PRKG2

Summary

PRKG2 (protein kinase cGMP-dependent 2, HGNC:9416) is a protein-coding gene on chromosome 4q21.21, encoding cGMP-dependent protein kinase 2 (Q13237). Crucial regulator of intestinal secretion and bone growth.

This gene encodes a protein that belongs to the serine/threonine protein kinase family of proteins. The encoded protein binds to and inhibits the activation of several receptor tyrosine kinases. The membrane-bound protein is a regulator of intestinal secretion, bone growth and renin secretion. Alternate splicing results in multiple transcript variants encoding distinct isoforms whose regulatory N-termini differ in length but whose C-terminal catalytic domains are identical.

Source: NCBI Gene 5593 — RefSeq curated summary.

At a glance

• Gene–disease (curated): acromesomelic dysplasia 4 (Strong, GenCC) — +1 more curated relationship
• GWAS associations: 47
• Clinical variants (ClinVar): 107 total — 6 pathogenic, 3 likely-pathogenic
• Phenotypes (HPO): 56
• Druggable target: yes — 10 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_006259

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:9416
Approved symbol	PRKG2
Name	protein kinase cGMP-dependent 2
Location	4q21.21
Locus type	gene with protein product
Status	Approved
Aliases	cGKII, PRKGR2, PKG2
Ensembl gene	ENSG00000138669
Ensembl biotype	protein_coding
OMIM	601591
Entrez	5593

Gene structure

Transcript identifiers

Ensembl transcripts: 18 — 15 protein_coding, 3 protein_coding_CDS_not_defined

ENST00000264399, ENST00000395578, ENST00000456882, ENST00000509169, ENST00000509474, ENST00000628926, ENST00000853037, ENST00000853038, ENST00000853039, ENST00000853040, ENST00000853041, ENST00000853042, ENST00000853043, ENST00000853044, ENST00000945147, ENST00000945148, ENST00000945149, ENST00000945150

RefSeq mRNA: 7 — MANE Select: NM_006259 NM_001282480, NM_001282481, NM_001282482, NM_001282483, NM_001282485, NM_001363401, NM_006259

CCDS: CCDS3589, CCDS64005

Canonical transcript exons

ENST00000264399 — 19 exons

Exon	Start	End
ENSE00001073124	81167161	81167224
ENSE00001073127	81171691	81171804
ENSE00001073133	81174793	81174959
ENSE00001073135	81169663	81169768
ENSE00001522150	81204587	81205060
ENSE00002271298	81214936	81215222
ENSE00003472975	81104370	81104432
ENSE00003476028	81105813	81105935
ENSE00003490252	81092386	81092452
ENSE00003531903	81140533	81140669
ENSE00003540466	81110448	81110611
ENSE00003561020	81148884	81148952
ENSE00003573125	81137393	81137482
ENSE00003617512	81142794	81142947
ENSE00003617731	81151960	81152054
ENSE00003620933	81153644	81153721
ENSE00003631528	81135155	81135296
ENSE00003671818	81144232	81144330
ENSE00003918605	81087375	81089803

Expression profiles

Bgee: expression breadth ubiquitous, 167 present calls, max score 82.76.

FANTOM5 (CAGE): breadth broad, TPM avg 1.3484 / max 215.4254, expressed in 297 samples.

FANTOM5 promoters (8 alternative TSS)

Promoter ID	TPM avg	Samples expressed
52777	0.9501	259
52775	0.1360	64
52776	0.1344	59
52774	0.0691	33
52780	0.0255	6
52781	0.0149	6
52778	0.0111	5
52779	0.0073	3

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
jejunal mucosa	UBERON:0000399	82.76	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	82.37	gold quality
tibia	UBERON:0000979	81.99	gold quality
mucosa of transverse colon	UBERON:0004991	76.86	gold quality
ganglionic eminence	UBERON:0004023	76.52	gold quality
ileal mucosa	UBERON:0000331	75.79	gold quality
duodenum	UBERON:0002114	74.42	gold quality
cortical plate	UBERON:0005343	73.74	gold quality
lower esophagus muscularis layer	UBERON:0035833	72.47	gold quality
lower esophagus	UBERON:0013473	72.40	gold quality
small intestine	UBERON:0002108	72.12	gold quality
rectum	UBERON:0001052	71.85	gold quality
small intestine Peyer’s patch	UBERON:0003454	71.69	gold quality
endometrium epithelium	UBERON:0004811	71.58	silver quality
esophagogastric junction muscularis propria	UBERON:0035841	69.88	gold quality
right atrium auricular region	UBERON:0006631	69.49	gold quality
cardiac atrium	UBERON:0002081	68.91	gold quality
calcaneal tendon	UBERON:0003701	68.68	gold quality
prefrontal cortex	UBERON:0000451	67.52	gold quality
diaphragm	UBERON:0001103	67.17	gold quality
skin of hip	UBERON:0001554	66.55	gold quality
intestine	UBERON:0000160	66.44	gold quality
transverse colon	UBERON:0001157	66.09	gold quality
left ventricle myocardium	UBERON:0006566	66.01	gold quality
colonic mucosa	UBERON:0000317	65.93	gold quality
cingulate cortex	UBERON:0003027	65.88	gold quality
embryo	UBERON:0000922	65.81	gold quality
anterior cingulate cortex	UBERON:0009835	65.58	gold quality
islet of Langerhans	UBERON:0000006	65.41	gold quality
secondary oocyte	CL:0000655	65.23	silver quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	4.77

