GRK1

Summary

GRK1 (G protein-coupled receptor kinase 1, HGNC:10013) is a protein-coding gene on chromosome 13q34, encoding Rhodopsin kinase GRK1 (Q15835). Retina-specific kinase involved in the signal turnoff via phosphorylation of rhodopsin (RHO), the G protein- coupled receptor that initiates the phototransduction cascade.

This gene encodes a member of the guanine nucleotide-binding protein (G protein)-coupled receptor kinase subfamily of the Ser/Thr protein kinase family. The protein phosphorylates rhodopsin and initiates its deactivation. Defects in GRK1 are known to cause Oguchi disease 2 (also known as stationary night blindness Oguchi type-2).

Source: NCBI Gene 6011 — RefSeq curated summary.

At a glance

• Gene–disease (curated): Oguchi disease (Definitive, ClinGen) — +1 more curated relationship
• Clinical variants (ClinVar): 109 total — 4 pathogenic, 16 likely-pathogenic
• Phenotypes (HPO): 14
• Druggable target: yes — 12 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_002929

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:10013
Approved symbol	GRK1
Name	G protein-coupled receptor kinase 1
Location	13q34
Locus type	gene with protein product
Status	Approved
Aliases	GPRK1, RK
Ensembl gene	ENSG00000185974
Ensembl biotype	protein_coding
OMIM	180381
Entrez	6011

Gene structure

Transcript identifiers

Ensembl transcripts: 3 — 1 protein_coding, 1 protein_coding_CDS_not_defined, 1 retained_intron

ENST00000335678, ENST00000545304, ENST00000606140

RefSeq mRNA: 1 — MANE Select: NM_002929 NM_002929

CCDS: CCDS81785

Canonical transcript exons

ENST00000335678 — 7 exons

Exon	Start	End
ENSE00001334819	113669687	113669814
ENSE00001334824	113671499	113671656
ENSE00001334831	113667219	113668085
ENSE00001759089	113723074	113723157
ENSE00001805752	113735068	113737736
ENSE00003504746	113731219	113731343
ENSE00003701473	113732884	113733085

Expression profiles

Bgee: expression breadth broad, 52 present calls, max score 86.27.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.2534 / max 138.5777, expressed in 10 samples.

FANTOM5 promoters (6 alternative TSS)

Promoter ID	TPM avg	Samples expressed
136248	0.1170	8
136244	0.0695	8
136245	0.0266	7
136246	0.0177	6
136247	0.0142	5
136249	0.0084	3

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	86.27	gold quality
right lobe of thyroid gland	UBERON:0001119	69.78	gold quality
left lobe of thyroid gland	UBERON:0001120	67.05	gold quality
thyroid gland	UBERON:0002046	66.58	gold quality
cortical plate	UBERON:0005343	55.71	gold quality
apex of heart	UBERON:0002098	55.65	gold quality
ventricular zone	UBERON:0003053	53.50	gold quality
ganglionic eminence	UBERON:0004023	51.65	silver quality
duodenum	UBERON:0002114	50.17	gold quality
bone marrow	UBERON:0002371	50.12	gold quality
bone marrow cell	CL:0002092	47.56	gold quality
prefrontal cortex	UBERON:0000451	45.72	gold quality
superior frontal gyrus	UBERON:0002661	42.45	silver quality
frontal cortex	UBERON:0001870	42.31	gold quality
fundus of stomach	UBERON:0001160	41.48	gold quality
heart left ventricle	UBERON:0002084	41.28	gold quality
primary visual cortex	UBERON:0002436	41.27	gold quality
cerebral cortex	UBERON:0000956	40.02	gold quality
right uterine tube	UBERON:0001302	39.94	silver quality
rectum	UBERON:0001052	38.98	silver quality
heart	UBERON:0000948	38.97	gold quality
substantia nigra	UBERON:0002038	38.96	silver quality
sural nerve	UBERON:0015488	38.92	gold quality
monocyte	CL:0000576	38.89	silver quality
right atrium auricular region	UBERON:0006631	38.29	gold quality
brain	UBERON:0000955	38.25	silver quality
body of stomach	UBERON:0001161	38.04	gold quality
stomach	UBERON:0000945	38.00	gold quality
Ammon’s horn	UBERON:0001954	37.91	silver quality
temporal lobe	UBERON:0001871	37.90	silver quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.57

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

11 targeting GRK1, 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-548AJ-5P	99.78	71.12	3085
HSA-MIR-548F-5P	99.78	71.02	3093
HSA-MIR-548G-5P	99.78	71.12	3085
HSA-MIR-548X-5P	99.78	71.12	3085
HSA-MIR-6740-3P	99.48	68.49	1392
HSA-MIR-4279	99.19	66.70	2437
HSA-MIR-4797-3P	97.48	67.14	989
HSA-MIR-3674	97.01	68.86	1171
HSA-MIR-376A-2-5P	96.43	68.06	715
HSA-MIR-4264	96.35	64.76	1480
HSA-MIR-6863	93.93	67.77	154

Literature-anchored findings (GeneRIF, showing 22)

• Phosphorylation of GRK1 and GRK7 by PKA occurs in the dark, when cAMP levels in photoreceptor cells are elevated. (PMID:15946941)
• The disease in the Pakistani family localizes to 13q34 and is caused by a novel deletion including Exon 3 of the GRK1 gene. (PMID:16319817)
• G protein-coupled receptor kinase site serine cluster has a role in beta2-adrenergic receptor internalization, desensitization, and beta-arrestin translocation (PMID:16407241)
• RhoK activation in brain microvascular endothelial cells could be a cause of blood-brain barrier impairment during HIV-1 encephalitis. (PMID:16478881)
• A novel homozygous GRK1 mutation (p.P391H) was found in 2 Japanese siblings with Oguchi disease. (PMID:17070587)
• Conserved bicoid homeodomain factors thus appear to be the key factors governing localization of GRK1 Enhancer/Promoter activity in retina and photoreceptors. (PMID:17524610)
• The authors found two different novel mutations in Japanese patients. The results indicate that a considerable number of GRK1 mutations exist in the Japanese population. (PMID:17765441)
• A GRK1 region close to its C-terminus also seemed to be the binding site for S-modulin/recoverin. (PMID:18266817)
• Genetic mapping supported the diagnosis of typical Oguchi disease in a Pakistani family and also resulted in the identification of a novel nonsense mutation (c.614C>A; p.S205X) in exon 1 of GRK1. (PMID:19753316)
• There are two genes that cause Oguchi disease: the G protein-coupled receptor kinase 1 gene and the S antigen gene. There is evidence that Oguchi disease and retinitis pigmentosa (RP) can coexist in the same family or even in the same individual (PMID:21922265)
• Defects in GRK1 or GRK7 cause patients to suffer from an inability to properly deactivate rhodopsin leading to problems with recovery and dark adaptation. (PMID:22183412)
• The selective thinning of the inner retinal layers in patients with GRM6 mutations suggests either reduced bipolar or ganglion cell numbers or altered synaptic structure in the inner retina. (PMID:22959359)
• Rho-kinase activity exhibits distinct circadian variation associated with alterations in coronary vasomotor responses and autonomic activity in VSA patients. (PMID:24670923)
• In the Ca(2+)/NCS-1.D2R peptide complex, the C-terminal region adopts a 310 helix-turn-310 helix, whereas in the GRK1 peptide complex it forms an a-helix (PMID:25979333)
• The identification of the c.1607_1610delCGGA mutation in a patient with Oguchi disease confirms the pathogenicity of this variant. (PMID:26349155)
• AAMP Regulates Endothelial Cell Migration and Angiogenesis Through RhoA/Rho Kinase Signaling. (PMID:26350504)
• Gene analysis determined a novel GRK1 mutation c.923T>C, which caused Oguchi disease in all siblings. This mutation, was demonstrated by amino acid alignment analysis to be in a phylogenetically conserved region and resulted in an amino acid change from leucine to proline at position 308. Thus, the present study reports a novel missense mutation of GRK1 in the affected members of a consanguineous Turkish family. (PMID:27511724)
• In conclusion, in the present report, a novel missense mutation in GRK1 gene in homozygous state was reported in an Italian patient affected with Oguchi disease. (PMID:28511019)
• Wide-field true-colour imaging and clinical characterization of a novel GRK1 mutation in Oguchi disease. (PMID:32146548)
• New variants and in silico analyses in GRK1 associated Oguchi disease. (PMID:33252155)
• Non-genetic and genetic rewiring underlie adaptation to hypomorphic alleles of an essential gene. (PMID:34528284)
• Disulfide Dimerization of Neuronal Calcium Sensor-1: Implications for Zinc and Redox Signaling. (PMID:34830487)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	grk1a	ENSDARG00000058803
mus_musculus	Grk1	ENSMUSG00000031450
rattus_norvegicus	Grk1	ENSRNOG00000018430
drosophila_melanogaster	Gprk2	FBGN0261988
caenorhabditis_elegans		WBGENE00001708

