PRKAR2A

Summary

PRKAR2A (protein kinase cAMP-dependent type II regulatory subunit alpha, HGNC:9391) is a protein-coding gene on chromosome 3p21.31, encoding cAMP-dependent protein kinase type II-alpha regulatory subunit (P13861). Regulatory subunit of the cAMP-dependent protein kinases involved in cAMP signaling in cells.

cAMP is a signaling molecule important for a variety of cellular functions. cAMP exerts its effects by activating the cAMP-dependent protein kinase, which transduces the signal through phosphorylation of different target proteins. The inactive kinase holoenzyme is a tetramer composed of two regulatory and 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. Four different regulatory subunits and three catalytic subunits have been identified in humans. The protein encoded by this gene is one of the regulatory subunits. This subunit can be phosphorylated by the activated catalytic subunit. It may interact with various A-kinase anchoring proteins and determine the subcellular localization of cAMP-dependent protein kinase. This subunit has been shown to regulate protein transport from endosomes to the Golgi apparatus and further to the endoplasmic reticulum (ER).

Source: NCBI Gene 5576 — RefSeq curated summary.

At a glance

• GWAS associations: 19
• Clinical variants (ClinVar): 67 total
• Druggable target: yes — 2 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_004157

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:9391
Approved symbol	PRKAR2A
Name	protein kinase cAMP-dependent type II regulatory subunit alpha
Location	3p21.31
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000114302
Ensembl biotype	protein_coding
OMIM	176910
Entrez	5576

Gene structure

Transcript identifiers

Ensembl transcripts: 21 — 14 protein_coding, 5 nonsense_mediated_decay, 2 retained_intron

ENST00000265563, ENST00000296446, ENST00000419216, ENST00000437821, ENST00000438535, ENST00000454963, ENST00000457914, ENST00000706570, ENST00000706571, ENST00000706572, ENST00000706573, ENST00000706574, ENST00000706575, ENST00000706576, ENST00000706577, ENST00000706578, ENST00000706579, ENST00000907504, ENST00000907505, ENST00000907506, ENST00000941073

RefSeq mRNA: 4 — MANE Select: NM_004157 NM_001321982, NM_001321983, NM_001321989, NM_004157

CCDS: CCDS2778, CCDS82771

Canonical transcript exons

ENST00000265563 — 11 exons

Exon	Start	End
ENSE00000768103	48752176	48752317
ENSE00000768105	48756379	48756444
ENSE00000768107	48765004	48765078
ENSE00001169115	48765248	48765349
ENSE00001296318	48782986	48783092
ENSE00001315035	48772955	48773108
ENSE00001318834	48790544	48790627
ENSE00001321402	48793997	48794049
ENSE00001335223	48807649	48807684
ENSE00001841831	48746586	48751718
ENSE00001926435	48847335	48847874

Expression profiles

Bgee: expression breadth ubiquitous, 291 present calls, max score 99.75.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 25.9432 / max 267.7466, expressed in 1814 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
42176	22.0878	1808
42175	1.9428	1132
42174	1.7281	1037
42173	0.1845	62

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
buccal mucosa cell	CL:0002336	99.75	gold quality
oocyte	CL:0000023	99.57	gold quality
secondary oocyte	CL:0000655	99.11	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	98.85	gold quality
olfactory bulb	UBERON:0002264	98.29	silver quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	98.23	gold quality
endothelial cell	CL:0000115	98.16	gold quality
biceps brachii	UBERON:0001507	98.10	gold quality
deltoid	UBERON:0001476	97.93	gold quality
tendon of biceps brachii	UBERON:0008188	97.90	gold quality
tibialis anterior	UBERON:0001385	97.84	gold quality
parotid gland	UBERON:0001831	97.71	gold quality
skeletal muscle tissue	UBERON:0001134	97.45	gold quality
gluteal muscle	UBERON:0002000	97.37	gold quality
triceps brachii	UBERON:0001509	97.22	gold quality
body of tongue	UBERON:0011876	97.22	gold quality
ileal mucosa	UBERON:0000331	97.07	gold quality
gingival epithelium	UBERON:0001949	97.05	gold quality
nipple	UBERON:0002030	97.04	gold quality
gingiva	UBERON:0001828	96.98	gold quality
left ventricle myocardium	UBERON:0006566	96.96	gold quality
mammary duct	UBERON:0001765	96.95	gold quality
vastus lateralis	UBERON:0001379	96.85	gold quality
pharyngeal mucosa	UBERON:0000355	96.69	gold quality
quadriceps femoris	UBERON:0001377	96.68	gold quality
jejunum	UBERON:0002115	96.68	gold quality
penis	UBERON:0000989	96.60	gold quality
epithelium of mammary gland	UBERON:0003244	96.56	gold quality
lower lobe of lung	UBERON:0008949	96.56	gold quality
tongue	UBERON:0001723	96.46	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	10.96

