PRKG1

Summary

PRKG1 (protein kinase cGMP-dependent 1, HGNC:9414) is a protein-coding gene on chromosome 10q11.23-q21.1, encoding cGMP-dependent protein kinase 1 (Q13976). Serine/threonine protein kinase that acts as a key mediator of the nitric oxide (NO)/cGMP signaling pathway.

Mammals have three different isoforms of cyclic GMP-dependent protein kinase (Ialpha, Ibeta, and II). These PRKG isoforms act as key mediators of the nitric oxide/cGMP signaling pathway and are important components of many signal transduction processes in diverse cell types. This PRKG1 gene on human chromosome 10 encodes the soluble Ialpha and Ibeta isoforms of PRKG by alternative transcript splicing. A separate gene on human chromosome 4, PRKG2, encodes the membrane-bound PRKG isoform II. The PRKG1 proteins play a central role in regulating cardiovascular and neuronal functions in addition to relaxing smooth muscle tone, preventing platelet aggregation, and modulating cell growth. This gene is most strongly expressed in all types of smooth muscle, platelets, cerebellar Purkinje cells, hippocampal neurons, and the lateral amygdala. Isoforms Ialpha and Ibeta have identical cGMP-binding and catalytic domains but differ in their leucine/isoleucine zipper and autoinhibitory sequences and therefore differ in their dimerization substrates and kinase enzyme activity.

Source: NCBI Gene 5592 — RefSeq curated summary.

At a glance

• Gene–disease (curated): familial thoracic aortic aneurysm and aortic dissection (Strong, ClinGen) — +1 more curated relationship
• GWAS associations: 32
• Clinical variants (ClinVar): 992 total — 1 pathogenic
• Phenotypes (HPO): 46
• Druggable target: yes — 15 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_006258

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:9414
Approved symbol	PRKG1
Name	protein kinase cGMP-dependent 1
Location	10q11.23-q21.1
Locus type	gene with protein product
Status	Approved
Aliases	PGK, PKG, PKG1
Ensembl gene	ENSG00000185532
Ensembl biotype	protein_coding
OMIM	176894
Entrez	5592

Gene structure

Transcript identifiers

Ensembl transcripts: 10 — 7 protein_coding, 3 protein_coding_CDS_not_defined

ENST00000373975, ENST00000373976, ENST00000373980, ENST00000401604, ENST00000643582, ENST00000643704, ENST00000645324, ENST00000645790, ENST00000646354, ENST00000672084

RefSeq mRNA: 4 — MANE Select: NM_006258 NM_001098512, NM_001374781, NM_001374782, NM_006258

CCDS: CCDS44399, CCDS7244, CCDS91244

Canonical transcript exons

ENST00000373980 — 18 exons

Exon	Start	End
ENSE00001290472	51153164	51153330
ENSE00001295696	51907507	51907570
ENSE00001300564	52288726	52288848
ENSE00001303642	52290224	52290290
ENSE00001311075	51467723	51467836
ENSE00001313981	52272392	52272481
ENSE00001317306	52280789	52280930
ENSE00001319764	51804585	51804690
ENSE00001321548	52288931	52288993
ENSE00001323221	52282153	52282316
ENSE00003230415	52271350	52271489
ENSE00003404591	52133840	52133905
ENSE00003404951	52161889	52161963
ENSE00003429550	52251570	52251666
ENSE00003487488	52054484	52054561
ENSE00003602134	52062537	52062631
ENSE00003848848	51074487	51074901
ENSE00003900047	52293802	52298350

Expression profiles

Bgee: expression breadth ubiquitous, 247 present calls, max score 97.78.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 7.8201 / max 148.0816, expressed in 1063 samples.

FANTOM5 promoters (11 alternative TSS)

Promoter ID	TPM avg	Samples expressed
104924	2.7539	808
104916	1.6398	605
104921	1.1113	573
104918	1.0982	527
104920	0.4206	248
104919	0.3547	182
104923	0.2452	129
104925	0.1292	51
104917	0.0343	12
104932	0.0264	10

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
saphenous vein	UBERON:0007318	97.78	gold quality
biceps brachii	UBERON:0001507	95.92	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	94.98	gold quality
descending thoracic aorta	UBERON:0002345	94.79	gold quality
thoracic aorta	UBERON:0001515	94.46	gold quality
ascending aorta	UBERON:0001496	94.42	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	94.39	gold quality
aorta	UBERON:0000947	93.52	gold quality
right coronary artery	UBERON:0001625	93.00	gold quality
urethra	UBERON:0000057	92.80	gold quality
popliteal artery	UBERON:0002250	92.80	gold quality
tibial artery	UBERON:0007610	92.78	gold quality
superficial temporal artery	UBERON:0001614	91.86	gold quality
colonic epithelium	UBERON:0000397	91.81	gold quality
heart right ventricle	UBERON:0002080	91.78	gold quality
cauda epididymis	UBERON:0004360	91.75	gold quality
coronary artery	UBERON:0001621	91.45	gold quality
left coronary artery	UBERON:0001626	91.23	gold quality
vena cava	UBERON:0004087	90.81	gold quality
calcaneal tendon	UBERON:0003701	90.80	gold quality
body of tongue	UBERON:0011876	88.75	gold quality
hindlimb stylopod muscle	UBERON:0004252	88.47	gold quality
muscle of leg	UBERON:0001383	87.95	gold quality
gastrocnemius	UBERON:0001388	87.81	gold quality
tibia	UBERON:0000979	86.61	gold quality
tendon	UBERON:0000043	86.37	gold quality
buccal mucosa cell	CL:0002336	86.28	silver quality
lower lobe of lung	UBERON:0008949	86.22	gold quality
muscle organ	UBERON:0001630	86.03	gold quality
visceral pleura	UBERON:0002401	85.62	gold quality

Single-cell (SCXA)

Detected in 9 experiment(s), a significant marker in 9.

Experiment	Marker?	Max mean expression
E-MTAB-11268	yes	10993.37
E-GEOD-131882	yes	7104.70
E-ANND-2	yes	6848.37
E-CURD-119	yes	6619.64
E-GEOD-180759	yes	3024.28
E-HCAD-35	yes	87.55
E-GEOD-135922	yes	24.58
E-HCAD-25	yes	9.20
E-ANND-3	yes	8.38

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): ESR1, FOXN1, FOXO1, HIF1A, JUN, NFKB, SP1, SP3, TP53, USF1, USF2

miRNA regulators (miRDB)

323 targeting PRKG1, 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-656-3P	100.00	72.15	2788
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-200B-3P	100.00	73.31	2693
HSA-MIR-200C-3P	100.00	73.35	2685
HSA-MIR-429	100.00	73.44	2698
HSA-MIR-513A-5P	100.00	69.77	2465
HSA-MIR-29A-3P	100.00	73.11	1835
HSA-MIR-29B-3P	100.00	73.18	1833
HSA-MIR-29C-3P	100.00	73.15	1833
HSA-MIR-196A-5P	100.00	68.16	684
HSA-MIR-196B-5P	100.00	68.16	681
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-4262	100.00	73.26	3931
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-6873-3P	100.00	71.42	2626
HSA-MIR-432-3P	100.00	67.86	705
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-181D-5P	99.99	73.04	2997
HSA-MIR-4531	99.99	69.70	3181
HSA-MIR-181A-5P	99.99	72.96	2995
HSA-MIR-181B-5P	99.99	72.97	2996
HSA-MIR-181C-5P	99.99	72.95	2996
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-103A-3P	99.98	69.14	1595
HSA-MIR-107	99.98	69.14	1595
HSA-MIR-548P	99.98	72.25	3784
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-12136	99.98	72.81	5713

Literature-anchored findings (GeneRIF, showing 40)