Paralogs (7): GRK3 (ENSG00000100077), GRK7 (ENSG00000114124), GRK4 (ENSG00000125388), RSKR (ENSG00000167524), GRK2 (ENSG00000173020), GRK6 (ENSG00000198055), GRK5 (ENSG00000198873)

Protein

Protein identifiers

Rhodopsin kinase GRK1 — Q15835 (reviewed: Q15835)

Alternative names: G protein-coupled receptor kinase 1

All UniProt accessions (1): Q15835

UniProt curated annotations — full annotation on UniProt →

Function. Retina-specific kinase involved in the signal turnoff via phosphorylation of rhodopsin (RHO), the G protein- coupled receptor that initiates the phototransduction cascade. This rapid desensitization is essential for scotopic vision and permits rapid adaptation to changes in illumination. May play a role in the maintenance of the outer nuclear layer in the retina.

Subunit / interactions. Interacts (via N-terminus) with RCVRN (via C-terminus); the interaction is Ca(2+)-dependent. Interacts (when prenylated) with PDE6D; this promotes release from membranes. May form a complex composed of RHO, GRK1 and RCVRN in a Ca(2+)-dependent manner; RCVRN prevents the interaction between GRK1 and RHO.

Subcellular location. Membrane. Cell projection. Cilium. Photoreceptor outer segment.

Tissue specificity. Retinal-specific. Expressed in rods and cones cells.

Post-translational modifications. Autophosphorylated, Ser-21 is a minor site of autophosphorylation compared to Ser-491 and Thr-492. Phosphorylation at Ser-21 is regulated by light and activated by cAMP. Farnesylation is required for full activity.

Disease relevance. Night blindness, congenital stationary, Oguchi type 2 (CSNBO2) [MIM:613411] A non-progressive retinal disorder characterized by impaired night vision, often associated with nystagmus and myopia. Congenital stationary night blindness Oguchi type is associated with fundus discoloration and abnormally slow dark adaptation. The disease is caused by variants affecting the gene represented in this entry.

Activity regulation. Inhibited by RCVRN, which prevents the interaction between GRK1 and RHO. Inhibition is calcium-dependent. Inhibited by phosphorylation of Ser-21.

Similarity. Belongs to the protein kinase superfamily. AGC Ser/Thr protein kinase family. GPRK subfamily.

RefSeq proteins (1): NP_002920* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000239	GPCR_kinase	Family
IPR000719	Prot_kinase_dom	Domain
IPR000961	AGC-kinase_C	Domain
IPR008271	Ser/Thr_kinase_AS	Active_site
IPR011009	Kinase-like_dom_sf	Homologous_superfamily
IPR016137	RGS	Domain
IPR017441	Protein_kinase_ATP_BS	Binding_site
IPR036305	RGS_sf	Homologous_superfamily
IPR037716	GRK1_dom	Domain
IPR044926	RGS_subdomain_2	Homologous_superfamily

Pfam: PF00069, PF00615

Enzyme classification (BRENDA):

• EC 2.7.11.14 — rhodopsin kinase (BRENDA: 15 organisms, 212 substrates, 103 inhibitors, 43 Km, 3 kcat entries)

Substrate kinetics (BRENDA)

6 substrates with measured Km, best-characterized 6. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
RHODOPSIN	0.0006–30	15
ATP	0.003–0.166	11
GTP	0.4–1	2
ATPGAMMAS	0.027	1
DDEASTTVSKTETSQVARRR	7.1	1
RRREEEEESAAA	2	1

Catalyzed reactions (Rhea), 2 shown:

• L-seryl-[rhodopsin] + ATP = O-phospho-L-seryl-[rhodopsin] + ADP + H(+) (RHEA:23356)
• L-threonyl-[rhodopsin] + ATP = O-phospho-L-threonyl-[rhodopsin] + ADP + H(+) (RHEA:56552)

UniProt features (32 total): sequence variant 9, modified residue 6, region of interest 4, domain 3, binding site 2, mutagenesis site 2, chain 1, propeptide 1, active site 1, lipid moiety-binding region 1, helix 1, compositionally biased region 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
5AFP	X-RAY DIFFRACTION	2.3

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q15835-F1	92.04	0.81

Functional residue map

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

Catalytic / active sites (1): 317 (proton acceptor)

Ligand- & substrate-binding residues (2): 196–204; 219

Post-translational modifications (7): 5, 8, 21, 491, 492, 560, 560

Mutagenesis-validated functional residues (2):

Position	Phenotype
21	not phosphorylated by pka.
219	loss of autophosphorylation and rho phosphorylation.