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

90 targeting PRKAR2A, 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-190A-3P	100.00	80.35	5520
HSA-MIR-196A-1-3P	99.99	72.15	2772
HSA-MIR-4500	99.99	72.72	2367
HSA-MIR-559	99.95	72.28	3609
HSA-MIR-548AB	99.95	71.31	3488
HSA-MIR-548A-5P	99.94	71.27	3482
HSA-MIR-548AD-5P	99.94	71.23	3502
HSA-MIR-548AE-5P	99.94	71.23	3502
HSA-MIR-548AK	99.94	71.24	3488
HSA-MIR-548AM-5P	99.94	71.24	3488
HSA-MIR-548AP-5P	99.94	71.14	3489
HSA-MIR-548AQ-5P	99.94	71.34	3426
HSA-MIR-548AR-5P	99.94	71.28	3515
HSA-MIR-548AS-5P	99.94	71.22	3482
HSA-MIR-548AU-5P	99.94	71.24	3488
HSA-MIR-548AY-5P	99.94	71.23	3502
HSA-MIR-548B-5P	99.94	71.23	3502
HSA-MIR-548BB-5P	99.94	71.27	3509
HSA-MIR-548C-5P	99.94	71.24	3488
HSA-MIR-548D-5P	99.94	71.23	3502
HSA-MIR-548H-5P	99.94	71.24	3488
HSA-MIR-548I	99.94	71.25	3481
HSA-MIR-548J-5P	99.94	71.14	3489
HSA-MIR-548O-5P	99.94	71.24	3488
HSA-MIR-548W	99.94	71.24	3488
HSA-MIR-548Y	99.94	71.28	3514
HSA-MIR-4760-3P	99.93	70.50	2385
HSA-MIR-381-3P	99.93	71.87	2854
HSA-MIR-300	99.92	71.76	2856
HSA-MIR-3529-3P	99.90	73.55	3045

Literature-anchored findings (GeneRIF, showing 20)

• findings indicate that increased particulate type II protein kinase A activity occurs throughout pregnancy therefore directing the cAMP quiescence signal to specific subcellular loci within myometrial smooth muscle cells (PMID:12727975)
• switching of PKA isozyme can cause tumor cells to undergo phenotypic reversion of the malignancy [revoew] (PMID:16394127)
• These data implicate the involvement of PKA-RIIalpha anchoring apical targeting of distinct proteins and glycosphingolipids to apical plasma membrane domains and suggest that rerouting may underlie the delayed Golgi-to-apical surface transport of MDR1. (PMID:16723498)
• The high-resolution crystal structures of the docking and dimerization (D/D) domain of the RIIalpha regulatory subunit of PKA in complex with the high-affinity anchoring peptide AKAP-IS explain the molecular basis for AKAP-regulatory subunit recognition. (PMID:17081989)
• The data suggest that centrosomal anchoring of RIIalpha and the interrelated subapical positioning of these centrosomes is required for oncostatin M-, but not cAMP-mediated, bile canalicular lumen development. (PMID:17494870)
• RIIalpha releases Calpha upon elevated cAMP alone, dependent on autophosphorylation of the RIIalpha inhibitory domain (PMID:17884635)
• Bacillus anthracis edema toxin altered the protein levels and activity of protein kinase A and exchange protein activated by cAMP (Epac), a recently identified cAMP-binding molecule. (PMID:19307216)
• ETO nervy homology region (NHR) 3 domain-PKA(RIIalpha) protein interaction does not appear to significantly contribute to AML1-ETO’s ability to induce leukemia. (PMID:20708017)
• RIaalpha and RIIaalpha were identified as cCMP-binding proteins. (PMID:22808067)
• Smad4 and the R subunit of the protein kinase A holoenzyme form a functional complex in vivo in response to TGFbeta. (PMID:23362281)
• while there is no change in type II regulatory (RIIalpha) or catalytic (Calpha) subunit expression, site specific RIIalpha (Ser96) and Calpha (Thr197) phosphorylation are increased in heart failure, as well as expression of type I regulatory subunit (RI) (PMID:23942052)
• These data demonstrate that some Kallmann syndrome-associated, intracellularly retained mutant PKR2 receptors can be functionally rescued, suggesting a potential treatment strategy for patients bearing such mutations. (PMID:24753254)
• Results show that mouse Prkar1a and human PRKAR2A exhibited a dynamic spatio-temporal expression in tooth development, whereas neither human PRKAR1A nor mouse Prkar2a showed their expression in odontogenesis. (PMID:24755349)
• we demonstrate that neurochondrin has strong isoform selectivity towards the RIIa subunit of PKA with nanomolar affinity (PMID:25916936)
• High PK-R2 expression is associated with colorectal cancer. (PMID:26372733)
• Prkar2a deficiency predisposes to hematopoietic malignancies in vivo. RIIalpha’s likely association with HS and DLBCL was hitherto unrecognized and may lead to better understanding of these rare neoplasms. (PMID:26608815)
• Disruption of Snapin-PKR2 interaction did not affect PKR2 signaling, but increased the ligand-induced degradation, implying a role of Snapin in the trafficking of PKR2. (PMID:26687946)
• Targeting the Regulatory Subunit R2Alpha of Protein Kinase A in Human Glioblastoma through shRNA-Expressing Lentiviral Vectors. (PMID:34372567)
• Protein Kinase A (PRKA) Activity Is Regulated by the Proteasome at the Onset of Human Sperm Capacitation. (PMID:34944009)
• Organoid models of fibrolamellar carcinoma mutations reveal hepatocyte transdifferentiation through cooperative BAP1 and PRKAR2A loss. (PMID:37137901)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	prkar2ab	ENSDARG00000009477
danio_rerio	prkar2aa	ENSDARG00000033184
mus_musculus	Prkar2a	ENSMUSG00000032601
rattus_norvegicus	Prkar2a	ENSRNOG00000020284
drosophila_melanogaster	Pka-R2	FBGN0022382

Paralogs (4): PRKAR2B (ENSG00000005249), PRKAR1A (ENSG00000108946), CNBD1 (ENSG00000176571), PRKAR1B (ENSG00000188191)

Protein

Protein identifiers

cAMP-dependent protein kinase type II-alpha regulatory subunit — P13861 (reviewed: P13861)

All UniProt accessions (14): P13861, A0A024R2W3, A0A0S2Z472, A0A9L9PX32, A0A9L9PXB0, A0A9L9PXB4, A0A9L9PXM7, A0A9L9PXP9, A0A9L9PY56, A0A9L9PY59, C9J830, H7C1L0, H7C330, H7C4A9

UniProt curated annotations — full annotation on UniProt →

Function. Regulatory subunit of the cAMP-dependent protein kinases involved in cAMP signaling in cells. Type II regulatory chains mediate membrane association by binding to anchoring proteins, including the MAP2 kinase.

