PRKACG

Summary

PRKACG (protein kinase cAMP-activated catalytic subunit gamma, HGNC:9382) is a protein-coding gene on chromosome 9q21.11, encoding cAMP-dependent protein kinase catalytic subunit gamma (P22612). Phosphorylates a large number of substrates in the cytoplasm and the nucleus.

Cyclic AMP-dependent protein kinase (PKA) consists of two catalytic subunits and a regulatory subunit dimer. This gene encodes the gamma form of its catalytic subunit. The gene is intronless and is thought to be a retrotransposon derived from the gene for the alpha form of the PKA catalytic subunit.

Source: NCBI Gene 5568 — RefSeq curated summary.

At a glance

• Gene–disease (curated): platelet-type bleeding disorder 19 (Supportive, GenCC)
• GWAS associations: 2
• Clinical variants (ClinVar): 75 total — 1 pathogenic
• Phenotypes (HPO): 9
• Druggable target: yes — 10 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_002732

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:9382
Approved symbol	PRKACG
Name	protein kinase cAMP-activated catalytic subunit gamma
Location	9q21.11
Locus type	gene with protein product
Status	Approved
Aliases	PKACg
Ensembl gene	ENSG00000165059
Ensembl biotype	protein_coding
OMIM	176893
Entrez	5568

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000377276

RefSeq mRNA: 1 — MANE Select: NM_002732 NM_002732

CCDS: CCDS6625

Canonical transcript exons

ENST00000377276 — 1 exons

Exon	Start	End
ENSE00001473380	69012504	69014113

Expression profiles

Bgee: expression breadth broad, 17 present calls, max score 89.98.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.0358 / max 31.1249, expressed in 3 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
100801	0.0358	3

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
sperm	CL:0000019	89.98	gold quality
male germ cell	CL:0000015	89.22	gold quality
left testis	UBERON:0004533	84.03	gold quality
right testis	UBERON:0004534	83.87	gold quality
testis	UBERON:0000473	81.73	gold quality
mucosa of urinary bladder	UBERON:0001259	80.25	gold quality
endometrium epithelium	UBERON:0004811	79.67	gold quality
type B pancreatic cell	CL:0000169	78.96	gold quality
olfactory bulb	UBERON:0002264	78.72	gold quality
buccal mucosa cell	CL:0002336	77.95	silver quality
epithelial cell of pancreas	CL:0000083	74.71	gold quality
hair follicle	UBERON:0002073	72.73	gold quality
paraflocculus	UBERON:0005351	72.05	silver quality
middle frontal gyrus	UBERON:0002702	70.68	silver quality
adult organism	UBERON:0007023	70.40	gold quality
decidua	UBERON:0002450	68.31	gold quality
cervix squamous epithelium	UBERON:0006922	68.17	gold quality
nasal cavity epithelium	UBERON:0005384	67.95	gold quality
thymus	UBERON:0002370	66.33	gold quality
diaphragm	UBERON:0001103	66.18	gold quality
amniotic fluid	UBERON:0000173	65.90	silver quality
blood vessel layer	UBERON:0004797	65.69	gold quality
tendon of biceps brachii	UBERON:0008188	64.55	silver quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	64.05	gold quality
quadriceps femoris	UBERON:0001377	63.89	gold quality
pancreatic ductal cell	CL:0002079	63.78	silver quality
vastus lateralis	UBERON:0001379	63.60	gold quality
tibia	UBERON:0000979	63.42	gold quality
triceps brachii	UBERON:0001509	63.16	gold quality
Brodmann (1909) area 10	UBERON:0013541	63.03	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.32

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

24 targeting PRKACG, 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-4775	99.98	75.00	6394
HSA-MIR-3605-5P	99.96	67.12	932
HSA-MIR-4492	99.87	68.25	3611
HSA-MIR-762	99.58	66.61	1994
HSA-MIR-7106-5P	99.53	67.47	3574
HSA-MIR-4498	99.47	67.42	2360
HSA-MIR-3064-5P	99.26	66.13	1497
HSA-MIR-3085-3P	99.26	66.16	1490
HSA-MIR-6504-5P	99.26	65.95	1487
HSA-MIR-6734-3P	99.15	66.27	1627
HSA-MIR-5001-5P	99.05	66.76	1972
HSA-MIR-1227-5P	98.65	65.32	1549
HSA-MIR-4691-5P	98.41	66.77	1343
HSA-MIR-6792-3P	98.41	66.86	1359
HSA-MIR-6776-3P	98.38	66.34	655
HSA-MIR-7111-3P	97.80	66.75	1467
HSA-MIR-4723-3P	97.67	65.91	1017
HSA-MIR-5196-3P	97.57	65.98	979
HSA-MIR-3127-5P	97.52	65.24	786
HSA-MIR-6769B-3P	97.41	65.53	1036
HSA-MIR-3183	97.40	65.68	978
HSA-MIR-1225-3P	97.29	64.60	876
HSA-MIR-6856-3P	96.47	66.27	781
HSA-MIR-4653-3P	96.26	67.03	725

Literature-anchored findings (GeneRIF, showing 6)

• PKA-mediated phosphorylation of GPIbbeta at Ser(166) negatively regulates VWF binding to GPIb-IX and is one of the mechanisms by which PKA mediates platelet inhibition (PMID:12361948)
• Results suggest that Cgamma and Calpha differ in structure and function in vitro, supporting the hypothesis that functionally different C-subunit isozymes could affect cAMP signal transduction downstream of protein kinase A activation. (PMID:15039079)
• In human primary pigmented nodular adrenocortical disease tissues, dexamethasone paradoxically stimulates cortisol release through a glucocorticoid receptor-mediated effect on PKA catalytic subunits. (PMID:19383776)
• Findings show that PKIB and PKA-C kinase can have critical functions of aggressive phenotype of PCs through Akt phosphorylation and that they should be a promising molecular target for PC treatment. (PMID:19483721)
• Results suggest that PKA can negatively regulate ERalpha, at least in part, through FoxH1. (PMID:19711044)
• The missense p.74Ile>Met PRKACG mutation is associated with a marked defect in proplatelet formation and a low level in filamin A in megakaryocytes. (PMID:25061177)

