import into cell	1
cell communication	1
cellular process	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
G protein-coupled receptor signaling pathway	1
phospholipase C activator activity	1
transport	1
intracellular protein localization	1
establishment of protein localization	1
cell activation	1
blood coagulation	1
signal transduction	1
epidermal growth factor receptor signaling pathway	1
regulation of epidermal growth factor receptor signaling pathway	1
positive regulation of ERBB signaling pathway	1
acylglycerol metabolic process	1
diacylglycerol metabolic process	1
acylglycerol catabolic process	1
phosphorylation	1
lipid modification	1
phospholipase C/protein kinase C signal transduction	1
negative regulation of intracellular signal transduction	1
positive regulation of receptor-mediated endocytosis	1
clathrin-dependent endocytosis	1
regulation of clathrin-dependent endocytosis	1
primary metabolic process	1
glycerophospholipid metabolic process	1
lipid metabolic process	1

Protein interactions and networks

STRING

788 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
DGKD	PLEK2	Q9NYT0	698
DGKD	PLEK	P08567	670
DGKD	DGKA	P23743	564
DGKD	ARRB1	P49407	462
DGKD	SAMD8	Q96LT4	441
DGKD	LMOD1	P29536	429
DGKD	DGKK	Q5KSL6	424
DGKD	PCTP	Q9UKL6	422
DGKD	ANK1	P16157	415
DGKD	ANK3	Q12955	415
DGKD	ANK2	Q01484	414
DGKD	DGKG	P49619	406
DGKD	DGKZ	Q13574	404
DGKD	DGKQ	P52824	402
DGKD	CHRM1	P11229	384

IntAct

18 interactions, top by confidence:

A	B	Type	Score
DGKD	DYSF	psi-mi:“MI:0403”(colocalization)	0.500
DGKD	DYSF	psi-mi:“MI:2364”(proximity)	0.500
DGKD	MYH13	psi-mi:“MI:0407”(direct interaction)	0.440
DGKD	H2BC9	psi-mi:“MI:0915”(physical association)	0.400
DGKD	MOK	psi-mi:“MI:0915”(physical association)	0.400
DGKD	FMR1	psi-mi:“MI:0915”(physical association)	0.370
DGKD	FXR2	psi-mi:“MI:0915”(physical association)	0.370
DGKD	Srek1	psi-mi:“MI:0915”(physical association)	0.370
TNFRSF14	DGKD	psi-mi:“MI:0915”(physical association)	0.370
NEK4	E2F8	psi-mi:“MI:0914”(association)	0.350
FEZ1	POLRMT	psi-mi:“MI:0914”(association)	0.350
DGKG	SMCHD1	psi-mi:“MI:0914”(association)	0.350
FEZ1	KCNN4	psi-mi:“MI:0914”(association)	0.350
DGKD		psi-mi:“MI:0915”(physical association)	0.000
DGKD	DYSF	psi-mi:“MI:0915”(physical association)	0.000
DGKD	HAX1	psi-mi:“MI:0915”(physical association)	0.000
DGKD	IGSF21	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (38): DGKD (Affinity Capture-MS), DGKD (Affinity Capture-MS), DGKD (Affinity Capture-MS), DGKD (Affinity Capture-MS), DGKD (Affinity Capture-RNA), DGKD (Affinity Capture-MS), DGKD (Affinity Capture-Western), HAX1 (Two-hybrid), IGSF21 (Two-hybrid), MOK (Proximity Label-MS), HIST1H2BH (Proximity Label-MS), DGKD (Two-hybrid), DGKD (Co-localization), DGKD (Affinity Capture-MS), SLC6A4 (Affinity Capture-Western)

ESM2 similar proteins: A0A0R4IXF6, A1A5R8, A9ZLX4, D3YXJ0, E9PUQ8, G3UZ78, O00750, O15164, O54828, P30052, P40818, P48984, P52963, P59997, P97496, Q02225, Q08AX9, Q08BR4, Q08D35, Q16760, Q1LUC3, Q2I6J1, Q3UWM4, Q498F0, Q5JSH3, Q5JTW2, Q5RHD1, Q60665, Q64398, Q68FF0, Q6INA9, Q6NSI8, Q6NVE8, Q6PDG5, Q6ZMT4, Q7ZVP1, Q80U87, Q86XP1, Q8C5W4, Q8N7X0

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

2 interactions.