Subunit / interactions. The inactive form of the enzyme is composed of two regulatory chains and two catalytic chains. Activation by cAMP produces two active catalytic monomers and a regulatory dimer that binds four cAMP molecules. Interacts with AKAP4 and CBFA2T3. Interacts with the phosphorylated form of PJA2. Interacts with MYRIP. This interaction may link PKA to components of the exocytosis machinery, thus facilitating exocytosis, including insulin release. Forms a complex composed of PRKAR2A, GSK3B and GSKIP through GSKIP interaction; facilitates PKA-induced phosphorylation and regulates GSK3B activity. Interacts with ADCY8; inhibits adenylate cyclase activity through PKA phosphorylation.

Subcellular location. Cytoplasm. Cell membrane.

Tissue specificity. Four types of regulatory chains are found: I-alpha, I-beta, II-alpha, and II-beta. Their expression varies among tissues and is in some cases constitutive and in others inducible.

Post-translational modifications. Phosphorylated by the activated catalytic chain.

Similarity. Belongs to the cAMP-dependent kinase regulatory chain family.

Isoforms (2)

UniProt ID	Names	Canonical?
P13861-1	1	yes
P13861-2	2

RefSeq proteins (4): NP_001308911, NP_001308912, NP_001308918, NP_004148* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000595	cNMP-bd_dom	Domain
IPR003117	cAMP_dep_PK_reg_su_I/II_a/b	Domain
IPR012198	cAMP_dep_PK_reg_su	Family
IPR014710	RmlC-like_jellyroll	Homologous_superfamily
IPR018488	cNMP-bd_CS	Conserved_site
IPR018490	cNMP-bd_dom_sf	Homologous_superfamily
IPR050503	cAMP-dep_PK_reg_su-like	Family

Pfam: PF00027, PF02197

UniProt features (24 total): modified residue 10, binding site 6, region of interest 2, helix 2, initiator methionine 1, chain 1, splice variant 1, compositionally biased region 1

Structure

Experimental structures (PDB)

8 structures.

PDB	Method	Resolution (Å)
2IZX	X-RAY DIFFRACTION	1.3
5H78	X-RAY DIFFRACTION	2
9NXN	X-RAY DIFFRACTION	2.1
4ZP3	X-RAY DIFFRACTION	2.63
5H77	X-RAY DIFFRACTION	3.2
5XBY	X-RAY DIFFRACTION	3.25
2KYG	SOLUTION NMR
8S8O	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P13861-F1	83.74	0.64

Functional residue map

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

Ligand- & substrate-binding residues (6): 347; 139–260; 208; 217; 261–404; 338

Post-translational modifications (10): 2, 48, 54, 58, 78, 80, 99, 215, 350, 395

Function

Pathways and Gene Ontology

Reactome pathways

53 pathways

ID	Pathway
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-432040	Vasopressin regulates renal water homeostasis via Aquaporins
R-HSA-442720	CREB1 phosphorylation through the activation of Adenylate Cyclase
R-HSA-5610787	Hedgehog ‘off’ state
R-HSA-9010642	ROBO receptors bind AKAP5
R-HSA-9634597	GPER1 signaling
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-111931	PKA-mediated phosphorylation of CREB
R-HSA-111933	Calmodulin induced events
R-HSA-111996	Ca-dependent events
R-HSA-111997	CaM pathway
R-HSA-112040	G-protein mediated events
R-HSA-112043	PLC beta mediated events
R-HSA-112314	Neurotransmitter receptors and postsynaptic signal transmission
R-HSA-112315	Transmission across Chemical Synapses
R-HSA-112316	Neuronal System
R-HSA-1266738	Developmental Biology
R-HSA-1430728	Metabolism
R-HSA-1489509	DAG and IP3 signaling
R-HSA-162582	Signal Transduction
R-HSA-163359	Glucagon signaling in metabolic regulation
R-HSA-163685	Integration of energy metabolism

MSigDB gene sets: 386 (showing top): GOBP_RESPONSE_TO_NITROGEN_COMPOUND, GOBP_REGULATION_OF_INFLAMMATORY_RESPONSE_TO_ANTIGENIC_STIMULUS, GOBP_REGULATION_OF_PHOSPHORYLATION, GOBP_INFLAMMATORY_RESPONSE, AAGTCCA_MIR422B_MIR422A, GOBP_RESPONSE_TO_FLUID_SHEAR_STRESS, GOBP_CELLULAR_RESPONSE_TO_FLUID_SHEAR_STRESS, MITSIADES_RESPONSE_TO_APLIDIN_DN, GOBP_REGULATION_OF_TRANSFERASE_ACTIVITY, LHX3_01, REACTOME_GLUCAGON_SIGNALING_IN_METABOLIC_REGULATION, GOBP_CELLULAR_RESPONSE_TO_OXYGEN_CONTAINING_COMPOUND, BIOCARTA_NOS1_PATHWAY, BONCI_TARGETS_OF_MIR15A_AND_MIR16_1, GOCC_MICROTUBULE_ORGANIZING_CENTER