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-2514859	Inactivation, recovery and regulation of the phototransduction cascade

MSigDB gene sets: 118 (showing top): GOBP_CELLULAR_RESPONSE_TO_LIGHT_STIMULUS, GOBP_PHOTOTRANSDUCTION, PID_CONE_PATHWAY, MODULE_75, MODULE_289, SETLUR_PROSTATE_CANCER_TMPRSS2_ERG_FUSION_DN, MODULE_379, GOBP_PHOTOTRANSDUCTION_VISIBLE_LIGHT, GOBP_SENSORY_PERCEPTION_OF_LIGHT_STIMULUS, chr13q34, GOBP_RESPONSE_TO_RADIATION, MODULE_259, GOBP_DETECTION_OF_LIGHT_STIMULUS, GOBP_RESPONSE_TO_ABIOTIC_STIMULUS, MODULE_88

GO Biological Process (9): visual perception (GO:0007601), regulation of G protein-coupled receptor signaling pathway (GO:0008277), regulation of signal transduction (GO:0009966), G protein-coupled opsin signaling pathway (GO:0016056), regulation of opsin-mediated signaling pathway (GO:0022400), protein autophosphorylation (GO:0046777), protein phosphorylation (GO:0006468), signal transduction (GO:0007165), response to light stimulus (GO:0009416)

GO Molecular Function (8): protein kinase activity (GO:0004672), ATP binding (GO:0005524), rhodopsin kinase activity (GO:0050254), nucleotide binding (GO:0000166), protein serine/threonine kinase activity (GO:0004674), G protein-coupled receptor kinase activity (GO:0004703), kinase activity (GO:0016301), transferase activity (GO:0016740)

GO Cellular Component (5): cytoplasm (GO:0005737), photoreceptor disc membrane (GO:0097381), photoreceptor outer segment (GO:0001750), membrane (GO:0016020), cell projection (GO:0042995)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
The phototransduction cascade	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
G protein-coupled receptor signaling pathway	2
sensory perception of light stimulus	1
regulation of signal transduction	1
signal transduction	1
regulation of cell communication	1
regulation of signaling	1
regulation of response to stimulus	1
phototransduction	1
phototransduction, visible light	1
cellular response to light stimulus	1
regulation of G protein-coupled receptor signaling pathway	1
G protein-coupled opsin signaling pathway	1
regulation of response to external stimulus	1
protein phosphorylation	1
phosphorylation	1
protein modification process	1
cell communication	1
cellular process	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
response to radiation	1
kinase activity	1
phosphotransferase activity, alcohol group as acceptor	1
catalytic activity, acting on a protein	1
adenyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
G protein-coupled receptor kinase activity	1
nucleoside phosphate binding	1
heterocyclic compound binding	1
protein kinase activity	1
protein serine/threonine kinase activity	1
transferase activity, transferring phosphorus-containing groups	1
catalytic activity	1
intracellular anatomical structure	1
photoreceptor outer segment	1
organelle membrane	1
photoreceptor cell cilium	1

Protein interactions and networks

STRING

968 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
GRK1	RHO	P08100	993
GRK1	SAG	P10523	975
GRK1	RCVRN	P35243	938
GRK1	ARRB1	P49407	768
GRK1	MPP4	Q96JB8	741
GRK1	ARRB2	P32121	715
GRK1	CALML6	Q8TD86	705
GRK1	CALML3	P27482	705
GRK1	CALML4	Q96GE6	705
GRK1	CALML5	Q9NZT1	705
GRK1	PDE6D	O43924	674
GRK1	GUCA1A	P43080	670
GRK1	NCS1	P36610	662
GRK1	ITPR2	Q14571	649
GRK1	ARR3	P36575	645

IntAct

2 interactions, top by confidence:

A	B	Type	Score
H2AZ2	GRK1	psi-mi:“MI:0915”(physical association)	0.400

BioGRID (11): H2AFV (Affinity Capture-MS), GRK1 (Reconstituted Complex), GRK1 (Reconstituted Complex), RHO (Biochemical Activity), RCVRN (Reconstituted Complex), SNCA (Biochemical Activity), SNCB (Biochemical Activity), SNCG (Biochemical Activity), GRK1 (Affinity Capture-MS), GRK6 (Negative Genetic), GRK1 (Dosage Lethality)

ESM2 similar proteins: A2VDV2, B6CZ17, B6CZ18, O75582, P05130, P09215, P09216, P10830, P13678, P16054, P20444, P28867, P90980, Q02111, Q02156, Q04759, Q05655, Q09537, Q15208, Q15835, Q16975, Q1XHL7, Q25378, Q2LZZ7, Q49HM9, Q5F3L1, Q5PU49, Q5R4K3, Q5R7A7, Q5R8M1, Q622Z7, Q63651, Q6PA14, Q6PFQ0, Q7TSE6, Q8BGW6, Q8R4V0, Q8WMV0, Q8WP15, Q8WTQ7

Diamond homologs: A0A194W8T8, A0A8I5ZNK2, A7A1P0, A9SY39, B0XXN8, B5DFG1, B5VNQ3, C4YRB7, D4A280, D6WMX4, E0W1I1, F4JBP3, G4N7X0, G4NDR3, O14328, O22042, O35099, O88506, O95382, O95747, O96013, P0CY23, P0CY24, P22216, P23561, P28829, P54265, P83510, Q03497, Q04759, Q09013, Q09298, Q09792, Q0KHV6, Q10407, Q15835, Q21029, Q40541, Q4P5N0, Q4WHP3

SIGNOR signaling

12 interactions.

A	Effect	B	Mechanism
PKA	“down-regulates activity”	GRK1	phosphorylation
GRK1	“down-regulates activity”	F2RL2	phosphorylation
GRK1	“down-regulates activity”	TIAM1	phosphorylation
GRK1	“down-regulates activity”	TIAM2	phosphorylation
GRK1	“down-regulates activity”	GRK1	phosphorylation
GRK1	“up-regulates activity”	RHO	phosphorylation

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	4
Likely pathogenic	16
Uncertain significance	61
Likely benign	15
Benign	6

Top pathogenic / likely-pathogenic (20)

Variant ID	HGVS	Classification
13009	NM_002929.3(GRK1):c.1069+3317_1195-753del	Pathogenic
155263	GRCh38/hg38 13q33.2-34(chr13:104968135-114340331)x1	Pathogenic
870427	NM_002929.3(GRK1):c.142_145del (p.Glu48fs)	Pathogenic
870437	NM_002929.3(GRK1):c.1177C>T (p.Arg393Ter)	Pathogenic
1710125	NM_002929.3(GRK1):c.508_516del (p.Tyr170_Leu172del)	Likely pathogenic
3370438	NM_002929.3(GRK1):c.712_714del (p.Glu238del)	Likely pathogenic
636033	NM_002929.3(GRK1):c.1384C>T (p.Gln462Ter)	Likely pathogenic
870428	NM_002929.3(GRK1):c.470T>C (p.Leu157Pro)	Likely pathogenic
870429	NM_002929.3(GRK1):c.595G>C (p.Gly199Arg)	Likely pathogenic
870430	NM_002929.3(GRK1):c.614C>A (p.Ser205Ter)	Likely pathogenic
870431	NM_002929.3(GRK1):c.827+625_883del	Likely pathogenic
870432	NM_002929.3(GRK1):c.923T>C (p.Leu308Pro)	Likely pathogenic
870433	NM_002929.3(GRK1):c.971del (p.Leu324fs)	Likely pathogenic
870434	NM_002929.3(GRK1):c.1084G>A (p.Glu362Lys)	Likely pathogenic
870435	NM_002929.3(GRK1):c.1129G>C (p.Ala377Pro)	Likely pathogenic
870436	NM_002929.3(GRK1):c.1138G>T (p.Val380Phe)	Likely pathogenic
870438	NM_002929.3(GRK1):c.1411_1412del (p.Pro471fs)	Likely pathogenic
870439	NM_002929.3(GRK1):c.1549_1559del (p.Pro517fs)	Likely pathogenic
870441	NM_002929.3(GRK1):c.55C>T (p.Arg19Ter)	Likely pathogenic
870442	NM_002929.3(GRK1):c.1312C>T (p.Arg438Cys)	Likely pathogenic

SpliceAI

1139 predictions. Top by Δscore:

Variant	Effect	Δscore
13:113669816:T:A	donor_loss	1.0000
13:113723154:CCAGG:C	donor_loss	1.0000
13:113723155:CAGG:C	donor_loss	1.0000
13:113723156:AGGTA:A	donor_loss	1.0000
13:113723158:G:GC	donor_loss	1.0000
13:113723158:G:GG	donor_gain	1.0000
13:113732878:CCACA:C	acceptor_loss	1.0000
13:113732879:CACA:C	acceptor_loss	1.0000
13:113732881:CA:C	acceptor_loss	1.0000
13:113732882:AGGT:A	acceptor_gain	1.0000
13:113732883:GGT:G	acceptor_gain	1.0000
13:113732883:GGTG:G	acceptor_gain	1.0000
13:113733017:A:G	donor_gain	1.0000
13:113733034:C:G	donor_gain	1.0000
13:113733058:G:GT	donor_gain	1.0000
13:113668073:G:GT	donor_gain	0.9900
13:113668086:G:GG	donor_gain	0.9900
13:113668087:T:A	donor_loss	0.9900
13:113669682:TTCA:T	acceptor_loss	0.9900
13:113669683:TCAGG:T	acceptor_loss	0.9900
13:113669684:CA:C	acceptor_loss	0.9900
13:113669685:A:AG	acceptor_gain	0.9900
13:113669685:AG:A	acceptor_gain	0.9900
13:113669685:AGGG:A	acceptor_loss	0.9900
13:113669685:AGGGT:A	acceptor_gain	0.9900
13:113669686:G:GG	acceptor_gain	0.9900
13:113669686:G:GT	acceptor_loss	0.9900
13:113669686:GG:G	acceptor_gain	0.9900
13:113669686:GGGT:G	acceptor_gain	0.9900
13:113669686:GGGTG:G	acceptor_gain	0.9900

AlphaMissense

3729 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
13:113668043:G:C	K219N	1.000
13:113668043:G:T	K219N	1.000
13:113671621:A:C	D317A	1.000
13:113723092:A:C	D335A	1.000
13:113723092:A:G	D335G	1.000
13:113723092:A:T	D335V	1.000
13:113723093:C:A	D335E	1.000
13:113723093:C:G	D335E	1.000
13:113667975:G:T	G197W	0.999
13:113667976:G:A	G197E	0.999
13:113667987:T:C	F201L	0.999
13:113667989:C:A	F201L	0.999
13:113667989:C:G	F201L	0.999
13:113668041:A:G	K219E	0.999
13:113669802:G:A	G272E	0.999
13:113671618:G:C	R316P	0.999
13:113671621:A:G	D317G	0.999
13:113671621:A:T	D317V	0.999
13:113671622:C:A	D317E	0.999
13:113671622:C:G	D317E	0.999
13:113671637:C:A	N322K	0.999
13:113671637:C:G	N322K	0.999
13:113671642:T:C	L324P	0.999
13:113723091:G:C	D335H	0.999
13:113731221:T:C	F358L	0.999
13:113731223:C:A	F358L	0.999
13:113731223:C:G	F358L	0.999
13:113667975:G:A	G197R	0.998
13:113667975:G:C	G197R	0.998
13:113667990:G:T	G202W	0.998

dbSNP variants (sampled 300 via entrez): RS1000017906 (13:113651392 C>A), RS1000048103 (13:113733534 T>A,C), RS1000052613 (13:113646576 G>A), RS1000101489 (13:113646815 A>G), RS1000160201 (13:113650066 G>C), RS1000323290 (13:113668078 G>A,T), RS1000400109 (13:113657380 C>T), RS1000432963 (13:113669271 C>A,T), RS1000439952 (13:113649203 G>A), RS1000607723 (13:113734072 G>A,C), RS1000660976 (13:113650295 G>A,T), RS1000721186 (13:113658290 G>A), RS1000805269 (13:113668974 C>T), RS1000890669 (13:113672213 G>T), RS1000961949 (13:113672313 G>A)

Disease associations

OMIM: gene MIM:180381 | disease phenotypes: MIM:613411, MIM:310500

GenCC curated gene-disease

Disease	Classification	Inheritance
Oguchi disease-2	Definitive	Autosomal recessive
Oguchi disease	Supportive	Autosomal recessive

ClinGen Gene-Disease Validity (1)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
Oguchi disease	Definitive	AR

Mondo (5): Oguchi disease-2 (MONDO:0013259), inherited retinal dystrophy (MONDO:0019118), congenital stationary night blindness (MONDO:0016293), Oguchi disease (MONDO:0019152), retinal disorder (MONDO:0005283)

Orphanet (3): Oguchi disease (Orphanet:75382), OBSOLETE: Inherited retinal disorder (Orphanet:71862), Congenital stationary night blindness (Orphanet:215)

HPO phenotypes

14 total (15 of 14 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000486	Strabismus
HP:0000505	Visual impairment
HP:0000510	Rod-cone dystrophy
HP:0000539	Abnormality of refraction
HP:0000545	Myopia
HP:0000608	Macular degeneration
HP:0000639	Nystagmus
HP:0000651	Diplopia
HP:0001123	Visual field defect
HP:0007641	Dyschromatopsia
HP:0007642	Early-onset non-progressive night blindness
HP:0007984	ERG: Reduced dark-adapted b-wave amplitude
HP:0030824	Mizuo phenomenon
HP:0000556	Retinal dystrophy

GWAS associations

0 associations (top):

MeSH disease descriptors (4)

Descriptor	Name	Tree numbers
D012164	Retinal Diseases	C11.768
D058499	Retinal Dystrophies	C11.768.585.658
C536122	Night blindness, congenital stationary (supp.)
C537743	Oguchi disease (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL5607 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

12 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 145,568 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL1789941	RUXOLITINIB	4	11,547
CHEMBL502835	NINTEDANIB	4	8,545
CHEMBL535	SUNITINIB	4	79,020
CHEMBL608533	MIDOSTAURIN	4	7,259
CHEMBL300138	ENZASTAURIN	3	3,209
CHEMBL428690	ALVOCIDIB	3	27,781
CHEMBL522892	DOVITINIB	3	4,944
CHEMBL603469	LESTAURTINIB	3
CHEMBL91829	RUBOXISTAURIN	3	77
CHEMBL1721885	SU-014813	2	363
CHEMBL475251	R-406	2	762
CHEMBL494089	GSK-690693	1	2,061

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

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: enzyme — Opsin/rhodopsin kinases

Most potent curated ligand interactions (1 total), top 1:

Ligand	Action	Affinity	Parameter
balanol	Inhibition	6.47	pIC50

Binding affinities (BindingDB)