Cross-species orthologs

7 orthologs

Organism	Symbol	Gene ID
danio_rerio	prkacba	ENSDARG00000001782
danio_rerio	prkg3	ENSDARG00000014232
danio_rerio	prkacab	ENSDARG00000016809
drosophila_melanogaster	Pka-C2	FBGN0000274
drosophila_melanogaster	Pkg21D	FBGN0000442
drosophila_melanogaster	CG12069	FBGN0039796
caenorhabditis_elegans		WBGENE00001173

Paralogs (5): PRKACA (ENSG00000072062), PRKG2 (ENSG00000138669), PRKACB (ENSG00000142875), PRKX (ENSG00000183943), PRKG1 (ENSG00000185532)

Protein

Protein identifiers

cAMP-dependent protein kinase catalytic subunit gamma — P22612 (reviewed: P22612)

All UniProt accessions (1): P22612

UniProt curated annotations — full annotation on UniProt →

Function. Phosphorylates a large number of substrates in the cytoplasm and the nucleus.

Subunit / interactions. A number of inactive tetrameric holoenzymes are produced by the combination of homo- or heterodimers of the different regulatory subunits associated with two catalytic subunits. cAMP causes the dissociation of the inactive holoenzyme into a dimer of regulatory subunits bound to four cAMP and two free monomeric catalytic subunits.

Tissue specificity. Testis specific. But important tissues such as brain and ovary have not been analyzed for the content of transcript.

Disease relevance. Bleeding disorder, platelet-type, 19 (BDPLT19) [MIM:616176] A disorder characterized by increased bleeding tendency due to platelet dysfunction. Clinical features include epistaxis, hematomas, bleeding after tooth extraction, and menorrhagia. The disease is caused by variants affecting the gene represented in this entry.

Activity regulation. Activated by cAMP.

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

RefSeq proteins (1): NP_002723* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000719	Prot_kinase_dom	Domain
IPR000961	AGC-kinase_C	Domain
IPR008271	Ser/Thr_kinase_AS	Active_site
IPR011009	Kinase-like_dom_sf	Homologous_superfamily
IPR017441	Protein_kinase_ATP_BS	Binding_site
IPR044109	STKc_PKA	Family

Pfam: PF00069

Enzyme classification (BRENDA):

• EC 2.7.11.11 — cAMP-dependent protein kinase (BRENDA: 43 organisms, 244 substrates, 131 inhibitors, 50 Km, 11 kcat entries)

Substrate kinetics (BRENDA)

15 substrates with measured Km, best-characterized 15. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
KEMPTIDE	0.0097–0.0609	11
ATP	0.0169–0.039	9
LEU-ARG-ARG-ALA-SER-LEU-GLY	0.023–0.043	4
N6-BENZYL-ATP	0.0011–0.1	2
PEPTIDE RRYSV	0.027–0.029	2
RFARKGSLREKNV	0.0253–0.05	2
RKRSRAE	0.0333–0.293	2
RKRSRKE	0.0333–0.5	2
RRLSSLRA	0.0503–0.338	2
HISTONE	0.73	1
N-(8-([4-[3-(ETHOXYCARBONYL)-6,8,8-TRIMETHYL-2-O	0.0019	1
N-(8-([[7-(DIETHYLAMINO)-2-OXO-2H-CHROMEN-3-YL]C	0.0022	1
N-(8-[[(11-OXO-2,3,6,7-TETRAHYDRO-1H,5H,11H-PYRA	0.0062	1
N6-PHENETHYL-ATP	0.0015	1
RRASVA	0.021	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 (14 total): sequence variant 3, domain 2, binding site 2, modified residue 2, initiator methionine 1, chain 1, sequence conflict 1, active site 1, lipid moiety-binding region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P22612-F1	94.91	0.93

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): 167 (proton acceptor)

Ligand- & substrate-binding residues (2): 50–58; 73

Post-translational modifications (3): 198, 339, 2

Function

Pathways and Gene Ontology

Reactome pathways

79 pathways

ID	Pathway
R-HSA-111931	PKA-mediated phosphorylation of CREB
R-HSA-163358	PKA-mediated phosphorylation of key metabolic factors
R-HSA-163560	Triglyceride catabolism
R-HSA-163615	PKA activation
R-HSA-164378	PKA activation in glucagon signalling
R-HSA-180024	DARPP-32 events
R-HSA-381676	Glucagon-like Peptide-1 (GLP1) regulates insulin secretion
R-HSA-392517	Rap1 signalling
R-HSA-422356	Regulation of insulin secretion
R-HSA-432040	Vasopressin regulates renal water homeostasis via Aquaporins
R-HSA-4420097	VEGFA-VEGFR2 Pathway
R-HSA-442720	CREB1 phosphorylation through the activation of Adenylate Cyclase
R-HSA-5610780	Degradation of GLI1 by the proteasome
R-HSA-5610783	Degradation of GLI2 by the proteasome
R-HSA-5610785	GLI3 is processed to GLI3R by the proteasome
R-HSA-5610787	Hedgehog ‘off’ state
R-HSA-5621575	CD209 (DC-SIGN) signaling
R-HSA-5687128	MAPK6/MAPK4 signaling
R-HSA-8853659	RET signaling
R-HSA-8963896	HDL assembly
R-HSA-9010642	ROBO receptors bind AKAP5
R-HSA-9634597	GPER1 signaling
R-HSA-9634600	Regulation of glycolysis by fructose 2,6-bisphosphate metabolism
R-HSA-9660821	ADORA2B mediated anti-inflammatory cytokines production
R-HSA-9664323	FCGR3A-mediated IL10 synthesis
R-HSA-983231	Factors involved in megakaryocyte development and platelet production
R-HSA-9856530	High laminar flow shear stress activates signaling by PIEZO1 and PECAM1:CDH5:KDR in endothelial cells
R-HSA-109582	Hemostasis
R-HSA-111885	Opioid Signalling
R-HSA-111933	Calmodulin induced events