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

111 targeting PRKG2, 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-513A-5P	100.00	69.77	2465
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-9-5P	100.00	72.28	2361
HSA-MIR-4533	100.00	69.48	2758
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-4482-3P	99.98	72.50	3147
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-433-3P	99.98	69.37	1203
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-302C-5P	99.97	72.56	3642
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-MIR-4666A-3P	99.96	71.71	3434
HSA-MIR-545-3P	99.95	70.74	2783
HSA-MIR-651-3P	99.94	73.48	5177
HSA-MIR-548J-3P	99.94	72.61	4881
HSA-MIR-144-3P	99.94	73.98	2698
HSA-MIR-101-3P	99.94	75.03	2230
HSA-MIR-548AE-3P	99.93	72.66	4867
HSA-MIR-548AH-3P	99.93	72.54	4872
HSA-MIR-548AM-3P	99.93	72.54	4872
HSA-MIR-548AQ-3P	99.93	72.66	4867
HSA-MIR-3119	99.92	71.34	2390

Literature-anchored findings (GeneRIF, showing 29)

• Inhibition of cGMP-dependent protein kinase II by its own splice isoform (PMID:12054676)
• results show that the fast phase of autophosphorylation of cGMP dependent protein kinase II has a small effect on its activity, whereas the secondary phase involving Ser126 phosphorylation may generate an active form (PMID:12764134)
• Characterization of the 4q21 breakpoint revealed PRKG2 as the likely gene partner to PDGFRB in myeloproliferative disorders. (PMID:18262053)
• Results suggest that the cGK II gene on chromosome 4q21 is most likely to harbour gout disease independently of hyperuricaemia and is inherited recessively. (PMID:18678579)
• Regulation of epithelial sodium channels by cGMP/PKGII. (PMID:19359370)
• PRKG2 inhibits cell proliferation, Sox9 expression and Akt phosphorylation in human glioma cell lines. (PMID:19543319)
• PKG II inhibits the proliferation of gastric cancer cells through blocking EGF-triggered MAPK signal transduction. (PMID:22012247)
• As an addition to PRKG2 and RASGEFIB genes, we propose to include BMP3 gene as the principal determinant of the observed common phenotype. (PMID:22303795)
• The results suggest that PKGII inhibits EGF-induced MAPK/JNK-mediated signal transduction and further confirmed that PKGII can block the activation of EGFR. (PMID:22427012)
• The work presented here demonstrates a novel antiproliferative and prodifferentiation role for PKG2 in the colon. (PMID:22556146)
• Downregulation of PKG2 was associated with malignant and benign breast tumors. (PMID:22791569)
• type II cGMPdependent protein kinase prevented the EGF-induced phosphorylation/activation of ERK and JNK, but not the phosphorylation of p38MAPK induced by EGF. (PMID:22940826)
• These data suggest that increased PKG II activity attenuates bFGFinduced proliferation and migration by inhibiting the MAPK/ERK signaling pathway, whereas PKG I does not (PMID:23404188)
• PKG II also inhibits the activation of the EGFR caused by diverse ligands of the receptor. (PMID:24534906)
• PKGII inhibits RhoA activity by binding to this small GTPase and causing phosphorylation at its Ser188 site. (PMID:24549567)
• Our replication study suggests that cGKII is not involved in gout susceptibility. (PMID:24882840)
• we determined a crystal structure of the PKG II LZ-Rab11b complex. The PKG II LZ domain presents a mostly nonpolar surface onto which Rab11b docks, through van der Waals interactions (PMID:25070890)
• Han Chinese patients with rs10033237 polymorphism of cGKII/PRKG2 gene are more likely to suffer from gout. (PMID:25688884)
• PKG II inhibits EGFinduced activation of HER2 through binding with and causing threonine 686 phosphorylation of this oncogenic protein. (PMID:26676300)
• The C-terminal cyclic nucleotide binding (CNB-B) domain of cGMP-dependent protein kinase II binds cGMP with higher affinity and selectivity when compared with its N-terminal CNB (CNB-A) domain. (PMID:26769964)
• the results indicated that PKG II could block c-Met activation via phosphorylating Ser985 (PMID:27147579)
• These affinity and activation measurements show that beta-phenyl-1,N2-ethenoguanosine 3’,5’-monophosphate (PET-cGMP) is most selective for PKG I, whereas 8-(4-chlorophenylthio)guanosine-3’-5’-cyclic monophosphate (8-pCPT-cGMP) is most selective for PKG II. (PMID:28793191)
• L-Arginine is a potential alternative to PKG II activation. (PMID:29401205)
• Comparative analysis of the backbone hydrogen/deuterium exchange patterns in PKG II:8-pCPT-cGMP and previously reported PKG Ibeta:cGMP XN structures suggests that the ability of these agonists to activate PKG is related to how effectively they quench dynamics of the cyclic nucleotide binding pocket and the surrounding regions. (PMID:29517905)
• These findings suggested a PKG II-specific phosphorylation site on EGFR. (PMID:31395339)
• Expression of PKG2 in ovarian cancer and its effect on epidermal growth factor receptor. (PMID:32521860)
• Biallelic cGMP-dependent type II protein kinase gene (PRKG2) variants cause a novel acromesomelic dysplasia. (PMID:33106379)
• Variable skeletal phenotypes associated with biallelic variants in PRKG2. (PMID:34782440)
• Natural history of clinical features in two brothers with acromesomelic dysplasia related to PRKG2. (PMID:36504352)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	prkg2	ENSDARG00000054741
mus_musculus	Prkg2	ENSMUSG00000029334
rattus_norvegicus	Prkg2	ENSRNOG00000002361
drosophila_melanogaster	Pka-C2	FBGN0000274
drosophila_melanogaster	CG12069	FBGN0039796