• Sp1 binding activity on the PKG-Ialpha promoter was detected … and this binding was inhibited by NO and cyclic nucleotides; PKG-Ialpha gene expression is driven by an Sp1 transcription mechanism (PMID:11884369)
• G-kinase I beta interacted specifically with TFII-I, an unusual transcriptional regulator that associates with multiple proteins to modulate both basal and signal-induced transcription (PMID:12082086)
• inhibits serum-response element-dependent transcription by inhibiting rho activation and functions (PMID:12119292)
• PKG appears to be solicited for P-selectin expression when cAMP levels are elevated which suggest a cAMP/PKG-dependent pathway of platelet activation. (PMID:12574812)
• PKG was found to be a target for phorbol 12-myristate 13-acetate (PMA)-responsive protein kinase C (PKC) (PMID:12609995)
• NPRA-PKG association may have a role in compartmentation of cGMP-mediated signaling and regulation of receptor sensitivity (PMID:12855709)
• dimerization of cGMP-dependent protein kinase Ibeta is mediated by an extensive amino-terminal leucine zipper motif, and dimerization modulates enzyme function (PMID:12933804)
• G-kinase regulates vasodilator-stimulated phosphoprotein activity (PMID:14679200)
• cyclic GMP-dependent protein kinase I binds to FHOD1 in vascular smooth muscle cells (PMID:15051728)
• PKG has a role in platelet secretion (PMID:15280395)
• CD38 is stimulated by sequential activation of IL8 receptor, IP(3)-mediated Ca(2+) rise, and cGMP/protein kinase G and plays an essential role in IL8-induced migration of LAK cells (PMID:15556942)
• Rap 1-GTP levels in platelets were reduced by NO-donors and activators of NO-sensitive soluble guanylyl cyclase (PMID:15711749)
• high-resolution structure of the coiled-coil domain of cGMP-dependent protein kinase Ialpha (PMID:16131665)
• cGMP-dependent protein kinase Ibeta binds to TFII-I and IRAG through a common interaction motif (PMID:16166082)
• Nitric oxide affects dendritic cell migration through the activation of cGMP kinase. (PMID:16249377)
• Data suggest an important role of PKG in the PMA-induced inhibition of TRPC channels in native endothelial cells. (PMID:16331690)
• regulatory domains of cGMP-dependent protein kinase Ialpha and Ibeta retain dimerization and native cGMP-binding properties and undergo isoform-specific conformational changes (PMID:16407222)
• cGMP-dependent protein kinase expression is regulated by Rho and Kruppel-like transcription factor-4 (PMID:16632465)
• PKGI interacts with tripartite motif (TRIM) protein TRIM39R. TRIM proteins, through diverse molecular pathways, are often observed to regulate important aspects of cellular homeostasis. (PMID:17601797)
• the leucine-zipper motif of PKG binds to that of MYPT1 to form a heterodimer; when the leucine-zipper motif of MYPT1 is absent, the PKG leucine-zipper motif binds to the coiled coil region and upstream segments of MYPT1 via formation of a heterotetramer (PMID:17904578)
• Presence of cGKI alpha and beta provides further evidence for a significant role of these enzymes in the control of smooth muscle function in human penile erectile tissue. (PMID:18194177)
• Activation of protein kinase G Increases the expression of p21CIP1, p27KIP1, and histidine triad protein 1 through Sp1. (PMID:18593937)
• These results strongly suggest that TRPC6 channels can be negatively regulated by the nitric oxide-cyclic GMP-protein kinase G pathway, probably via T69 phosphorylation of the N-terminal. (PMID:18617565)
• PDE5 inhibition can differentially impact selected cellular functions of platelets, and perhaps of other cell types (PMID:18757735)
• analysis of the interaction between the coiled coil leucine zipper of cGMP-dependent protein kinase Ialpha and the C terminus of the myosin binding subunit of the myosin light chain phosphatase (PMID:18782776)
• IFN-gamma exerted a delayed suppressive effect on K(+) channels by enhancing iNOS expression and an acute stimulatory effect, which was independent of either NO pathways or phosphorylation mediated by PKA, PKG, and PI3K in renal proximal tubule cells. (PMID:18945831)
• resulting in a dose- and time-dependent increase in phospho-VASP (PMID:18983522)
• PKG phosphorylates the N2-B and N2-A domains of titin. (PMID:19023132)
• cGKI has a dual function in BMP signalling: (1) it modulates BMP receptor/Smad activity at the plasma membrane and (2) after redistribution to the nucleus, it further regulates transcription as a nuclear co-factor for Smads. (PMID:19424179)
• loss of caveolin-1 leads to hyperactive eNOS and subsequent tyrosine nitration-dependent impairment of PKG activity, which results in pulmonary hypertension. (PMID:19487814)
• These findings provide evidence of a physical and compartmentalized association between SERT and PKGIalpha that supports. (PMID:19656393)
• PDE5-inhibition blocks TRPC6 channel activation and associated Cn/NFAT activation signaling by PKG-dependent channel phosphorylation (PMID:19961855)
• Data show that SS increased intracellular cGMP levels and activated protein kinase G, and selectively inhibited PDE5 in breast tumor cells. (PMID:19996273)
• PKG-Ialpha directly phosphorylates Bad at ser155, which may participate anti-apoptotic/cytoprotective effects in neural cells (PMID:20043968)
• Stduies indicate that cGMP-dependent protein kinase I modulates the RhoA-ROCK pathway and insulin receptor signaling to elicit BAT differentiation and stimulate thermogenesis. (PMID:20068229)
• PKG inhibits TCF signaling in colon cancer cells by blocking beta-catenin expression and activating FOXO4. (PMID:20348951)
• The data suggest an important role of Src/PKG-Ialpha interaction in promoting DNA synthesis/cell proliferation in human ovarian cancer cells. (PMID:20371672)
• disruption of the IP3R1-IRAG calcium regulation system is a novel cause of dysfunctional osteoclasts unrelated to defects in attachment proteins or acid secretion (PMID:20567233)
• iNOS acts as a molecular switch for the heterogeneous effects of microgravity on macrovascular, endocardial and microvascular endothelial cells via the cyclic guanosine monophosphate (cGMP)-PKG dependent pathway. (PMID:20600009)
• structure provides molecular details of this unique leucine/isoleucine zipper, revealing specific hydrophobic and ionic interactions that mediate dimerization and demonstrating the topology of the GKAP interaction surface. (PMID:20826808)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	prkg1b	ENSDARG00000031702
mus_musculus	Prkg1	ENSMUSG00000052920
rattus_norvegicus	Prkg1	ENSRNOG00000053728
drosophila_melanogaster	Pka-C2	FBGN0000274
drosophila_melanogaster	CG12069	FBGN0039796

Paralogs (5): PRKACA (ENSG00000072062), PRKG2 (ENSG00000138669), PRKACB (ENSG00000142875), PRKACG (ENSG00000165059), PRKX (ENSG00000183943)

Protein

Protein identifiers

cGMP-dependent protein kinase 1 — Q13976 (reviewed: Q13976)

Alternative names: cGMP-dependent protein kinase I

All UniProt accessions (6): Q13976, A0A2R8Y507, A0A2R8YE50, A0A2R8YH74, A0A5F9ZGW0, B1ALS0

UniProt curated annotations — full annotation on UniProt →

Function. Serine/threonine protein kinase that acts as a key mediator of the nitric oxide (NO)/cGMP signaling pathway. GMP binding activates PRKG1, which phosphorylates serines and threonines on many cellular proteins. Numerous protein targets for PRKG1 phosphorylation are implicated in modulating cellular calcium, but the contribution of each of these targets may vary substantially among cell types. Proteins that are phosphorylated by PRKG1 regulate platelet activation and adhesion, smooth muscle contraction, cardiac function, gene expression, feedback of the NO-signaling pathway, and other processes involved in several aspects of the CNS like axon guidance, hippocampal and cerebellar learning, circadian rhythm and nociception. Smooth muscle relaxation is mediated through lowering of intracellular free calcium, by desensitization of contractile proteins to calcium, and by decrease in the contractile state of smooth muscle or in platelet activation. Regulates intracellular calcium levels via several pathways: phosphorylates IRAG1 and inhibits IP3-induced Ca(2+) release from intracellular stores, phosphorylation of KCNMA1 (BKCa) channels decreases intracellular Ca(2+) levels, which leads to increased opening of this channel. PRKG1 phosphorylates the canonical transient receptor potential channel (TRPC) family which inactivates the associated inward calcium current. Another mode of action of NO/cGMP/PKGI signaling involves PKGI-mediated inactivation of the Ras homolog gene family member A (RhoA). Phosphorylation of RHOA by PRKG1 blocks the action of this protein in myriad processes: regulation of RHOA translocation; decreasing contraction; controlling vesicle trafficking, reduction of myosin light chain phosphorylation resulting in vasorelaxation. Activation of PRKG1 by NO signaling also alters gene expression in a number of tissues. In smooth muscle cells, increased cGMP and PRKG1 activity influence expression of smooth muscle-specific contractile proteins, levels of proteins in the NO/cGMP signaling pathway, down-regulation of the matrix proteins osteopontin and thrombospondin-1 to limit smooth muscle cell migration and phenotype. Regulates vasodilator-stimulated phosphoprotein (VASP) functions in platelets and smooth muscle.

Subunit / interactions. Isoform alpha: parallel homodimer or heterodimer and also heterotetramer. Interacts directly with PPP1R12A. Non-covalent dimer of dimer of PRKG1-PRKG1 and PPP1R12A-PPP1R12A. This interaction targets PRKG1 to stress fibers to mediate smooth muscle cell relaxation and vasodilation in responses to rises in cGMP. Isoform beta: antiparallel homodimer. Part of cGMP kinase signaling complex at least composed of ACTA2/alpha-actin, CNN1/calponin H1, PLN/phospholamban, PRKG1 and ITPR1. Interacts with IRAG1. Forms a stable complex with ITPR1, IRAG1, and isoform beta of PRKG1. Interacts with TRPC7 (via ankyrin repeat domain). Isoform alpha interacts with RGS2. Interacts with GTF2I.

Subcellular location. Cytoplasm.

Tissue specificity. Primarily expressed in lung and placenta.

Post-translational modifications. Autophosphorylation increases kinase activity. 65 kDa monomer is produced by proteolytic cleavage.

Disease relevance. Aortic aneurysm, familial thoracic 8 (AAT8) [MIM:615436] A disease characterized by permanent dilation of the thoracic aorta usually due to degenerative changes in the aortic wall. It is primarily associated with a characteristic histologic appearance known as ‘medial necrosis’ or ‘Erdheim cystic medial necrosis’ in which there is degeneration and fragmentation of elastic fibers, loss of smooth muscle cells, and an accumulation of basophilic ground substance. The disease is caused by variants affecting the gene represented in this entry.

Activity regulation. In the absence of cGMP, PRKG1 activity is suppressed by autoinhibitory contacts.

Domain organisation. Composed of an N-terminal leucine-zipper domain followed by an autoinhibitory domain, which mediate homodimer formation and inhibit kinase activity, respectively. Next, two cGMP-binding domains are followed by the catalytic domain at the C-terminus. Binding of cGMP to cGMP-binding domains results in a conformational change that activates kinase activity by removing the autoinhibitory domain from the catalytic cleft leaving the catalytic domain free to phosphorylate downstream substrates. Isoforms alpha and beta have identical cGMP-binding and catalytic domains but differ in their leucine zipper and autoinhibitory sequences and therefore differ in their dimerization substrates and kinase enzyme activity. Heterotetramerization is mediated by the interaction between a coiled-coil of PRKG1 and the leucine/isoleucine zipper of PPP1R12A/MBS, the myosin-binding subunit of the myosin phosphatase.