MSigDB gene sets: 281 (showing top): REACTOME_TRIGLYCERIDE_CATABOLISM, REACTOME_INNATE_IMMUNE_SYSTEM, YAGI_AML_WITH_INV_16_TRANSLOCATION, KEGG_HEDGEHOG_SIGNALING_PATHWAY, REACTOME_ADAPTIVE_IMMUNE_SYSTEM, GOBP_RESPONSE_TO_FLUID_SHEAR_STRESS, KEGG_MAPK_SIGNALING_PATHWAY, GCANCTGNY_MYOD_Q6, GOBP_INSULIN_SECRETION, GOBP_CELLULAR_RESPONSE_TO_FLUID_SHEAR_STRESS, GOBP_POSITIVE_REGULATION_OF_PROTEIN_LOCALIZATION, GOBP_REGULATION_OF_HORMONE_LEVELS, GOBP_HORMONE_TRANSPORT, GOBP_PROTEIN_LIPID_COMPLEX_ASSEMBLY, GOBP_MALE_GAMETE_GENERATION

GO Biological Process (8): renal water homeostasis (GO:0003091), adenylate cyclase-activating G protein-coupled receptor signaling pathway (GO:0007189), spermatogenesis (GO:0007283), male gonad development (GO:0008584), positive regulation of insulin secretion (GO:0032024), high-density lipoprotein particle assembly (GO:0034380), vascular endothelial cell response to laminar fluid shear stress (GO:0097700), protein phosphorylation (GO:0006468)

GO Molecular Function (11): protein serine/threonine kinase activity (GO:0004674), cAMP-dependent protein kinase activity (GO:0004691), ATP binding (GO:0005524), potassium channel inhibitor activity (GO:0019870), protein kinase A regulatory subunit binding (GO:0034237), protein serine kinase activity (GO:0106310), nucleotide binding (GO:0000166), protein kinase activity (GO:0004672), protein binding (GO:0005515), kinase activity (GO:0016301), transferase activity (GO:0016740)

GO Cellular Component (5): nucleus (GO:0005634), nucleoplasm (GO:0005654), cytosol (GO:0005829), cAMP-dependent protein kinase complex (GO:0005952), ciliary base (GO:0097546)

Reactome top-level categories

Rollup of top-17 pathways:

Category	Pathways
Hedgehog ‘off’ state	3
Integration of energy metabolism	2
Calmodulin induced events	1
Triglyceride metabolism	1
PKA-mediated phosphorylation of CREB	1
Glucagon signaling in metabolic regulation	1
Opioid Signalling	1
Regulation of insulin secretion	1
Adaptive Immune System	1
Aquaporin-mediated transport	1
Signaling by VEGF	1
Post NMDA receptor activation events	1
Signaling by Hedgehog	1
C-type lectin receptors (CLRs)	1
MAPK family signaling cascades	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
protein kinase activity	2
renal system process	1
multicellular organismal-level water homeostasis	1
adenylate cyclase-modulating G protein-coupled receptor signaling pathway	1
adenylate cyclase activator activity	1
developmental process involved in reproduction	1
male gamete generation	1
gonad development	1
development of primary male sexual characteristics	1
insulin secretion	1
positive regulation of protein secretion	1
regulation of insulin secretion	1
positive regulation of peptide hormone secretion	1
plasma lipoprotein particle assembly	1
cellular response to laminar fluid shear stress	1
vascular endothelial cell response to fluid shear stress	1
phosphorylation	1
protein modification process	1
cyclic nucleotide-dependent protein kinase activity	1
cAMP binding	1
adenyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
potassium channel activity	1
ion channel inhibitor activity	1
potassium channel regulator activity	1
protein kinase A 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
binding	1
transferase activity, transferring phosphorus-containing groups	1
catalytic activity	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
cytoplasm	1
intracellular protein-containing complex	1
serine/threonine protein kinase complex	1

Protein interactions and networks

STRING

6638 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PRKACG	AKAP1	Q92667	998
PRKACG	AKAP12	Q02952	989
PRKACG	AKAP5	P24588	985
PRKACG	EZR	P15311	983
PRKACG	CALML3	P27482	979
PRKACG	CALML4	Q96GE6	979
PRKACG	CALML5	Q9NZT1	979
PRKACG	CALM1	P02593	978
PRKACG	CALML6	Q8TD86	978
PRKACG	RAPGEF3	O95398	974
PRKACG	AKAP9	Q99996	967
PRKACG	RAPGEF4	Q8WZA2	967
PRKACG	AKAP6	Q13023	951
PRKACG	CREB1	P16220	945
PRKACG	SUFU	Q9UMX1	929

IntAct

53 interactions, top by confidence:

A	B	Type	Score
PRKACB	PRKAR1A	psi-mi:“MI:0914”(association)	0.790
VAPB	FAM83G	psi-mi:“MI:0914”(association)	0.730
DYNLL1	BLTP3B	psi-mi:“MI:0914”(association)	0.730
PRKACA	VAPB	psi-mi:“MI:0914”(association)	0.730
DYNLL2	BLTP3B	psi-mi:“MI:0914”(association)	0.640
APP	PRKACG	psi-mi:“MI:0915”(physical association)	0.560
PRKACB	PRKAR1A	psi-mi:“MI:0914”(association)	0.550
PRKACG	UBB	psi-mi:“MI:0914”(association)	0.530
MLF1	NDC80	psi-mi:“MI:0914”(association)	0.530
MRPS15	MRPS14	psi-mi:“MI:0914”(association)	0.530
GPR161	USP12	psi-mi:“MI:0914”(association)	0.530
ST8SIA3	KLRG2	psi-mi:“MI:0914”(association)	0.530
TFDP3	E2F3	psi-mi:“MI:0914”(association)	0.530
CCNL2	ZBTB43	psi-mi:“MI:0914”(association)	0.530
PKIG	TYMS	psi-mi:“MI:0914”(association)	0.530
MRPS15	PRKACG	psi-mi:“MI:0914”(association)	0.530
GPR161	PRKAR1A	psi-mi:“MI:0914”(association)	0.530
AKAP14	PRKAR2A	psi-mi:“MI:0914”(association)	0.530
PELI3	PRKACG	psi-mi:“MI:0915”(physical association)	0.400
CETP	PRKACG	psi-mi:“MI:0915”(physical association)	0.370
PRKACG	CDK17	psi-mi:“MI:0915”(physical association)	0.370
AKAP14	EFCAB7	psi-mi:“MI:0914”(association)	0.350

BioGRID (126): PRKACG (Affinity Capture-MS), PRKACG (Affinity Capture-MS), PRKACG (Affinity Capture-MS), PRKAR2B (Affinity Capture-MS), PRKAR1A (Affinity Capture-MS), AKAP5 (Affinity Capture-MS), PRKACG (Affinity Capture-MS), PRKACG (Affinity Capture-MS), PDE4DIP (Affinity Capture-MS), AKAP9 (Affinity Capture-MS), AKAP7 (Affinity Capture-MS), PRKACG (Affinity Capture-MS), AKAP1 (Affinity Capture-MS), PRKACG (Affinity Capture-MS), UBB (Affinity Capture-MS)

ESM2 similar proteins: A1CPG7, A8KBH6, A8X6H1, A8XW88, O62846, P00517, P04409, P05126, P05131, P05132, P05383, P05696, P05771, P05772, P0C431, P10102, P12370, P17252, P17612, P20444, P21137, P22612, P22694, P25321, P27791, P36887, P49673, P51817, P54644, P68180, P68181, P68182, P68403, P68404, Q0D0P5, Q13237, Q16974, Q2H332, Q2WGK3, Q52PH6

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

14 interactions.

A	Effect	B	Mechanism
PRKACG	up-regulates	NOS3	phosphorylation
PRKACG	up-regulates	MYBPC3	phosphorylation
PRKACG	“down-regulates activity”	TENT2	phosphorylation
PRKACG	“down-regulates activity”	PHKA2	phosphorylation
PRKACG	“down-regulates activity”	PHKA1	phosphorylation
PRKACG	down-regulates	BAD	phosphorylation
PRKACG	“down-regulates activity”	BAD	phosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 60 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
PKA activation in glucagon signalling	5	76.3×	9e-07
PKA activation	5	72.1×	9e-07
PKA-mediated phosphorylation of CREB	5	64.9×	1e-06
DARPP-32 events	5	54.1×	3e-06
Anti-inflammatory response favouring Leishmania parasite infection	5	44.8×	5e-06
Leishmania parasite growth and survival	5	44.8×	5e-06
Calmodulin induced events	5	43.3×	5e-06
CaM pathway	5	43.3×	5e-06

GO biological processes:

GO term	Partners	Fold	FDR
vascular endothelial cell response to laminar fluid shear stress	5	66.6×	5e-06
renal water homeostasis	5	46.4×	2e-05
adenylate cyclase-activating G protein-coupled receptor signaling pathway	6	12.3×	1e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	59
Likely benign	5
Benign	8

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
3245327	NC_000009.11:g.(?71627953)(72006720_?)del	Pathogenic

SpliceAI

69 predictions. Top by Δscore:

Variant	Effect	Δscore
9:69013727:CTCCA:C	donor_gain	0.9800
9:69013728:TCCAT:T	donor_gain	0.9800
9:69013729:CCATC:C	donor_gain	0.9800
9:69013731:A:AC	donor_gain	0.9800
9:69013726:A:AC	donor_gain	0.9600
9:69013727:C:CC	donor_gain	0.9600
9:69013726:ACT:A	donor_gain	0.8800
9:69013727:CTC:C	donor_gain	0.8800
9:69013729:C:CA	donor_gain	0.8300
9:69013727:CT:C	donor_gain	0.8200
9:69013724:G:T	donor_gain	0.7000
9:69013755:T:TA	donor_gain	0.6300
9:69013728:T:C	donor_gain	0.6000
9:69013054:C:CA	donor_gain	0.5600
9:69013066:T:TA	donor_gain	0.5100
9:69013730:CA:C	donor_gain	0.5100
9:69013264:C:CT	donor_gain	0.5000
9:69013265:C:CT	donor_gain	0.5000
9:69013092:T:TA	donor_gain	0.4600
9:69013647:GC:G	acceptor_gain	0.4600
9:69013345:T:TA	donor_gain	0.4500
9:69013729:C:CG	donor_gain	0.4500
9:69013732:TC:T	donor_gain	0.4400
9:69013331:C:CA	donor_gain	0.4200
9:69013053:T:TA	donor_gain	0.4100
9:69013234:T:A	donor_gain	0.3900
9:69013328:C:CT	donor_gain	0.3700
9:69013158:TCC:T	donor_gain	0.3600
9:69013277:GCTCC:G	acceptor_gain	0.3600
9:69013047:G:C	donor_gain	0.3400