Paralogs (5): PRKACA (ENSG00000072062), PRKACB (ENSG00000142875), PRKACG (ENSG00000165059), PRKX (ENSG00000183943), PRKG1 (ENSG00000185532)

Protein

Protein identifiers

cGMP-dependent protein kinase 2 — Q13237 (reviewed: Q13237)

Alternative names: cGMP-dependent protein kinase II

All UniProt accessions (2): Q13237, A0A140VJM3

UniProt curated annotations — full annotation on UniProt →

Function. Crucial regulator of intestinal secretion and bone growth. Phosphorylates and activates CFTR on the plasma membrane. Plays a key role in intestinal secretion by regulating cGMP-dependent translocation of CFTR in jejunum. Acts downstream of NMDAR to activate the plasma membrane accumulation of GRIA1/GLUR1 in synapse and increase synaptic plasticity. Phosphorylates GRIA1/GLUR1 at Ser-863. Acts as a regulator of gene expression and activator of the extracellular signal-regulated kinases MAPK3/ERK1 and MAPK1/ERK2 in mechanically stimulated osteoblasts. Under fluid shear stress, mediates ERK activation and subsequent induction of FOS, FOSL1/FRA1, FOSL2/FRA2 and FOSB that play a key role in the osteoblast anabolic response to mechanical stimulation.

Subunit / interactions. Interacts with GRIA1/GLUR1.

Subcellular location. Apical cell membrane.

Tissue specificity. Highly concentrated in brain, lung and intestinal mucosa.

Post-translational modifications. Myristoylation mediates membrane localization.

Disease relevance. Spondylometaphyseal dysplasia, Pagnamenta type (SMDP) [MIM:619638] A form of spondylometaphyseal dysplasia, a group of short stature disorders distinguished by abnormalities in the vertebrae and the metaphyses of the tubular bones. SMDP is an autosomal recessive form characterized by short stature and mild platyspondyly with no disproportion between the limbs. Mild metaphyseal changes are present. The disease is caused by variants affecting the gene represented in this entry. Acromesomelic dysplasia 4 (AMD4) [MIM:619636] A form of acromesomelic dysplasia, a skeletal disorder characterized by short stature, very short limbs and hand/foot malformations. The severity of limb abnormalities increases from proximal to distal with profoundly affected hands and feet showing brachydactyly and/or rudimentary fingers (knob-like fingers). AMD4 radiographic hallmarks include mild to moderate platyspondyly, moderate brachydactyly, iliac flaring, and metaphyseal alterations of the long bones that progressively increase with age. AMD4 inheritance is autosomal recessive. The disease is caused by variants affecting the gene represented in this entry.

Activity regulation. Binding of cGMP results in enzyme activation.

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

Isoforms (2)

UniProt ID	Names	Canonical?
Q13237-1	1	yes
Q13237-2	2

RefSeq proteins (7): NP_001269409, NP_001269410, NP_001269411, NP_001269412, NP_001269414, NP_001350330, NP_006250* (*=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
IPR035014	STKc_cGK	Domain

Pfam: PF00027, PF00069

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 (64 total): strand 14, helix 12, binding site 11, region of interest 5, modified residue 4, sequence variant 4, sequence conflict 4, domain 2, mutagenesis site 2, initiator methionine 1, chain 1, active site 1, lipid moiety-binding region 1, splice variant 1, coiled-coil region 1

Structure

Experimental structures (PDB)

6 structures.

PDB	Method	Resolution (Å)
5JIX	X-RAY DIFFRACTION	1.47
5JIZ	X-RAY DIFFRACTION	1.5
5C8W	X-RAY DIFFRACTION	1.8
5BV6	X-RAY DIFFRACTION	1.94
5C6C	X-RAY DIFFRACTION	2.05
6BQ8	X-RAY DIFFRACTION, NEUTRON DIFFRACTION	2,2.2

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q13237-F1	82.45	0.52

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): 576 (proton acceptor)

Ligand- & substrate-binding residues (11): 232–235; 232–235; 242–243; 242–243; 347; 356–359; 366–367; 412; 415; 459–467; 482

Post-translational modifications (5): 110, 117, 431, 609, 2

Mutagenesis-validated functional residues (2):

Position	Phenotype
412	reduces cgmp binding affinity; when associated with a-415.
415	reduces cgmp binding affinity; when associated with a-412.

Function

Pathways and Gene Ontology

Reactome pathways

17 pathways

ID	Pathway
R-HSA-1474151	Tetrahydrobiopterin (BH4) synthesis, recycling, salvage and regulation
R-HSA-4086398	Ca2+ pathway
R-HSA-418457	cGMP effects
R-HSA-9648002	RAS processing
R-HSA-9918432	Maturation of DENV proteins
R-HSA-109582	Hemostasis
R-HSA-1430728	Metabolism
R-HSA-162582	Signal Transduction
R-HSA-195721	Signaling by WNT
R-HSA-196854	Metabolism of vitamins and cofactors
R-HSA-3858494	Beta-catenin independent WNT signaling
R-HSA-392154	Nitric oxide stimulates guanylate cyclase
R-HSA-418346	Platelet homeostasis
R-HSA-5673001	RAF/MAP kinase cascade
R-HSA-5683057	MAPK family signaling cascades
R-HSA-5684996	MAPK1/MAPK3 signaling
R-HSA-8978934	Metabolism of cofactors

