GRK5

Summary

GRK5 (G protein-coupled receptor kinase 5, HGNC:4544) is a protein-coding gene on chromosome 10q26.11, encoding G protein-coupled receptor kinase 5 (P34947). Serine/threonine kinase that phosphorylates preferentially the activated forms of a variety of G-protein-coupled receptors (GPCRs).

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 the activated forms of G protein-coupled receptors thus initiating their deactivation. It has also been shown to play a role in regulating the motility of polymorphonuclear leukocytes (PMNs).

Source: NCBI Gene 2869 — RefSeq curated summary.

At a glance

• GWAS associations: 23
• Clinical variants (ClinVar): 104 total
• Druggable target: yes — 8 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_005308

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:4544
Approved symbol	GRK5
Name	G protein-coupled receptor kinase 5
Location	10q26.11
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000198873
Ensembl biotype	protein_coding
OMIM	600870
Entrez	2869

Gene structure

Transcript identifiers

Ensembl transcripts: 9 — 8 protein_coding, 1 retained_intron

ENST00000369108, ENST00000392870, ENST00000857194, ENST00000857195, ENST00000857196, ENST00000857197, ENST00000931752, ENST00000943822, ENST00000943823

RefSeq mRNA: 1 — MANE Select: NM_005308 NM_005308

CCDS: CCDS7612

Canonical transcript exons

ENST00000392870 — 16 exons

Exon	Start	End
ENSE00000614251	119424993	119425085
ENSE00000614256	119441999	119442088
ENSE00000614258	119448123	119448260
ENSE00000725966	119423166	119423266
ENSE00000725983	119431387	119431527
ENSE00000725987	119436651	119436841
ENSE00000725993	119439731	119439768
ENSE00000726009	119443544	119443752
ENSE00000726019	119452671	119452808
ENSE00000726024	119453145	119453276
ENSE00001448823	119454969	119459745
ENSE00001448825	119207571	119207969
ENSE00002526508	119430375	119430438
ENSE00002535258	119326516	119326611
ENSE00003471518	119380815	119380927
ENSE00003650498	119396695	119396772

Expression profiles

Bgee: expression breadth ubiquitous, 270 present calls, max score 97.73.

FANTOM5 (CAGE): breadth broad, TPM avg 2.6171 / max 60.6360, expressed in 912 samples.

FANTOM5 promoters (7 alternative TSS)

Promoter ID	TPM avg	Samples expressed
107309	0.6696	410
107308	0.6216	325
107307	0.4513	238
107310	0.3915	192
107311	0.2723	129
206010	0.1696	60
107312	0.0411	11

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
saphenous vein	UBERON:0007318	97.73	gold quality
pylorus	UBERON:0001166	97.66	gold quality
synovial joint	UBERON:0002217	97.35	gold quality
cardia of stomach	UBERON:0001162	96.63	gold quality
blood vessel layer	UBERON:0004797	96.23	gold quality
lower lobe of lung	UBERON:0008949	96.13	gold quality
pericardium	UBERON:0002407	95.00	gold quality
jejunal mucosa	UBERON:0000399	94.76	gold quality
layer of synovial tissue	UBERON:0007616	93.99	gold quality
urethra	UBERON:0000057	93.78	gold quality
right lung	UBERON:0002167	93.45	gold quality
visceral pleura	UBERON:0002401	92.59	gold quality
tendon of biceps brachii	UBERON:0008188	92.41	gold quality
jejunum	UBERON:0002115	92.00	gold quality
vena cava	UBERON:0004087	90.68	gold quality
heart right ventricle	UBERON:0002080	90.25	gold quality
right coronary artery	UBERON:0001625	90.20	gold quality
lung	UBERON:0002048	90.01	gold quality
decidua	UBERON:0002450	89.94	gold quality
superficial temporal artery	UBERON:0001614	89.89	gold quality
thoracic aorta	UBERON:0001515	89.59	gold quality
ascending aorta	UBERON:0001496	89.57	gold quality
pleura	UBERON:0000977	89.15	gold quality
aorta	UBERON:0000947	88.65	gold quality
apex of heart	UBERON:0002098	88.42	gold quality
upper lobe of lung	UBERON:0008948	87.94	gold quality
popliteal artery	UBERON:0002250	87.85	gold quality
tibial artery	UBERON:0007610	87.82	gold quality
myocardium	UBERON:0002349	87.72	gold quality
coronary artery	UBERON:0001621	87.68	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	8.71

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): NFKB, STAT5A, STAT5B

miRNA regulators (miRDB)

72 targeting GRK5, 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-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-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-548C-3P	99.99	74.01	7587
HSA-MIR-4482-3P	99.98	72.50	3147
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-4745-5P	99.98	65.95	1028
HSA-MIR-32-5P	99.98	75.21	1964
HSA-MIR-92A-3P	99.98	75.21	1960
HSA-MIR-92B-3P	99.98	75.25	1955
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-4789-5P	99.98	70.76	2721
HSA-MIR-23A-3P	99.95	74.24	3163
HSA-MIR-23B-3P	99.95	74.24	3163
HSA-MIR-23C	99.95	73.92	3192
HSA-MIR-539-5P	99.93	70.30	2855
HSA-MIR-627-3P	99.90	71.42	3316
HSA-MIR-153-5P	99.89	73.86	6317
HSA-MIR-4492	99.87	68.25	3611
HSA-MIR-4698	99.84	71.41	4303
HSA-MIR-1323	99.83	69.89	2471
HSA-MIR-4495	99.82	72.08	3080

Literature-anchored findings (GeneRIF, showing 40)