AlphaMissense

2330 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
9:69013376:G:C	F239L	0.992
9:69013376:G:T	F239L	0.992
9:69013378:A:G	F239L	0.992
9:69013426:A:G	W223R	0.992
9:69013426:A:T	W223R	0.992
9:69013538:G:C	D185E	0.991
9:69013538:G:T	D185E	0.991
9:69013539:T:A	D185V	0.991
9:69013801:C:G	A98P	0.989
9:69013204:A:G	W297R	0.988
9:69013204:A:T	W297R	0.988
9:69013252:G:T	R281S	0.987
9:69013417:C:A	G226W	0.987
9:69013605:A:G	L163P	0.987
9:69013540:C:G	D185H	0.986
9:69013593:T:A	D167V	0.986
9:69013186:A:G	W303R	0.985
9:69013186:A:T	W303R	0.985
9:69013424:C:A	W223C	0.985
9:69013424:C:G	W223C	0.985
9:69013862:C:A	K77N	0.985
9:69013862:C:G	K77N	0.985
9:69013429:A:G	W222R	0.984
9:69013429:A:T	W222R	0.984
9:69013539:T:G	D185A	0.984
9:69013928:G:C	F55L	0.984
9:69013928:G:T	F55L	0.984
9:69013930:A:G	F55L	0.984
9:69013586:C:A	K169N	0.983
9:69013586:C:G	K169N	0.983

dbSNP variants (sampled 300 via entrez): RS1003668540 (9:69015340 C>T), RS1004674204 (9:69012231 T>G), RS1006778927 (9:69012562 C>A), RS1007207719 (9:69014671 C>T), RS1007903139 (9:69015457 G>C), RS1008305850 (9:69015085 T>A), RS1008788995 (9:69015886 T>C), RS1010262108 (9:69012452 G>C,T), RS1010415111 (9:69015842 AACAACAC>A), RS1011241493 (9:69012323 A>C), RS1011251340 (9:69012533 T>C), RS1012321767 (9:69015805 C>T), RS1014514538 (9:69014170 G>GGCTGGCTGC), RS1016513377 (9:69013131 C>T), RS1016796729 (9:69014335 CATT>C)

Disease associations

OMIM: gene MIM:176893 | disease phenotypes: MIM:616176

GenCC curated gene-disease

Disease	Classification	Inheritance
platelet-type bleeding disorder 19	Supportive	Autosomal recessive

ClinGen Gene-Disease Validity (1)

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

Disease	Classification	Inheritance
platelet-type bleeding disorder 19	Disputed	AR

Mondo (1): platelet-type bleeding disorder 19 (MONDO:0014518)

Orphanet (1): Severe autosomal recessive macrothrombocytopenia (Orphanet:438207)

HPO phenotypes

9 total (9 of 9 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000132	Menorrhagia
HP:0000421	Epistaxis
HP:0001873	Thrombocytopenia
HP:0001892	Abnormal bleeding
HP:0001903	Anemia
HP:0003593	Infantile onset
HP:0007420	Spontaneous hematomas
HP:0040185	Macrothrombocytopenia

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST003542_111	Night sleep phenotypes	1.000000e-06
GCST009391_726	Metabolite levels	5.000000e-07

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0009774	serine measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (2): CHEMBL2094138 (PROTEIN FAMILY), CHEMBL2743 (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: 49,360 (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
CHEMBL2396661	ALPELISIB	4	6,070
CHEMBL38380	FASUDIL	3	11,953
CHEMBL1088752	LOSMAPIMOD	3	865
CHEMBL574737	UCN-01	2	2,217
CHEMBL575448	BMS-754807	2	406
CHEMBL6246	ELLAGIC ACID	2	23,148
CHEMBL411907	SONOLISIB	2	2,705
CHEMBL495727	AT-9283	2	1,376
CHEMBL496102	AMG-208	2	387
CHEMBL3128043	PF-03758309	1	233

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

GtoPdb / IUPHAR curated pharmacology

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

Target class: enzyme — Protein kinase A (PKA) family

Binding affinities (BindingDB)

2 measured of 2 human assays (2 total across all organisms); most potent 2 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value
CHEMBL5188493	IC50	2.6 nM
CHEMBL5181354	IC50	159 nM

ChEMBL bioactivities

261 potent at pChembl≥5 of 324 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
10.00	IC50	0.1	nM	CHEMBL213618
10.00	Kd	0.1	nM	CHEMBL5183651
9.15	IC50	0.7	nM	STAUROSPORINE
9.05	IC50	0.9	nM	STAUROSPORINE
9.00	IC50	1	nM	CHEMBL207544
8.96	IC50	1.1	nM	CHEMBL3613610
8.89	IC50	1.29	nM	STAUROSPORINE
8.70	Kd	2	nM	AMG-208
8.68	IC50	2.1	nM	CHEMBL383264
8.66	IC50	2.2	nM	CHEMBL3613609
8.59	IC50	2.6	nM	CHEMBL3613599
8.59	IC50	2.6	nM	CHEMBL5188493
8.57	IC50	2.7	nM	CHEMBL3613605
8.52	IC50	3	nM	CHEMBL436718
8.52	Kd	3	nM	AT-9283
8.47	Ki	3.4	nM	CHEMBL365598
8.44	IC50	3.6	nM	STAUROSPORINE
8.42	IC50	3.8	nM	CHEMBL3613612
8.41	Ki	3.9	nM	CHEMBL193697
8.40	Ki	4	nM	CHEMBL436718
8.40	IC50	4	nM	BALANOL
8.40	IC50	4	nM	STAUROSPORINE
8.33	Ki	4.7	nM	BALANOL
8.30	IC50	5	nM	CHEMBL378963
8.30	IC50	5	nM	CHEMBL226625
8.29	IC50	5.1	nM	CHEMBL3613611
8.27	IC50	5.4	nM	CHEMBL3613603
8.24	IC50	5.8	nM	CHEMBL3613606
8.19	IC50	6.5	nM	STAUROSPORINE
8.19	IC50	6.49	nM	STAUROSPORINE
8.17	IC50	6.8	nM	CHEMBL226148
8.17	IC50	6.8	nM	STAUROSPORINE
8.15	IC50	7	nM	CHEMBL3613604
8.15	Kd	7	nM	SONOLISIB
8.15	IC50	7	nM	CHEMBL427422
8.10	IC50	8	nM	CHEMBL210390
8.09	IC50	8.2	nM	STAUROSPORINE
8.05	IC50	9	nM	CHEMBL438483
7.89	IC50	13	nM	CHEMBL226898
7.82	IC50	15	nM	CHEMBL228042
7.82	IC50	15	nM	CHEMBL376569
7.82	IC50	15	nM	CHEMBL388312
7.82	IC50	15	nM	STAUROSPORINE
7.80	Ki	16	nM	CHEMBL379218
7.80	IC50	16	nM	CHEMBL374808
7.80	IC50	16	nM	STAUROSPORINE
7.75	IC50	18	nM	CHEMBL374805
7.73	IC50	18.5	nM	CHEMBL291126
7.72	IC50	19	nM	STAUROSPORINE
7.66	IC50	22	nM	CHEMBL3613607