MSigDB gene sets: 305 (showing top): GOBP_CARTILAGE_DEVELOPMENT, GOBP_SKELETAL_SYSTEM_DEVELOPMENT, GOBP_REGULATION_OF_CARTILAGE_DEVELOPMENT, GOBP_POLYOL_METABOLIC_PROCESS, GOBP_POSITIVE_REGULATION_OF_PROTEIN_LOCALIZATION, GOBP_PROTEIN_LOCALIZATION_TO_CELL_PERIPHERY, GOBP_PTERIDINE_CONTAINING_COMPOUND_METABOLIC_PROCESS, GOBP_POSITIVE_REGULATION_OF_CELL_DIFFERENTIATION, GROSS_ELK3_TARGETS_DN, GROSS_HYPOXIA_VIA_ELK3_DN, GOBP_CHONDROCYTE_DIFFERENTIATION, GOBP_REGULATION_OF_CHONDROCYTE_DIFFERENTIATION, GOBP_DIOL_METABOLIC_PROCESS, GOTZMANN_EPITHELIAL_TO_MESENCHYMAL_TRANSITION_DN, GOBP_POSITIVE_REGULATION_OF_CARTILAGE_DEVELOPMENT

GO Biological Process (8): signal transduction (GO:0007165), positive regulation of chondrocyte differentiation (GO:0032332), intracellular signal transduction (GO:0035556), tetrahydrobiopterin metabolic process (GO:0046146), protein localization to plasma membrane (GO:0072659), positive regulation of protein localization (GO:1903829), negative regulation of chloride transport (GO:2001226), protein phosphorylation (GO:0006468)

GO Molecular Function (11): cGMP-dependent protein kinase activity (GO:0004692), ATP binding (GO:0005524), cGMP binding (GO:0030553), identical protein binding (GO:0042802), mitogen-activated protein kinase binding (GO:0051019), protein serine kinase activity (GO:0106310), nucleotide binding (GO:0000166), protein kinase activity (GO:0004672), protein serine/threonine kinase activity (GO:0004674), kinase activity (GO:0016301), transferase activity (GO:0016740)

GO Cellular Component (5): cytosol (GO:0005829), apical plasma membrane (GO:0016324), nuclear membrane (GO:0031965), plasma membrane (GO:0005886), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-13 pathways:

Category	Pathways
Signal Transduction	2
Metabolism of cofactors	1
Beta-catenin independent WNT signaling	1
Nitric oxide stimulates guanylate cyclase	1
RAF/MAP kinase cascade	1
Dengue Virus Genome Translation and Replication	1
Metabolism	1
Signaling by WNT	1
Platelet homeostasis	1
Hemostasis	1
MAPK1/MAPK3 signaling	1
MAPK family signaling cascades	1
Metabolism of vitamins and cofactors	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
protein kinase activity	2
cellular anatomical structure	2
cell communication	1
cellular process	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
chondrocyte differentiation	1
regulation of chondrocyte differentiation	1
positive regulation of cell differentiation	1
positive regulation of cartilage development	1
intracellular anatomical structure	1
signal transduction	1
diol metabolic process	1
pteridine-containing compound metabolic process	1
protein localization to membrane	1
protein localization to cell periphery	1
intracellular protein localization	1
regulation of protein localization	1
positive regulation of biological process	1
chloride transport	1
negative regulation of monoatomic anion transport	1
regulation of chloride transport	1
phosphorylation	1
protein modification process	1
cyclic nucleotide-dependent protein kinase activity	1
cGMP binding	1
adenyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
cyclic nucleotide binding	1
guanyl ribonucleotide binding	1
anion binding	1
protein binding	1
protein kinase binding	1
nucleoside phosphate binding	1
heterocyclic compound binding	1
kinase activity	1
phosphotransferase activity, alcohol group as acceptor	1
catalytic activity, acting on a protein	1
transferase activity, transferring phosphorus-containing groups	1

Protein interactions and networks

STRING

1652 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PRKG2	RASGEF1B	Q0VAM2	918
PRKG2	GUCA2A	Q02747	850
PRKG2	GRIA1	P42261	650
PRKG2	EMD	P50402	633
PRKG2	GUCY2C	P25092	585
PRKG2	GUCA2B	Q16661	585
PRKG2	SOX9	P48436	584
PRKG2	COL2A1	P02458	583
PRKG2	NPR3	P17342	542
PRKG2	MATN1	P21941	527
PRKG2	SLC9A3	P48764	523
PRKG2	COL10A1	Q03692	523
PRKG2	PDE5A	O76074	519
PRKG2	ITPR1	Q14643	519
PRKG2	CFTR	P13569	500

IntAct

9 interactions, top by confidence:

A	B	Type	Score
UNC119	UNC119B	psi-mi:“MI:0914”(association)	0.640
UNC119	PDE8A	psi-mi:“MI:0914”(association)	0.530
PRKG2	PKM	psi-mi:“MI:0217”(phosphorylation reaction)	0.440
PRKG2	CDKL5	psi-mi:“MI:0915”(physical association)	0.400
PRKG2	HSP90AB1	psi-mi:“MI:0915”(physical association)	0.400
PRKG2	PDE9A	psi-mi:“MI:0915”(physical association)	0.000
NPHP3	PRKG2	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (17): PRKG2 (Affinity Capture-MS), PRKG2 (Two-hybrid), PRKG2 (Reconstituted Complex), PRKG2 (Affinity Capture-MS), PDE9A (Affinity Capture-MS), PRKG2 (Affinity Capture-MS), MYLK (Biochemical Activity), PRKG2 (Affinity Capture-MS), PRKG2 (Affinity Capture-MS), RAB11B (Reconstituted Complex), RAB11B (Co-crystal Structure), RAB11B (Co-localization), SLC6A15 (Cross-Linking-MS (XL-MS)), PRKG2 (Reconstituted Complex), PRKG2 (Affinity Capture-Luminescence)

ESM2 similar proteins: A0A2I0BVG8, A0A509AHB6, A0A509AKL0, A5K0N4, A8X6H1, A8X6H4, A8XNJ6, O15865, O61267, O64629, O94737, P05130, P07278, P09215, P21901, P23298, P24723, P28867, P42680, P54644, P62343, P62344, P62345, P81900, P90980, Q05655, Q13237, Q26619, Q2PJ68, Q54CY9, Q54QB1, Q55GV3, Q5BKK4, Q5F3L1, Q5PU49, Q61410, Q64595, Q64617, Q6GLY8, Q6GPN6

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

21 interactions.