• Human substance P receptor undergoes agonist-dependent phosphorylation by G protein-coupled receptor kinase 5 in vitro. (PMID:12067742)
• Data indicate that GRK5 does not regulate the sorting of human beta 2-adrenoceptors in the endocytic pathway. (PMID:14691047)
• a group of hydrophobic amino acids within the membrane binding motif is critical to mediating the PM localization of GRK5 (PMID:14976207)
• GRK5 has a DNA-binding nuclear localization sequence (PMID:15542828)
• High expression was detected in septic neutrophils and control cells treated with cytokines plus LPS. (PMID:16849637)
• Results show that GRK5 plays a distinctive role in the phosphorylation of the beta2AR. (PMID:18034461)
• GRK5-Leu41 represents a gain-of-function polymorphism that evokes enhanced loss-of-function of beta2AR during persistent agonist exposure, and thus may contribute to beta-agonist variability in asthma treatment of African-Americans. (PMID:18622265)
• GRK5 overexpression causes nuclear accumulation of IkappaB alpha, leading to the inhibition of NFkappaB transcriptional activity. (PMID:19008357)
• Reciprocity of regulation between platelet-derived growth factor receptor beta (PDGFRbeta) and GRK5, or their activation/deactivation cycle, mirrors other reciprocal regulatory mechanisms affecting tyrosine kinases. (PMID:19092051)
• Data suggest that GRK2, but not GRK5, is correlated with increasing blood pressure in black Americans (PMID:19487588)
• beta-arrestin1 phosphorylation by GRK5 regulates G protein-independent signalling (PMID:19661922)
• Results identify GRK5/6 as novel kinases for the single transmembrane receptor LRP6 during Wnt signaling. (PMID:19801552)
• GRK5 Gln41Leu polymorphism is not associated with sensitivity to beta(1)-adrenergic blockade in humans. (PMID:19842931)
• it has been demonstrated that the GRK5 L41 variant causes a negative inotropic effect under conditions of acute catecholamine stimulationl8AAg (PMID:20023040)
• This study uncovered previously unrecognized functionally important sites in the regulator of G-protein signaling homology domain of GRK5 kinase. (PMID:20038610)
• GRK5 as a novel kinase of p53, as well as a negative regulator of p53-mediated signal transduction. (PMID:20124405)
• This study shows for the first time that GRK5 negatively regulates VEGF signaling in human coronary artery endothelial cells. (PMID:20443868)
• Studies seem to indicate that mild, soluble, Beta-amyloid accumulation can lead to a reduced membrane (functional) and an elevated cytosolic GRK2/5. (PMID:20730384)
• The GRK5 Leu41 allele protects from adverse cardiovascular outcomes in treated hypertensives. (PMID:21127457)
• GRK5 gene does not confer risk to sporadic Parkinson’s disease in our sample from Southern Italy. (PMID:21184589)
• GRK5 mediates cell growth suppression by TIG1A. Thus, TIG1 may participate in the downregulation of G-protein coupled signaling by upregulating GRK5 expression. (PMID:21575264)
• Hip has been identified as a novel substrate of GRK5 in vitro and in cells, and phosphorylation of Hip by GRK5 plays a role in modulating CXCR4 internalization (PMID:21728385)
• GRK5 is a transcriptional modifier of a subset of Galphaq-downregulated genes, acting in opposition to the pathological effects of Galphaq and normalizing levels of these transcripts. (PMID:21768220)
• A reduced cortical concentration of GRK5 in schizophrenia (resembling that in aging) may result in altered G protein-dependent signaling, thus contributing to prefrontal deficits in schizophrenia. (PMID:21784156)
• Increased GRK5 expression in the failing myocardium suggests a relevant role in human heart failure. (PMID:22196842)
• GRK5 is localized in the centrosome and regulates microtubule nucleation and normal cell cycle progression. (PMID:22223642)
• GRK5 phosphorylates Ser-4 in nucleophosmin and regulates the sensitivity of cells to PLK1 inhibition. (PMID:22467873)
• A genome-wide association study identifies GRK5 and RASGRP1 as type 2 diabetes loci in Chinese Hans. (PMID:22961080)
• These data suggest cell type- and subcellular compartment-dependent differences in GRK/arrestin-mediated desensitization and signaling. (PMID:23139825)
• DNA-binding ability of GRK5 requires both the NLS and an N-terminal calmodulin (CaM)-binding site (PMID:23658733)
• we show, for the first time, that knocking down the expression of GRK5 decreased the proliferation rate of gliioblastoma stem cells in contrast to control. (PMID:23693024)
• In the largest genotyped TC cohort in the literature, we have found no association of genetic variants in the ERalpha, beta1AR, beta2AR, or COMT genes, or with the previously implicated GRK5, with occurrence of the syndrome. (PMID:23794609)
• genetic polymorophism is associated with plasma viscosity (PMID:24178511)
• GRK5 intronic (CA)n polymorphisms associated with type 2 diabetes in Chinese Hainan Island. (PMID:24594703)
• Low levels of GRK2/GRK5 causes a slow and not complete desensitization/down-regulation of GPR17. (PMID:24613411)
• Results demonstrate crosstalk among WIP1, CXCR4 and GRK5, which may be important for the aggressive phenotype of a subclass of medulloblastomas in children. (PMID:24632620)
• GRK5 regulates prostate cancer cell migration and invasion. GRK5 forms a complex with moesin, phosphorylates moesin principally on T66 residue, and regulates cellular distribution of moesin. (PMID:24755472)
• GRK5 dimerization is important for its plasma membrane localization and function. (PMID:24807909)
• A significant difference in the frequency of GRK5 polymorphism was found between Takotsubo cardiomyopathy patients and controls, supporting a genetic predisposition to this cardiac syndrome. (PMID:25010510)
• G protein-coupled receptor kinase 5 gene polymorphisms may have a role in postoperative atrial fibrillation after coronary artery bypass grafting in patients receiving beta-blockers (PMID:25049040)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
mus_musculus	Grk5	ENSMUSG00000003228
rattus_norvegicus	Grk5	ENSRNOG00000011439
drosophila_melanogaster	Gprk1	FBGN0260798
drosophila_melanogaster	Gprk2	FBGN0261988
caenorhabditis_elegans		WBGENE00001708
caenorhabditis_elegans		WBGENE00001709

Paralogs (7): GRK3 (ENSG00000100077), GRK7 (ENSG00000114124), GRK4 (ENSG00000125388), RSKR (ENSG00000167524), GRK2 (ENSG00000173020), GRK1 (ENSG00000185974), GRK6 (ENSG00000198055)

Protein

Protein identifiers

G protein-coupled receptor kinase 5 — P34947 (reviewed: P34947)

Alternative names: G protein-coupled receptor kinase GRK5

All UniProt accessions (1): P34947

UniProt curated annotations — full annotation on UniProt →

Function. Serine/threonine kinase that phosphorylates preferentially the activated forms of a variety of G-protein-coupled receptors (GPCRs). Such receptor phosphorylation initiates beta-arrestin-mediated receptor desensitization, internalization, and signaling events leading to their down-regulation. Phosphorylates a variety of GPCRs, including adrenergic receptors, muscarinic acetylcholine receptors (more specifically Gi-coupled M2/M4 subtypes), dopamine receptors and opioid receptors. In addition to GPCRs, also phosphorylates various substrates: Hsc70-interacting protein/ST13, TP53/p53, HDAC5, and arrestin-1/ARRB1. Phosphorylation of ARRB1 by GRK5 inhibits G-protein independent MAPK1/MAPK3 signaling downstream of 5HT4-receptors. Phosphorylation of HDAC5, a repressor of myocyte enhancer factor 2 (MEF2) leading to nuclear export of HDAC5 and allowing MEF2-mediated transcription. Phosphorylation of TP53/p53, a crucial tumor suppressor, inhibits TP53/p53-mediated apoptosis. Phosphorylation of ST13 regulates internalization of the chemokine receptor. Phosphorylates rhodopsin (RHO) (in vitro) and a non G-protein-coupled receptor, LRP6 during Wnt signaling (in vitro).

Subunit / interactions. Interacts with ST13 (via the C-terminus 303-319 AA). Interacts with TP53/p53. Interacts with HTR4 (via C-terminus 330-346 AA); this interaction is promoted by 5-HT (serotonin). Interacts with HDAC5. Interacts with GIT1.

Subcellular location. Cytoplasm. Nucleus. Cell membrane.

Tissue specificity. Highest levels in heart, placenta, lung > skeletal muscle > brain, liver, pancreas > kidney.

Post-translational modifications. Autophosphorylated. Autophosphorylation may play a critical role in the regulation of GRK5 kinase activity.

Activity regulation. Inhibited by calmodulin with an IC(50) of 50 nM. Calmodulin inhibits GRK5 association with receptor and phospholipid.

Induction. Overexpressed during heart failure.

Polymorphism. Variant Leu-41 variant is rare in European-Americans individuals but common in African-Americans individuals (40% of the African-American individuals studied carry at least one allele). Variant leu-41 is associated with decreased mortality in African-Americans with heart failure or cardiac ischemia.

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

RefSeq proteins (1): NP_005299* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000239	GPCR_kinase	Family
IPR000719	Prot_kinase_dom	Domain
IPR000961	AGC-kinase_C	Domain
IPR011009	Kinase-like_dom_sf	Homologous_superfamily
IPR016137	RGS	Domain
IPR017441	Protein_kinase_ATP_BS	Binding_site
IPR036305	RGS_sf	Homologous_superfamily
IPR044926	RGS_subdomain_2	Homologous_superfamily

Pfam: PF00069, PF00615

Enzyme classification (BRENDA):

• EC 2.7.11.16 — G-protein-coupled receptor kinase (BRENDA: 5 organisms, 89 substrates, 34 inhibitors, 5 Km, 0 kcat entries)

Substrate kinetics (BRENDA)

2 substrates with measured Km, best-characterized 2. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
ATP	0.014–0.02	3
RHODOPSIN	0.0012–0.0018	2

Catalyzed reactions (Rhea), 1 shown:

• [G-protein-coupled receptor] + ATP = [G-protein-coupled receptor]-phosphate + ADP + H(+) (RHEA:12008)

UniProt features (89 total): helix 33, strand 16, mutagenesis site 12, sequence variant 7, turn 4, region of interest 4, domain 3, modified residue 3, compositionally biased region 2, binding site 2, chain 1, active site 1, short sequence motif 1

Structure

Experimental structures (PDB)

23 structures.