PubChem BioAssay actives

201 with measured affinity, of 1067 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-[(2S)-1-amino-3-(2,4-dichlorophenyl)propan-2-yl]-5-[2-(methylamino)pyrimidin-4-yl]thiophene-2-carboxamide	269862: Inhibition of PKA	ic50	0.0001	uM
9-[4-(4a,7-dihydro-4H-pyrrolo[2,3-d]pyrimidin-4-yl)piperazin-1-yl]-N-[(2R)-5-(diaminomethylideneamino)-1-[[(2R)-5-(diaminomethylideneamino)-1-[[(2R)-5-(diaminomethylideneamino)-1-[[(2R)-5-(diaminomethylideneamino)-1-[[(2R)-5-(diaminomethylideneamino)-1-[[(2R)-5-(diaminomethylideneamino)-1-[[(2R)-1,6-diamino-1-oxohexan-2-yl]amino]-1-oxopentan-2-yl]amino]-1-oxopentan-2-yl]amino]-1-oxopentan-2-yl]amino]-1-oxopentan-2-yl]amino]-1-oxopentan-2-yl]amino]-1-oxopentan-2-yl]-9-oxononanamide	1846294: Binding affinity to PKA (unknown origin) assessed as dissociation constant	kd	0.0001	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	1941062: Inhibition of PKA (unknown origin)	ic50	0.0007	uM
methyl 3-[[4-(aminomethyl)-1-(5-methyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl)piperidine-4-carbonyl]amino]benzoate	1244620: Inhibition of PKA (unknown origin) by radiometric assay	ic50	0.0010	uM
methyl 3-[[1-(5-cyano-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-4-[(dimethylamino)methyl]piperidine-4-carbonyl]amino]benzoate	1244620: Inhibition of PKA (unknown origin) by radiometric assay	ic50	0.0010	uM
methyl 3-[[4-[(dimethylamino)methyl]-1-(5-fluoro-7H-pyrrolo[2,3-d]pyrimidin-4-yl)piperidine-4-carbonyl]amino]benzoate	1244620: Inhibition of PKA (unknown origin) by radiometric assay	ic50	0.0010	uM
(2S)-1-[(6-ethynyl-5-isoquinolin-6-yl-3-pyridinyl)oxy]-3-(1H-indol-3-yl)propan-2-amine	265591: Inhibition of PKA at 5 uM ATP	ic50	0.0010	uM
[3-[[4-(aminomethyl)-1-(5-methyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl)piperidine-4-carbonyl]amino]phenyl] N,N-dimethylcarbamate	1244620: Inhibition of PKA (unknown origin) by radiometric assay	ic50	0.0010	uM
methyl 3-[[4-[(dimethylamino)methyl]-1-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)piperidine-4-carbonyl]amino]benzoate	1244620: Inhibition of PKA (unknown origin) by radiometric assay	ic50	0.0011	uM
7-methoxy-4-[(6-phenyl-[1,2,4]triazolo[4,3-b]pyridazin-3-yl)methoxy]quinoline	1425125: 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	0.0020	uM
(2S)-1-(1H-indol-3-yl)-3-[(5-isoquinolin-6-yl-3-pyridinyl)oxy]propan-2-amine	262972: Inhibition of PKA at 10 uM ATP	ic50	0.0021	uM
prop-2-ynyl 3-[[4-[(dimethylamino)methyl]-1-(5-methyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl)piperidine-4-carbonyl]amino]benzoate	1244620: Inhibition of PKA (unknown origin) by radiometric assay	ic50	0.0022	uM
N-[3-[2-[2-[3-[[2-[2-[[(4R,9S,12S,15S,18S,21S,24R)-4-[(2-amino-2-oxoethyl)carbamoyl]-9,18-dibenzyl-15-(3-carbamimidamidopropyl)-21-[(1R)-1-hydroxyethyl]-6,8,11,14,17,20,23-heptaoxo-12-propan-2-yl-1,2-dithia-5,7,10,13,16,19,22-heptazacyclopentacos-24-yl]amino]-2-oxoethoxy]acetyl]amino]propoxy]ethoxy]ethoxy]propyl]-N’-[(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]-N’-methylbutanediamide	1846292: Inhibition of PKA (unknown origin)	ic50	0.0026	uM
[3-[[4-[(dimethylamino)methyl]-1-(5-methyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl)piperidine-4-carbonyl]amino]phenyl] N,N-dimethylcarbamate	1244620: Inhibition of PKA (unknown origin) by radiometric assay	ic50	0.0026	uM
methyl 4-[[4-[(dimethylamino)methyl]-1-(5-methyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl)piperidine-4-carbonyl]amino]benzoate	1244620: Inhibition of PKA (unknown origin) by radiometric assay	ic50	0.0027	uM
1-cyclopropyl-3-[5-[6-(morpholin-4-ylmethyl)-1H-benzimidazol-2-yl]-1H-pyrazol-4-yl]urea	1425125: 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	0.0030	uM
(2S)-5-(diaminomethylideneamino)-2-[[(2S)-5-(diaminomethylideneamino)-2-[[(2S)-5-(diaminomethylideneamino)-2-[[(2S)-5-(diaminomethylideneamino)-2-[[(2S)-5-(diaminomethylideneamino)-2-[[(2S)-5-(diaminomethylideneamino)-2-[[(2S)-3-hydroxy-2-[3-[2-(isoquinolin-5-ylsulfonylamino)ethylamino]propanoylamino]propanoyl]amino]pentanoyl]amino]pentanoyl]amino]pentanoyl]amino]pentanoyl]amino]pentanoyl]amino]pentanoic acid	164138: Inhibition of cAMP-dependent protein kinase (PKA).	ic50	0.0030	uM
3-hydroxy-2-[4-[(3R,4R)-3-[(4-hydroxybenzoyl)amino]azepan-4-yl]oxycarbonylbenzoyl]benzoic acid	254305: Inhibitory constant against the protein kinase A	ki	0.0034	uM
methyl 3-[[4-[(dimethylamino)methyl]-1-(1H-pyrazolo[3,4-b]pyridin-4-yl)piperidine-4-carbonyl]amino]benzoate	1244620: Inhibition of PKA (unknown origin) by radiometric assay	ic50	0.0038	uM
2-[2,6-dihydroxy-4-[(3R,4R)-3-[(4-hydroxybenzoyl)amino]azepan-4-yl]oxycarbonylbenzoyl]benzoic acid	254305: Inhibitory constant against the protein kinase A	ki	0.0039	uM