A	Effect	B	Mechanism
PRKG2	down-regulates	HSPB1	phosphorylation
PRKG2	unknown	LASP1	phosphorylation
PRKG2	“up-regulates activity”	PTPN6	phosphorylation
PRKG2	“down-regulates activity”	PDGFRB	phosphorylation
PRKG2	“up-regulates activity”	GRIA1	phosphorylation
PRKG2	“down-regulates activity”	SOX9	phosphorylation
PRKG2	“up-regulates activity”	FOXO1	phosphorylation
PRKG2	“down-regulates activity”	GSK3B	phosphorylation
PRKG2	“down-regulates activity”	SLC9A3	phosphorylation
PRKG2	up-regulates	PTS	phosphorylation
PRKG2	“down-regulates activity”	HCN2	phosphorylation
PRKG2	“down-regulates activity”	PLCB3	phosphorylation
PRKG2	“down-regulates activity”	CTH	phosphorylation
PRKG2	“down-regulates activity”	EGFR	phosphorylation

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	6
Likely pathogenic	3
Uncertain significance	55
Likely benign	9
Benign	5

Top pathogenic / likely-pathogenic (9)

Variant ID	HGVS	Classification
1326257	NM_006259.3(PRKG2):c.1705C>T (p.Arg569Ter)	Pathogenic
1326258	NM_006259.3(PRKG2):c.491dup (p.Asn164fs)	Pathogenic
1326259	NM_006259.3(PRKG2):c.2282dup (p.Asp761fs)	Pathogenic
2164608	NM_006259.3(PRKG2):c.1904_1905insCACCTCTTCAGAGAAATGCAAAAATAACCTAACTAGTGATAAAGTGTATATACTTTAAGAGCGTA (p.Ser635_Leu636insThrSerSerGluLysCysLysAsnAsnLeuThrSerAspLysValTyrIleLeuTer)	Pathogenic
2171670	NM_006259.3(PRKG2):c.1901_1902insCAGCCACCTCTTCAGAGAAATGCAAAAATAACCTAACTAGTGATAAAGTGTATATACTTTAAGAGC (p.Trp634delinsCysSerHisLeuPheArgGluMetGlnLysTer)	Pathogenic
2502276	NM_006259.3(PRKG2):c.1154+1G>A	Pathogenic
2501812	NM_006259.3(PRKG2):c.1409T>G (p.Val470Gly)	Likely pathogenic
4082151	NM_006259.3(PRKG2):c.1630G>T (p.Asp544Tyr)	Likely pathogenic
4537385	NM_006259.3(PRKG2):c.1074del (p.Ala359fs)	Likely pathogenic

SpliceAI

3207 predictions. Top by Δscore:

Variant	Effect	Δscore
4:81105808:CTCA:C	donor_loss	1.0000
4:81105811:ACCT:A	donor_loss	1.0000
4:81105812:C:CT	donor_loss	1.0000
4:81105931:GTGGG:G	acceptor_gain	1.0000
4:81105932:TGGG:T	acceptor_gain	1.0000
4:81105933:GGG:G	acceptor_gain	1.0000
4:81105933:GGGC:G	acceptor_loss	1.0000
4:81105934:GG:G	acceptor_gain	1.0000
4:81105934:GGCT:G	acceptor_loss	1.0000
4:81105935:GCT:G	acceptor_loss	1.0000
4:81105936:C:CC	acceptor_gain	1.0000
4:81105937:T:G	acceptor_loss	1.0000
4:81105940:A:AC	acceptor_gain	1.0000
4:81105940:A:C	acceptor_gain	1.0000
4:81110446:A:AC	donor_gain	1.0000
4:81110447:C:CC	donor_gain	1.0000
4:81135295:CT:C	acceptor_gain	1.0000
4:81140526:CACTT:C	donor_loss	1.0000
4:81140527:ACTT:A	donor_loss	1.0000
4:81140528:CTTAC:C	donor_loss	1.0000
4:81140529:TTAC:T	donor_loss	1.0000
4:81140530:TA:T	donor_loss	1.0000
4:81140531:A:AC	donor_gain	1.0000
4:81140531:A:T	donor_loss	1.0000
4:81140531:ACTT:A	donor_gain	1.0000
4:81140532:C:CA	donor_gain	1.0000
4:81140532:CTT:C	donor_gain	1.0000
4:81140532:CTTC:C	donor_gain	1.0000
4:81140532:CTTCA:C	donor_gain	1.0000
4:81140669:CCT:C	acceptor_loss	1.0000