PDB	Method	Resolution (Å)
4TND	X-RAY DIFFRACTION	1.8
6PJX	X-RAY DIFFRACTION	1.96
4TNB	X-RAY DIFFRACTION	2.11
8UAP	X-RAY DIFFRACTION	2.5
9CKP	X-RAY DIFFRACTION	2.6
9BRG	X-RAY DIFFRACTION	2.7
9BRK	X-RAY DIFFRACTION	2.7
9CKQ	X-RAY DIFFRACTION	2.7
9BRL	X-RAY DIFFRACTION	2.73
9BRM	X-RAY DIFFRACTION	2.73
8UAQ	X-RAY DIFFRACTION	2.8
9BRE	X-RAY DIFFRACTION	2.8
9BRJ	X-RAY DIFFRACTION	2.8
9BRO	X-RAY DIFFRACTION	2.8
9BRP	X-RAY DIFFRACTION	2.8
9CKO	X-RAY DIFFRACTION	2.8
9CKR	X-RAY DIFFRACTION	2.8
9BRF	X-RAY DIFFRACTION	2.84
9BRI	X-RAY DIFFRACTION	2.9
9BRN	X-RAY DIFFRACTION	2.9
9CKS	X-RAY DIFFRACTION	3.08
9BRH	X-RAY DIFFRACTION	3.69
9MX2	X-RAY DIFFRACTION	3.9

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P34947-F1	90.75	0.80

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): 311 (proton acceptor)

Ligand- & substrate-binding residues (2): 192–200; 215

Post-translational modifications (3): 484, 485, 579

Mutagenesis-validated functional residues (12):

Position	Phenotype
215	failed to phosphorylate p53/tp53.
388	nuclear exclusion; when associated with a-389; a-391; a-393 and a-394.
389	nuclear exclusion; when associated with a-388; a-391; a-393 and a-394.
391	nuclear exclusion; when associated with a-388; a-389; a-393 and a-394.
393	nuclear exclusion; when associated with a-388; a-389; a-391 and a-394.
394	nuclear exclusion; when associated with a-388; a-389; a-391 and a-393.
484	15-20 fold defects in kinase activity; when associated with a-485.
485	15-20 fold defects in kinase activity; when associated with a-484.
550	no detectable plasma membrane localization; when associated with a-551; a-554; and a-555.
551	no detectable plasma membrane localization; when associated with a-550; a-554; and a-555.
554	no detectable plasma membrane localization; when associated with a-550; a-551; and a-555.
555	no detectable plasma membrane localization; when associated with a-550; a-551; and a-554.

Function

Pathways and Gene Ontology

Reactome pathways

2 pathways

ID	Pathway
R-HSA-416476	G alpha (q) signalling events
R-HSA-418555	G alpha (s) signalling events

MSigDB gene sets: 294 (showing top): GSE37336_LY6C_POS_VS_NEG_NAIVE_CD4_TCELL_DN, CREL_01, BENPORATH_ES_WITH_H3K27ME3, CHIARADONNA_NEOPLASTIC_TRANSFORMATION_KRAS_DN, MODULE_571, DACOSTA_UV_RESPONSE_VIA_ERCC3_XPCS_DN, PEREZ_TP63_TARGETS, GCANCTGNY_MYOD_Q6, MODULE_64, AAGCCAT_MIR135A_MIR135B, MAZ_Q6, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, GGAMTNNNNNTCCY_UNKNOWN, CAGCTG_AP4_Q5, STOSSI_RESPONSE_TO_ESTRADIOL

GO Biological Process (14): apoptotic process (GO:0006915), G protein-coupled receptor signaling pathway (GO:0007186), adenylate cyclase-modulating G protein-coupled receptor signaling pathway (GO:0007188), tachykinin receptor signaling pathway (GO:0007217), regulation of G protein-coupled receptor signaling pathway (GO:0008277), positive regulation of cell population proliferation (GO:0008284), regulation of signal transduction (GO:0009966), Wnt signaling pathway (GO:0016055), negative regulation of apoptotic process (GO:0043066), fat cell differentiation (GO:0045444), protein autophosphorylation (GO:0046777), regulation of cell cycle (GO:0051726), protein phosphorylation (GO:0006468), signal transduction (GO:0007165)

GO Molecular Function (12): protein kinase activity (GO:0004672), protein serine/threonine kinase activity (GO:0004674), G protein-coupled receptor kinase activity (GO:0004703), protein kinase C binding (GO:0005080), ATP binding (GO:0005524), phospholipid binding (GO:0005543), beta-adrenergic receptor kinase activity (GO:0047696), nucleotide binding (GO:0000166), protein binding (GO:0005515), lipid binding (GO:0008289), kinase activity (GO:0016301), transferase activity (GO:0016740)

GO Cellular Component (7): cytoplasm (GO:0005737), cytosol (GO:0005829), plasma membrane (GO:0005886), nuclear speck (GO:0016607), nuclear membrane (GO:0031965), nucleus (GO:0005634), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
GPCR downstream signalling	2

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
G protein-coupled receptor signaling pathway	3
cellular anatomical structure	3
signal transduction	2
regulation of cellular process	2
protein kinase activity	2
binding	2
programmed cell death	1
apoptotic signaling pathway	1
execution phase of apoptosis	1
G protein-coupled receptor activity	1
adenylate cyclase activity	1
regulation of signal transduction	1
cell population proliferation	1
regulation of cell population proliferation	1
positive regulation of cellular process	1
regulation of cell communication	1
regulation of signaling	1
regulation of response to stimulus	1
cell surface receptor signaling pathway	1
apoptotic process	1
regulation of apoptotic process	1
negative regulation of programmed cell death	1
cell differentiation	1
protein phosphorylation	1
cell cycle	1
phosphorylation	1
protein modification process	1
cell communication	1
cellular process	1
signaling	1
cellular response to stimulus	1
kinase activity	1
phosphotransferase activity, alcohol group as acceptor	1
catalytic activity, acting on a protein	1
protein serine/threonine kinase activity	1
protein kinase binding	1
adenyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
lipid binding	1
nucleoside phosphate binding	1

Protein interactions and networks

STRING

1368 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
GRK5	GIT1	Q9Y2X7	997
GRK5	GIT2	Q14161	934
GRK5	ARRB2	P32121	865
GRK5	ARRB1	P49407	841
GRK5	SAG	P10523	802
GRK5	ADRB2	P07550	751
GRK5	ARHGEF6	Q15052	736
GRK5	ADRB1	P08588	736
GRK5	RHO	P08100	697
GRK5	PEBP1	P30086	659
GRK5	CABP1	Q9NZU7	630
GRK5	PXN	P49023	622
GRK5	CABP5	Q9NP86	616
GRK5	CABP2	Q9NPB3	594
GRK5	ADRA2A	P08913	563

IntAct

14 interactions, top by confidence:

A	B	Type	Score
Htr4	GRK5	psi-mi:“MI:0407”(direct interaction)	0.630
GRK5	Htr4	psi-mi:“MI:0915”(physical association)	0.630
Htr4	GRK5	psi-mi:“MI:0915”(physical association)	0.630
Htr4	GRK5	psi-mi:“MI:0914”(association)	0.630
NFKBIA	GRK5	psi-mi:“MI:0407”(direct interaction)	0.560
Htr4	SRC	psi-mi:“MI:0915”(physical association)	0.540
CHUK	GRK5	psi-mi:“MI:0915”(physical association)	0.400
GRK6	GRK5	psi-mi:“MI:0914”(association)	0.350
Htr4	ARRB2	psi-mi:“MI:0914”(association)	0.350
ARRB1	GRK5	psi-mi:“MI:0914”(association)	0.350

BioGRID (184): GRK5 (Affinity Capture-RNA), GRK5 (Affinity Capture-RNA), GRK5 (Affinity Capture-MS), GRK5 (Reconstituted Complex), GRK5 (Affinity Capture-MS), GRK5 (Reconstituted Complex), GRK5 (Reconstituted Complex), GRK5 (Affinity Capture-Western), AVPR1A (Affinity Capture-Western), AVPR2 (Affinity Capture-Western), TACR1 (Biochemical Activity), SNCA (Biochemical Activity), SNCA (Biochemical Activity), SNCB (Biochemical Activity), SNCG (Biochemical Activity)

ESM2 similar proteins: A0A8C0TYJ0, A0A8I5ZNK2, A5D7H2, O55047, O88506, O94806, O95747, P00535, P11273, P32298, P34947, P43249, P49137, Q08CW1, Q12959, Q13033, Q15139, Q15700, Q16644, Q1ECX4, Q28C55, Q3SYZ2, Q3UMW7, Q5PYH5, Q5PYH6, Q5R372, Q5R495, Q5RCW6, Q5XIS9, Q62101, Q62696, Q62833, Q63622, Q66H84, Q6P9R2, Q811D0, Q863I2, Q86UE8, Q8BZ03, Q8C0V0

Diamond homologs: A1A4I4, A1Z7T0, A7MBL8, B6CZ17, B6CZ18, J9W0G9, O08874, O19111, O70291, O70293, O97627, P04409, P05130, P05696, P09215, P09217, P10102, P10830, P12688, P13678, P16054, P17252, P18961, P21146, P23298, P24723, P25098, P26817, P26818, P26819, P28327, P28867, P31748, P31749, P31750, P31751, P32298, P32865, P32866, P34102

SIGNOR signaling

21 interactions.

