DGKQ

Summary

DGKQ (diacylglycerol kinase theta, HGNC:2856) is a protein-coding gene on chromosome 4p16.3, encoding Diacylglycerol kinase theta (P52824). 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 contains three cysteine-rich domains, a proline-rich region, and a pleckstrin homology domain with an overlapping Ras-associating domain. It is localized in the speckle domains of the nucleus, and mediates the regeneration of phosphatidylinositol (PI) from diacylglycerol in the PI-cycle during cell signal transduction.

Source: NCBI Gene 1609 — RefSeq curated summary.

At a glance

• GWAS associations: 26
• Clinical variants (ClinVar): 250 total
• MANE Select transcript: NM_001347

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:2856
Approved symbol	DGKQ
Name	diacylglycerol kinase theta
Location	4p16.3
Locus type	gene with protein product
Status	Approved
Aliases	DAGK, DAGK7
Ensembl gene	ENSG00000145214
Ensembl biotype	protein_coding
OMIM	601207
Entrez	1609

Gene structure

Transcript identifiers

Ensembl transcripts: 9 — 8 protein_coding, 1 protein_coding_CDS_not_defined

ENST00000273814, ENST00000502309, ENST00000509465, ENST00000510286, ENST00000515182, ENST00000932945, ENST00000932946, ENST00000932947, ENST00000970135

RefSeq mRNA: 1 — MANE Select: NM_001347 NM_001347

CCDS: CCDS3342

Canonical transcript exons

ENST00000273814 — 23 exons

Exon	Start	End
ENSE00000969338	970993	971072
ENSE00000969339	968811	968910
ENSE00000969340	968479	968564
ENSE00000969341	968282	968407
ENSE00000969342	967880	968027
ENSE00000969343	967728	967802
ENSE00000969344	967549	967649
ENSE00000969345	967129	967361
ENSE00000969349	965928	966078
ENSE00000969352	963139	963290
ENSE00000969353	962772	962920
ENSE00000969354	962435	962613
ENSE00000969355	961982	962082
ENSE00000969356	961688	961834
ENSE00000969357	961467	961578
ENSE00000969359	961049	961201
ENSE00001309741	973212	973569
ENSE00001862299	958887	960721
ENSE00003480064	965491	965529
ENSE00003623467	966964	967054
ENSE00003630945	965176	965291
ENSE00003660137	966466	966527
ENSE00003668886	966748	966802

Expression profiles

Bgee: expression breadth ubiquitous, 235 present calls, max score 98.22.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 7.5826 / max 118.9985, expressed in 1773 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
51032	7.5826	1773

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
ileal mucosa	UBERON:0000331	98.22	gold quality
pancreatic ductal cell	CL:0002079	94.74	silver quality
granulocyte	CL:0000094	94.17	gold quality
jejunal mucosa	UBERON:0000399	93.40	gold quality
mucosa of transverse colon	UBERON:0004991	93.38	gold quality
right hemisphere of cerebellum	UBERON:0014890	91.48	gold quality
cerebellar hemisphere	UBERON:0002245	90.59	gold quality
cerebellar cortex	UBERON:0002129	90.44	gold quality
epithelial cell of pancreas	CL:0000083	90.34	silver quality
cerebellum	UBERON:0002037	89.92	gold quality
colonic mucosa	UBERON:0000317	88.86	gold quality
transverse colon	UBERON:0001157	88.76	gold quality
middle temporal gyrus	UBERON:0002771	88.50	gold quality
small intestine Peyer’s patch	UBERON:0003454	88.48	gold quality
duodenum	UBERON:0002114	88.43	gold quality
mucosa of sigmoid colon	UBERON:0004993	87.95	gold quality
thymus	UBERON:0002370	87.71	gold quality
small intestine	UBERON:0002108	87.67	gold quality
upper arm skin	UBERON:0004263	87.21	gold quality
right frontal lobe	UBERON:0002810	86.89	gold quality
Brodmann (1909) area 23	UBERON:0013554	86.87	gold quality
blood	UBERON:0000178	85.90	gold quality
skin of hip	UBERON:0001554	85.18	gold quality
colon	UBERON:0001155	84.98	gold quality
intestine	UBERON:0000160	84.92	gold quality
spleen	UBERON:0002106	84.91	gold quality
large intestine	UBERON:0000059	84.79	gold quality
Brodmann (1909) area 9	UBERON:0013540	84.42	gold quality
primary visual cortex	UBERON:0002436	84.21	gold quality
anterior cingulate cortex	UBERON:0009835	84.21	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-MTAB-6386	no	82.33
E-ANND-3	no	2.41