AlphaMissense

5021 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
4:81104414:C:A	R694S	1.000
4:81104414:C:G	R694S	1.000
4:81135207:C:A	R575I	1.000
4:81148941:C:A	R366M	1.000
4:81089725:A:G	W758R	0.999
4:81089725:A:T	W758R	0.999
4:81092451:A:G	W710R	0.999
4:81092451:A:T	W710R	0.999
4:81104409:C:T	G696E	0.999
4:81104410:C:G	G696R	0.999
4:81104410:C:T	G696R	0.999
4:81104415:C:A	R694M	0.999
4:81104415:C:G	R694T	0.999
4:81110460:A:G	L643P	0.999
4:81110472:A:G	L639P	0.999
4:81110478:C:T	G637E	0.999
4:81110479:C:G	G637R	0.999
4:81110479:C:T	G637R	0.999
4:81110488:A:G	W634R	0.999
4:81110488:A:T	W634R	0.999
4:81110542:A:G	Y616H	0.999
4:81110553:C:T	G612E	0.999
4:81110554:C:A	G612W	0.999
4:81110597:A:C	F597L	0.999
4:81110597:A:T	F597L	0.999
4:81110599:A:G	F597L	0.999
4:81110601:C:T	G596E	0.999
4:81110606:G:C	D594E	0.999
4:81110606:G:T	D594E	0.999
4:81110607:T:A	D594V	0.999

dbSNP variants (sampled 300 via entrez): RS1000004830 (4:81212387 TAAAC>T), RS10000303 (4:81169535 T>C), RS1000031248 (4:81191143 T>C), RS1000057426 (4:81102602 A>G), RS1000068402 (4:81133725 T>C), RS1000098098 (4:81198607 C>T), RS1000101580 (4:81158799 C>A,G), RS1000116459 (4:81208511 T>C,G), RS1000129062 (4:81128273 G>A,T), RS1000148099 (4:81150315 T>A,C), RS1000148441 (4:81187410 C>A,T), RS1000165080 (4:81175046 T>C), RS1000217587 (4:81125036 T>C,G), RS1000226511 (4:81172449 A>G), RS1000243529 (4:81105858 C>G)

Disease associations

OMIM: gene MIM:601591 | disease phenotypes: MIM:619636, MIM:619638

GenCC curated gene-disease

Disease	Classification	Inheritance
acromesomelic dysplasia 4	Strong	Autosomal recessive
spondylometaphyseal dysplasia, pagnamenta type	Strong	Autosomal recessive

Mondo (2): acromesomelic dysplasia 4 (MONDO:0030553), spondylometaphyseal dysplasia, pagnamenta type (MONDO:0030487)

Orphanet (0):

HPO phenotypes

56 total (30 of 56 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000303	Mandibular prognathia
HP:0000307	Pointed chin
HP:0000325	Triangular face
HP:0000369	Low-set ears
HP:0000431	Wide nasal bridge
HP:0000574	Thick eyebrow
HP:0000592	Blue sclerae
HP:0000664	Synophrys
HP:0000884	Prominent sternum
HP:0000920	Enlargement of the costochondral junction
HP:0000926	Platyspondyly
HP:0000998	Hypertrichosis
HP:0001252	Hypotonia
HP:0001500	Broad finger
HP:0001537	Umbilical hernia
HP:0001709	Third degree atrioventricular block
HP:0001763	Pes planus
HP:0001831	Short toe
HP:0001837	Broad toe
HP:0001852	Sandal gap
HP:0002230	Generalized hirsutism
HP:0002645	Wormian bones
HP:0002750	Delayed skeletal maturation
HP:0002753	Thin bony cortex
HP:0002857	Genu valgum
HP:0002938	Lumbar hyperlordosis
HP:0002942	Thoracic kyphosis
HP:0002943	Thoracic scoliosis
HP:0002970	Genu varum

GWAS associations

47 associations (top):

Study	Trait	p-value
GCST000175_43	Height	2.000000e-06
GCST000372_8	Height	2.000000e-08
GCST001353_8	HIV-1 susceptibility	9.000000e-06
GCST001876_7	Pubertal anthropometrics	1.000000e-07
GCST001956_15	Height	4.000000e-18
GCST002587_7	Blood pressure (smoking interaction)	6.000000e-07
GCST002647_140	Height	8.000000e-48
GCST004063_101	Waist circumference adjusted for body mass index	2.000000e-13
GCST004063_131	Waist circumference adjusted for body mass index	6.000000e-13
GCST004067_167	Hip circumference adjusted for BMI	3.000000e-06
GCST004067_225	Hip circumference adjusted for BMI	2.000000e-10
GCST004067_60	Hip circumference adjusted for BMI	1.000000e-13
GCST004500_1	Waist circumference adjusted for BMI (adjusted for smoking behaviour)	1.000000e-06
GCST004500_14	Waist circumference adjusted for BMI (adjusted for smoking behaviour)	1.000000e-09
GCST004501_123	Waist circumference adjusted for BMI (joint analysis main effects and smoking interaction)	2.000000e-09
GCST004501_124	Waist circumference adjusted for BMI (joint analysis main effects and smoking interaction)	2.000000e-06
GCST004504_90	Waist circumference adjusted for BMI in non-smokers	6.000000e-06
GCST004504_91	Waist circumference adjusted for BMI in non-smokers	8.000000e-09
GCST004562_120	Waist circumference adjusted for body mass index	5.000000e-09
GCST004562_182	Waist circumference adjusted for body mass index	1.000000e-09
GCST004562_201	Waist circumference adjusted for body mass index	4.000000e-06
GCST004563_164	Waist circumference adjusted for BMI (joint analysis main effects and physical activity interaction)	6.000000e-06
GCST004563_232	Waist circumference adjusted for BMI (joint analysis main effects and physical activity interaction)	2.000000e-09
GCST004563_97	Waist circumference adjusted for BMI (joint analysis main effects and physical activity interaction)	1.000000e-08
GCST004564_47	Waist circumference adjusted for BMI in active individuals	4.000000e-06
GCST004564_48	Waist circumference adjusted for BMI in active individuals	4.000000e-06
GCST007559_13	Sleep duration (short sleep)	3.000000e-09
GCST008163_503	Height	6.000000e-18
GCST008839_403	Height	7.000000e-10
GCST008839_421	Height	3.000000e-38