Miscellaneous. The 3D structures in complex with cGMP and cAMP describe the hydrogen bonding interactions that modulate high selectivity for cGMP in the CNB-B domain, and reveal that all these contacts are disrupted in the structure with cAMP, explaining the low affinity of the enzyme for cAMP and the fact that cAMP can only weakly activate PKG.

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

Isoforms (3)

UniProt ID	Names	Canonical?
Q13976-1	Alpha, CGK1-alpha	yes
Q13976-2	Beta, CGK1-beta
Q13976-3	3

RefSeq proteins (4): NP_001091982, NP_001361710, NP_001361711, NP_006249* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000595	cNMP-bd_dom	Domain
IPR000719	Prot_kinase_dom	Domain
IPR000961	AGC-kinase_C	Domain
IPR002374	cGMP_dep_kinase	Family
IPR008271	Ser/Thr_kinase_AS	Active_site
IPR011009	Kinase-like_dom_sf	Homologous_superfamily
IPR014710	RmlC-like_jellyroll	Homologous_superfamily
IPR017441	Protein_kinase_ATP_BS	Binding_site
IPR018488	cNMP-bd_CS	Conserved_site
IPR018490	cNMP-bd_dom_sf	Homologous_superfamily
IPR031831	PKcGMP_CC	Domain
IPR035014	STKc_cGK	Domain

Pfam: PF00027, PF00069, PF16808

Enzyme classification (BRENDA):

• EC 2.7.11.12 — cGMP-dependent protein kinase (BRENDA: 30 organisms, 165 substrates, 115 inhibitors, 20 Km, 0 kcat entries)

Substrate kinetics (BRENDA)

11 substrates with measured Km, best-characterized 11. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
ATP	0.0104–0.0139	3
RKRSRAE	0.0263–0.0313	3
GRTGRRNSI	0.062	1
HUMAN SEROTONIN TRANSPORTER	0.0002	1
HUMAN SEROTONIN TRANSPORTER I425V	0.0003	1
HUMAN SEROTONIN TRANSPORTER T267A	0.0002	1
HUMAN SEROTONIN TRANSPORTER T267A/I425V	0.0001	1
HUMAN SEROTONIN TRANSPORTER T267D	0.0001	1
HUMAN SEROTONIN TRANSPORTER T267D/I425V	0.0001	1
HUMAN SEROTONIN TRANSPORTER T267E	0.0001	1
SEPTIN 3 PEPTIDE 86-98	0.0865	1

Catalyzed reactions (Rhea), 2 shown:

• L-seryl-[protein] + ATP = O-phospho-L-seryl-[protein] + ADP + H(+) (RHEA:17989)
• L-threonyl-[protein] + ATP = O-phospho-L-threonyl-[protein] + ADP + H(+) (RHEA:46608)

UniProt features (106 total): helix 29, strand 25, binding site 13, mutagenesis site 9, region of interest 6, turn 5, sequence variant 5, modified residue 3, splice variant 3, domain 2, initiator methionine 1, chain 1, coiled-coil region 1, compositionally biased region 1, active site 1, disulfide bond 1

Structure

Experimental structures (PDB)

26 structures.

PDB	Method	Resolution (Å)
7MBJ	X-RAY DIFFRACTION	1.26
5L0N	X-RAY DIFFRACTION	1.28
4QX5	X-RAY DIFFRACTION	1.32
7SSB	X-RAY DIFFRACTION	1.4
5JAX	X-RAY DIFFRACTION	1.49
5J48	X-RAY DIFFRACTION	1.49
4KU7	X-RAY DIFFRACTION	1.65
5JD7	X-RAY DIFFRACTION	1.75
6BG2	X-RAY DIFFRACTION	1.83
4R4M	X-RAY DIFFRACTION	1.92
6BDL	X-RAY DIFFRACTION	1.96
6C0T	X-RAY DIFFRACTION	1.98
7T4U	X-RAY DIFFRACTION	1.99
4KU8	X-RAY DIFFRACTION	1.99
7T4T	X-RAY DIFFRACTION	2.08
4QXK	X-RAY DIFFRACTION, NEUTRON DIFFRACTION	2.2
7T4W	X-RAY DIFFRACTION	2.23
4R4L	X-RAY DIFFRACTION	2.25
3NMD	X-RAY DIFFRACTION	2.27
7T4V	X-RAY DIFFRACTION	2.28
7LV3	X-RAY DIFFRACTION	2.41
3OCP	X-RAY DIFFRACTION	2.49
4Z07	X-RAY DIFFRACTION	2.5
3OGJ	X-RAY DIFFRACTION	2.75
3OD0	X-RAY DIFFRACTION	2.9
1ZXA	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q13976-F1	86.87	0.55

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): 484 (proton acceptor)

Ligand- & substrate-binding residues (13): 167–170; 167–170; 177–178; 177–178; 282; 291–294; 291–294; 301–302; 301–302; 336; 336; 366–374 …

Post-translational modifications (3): 2, 59, 515

Disulfide bonds (1): 43

Mutagenesis-validated functional residues (9):

Position	Phenotype
12	loss of binding to ppp1r12a.
19	loss of binding to ppp1r12a.
26	loss of binding to ppp1r12a.
33	loss of binding to ppp1r12a.
40	loss of binding to ppp1r12a.
281	reduces cgmp binding affinity.
282	reduces cgmp binding affinity.
302	reduces cgmp binding affinity.
336	reduces cgmp binding affinity.

Function

Pathways and Gene Ontology

Reactome pathways

7 pathways

ID	Pathway
R-HSA-4086398	Ca2+ pathway
R-HSA-392517	Rap1 signalling
R-HSA-418457	cGMP effects
R-HSA-9918432	Maturation of DENV proteins
R-HSA-162582	Signal Transduction
R-HSA-195721	Signaling by WNT
R-HSA-3858494	Beta-catenin independent WNT signaling

MSigDB gene sets: 453 (showing top): GOBP_DENDRITE_DEVELOPMENT, GOBP_REGULATION_OF_CELL_ACTIVATION, BENPORATH_ES_WITH_H3K27ME3, GOBP_NEGATIVE_REGULATION_OF_SMOOTH_MUSCLE_CELL_PROLIFERATION, GOBP_REGULATION_OF_WOUND_HEALING, GOBP_CIRCULATORY_SYSTEM_PROCESS, REACTOME_ADAPTIVE_IMMUNE_SYSTEM, GOBP_SKELETAL_SYSTEM_DEVELOPMENT, GOBP_REGULATION_OF_COAGULATION, GOBP_NEGATIVE_REGULATION_OF_MUSCLE_CONTRACTION, GOBP_NEGATIVE_REGULATION_OF_PLATELET_ACTIVATION, GOBP_PLATELET_ACTIVATION, GOBP_GROWTH, GOBP_REGULATION_OF_SMOOTH_MUSCLE_CONTRACTION, GOBP_NEGATIVE_REGULATION_OF_CELL_CELL_ADHESION

GO Biological Process (27): neuron migration (GO:0001764), signal transduction (GO:0007165), positive regulation of cytosolic calcium ion concentration (GO:0007204), spermatid development (GO:0007286), negative regulation of inositol phosphate biosynthetic process (GO:0010920), negative regulation of glutamate secretion (GO:0014050), dendrite development (GO:0016358), obsolete cGMP-mediated signaling (GO:0019934), cerebellum development (GO:0021549), forebrain development (GO:0030900), positive regulation of circadian rhythm (GO:0042753), regulation of vascular permeability (GO:0043114), collateral sprouting (GO:0048668), relaxation of vascular associated smooth muscle (GO:0060087), cell growth involved in cardiac muscle cell development (GO:0061049), negative regulation of platelet aggregation (GO:0090331), bone growth (GO:0098868), negative regulation of vascular associated smooth muscle cell proliferation (GO:1904706), negative regulation of vascular associated smooth muscle cell migration (GO:1904753), regulation of testosterone biosynthetic process (GO:2000224), protein phosphorylation (GO:0006468), heart development (GO:0007507), negative regulation of smooth muscle cell migration (GO:0014912), actin cytoskeleton organization (GO:0030036), vasodilation (GO:0042311), regulation of GTPase activity (GO:0043087), negative regulation of smooth muscle contraction (GO:0045986)

GO Molecular Function (14): protein kinase activity (GO:0004672), cGMP-dependent protein kinase activity (GO:0004692), calcium channel regulator activity (GO:0005246), ATP binding (GO:0005524), cGMP binding (GO:0030553), identical protein binding (GO:0042802), mitogen-activated protein kinase p38 binding (GO:0048273), protein serine kinase activity (GO:0106310), nucleotide binding (GO:0000166), catalytic activity (GO:0003824), protein serine/threonine kinase activity (GO:0004674), protein binding (GO:0005515), kinase activity (GO:0016301), transferase activity (GO:0016740)

GO Cellular Component (7): acrosomal vesicle (GO:0001669), nucleoplasm (GO:0005654), cytoplasm (GO:0005737), Golgi apparatus (GO:0005794), cytosol (GO:0005829), plasma membrane (GO:0005886), sarcolemma (GO:0042383)

Reactome top-level categories

Rollup of top-6 pathways:

Category	Pathways
Beta-catenin independent WNT signaling	1
Adaptive Immune System	1
Nitric oxide stimulates guanylate cyclase	1
Dengue Virus Genome Translation and Replication	1
Signal Transduction	1
Signaling by WNT	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
anatomical structure development	3
cellular anatomical structure	3
regulation of biological quality	2
developmental cell growth	2
protein kinase activity	2
cytoplasm	2
cell migration	1
generation of neurons	1
cell communication	1
cellular process	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
germ cell development	1
spermatid differentiation	1
negative regulation of phosphorus metabolic process	1
regulation of inositol phosphate biosynthetic process	1
inositol phosphate biosynthetic process	1
negative regulation of carbohydrate metabolic process	1
negative regulation of alcohol biosynthetic process	1
glutamate secretion	1
regulation of glutamate secretion	1
negative regulation of organic acid transport	1
negative regulation of amino acid transport	1
negative regulation of secretion by cell	1
neuron projection development	1
metencephalon development	1
brain development	1
circadian rhythm	1
regulation of circadian rhythm	1
positive regulation of biological process	1
vascular process in circulatory system	1
blood circulation	1
axonogenesis	1
developmental growth involved in morphogenesis	1
vasodilation	1
relaxation of smooth muscle	1
negative regulation of smooth muscle contraction	1
physiological cardiac muscle hypertrophy	1
cardiac muscle cell development	1

Protein interactions and networks

STRING

0 interactions, top by confidence (×1000):

IntAct

40 interactions, top by confidence:

A	B	Type	Score
PSMC5	PSMD11	psi-mi:“MI:0914”(association)	0.730
PRKG1	LMO2	psi-mi:“MI:0915”(physical association)	0.670
ZNF646	PRKG1	psi-mi:“MI:0915”(physical association)	0.670
FAM124A	PRKG1	psi-mi:“MI:0915”(physical association)	0.670
LMO2	PRKG1	psi-mi:“MI:0915”(physical association)	0.670
PRKG1	ZNF646	psi-mi:“MI:0915”(physical association)	0.670
PRKG1	FAM124A	psi-mi:“MI:0915”(physical association)	0.670
DDX31	IGLL5	psi-mi:“MI:0914”(association)	0.530
BMPR2	PRKG1	psi-mi:“MI:0915”(physical association)	0.520
PRKG1	BMPR2	psi-mi:“MI:0915”(physical association)	0.520
PRKG1	Gkap1	psi-mi:“MI:0915”(physical association)	0.510
Gkap1	PRKG1	psi-mi:“MI:0915”(physical association)	0.510
PRKG1	PDE5A	psi-mi:“MI:0914”(association)	0.500
PDE5A	PRKG1	psi-mi:“MI:0914”(association)	0.500
PDE5A	PRKG1	psi-mi:“MI:0915”(physical association)	0.500
	PRKG1	psi-mi:“MI:0915”(physical association)	0.400
SMAD4	PRKG1	psi-mi:“MI:0915”(physical association)	0.400
ITPR1	PDE5A	psi-mi:“MI:0914”(association)	0.350
PRKG1	ACACB	psi-mi:“MI:0914”(association)	0.350
TNIK	STRN	psi-mi:“MI:0914”(association)	0.350
GAGE1	UBB	psi-mi:“MI:0914”(association)	0.350
PRKG1	ZKSCAN1	psi-mi:“MI:0914”(association)	0.350
CORO2B	SHC1	psi-mi:“MI:0914”(association)	0.350

BioGRID (70): PRKG1 (Two-hybrid), ZNF646 (Two-hybrid), FAM124A (Two-hybrid), WDR77 (Reconstituted Complex), WDR77 (Affinity Capture-Western), PRKG1 (Affinity Capture-Western), WDR77 (Biochemical Activity), AR (Biochemical Activity), PTK2 (Affinity Capture-MS), ZKSCAN1 (Affinity Capture-MS), PRKG1 (Affinity Capture-MS), PRKG1 (Affinity Capture-MS), PRKG1 (Affinity Capture-MS), PRKG1 (Reconstituted Complex), PRKG1 (Affinity Capture-Western)

ESM2 similar proteins: A0A1L8EV45, C9WPN6, F1QGW6, F6RQL9, O73723, O77676, P00516, P0C605, P20461, P23258, P23330, P31321, P32392, P35250, P41091, P53033, P61157, P61158, P62482, P62483, P81795, P83887, P83888, Q05B83, Q0VCD2, Q13126, Q13303, Q13976, Q27955, Q2KHU8, Q2KJ81, Q2VIR3, Q32KM1, Q4V7C7, Q5R797, Q5R8R1, Q5ZHS1, Q5ZMS3, Q641P0, Q641W4

Diamond homologs: A0A509AKL0, A1A4I4, A5K0N4, A7MBL8, A8XJQ6, A8XNJ6, A8XW88, F4HYG2, G1X456, J9W0G9, O42632, O43930, O77676, P00516, P00517, P04409, P05131, P05132, P05383, P05696, P05986, P06244, P06245, P0C605, P10102, P10665, P10666, P11792, P12370, P12688, P16911, P16912, P17252, P17612, P18652, P18654, P18961, P20444, P21137, P22612

SIGNOR signaling

57 interactions.

A	Effect	B	Mechanism
PRKG1	unknown	VASP	phosphorylation
PRKG1	down-regulates	TRPC3	phosphorylation
PRKG1	up-regulates	FHOD1	phosphorylation
PRKG1	down-regulates	HRH1	phosphorylation
PRKG1	“up-regulates activity”	TNNI3	phosphorylation
PRKG1	up-regulates	SLC6A4	phosphorylation
PRKG1	up-regulates	CFTR	phosphorylation
PRKG1	down-regulates	HSPB1	phosphorylation
PRKG1	up-regulates	PPP1R17	phosphorylation
PRKG1	“down-regulates activity”	ENAH	phosphorylation
PRKG1	“down-regulates activity”	VASP	phosphorylation
PRKG1	“down-regulates activity”	EVL	phosphorylation
PRKG1	“up-regulates activity”	RGS18	phosphorylation
PRKG1	“up-regulates activity”	PRKAR1A	phosphorylation
PRKG1	“up-regulates activity”	PLN	phosphorylation
PRKG1	“down-regulates activity”	GSK3B	phosphorylation
PRKG1	up-regulates	PTS	phosphorylation

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	407
Likely benign	443
Benign	77

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
65477	NM_006258.4(PRKG1):c.575G>A (p.Arg192Gln)	Pathogenic

SpliceAI

4005 predictions. Top by Δscore:

Variant	Effect	Δscore
10:50991624:G:GT	donor_gain	1.0000
10:50991640:GAAAG:G	donor_gain	1.0000
10:50991642:AAGGT:A	donor_loss	1.0000
10:50991643:AGGTA:A	donor_loss	1.0000
10:50991644:GGTA:G	donor_loss	1.0000
10:50991646:T:A	donor_loss	1.0000
10:51153161:TAG:T	acceptor_loss	1.0000
10:51153162:A:AG	acceptor_gain	1.0000
10:51153162:A:T	acceptor_loss	1.0000
10:51153163:G:GA	acceptor_loss	1.0000
10:51153163:G:GG	acceptor_gain	1.0000
10:51153327:GAAGG:G	donor_loss	1.0000
10:51153328:A:T	donor_gain	1.0000
10:51153330:GG:G	donor_loss	1.0000
10:51153332:T:A	donor_loss	1.0000
10:51443567:A:T	donor_gain	1.0000
10:51467719:TTAG:T	acceptor_loss	1.0000
10:51467720:TA:T	acceptor_loss	1.0000
10:51467721:A:AG	acceptor_gain	1.0000
10:51467721:AGAT:A	acceptor_gain	1.0000
10:51467722:G:GG	acceptor_gain	1.0000
10:51467722:GATG:G	acceptor_gain	1.0000
10:51467833:AAGAG:A	donor_loss	1.0000
10:51467834:AGA:A	donor_gain	1.0000
10:51467834:AGAG:A	donor_loss	1.0000
10:51467835:GA:G	donor_gain	1.0000
10:51467835:GAG:G	donor_gain	1.0000
10:51467835:GAGTA:G	donor_loss	1.0000
10:51467836:AGTAA:A	donor_loss	1.0000
10:51467837:G:GG	donor_gain	1.0000

AlphaMissense

4552 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
10:51153178:T:A	I94K	1.000
10:51153186:G:C	A97P	1.000
10:51153200:T:A	N101K	1.000
10:51153200:T:G	N101K	1.000
10:51153204:T:C	F103L	1.000
10:51153205:T:C	F103S	1.000
10:51153205:T:G	F103C	1.000
10:51153206:T:A	F103L	1.000
10:51153206:T:G	F103L	1.000
10:51153306:G:A	G137R	1.000
10:51153306:G:C	G137R	1.000
10:51153306:G:T	G137W	1.000
10:51153307:G:A	G137E	1.000
10:51153322:T:A	V142D	1.000
10:51467738:T:A	V150D	1.000
10:51467788:G:A	G167R	1.000
10:51467788:G:C	G167R	1.000
10:51467788:G:T	G167W	1.000
10:51467789:G:A	G167E	1.000
10:51467789:G:T	G167V	1.000
10:51467792:A:T	E168V	1.000
10:51467795:T:C	L169S	1.000
10:51467795:T:G	L169W	1.000
10:51467797:G:C	A170P	1.000
10:51467798:C:A	A170D	1.000
10:51467798:C:T	A170V	1.000
10:51467804:T:A	L172H	1.000
10:51467804:T:C	L172P	1.000
10:51467806:T:C	Y173H	1.000
10:51467806:T:G	Y173D	1.000

dbSNP variants (sampled 300 via entrez): RS1000002163 (10:51325965 G>A), RS1000004898 (10:51828063 C>T), RS1000009267 (10:51241614 C>G), RS1000012193 (10:52224418 C>T), RS1000013189 (10:51287396 T>C), RS1000013243 (10:51370176 A>G), RS1000013370 (10:51807471 A>C), RS1000015836 (10:51641069 C>G,T), RS1000016518 (10:52094851 A>T), RS1000017708 (10:51101695 T>C), RS1000022258 (10:52176445 G>A,T), RS1000022276 (10:51501946 A>G), RS1000024036 (10:51847249 A>G), RS1000026181 (10:51968829 A>G), RS1000028029 (10:51544741 C>T)