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

8 targets.

Target	Regulation
CYP11A1	Activation
CYP17A1	Activation
CYP21A2	Repression
HSD3B2	Activation
LDLR	Activation
LIPE	Activation
SCARB1	Activation
STAR	Activation

Upstream regulators (CollecTRI, top): NR1H4, NR5A1, SREBF1

miRNA regulators (miRDB)

44 targeting DGKQ, 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-4283	100.00	66.42	2097
HSA-MIR-4692	100.00	67.32	2066
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-4514	99.99	67.10	1870
HSA-MIR-4267	99.96	66.53	2368
HSA-MIR-302E	99.96	70.74	2669
HSA-MIR-185-3P	99.95	67.01	1743
HSA-MIR-22-3P	99.93	68.13	917
HSA-MIR-329-3P	99.91	66.56	1234
HSA-MIR-362-3P	99.91	66.38	1267
HSA-MIR-9902	99.89	69.15	2250
HSA-MIR-3941	99.86	70.54	2735
HSA-MIR-3612	99.45	66.02	1333
HSA-MIR-650	99.45	65.77	1309
HSA-MIR-4721	99.26	66.05	818
HSA-MIR-4685-5P	99.25	65.99	1563
HSA-MIR-6837-5P	99.25	65.47	1632
HSA-MIR-4758-3P	99.12	63.96	869
HSA-MIR-143-5P	98.98	68.87	946
HSA-MIR-3922-5P	98.77	66.53	1059
HSA-MIR-603	98.58	68.28	1603
HSA-MIR-5187-5P	98.54	67.94	952
HSA-MIR-3944-5P	98.50	67.55	997
HSA-MIR-4733-3P	98.35	65.20	994
HSA-MIR-4717-5P	98.19	67.97	894
HSA-MIR-4443	98.02	66.25	1928
HSA-MIR-4446-3P	97.91	64.29	991
HSA-MIR-4675	97.69	64.82	774
HSA-MIR-4741	97.69	64.14	883
HSA-MIR-6799-3P	97.35	65.60	1302

Literature-anchored findings (GeneRIF, showing 11)

• Nuclear DGK-theta co-localizes with phosphatidylinositol 4,5-bisphosphate (PIP(2)) in domains that correspond to nuclear speckles. (PMID:12799190)
• DGK interacts selectively with and is phosphorylated by PKCepsilon and -eta and peptide agonist-induced selective activation of PKCepsilon directly leads to DGK translocation (PMID:15632189)
• Data show that cyclic AMP-stimulated interaction between steroidogenic factor 1 and diacylglycerol kinase theta facilitates induction of CYP17. (PMID:17664281)
• DGKtheta; translocation and activity is regulated by the concerted activity of EGFR and PKC. (PMID:22732145)
• DGK-theta; directly interacts with, and is activated by, basic proteins such as histone H1 and Tau with nm affinity, consistent with a potential role for a polybasic protein or protein domain in the activation of this enzyme. (PMID:23091060)
• The SF1 and SREBP1 activate DGKtheta; transcription in a cAMP-dependent manner in human adrenocortical cells. (PMID:23610160)
• This study found that the minor alleles of GAK rs1564282 and DGKQ rs11248060 significantly increase the risk of PD in Han Chinese populations. (PMID:23618683)
• Data suggest that diacylglycerol kinase theta is a key mediator of bile-acid-stimulated modulation of farnesoid X receptor/mTOR complex 2/Akt signaling pathway and glucose metabolism/homoeostasis in hepatocytes. (PMID:23767959)
• these data demonstrate that DGKtheta; plays an important role in steroid hormone production in human adrenocortical cells (PMID:24369117)
• Roles of DGKs in neurons: Postsynaptic functions? (PMID:31836314)
• Association study of MCCC1/LAMP3 and DGKQ variants with Parkinson’s disease in patients of Malay ancestry. (PMID:33559030)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
mus_musculus	Dgkq	ENSMUSG00000004815
rattus_norvegicus	Dgkq	ENSRNOG00000024112
drosophila_melanogaster	CG31140	FBGN0051140
caenorhabditis_elegans		WBGENE00000958