A	Effect	B	Mechanism
GRK5	“down-regulates activity”	SNCA	phosphorylation
GRK5	down-regulates	TP53	phosphorylation
GRK5	up-regulates	LRP6	phosphorylation
GRK5	“down-regulates activity”	BDKRB2	phosphorylation
GRK5	“up-regulates activity”	ST13	phosphorylation
GRK5	“up-regulates activity”	NTSR1	phosphorylation
GRK5	down-regulates	NR3C2	phosphorylation
GRK5	“down-regulates activity”	HDAC5	phosphorylation
PDGFRB	“up-regulates activity”	GRK5	phosphorylation
GRK5	“down-regulates quantity”	CXCR4	phosphorylation
GRK5	unknown	ADRB2	phosphorylation
GRK5	“up-regulates activity”	GRK5	phosphorylation
GRK5	“down-regulates activity”	SNCB	phosphorylation

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	76
Likely benign	5
Benign	7

Top pathogenic / likely-pathogenic (0)

SpliceAI

3856 predictions. Top by Δscore:

Variant	Effect	Δscore
10:119207966:G:T	donor_gain	1.0000
10:119207967:A:T	donor_gain	1.0000
10:119294047:G:GT	donor_gain	1.0000
10:119396687:T:A	acceptor_gain	1.0000
10:119396692:TA:T	acceptor_loss	1.0000
10:119396693:A:AG	acceptor_gain	1.0000
10:119396693:A:AT	acceptor_loss	1.0000
10:119396694:G:GT	acceptor_gain	1.0000
10:119396694:GGCA:G	acceptor_gain	1.0000
10:119396772:GGTAA:G	donor_loss	1.0000
10:119396773:GTAAG:G	donor_loss	1.0000
10:119396774:T:A	donor_loss	1.0000
10:119423164:A:AG	acceptor_gain	1.0000
10:119423165:G:GA	acceptor_gain	1.0000
10:119423165:GT:G	acceptor_gain	1.0000
10:119423165:GTC:G	acceptor_gain	1.0000
10:119423165:GTCC:G	acceptor_gain	1.0000
10:119423165:GTCCC:G	acceptor_gain	1.0000
10:119423262:GCACA:G	donor_gain	1.0000
10:119423267:G:GG	donor_gain	1.0000
10:119424987:CACTA:C	acceptor_loss	1.0000
10:119424989:CTAGG:C	acceptor_loss	1.0000
10:119424990:TAGGT:T	acceptor_loss	1.0000
10:119424991:A:T	acceptor_loss	1.0000
10:119425086:G:GA	donor_loss	1.0000
10:119425087:T:A	donor_loss	1.0000
10:119431528:G:GG	donor_gain	1.0000
10:119431529:T:A	donor_loss	1.0000
10:119436645:TCCCA:T	acceptor_loss	1.0000
10:119436646:CCCAG:C	acceptor_loss	1.0000

AlphaMissense

3920 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
10:119207939:G:C	A8P	1.000
10:119207940:C:A	A8D	1.000
10:119207944:C:A	N9K	1.000
10:119207944:C:G	N9K	1.000
10:119430398:T:C	F186S	1.000
10:119430401:G:C	R187T	1.000
10:119430401:G:T	R187M	1.000
10:119430402:G:C	R187S	1.000
10:119430402:G:T	R187S	1.000
10:119430406:T:G	Y189D	1.000
10:119430410:G:C	R190P	1.000
10:119430416:T:A	L192Q	1.000
10:119430418:G:A	G193R	1.000
10:119430418:G:C	G193R	1.000
10:119430419:G:A	G193E	1.000
10:119430419:G:T	G193V	1.000
10:119430422:A:T	K194I	1.000
10:119430423:A:C	K194N	1.000
10:119430423:A:T	K194N	1.000
10:119430424:G:A	G195R	1.000
10:119430424:G:C	G195R	1.000
10:119430424:G:T	G195W	1.000
10:119430425:G:A	G195E	1.000
10:119430425:G:T	G195V	1.000
10:119430427:G:C	G196R	1.000
10:119430428:G:A	G196D	1.000
10:119430430:T:A	F197I	1.000
10:119430430:T:C	F197L	1.000
10:119430430:T:G	F197V	1.000
10:119430431:T:C	F197S	1.000

dbSNP variants (sampled 300 via entrez): RS1000010065 (10:119303455 G>A), RS1000029039 (10:119381792 T>A,C,G), RS1000039141 (10:119243160 C>T), RS1000090481 (10:119417977 C>T), RS1000131432 (10:119263316 C>T), RS1000132304 (10:119229995 C>T), RS1000138948 (10:119335341 G>A), RS1000145375 (10:119355055 C>T), RS1000148608 (10:119389628 G>A), RS1000164221 (10:119239327 C>A,T), RS1000168921 (10:119440162 C>T), RS1000190964 (10:119208357 G>A), RS1000193050 (10:119259255 G>A), RS1000198977 (10:119299943 C>T), RS1000203225 (10:119452929 A>C,G,T)

Disease associations

OMIM: gene MIM:600870 | disease phenotypes:

GenCC curated gene-disease

Mondo (1): neurodevelopmental disorder (MONDO:0700092)

Orphanet (0):

HPO phenotypes

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

GWAS associations

23 associations (top):

Study	Trait	p-value
GCST001666_1	Type 2 diabetes	7.000000e-09
GCST001762_5	Obesity-related traits	2.000000e-06
GCST003560_20	Coronary artery aneurysm in Kawasaki disease	9.000000e-06
GCST004599_11	Mean platelet volume	7.000000e-18
GCST004616_83	Platelet distribution width	7.000000e-14
GCST004955_1	Risky sexual behaviors in alcohol dependence	1.000000e-09
GCST006856_1	Methadone dose in opioid dependence	4.000000e-06
GCST006856_2	Methadone dose in opioid dependence	9.000000e-06
GCST008163_571	Height	2.000000e-06
GCST009030_15	Venous thromboembolism	2.000000e-12
GCST009097_14	Venous thromboembolism	2.000000e-18
GCST009253_3	Early onset periodontitis x smoking status interaction	6.000000e-07
GCST010601_1	Thrombin-induced platelet aggregation	3.000000e-42
GCST011913_1	Thymus and reactivation regulated chemokine levels	1.000000e-75
GCST90000025_179	Appendicular lean mass	7.000000e-27
GCST90000025_180	Appendicular lean mass	3.000000e-10
GCST90002388_527	Lymphocyte count	6.000000e-15
GCST90002389_455	Lymphocyte percentage of white cells	2.000000e-12
GCST90002395_39	Mean platelet volume	1.000000e-43
GCST90002399_55	Neutrophil percentage of white cells	5.000000e-11
GCST90002401_172	Platelet distribution width	9.000000e-31
GCST90002402_331	Platelet count	7.000000e-15
GCST90020029_303	Waist circumference adjusted for body mass index	4.000000e-08

EFO canonical traits (10, from GWAS)

EFO ID	Trait name
EFO:0004626	IGFBP-3 measurement
EFO:0007984	platelet component distribution width
EFO:0007907	methadone dose measurement
EFO:0006527	smoking status measurement
EFO:0004980	appendicular lean mass
EFO:0004587	lymphocyte count
EFO:0007993	lymphocyte percentage of leukocytes
EFO:0007990	neutrophil percentage of leukocytes
EFO:0004309	platelet count
EFO:0007789	BMI-adjusted waist circumference

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D065886	Neurodevelopmental Disorders	F03.625

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL5678 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

8 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 91,782 (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
CHEMBL1983268	ENTRECTINIB	4	3,510
CHEMBL3622821	UPADACITINIB	4	2,726
CHEMBL535	SUNITINIB	4	79,020
CHEMBL483158	ALISERTIB	3	2,305
CHEMBL565612	SOTRASTAURIN	2	1,355
CHEMBL1084546	PF-00562271	1	399
CHEMBL1980391	RG-1530	1	37
CHEMBL259084	MLN-8054	1	2,430

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

PharmGKB clinical annotations

7 annotations.