A	Effect	B	Mechanism
PRKCA	“down-regulates activity”	DGKD	phosphorylation

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	149
Likely benign	21
Benign	12

Top pathogenic / likely-pathogenic (0)

SpliceAI

6377 predictions. Top by Δscore:

Variant	Effect	Δscore
2:233354671:GAAG:G	donor_gain	1.0000
2:233354674:GGTG:G	donor_loss	1.0000
2:233388256:GACC:G	acceptor_gain	1.0000
2:233388363:CAAAG:C	donor_loss	1.0000
2:233388364:AAAG:A	donor_loss	1.0000
2:233388366:AG:A	donor_loss	1.0000
2:233388367:GG:G	donor_loss	1.0000
2:233388368:GTG:G	donor_loss	1.0000
2:233388369:T:A	donor_loss	1.0000
2:233390400:TAG:T	acceptor_loss	1.0000
2:233390401:A:AG	acceptor_gain	1.0000
2:233390401:A:AT	acceptor_loss	1.0000
2:233390402:G:GA	acceptor_gain	1.0000
2:233390402:GT:G	acceptor_gain	1.0000
2:233390402:GTC:G	acceptor_gain	1.0000
2:233390402:GTCA:G	acceptor_gain	1.0000
2:233390402:GTCAA:G	acceptor_gain	1.0000
2:233390480:TACGG:T	donor_loss	1.0000
2:233390482:CGG:C	donor_loss	1.0000
2:233390484:G:GC	donor_loss	1.0000
2:233390484:G:GG	donor_gain	1.0000
2:233390485:T:G	donor_loss	1.0000
2:233434472:G:GT	donor_gain	1.0000
2:233434495:A:T	donor_gain	1.0000
2:233434900:GG:G	donor_gain	1.0000
2:233434901:GG:G	donor_gain	1.0000
2:233435816:A:AG	acceptor_gain	1.0000
2:233435817:G:GG	acceptor_gain	1.0000
2:233436312:GCAGA:G	acceptor_loss	1.0000
2:233436314:A:AG	acceptor_gain	1.0000

AlphaMissense

7976 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
2:233388330:T:C	L77P	1.000
2:233388345:T:C	L82P	1.000
2:233390479:T:C	F115S	1.000
2:233434440:T:A	W137R	1.000
2:233434440:T:C	W137R	1.000
2:233434811:T:A	W166R	1.000
2:233434811:T:C	W166R	1.000
2:233434833:G:C	R173T	1.000
2:233434833:G:T	R173M	1.000
2:233434834:G:C	R173S	1.000
2:233434834:G:T	R173S	1.000
2:233434844:T:A	C177S	1.000
2:233434844:T:C	C177R	1.000
2:233434845:G:A	C177Y	1.000
2:233434845:G:C	C177S	1.000
2:233434845:G:T	C177F	1.000
2:233434846:C:G	C177W	1.000
2:233434849:T:A	N178K	1.000
2:233434849:T:G	N178K	1.000
2:233434853:T:C	C180R	1.000
2:233434854:G:A	C180Y	1.000
2:233434855:C:G	C180W	1.000
2:233434886:G:A	G191R	1.000
2:233434886:G:C	G191R	1.000
2:233434887:G:A	G191E	1.000
2:233434895:T:C	C194R	1.000
2:233434896:G:A	C194Y	1.000
2:233434897:C:G	C194W	1.000
2:233435820:T:C	C197R	1.000
2:233435821:G:A	C197Y	1.000