Paralogs (9): DGKG (ENSG00000058866), DGKA (ENSG00000065357), DGKD (ENSG00000077044), DGKH (ENSG00000102780), DGKB (ENSG00000136267), DGKZ (ENSG00000149091), DGKE (ENSG00000153933), DGKI (ENSG00000157680), DGKK (ENSG00000274588)

Protein

Protein identifiers

Diacylglycerol kinase theta — P52824 (reviewed: P52824)

Alternative names: Diglyceride kinase theta

All UniProt accessions (5): A0A140VKC1, D6RJB4, P52824, H0Y8Q7, H0YA20

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. Within the adrenocorticotropic hormone signaling pathway, produces phosphatidic acid which in turn activates NR5A1 and subsequent steroidogenic gene transcription. Also functions downstream of the nerve growth factor signaling pathway being specifically activated in the nucleus by the growth factor. Through its diacylglycerol activity also regulates synaptic vesicle endocytosis.

Subunit / interactions. Interacts with RHOA (constitutively activated, GTP-bound); the interaction inhibits DGKQ. Interacts with PRKCE. Interacts with PRKCH. Interacts with PLCB1. Interacts with NR5A1; the interaction requires both LXXLL motifs in DGKQ and is required for full phosphatidic acid-mediated activation of NR5A1.

Subcellular location. Cytoplasm. Cytosol. Cell membrane. Synapse. Cytoskeleton. Nucleus. Nucleus speckle. Nucleus matrix.

Post-translational modifications. Phosphorylated by PRKCE and PRKCH in vitro.

Activity regulation. Activated by phosphatidylserine.

Domain organisation. The L-X-X-L-L repeats are both required for binding and phosphatidic acid-mediated activation of the nuclear receptor NR5A1.

Pathway. Lipid metabolism; glycerolipid metabolism.

Similarity. Belongs to the eukaryotic diacylglycerol kinase family.

RefSeq proteins (1): NP_001338* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000159	RA_dom	Domain
IPR000756	Diacylglycerol_kin_accessory	Domain
IPR001206	Diacylglycerol_kinase_cat_dom	Domain
IPR002219	PKC_DAG/PE	Domain
IPR016064	NAD/diacylglycerol_kinase_sf	Homologous_superfamily
IPR017438	ATP-NAD_kinase_N	Homologous_superfamily
IPR029071	Ubiquitin-like_domsf	Homologous_superfamily
IPR037607	DGK	Family
IPR046349	C1-like_sf	Homologous_superfamily
IPR056392	DGKtheta_RBD	Domain

Pfam: PF00130, PF00609, PF00781, PF00788, PF24099

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), 7 shown:

• a 1,2-diacyl-sn-glycerol + ATP = a 1,2-diacyl-sn-glycero-3-phosphate + ADP + H(+) (RHEA:10272)
• a 1-O-alkyl-sn-glycerol + ATP = a 1-O-alkyl-sn-glycero-3-phosphate + ADP + H(+) (RHEA:16937)
• 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-O-hexadecyl-sn-glycerol + ATP = 1-O-hexadecyl-sn-glycero-3-phosphate + ADP + H(+) (RHEA:41672)
• 1-O-hexadecyl-2-acetyl-sn-glycerol + ATP = 1-O-hexadecyl-2-acetyl-sn-glycero-3-phosphate + ADP + H(+) (RHEA:41676)
• 1-O-alkyl-2-acyl-sn-glycerol + ATP = 1-O-alkyl-2-acyl-sn-glycero-3-phosphate + ADP + H(+) (RHEA:44072)