Variant	Type	Level	Drugs	Phenotypes
rs10787959	Efficacy	3	Beta Blocking Agents	Coronary Artery Disease
rs11198893	Efficacy	3	Beta Blocking Agents	Coronary Artery Disease
rs2230345	Efficacy	3	Antihypertensives;Beta Blocking Agents	Heart Diseases
rs2230345	Efficacy	4	Beta Blocking Agents	Heart Failure
rs3740563	Efficacy	3	Beta Blocking Agents	Coronary Artery Disease
rs4752292	Efficacy	3	Beta Blocking Agents	Coronary Artery Disease
rs915120	Efficacy	3	citalopram;escitalopram	Depressive Disorder

PharmGKB variants

8 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs915120	GRK5	3	0.00	1	citalopram;escitalopram
rs2230345	GRK5	3	1.50	2	Beta Blocking Agents;Antihypertensives;Beta Blocking Agents
rs4752269	EIF3A, GRK5		0.00	0
rs10787959	GRK5	3	3.50	1	Beta Blocking Agents
rs3740563	GRK5	3	4.00	1	Beta Blocking Agents
rs11198893	GRK5	3	4.00	1	Beta Blocking Agents
rs4752292	GRK5	3	3.50	1	Beta Blocking Agents
rs2230349	GRK5		0.00	0

PharmGKB dosing guidelines

1 guidelines.

Source	Drug	Guideline	Dosing?	Recommendation?
CPIC	acebutolol;atenolol;betaxolol;bisoprolol;carvedilol;esmolol;labetalol;metoprolol;nadolol;nebivolol;pindolol;propranolol;sotalol	Annotation of CPIC Guideline for acebutolol, atenolol, betaxolol, bisoprolol, carvedilol, esmolol, labetalol, metoprolol, nadolol, nebivolol, pindolol, propranolol, sotalol and ADRA2C, ADRB1, GRK4, GRK5

GtoPdb / IUPHAR curated pharmacology

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

Target class: enzyme — GRK4 subfamily

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

Ligand	Action	Affinity	Parameter
compound 1o [PMID: 24210504]	Inhibition	7.23	pIC50

Binding affinities (BindingDB)

38 measured of 39 human assays (83 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

299 potent at pChembl≥5 of 392 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
8.42	IC50	3.8	nM	CHEMBL4786599
8.07	IC50	8.6	nM	CHEMBL4785430
8.00	IC50	10	nM	CHEMBL5569207
7.92	IC50	12	nM	CHEMBL4877302
7.82	IC50	15	nM	CHEMBL4800665
7.82	IC50	15	nM	CHEMBL4780266
7.72	Ki	19	nM	CHEMBL4786599
7.72	IC50	19	nM	CHEMBL4786599
7.70	IC50	20	nM	CHEMBL5415336
7.68	IC50	21	nM	CHEMBL4782014
7.61	IC50	24.6	nM	STAUROSPORINE
7.60	Ki	25.12	nM	CHEMBL1980995
7.58	IC50	26	nM	CHEMBL4854871
7.54	IC50	29	nM	CHEMBL4794078
7.52	IC50	30	nM	CHEMBL5573333
7.52	IC50	30	nM	CHEMBL5565079
7.52	IC50	30	nM	CHEMBL6162554
7.40	IC50	40	nM	CHEMBL5556746
7.40	Ki	39.81	nM	CHEMBL1980407
7.36	IC50	44	nM	CHEMBL4785430
7.32	IC50	48	nM	CHEMBL4781735
7.29	IC50	51	nM	CHEMBL4847703
7.25	IC50	56	nM	CHEMBL6159900
7.23	IC50	59	nM	CHEMBL3093151
7.22	IC50	60	nM	CHEMBL5571690
7.22	IC50	60	nM	CHEMBL6164393
7.13	IC50	73.3	nM	STAUROSPORINE
7.10	IC50	80	nM	CHEMBL4787507
7.10	Ki	79.43	nM	CHEMBL1988581
7.10	Ki	79.43	nM	CHEMBL1988141
7.07	IC50	85.6	nM	STAUROSPORINE
7.06	IC50	87	nM	CHEMBL4779427
7.04	IC50	91	nM	CHEMBL4786185
7.02	IC50	95	nM	CHEMBL4786846
7.00	Ki	100	nM	CHEMBL3729453
7.00	Ki	100	nM	CHEMBL3732018
6.96	IC50	110	nM	CHEMBL4799210
6.96	Ki	110	nM	CHEMBL4785430
6.96	IC50	110	nM	CHEMBL5573597
6.96	IC50	110	nM	CHEMBL6151812
6.92	IC50	120	nM	CHEMBL3093260
6.89	IC50	130	nM	CHEMBL4777196
6.89	IC50	130	nM	CHEMBL4784634
6.89	IC50	130	nM	CHEMBL5565274
6.85	IC50	140	nM	CHEMBL3093258
6.85	IC50	140	nM	CHEMBL4798127
6.85	IC50	140	nM	CHEMBL4225427
6.80	IC50	160	nM	BALANOL
6.80	Ki	158.5	nM	CHEMBL1973359
6.70	Ki	199.5	nM	CHEMBL2007574