Disease associations

OMIM: gene MIM:176894 | disease phenotypes: MIM:615436, MIM:607086, MIM:181500

GenCC curated gene-disease

Disease	Classification	Inheritance
aortic aneurysm, familial thoracic 8	Strong	Autosomal dominant
familial thoracic aortic aneurysm and aortic dissection	Strong	Unknown

ClinGen Gene-Disease Validity (1)

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

Disease	Classification	Inheritance
familial thoracic aortic aneurysm and aortic dissection	Strong	AD

Mondo (4): aortic aneurysm, familial thoracic 8 (MONDO:0014187), familial thoracic aortic aneurysm and aortic dissection (MONDO:0019625), schizophrenia (MONDO:0005090), connective tissue disorder (MONDO:0003900)

Orphanet (2): Familial thoracic aortic aneurysm and aortic dissection (Orphanet:91387), NON RARE IN EUROPE: Schizophrenia (Orphanet:3140)

HPO phenotypes

46 total (30 of 46 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000023	Inguinal hernia
HP:0000098	Tall stature
HP:0000278	Retrognathia
HP:0000316	Hypertelorism
HP:0000525	Abnormality iris morphology
HP:0000766	Abnormal sternum morphology
HP:0000822	Hypertension
HP:0000965	Cutis marmorata
HP:0000978	Bruising susceptibility
HP:0001166	Arachnodactyly
HP:0001297	Stroke
HP:0001640	Cardiomegaly
HP:0001643	Patent ductus arteriosus
HP:0001647	Bicuspid aortic valve
HP:0001659	Aortic regurgitation
HP:0001677	Coronary artery atherosclerosis
HP:0001763	Pes planus
HP:0002105	Hemoptysis
HP:0002107	Pneumothorax
HP:0002138	Subarachnoid hemorrhage
HP:0002140	Ischemic stroke
HP:0002326	Transient ischemic attack
HP:0002616	Aortic root aneurysm
HP:0002647	Aortic dissection
HP:0002650	Scoliosis
HP:0002686	Pregnancy history
HP:0002705	High, narrow palate
HP:0002875	Exertional dyspnea
HP:0003549	Abnormality of connective tissue

GWAS associations

32 associations (top):

Study	Trait	p-value
GCST001226_2	Asthma	5.000000e-07
GCST001762_913	Obesity-related traits	7.000000e-06
GCST002666_2	Interferon alpha levels in systemic lupus erythematosus	3.000000e-08
GCST002668_5	Mammographic density (non-dense area)	3.000000e-06
GCST003054_3	Gait rhythm	1.000000e-06
GCST003773_17	Loneliness (multivariate analysis)	5.000000e-06
GCST004225_1	Alcohol misuse (trauma interaction)	2.000000e-08
GCST004521_153	Autism spectrum disorder or schizophrenia	3.000000e-08
GCST005196_32	Coronary artery disease	3.000000e-06
GCST005790_17	Rosacea symptom severity	3.000000e-06
GCST006225_3	Anti-chlamydia trachomatis IgG seropositivity	6.000000e-07
GCST007006_8	Logical memory (delayed recall) in normal cognition	2.000000e-08
GCST007201_112	Schizophrenia	5.000000e-07
GCST007201_339	Schizophrenia	1.000000e-06
GCST007393_6	Mitochondrial DNA copy number	6.000000e-07
GCST007672_15	3-month functional outcome in ischaemic stroke (modified Rankin score)	2.000000e-06
GCST007856_40	Colorectal cancer or advanced adenoma	5.000000e-10
GCST008158_1	Body mass index	6.000000e-06
GCST008163_30	Height	5.000000e-06
GCST008839_520	Height	1.000000e-09
GCST009615_11	Triglyceride levels x loop diuretics use interaction	1.000000e-07
GCST010988_440	Adult body size	2.000000e-08
GCST011176_20	Stroke	3.000000e-07
GCST011687_8	Systolic blood pressure	9.000000e-08
GCST011741_18	LDL cholesterol levels in HIV infection	6.000000e-06
GCST011741_3	LDL cholesterol levels in HIV infection	6.000000e-06
GCST011743_21	HDL cholesterol levels in HIV infection	2.000000e-07
GCST012103_2	Arthritis (juvenile idiopathic)	3.000000e-06
GCST90000025_402	Appendicular lean mass	2.000000e-15
GCST90000025_403	Appendicular lean mass	3.000000e-14

EFO canonical traits (17, from GWAS)

EFO ID	Trait name
EFO:0006517	interferon alpha measurement
EFO:0005941	mammographic density measurement
EFO:0006504	non-dense area measurement
EFO:0007865	loneliness measurement
EFO:0007781	stressful life event measurement
EFO:0007835	alcohol dependence measurement
EFO:0009180	rosacea severity measurement
EFO:0009330	Chlamydia trachomatis seropositivity
EFO:0004874	memory performance
EFO:0006312	mitochondrial DNA measurement
EFO:0009603	stroke outcome severity measurement
EFO:0004340	body mass index
EFO:0004530	triglyceride measurement
EFO:0006335	systolic blood pressure
EFO:0004611	low density lipoprotein cholesterol measurement
EFO:0004612	high density lipoprotein cholesterol measurement
EFO:0004980	appendicular lean mass

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D003240	Connective Tissue Diseases	C17.300

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4273 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

15 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 39,011 (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
CHEMBL1287853	FEDRATINIB	4	3,554
CHEMBL2035187	PACRITINIB	4	3,345
CHEMBL2325741	CAPIVASERTIB	4	2,157
CHEMBL502835	NINTEDANIB	4	8,545
CHEMBL608533	MIDOSTAURIN	4	7,259
CHEMBL2177390	IPATASERTIB	3	2,231
CHEMBL223360	LINIFANIB	3	3,925
CHEMBL300138	ENZASTAURIN	3	3,209
CHEMBL603469	LESTAURTINIB	3
CHEMBL1667969	SAR-407899 FREE BASE	2	157
CHEMBL1967878	CENISERTIB	2	358
CHEMBL565612	SOTRASTAURIN	2	1,355
CHEMBL1908397	KW-2449	1	622
CHEMBL3128043	PF-03758309	1	233
CHEMBL494089	GSK-690693	1	2,061

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

PharmGKB variants

1 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs12248467	PRKG1		0.00	0

GtoPdb / IUPHAR curated pharmacology

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

Target class: enzyme — Protein kinase G (PKG) family

Most potent curated ligand interactions (4 total), top 4:

Ligand	Action	Affinity	Parameter
aplithianine A	Inhibition	7.96	pIC50
GSK690693	Inhibition	7.48	pIC50
ipatasertib	Inhibition	7.16	pIC50
allosteric modulator 33 [PMID: 35878399]	Activation	6.28	pEC50

Binding affinities (BindingDB)

7 measured of 10 human assays (11 total across all organisms); most potent 7 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
Staurosporine	KD	1.7 nM
PET-cGMP	EC50	5.8 nM
5-(1,4-diazepan-1-ylsulfonyl)isoquinoline	KD	50 nM	US-11198680: Rho kinase inhibitor BA-1049 (R) and active metabolites thereof
PKC-412	KD	190 nM
8-pCP-cGMP	EC50	206 nM
2-amino-8-bromo-9-[(2R,4aR,6R,7R,7aS)-2,7-dihydroxy-2-oxotetrahydro-2H,4H-2lambda5-furo[3,2-d][1,3,2]dioxaphosphinin-6-yl]-1,9-dihydro-6H-purin-6-one	EC50	765 nM
CHEMBL5207745	EC50	43000 nM