UniProt features (29 total): mutagenesis site 9, compositionally biased region 3, sequence conflict 3, zinc finger region 3, region of interest 3, domain 2, short sequence motif 2, modified residue 2, chain 1, sequence variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P52824-F1	82.56	0.60

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 (2): 22, 26

Mutagenesis-validated functional residues (9):

Position	Phenotype
100	abolishes translocation to the plasma membrane.
160	abolishes translocation to the plasma membrane.
226	abolishes translocation to the plasma membrane.
237	loss of diacylglycerol kinase activity. no effect on translocation to the plasma membrane.
241	no effect on diacylglycerol kinase activity.
242	no effect on diacylglycerol kinase activity.
245	decreased diacylglycerol kinase activity.
246	loss of diacylglycerol kinase activity.
648	loss of diacylglycerol kinase activity. loss of function is synaptic endocytosis.

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-114508	Effects of PIP2 hydrolysis

MSigDB gene sets: 218 (showing top): GOBP_LIPID_MODIFICATION, GOBP_RESPONSE_TO_NITROGEN_COMPOUND, GOBP_PHOSPHOLIPID_METABOLIC_PROCESS, GOBP_CELLULAR_RESPONSE_TO_LIPID, REACTOME_PLATELET_ACTIVATION_SIGNALING_AND_AGGREGATION, GOBP_GLUCOCORTICOID_METABOLIC_PROCESS, GOBP_PLATELET_ACTIVATION, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_UP, GOBP_C21_STEROID_HORMONE_METABOLIC_PROCESS, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_UP, GOBP_REGULATION_OF_HORMONE_LEVELS, GOBP_ORGANOPHOSPHATE_METABOLIC_PROCESS, GOBP_VESICLE_MEDIATED_TRANSPORT, GOBP_CELLULAR_RESPONSE_TO_OXYGEN_CONTAINING_COMPOUND, GOBP_KETONE_METABOLIC_PROCESS

GO Biological Process (25): regulation of gluconeogenesis (GO:0006111), regulation of transcription by RNA polymerase II (GO:0006357), phosphatidic acid biosynthetic process (GO:0006654), epidermal growth factor receptor signaling pathway (GO:0007173), G protein-coupled receptor signaling pathway (GO:0007186), adenylate cyclase-activating G protein-coupled receptor signaling pathway (GO:0007189), phospholipase C-activating G protein-coupled receptor signaling pathway (GO:0007200), positive regulation of gene expression (GO:0010628), negative regulation of gene expression (GO:0010629), platelet activation (GO:0030168), intracellular signal transduction (GO:0035556), diacylglycerol metabolic process (GO:0046339), glycerolipid metabolic process (GO:0046486), lipid phosphorylation (GO:0046834), response to cAMP (GO:0051591), thrombin-activated receptor signaling pathway (GO:0070493), positive regulation of protein kinase C signaling (GO:0090037), regulation of cholesterol metabolic process (GO:0090181), regulation of synaptic vesicle endocytosis (GO:1900242), cellular response to bile acid (GO:1903413), regulation of TORC1 signaling (GO:1903432), regulation of cortisol biosynthetic process (GO:2000064), regulation of progesterone biosynthetic process (GO:2000182), lipid metabolic process (GO:0006629), signal transduction (GO:0007165)

GO Molecular Function (15): ATP-dependent diacylglycerol kinase activity (GO:0004143), diacylglycerol-dependent serine/threonine kinase activity (GO:0004697), ATP binding (GO:0005524), zinc ion binding (GO:0008270), kinase binding (GO:0019900), transmembrane receptor protein tyrosine kinase activator activity (GO:0030297), receptor tyrosine kinase binding (GO:0030971), phospholipase binding (GO:0043274), alkylglycerol kinase activity (GO:0047649), DNA-binding transcription factor binding (GO:0140297), nucleotide binding (GO:0000166), protein binding (GO:0005515), kinase activity (GO:0016301), transferase activity (GO:0016740), metal ion binding (GO:0046872)