GO Biological Process (10): negative regulation of inflammatory response to antigenic stimulus (GO:0002862), renal water homeostasis (GO:0003091), adenylate cyclase-activating G protein-coupled receptor signaling pathway (GO:0007189), chemical synaptic transmission (GO:0007268), intracellular signal transduction (GO:0035556), cellular response to glucagon stimulus (GO:0071377), vascular endothelial cell response to laminar fluid shear stress (GO:0097700), negative regulation of cAMP/PKA signal transduction (GO:0141162), regulation of protein phosphorylation (GO:0001932), binding of sperm to zona pellucida (GO:0007339)

GO Molecular Function (9): cAMP-dependent protein kinase inhibitor activity (GO:0004862), cAMP-dependent protein kinase regulator activity (GO:0008603), protein domain specific binding (GO:0019904), cAMP binding (GO:0030552), ubiquitin protein ligase binding (GO:0031625), protein kinase A catalytic subunit binding (GO:0034236), nucleotide binding (GO:0000166), protein binding (GO:0005515), kinase activity (GO:0016301)

GO Cellular Component (14): cytoplasm (GO:0005737), centrosome (GO:0005813), cytosol (GO:0005829), plasma membrane (GO:0005886), focal adhesion (GO:0005925), cAMP-dependent protein kinase complex (GO:0005952), membrane (GO:0016020), nucleotide-activated protein kinase complex (GO:0031588), protein-containing complex (GO:0032991), plasma membrane raft (GO:0044853), synapse (GO:0045202), extracellular exosome (GO:0070062), ciliary base (GO:0097546), axoneme (GO:0005930)

Reactome top-level categories

Rollup of top-18 pathways:

Category	Pathways
Opioid Signalling	2
Anti-inflammatory response favouring Leishmania parasite infection	2
PKA-mediated phosphorylation of CREB	1
Glucagon signaling in metabolic regulation	1
Regulation of insulin secretion	1
Aquaporin-mediated transport	1
Post NMDA receptor activation events	1
Signaling by Hedgehog	1
Signaling by ROBO receptors	1
G alpha (s) signalling events	1
Hemostasis	1
Response of endothelial cells to shear stress	1
G alpha (i) signalling events	1
Calmodulin induced events	1
CaM pathway	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	5
intracellular anatomical structure	2
cAMP-dependent protein kinase activity	2
intracellular protein-containing complex	2
inflammatory response to antigenic stimulus	1
regulation of inflammatory response to antigenic stimulus	1
negative regulation of inflammatory response	1
negative regulation of immune response	1
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
anterograde trans-synaptic signaling	1
signal transduction	1
response to glucagon	1
cellular response to peptide hormone stimulus	1
cellular response to laminar fluid shear stress	1
vascular endothelial cell response to fluid shear stress	1
cAMP/PKA signal transduction	1
regulation of cAMP/PKA signal transduction	1
negative regulation of intracellular signal transduction	1
protein phosphorylation	1
regulation of protein modification process	1
regulation of phosphorylation	1
sperm-egg recognition	1
cAMP-dependent protein kinase regulator activity	1
protein serine/threonine kinase inhibitor activity	1
protein kinase regulator activity	1
protein binding	1
cyclic nucleotide binding	1
adenyl ribonucleotide binding	1
anion binding	1
ubiquitin-like protein ligase binding	1
protein kinase binding	1
protein kinase A binding	1
nucleoside phosphate binding	1
heterocyclic compound binding	1
binding	1
transferase activity, transferring phosphorus-containing groups	1
centriole	1

Protein interactions and networks

STRING

2210 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PRKAR2A	PRKACA	P17612	901
PRKAR2A	PRKACB	P22694	869
PRKAR2A	PRKACG	P22612	852
PRKAR2A	CMYA5	Q8N3K9	835
PRKAR2A	CABYR	O75952	732
PRKAR2A	SPA17	Q15506	711
PRKAR2A	AKAP1	Q92667	666
PRKAR2A	RAB32	Q13637	640
PRKAR2A	ABHD2	P08910	592
PRKAR2A	AKAP4	Q5JQC9	537
PRKAR2A	PRKAR1B	P31321	506
PRKAR2A	AKAP11	Q9UKA4	479
PRKAR2A	PALM2AKAP2	Q9Y2D5	468
PRKAR2A	TUFM	P49411	452
PRKAR2A	PRKX	P51817	439

IntAct

200 interactions, top by confidence:

A	B	Type	Score
PRKAA1	PRKAB2	psi-mi:“MI:0914”(association)	0.950
CSNK1E	PER1	psi-mi:“MI:0914”(association)	0.840
AKAP1	PRKAR2A	psi-mi:“MI:0915”(physical association)	0.810
PRKAR2A	AKAP1	psi-mi:“MI:0915”(physical association)	0.810
PRKACB	PRKAR1A	psi-mi:“MI:0914”(association)	0.790
AKAP5	PRKAR2A	psi-mi:“MI:0915”(physical association)	0.760
AKAP5	PRKAR2A	psi-mi:“MI:2364”(proximity)	0.760
AKAP5	PRKAR2A	psi-mi:“MI:0407”(direct interaction)	0.760
DYNLL1	BLTP3B	psi-mi:“MI:0914”(association)	0.730
PRKACA	VAPB	psi-mi:“MI:0914”(association)	0.730
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
	PRKAR1A	psi-mi:“MI:0914”(association)	0.700
DYNLL2	BLTP3B	psi-mi:“MI:0914”(association)	0.640
	PRKAR2A	psi-mi:“MI:0915”(physical association)	0.640
	PRKAR2A	psi-mi:“MI:0403”(colocalization)	0.640
PRKAR2A		psi-mi:“MI:0915”(physical association)	0.640
	PRKAR2A	psi-mi:“MI:0407”(direct interaction)	0.640
	PRKAR2A	psi-mi:“MI:0217”(phosphorylation reaction)	0.590
AKAP8	PRKAR2A	psi-mi:“MI:0407”(direct interaction)	0.570
AKAP8	PRKAR2A	psi-mi:“MI:0915”(physical association)	0.570
AKAP8	PRKAR2A	psi-mi:“MI:0403”(colocalization)	0.570
AKAP12	PRKAR2A	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (352): PRKAR2A (Biochemical Activity), PRKAR2A (Affinity Capture-MS), PRKAR2A (Affinity Capture-MS), PRKAR2A (Affinity Capture-MS), PRKAR2A (Affinity Capture-MS), PRKAR2A (Co-fractionation), PRKAR2A (Reconstituted Complex), PRKAR2A (Proximity Label-MS), PRKAR2A (Affinity Capture-MS), PRKAR2A (Affinity Capture-MS), PRKAR2A (Affinity Capture-MS), PRKAR2A (Affinity Capture-MS), PRKAR2A (Affinity Capture-MS), PRKAR2A (Affinity Capture-MS), PRKAR2A (Affinity Capture-MS)

ESM2 similar proteins: A2QCJ2, A8X6H1, G4NEB8, J9VSG5, O14448, O42794, O59922, O76360, P00515, P05207, P07278, P12367, P12368, P12369, P13861, P30625, P31320, P31322, P31323, P31324, P32023, P81900, P93025, Q00078, Q01386, Q03042, Q03043, Q13237, Q26619, Q2URJ0, Q4IPN9, Q4WRC2, Q4WVG0, Q4X0Z7, Q5AZT7, Q5BEP0, Q61410, Q64595, Q6BZG7, Q6C2X0

Diamond homologs: A0A509AKL0, A0R3F9, A5K0N4, O14448, O42794, O59922, P00514, P00515, P00516, P05207, P05987, P07278, P07802, P09456, P0C605, P10644, P12367, P12368, P12369, P12849, P13861, P16905, P30625, P31319, P31320, P31321, P31322, P31323, P31324, P32023, P34578, P36600, P49605, P81377, P81900, P86244, Q01386, Q03042, Q13976, Q26619

SIGNOR signaling

6 interactions.

A	Effect	B	Mechanism
PDE4DIP	up-regulates	PRKAR2A	binding
PRKAR2A	“down-regulates activity”	PRKACA	binding
PRKAR2A	“down-regulates activity”	PRKACB	binding
“3’,5’-cyclic AMP”	“down-regulates activity”	PRKAR2A	“chemical inhibition”
PJA2	“down-regulates quantity by destabilization”	PRKAR2A	polyubiquitination
PRKAR2A	“up-regulates activity”	PRKAR2A	phosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 197 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	25.8×	3e-05
PKA activation	5	24.4×	4e-05
PKA-mediated phosphorylation of CREB	5	22.0×	7e-05
Centrosome maturation	10	19.5×	6e-09
DARPP-32 events	5	18.3×	1e-04
Loss of Nlp from mitotic centrosomes	14	17.1×	2e-11
Loss of proteins required for interphase microtubule organization from the centrosome	14	17.1×	2e-11
AURKA Activation by TPX2	14	16.4×	3e-11

GO biological processes:

GO term	Partners	Fold	FDR
vascular endothelial cell response to laminar fluid shear stress	5	23.2×	1e-03
positive regulation of microtubule polymerization	5	21.3×	1e-03
renal water homeostasis	5	16.2×	3e-03
spindle assembly	5	14.0×	6e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	52
Likely benign	3
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

2618 predictions. Top by Δscore:

Variant	Effect	Δscore
3:48751587:A:AC	donor_gain	1.0000
3:48751587:ACTG:A	donor_gain	1.0000
3:48751587:ACTGC:A	donor_gain	1.0000
3:48751588:C:CC	donor_gain	1.0000
3:48751588:CTG:C	donor_gain	1.0000
3:48751588:CTGC:C	donor_gain	1.0000
3:48751588:CTGCC:C	donor_gain	1.0000
3:48751716:TAA:T	acceptor_gain	1.0000
3:48751719:C:CA	acceptor_loss	1.0000
3:48751719:C:CC	acceptor_gain	1.0000
3:48751724:T:C	acceptor_gain	1.0000
3:48751724:T:TC	acceptor_gain	1.0000
3:48751727:T:C	acceptor_gain	1.0000
3:48751727:T:TC	acceptor_gain	1.0000
3:48756377:AC:A	donor_gain	1.0000
3:48756378:CC:C	donor_gain	1.0000
3:48756378:CCCTG:C	donor_gain	1.0000
3:48765001:CACCT:C	donor_loss	1.0000
3:48765002:A:AC	donor_gain	1.0000
3:48765002:ACCTG:A	donor_loss	1.0000
3:48765003:C:CC	donor_gain	1.0000
3:48765074:GACAC:G	acceptor_gain	1.0000
3:48765075:ACAC:A	acceptor_gain	1.0000
3:48765076:CAC:C	acceptor_gain	1.0000
3:48765076:CACC:C	acceptor_gain	1.0000
3:48765077:AC:A	acceptor_gain	1.0000
3:48765078:CC:C	acceptor_gain	1.0000
3:48765079:C:CC	acceptor_gain	1.0000
3:48765079:C:T	acceptor_gain	1.0000
3:48765079:CTG:C	acceptor_loss	1.0000