38 measured of 39 human assays (39 total across all organisms); most potent 38 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
4-[4-fluoro-3-[(2-methoxyphenyl)methylcarbamoyl]phenyl]-N-(1H-indazol-5-yl)-6-methyl-2-oxo-3,4-dihydro-1H-pyrimidine-5-carboxamide	IC50	60 nM	US-10023564: G protein-coupled receptor kinase 2 inhibitors and methods for use of the same
4-[3-[(2,6-dimethylphenyl)methylcarbamoyl]-4-fluorophenyl]-N-(1H-indazol-5-yl)-6-methyl-2-oxo-3,4-dihydro-1H-pyrimidine-5-carboxamide	IC50	70 nM	US-10023564: G protein-coupled receptor kinase 2 inhibitors and methods for use of the same
4-[3-[(2,6-difluorophenyl)methylcarbamoyl]-4-fluorophenyl]-N-(1H-indazol-5-yl)-6-methyl-2-oxo-3,4-dihydro-1H-pyrimidine-5-carboxamide	IC50	120 nM	US-10023564: G protein-coupled receptor kinase 2 inhibitors and methods for use of the same
4-[3-[(2,6-dichlorophenyl)methylcarbamoyl]-4-fluorophenyl]-N-(1H-indazol-5-yl)-6-methyl-2-oxo-3,4-dihydro-1H-pyrimidine-5-carboxamide	IC50	130 nM	US-10023564: G protein-coupled receptor kinase 2 inhibitors and methods for use of the same
4-[3-[(2,6-dimethoxyphenyl)methylcarbamoyl]-4-fluorophenyl]-N-(1H-indazol-5-yl)-6-methyl-2-oxo-3,4-dihydro-1H-pyrimidine-5-carboxamide	IC50	130 nM	US-10023564: G protein-coupled receptor kinase 2 inhibitors and methods for use of the same
4-[4-fluoro-3-(pyridin-2-ylmethylcarbamoyl)phenyl]-N-(1H-indazol-5-yl)-6-methyl-2-oxo-3,4-dihydro-1H-pyrimidine-5-carboxamide	IC50	150 nM	US-10023564: G protein-coupled receptor kinase 2 inhibitors and methods for use of the same
E22	IC50	180 nM	US-10023564: G protein-coupled receptor kinase 2 inhibitors and methods for use of the same
4-[4-fluoro-3-[(3-fluorophenyl)methylcarbamoyl]phenyl]-N-(1H-indazol-5-yl)-6-methyl-2-oxo-3,4-dihydro-1H-pyrimidine-5-carboxamide	IC50	200 nM	US-10023564: G protein-coupled receptor kinase 2 inhibitors and methods for use of the same
4-[3-[2-(2,6-dimethylphenyl)ethylcarbamoyl]-4-fluorophenyl]-N-(1H-indazol-5-yl)-6-methyl-2-oxo-3,4-dihydro-1H-pyrimidine-5-carboxamide	IC50	230 nM	US-10023564: G protein-coupled receptor kinase 2 inhibitors and methods for use of the same
E24	IC50	240 nM	US-10023564: G protein-coupled receptor kinase 2 inhibitors and methods for use of the same
4-[4-fluoro-3-(2-pyridin-2-ylethylcarbamoyl)phenyl]-N-(1H-indazol-5-yl)-6-methyl-2-oxo-3,4-dihydro-1H-pyrimidine-5-carboxamide	IC50	280 nM	US-10023564: G protein-coupled receptor kinase 2 inhibitors and methods for use of the same
E27	IC50	320 nM	US-10023564: G protein-coupled receptor kinase 2 inhibitors and methods for use of the same
4-[4-fluoro-3-[(3-methoxyphenyl)methylcarbamoyl]phenyl]-N-(1H-indazol-5-yl)-6-methyl-2-oxo-3,4-dihydro-1H-pyrimidine-5-carboxamide	IC50	420 nM	US-10023564: G protein-coupled receptor kinase 2 inhibitors and methods for use of the same
4-[3-[2-[(2,6-dimethoxyphenyl)methylamino]-2-oxoethyl]-4-fluorophenyl]-N-(1H-indazol-5-yl)-6-methyl-2-oxo-3,4-dihydro-1H-pyrimidine-5-carboxamide	IC50	450 nM	US-10023564: G protein-coupled receptor kinase 2 inhibitors and methods for use of the same
4-[4-fluoro-3-[(4-methoxyphenyl)methylcarbamoyl]phenyl]-N-(1H-indazol-5-yl)-6-methyl-2-oxo-3,4-dihydro-1H-pyrimidine-5-carboxamide	IC50	460 nM	US-10023564: G protein-coupled receptor kinase 2 inhibitors and methods for use of the same
E32	IC50	500 nM	US-10023564: G protein-coupled receptor kinase 2 inhibitors and methods for use of the same
E33	IC50	680 nM	US-10023564: G protein-coupled receptor kinase 2 inhibitors and methods for use of the same
4-[3-(benzylcarbamoyl)-4-fluorophenyl]-N-(1H-indazol-5-yl)-6-methyl-2-oxo-3,4-dihydro-1H-pyrimidine-5-carboxamide	IC50	690 nM	US-10023564: G protein-coupled receptor kinase 2 inhibitors and methods for use of the same
E20	IC50	740 nM	US-10023564: G protein-coupled receptor kinase 2 inhibitors and methods for use of the same
GSK-180736A	IC50	770 nM	US-10023564: G protein-coupled receptor kinase 2 inhibitors and methods for use of the same
E23	IC50	820 nM	US-10023564: G protein-coupled receptor kinase 2 inhibitors and methods for use of the same
E35	IC50	960 nM	US-10023564: G protein-coupled receptor kinase 2 inhibitors and methods for use of the same
E26	IC50	1200 nM	US-10023564: G protein-coupled receptor kinase 2 inhibitors and methods for use of the same
E34	IC50	1200 nM	US-10023564: G protein-coupled receptor kinase 2 inhibitors and methods for use of the same
4-[3-[[2,6-bis(trifluoromethyl)phenyl]methylcarbamoyl]-4-fluorophenyl]-N-(1H-indazol-5-yl)-6-methyl-2-oxo-3,4-dihydro-1H-pyrimidine-5-carboxamide	IC50	1200 nM	US-10023564: G protein-coupled receptor kinase 2 inhibitors and methods for use of the same
E31	IC50	1500 nM	US-10023564: G protein-coupled receptor kinase 2 inhibitors and methods for use of the same
4-[4-fluoro-3-[(3-methyl-2-pyridinyl)methylcarbamoyl]phenyl]-N-(1H-indazol-5-yl)-6-methyl-2-oxo-3,4-dihydro-1H-pyrimidine-5-carboxamide	IC50	1900 nM	US-10023564: G protein-coupled receptor kinase 2 inhibitors and methods for use of the same
E36	IC50	2600 nM	US-10023564: G protein-coupled receptor kinase 2 inhibitors and methods for use of the same
4-[4-fluoro-3-(isoquinolin-1-ylmethylcarbamoyl)phenyl]-N-(1H-indazol-5-yl)-6-methyl-2-oxo-3,4-dihydro-1H-pyrimidine-5-carboxamide	IC50	2600 nM	US-10023564: G protein-coupled receptor kinase 2 inhibitors and methods for use of the same
4-[3-[[3,5-bis(trifluoromethyl)phenyl]methylcarbamoyl]-4-fluorophenyl]-N-(1H-indazol-5-yl)-6-methyl-2-oxo-3,4-dihydro-1H-pyrimidine-5-carboxamide	IC50	2700 nM	US-10023564: G protein-coupled receptor kinase 2 inhibitors and methods for use of the same
E37	IC50	4000 nM	US-10023564: G protein-coupled receptor kinase 2 inhibitors and methods for use of the same
4-[4-fluoro-3-(methylcarbamoyl)phenyl]-N-(1H-indazol-5-yl)-6-methyl-2-oxo-3,4-dihydro-1H-pyrimidine-5-carboxamide	IC50	4300 nM	US-10023564: G protein-coupled receptor kinase 2 inhibitors and methods for use of the same
4-[4-fluoro-3-(2-pyridin-4-ylethylcarbamoyl)phenyl]-N-(1H-indazol-5-yl)-6-methyl-2-oxo-3,4-dihydro-1H-pyrimidine-5-carboxamide	IC50	5150 nM	US-10023564: G protein-coupled receptor kinase 2 inhibitors and methods for use of the same
E25	IC50	5200 nM	US-10023564: G protein-coupled receptor kinase 2 inhibitors and methods for use of the same
E38	IC50	7000 nM	US-10023564: G protein-coupled receptor kinase 2 inhibitors and methods for use of the same
E21	IC50	14600 nM	US-10023564: G protein-coupled receptor kinase 2 inhibitors and methods for use of the same
4-[3-[2-[(2,6-dimethylphenyl)methylamino]-2-oxoethyl]-4-fluorophenyl]-N-(1H-indazol-5-yl)-6-methyl-2-oxo-3,4-dihydro-1H-pyrimidine-5-carboxamide	IC50	25000 nM	US-10023564: G protein-coupled receptor kinase 2 inhibitors and methods for use of the same
E19	IC50	51000 nM	US-10023564: G protein-coupled receptor kinase 2 inhibitors and methods for use of the same