GO Cellular Component (15): nucleus (GO:0005634), nucleolus (GO:0005730), cytoplasm (GO:0005737), endosome (GO:0005768), cytosol (GO:0005829), cytoskeleton (GO:0005856), plasma membrane (GO:0005886), vesicle membrane (GO:0012506), membrane (GO:0016020), nuclear matrix (GO:0016363), nuclear speck (GO:0016607), presynapse (GO:0098793), postsynapse (GO:0098794), glutamatergic synapse (GO:0098978), synapse (GO:0045202)

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	3
signal transduction	2
G protein-coupled receptor signaling pathway	2
gene expression	2
regulation of gene expression	2
intracellular anatomical structure	2
phosphotransferase activity, alcohol group as acceptor	2
enzyme binding	2
nuclear lumen	2
intracellular membraneless organelle	2
gluconeogenesis	1
regulation of glucose metabolic process	1
regulation of carbohydrate biosynthetic process	1
regulation of DNA-templated transcription	1
transcription by RNA polymerase II	1
phosphatidic acid metabolic process	1
glycerophospholipid biosynthetic process	1
ERBB signaling pathway	1
G protein-coupled receptor activity	1
adenylate cyclase-modulating G protein-coupled receptor signaling pathway	1
adenylate cyclase activator activity	1
phospholipase C activator activity	1
positive regulation of macromolecule biosynthetic process	1
negative regulation of macromolecule biosynthetic process	1
cell activation	1
blood coagulation	1
acylglycerol metabolic process	1
lipid metabolic process	1
phosphorylation	1
lipid modification	1
response to purine-containing compound	1
response to organophosphorus	1
response to oxygen-containing compound	1
protein kinase C signaling	1
regulation of protein kinase C signaling	1
positive regulation of intracellular signal transduction	1
cholesterol metabolic process	1
regulation of steroid metabolic process	1
regulation of small molecule metabolic process	1

Protein interactions and networks

STRING

1330 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
DGKQ	TMEM175	Q9BSA9	713
DGKQ	GAK	O14976	707
DGKQ	RHOA	P06749	646
DGKQ	PLEK2	Q9NYT0	637
DGKQ	MCCC1	Q96RQ3	636
DGKQ	PLEK	P08567	634
DGKQ	STK39	Q9UEW8	627
DGKQ	SYT11	Q9BT88	603
DGKQ	CCDC62	Q6P9F0	602
DGKQ	RASGRP1	O95267	592
DGKQ	GBA1	P04062	590
DGKQ	DGKH	Q86XP1	516
DGKQ	RIT2	Q99578	505
DGKQ	PLD2	O14939	504
DGKQ	ACMSD	Q8TDX5	492

IntAct

11 interactions, top by confidence:

A	B	Type	Score
NOTCH2NLC	DGKQ	psi-mi:“MI:0915”(physical association)	0.560
HAVCR2	TCAF2	psi-mi:“MI:0914”(association)	0.530
EMILIN1	METTL15	psi-mi:“MI:0914”(association)	0.530
DGKQ	TOR1A	psi-mi:“MI:0915”(physical association)	0.400
	PLEKHG3	psi-mi:“MI:0914”(association)	0.350
	HLA-C	psi-mi:“MI:0914”(association)	0.350
SF3B3	MYO9A	psi-mi:“MI:0914”(association)	0.350
DGKQ	NOTCH2NLC	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (23): DGKQ (Affinity Capture-RNA), DGKQ (Affinity Capture-MS), DGKQ (Affinity Capture-MS), NOTCH2NL (Two-hybrid), NBPF19 (Two-hybrid), DGKQ (Proximity Label-MS), DGKQ (Affinity Capture-Western), DGKQ (Reconstituted Complex), DGKQ (Affinity Capture-MS), DGKQ (Affinity Capture-MS), DGKQ (Affinity Capture-MS), DGKQ (Affinity Capture-RNA), HOXA1 (Two-hybrid), DGKQ (Proximity Label-MS), DGKQ (Proximity Label-MS)