AlphaMissense

2653 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
3:48765335:A:C	F237L	1.000
3:48765335:A:T	F237L	1.000
3:48765337:A:G	F237L	1.000
3:48772956:A:G	L232P	1.000
3:48772963:A:G	W230R	1.000
3:48772963:A:T	W230R	1.000
3:48772972:C:G	G227R	1.000
3:48772983:G:T	A223D	1.000
3:48772989:A:T	I221N	1.000
3:48772995:G:T	A219D	1.000
3:48772996:C:G	A219P	1.000
3:48773000:T:A	R217S	1.000
3:48773000:T:G	R217S	1.000
3:48773001:C:A	R217I	1.000
3:48773001:C:G	R217T	1.000
3:48773019:A:C	L211R	1.000
3:48773019:A:G	L211P	1.000
3:48773019:A:T	L211Q	1.000
3:48773022:G:T	A210D	1.000
3:48773025:A:G	L209P	1.000
3:48773025:A:T	L209Q	1.000
3:48773028:T:A	E208V	1.000
3:48773031:C:A	G207V	1.000
3:48773031:C:T	G207E	1.000
3:48773032:C:G	G207R	1.000
3:48773032:C:T	G207R	1.000
3:48773033:A:C	F206L	1.000
3:48773033:A:T	F206L	1.000
3:48773034:A:G	F206S	1.000
3:48773035:A:G	F206L	1.000

dbSNP variants (sampled 300 via entrez): RS1000046043 (3:48759131 G>A), RS1000056000 (3:48751150 C>A,T), RS1000068571 (3:48757027 A>C), RS1000108747 (3:48799438 G>A), RS1000118130 (3:48778470 C>T), RS1000155583 (3:48832992 A>G), RS1000228183 (3:48753064 C>A), RS1000255882 (3:48778793 C>CA), RS1000260314 (3:48806225 T>C), RS1000282478 (3:48760851 A>G), RS1000304174 (3:48784813 G>A), RS1000366827 (3:48793132 T>A), RS1000391303 (3:48767453 T>C), RS1000403931 (3:48839674 G>A), RS1000408338 (3:48839431 G>A)

Disease associations

OMIM: gene MIM:176910 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

19 associations (top):

Study	Trait	p-value
GCST003818_48	Resting heart rate	3.000000e-13
GCST004131_23	Inflammatory bowel disease	1.000000e-33
GCST004132_17	Crohn’s disease	3.000000e-23
GCST004133_11	Ulcerative colitis	8.000000e-20
GCST006979_64	Heel bone mineral density	3.000000e-37
GCST007565_146	Morning person	6.000000e-17
GCST008839_261	Height	1.000000e-07
GCST008840_1	Depressive symptom (depressed mood) (binary trait)	8.000000e-10
GCST008858_1	Depressive symptom (depressed mood) (ordinal trait)	4.000000e-10
GCST010698_80	Subcortical volume (min-P)	3.000000e-24
GCST010699_110	Brain morphology (min-P)	4.000000e-08
GCST010701_52	Cortical surface area (MOSTest)	1.000000e-16
GCST010702_36	Subcortical volume (MOSTest)	1.000000e-10
GCST010703_262	Brain morphology (MOSTest)	2.000000e-13
GCST012227_987	Hip circumference adjusted for BMI	5.000000e-08
GCST012232_6	Lipoprotein (a) levels	5.000000e-09
GCST012490_108	Femur bone mineral density x serum urate levels interaction	1.000000e-08
GCST90020025_1949	Waist-to-hip ratio adjusted for BMI	2.000000e-15
GCST90020027_105	Waist-hip index	2.000000e-16

EFO canonical traits (8, from GWAS)

EFO ID	Trait name
EFO:0009270	heel bone mineral density
EFO:0008328	chronotype measurement
EFO:0007006	depressive symptom measurement
EFO:0004346	neuroimaging measurement
EFO:0008039	BMI-adjusted hip circumference
EFO:0006925	lipoprotein A measurement
EFO:0004531	urate measurement
EFO:0007788	BMI-adjusted waist-hip ratio

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL2221 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

2 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 2,712 (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
CHEMBL482967	CYC-116	1	651
CHEMBL494089	GSK-690693	1	2,061

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

GtoPdb / IUPHAR curated pharmacology

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

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

ChEMBL bioactivities

15 potent at pChembl≥5 of 15 total, top 15 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
7.46	Kd	35	nM	CHEMBL4203735
7.31	Kd	49	nM	CHEMBL4207455
7.28	Kd	52	nM	GSK-690693
7.28	Kd	53	nM	CHEMBL4211508
7.16	Kd	69	nM	CHEMBL4204708
7.12	Kd	76	nM	CHEMBL4215761
7.10	Kd	80	nM	CHEMBL4211816
6.98	Kd	105	nM	CHEMBL4204281
6.71	Kd	193	nM	CHEMBL4213005
6.55	Kd	283	nM	CHEMBL4205523
6.49	Kd	324.7	nM	CHEMBL5653589
6.49	ED50	324.7	nM	CHEMBL5653589
5.46	Kd	3455	nM	CYC-116
5.08	Kd	8244	nM	CHEMBL3752910
5.08	ED50	8244	nM	CHEMBL3752910