ChEMBL bioactivities

45 potent at pChembl≥5 of 65 total, top 40 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
9.01	Kd	0.97	nM	STAUROSPORINE
7.62	Kd	24	nM	LESTAURTINIB
7.28	IC50	52	nM	CHEMBL4877302
7.24	IC50	57.8	nM	STAUROSPORINE
7.16	IC50	70	nM	CHEMBL3809796
7.11	IC50	78.1	nM	STAUROSPORINE
7.07	Kd	85	nM	MIDOSTAURIN
7.00	IC50	100	nM	CHEMBL3809796
7.00	IC50	99.5	nM	STAUROSPORINE
6.96	Kd	109	nM	CHEMBL4576489
6.91	Kd	122	nM	CHEMBL4465866
6.75	Ki	180	nM	SANGIVAMYCIN
6.72	IC50	190	nM	CHEMBL4854871
6.57	IC50	270	nM	CHEMBL4072828
6.54	Kd	290	nM	SUNITINIB
6.47	IC50	340	nM	BALANOL
6.39	Kd	410	nM	TAE-684
6.35	IC50	450	nM	CHEMBL4847703
6.21	Kd	610	nM	GSK-690693
6.19	Kd	650	nM	ALVOCIDIB
6.14	Kd	730	nM	RUXOLITINIB
6.10	Kd	800	nM	RUBOXISTAURIN
6.08	Kd	830	nM	CHEMBL464552
6.06	Kd	870	nM	R-406
6.03	Kd	930	nM	CHEMBL1241674
6.00	IC50	1000	nM	TP-030-1
6.00	IC50	1000	nM	TP-030-2
6.00	IC50	1000	nM	TP-030n
6.00	Kd	1000	nM	NINTEDANIB
5.96	Kd	1100	nM	SU-014813
5.96	Kd	1100	nM	PHA-665752
5.85	Kd	1400	nM	CGP-52421
5.77	Kd	1700	nM	CHEMBL1908395
5.77	Kd	1700	nM	ENZASTAURIN
5.66	Kd	2200	nM	DOVITINIB
5.52	IC50	3000	nM	CHEMBL4228779
5.51	IC50	3100	nM	CHEMBL1738877
5.46	IC50	3500	nM	CHEMBL4228779
5.41	IC50	3900	nM	CHEMBL3808660
5.05	IC50	9000	nM	CHEMBL1738878