dbSNP variants (sampled 300 via entrez): RS1000021365 (2:233463847 G>A,T), RS1000038707 (2:233383864 C>G,T), RS1000061251 (2:233412975 CAATTTGCCATT>C), RS1000092030 (2:233384076 G>A), RS1000161383 (2:233403679 G>A), RS1000161763 (2:233437689 G>A), RS1000173561 (2:233407928 C>T), RS1000185491 (2:233441487 T>C), RS1000215696 (2:233414801 T>A), RS1000229006 (2:233365160 C>A,T), RS1000244544 (2:233445575 C>A,T), RS1000274551 (2:233381515 G>A,T), RS1000305888 (2:233362681 C>A,T), RS1000328059 (2:233436797 G>A), RS1000337423 (2:233362862 C>T)

Disease associations

OMIM: gene MIM:601826 | disease phenotypes:

GenCC curated gene-disease

Mondo (1): dilated cardiomyopathy (MONDO:0005021)

Orphanet (1): Dilated cardiomyopathy (Orphanet:217604)

HPO phenotypes

1 total (1 of 1 shown, HPO-id order):

HPO	Term
HP:0001644	Dilated cardiomyopathy

GWAS associations

21 associations (top):

Study	Trait	p-value
GCST000730_9	Bilirubin levels	3.000000e-19
GCST000769_8	Calcium levels	9.000000e-06
GCST001438_2	Crohn’s disease	1.000000e-12
GCST002201_2	Calcium levels	8.000000e-11
GCST004607_253	Plateletcrit	5.000000e-12
GCST005348_60	Total body bone mineral density	4.000000e-08
GCST005982_12	Calcium levels	8.000000e-17
GCST006065_5	Glaucoma (primary open-angle)	2.000000e-08
GCST007847_94	Type 2 diabetes	2.000000e-09
GCST009598_3	Kidney stones	4.000000e-11
GCST009599_6	Kidney stones	2.000000e-08
GCST009676_15	Urinary calcium excretion	1.000000e-06
GCST009676_2	Urinary calcium excretion	2.000000e-07
GCST010048_2	Bilirubin levels	3.000000e-08
GCST010118_19	Type 2 diabetes	2.000000e-15
GCST012490_106	Femur bone mineral density x serum urate levels interaction	1.000000e-08
GCST012490_465	Femur bone mineral density x serum urate levels interaction	6.000000e-10
GCST90000025_714	Appendicular lean mass	4.000000e-10
GCST90002388_183	Lymphocyte count	1.000000e-14
GCST90002400_347	Plateletcrit	2.000000e-30
GCST90002402_293	Platelet count	6.000000e-22

EFO canonical traits (7, from GWAS)

EFO ID	Trait name
EFO:0004570	bilirubin measurement
EFO:0004838	calcium measurement
EFO:0007985	platelet crit
EFO:0004531	urate measurement
EFO:0004980	appendicular lean mass
EFO:0004587	lymphocyte count
EFO:0004309	platelet count

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D002311	Cardiomyopathy, Dilated	C14.280.195.160; C14.280.238.070; C16.320.488.750

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL1075120 (SINGLE PROTEIN)