ESM2 similar proteins: A0A061IR73, A0A7N9VSG0, A7YSY2, D3KCC4, D3ZU57, D4A2B7, O08644, O15197, O19179, O43542, O75064, O95382, P0C0K6, P0C0K7, P51840, P52785, P52824, P54777, Q02846, Q05932, Q13470, Q13608, Q1HG60, Q3ZBE0, Q4KM32, Q5JZY3, Q643R3, Q6MG64, Q6NVG1, Q6ZPS2, Q76MJ5, Q7TNJ2, Q80SX8, Q8BYG9, Q8IZY2, Q8NFF5, Q8R5G7, Q8TDZ2, Q8WWN8, Q91V24

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.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	189
Likely benign	26
Benign	7

Top pathogenic / likely-pathogenic (0)

SpliceAI

4097 predictions. Top by Δscore:

Variant	Effect	Δscore
4:961461:GCTCA:G	donor_loss	1.0000
4:961462:CTCA:C	donor_loss	1.0000
4:961464:CACCA:C	donor_loss	1.0000
4:961583:C:CT	acceptor_gain	1.0000
4:961585:C:CT	acceptor_gain	1.0000
4:961586:A:C	acceptor_gain	1.0000
4:961736:T:TA	donor_gain	1.0000
4:961835:C:CC	acceptor_gain	1.0000
4:961835:C:T	acceptor_loss	1.0000
4:961979:TA:T	donor_loss	1.0000
4:961980:A:C	donor_loss	1.0000
4:962429:CTGTA:C	donor_loss	1.0000
4:962430:TGTAC:T	donor_loss	1.0000
4:962431:GTAC:G	donor_loss	1.0000
4:962432:TACC:T	donor_loss	1.0000
4:962433:A:C	donor_loss	1.0000
4:962434:C:CA	donor_loss	1.0000
4:962612:CC:C	acceptor_gain	1.0000
4:962613:CC:C	acceptor_gain	1.0000
4:962614:C:T	acceptor_gain	1.0000
4:963134:CTCA:C	donor_loss	1.0000
4:963135:TCAC:T	donor_loss	1.0000
4:963136:CACCC:C	donor_loss	1.0000
4:963137:A:AC	donor_gain	1.0000
4:963137:AC:A	donor_gain	1.0000
4:963138:C:CC	donor_gain	1.0000
4:963138:CC:C	donor_gain	1.0000
4:963153:T:TA	donor_gain	1.0000
4:963246:C:CT	acceptor_gain	1.0000
4:963285:CGCG:C	acceptor_gain	1.0000

AlphaMissense

6071 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
4:961577:A:G	W822R	0.999
4:961577:A:T	W822R	0.999
4:961990:G:C	F769L	0.999
4:961990:G:T	F769L	0.999
4:961992:A:G	F769L	0.999
4:962023:G:C	F758L	0.999
4:962023:G:T	F758L	0.999
4:962025:A:G	F758L	0.999
4:962506:A:G	W715R	0.999
4:962506:A:T	W715R	0.999
4:962587:A:G	W688R	0.999
4:962587:A:T	W688R	0.999
4:962607:T:A	D681V	0.999
4:962607:T:G	D681A	0.999
4:962609:A:C	N680K	0.999
4:962609:A:T	N680K	0.999
4:973263:A:G	C74R	0.999
4:961556:A:G	W829R	0.998
4:961556:A:T	W829R	0.998
4:961575:C:A	W822C	0.998
4:961575:C:G	W822C	0.998
4:961703:A:G	F816S	0.998
4:961709:A:G	L814P	0.998
4:961991:A:G	F769S	0.998
4:962024:A:G	F758S	0.998
4:962585:C:A	W688C	0.998
4:962585:C:G	W688C	0.998
4:962607:T:C	D681G	0.998
4:971046:A:G	C100R	0.998
4:973237:C:A	W82C	0.998