2-[2,6-dihydroxy-4-[(3R,4R)-3-[(4-hydroxybenzoyl)amino]azepan-4-yl]oxycarbonylbenzoyl]-3-hydroxybenzoic acid	1902445: Inhibition of PKA (unknown origin)	ic50	0.0040	uM
(2S)-1-[(6-chloro-5-isoquinolin-6-yl-3-pyridinyl)oxy]-3-(1H-indol-3-yl)propan-2-amine	265591: Inhibition of PKA at 5 uM ATP	ic50	0.0050	uM
(2S)-1-[[5-(3-methyl-2H-indazol-5-yl)-3-pyridinyl]oxy]-3-[3-(trifluoromethyl)phenyl]propan-2-amine	290880: Inhibition of PKA	ic50	0.0050	uM
methyl 3-[[4-[(dimethylamino)methyl]-1-(1H-pyrazolo[5,4-d]pyrimidin-4-yl)piperidine-4-carbonyl]amino]benzoate	1244620: Inhibition of PKA (unknown origin) by radiometric assay	ic50	0.0051	uM
methyl 2-[3-[[4-[(dimethylamino)methyl]-1-(5-methyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl)piperidine-4-carbonyl]amino]phenoxy]acetate	1244620: Inhibition of PKA (unknown origin) by radiometric assay	ic50	0.0054	uM
propyl 3-[[4-[(dimethylamino)methyl]-1-(5-methyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl)piperidine-4-carbonyl]amino]benzoate	1244620: Inhibition of PKA (unknown origin) by radiometric assay	ic50	0.0058	uM
(2S)-1-[[5-(3-chloro-2H-indazol-5-yl)-3-pyridinyl]oxy]-3-(1H-indol-3-yl)propan-2-amine	287580: Inhibition of PKA	ic50	0.0068	uM
methyl 2-[3-[[4-[(dimethylamino)methyl]-1-(5-methyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl)piperidine-4-carbonyl]amino]phenyl]acetate	1244620: Inhibition of PKA (unknown origin) by radiometric assay	ic50	0.0070	uM
(2S)-1-(2,3-difluorophenyl)-3-[[5-(3-methyl-2H-pyrazolo[3,4-c]pyridin-5-yl)-3-pyridinyl]oxy]propan-2-amine	290880: Inhibition of PKA	ic50	0.0070	uM
[(3aR,6E,9S,9aR,10R,11aS)-6-[[bis(prop-2-enyl)amino]methylidene]-5-hydroxy-9-(methoxymethyl)-9a,11a-dimethyl-1,4,7-trioxo-2,3,3a,9,10,11-hexahydroindeno[4,5-h]isochromen-10-yl] acetate	1425125: 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	0.0070	uM
6-[5-[(2S)-2-amino-3-(1H-indol-3-yl)propoxy]-3-pyridinyl]isoquinolin-3-amine	265591: Inhibition of PKA at 5 uM ATP	ic50	0.0080	uM
(2S)-1-(2,3-difluorophenyl)-3-[[5-(3-methyl-2H-indazol-5-yl)-3-pyridinyl]oxy]propan-2-amine	290880: Inhibition of PKA	ic50	0.0090	uM
(1S)-2-amino-1-(4-chlorophenyl)-1-[4-(1H-pyrazol-4-yl)phenyl]ethanol	1953173: Inhibition of PKA (unknown origin)	ic50	0.0100	uM
(2S)-1-[[5-(3-methyl-2H-pyrazolo[3,4-c]pyridin-5-yl)-3-pyridinyl]oxy]-3-[3-(trifluoromethyl)phenyl]propan-2-amine	290880: Inhibition of PKA	ic50	0.0130	uM
(2S)-1-[[5-(3-chloro-2H-pyrazolo[3,4-c]pyridin-5-yl)-3-pyridinyl]oxy]-3-[3-(trifluoromethyl)phenyl]propan-2-amine	290880: Inhibition of PKA	ic50	0.0150	uM
(2S)-1-(1H-indol-3-yl)-3-[[5-(3-methyl-2H-pyrazolo[3,4-c]pyridin-5-yl)-3-pyridinyl]oxy]propan-2-amine	287580: Inhibition of PKA	ic50	0.0150	uM
1-(4-chlorophenyl)-N-methyl-1-[4-(7H-purin-6-yl)phenyl]methanamine	286920: Inhibition of PKA by radiometric filter binding assay	ic50	0.0150	uM
(2S)-1-[[5-(3-methyl-2H-indazol-5-yl)-3-pyridinyl]oxy]-3-phenylpropan-2-amine	266592: Inhibition of PKA	ki	0.0160	uM
(2S)-1-(1H-indol-3-yl)-3-[[5-[3-(trifluoromethyl)-2H-indazol-5-yl]-3-pyridinyl]oxy]propan-2-amine	287580: Inhibition of PKA	ic50	0.0160	uM
(2S)-1-[[5-(1H-indazol-5-yl)-3-pyridinyl]oxy]-3-(1H-indol-3-yl)propan-2-amine	287580: Inhibition of PKA	ic50	0.0180	uM
propan-2-yl 3-[[4-[(dimethylamino)methyl]-1-(5-methyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl)piperidine-4-carbonyl]amino]benzoate	1244620: Inhibition of PKA (unknown origin) by radiometric assay	ic50	0.0220	uM
methyl 3-[[4-[(dimethylamino)methyl]-1-(5-methyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl)piperidine-4-carbonyl]amino]benzoate	1244620: Inhibition of PKA (unknown origin) by radiometric assay	ic50	0.0240	uM
butan-2-yl 3-[[4-[(dimethylamino)methyl]-1-(5-methyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl)piperidine-4-carbonyl]amino]benzoate	1244620: Inhibition of PKA (unknown origin) by radiometric assay	ic50	0.0240	uM
(2S)-1-[[5-(3-methyl-2H-pyrazolo[3,4-c]pyridin-5-yl)-3-pyridinyl]oxy]-3-phenylpropan-2-amine	287580: Inhibition of PKA	ic50	0.0320	uM
(2S)-1-[[5-(3-ethenyl-1H-pyrazolo[3,4-c]pyridin-5-yl)-3-pyridinyl]oxy]-3-phenylpropan-2-amine	287580: Inhibition of PKA	ic50	0.0320	uM
6-[4-[4-(4-chlorophenyl)piperidin-4-yl]phenyl]-7H-purine	286920: Inhibition of PKA by radiometric filter binding assay	ic50	0.0330	uM
(2S)-1-(1H-indol-3-yl)-3-[[5-[(E)-2-pyridin-4-ylethenyl]-3-pyridinyl]oxy]propan-2-amine	262364: Inhibition of PKA using 10 uM ATP	ic50	0.0380	uM
(2S)-1-[[5-(3-chloro-2H-pyrazolo[3,4-c]pyridin-5-yl)-3-pyridinyl]oxy]-3-phenylpropan-2-amine	287580: Inhibition of PKA	ic50	0.0460	uM
(2S)-1-[[5-(3-fluoroisoquinolin-6-yl)-3-pyridinyl]oxy]-3-(1H-indol-3-yl)propan-2-amine	265591: Inhibition of PKA at 5 uM ATP	ic50	0.0480	uM
N-[2-[[(E)-3-(4-bromophenyl)prop-2-enyl]amino]ethyl]isoquinoline-5-sulfonamide;hydrochloride	1876038: Inhibition of PKA (unknown origin)	ic50	0.0500	uM