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

CTD chemical–gene interactions

28 total (human), top 28 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
GSK-J4	increases expression	1
FR900359	decreases phosphorylation	1
bisphenol F	affects cotreatment, decreases methylation	1
dicrotophos	increases expression	1
bisphenol A	decreases methylation	1
arsenite	increases expression	1
sodium arsenite	increases expression	1
potassium chromate(VI)	affects cotreatment, decreases expression	1
epigallocatechin gallate	affects cotreatment, decreases expression	1
di-n-butylphosphoric acid	affects expression	1
2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one	affects localization, decreases reaction	1
clothianidin	increases expression	1
2-(1H-indazol-4-yl)-6-(4-methanesulfonylpiperazin-1-ylmethyl)-4-morpholin-4-ylthieno(3,2-d)pyrimidine	affects localization, decreases reaction	1
Sunitinib	increases expression	1
Fulvestrant	affects cotreatment, decreases methylation	1
Acetaminophen	increases expression	1
Arsenic	affects methylation	1
Cadmium	decreases expression, increases abundance	1
Glucose	decreases reaction, affects localization	1
Phthalic Acids	increases methylation	1
Progesterone	decreases expression	1
Testosterone	decreases expression	1
Tobacco Smoke Pollution	decreases expression	1
Tretinoin	decreases expression	1
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	decreases expression	1
Cyclosporine	increases expression	1
Cadmium Chloride	decreases expression, increases abundance	1
Vitamin K 3	affects 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
CHEMBL1109755	Binding	Inhibition of DAGdelta1 up to 100 uM	Discovery, biological evaluation, and structure-activity relationship of amidine based sphingosine kinase inhibitors. — J Med Chem

Cellosaurus cell lines

5 cell lines: 4 cancer cell line, 1 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B1Q2	Abcam HeLa DGKD KO	Cancer cell line	Female
CVCL_D7NJ	Ubigene A-549 DGKD KO	Cancer cell line	Male
CVCL_D8JZ	Ubigene HCT 116 DGKD KO	Cancer cell line	Male
CVCL_D9D8	Ubigene HEK293 DGKD KO	Transformed cell line	Female
CVCL_E0BN	Ubigene HeLa DGKD KO	Cancer cell line	Female