PubChem BioAssay actives

39 with measured affinity, of 269 total; 32 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
(2S,3R,4R,6R)-3-methoxy-2-methyl-4-(methylamino)-29-oxa-1,7,17-triazaoctacyclo[12.12.2.12,6.07,28.08,13.015,19.020,27.021,26]nonacosa-8,10,12,14,19,21,23,25,27-nonaen-16-one	624898: Binding constant for GRK1 kinase domain	kd	0.0010	uM
(15S,16S,18R)-16-hydroxy-16-(hydroxymethyl)-15-methyl-28-oxa-4,14,19-triazaoctacyclo[12.11.2.115,18.02,6.07,27.08,13.019,26.020,25]octacosa-1,6,8,10,12,20,22,24,26-nonaen-3-one	507963: Binding affinity to GRK1	kd	0.0240	uM
2-N-[(4-chloro-2-methoxyphenyl)methyl]-4-N-(5-ethyl-1H-pyrazol-3-yl)-5-methoxyquinazoline-2,4-diamine	1751895: Inhibition of human GRK1 using casein as substrate in presence of [gamma33P]ATP by radiometric hotspot kinase assay	ic50	0.0520	uM
Midostaurin	507963: Binding affinity to GRK1	kd	0.0850	uM
4-[4-fluoro-3-(isoquinolin-1-ylmethylcarbamoyl)phenyl]-N-(1H-indazol-5-yl)-6-methyl-2-oxo-3,4-dihydro-1H-pyrimidine-5-carboxamide	1302238: Inhibition of GRK1 (unknown origin) using tubulin as substrate by SDS-PAGE method	ic50	0.1000	uM
3-(2,2-difluoro-10,12-dimethyl-1-aza-3-azonia-2-boranuidatricyclo[7.3.0.03,7]dodeca-3,5,7,9,11-pentaen-4-yl)-N-[2-[2-[2-[2-[[(2S,3R,4R,6R)-3-methoxy-2-methyl-16-oxo-29-oxa-1,7,17-triazaoctacyclo[12.12.2.12,6.07,28.08,13.015,19.020,27.021,26]nonacosa-8,10,12,14,19,21,23,25,27-nonaen-4-yl]-methylamino]ethoxy]ethoxy]ethoxy]ethyl]propanamide	1526256: Binding affinity to recombinant full-length N-terminal His-FLAG-GST-tagged GRK1 (unknown origin) expressed in baculovirus infected Sf9 insect cells incubated for 1 hr by TR-FRET assay	kd	0.1090	uM
3-(2,2-difluoro-10,12-dimethyl-1-aza-3-azonia-2-boranuidatricyclo[7.3.0.03,7]dodeca-3,5,7,9,11-pentaen-4-yl)-N-[2-[2-[2-[2-[[(2S,3R,4R,6R)-3-methoxy-2-methyl-16-oxo-29-oxa-1,7,17-triazaoctacyclo[12.12.2.12,6.07,28.08,13.015,19.020,27.021,26]nonacosa-8,10,12,14,19,21,23,25,27-nonaen-4-yl]amino]ethoxy]ethoxy]ethoxy]ethyl]propanamide	1526256: Binding affinity to recombinant full-length N-terminal His-FLAG-GST-tagged GRK1 (unknown origin) expressed in baculovirus infected Sf9 insect cells incubated for 1 hr by TR-FRET assay	kd	0.1220	uM
4-amino-7-[(2R,3R,4S,5R)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]pyrrolo[2,3-d]pyrimidine-5-carboxamide	357074: Inhibition of rhodopsin kinase	ki	0.1800	uM
4-N-(5-ethyl-1H-pyrazol-3-yl)-2-N-[(1S)-1-(5-fluoro-2-pyridinyl)ethyl]-5-methoxyquinazoline-2,4-diamine	1751895: Inhibition of human GRK1 using casein as substrate in presence of [gamma33P]ATP by radiometric hotspot kinase assay	ic50	0.1900	uM
3-(9-oxa-3,4,6,12-tetrazatricyclo[8.4.0.02,6]tetradeca-1(10),2,4,11,13-pentaen-5-ylmethylamino)-N-[[2-(trifluoromethyl)phenyl]methyl]benzamide	1457943: Inhibition of recombinant human GST-tagged GRK1 expressed in baculovirus infected fall armyworm Sf9 cells after 60 mins by LanthaScreen eu kinase binding assay	ic50	0.2700	uM
Sunitinib	507963: Binding affinity to GRK1	kd	0.2900	uM
2-[2,6-dihydroxy-4-[(3R,4R)-3-[(4-hydroxybenzoyl)amino]azepan-4-yl]oxycarbonylbenzoyl]-3-hydroxybenzoic acid	464307: Inhibition of GRK1-mediated bovine tubulin phosphorylation by scintillation counting	ic50	0.3400	uM
5-chloro-2-N-[2-methoxy-4-[4-(4-methylpiperazin-1-yl)piperidin-1-yl]phenyl]-4-N-(2-propan-2-ylsulfonylphenyl)pyrimidine-2,4-diamine	624898: Binding constant for GRK1 kinase domain	kd	0.4100	uM
4-N-(5-ethyl-1H-pyrazol-3-yl)-2-N-[(5-fluoro-2-pyridinyl)methyl]-5-methoxyquinazoline-2,4-diamine	1751895: Inhibition of human GRK1 using casein as substrate in presence of [gamma33P]ATP by radiometric hotspot kinase assay	ic50	0.4500	uM
4-[2-(4-amino-1,2,5-oxadiazol-3-yl)-1-ethyl-7-[[(3S)-piperidin-3-yl]methoxy]imidazo[4,5-c]pyridin-4-yl]-2-methylbut-3-yn-2-ol	624898: Binding constant for GRK1 kinase domain	kd	0.6100	uM
2-(2-chlorophenyl)-5,7-dihydroxy-8-[(3S,4R)-3-hydroxy-1-methylpiperidin-4-yl]chromen-4-one	624898: Binding constant for GRK1 kinase domain	kd	0.6500	uM
Ruxolitinib	624898: Binding constant for GRK1 kinase domain	kd	0.7300	uM
(18S)-18-[(dimethylamino)methyl]-17-oxa-4,14,21-triazahexacyclo[19.6.1.17,14.02,6.08,13.022,27]nonacosa-1(28),2(6),7(29),8,10,12,22,24,26-nonaene-3,5-dione	624898: Binding constant for GRK1 kinase domain	kd	0.8000	uM
2-[[2-[[1-[2-(dimethylamino)acetyl]-5-methoxy-2,3-dihydroindol-6-yl]amino]-7H-pyrrolo[2,3-d]pyrimidin-4-yl]amino]-6-fluoro-N-methylbenzamide	624898: Binding constant for GRK1 kinase domain	kd	0.8300	uM
6-[[5-fluoro-2-(3,4,5-trimethoxyanilino)pyrimidin-4-yl]amino]-2,2-dimethyl-4H-pyrido[3,2-b][1,4]oxazin-3-one	624898: Binding constant for GRK1 kinase domain	kd	0.8700	uM
2-(4-amino-1-propan-2-ylpyrazolo[3,4-d]pyrimidin-3-yl)-1H-indol-5-ol	624898: Binding constant for GRK1 kinase domain	kd	0.9300	uM
methyl 2-hydroxy-3-[N-[4-[methyl-[2-(4-methylpiperazin-1-yl)acetyl]amino]phenyl]-C-phenylcarbonimidoyl]-1H-indole-6-carboxylate	624898: Binding constant for GRK1 kinase domain	kd	1.0000	uM
5-[(Z)-(5-fluoro-2-oxo-1H-indol-3-ylidene)methyl]-N-[(2S)-2-hydroxy-3-morpholin-4-ylpropyl]-2,4-dimethyl-1H-pyrrole-3-carboxamide	624898: Binding constant for GRK1 kinase domain	kd	1.1000	uM
(3Z)-5-[(2,6-dichlorophenyl)methylsulfonyl]-3-[[3,5-dimethyl-4-[(2R)-2-(pyrrolidin-1-ylmethyl)pyrrolidine-1-carbonyl]-1H-pyrrol-2-yl]methylidene]-1H-indol-2-one	624898: Binding constant for GRK1 kinase domain	kd	1.1000	uM
N-[(2S,3R,4R,6R,18S)-18-hydroxy-3-methoxy-2-methyl-16-oxo-29-oxa-1,7,17-triazaoctacyclo[12.12.2.12,6.07,28.08,13.015,19.020,27.021,26]nonacosa-8,10,12,14,19,21,23,25,27-nonaen-4-yl]-N-methylbenzamide	507963: Binding affinity to GRK1	kd	1.4000	uM
3-(1-methylindol-3-yl)-4-[1-[1-(pyridin-2-ylmethyl)piperidin-4-yl]indol-3-yl]pyrrole-2,5-dione	624898: Binding constant for GRK1 kinase domain	kd	1.7000	uM
5-cyano-N-[2-(cyclohexen-1-yl)-4-[1-[2-(dimethylamino)acetyl]piperidin-4-yl]phenyl]-1H-imidazole-2-carboxamide;hydrochloride	624898: Binding constant for GRK1 kinase domain	kd	1.7000	uM
4-amino-5-fluoro-3-[6-(4-methylpiperazin-1-yl)-1H-benzimidazol-2-yl]-1H-quinolin-2-one	624898: Binding constant for GRK1 kinase domain	kd	2.2000	uM
4-[3-[(5-ethyl-1,2,4-oxadiazol-3-yl)methylcarbamoyl]-4-fluorophenyl]-N-(1H-indazol-5-yl)-6-methyl-2-oxo-3,4-dihydro-1H-pyrimidine-5-carboxamide	1391755: Inhibition of GRK1 (unknown origin) preincubated for 10 mins followed by peptide substrate and ATP addition measured after 1 hr by TR-FRET assay	ic50	3.0000	uM
3-[(4-methyl-5-pyridin-4-yl-1,2,4-triazol-3-yl)methylamino]-N-[[2-(trifluoromethyl)phenyl]methyl]benzamide	1457943: Inhibition of recombinant human GST-tagged GRK1 expressed in baculovirus infected fall armyworm Sf9 cells after 60 mins by LanthaScreen eu kinase binding assay	ic50	3.1000	uM
4-[4-fluoro-3-(pyridin-2-ylmethylcarbamoyl)phenyl]-N-(1H-indazol-5-yl)-6-methyl-2-oxo-3,4-dihydro-1H-pyrimidine-5-carboxamide	1302238: Inhibition of GRK1 (unknown origin) using tubulin as substrate by SDS-PAGE method	ic50	3.9000	uM
N-[(2,6-difluorophenyl)methyl]-3-[(4-propyl-5-pyrimidin-4-yl-1,2,4-triazol-3-yl)methylamino]benzamide	1302238: Inhibition of GRK1 (unknown origin) using tubulin as substrate by SDS-PAGE method	ic50	9.0000	uM