PubChem BioAssay actives

162 with measured affinity, of 1093 total; 50 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
(3Z)-3-[[4-[(2-chloroacetyl)amino]-3,5-dimethyl-1H-pyrrol-2-yl]methylidene]-N-[(2R)-1-(4-fluorophenyl)propan-2-yl]-2-oxo-1H-indole-5-carboxamide	1744429: Inhibition of human GRK5 using porcine brain tubulin as substrate incubated for 3 to 5 mins by [gamma32P]ATP based radiometric assay	ic50	0.0038	uM
(3Z)-3-[[4-[(2-bromoacetyl)amino]-3,5-dimethyl-1H-pyrrol-2-yl]methylidene]-2-oxo-N-[(1R)-1-phenylethyl]-1H-indole-5-carboxamide	1744429: Inhibition of human GRK5 using porcine brain tubulin as substrate incubated for 3 to 5 mins by [gamma32P]ATP based radiometric assay	ic50	0.0086	uM
(3Z)-N-[(1R)-1-(4-fluorophenyl)ethyl]-3-[[4-[[2-(furan-2-yl)-2-oxoacetyl]amino]-3,5-dimethyl-1H-pyrrol-2-yl]methylidene]-2-oxo-1H-indole-5-carboxamide	2087718: Inhibition of human GRK5 (1 to 590) expressed in Escherichia coli using tubulin as substrate incubated for 5 mins in presence of [gamma-32P]-ATP by radiometric assay	ic50	0.0100	uM
2-N-[(4-chloro-2-methoxyphenyl)methyl]-4-N-(5-ethyl-1H-pyrazol-3-yl)-5-methoxyquinazoline-2,4-diamine	1751899: Inhibition of recombinant full length human GRK5 using casein as substrate incubated for 40 mins in presence of [gamma-33ATP] by scintillation counting based radiometry assay	ic50	0.0120	uM
(3Z)-3-[[4-[2-(diethylamino)ethylcarbamoyl]-3,5-dimethyl-1H-pyrrol-2-yl]methylidene]-2-oxo-N-[(1R)-1-phenylethyl]-1H-indole-5-carboxamide	1744429: Inhibition of human GRK5 using porcine brain tubulin as substrate incubated for 3 to 5 mins by [gamma32P]ATP based radiometric assay	ic50	0.0150	uM
(3Z)-3-[[4-[(2-bromoacetyl)amino]-3,5-dimethyl-1H-pyrrol-2-yl]methylidene]-N-[(2R)-1-(4-fluorophenyl)propan-2-yl]-2-oxo-1H-indole-5-carboxamide	1744429: Inhibition of human GRK5 using porcine brain tubulin as substrate incubated for 3 to 5 mins by [gamma32P]ATP based radiometric assay	ic50	0.0150	uM
7-[3-[4-(3-aminopropylamino)butylamino]propylamino]-2-(2-chlorophenyl)-6-fluoro-3H-quinazolin-4-one	2000136: Inhibition of GRK5 (unknown origin)	ic50	0.0200	uM
(3Z)-3-[[3,5-dimethyl-4-(prop-2-ynylcarbamoyl)-1H-pyrrol-2-yl]methylidene]-2-oxo-N-[(1R)-1-phenylethyl]-1H-indole-5-carboxamide	1744429: Inhibition of human GRK5 using porcine brain tubulin as substrate incubated for 3 to 5 mins by [gamma32P]ATP based radiometric assay	ic50	0.0210	uM
(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	1715330: Inhibition of human GRK5 using casein as substrate by [gamma-33P]-ATP assay	ic50	0.0246	uM
4-N-(5-ethyl-1H-pyrazol-3-yl)-2-N-[(1S)-1-(5-fluoro-2-pyridinyl)ethyl]-5-methoxyquinazoline-2,4-diamine	1751899: Inhibition of recombinant full length human GRK5 using casein as substrate incubated for 40 mins in presence of [gamma-33ATP] by scintillation counting based radiometry assay	ic50	0.0260	uM
(3Z)-3-[[4-[(2-chloroacetyl)amino]-3,5-dimethyl-1H-pyrrol-2-yl]methylidene]-N-[(2R)-1-(3-methylphenyl)propan-2-yl]-2-oxo-1H-indole-5-carboxamide	1744429: Inhibition of human GRK5 using porcine brain tubulin as substrate incubated for 3 to 5 mins by [gamma32P]ATP based radiometric assay	ic50	0.0290	uM
(3Z)-3-[[3,5-dimethyl-4-(2-oxopropanoylamino)-1H-pyrrol-2-yl]methylidene]-N-[(1R)-1-(4-fluorophenyl)ethyl]-2-oxo-1H-indole-5-carboxamide	2087718: Inhibition of human GRK5 (1 to 590) expressed in Escherichia coli using tubulin as substrate incubated for 5 mins in presence of [gamma-32P]-ATP by radiometric assay	ic50	0.0300	uM
(3Z)-N-[(4-fluorophenyl)methyl]-3-[[4-[[(2S)-2-(furan-2-yl)-2-hydroxyacetyl]amino]-3,5-dimethyl-1H-pyrrol-2-yl]methylidene]-2-oxo-1H-indole-5-carboxamide	2087718: Inhibition of human GRK5 (1 to 590) expressed in Escherichia coli using tubulin as substrate incubated for 5 mins in presence of [gamma-32P]-ATP by radiometric assay	ic50	0.0300	uM
(3Z)-N-[(1R)-1-(4-fluorophenyl)ethyl]-3-[[4-[[(2S)-2-hydroxypropanoyl]amino]-3,5-dimethyl-1H-pyrrol-2-yl]methylidene]-2-oxo-1H-indole-5-carboxamide	2087718: Inhibition of human GRK5 (1 to 590) expressed in Escherichia coli using tubulin as substrate incubated for 5 mins in presence of [gamma-32P]-ATP by radiometric assay	ic50	0.0400	uM
(3Z)-3-[[3,5-dimethyl-4-(prop-2-enylcarbamoyl)-1H-pyrrol-2-yl]methylidene]-2-oxo-N-[(1R)-1-phenylethyl]-1H-indole-5-carboxamide	1744429: Inhibition of human GRK5 using porcine brain tubulin as substrate incubated for 3 to 5 mins by [gamma32P]ATP based radiometric assay	ic50	0.0480	uM
4-N-(5-ethyl-1H-pyrazol-3-yl)-2-N-[(5-fluoro-2-pyridinyl)methyl]-5-methoxyquinazoline-2,4-diamine	1751899: Inhibition of recombinant full length human GRK5 using casein as substrate incubated for 40 mins in presence of [gamma-33ATP] by scintillation counting based radiometry assay	ic50	0.0510	uM
5-(1-piperidin-4-ylpyrazol-4-yl)-3-(6-pyrrolidin-1-yl-1,3-benzoxazol-2-yl)pyridin-2-amine	1058426: Inhibition of GRK-5 (unknown origin) preincubated with enzyme for 10 mins before adding peptide substrate and ATP measured after 1 hr by LANCE-TR-FRET assay	ic50	0.0590	uM
(3Z)-N-[(1R)-1-(4-fluorophenyl)ethyl]-3-[[4-[[(2S)-2-hydroxy-2-phenylacetyl]amino]-3,5-dimethyl-1H-pyrrol-2-yl]methylidene]-2-oxo-1H-indole-5-carboxamide	2087718: Inhibition of human GRK5 (1 to 590) expressed in Escherichia coli using tubulin as substrate incubated for 5 mins in presence of [gamma-32P]-ATP by radiometric assay	ic50	0.0600	uM
(3Z)-3-[[4-[(3-chloro-2-hydroxypropanoyl)amino]-3,5-dimethyl-1H-pyrrol-2-yl]methylidene]-2-oxo-N-[(1R)-1-phenylethyl]-1H-indole-5-carboxamide	1744429: Inhibition of human GRK5 using porcine brain tubulin as substrate incubated for 3 to 5 mins by [gamma32P]ATP based radiometric assay	ic50	0.0800	uM
(3Z)-3-[[4-[(2-chloroacetyl)amino]-3,5-dimethyl-1H-pyrrol-2-yl]methylidene]-N-[(2S)-3-methyl-1-phenylbutan-2-yl]-2-oxo-1H-indole-5-carboxamide	1744429: Inhibition of human GRK5 using porcine brain tubulin as substrate incubated for 3 to 5 mins by [gamma32P]ATP based radiometric assay	ic50	0.0870	uM
(3Z)-3-[[4-(but-3-ynylcarbamoyl)-3,5-dimethyl-1H-pyrrol-2-yl]methylidene]-2-oxo-N-[(1R)-1-phenylethyl]-1H-indole-5-carboxamide	1744429: Inhibition of human GRK5 using porcine brain tubulin as substrate incubated for 3 to 5 mins by [gamma32P]ATP based radiometric assay	ic50	0.0910	uM
(3Z)-N-(3-benzyloxetan-3-yl)-3-[[4-[(2-chloroacetyl)amino]-3,5-dimethyl-1H-pyrrol-2-yl]methylidene]-2-oxo-1H-indole-5-carboxamide	1744429: Inhibition of human GRK5 using porcine brain tubulin as substrate incubated for 3 to 5 mins by [gamma32P]ATP based radiometric assay	ic50	0.0950	uM
(3Z)-3-[[4-[(2-chloroacetyl)amino]-3,5-dimethyl-1H-pyrrol-2-yl]methylidene]-N-[(2R)-1-(4-chlorophenyl)propan-2-yl]-2-oxo-1H-indole-5-carboxamide	1744429: Inhibition of human GRK5 using porcine brain tubulin as substrate incubated for 3 to 5 mins by [gamma32P]ATP based radiometric assay	ic50	0.1100	uM
(3Z)-N-[(4-fluorophenyl)methyl]-3-[[4-[[(2R)-2-hydroxy-2-phenylacetyl]amino]-3,5-dimethyl-1H-pyrrol-2-yl]methylidene]-2-oxo-1H-indole-5-carboxamide	2087718: Inhibition of human GRK5 (1 to 590) expressed in Escherichia coli using tubulin as substrate incubated for 5 mins in presence of [gamma-32P]-ATP by radiometric assay	ic50	0.1100	uM
5-(1-piperidin-4-ylpyrazol-4-yl)-3-(5-pyrrolidin-1-yl-1,3-benzoxazol-2-yl)pyridin-2-amine	1058426: Inhibition of GRK-5 (unknown origin) preincubated with enzyme for 10 mins before adding peptide substrate and ATP measured after 1 hr by LANCE-TR-FRET assay	ic50	0.1200	uM
(3Z)-3-[[4-[(2-chloroacetyl)amino]-3,5-dimethyl-1H-pyrrol-2-yl]methylidene]-2-oxo-N-[(1R)-1-pyridin-4-ylethyl]-1H-indole-5-carboxamide	1744429: Inhibition of human GRK5 using porcine brain tubulin as substrate incubated for 3 to 5 mins by [gamma32P]ATP based radiometric assay	ic50	0.1300	uM
(3Z)-3-[[4-[(2-chloroacetyl)amino]-3,5-dimethyl-1H-pyrrol-2-yl]methylidene]-2-oxo-N-(2-phenylethyl)-1H-indole-5-carboxamide	1744429: Inhibition of human GRK5 using porcine brain tubulin as substrate incubated for 3 to 5 mins by [gamma32P]ATP based radiometric assay	ic50	0.1300	uM