PubChem BioAssay actives

13 with measured affinity, of 249 total; 13 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
(2S)-6-amino-2-[[(2S)-2-[[(2S)-2-[[(2S,5S,8S,11S,15E,20S)-20-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-6-amino-2-[[(2S)-2-[[(2S)-2-[[(2S)-6-amino-2-[[(2S)-6-amino-2-[[2-[2-[2-(2-aminoethoxy)ethoxy]ethoxy]acetyl]amino]hexanoyl]amino]hexanoyl]amino]-4-methylpentanoyl]amino]propanoyl]amino]hexanoyl]amino]-3-phenylpropanoyl]amino]-4-methylpentanoyl]amino]-3-methylbutanoyl]amino]-3-hydroxypropanoyl]amino]-8-(4-aminobutyl)-2,11,20-trimethyl-5-(2-methylpropyl)-3,6,9,21-tetraoxo-1,4,7,10-tetrazacyclohenicos-15-ene-11-carbonyl]amino]propanoyl]amino]-4-methylpentanoyl]amino]hexanoic acid	1374579: Binding affinity to recombinant human full length PKA-R2alpha expressed in Escherichia coli BL21 DE3-RIL cells assessed as reduction in interaction with AKAP by fluorescence polarization analysis	kd	0.0350	uM
(2S)-6-amino-2-[[(2S)-2-[[(2S)-2-[[(2S,5S,8S,11S,15E,20S)-20-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-6-amino-2-[[(2S)-2-[[(2S)-2-[[(2S)-6-amino-2-[[(2S)-6-amino-2-[[2-[2-[2-(2-aminoethoxy)ethoxy]ethoxy]acetyl]amino]hexanoyl]amino]hexanoyl]amino]-4-methylpentanoyl]amino]propanoyl]amino]hexanoyl]amino]-3-phenylpropanoyl]amino]-4-methylpentanoyl]amino]-3-methylbutanoyl]amino]-3-hydroxypropanoyl]amino]-2,8,11,20-tetramethyl-5-(2-methylpropyl)-3,6,9,21-tetraoxo-1,4,7,10-tetrazacyclohenicos-15-ene-11-carbonyl]amino]propanoyl]amino]-4-methylpentanoyl]amino]hexanoic acid	1374579: Binding affinity to recombinant human full length PKA-R2alpha expressed in Escherichia coli BL21 DE3-RIL cells assessed as reduction in interaction with AKAP by fluorescence polarization analysis	kd	0.0490	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	1425128: 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	0.0520	uM
(2S)-6-amino-2-[[(2S)-2-[[(2S)-2-[[(2S,5S,8S,11S,15E,20S)-20-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-6-amino-2-[[(2S)-6-amino-2-[[2-[2-[2-(2-aminoethoxy)ethoxy]ethoxy]acetyl]amino]hexanoyl]amino]hexanoyl]amino]-4-methylpentanoyl]amino]propanoyl]amino]propanoyl]amino]-3-phenylpropanoyl]amino]-4-methylpentanoyl]amino]-3-methylbutanoyl]amino]-3-hydroxypropanoyl]amino]-8-(4-aminobutyl)-2,11,20-trimethyl-5-(2-methylpropyl)-3,6,9,21-tetraoxo-1,4,7,10-tetrazacyclohenicos-15-ene-11-carbonyl]amino]propanoyl]amino]-4-methylpentanoyl]amino]hexanoic acid	1374579: Binding affinity to recombinant human full length PKA-R2alpha expressed in Escherichia coli BL21 DE3-RIL cells assessed as reduction in interaction with AKAP by fluorescence polarization analysis	kd	0.0530	uM
(2S)-6-amino-2-[[(2S)-2-[[(2S)-2-[[(2S,5S,8S,11S,15E,20S)-20-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-6-amino-2-[[(2S)-2-[[(2S)-2-[[(2S)-6-amino-2-[[(2S)-6-amino-2-[[2-[2-[2-(2-aminoethoxy)ethoxy]ethoxy]acetyl]amino]hexanoyl]amino]hexanoyl]amino]-4-methylpentanoyl]amino]propanoyl]amino]hexanoyl]amino]-3-phenylpropanoyl]amino]-4-methylpentanoyl]amino]-3-methylbutanoyl]amino]propanoyl]amino]-8-(4-aminobutyl)-2,11,20-trimethyl-5-(2-methylpropyl)-3,6,9,21-tetraoxo-1,4,7,10-tetrazacyclohenicos-15-ene-11-carbonyl]amino]propanoyl]amino]-4-methylpentanoyl]amino]hexanoic acid	1374579: Binding affinity to recombinant human full length PKA-R2alpha expressed in Escherichia coli BL21 DE3-RIL cells assessed as reduction in interaction with AKAP by fluorescence polarization analysis	kd	0.0690	uM
(2S)-6-amino-2-[[(2S)-2-[[(2S)-2-[[(2S,5S,8S,11S,15E,20S)-20-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-6-amino-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-6-amino-2-[[2-[2-[2-(2-aminoethoxy)ethoxy]ethoxy]acetyl]amino]hexanoyl]amino]propanoyl]amino]-4-methylpentanoyl]amino]propanoyl]amino]hexanoyl]amino]-3-phenylpropanoyl]amino]-4-methylpentanoyl]amino]-3-methylbutanoyl]amino]-3-hydroxypropanoyl]amino]-8-(4-aminobutyl)-2,11,20-trimethyl-5-(2-methylpropyl)-3,6,9,21-tetraoxo-1,4,7,10-tetrazacyclohenicos-15-ene-11-carbonyl]amino]propanoyl]amino]-4-methylpentanoyl]amino]hexanoic acid	1374579: Binding affinity to recombinant human full length PKA-R2alpha expressed in Escherichia coli BL21 DE3-RIL cells assessed as reduction in interaction with AKAP by fluorescence polarization analysis	kd	0.0760	uM