CTD chemical–gene interactions

16 total (human), top 16 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
bisphenol A	affects cotreatment, increases methylation	1
sodium arsenite	increases expression	1
benzo(e)pyrene	decreases methylation	1
aflatoxin B2	decreases methylation	1
CGP 52608	increases reaction, affects binding	1
Resveratrol	decreases expression, affects cotreatment	1
Fulvestrant	affects cotreatment, increases methylation	1
Air Pollutants	increases abundance, increases expression	1
Atrazine	increases expression	1
Benzo(a)pyrene	decreases methylation, increases methylation	1
Malathion	increases expression	1
Methapyrilene	decreases methylation	1
Plant Extracts	affects cotreatment, decreases expression	1
Valproic Acid	increases methylation	1
Cyclosporine	decreases methylation	1
Particulate Matter	increases abundance, increases expression	1

ChEMBL screening assays

123 unique, capped per target: 123 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1106955	Binding	Inhibition of GRK1-mediated bovine tubulin phosphorylation by scintillation counting	Structure of human G protein-coupled receptor kinase 2 in complex with the kinase inhibitor balanol. — J Med Chem

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT01955135	PHASE4	COMPLETED	Anesthesia for Retinopathy of Prematurity
NCT04224207	PHASE3	COMPLETED	Management of Retinitis Pigmentosa by Mesenchymal Stem Cells by Wharton’s Jelly Derived Mesenchymal Stem Cells
NCT07082855	PHASE3	NOT_YET_RECRUITING	A Multicenter, Randomized, Double-Blind, Controlled Clinical Study of Minocycline for the Treatment of Retinitis Pigmentosa
NCT03763227	PHASE2	COMPLETED	Intravitreal Ranibizumab (Lucentis®) in the Treatment of Non-leaking Macular Cysts in Retinal Dystrophy
NCT04068207	PHASE2	COMPLETED	Minocycline Treatment in Retinitis Pigmentosa
NCT04945772	PHASE2	COMPLETED	Efficacy and Safety of MCO-010 Optogenetic Therapy in Adults With Retinitis Pigmentosa [RESTORE]
NCT01373476	PHASE2	COMPLETED	Multicentre, Randomized, Controlled Trial of Qideng Mingmu Capsule in The Treatment of Diabetic Retinopathy
NCT01793090	PHASE2	COMPLETED	EPI-743 in Cobalamin C Defect: Effects on Visual and Neurological Impairment
NCT05902962	PHASE1	COMPLETED	SAD of IVT VP-001 in PRPF31 Mutation-Associated Retinal Dystrophy Subjects
NCT06319872	PHASE1	RECRUITING	The Effects of Disulfiram (Antabuse®) on Visual Acuity in Patients With Retinal Degeneration
NCT06455826	PHASE1	COMPLETED	MAD of IVT VP-001 in PRPF31 Mutation-Associated Retinal Dystrophy Subjects (Wallaby)
NCT04855045	PHASE2/PHASE3	UNKNOWN	An Open-label, Dose Escalation and Double-masked, Randomized, Controlled Trial Evaluating Safety and Tolerability of Sepofarsen in Children (<8 Years of Age) With LCA10 Caused by Mutations in the CEP290 Gene.
NCT03872479	PHASE1/PHASE2	UNKNOWN	Single Ascending Dose Study in Participants With LCA10
NCT04123626	PHASE1/PHASE2	ACTIVE_NOT_RECRUITING	A Study to Evaluate the Safety and Tolerability of QR-1123 in Subjects With Autosomal Dominant Retinitis Pigmentosa Due to the P23H Mutation in the RHO Gene
NCT04545736	PHASE1/PHASE2	RECRUITING	Oral Metformin for Treatment of ABCA4 Retinopathy
NCT06212297	PHASE1/PHASE2	ACTIVE_NOT_RECRUITING	Fellow-eye Study (FE) of LX101 in Subjects With Inherited Retinal Dystrophy
NCT06852963	PHASE1/PHASE2	ACTIVE_NOT_RECRUITING	A Repeat-Dose, Open-Label, Two Arm Safety and Efficacy Study of Two Doses of VP-001 Administered Intravitreally in Participants With Confirmed PRPF31 Mutation-Associated Retinal Dystrophy, Including Participants Previously Treated With VP001
NCT07177196	PHASE1/PHASE2	ACTIVE_NOT_RECRUITING	Personalized Antisense Oligonucleotide Therapy for a Single Participant With PRPH2 Mutation Associated With Retinal Dystrophy
NCT07063030	EARLY_PHASE1	RECRUITING	A Study of LX107 Gene Therapy in AIPL1-IRD Patients
NCT01546181	Not specified	COMPLETED	Retinal Imaging by Adaptive Optics in Healthy Eyes and During Retinal and General Diseases
NCT01876147	Not specified	COMPLETED	Visual and Functional Assessment in Low Vision Patients
NCT01920867	Not specified	UNKNOWN	Stem Cell Ophthalmology Treatment Study
NCT02014389	Not specified	RECRUITING	Evaluation of Objective Perimetry Using Chromatic Multifocal Pupillometer
NCT02983305	Not specified	COMPLETED	Optical Head-Mounted Display Technology for Low Vision Rehabilitation
NCT03592017	Not specified	COMPLETED	Performance of Long-wavelength Autofluorescence Imaging
NCT03662386	Not specified	TERMINATED	Prospective Analysis of Genotype-phenotype Correlations Observed in a Large Cohort of Patients With Hereditary Retinal Dystrophies - GEPHIRD
NCT03691168	Not specified	UNKNOWN	Multi-center Observation of the Natural Course of Inherited Retinal Dystrophies
NCT03843840	Not specified	COMPLETED	Dual Wavelength OCT
NCT03853252	Not specified	COMPLETED	iPS Cells of Patients for Models of Retinal Dystrophies
NCT05130385	Not specified	UNKNOWN	High Resolution Optical Coherence Tomography
NCT05294978	Not specified	RECRUITING	EyeConic: Qualification for Cone-Optogenetics
NCT05573984	Not specified	ACTIVE_NOT_RECRUITING	Natural History of PRPF31 Mutation-Associated Retinal Dystrophy
NCT05793515	Not specified	COMPLETED	Mechanisms of Inherited Retinal Dystrophies Using Whole Genome Sequencing and in Vitro and in Vivo Models
NCT05820100	Not specified	COMPLETED	Observational Study to Assess the Reliability and Validity of the MLYMT and MLSDT
NCT05976139	Not specified	RECRUITING	Micropulsed Laser in Patients With Macular Oedema in Retinal Dystrophies
NCT06162585	Not specified	ACTIVE_NOT_RECRUITING	Non-Interventional Long Term Follow-up Study of Participants Previously Enrolled in the RESTORE Study
NCT06177977	Not specified	RECRUITING	SS-HH-OCT as a Novel Diagnostic Modality for Early-Onset Retinal Dystrophies (EORDs)
NCT06375239	Not specified	RECRUITING	Observational Study to Assess Endpoint Operational Feasibility & Measurement Properties in Patients with Retinal Degeneration
NCT06908161	Not specified	NOT_YET_RECRUITING	Functional Assessments in Vision Impairment
NCT07085533	Not specified	RECRUITING	Natural History Study of Inherited Retinal Diseases