ChEMBL bioactivities

232 potent at pChembl≥5 of 285 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
9.00	IC50	1	nM	CHEMBL4448806
9.00	IC50	1	nM	CHEMBL5278787
9.00	Ki	1	nM	CHEMBL1990254
8.95	IC50	1.12	nM	STAUROSPORINE
8.92	IC50	1.19	nM	STAUROSPORINE
8.91	IC50	1.23	nM	STAUROSPORINE
8.90	Kd	1.245	nM	CHEMBL3752910
8.90	Ki	1.259	nM	CHEMBL2001751
8.90	Ki	1.259	nM	CHEMBL1990254
8.90	Ki	1.259	nM	CHEMBL1998121
8.89	Kd	1.3	nM	CHEMBL2023841
8.80	Kd	1.6	nM	BALANOL
8.61	ED50	2.458	nM	CHEMBL3752910
8.60	Ki	2.512	nM	CHEMBL1976240
8.55	IC50	2.84	nM	STAUROSPORINE
8.49	Kd	3.2	nM	CHEMBL2023845
8.48	IC50	3.34	nM	STAUROSPORINE
8.40	Kd	4	nM	SAR-407899 FREE BASE
8.33	IC50	4.65	nM	STAUROSPORINE
8.30	IC50	5	nM	STAUROSPORINE
8.30	Ki	5.012	nM	CHEMBL1988608
8.20	Ki	6.31	nM	CHEMBL592030
8.10	Ki	7.943	nM	CHEMBL1975121
8.10	Ki	7.943	nM	CHEMBL1965836
8.10	Ki	7.943	nM	CHEMBL1991063
8.00	Ki	10	nM	CHEMBL1975128
8.00	Ki	10	nM	CHEMBL1974870
7.96	IC50	11	nM	CHEMBL5433617
7.90	Ki	12.59	nM	CHEMBL1982711
7.89	Kd	13	nM	CHEMBL2023714
7.85	Kd	14	nM	NINTEDANIB
7.82	IC50	15	nM	CHEMBL5433617
7.82	Ki	15	nM	PF-03758309
7.80	Ki	15.85	nM	CHEMBL1998159
7.80	Ki	15.85	nM	CHEMBL1974288
7.77	IC50	17	nM	CHEMBL4459800
7.70	Ki	19.95	nM	CHEMBL225519
7.70	Ki	19.95	nM	CHEMBL2006188
7.60	Ki	25.12	nM	CHEMBL1682552
7.60	Ki	25.12	nM	CHEMBL1991188
7.50	Kd	32	nM	STAUROSPORINE
7.50	Ki	31.62	nM	CHEMBL1980489
7.50	Ki	31.62	nM	CHEMBL1682553
7.50	Ki	31.62	nM	CHEMBL1974935
7.50	Ki	31.62	nM	CHEMBL1979252
7.50	Ki	31.62	nM	CHEMBL2007296
7.48	IC50	33	nM	GSK-690693
7.47	IC50	34	nM	PF-03758309
7.41	IC50	39	nM	CHEMBL5181094
7.40	Ki	39.81	nM	BAY-549