EFO canonical traits (9, from GWAS)

EFO ID	Trait name
EFO:0000180	HIV-1 infection
EFO:0001382	puberty
EFO:0006335	systolic blood pressure
EFO:0006526	pack-years measurement
EFO:0007789	BMI-adjusted waist circumference
EFO:0008039	BMI-adjusted hip circumference
EFO:0004318	smoking behavior
EFO:0008002	physical activity measurement
EFO:0009819	comparative body size at age 10, self-reported

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL2896 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

10 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 29,095 (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
CHEMBL1789941	RUXOLITINIB	4	11,547
CHEMBL608533	MIDOSTAURIN	4	7,259
CHEMBL300138	ENZASTAURIN	3	3,209
CHEMBL603469	LESTAURTINIB	3
CHEMBL91829	RUBOXISTAURIN	3	77
CHEMBL475251	R-406	2	762
CHEMBL1908397	KW-2449	1	622
CHEMBL494089	GSK-690693	1	2,061
CHEMBL5426285	5-(6-BENZOTHIAZOLYLMETHYLENE)-3,5-DIHYDRO-2-(((1S)-1-(METHOXYMETHYL)-3-METHYLBUTYL)AMINO)-4H-IMIDAZOL-4-ONE, (5Z)-	1	4

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

GtoPdb / IUPHAR curated pharmacology

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

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

Most potent curated ligand interactions (2 total), top 2:

Ligand	Action	Affinity	Parameter
compound 32 [PMID: 20471253]	Inhibition	7.62	pIC50
aplithianine A	Inhibition	7.47	pIC50

Binding affinities (BindingDB)

5 measured of 5 human assays (5 total across all organisms); most potent 5 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value
Staurosporine	KD	1.7 nM
PET-cGMP	EC50	5.8 nM
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

ChEMBL bioactivities

118 potent at pChembl≥5 of 118 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
8.60	IC50	2.512	nM	CHEMBL5278787
8.60	Ki	2.512	nM	CHEMBL1990254
8.51	Kd	3.1	nM	GSK-690693
8.50	Ki	3.162	nM	CHEMBL1990254
8.40	Ki	3.981	nM	CHEMBL2001751
8.40	Ki	3.981	nM	CHEMBL1976240
8.24	IC50	5.77	nM	STAUROSPORINE
8.15	IC50	7.06	nM	STAUROSPORINE
8.10	Ki	7.943	nM	CHEMBL1991063
7.90	Ki	12.59	nM	CHEMBL1974870
7.80	Kd	16	nM	STAUROSPORINE
7.80	Ki	15.85	nM	CHEMBL1975121
7.72	Kd	19	nM	CHEMBL379218
7.70	Ki	19.95	nM	CHEMBL592030
7.70	Ki	19.95	nM	CHEMBL2006188
7.70	Ki	19.95	nM	CHEMBL1991188
7.62	IC50	24	nM	CHEMBL1082821
7.60	Kd	25	nM	LESTAURTINIB
7.60	Ki	25.12	nM	CHEMBL1965836
7.60	Ki	25.12	nM	CHEMBL1682552
7.58	IC50	26.5	nM	STAUROSPORINE
7.50	Ki	31.62	nM	CHEMBL1998159
7.50	Ki	31.62	nM	CHEMBL1974288
7.47	IC50	34	nM	CHEMBL5433617
7.40	Ki	39.81	nM	CHEMBL1981782
7.40	Ki	39.81	nM	CHEMBL1975900
7.40	Ki	39.81	nM	GSK-269962A
7.40	Ki	39.81	nM	CHEMBL1682553
7.40	Ki	39.81	nM	CHEMBL1998121
7.36	Kd	44	nM	CHEMBL4576489
7.30	Ki	50.12	nM	CHEMBL2005936
7.30	Ki	50.12	nM	CHEMBL1999428
7.30	Ki	50.12	nM	CHEMBL1970217
7.19	Kd	65	nM	CHEMBL4465866
7.13	Kd	74	nM	MIDOSTAURIN
7.10	Ki	79.43	nM	CHEMBL1969049
7.10	Ki	79.43	nM	CHEMBL225519
7.00	Ki	100	nM	CHEMBL1974935
6.93	IC50	118	nM	5-(6-BENZOTHIAZOLYLMETHYLENE)-3,5-DIHYDRO-2-(((1S)-1-(METHOXYMETHYL)-3-METHYLBUTYL)AMINO)-4H-IMIDAZOL-4-ONE, (5Z)-
6.90	Ki	125.9	nM	CHEMBL1967544
6.80	Ki	158.5	nM	CHEMBL2003341
6.80	Ki	158.5	nM	CHEMBL1993548
6.80	Ki	158.5	nM	CHEMBL1982711
6.80	Ki	158.5	nM	CHEMBL2007296
6.77	Kd	170	nM	ENZASTAURIN
6.70	Ki	199.5	nM	CHEMBL1975128
6.70	Ki	199.5	nM	CHEMBL1996931
6.62	Kd	240	nM	TAE-684
6.60	Ki	251.2	nM	CHEMBL1988608
6.50	Ki	316.2	nM	BAY-549