(3Z)-N-[(1R)-1-(4-fluorophenyl)ethyl]-3-[[4-[[(2R)-2-hydroxypropanoyl]amino]-3,5-dimethyl-1H-pyrrol-2-yl]methylidene]-2-oxo-1H-indole-5-carboxamide	2087718: Inhibition of human GRK5 (1 to 590) expressed in Escherichia coli using tubulin as substrate incubated for 5 mins in presence of [gamma-32P]-ATP by radiometric assay	ic50	0.1300	uM
(3Z)-3-[[4-[(2-chloroacetyl)amino]-3,5-dimethyl-1H-pyrrol-2-yl]methylidene]-N-[(2R)-1-(3-chlorophenyl)propan-2-yl]-2-oxo-1H-indole-5-carboxamide	1744429: Inhibition of human GRK5 using porcine brain tubulin as substrate incubated for 3 to 5 mins by [gamma32P]ATP based radiometric assay	ic50	0.1400	uM
3-(5-piperidin-1-yl-1,3-benzoxazol-2-yl)-5-(1-piperidin-4-ylpyrazol-4-yl)pyridin-2-amine	1058426: Inhibition of GRK-5 (unknown origin) preincubated with enzyme for 10 mins before adding peptide substrate and ATP measured after 1 hr by LANCE-TR-FRET assay	ic50	0.1400	uM
2-[2,6-dihydroxy-4-[(3R,4R)-3-[(4-hydroxybenzoyl)amino]azepan-4-yl]oxycarbonylbenzoyl]-3-hydroxybenzoic acid	464311: Inhibition of GRK5-mediated bovine tubulin phosphorylation by scintillation counting	ic50	0.1600	uM
2-[2-amino-5-(1-piperidin-4-ylpyrazol-4-yl)-3-pyridinyl]-7-phenyl-1,3-benzoxazol-6-ol	1058426: Inhibition of GRK-5 (unknown origin) preincubated with enzyme for 10 mins before adding peptide substrate and ATP measured after 1 hr by LANCE-TR-FRET assay	ic50	0.2100	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	1744437: Inhibition of human GRK5 C474S mutant using porcine brain tubulin as substrate incubated for 3 to 5 mins by [gamma32P]ATP based radiometric assay	ic50	0.2200	uM
2-[[2-[2-methoxy-4-(prop-2-enoylamino)anilino]-7H-pyrrolo[2,3-d]pyrimidin-4-yl]amino]benzamide	1611777: Inhibition of human GRK5 using tubulin as substrate measured after 4 hrs by [gamma-32P]-ATP assay	ic50	0.2200	uM
2-[[2-[5-[[(E)-4-(dimethylamino)but-2-enoyl]amino]-2-methoxyanilino]-7H-pyrrolo[2,3-d]pyrimidin-4-yl]amino]benzamide	1611774: Inhibition of human GRK5 using tubulin as substrate measured after 0 mins by [gamma-32P]-ATP assay	ic50	0.2200	uM
(3Z)-3-[[4-[(2-chloroacetyl)amino]-3,5-dimethyl-1H-pyrrol-2-yl]methylidene]-2-oxo-N-[(1R)-1-phenylethyl]-1H-indole-5-carboxamide	1744429: Inhibition of human GRK5 using porcine brain tubulin as substrate incubated for 3 to 5 mins by [gamma32P]ATP based radiometric assay	ic50	0.2200	uM
4-[4-fluoro-3-[[3-(methoxymethyl)-1,2,4-oxadiazol-5-yl]methylcarbamoyl]phenyl]-N-(1H-indazol-5-yl)-6-methyl-2-oxo-3,4-dihydro-1H-pyrimidine-5-carboxamide	1391756: Inhibition of GRK5 (unknown origin) preincubated for 10 mins followed by peptide substrate and ATP addition measured after 1 hr by TR-FRET assay	ic50	0.2600	uM
4-[3-[(3-ethoxy-1,2,4-oxadiazol-5-yl)methylcarbamoyl]-4-fluorophenyl]-N-(1H-indazol-5-yl)-6-methyl-2-oxo-3,4-dihydro-1H-pyrimidine-5-carboxamide	2000136: Inhibition of GRK5 (unknown origin)	ic50	0.2600	uM
(3Z)-3-[[4-[[(E)-2-cyano-4,4-dimethylpent-2-enoyl]amino]-3,5-dimethyl-1H-pyrrol-2-yl]methylidene]-2-oxo-N-[(1R)-1-phenylethyl]-1H-indole-5-carboxamide	1744429: Inhibition of human GRK5 using porcine brain tubulin as substrate incubated for 3 to 5 mins by [gamma32P]ATP based radiometric assay	ic50	0.2800	uM
2-[[2-[4-[[(E)-4-(dimethylamino)but-2-enoyl]amino]-2-methoxyanilino]-7H-pyrrolo[2,3-d]pyrimidin-4-yl]amino]benzamide	1611775: Inhibition of human GRK5 using tubulin as substrate measured after 30 mins by [gamma-32P]-ATP assay	ic50	0.3000	uM
(3Z)-3-[[4-[[(E)-4-(dimethylamino)but-2-enoyl]amino]-3,5-dimethyl-1H-pyrrol-2-yl]methylidene]-2-oxo-N-[(1R)-1-phenylethyl]-1H-indole-5-carboxamide	1744429: Inhibition of human GRK5 using porcine brain tubulin as substrate incubated for 3 to 5 mins by [gamma32P]ATP based radiometric assay	ic50	0.3600	uM
3-[6-amino-5-(7-pyridin-2-yl-1,3-benzoxazol-2-yl)-3-pyridinyl]-N-(2-morpholin-4-ylethyl)benzamide	1058426: Inhibition of GRK-5 (unknown origin) preincubated with enzyme for 10 mins before adding peptide substrate and ATP measured after 1 hr by LANCE-TR-FRET assay	ic50	0.3600	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	1391756: Inhibition of GRK5 (unknown origin) preincubated for 10 mins followed by peptide substrate and ATP addition measured after 1 hr by TR-FRET assay	ic50	0.3800	uM
(3Z)-3-[[4-[(2-chloroacetyl)amino]-3,5-dimethyl-1H-pyrrol-2-yl]methylidene]-2-oxo-N-[(1R)-1-pyridin-2-ylethyl]-1H-indole-5-carboxamide	1744429: Inhibition of human GRK5 using porcine brain tubulin as substrate incubated for 3 to 5 mins by [gamma32P]ATP based radiometric assay	ic50	0.4500	uM
2-[2-amino-5-(1-piperidin-4-ylpyrazol-4-yl)-3-pyridinyl]-7-(4-methoxyphenyl)-1,3-benzoxazol-6-ol	1058426: Inhibition of GRK-5 (unknown origin) preincubated with enzyme for 10 mins before adding peptide substrate and ATP measured after 1 hr by LANCE-TR-FRET assay	ic50	0.4500	uM
2-[2-amino-5-(1-piperidin-4-ylpyrazol-4-yl)-3-pyridinyl]-N-butyl-1,3-benzoxazol-5-amine	1058426: Inhibition of GRK-5 (unknown origin) preincubated with enzyme for 10 mins before adding peptide substrate and ATP measured after 1 hr by LANCE-TR-FRET assay	ic50	0.5000	uM
2-[2-amino-5-(1-piperidin-4-ylpyrazol-4-yl)-3-pyridinyl]-1,3-benzoxazol-5-amine	1058426: Inhibition of GRK-5 (unknown origin) preincubated with enzyme for 10 mins before adding peptide substrate and ATP measured after 1 hr by LANCE-TR-FRET assay	ic50	0.5200	uM
2-[2-amino-5-(1-piperidin-4-ylpyrazol-4-yl)-3-pyridinyl]-7-(1H-indazol-6-yl)-1,3-benzoxazol-6-ol	1058426: Inhibition of GRK-5 (unknown origin) preincubated with enzyme for 10 mins before adding peptide substrate and ATP measured after 1 hr by LANCE-TR-FRET assay	ic50	0.5300	uM
3-[2-[2-amino-5-(1-piperidin-4-ylpyrazol-4-yl)-3-pyridinyl]-1,3-benzoxazol-6-yl]-1-(4-methoxyphenyl)-1-phenylurea	1058426: Inhibition of GRK-5 (unknown origin) preincubated with enzyme for 10 mins before adding peptide substrate and ATP measured after 1 hr by LANCE-TR-FRET assay	ic50	0.5500	uM
N-[2-[2-amino-5-(1-piperidin-4-ylpyrazol-4-yl)-3-pyridinyl]-1,3-benzoxazol-6-yl]-4-fluorobenzamide	1058426: Inhibition of GRK-5 (unknown origin) preincubated with enzyme for 10 mins before adding peptide substrate and ATP measured after 1 hr by LANCE-TR-FRET assay	ic50	0.6400	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	affects expression, affects methylation, decreases expression	8
Valproic Acid	affects cotreatment, increases expression, affects expression, decreases expression	7
bisphenol A	increases expression, affects cotreatment, decreases methylation	3
Tetrachlorodibenzodioxin	increases expression	3
bisphenol S	affects cotreatment, increases methylation, increases expression	2
Arsenic	affects methylation, decreases methylation, increases abundance	2
Calcitriol	increases expression, affects cotreatment	2
Dexamethasone	increases expression, affects cotreatment	2
Tamoxifen	affects expression, affects cotreatment, increases expression	2
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	decreases expression	2
Aflatoxin B1	affects expression, decreases methylation	2
Raloxifene Hydrochloride	affects cotreatment, increases expression, affects expression	2
GSK-J4	increases expression	1
bisphenol F	affects cotreatment, increases expression	1
triphenyl phosphate	affects expression	1
pirinixic acid	affects binding, decreases expression, increases activity	1
methylselenic acid	increases expression	1
trichostatin A	increases expression	1
sodium arsenite	increases expression	1
cobaltous chloride	decreases expression	1
benzo(e)pyrene	increases methylation	1
aflatoxin B2	affects methylation	1
cadmium sulfate	increases expression	1
di-n-butylphosphoric acid	affects expression	1
seocalcitol	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	increases expression, affects cotreatment	1
dorsomorphin	affects cotreatment, increases expression	1
Resveratrol	affects cotreatment, increases expression	1
Temozolomide	decreases expression	1
Sunitinib	increases expression	1