CTD chemical–gene interactions

15 total (human), top 15 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	increases methylation, affects cotreatment, increases expression	2
bisphenol A	affects cotreatment, increases expression	1
CGP 52608	affects binding, increases reaction	1
Resveratrol	affects cotreatment, decreases expression	1
Air Pollutants	decreases expression, increases abundance	1
Arsenic	affects methylation	1
Benzo(a)pyrene	decreases methylation	1
Dexamethasone	increases expression, affects cotreatment	1
Hydralazine	affects cotreatment, increases expression	1
Indomethacin	affects cotreatment, increases expression	1
Plant Extracts	affects cotreatment, decreases expression	1
Vanadium	decreases expression	1
1-Methyl-3-isobutylxanthine	affects cotreatment, increases expression	1
Particulate Matter	decreases expression, increases abundance	1
Coal Ash	decreases expression	1

ChEMBL screening assays

268 unique, capped per target: 261 binding, 6 functional, 1 admet

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1052130	Binding	Percent residual PKA activity in the presence of 10uM inhibitor	Biochemical and three-dimensional-structural study of the specific inhibition of protein kinase CK2 by [5-oxo-5,6-dihydroindolo-(1,2-a)quinazolin-7-yl]acetic acid (IQA). — Biochem J
CHEMBL630618	Functional	Activation of cAMP dependent protein kinase (PKA)	Bioactivatable derivatives of 8-substituted cAMP-analogues — Bioorg Med Chem Lett
CHEMBL4606503	ADMET	Inhibition of recombinant human full-length N-terminal GST-tagged PKAcgamma expressed in baculovirus infected Sf9 insect cells at 1 uM by Lanthascreen assay relative to control	Optimizing Pyrazolopyrimidine Inhibitors of Calcium Dependent Protein Kinase 1 for Treatment of Acute and Chronic Toxoplasmosis. — J Med Chem

Clinical trials (associated diseases)

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