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00374465	PHASE4	UNKNOWN	Therapy With Verapamil or Carvedilol in Chronic Heart Failure
NCT01293903	PHASE4	COMPLETED	Study of Qiliqiangxin Capsule to Treat Dilated Cardiomyopathy
NCT01557140	PHASE4	COMPLETED	A Randomized Trial of Carvedilol in Chronic Chagas Cardiomyopathy
NCT01917149	PHASE4	COMPLETED	Supramaximal Titrated Inhibition of RAAS in Dilated Cardiomyopathy
NCT02115581	PHASE4	COMPLETED	Coenzyme Q10 Supplementation in Children With Idiopathic Dilated Cardiomyopathy
NCT06236022	PHASE4	RECRUITING	The Effects of Sirolimus in Patients With Dilated Cardiomyopathy Infected With Kaposi Sarcoma-associated Virus
NCT00333827	PHASE3	COMPLETED	Cell Therapy In Dilated Cardiomyopathy
NCT00505154	PHASE3	COMPLETED	Effect of Rosuvastatin on Left Ventricular Remodeling
NCT01223703	PHASE3	COMPLETED	PUFAs and Left Ventricular Function in Heart Failure
NCT01583114	PHASE3	TERMINATED	PREclinical Mutation CARriers From Families With DIlated Cardiomyopathy and ACE Inhibitors
NCT01914081	PHASE3	UNKNOWN	Resveratrol: A Potential Anti- Remodeling Agent in Heart Failure, From Bench to Bedside
NCT02989181	PHASE3	UNKNOWN	Continues Positive Airway Pressure Treatment for Patients With Dilated Cardiomyopathy and Obstructive Sleep Apnea
NCT03439514	PHASE3	TERMINATED	A Study of ARRY-371797 (PF-07265803) in Patients With Symptomatic Dilated Cardiomyopathy Due to a Lamin A/C Gene Mutation
NCT05237323	PHASE3	COMPLETED	Micophenolate Mofetil Versus Azathioprine in Myocarditis
NCT05849766	PHASE3	COMPLETED	Effect of Dapagliflozin on Cardiac Structure, Function and Secondary Mitral Regurgitation in Patients with Left Ventricle Dysfunction
NCT06250257	PHASE3	RECRUITING	Bromocriptine in Dilated Cardiomyopathy Among Women of Reproductive Age
NCT00629018	PHASE2	COMPLETED	Safety and Efficacy Study of Stem Cell Transplantation to Treat Dilated Cardiomyopathy
NCT00629096	PHASE2	COMPLETED	Intracoronary Infusion of Autologous Bone Marrow Cells for Treatment of Idiopathic Dilated Cardiomyopathy
NCT00765518	PHASE2	COMPLETED	Use of Ixmyelocel-T (Formerly Cardiac Repair Cell [CRC] Treatment) in Patients With Heart Failure Due to Dilated Cardiomyopathy (IMPACT-DCM)
NCT00847964	PHASE2	COMPLETED	Safety and Feasibility of Algisyl-LVR™ as a Method of Left Ventricular Restoration in Patients With DCM Undergoing Open-heart Surgery
NCT01020968	PHASE2	COMPLETED	Use of Ixmyelocel-T (Formerly Catheter-based Cardiac Repair Cell [CRC]) Treatment in Patients With Heart Failure Due to Dilated Cardiomyopathy
NCT01302171	PHASE2	COMPLETED	Bone Marrow Derived Adult Stem Cells for Dilated Cardiomyopathy
NCT01350310	PHASE2	COMPLETED	Safety and Efficacy Study of Intramyocardial Stem Cell Therapy in Patients With Dilated Cardiomyopathy
NCT02133911	PHASE2	COMPLETED	A Pilot Trial of Ranolazine to Treat Patients With Dilated Cardiomyopathy
NCT03071653	PHASE2	SUSPENDED	Left Cardiac Sympathetic Denervation for Cardiomyopathy Feasibility Pilot Study
NCT03572660	PHASE2	ACTIVE_NOT_RECRUITING	Use of Bone Marrow Derived Stem Cell and G-CSF With Circulatory Assistance in the Treatment of DCM
NCT03775070	PHASE2	COMPLETED	Simvastatin Therapy in Patients With Dilated Cardiomyopathy.
NCT04405804	PHASE2	UNKNOWN	Early Administration of Ivabradine in Children With Heart Failure
NCT05410873	PHASE2	COMPLETED	Examining the Effects of Mitochondrial Oxidative Stress in DCM
NCT06632834	PHASE2	RECRUITING	Outcome-targeted Therapy: Principle and Outcome Evaluation: Clinical Study and Phenotype-genotype Correlation
NCT00585546	PHASE1	TERMINATED	Harefield Recovery Protocol Study for Patients With Refractory Chronic Heart Failure
NCT02293603	PHASE1	UNKNOWN	Dilated cardiomYopathy iNtervention With Allogeneic MyocardIally-regenerative Cells (DYNAMIC)
NCT03062956	PHASE1	COMPLETED	A Single Ascending Dose Study Assessing the Safety, Tolerability, PK and PD of MYK-491
NCT03129568	PHASE1	COMPLETED	Transcoronary Infusion of Cardiac Progenitor Cells in Pediatric Dilated Cardiomyopathy
NCT04982081	PHASE1	UNKNOWN	Treating Congestive HF With hiPSC-CMs Through Endocardial Injection
NCT06381466	PHASE1	TERMINATED	A Study to Investigate Safety, Tolerability, and Pharmacokinetics of Oral AZD0233 Compared With Placebo in Healthy Adult Participants.
NCT06464588	PHASE1	RECRUITING	A Phase 1 Open-Label Study of the Safety of Intravenous Allogeneic Neonatal Mesenchymal Cells (nMSCs) in Young Adult (1A) and Pediatric (1B) Patients With Dilated Cardiomyopathy (DCM)
NCT06902896	PHASE1	COMPLETED	Safety and Efficacy of FAP iCDC in End-stage Dilated Cardiomyopathy
NCT07137338	PHASE1	RECRUITING	A Phase 1 AAV Gene Therapy Trial Evaluating Safety and Preliminary Efficacy of RP-A701 in Subjects With BAG3 Dilated Cardiomyopathy
NCT07241104	PHASE1	RECRUITING	A Study of AZD4063 in PLN R14del Dilated Cardiomyopathy