ChEMBL screening assays

172 unique, capped per target: 171 binding, 1 functional

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1037597	Binding	Residual activity of GRK5 at 1 uM by microplate scintillation counting	Substituted 2-arylbenzothiazoles as kinase inhibitors: hit-to-lead optimization. — Bioorg Med Chem
CHEMBL1963789	Functional	PUBCHEM_BIOASSAY: Navigating the Kinome. (Class of assay: other) Panel member name: GPRK5	PubChem BioAssay data set

Cellosaurus cell lines

3 cell lines: 3 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_SQ54	HAP1 GRK5 (-) 1	Cancer cell line	Male
CVCL_SQ55	HAP1 GRK5 (-) 2	Cancer cell line	Male
CVCL_SQ56	HAP1 GRK5 (-) 3	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT04586348	PHASE4	UNKNOWN	Prenatal Iodine Supplementation and Early Childhood Neurodevelopment
NCT04873115	PHASE4	UNKNOWN	Double-blind, Placebo-controlled, Randomized Clinical Trial Comparing the Efficacy and Safety of Sialanar Plus orAl rehabiLitation Against Placebo Plus Oral Rehabilitation for chIldren and Adolescents With seVere Sialorrhoea and Neurodisabilties,
NCT02559102	PHASE3	COMPLETED	Dexmedetomidine Sedation Versus General Anaesthesia for Inguinal Hernia Surgery in Infants
NCT02757079	PHASE3	COMPLETED	Study of the Efficacy and Safety of NPC-15 for Sleep Disorders of Children With Neurodevelopmental Disorders
NCT06915480	PHASE3	RECRUITING	Reducing Missed Appointments
NCT07377032	PHASE3	RECRUITING	TAP-GRIN: Interventional Study on Patients With GRIN-related Neurodevelopmental Disorders
NCT02909959	PHASE2	COMPLETED	Sulforaphane for the Treatment of Young Men With Autism Spectrum Disorder
NCT06081348	PHASE2	RECRUITING	Sertraline vs. Placebo in the Treatment of Anxiety in Children and AdoLescents With NeurodevelopMental Disorders
NCT06352372	PHASE2	COMPLETED	Safety and Efficacy of tPBM for Epileptiform Activity in Autism
NCT00503191	PHASE1	COMPLETED	NeuroModulation Technique Treatment of Autism
NCT04475848	PHASE1	COMPLETED	A Study to Investigate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics and Food Effect of RO6953958 in Healthy Participants
NCT06300398	PHASE1	COMPLETED	IAMA-6 Oral Dose Study in Healthy Adults
NCT01783041	PHASE2/PHASE3	COMPLETED	Effect of Early L-Carnitine Supplementation on Neurodevelopmental Outcomes in Very Preterm Infants
NCT05767385	PHASE2/PHASE3	RECRUITING	Fetal Cerebrovascular Autoregulation in Congenital Heart Disease and Association With Neonatal Neurobehavior
NCT05675098	EARLY_PHASE1	NOT_YET_RECRUITING	Central Nervous System Stimulants and Physical Function in Children With Cerebral Palsy
NCT00783783	Not specified	COMPLETED	CYP2D6 Pharmacogenetics in Risperidone-Treated Children
NCT01778504	Not specified	RECRUITING	Studying Childhood-onset Behavioral, Psychiatric, and Developmental Disorders
NCT01850784	Not specified	UNKNOWN	High Energy Formula Feeding in Infants With Congenital Heart Disease
NCT01922791	Not specified	COMPLETED	Nutrition and Pregnancy Intervention Study
NCT01942525	Not specified	UNKNOWN	Influence of Intrauterine Growth Restriction on Amplitude-integrated EEG in Preterm Infants
NCT02003170	Not specified	COMPLETED	Etiology and Early Diagnosis of Neurodevelopmental Disorders
NCT02118649	Not specified	ACTIVE_NOT_RECRUITING	Enhancing Behavior and Brain Response to Visual Targets Using a Computer Game
NCT02557191	Not specified	TERMINATED	Biomarkers, Neurodevelopment and Preterm Infants
NCT02690675	Not specified	COMPLETED	Iron Supplement Effect on Child Development
NCT02694003	Not specified	COMPLETED	Better Nights, Better Days for Children With Neurodevelopment Disorders
NCT02792894	Not specified	COMPLETED	Family Networks (FaNs) for Children With Developmental Disorders and Delays
NCT02871674	Not specified	UNKNOWN	Good Night Project: Behavioural Sleep Interventions for Children With ADHD: A Randomised Controlled Trial
NCT02887157	Not specified	COMPLETED	Analyzing Retinal Microanatomy in ROP
NCT02898298	Not specified	COMPLETED	Positive Emotion Regulation Training in Children, Adolescents and Young Adults With and Without Developmental Disorder
NCT02912780	Not specified	UNKNOWN	Introduction of Microsystems in a Level 3 Neonatal Intensive Care Unit
NCT03023293	Not specified	COMPLETED	n-3 PUFAs, Irisin and Maternal Glucose Metabolism From Pregnancy to Postpartum
NCT03023644	Not specified	COMPLETED	Improving Neurodevelopmental Outcomes in Children With Congenital Heart Disease: An Intervention Study
NCT03032991	Not specified	UNKNOWN	Early Biomarkers of Neurodevelopment in Offspring of Diabetic Mothers
NCT03088189	Not specified	TERMINATED	Effect of Parental Peri-conceptional Vitamin B12 Supplementation on Infant Neurocognitive Development in Offspring
NCT03096028	Not specified	COMPLETED	Developmental Origins of Mental Health Disorders
NCT03148782	Not specified	COMPLETED	Brain Plasticity Underlying Acquisition of New Organizational Skills in Children-R61 Phase
NCT03172104	Not specified	COMPLETED	Neurobehavioural Development of Infants Born <30 Weeks Gestational Age Between Birth and Five Years of Age
NCT03222375	Not specified	RECRUITING	SQUED™ Series 28.1 Home-use and Treatment of Autowave Reverberator of Autism
NCT03229928	Not specified	COMPLETED	Clinical Testing of a Real-Time Behavior Measurement Tool: Measuring Outcomes for CHAnge
NCT03232489	Not specified	UNKNOWN	Study for the Evaluation of the Feasibility of Applying Advanced MRI Scanning in Pediatric Clinical Practice