dbSNP variants (sampled 300 via entrez): RS1000212392 (4:963512 C>T), RS1000260949 (4:960082 T>C), RS10003371 (4:973318 G>A,T), RS1000350886 (4:961929 G>A,C,T), RS1000363006 (4:975208 C>T), RS1000496108 (4:972105 G>A), RS1000496933 (4:965723 G>C), RS10005289 (4:970661 C>A,G), RS1000551515 (4:967464 G>C), RS10005591 (4:970958 C>A,T), RS1000608815 (4:969758 C>T), RS1000631284 (4:959897 G>A), RS1000671604 (4:963900 G>A), RS1000702820 (4:964114 C>T), RS1000780645 (4:974299 C>T)

Disease associations

OMIM: gene MIM:601207 | disease phenotypes: MIM:276900

GenCC curated gene-disease

Mondo (1): Usher syndrome (MONDO:0019501)

Orphanet (1): Usher syndrome (Orphanet:886)

HPO phenotypes

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

GWAS associations

26 associations (top):

Study	Trait	p-value
GCST000261_1	Parkinson’s disease (familial)	7.000000e-07
GCST000567_4	Parkinson’s disease	2.000000e-06
GCST001430_9	Parkinson’s disease	3.000000e-09
GCST001445_3	Parkinson’s disease	3.000000e-12
GCST002544_16	Parkinson’s disease	1.000000e-43
GCST003129_30	Primary biliary cholangitis	9.000000e-12
GCST004878_15	Sjögren’s syndrome	8.000000e-06
GCST004902_45	Parkinson’s disease	1.000000e-50
GCST005334_4	Limited cutaneous systemic scleroderma	2.000000e-06
GCST005336_3	Systemic sclerosis	2.000000e-06
GCST005752_128	Systemic lupus erythematosus	2.000000e-11
GCST006051_4	Idiopathic inflammatory myopathy	6.000000e-07
GCST007278_12	Systemic seropositive rheumatic diseases (Systemic sclerosis or systemic lupus erythematosus or rheumatoid arthritis or idiopathic inflammatory myopathies)	1.000000e-08
GCST007400_19	Systemic lupus erythematosus	2.000000e-08
GCST009131_9	Systemic sclerosis	5.000000e-11
GCST010049_9	Parkinson’s disease	7.000000e-06
GCST010241_408	Apolipoprotein A1 levels	2.000000e-10
GCST010242_5	HDL cholesterol levels	7.000000e-18
GCST010244_437	Triglyceride levels	2.000000e-09
GCST010658_6	High density lipoprotein cholesterol levels	7.000000e-13
GCST010659_10	Waist circumference	2.000000e-06
GCST011956_78	Systemic lupus erythematosus	8.000000e-10
GCST90020025_1040	Waist-to-hip ratio adjusted for BMI	2.000000e-09
GCST90020025_1046	Waist-to-hip ratio adjusted for BMI	4.000000e-13
GCST90020027_1863	Waist-hip index	3.000000e-09
GCST90020027_1869	Waist-hip index	8.000000e-13

EFO canonical traits (5, from GWAS)

EFO ID	Trait name
EFO:1001017	limited scleroderma
EFO:0004614	apolipoprotein A 1 measurement
EFO:0004612	high density lipoprotein cholesterol measurement
EFO:0004530	triglyceride measurement
EFO:0007788	BMI-adjusted waist-hip ratio

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D052245	Usher Syndromes	C09.218.458.341.186.500.500; C09.218.458.341.887.886; C10.597.751.418.341.186.500.500; C10.597.751.418.341.887.886; C10.597.751.941.162.625.500; C11.768.585.658.500.813; C11.966.075.375.500; C16.131.077.299.500; C16.320.290.684.500; C23.888.592.763.393.341.887.886