PubChem BioAssay actives

113 with measured affinity, of 1505 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
N-[(1S)-2-amino-1-phenylethyl]-4-pyridin-4-ylbenzamide	1948864: Inhibition of PRKG1 (unknown origin)	ic50	0.0010	uM
N-[(1R)-1-(3-methoxyphenyl)ethyl]-4-pyridin-4-ylbenzamide	1531986: Inhibition of PKG1A (unknown origin) incubated for 2 hrs by AbbVie kinase panel assay	ic50	0.0010	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	1715199: Inhibition of human PKG1alpha using LRRASLG as substrate by [gamma-33P]-ATP assay	ic50	0.0011	uM
4-methyl-3-[(1-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2149086: Binding affinity to human PRKG1 incubated for 45 mins by Kinobead based pull down assay	kd	0.0012	uM
N-[(2R)-1-[[6-[[(2R)-1-[[(2R)-1-[[(2R)-1-[[(2R)-1-[[(2R)-1-[[(2R)-1-[[(2R)-1-amino-6-[[2-[24-(hydroxy-methylidene-oxo-lambda6-sulfanyl)-5,5,27,27-tetramethyl-16-oxa-12-aza-20-azoniaheptacyclo[15.11.0.03,15.04,12.06,11.020,28.021,26]octacosa-1,3,6(11),7,9,20(28),21(26),22,24-nonaen-8-yl]acetyl]amino]-1-oxohexan-2-yl]amino]-5-carbamimidamido-1-oxopentan-2-yl]amino]-5-carbamimidamido-1-oxopentan-2-yl]amino]-5-carbamimidamido-1-oxopentan-2-yl]amino]-5-carbamimidamido-1-oxopentan-2-yl]amino]-5-carbamimidamido-1-oxopentan-2-yl]amino]-5-carbamimidamido-1-oxopentan-2-yl]amino]-6-oxohexyl]amino]-5-carbamimidamido-1-oxopentan-2-yl]-8-[2-(isoquinolin-5-ylsulfonylamino)ethylamino]octanamide	659382: Binding affinity to His6-tagged recombinant human PKG1alpha by fluorescence anisotropy assay in absence of cGMP	kd	0.0013	uM
2-[2,6-dihydroxy-4-[(3R,4R)-3-[(4-hydroxybenzoyl)amino]azepan-4-yl]oxycarbonylbenzoyl]-3-hydroxybenzoic acid	1315724: Binding affinity to human recombinant N-terminal GST-tagged PKGalpha expressed in Baculovirus infected insect Sf9 cells using RKRSRAE as substrate in presence of [gamma-32P]ATP	kd	0.0016	uM
3-[(4aR,6R,7R,7aS)-2,7-dihydroxy-2-oxo-4a,6,7,7a-tetrahydro-4H-furo[3,2-d][1,3,2]dioxaphosphinin-6-yl]-6-phenyl-5H-imidazo[1,2-a]purin-9-one	1794861: Microfluidic Mobility-Shift Assay from Article 10.1021/acschembio.7b00369: “Structural Basis of Analog Specificity in PKG I and II.”	ec50	0.0020	uM
9-[(4aR,6R,7R,7aS)-2,7-dihydroxy-2-oxo-4a,6,7,7a-tetrahydro-4H-furo[3,2-d][1,3,2]dioxaphosphinin-6-yl]-2-amino-8-bromo-5H-purin-6-one	1794861: Microfluidic Mobility-Shift Assay from Article 10.1021/acschembio.7b00369: “Structural Basis of Analog Specificity in PKG I and II.”	ec50	0.0020	uM
3-[[(2R)-6-amino-1-[[N-[(4R)-5-amino-4-[[(2R)-5-carbamimidamido-2-[[(2R)-5-carbamimidamido-2-[[(2R)-5-carbamimidamido-2-[[(2R)-5-carbamimidamido-2-[[(2R)-5-carbamimidamido-2-[6-[2-(isoquinolin-5-ylsulfonylamino)ethylamino]hexanoylamino]pentanoyl]amino]pentanoyl]amino]pentanoyl]amino]pentanoyl]amino]pentanoyl]amino]-5-oxopentyl]carbamimidoyl]amino]-1-oxohexan-2-yl]carbamoyl]-4-[3,6-bis(dimethylamino)-3H-xanthen-9-yl]benzoic acid	659382: Binding affinity to His6-tagged recombinant human PKG1alpha by fluorescence anisotropy assay in absence of cGMP	kd	0.0032	uM
6-piperidin-4-yloxy-2H-isoquinolin-1-one	1425138: Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry.	kd	0.0040	uM
9-[(4aR,6R,7R,7aS)-2,7-dihydroxy-2-oxo-4a,6,7,7a-tetrahydro-4H-furo[3,2-d][1,3,2]dioxaphosphinin-6-yl]-2-amino-8-(4-chlorophenyl)sulfanyl-5H-purin-6-one	1794861: Microfluidic Mobility-Shift Assay from Article 10.1021/acschembio.7b00369: “Structural Basis of Analog Specificity in PKG I and II.”	ec50	0.0042	uM
6-(3-methylimidazol-4-yl)-4-(7H-purin-6-yl)-2,3-dihydro-1,4-thiazine	2019959: Inhibition of PKG1 alpha (unknown origin)	ic50	0.0110	uM
N-[(2R)-1-[[(2R)-1-[[(2R)-1-[[(2R)-1-[[(2R)-1-[[(2R)-1-amino-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]-6-[2-(isoquinolin-5-ylsulfonylamino)ethylamino]hexanamide	659391: Displacement of fluorescent-ARC-583/ARC-1042/ARC-1059 from His6-tagged recombinant human PKG1alpha by fluorescence anisotropy assay	kd	0.0130	uM
methyl 2-hydroxy-3-[N-[4-[methyl-[2-(4-methylpiperazin-1-yl)acetyl]amino]phenyl]-C-phenylcarbonimidoyl]-1H-indole-6-carboxylate	625052: Binding constant for PRKG1 kinase domain	kd	0.0140	uM
N-[(1S)-2-(dimethylamino)-1-phenylethyl]-6,6-dimethyl-3-[(2-methylthieno[3,2-d]pyrimidin-4-yl)amino]-1,4-dihydropyrrolo[3,4-d]pyrazole-5-carboxamide	2167993: Inhibition of human PRKG1 assessed as inhibition constant in presence of ATP	ki	0.0150	uM
4-(2-fluoro-4-pyridinyl)-N-[(1R)-1-(3-methoxyphenyl)ethyl]benzamide	1881165: Inhibition of full length recombinant N-terminal GST-tagged human PKG expressed in baculovirus infected Sf9 insect cells using RSK as substrate preincubated for 15 mins followed by substrate addition and measured after 30 mins in presence of ATP by ADP Glo kinase assay	ic50	0.0170	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	391391: Inhibition of human PKG1beta	ic50	0.0330	uM
N-[(1R)-1-(3-methoxyphenyl)ethyl]-6-pyridin-4-ylpyridine-3-carboxamide	1881165: Inhibition of full length recombinant N-terminal GST-tagged human PKG expressed in baculovirus infected Sf9 insect cells using RSK as substrate preincubated for 15 mins followed by substrate addition and measured after 30 mins in presence of ATP by ADP Glo kinase assay	ic50	0.0390	uM
(2S)-2-(4-chlorophenyl)-1-[4-[(5R,7R)-7-hydroxy-5-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-yl]piperazin-1-yl]-3-(propan-2-ylamino)propan-1-one	708127: Inhibition of PRKG1beta	ic50	0.0690	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	1526268: Binding affinity to recombinant full-length N-terminal His-FLAG-tagged PRKG1 (unknown origin) expressed in baculovirus infected Sf9 insect cells incubated for 1 hr by TR-FRET assay	kd	0.0850	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	1526268: Binding affinity to recombinant full-length N-terminal His-FLAG-tagged PRKG1 (unknown origin) expressed in baculovirus infected Sf9 insect cells incubated for 1 hr by TR-FRET assay	kd	0.1090	uM
Midostaurin	435546: Binding constant for PRKG1 kinase domain	kd	0.2500	uM
(2S)-1-[[5-(3-methyl-2H-indazol-5-yl)-3-pyridinyl]oxy]-3-phenylpropan-2-amine	625052: Binding constant for PRKG1 kinase domain	kd	0.2700	uM
3-amino-4-[[(2S,3S)-3-[(1S)-1-(3,5-dichlorophenyl)-2-hydroxyethoxy]-2-phenylpiperidin-1-yl]methyl]benzoic acid	1885708: Activation of cGMP induced partially activated state recombinant PKG1alpha (unknown origin) using Glass-tide peptide substrate incubated for 30 mins followed by ATP addition and measured after 2 hr in presence of cGMP by ADP-GLO Max Assay	ec50	0.2900	uM
Capivasertib	1425138: Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry.	kd	0.2970	uM
6-(2-fluoro-4-pyridinyl)-N-[(1R)-1-(3-methoxyphenyl)ethyl]pyridine-3-carboxamide	1881165: Inhibition of full length recombinant N-terminal GST-tagged human PKG expressed in baculovirus infected Sf9 insect cells using RSK as substrate preincubated for 15 mins followed by substrate addition and measured after 30 mins in presence of ATP by ADP Glo kinase assay	ic50	0.3200	uM
4-[[(2S,3S)-3-[(1S)-1-(3,5-dichlorophenyl)-2-methylsulfonylethoxy]-2-phenylpiperidin-1-yl]methyl]-3-methylbenzoic acid	1885708: Activation of cGMP induced partially activated state recombinant PKG1alpha (unknown origin) using Glass-tide peptide substrate incubated for 30 mins followed by ATP addition and measured after 2 hr in presence of cGMP by ADP-GLO Max Assay	ec50	0.3300	uM
4-[[(2S,3S)-3-[(1S)-1-(3,5-dichlorophenyl)-3-hydroxy-3-methylbutoxy]-2-phenylpiperidin-1-yl]methyl]-3-methylbenzoic acid	1885708: Activation of cGMP induced partially activated state recombinant PKG1alpha (unknown origin) using Glass-tide peptide substrate incubated for 30 mins followed by ATP addition and measured after 2 hr in presence of cGMP by ADP-GLO Max Assay	ec50	0.3300	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	508050: Binding affinity to PRKG1	kd	0.3700	uM
5-[[(2S,3S)-3-[(1S)-1-(3,5-dichlorophenyl)-2-hydroxyethoxy]-2-phenylpiperidin-1-yl]methyl]-6-methylpyridine-2-carboxylic acid	1885708: Activation of cGMP induced partially activated state recombinant PKG1alpha (unknown origin) using Glass-tide peptide substrate incubated for 30 mins followed by ATP addition and measured after 2 hr in presence of cGMP by ADP-GLO Max Assay	ec50	0.3700	uM
2-[[(2S,3S)-3-[(1S)-1-(3,5-dichlorophenyl)-2-hydroxyethoxy]-2-phenylpiperidin-1-yl]methyl]-3H-benzimidazole-5-carboxylic acid	1885708: Activation of cGMP induced partially activated state recombinant PKG1alpha (unknown origin) using Glass-tide peptide substrate incubated for 30 mins followed by ATP addition and measured after 2 hr in presence of cGMP by ADP-GLO Max Assay	ec50	0.3800	uM
3-(2-aminoethyl)-4-[[(2S,3S)-3-[(1S)-1-(3,5-dichlorophenyl)-2-hydroxyethoxy]-2-phenylpiperidin-1-yl]methyl]benzoic acid	1885708: Activation of cGMP induced partially activated state recombinant PKG1alpha (unknown origin) using Glass-tide peptide substrate incubated for 30 mins followed by ATP addition and measured after 2 hr in presence of cGMP by ADP-GLO Max Assay	ec50	0.4200	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	625052: Binding constant for PRKG1 kinase domain	kd	0.4300	uM
4-[[(2S,3S)-3-[(1S)-1-(3,5-dichlorophenyl)-2-(methanesulfonamido)ethoxy]-2-phenylpiperidin-1-yl]methyl]-3-methylbenzoic acid	1885708: Activation of cGMP induced partially activated state recombinant PKG1alpha (unknown origin) using Glass-tide peptide substrate incubated for 30 mins followed by ATP addition and measured after 2 hr in presence of cGMP by ADP-GLO Max Assay	ec50	0.4800	uM
N-[2-[[(E)-3-(4-bromophenyl)prop-2-enyl]amino]ethyl]isoquinoline-5-sulfonamide	1799810: Enzyme Assay from Article : “Inhibition of forskolin-induced neurite outgrowth and protein phosphorylation by a newly synthesized selective inhibitor of cyclic AMP-dependent protein kinase, N-[2-(p-bromocinnamylamino)ethyl]-5-isoquinolinesulfonamide (H-89), of PC12D pheochromocytoma cells.”	ki	0.4800	uM
4-(dimethylamino)-N-[3-[[2-(4-oxochromen-7-yl)oxyacetyl]amino]phenyl]benzamide	1580723: Inhibition of recombinant full length human PKG1alpha using RRRLSFAEPG as substrate incubated for 40 mins in presence of [gamma-33P]ATP and 10 uM ATP by radiometric scintillation counting analysis	ic50	0.5170	uM
4-[[(2S,3S)-3-[(1S)-1-(3,5-dichlorophenyl)-2-hydroxyethoxy]-2-phenylpiperidin-1-yl]methyl]-3-nitrobenzoic acid	1885708: Activation of cGMP induced partially activated state recombinant PKG1alpha (unknown origin) using Glass-tide peptide substrate incubated for 30 mins followed by ATP addition and measured after 2 hr in presence of cGMP by ADP-GLO Max Assay	ec50	0.5200	uM
N-[(2R)-6-amino-1-[[6-[[(2R)-1-[[(2R)-1-amino-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-6-oxohexyl]amino]-1-oxohexan-2-yl]-8-(4-isoquinolin-5-ylsulfonyl-1,4-diazepan-1-yl)octanamide	659391: Displacement of fluorescent-ARC-583/ARC-1042/ARC-1059 from His6-tagged recombinant human PKG1alpha by fluorescence anisotropy assay	kd	0.6300	uM
N-[2-[[(E)-3-phenylprop-2-enyl]amino]ethyl]isoquinoline-5-sulfonamide	1799810: Enzyme Assay from Article : “Inhibition of forskolin-induced neurite outgrowth and protein phosphorylation by a newly synthesized selective inhibitor of cyclic AMP-dependent protein kinase, N-[2-(p-bromocinnamylamino)ethyl]-5-isoquinolinesulfonamide (H-89), of PC12D pheochromocytoma cells.”	ki	0.7600	uM
methyl 4-[[(2S,3S)-3-[(1S)-1-(3,5-dichlorophenyl)-2-hydroxyethoxy]-2-phenylpiperidin-1-yl]methyl]-3-methylbenzoate	1885708: Activation of cGMP induced partially activated state recombinant PKG1alpha (unknown origin) using Glass-tide peptide substrate incubated for 30 mins followed by ATP addition and measured after 2 hr in presence of cGMP by ADP-GLO Max Assay	ec50	0.9000	uM
4-[[(2S,3S)-3-[(1S)-1-(3,5-dichlorophenyl)-2-hydroxyethoxy]-2-phenylpiperidin-1-yl]methyl]-3-methylbenzoic acid	1885708: Activation of cGMP induced partially activated state recombinant PKG1alpha (unknown origin) using Glass-tide peptide substrate incubated for 30 mins followed by ATP addition and measured after 2 hr in presence of cGMP by ADP-GLO Max Assay	ec50	1.0000	uM
4-[[(2S,3S)-3-[(1S)-1-(3,5-dichlorophenyl)-2-hydroxyethoxy]-2-phenylpiperidin-1-yl]methyl]-3-(methoxycarbonylamino)benzoic acid	1885708: Activation of cGMP induced partially activated state recombinant PKG1alpha (unknown origin) using Glass-tide peptide substrate incubated for 30 mins followed by ATP addition and measured after 2 hr in presence of cGMP by ADP-GLO Max Assay	ec50	1.0000	uM
3-(1-methylindol-3-yl)-4-[1-[1-(pyridin-2-ylmethyl)piperidin-4-yl]indol-3-yl]pyrrole-2,5-dione	625052: Binding constant for PRKG1 kinase domain	kd	1.1000	uM
4-[[(2S,3S)-3-[(1S)-1-(3-chlorophenyl)-2-hydroxyethoxy]-2-phenylpiperidin-1-yl]methyl]-3-methylbenzoic acid	1885708: Activation of cGMP induced partially activated state recombinant PKG1alpha (unknown origin) using Glass-tide peptide substrate incubated for 30 mins followed by ATP addition and measured after 2 hr in presence of cGMP by ADP-GLO Max Assay	ec50	1.3000	uM
4-[[(2S,3S)-3-[(1S)-1-(3,5-difluorophenyl)-2-hydroxyethoxy]-2-phenylpiperidin-1-yl]methyl]-3-methylbenzoic acid	1885708: Activation of cGMP induced partially activated state recombinant PKG1alpha (unknown origin) using Glass-tide peptide substrate incubated for 30 mins followed by ATP addition and measured after 2 hr in presence of cGMP by ADP-GLO Max Assay	ec50	1.5000	uM
Pacritinib	1425138: Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry.	kd	1.5160	uM
(2R)-N-[(1R)-1-(3-fluoro-5-methoxyphenyl)ethyl]-4-(3-fluoro-4-pyridinyl)-2-methylpiperazine-1-carboxamide	1881165: Inhibition of full length recombinant N-terminal GST-tagged human PKG expressed in baculovirus infected Sf9 insect cells using RSK as substrate preincubated for 15 mins followed by substrate addition and measured after 30 mins in presence of ATP by ADP Glo kinase assay	ic50	1.7000	uM
3-cyclopropyl-4-[[(2S,3S)-3-[(1S)-1-(3,5-dichlorophenyl)-2-hydroxyethoxy]-2-phenylpiperidin-1-yl]methyl]benzoic acid	1885708: Activation of cGMP induced partially activated state recombinant PKG1alpha (unknown origin) using Glass-tide peptide substrate incubated for 30 mins followed by ATP addition and measured after 2 hr in presence of cGMP by ADP-GLO Max Assay	ec50	1.8000	uM
4-[[(2S,3S)-3-[(1S)-1-(3,5-dichlorophenyl)-2-[(2,2,2-trifluoroacetyl)amino]ethoxy]-2-phenylpiperidin-1-yl]methyl]-3-methylbenzoic acid	1885708: Activation of cGMP induced partially activated state recombinant PKG1alpha (unknown origin) using Glass-tide peptide substrate incubated for 30 mins followed by ATP addition and measured after 2 hr in presence of cGMP by ADP-GLO Max Assay	ec50	1.8000	uM
4-(3-fluoro-4-pyridinyl)-N-[(1R)-1-(3-methoxyphenyl)ethyl]piperazine-1-carboxamide	1881165: Inhibition of full length recombinant N-terminal GST-tagged human PKG expressed in baculovirus infected Sf9 insect cells using RSK as substrate preincubated for 15 mins followed by substrate addition and measured after 30 mins in presence of ATP by ADP Glo kinase assay	ic50	1.8300	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
bisphenol A	affects cotreatment, increases methylation, increases expression	4
Valproic Acid	affects cotreatment, increases expression	3
Aflatoxin B1	decreases expression, decreases methylation	3
sulindac sulfone	increases expression	2
Benzo(a)pyrene	increases expression, increases methylation	2
Nickel	decreases expression	2
Phenylmercuric Acetate	affects cotreatment, decreases expression	2
Okadaic Acid	affects cotreatment, decreases reaction, increases activity, decreases expression	2
FR900359	increases phosphorylation	1
bisphenol F	affects cotreatment, increases expression	1
ammonium 2,3,3,3-tetrafluoro-2-(heptafluoropropoxy)-propanoate	affects cotreatment, affects expression	1
geldanamycin	increases expression	1
testosterone enanthate	affects expression	1
methylmercuric chloride	decreases expression	1
methyleugenol	decreases expression	1
trichostatin A	increases expression	1
8-bromocyclic GMP	affects cotreatment, increases activity	1
11-nor-delta(9)-tetrahydrocannabinol-9-carboxylic acid	affects methylation, increases abundance	1
sodium arsenite	increases expression	1
tetrabromobisphenol A	increases expression	1
perfluorooctanoic acid	affects cotreatment, affects expression	1
benzo(e)pyrene	decreases methylation	1
aflatoxin B2	increases methylation	1
avobenzone	decreases expression	1
8-((4-chlorophenyl)thio)cyclic-3’,5’-GMP	increases reaction, affects binding, increases phosphorylation, affects cotreatment, decreases reaction (+1 more)	1
calyculin A	affects cotreatment, decreases reaction, increases activity	1
KT 5823	increases reaction, affects cotreatment, decreases reaction, increases activity, affects binding (+1 more)	1
perfluorooctane sulfonic acid	affects expression, affects cotreatment	1
3-(5’-hydroxymethyl-2’-furyl)-1-benzylindazole	increases expression	1
Y 27632	increases activity, affects cotreatment, decreases reaction	1