PubChem BioAssay actives

45 with measured affinity, of 296 total; 24 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
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	0.0010	uM
N-[(1S)-2-amino-1-phenylethyl]-4-pyridin-4-ylbenzamide	1948865: Inhibition of PRKG2 (unknown origin)	ic50	0.0025	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	625053: Binding constant for PRKG2 kinase domain	kd	0.0031	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	0.0053	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	1531851: Inhibition of human PKG2 using LRRASLG as substrate by [gamma-33P]-ATP assay	ic50	0.0058	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	0.0110	uM
(2S)-1-[[5-(3-methyl-2H-indazol-5-yl)-3-pyridinyl]oxy]-3-phenylpropan-2-amine	625053: Binding constant for PRKG2 kinase domain	kd	0.0190	uM
(3S,4R)-N-(7-chloro-1-oxo-2H-isoquinolin-6-yl)-4-(4-chlorophenyl)pyrrolidine-3-carboxamide	483959: Inhibition of PRKG2	ic50	0.0240	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	508051: Binding affinity to PRKG2	kd	0.0250	uM
6-(3-methylimidazol-4-yl)-4-(7H-purin-6-yl)-2,3-dihydro-1,4-thiazine	2019961: Inhibition of PKG2 (unknown origin)	ic50	0.0340	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	1526286: Binding affinity to recombinant full-length N-terminal His-FLAG-tagged PRKG2 (unknown origin) expressed in baculovirus infected Sf9 insect cells incubated for 1 hr by TR-FRET assay	kd	0.0440	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	1526286: Binding affinity to recombinant full-length N-terminal His-FLAG-tagged PRKG2 (unknown origin) expressed in baculovirus infected Sf9 insect cells incubated for 1 hr by TR-FRET assay	kd	0.0650	uM
Midostaurin	435322: Binding constant for PRKG2 kinase domain	kd	0.0740	uM
(5Z)-5-(1,3-benzothiazol-6-ylmethylidene)-2-[(2R)-1-methoxy-4-methylpentan-2-yl]iminoimidazolidin-4-one	2024510: Inhibition of human PRKG2 assessed as remaining activity by eurofins-cerep kinase profiler analysis	ic50	0.1180	uM
3-(1-methylindol-3-yl)-4-[1-[1-(pyridin-2-ylmethyl)piperidin-4-yl]indol-3-yl]pyrrole-2,5-dione	625053: Binding constant for PRKG2 kinase domain	kd	0.1700	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	625053: Binding constant for PRKG2 kinase domain	kd	0.2400	uM
(2S)-1-[4-[2-(difluoromethyl)-4-pyridinyl]-2-(trifluoromethyl)phenoxy]-2,4-dimethylpentan-2-amine	1826925: Inhibition of PKG2 (unknown origin)	ic50	0.3800	uM
(2S)-1-[2-(difluoromethyl)-4-[2-(difluoromethyl)-4-pyridinyl]phenoxy]-2,4-dimethylpentan-2-amine	1826925: Inhibition of PKG2 (unknown origin)	ic50	0.4200	uM
2-(4-amino-1-propan-2-ylpyrazolo[3,4-d]pyrimidin-3-yl)-1H-indol-5-ol	625053: Binding constant for PRKG2 kinase domain	kd	0.5200	uM
Ruxolitinib	625053: Binding constant for PRKG2 kinase domain	kd	0.6900	uM
[4-[(E)-2-(1H-indazol-3-yl)ethenyl]phenyl]-piperazin-1-ylmethanone	625053: Binding constant for PRKG2 kinase domain	kd	0.8000	uM
Fedratinib	625053: Binding constant for PRKG2 kinase domain	kd	1.6000	uM
(18S)-18-[(dimethylamino)methyl]-17-oxa-4,14,21-triazahexacyclo[19.6.1.17,14.02,6.08,13.022,27]nonacosa-1(28),2(6),7(29),8,10,12,22,24,26-nonaene-3,5-dione	435322: Binding constant for PRKG2 kinase domain	kd	3.1000	uM
6-[[5-fluoro-2-(3,4,5-trimethoxyanilino)pyrimidin-4-yl]amino]-2,2-dimethyl-4H-pyrido[3,2-b][1,4]oxazin-3-one	625053: Binding constant for PRKG2 kinase domain	kd	3.6000	uM

CTD chemical–gene interactions

23 total (human), top 23 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	decreases expression, increases expression	3
FR900359	affects phosphorylation	1
sotorasib	affects cotreatment, decreases expression	1
bisphenol A	increases expression	1
CGP 52608	affects binding, increases reaction	1
fatostatin	decreases expression	1
trametinib	affects cotreatment, decreases expression	1
(+)-JQ1 compound	decreases expression	1
NVP-BKM120	affects cotreatment, decreases expression	1
Benzo(a)pyrene	increases methylation	1
Cisplatin	increases expression	1
Lead	affects expression	1
Potassium Dichromate	increases expression	1
Silicon Dioxide	decreases expression	1
Streptozocin	increases response to substance, decreases expression	1
Uric Acid	decreases expression	1
Valproic Acid	affects expression	1
Vanadium	decreases expression	1
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	decreases expression	1
Asbestos, Crocidolite	decreases expression	1
Antirheumatic Agents	increases expression	1
Okadaic Acid	decreases expression	1
Coal Ash	increases expression	1

ChEMBL screening assays

171 unique, capped per target: 170 binding, 1 functional

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1011946	Binding	Inhibition of PKG2 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
CHEMBL1963702	Functional	PUBCHEM_BIOASSAY: Navigating the Kinome. (Class of assay: other) Panel member name: PRKG2	PubChem BioAssay data set

Cellosaurus cell lines

4 cell lines: 3 cancer cell line, 1 induced pluripotent stem cell

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

Cellosaurus	Name	Category	Sex
CVCL_A7JB	IGIBi007-A	Induced pluripotent stem cell	Female
CVCL_D7YQ	Ubigene A-549 PRKG2 KO	Cancer cell line	Male
CVCL_TH03	HAP1 PRKG2 (-) 1	Cancer cell line	Male
CVCL_TH04	HAP1 PRKG2 (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

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