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

22 total (human), top 22 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
trichostatin A	affects cotreatment, decreases expression	2
Air Pollutants	affects expression, increases abundance, increases expression	2
Valproic Acid	increases expression, increases methylation	2
p-Chloromercuribenzoic Acid	affects cotreatment, decreases expression	2
quercitrin	affects expression	1
sodium arsenite	increases expression	1
beta-methylcholine	affects expression	1
di-n-butylphosphoric acid	affects expression	1
perfluorooctane sulfonic acid	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
dorsomorphin	affects cotreatment, decreases expression	1
jinfukang	increases expression	1
Caffeine	decreases phosphorylation	1
Ozone	affects expression, increases abundance	1
Smoke	decreases expression	1
Tobacco Smoke Pollution	decreases expression	1
Urethane	increases expression	1
Vanadium	decreases expression	1
Sodium Selenite	decreases expression	1
Acrylamide	decreases expression	1
Particulate Matter	increases abundance, increases expression	1
Coal Ash	decreases expression	1

Cellosaurus cell lines

3 cell lines: 2 cancer cell line, 1 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_D7NN	Ubigene A-549 DGKQ KO	Cancer cell line	Male
CVCL_D9DB	Ubigene HEK293 DGKQ KO	Transformed cell line	Female
CVCL_E0TY	Ubigene Hep G2 DGKQ KO	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT07290530	PHASE3	NOT_YET_RECRUITING	24-Month Trial of NPI-001 for the Preservation of Photoreceptors in Retinitis Pigmentosa Associated With Usher Syndrome
NCT02065011	PHASE2	ACTIVE_NOT_RECRUITING	A Study to Determine the Long-Term Safety, Tolerability and Biological Activity of SAR421869 in Patients With Usher Syndrome Type 1B
NCT01505062	PHASE1/PHASE2	TERMINATED	Study of SAR421869 in Participants With Retinitis Pigmentosa Associated With Usher Syndrome Type 1B
NCT04355689	PHASE1/PHASE2	ACTIVE_NOT_RECRUITING	Safety and Efficacy of NPI-001 Tablets for RP Associated With Usher Syndrome
NCT06789445	PHASE1/PHASE2	RECRUITING	A Study to Investigate the Safety of OpCT-001 in Adults Who Have Primary Photoreceptor Disease (CLARICO)
NCT00004345	Not specified	TERMINATED	Study of Dietary N-3 Fatty Acids in Patients With Retinitis Pigmentosa and Usher Syndrome
NCT00016471	Not specified	COMPLETED	A Genetic Analysis of Usher Syndrome in Ashkenazi Jews
NCT00106743	Not specified	COMPLETED	Natural History and Genetic Studies of Usher Syndrome
NCT01954953	Not specified	UNKNOWN	Clinical and Genetic Examination of Usher Syndrome Patients’ Cohort in Europe
NCT02435940	Not specified	RECRUITING	Inherited Retinal Degenerative Disease Registry
NCT03319524	Not specified	COMPLETED	Clinical and Genetic Testing of Patients With Usher Syndrome
NCT03901391	Not specified	COMPLETED	Prospective Open Clinical and Genetic Study of Patients With Retinitis Pigmentosa
NCT03990727	Not specified	UNKNOWN	Phenotype Correlates Genotype of Inherited Retina Dystrophies, Retinitis Pigmentosa, Con>Rod Dystrophies.
NCT04665726	Not specified	RECRUITING	Natural History Study of Usher Syndrome ( Light4Deaf )
NCT04906135	Not specified	COMPLETED	Auditory Neural Function in Implanted Patients With Usher Syndrome
NCT05355415	Not specified	RECRUITING	Adaptive Optics Imaging of Outer Retinal Diseases
NCT07278843	Not specified	RECRUITING	Natural History of Photoreceptor Degeneration in USH1B: Clinical Parameters and Validation of Functional Vision Tests in MYO7A
NCT07548944	Not specified	RECRUITING	Observational Study to Investigate the Short-term Effects of Transcorneal Electrical Stimulation on Visual Performance