ChEMBL screening assays

356 unique, capped per target: 355 binding, 1 functional

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1011945	Binding	Inhibition of PKG1 at 100 nM relative to control	Structural analysis of ARC-type inhibitor (ARC-1034) binding to protein kinase A catalytic subunit and rational design of bisubstrate analogue inhibitors of basophilic protein kinases. — J Med Chem
CHEMBL1963695	Functional	PUBCHEM_BIOASSAY: Navigating the Kinome. (Class of assay: other) Panel member name: PRKG1	PubChem BioAssay data set

Cellosaurus cell lines

1 cell lines: 1 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_D9PV	Ubigene HEK293 PRKG1 KO	Transformed cell line	Female

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00000374	PHASE4	COMPLETED	Treatment for First-Episode Schizophrenia
NCT00001656	PHASE4	COMPLETED	Comparison of Clozapine vs Olanzapine in Childhood-Onset Psychotic Disorders
NCT00007774	PHASE4	COMPLETED	To Determine if Olanzapine is More Cost Effective Than Haloperidol for the Treatment of Schizophrenia
NCT00014001	PHASE4	COMPLETED	CATIE- Schizophrenia Trial
NCT00018668	PHASE4	COMPLETED	Antipsychotic Response in Schizophrenia
NCT00034801	PHASE4	COMPLETED	Olanzapine Versus Active Comparator in the Treatment of Depression in Patients With Schizophrenia
NCT00034905	PHASE4	COMPLETED	A Comparison of Seroquel vs. Risperidone in Schizophrenia
NCT00036088	PHASE4	COMPLETED	Olanzapine Versus An Active Comparator in the Treatment of Schizophrenia
NCT00044187	PHASE4	COMPLETED	The Assessment of a Weight-Gain Agent for the Treatment of Olanzapine-Associated Anti-Obesity Agent in Patients With Schizophrenia, Schizophreniform Disorder, Schizoaffective Disorder, and Bipolar I Disorder
NCT00044655	PHASE4	COMPLETED	Switching Medication to Treat Schizophrenia
NCT00048828	PHASE4	COMPLETED	Treating Drug-Resistant Childhood Schizophrenia
NCT00053703	PHASE4	COMPLETED	Treatment of Early Onset Schizophrenia Spectrum Disorders (TEOSS)
NCT00056498	PHASE4	COMPLETED	Risperidone Treatment in Schizophrenia Patients Who Are Currently Taking Clozapine
NCT00061802	PHASE4	COMPLETED	Efficacy and Safety of Two Atypical Antipsychotics vs. Placebo in Patients With an Acute Exacerbation of Either Schizophrenia or Schizoaffective Disorder
NCT00080327	PHASE4	COMPLETED	Study of Three Doses of Aripiprazole in Patients With Acute Schizophrenia
NCT00088049	PHASE4	COMPLETED	Study of Olanzapine vs. Aripiprazole in the Treatment of Schizophrenia
NCT00090012	PHASE4	COMPLETED	Comparison of Continuing Olanzapine to Switching to Quetiapine in Overweight or Obese Patients With Schizophrenia and Schizoaffective Disorder
NCT00100776	PHASE4	COMPLETED	Efficacy of High Dose Olanzapine for the Treatment of Schizophrenia and Schizoaffective Disorder
NCT00103571	PHASE4	COMPLETED	Olanzapine Versus Aripiprazole in the Treatment of Acutely Ill Patients With Schizophrenia
NCT00108368	PHASE4	COMPLETED	The Effects of Risperidone and Olanzapine on Thinking
NCT00114595	PHASE4	COMPLETED	Ethyl-Eicosapentaenoic Acid and Tardive Dyskinesia
NCT00130923	PHASE4	COMPLETED	Risperidone Long-acting Versus Oral Risperidone in Patients With Schizophrenia and Alcohol Use Disorder
NCT00137020	PHASE4	COMPLETED	Clinical Effect Of Cross Titration Of Antipsychotics With Ziprasidone In Schizophrenia Or Schizoaffective Disorder
NCT00140166	PHASE4	COMPLETED	Treatment of Acute Schizophrenia With Vitamin Therapy
NCT00145847	PHASE4	COMPLETED	Naltrexone Treatment of Alcohol Abuse in Schizophrenia
NCT00148564	PHASE4	COMPLETED	Energy Homeostasis Under Treatment With Atypical Antipsychotics
NCT00156715	PHASE4	COMPLETED	Efficacy of Quetiapine in the Treatment of Patients With Schizophrenia and a Comorbid Substance Use Disorder
NCT00158223	PHASE4	COMPLETED	Effectiveness of Pimozide in Augmenting the Effects of Clozapine in the Treatment of Schizophrenia
NCT00159081	PHASE4	COMPLETED	One Year Drug Treatment in First-Episode Schizophrenia
NCT00159120	PHASE4	COMPLETED	Maintenance Treatment vs. Stepwise Drug Discontinuation in First-Episode Schizophrenia
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NCT00159757	PHASE4	TERMINATED	12 Week Open, Non-Comparative Switch Study Of Oral Ziprazidone In Previously Treated Schizophrenic Patients
NCT00167817	PHASE4	COMPLETED	Effect of Switch to Aripiprazole on Health and Smoking Parameters in Patients With Schizophrenia: A Pilot Study
NCT00169026	PHASE4	TERMINATED	Alcoholism and Schizophrenia: Effects of Clozapine
NCT00169039	PHASE4	TERMINATED	Clozapine Versus Chlorpromazine for Treatment-Unresponsive Schizophrenia
NCT00169065	PHASE4	COMPLETED	Effectiveness of Clozapine Versus Olanzapine for Treatment-resistant Schizophrenia
NCT00169091	PHASE4	TERMINATED	Clozapine Versus Haloperidol for Treating the First Episode of Schizophrenia
NCT00176423	PHASE4	COMPLETED	Efficacy Study of Galantamine for Cognitive Impairments in Schizophrenia
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