(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S,5S,8S,11S,15E,20S)-20-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-6-amino-2-[[(2S)-2-[[(2S)-2-[[(2S)-6-amino-2-[[(2S)-6-amino-2-[[2-[2-[2-(2-aminoethoxy)ethoxy]ethoxy]acetyl]amino]hexanoyl]amino]hexanoyl]amino]-4-methylpentanoyl]amino]propanoyl]amino]hexanoyl]amino]-3-phenylpropanoyl]amino]-4-methylpentanoyl]amino]-3-methylbutanoyl]amino]-3-hydroxypropanoyl]amino]-8-(4-aminobutyl)-2,11,20-trimethyl-5-(2-methylpropyl)-3,6,9,21-tetraoxo-1,4,7,10-tetrazacyclohenicos-15-ene-11-carbonyl]amino]propanoyl]amino]-4-methylpentanoyl]amino]propanoic acid	1374579: Binding affinity to recombinant human full length PKA-R2alpha expressed in Escherichia coli BL21 DE3-RIL cells assessed as reduction in interaction with AKAP by fluorescence polarization analysis	kd	0.0800	uM
(2S)-6-amino-2-[[(2S)-2-[[(2S)-2-[[(2S,5S,8S,11S,15E,20S)-20-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-6-amino-2-[[(2S)-2-[[(2S)-2-[[(2S)-6-amino-2-[[(2S)-6-amino-2-[[2-[2-[2-(2-aminoethoxy)ethoxy]ethoxy]acetyl]amino]hexanoyl]amino]hexanoyl]amino]-4-methylpentanoyl]amino]propanoyl]amino]hexanoyl]amino]propanoyl]amino]-4-methylpentanoyl]amino]-3-methylbutanoyl]amino]-3-hydroxypropanoyl]amino]-8-(4-aminobutyl)-2,11,20-trimethyl-5-(2-methylpropyl)-3,6,9,21-tetraoxo-1,4,7,10-tetrazacyclohenicos-15-ene-11-carbonyl]amino]propanoyl]amino]-4-methylpentanoyl]amino]hexanoic acid	1374579: Binding affinity to recombinant human full length PKA-R2alpha expressed in Escherichia coli BL21 DE3-RIL cells assessed as reduction in interaction with AKAP by fluorescence polarization analysis	kd	0.1050	uM
(2S)-6-amino-2-[[(2S)-2-[[(2S)-2-[[(2S,5S,8S,11S,15E,20S)-20-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-6-amino-2-[[(2S)-2-[[(2S)-2-[[(2S)-6-amino-2-[[(2S)-2-[[2-[2-[2-(2-aminoethoxy)ethoxy]ethoxy]acetyl]amino]propanoyl]amino]hexanoyl]amino]-4-methylpentanoyl]amino]propanoyl]amino]hexanoyl]amino]-3-phenylpropanoyl]amino]-4-methylpentanoyl]amino]-3-methylbutanoyl]amino]-3-hydroxypropanoyl]amino]-8-(4-aminobutyl)-2,11,20-trimethyl-5-(2-methylpropyl)-3,6,9,21-tetraoxo-1,4,7,10-tetrazacyclohenicos-15-ene-11-carbonyl]amino]propanoyl]amino]-4-methylpentanoyl]amino]hexanoic acid	1374579: Binding affinity to recombinant human full length PKA-R2alpha expressed in Escherichia coli BL21 DE3-RIL cells assessed as reduction in interaction with AKAP by fluorescence polarization analysis	kd	0.1930	uM
(2S)-6-amino-2-[[(2S)-2-[[(2S)-2-[[(2S,5S,8S,11S,15E,20S)-20-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-6-amino-2-[[(2S)-2-[[(2S)-2-[[(2S)-6-amino-2-[[(2S)-6-amino-2-[[2-[2-[2-(2-aminoethoxy)ethoxy]ethoxy]acetyl]amino]hexanoyl]amino]hexanoyl]amino]-4-methylpentanoyl]amino]propanoyl]amino]hexanoyl]amino]-3-phenylpropanoyl]amino]-4-methylpentanoyl]amino]-3-methylbutanoyl]amino]-3-hydroxypropanoyl]amino]-8-(4-aminobutyl)-2,11,20-trimethyl-5-(2-methylpropyl)-3,6,9,21-tetraoxo-1,4,7,10-tetrazacyclohenicos-15-ene-11-carbonyl]amino]propanoyl]amino]propanoyl]amino]hexanoic acid	1374579: Binding affinity to recombinant human full length PKA-R2alpha expressed in Escherichia coli BL21 DE3-RIL cells assessed as reduction in interaction with AKAP by fluorescence polarization analysis	kd	0.2830	uM
4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2149075: Binding affinity to human PRKAR2A incubated for 45 mins by Kinobead based pull down assay	kd	0.3247	uM
4-methyl-5-[2-(4-morpholin-4-ylanilino)pyrimidin-4-yl]-1,3-thiazol-2-amine	1425128: 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	3.4550	uM
4-methyl-3-[(1-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2149075: Binding affinity to human PRKAR2A incubated for 45 mins by Kinobead based pull down assay	kd	8.2442	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
bisphenol A	increases expression, decreases expression	4
Valproic Acid	affects cotreatment, increases expression	3
sodium arsenite	increases reaction, increases expression, affects binding	2
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	2
Resveratrol	increases expression, decreases reaction, increases phosphorylation	2
Estradiol	increases expression	2
Smoke	decreases expression	2
FR900359	increases phosphorylation	1
bisphenol F	increases expression	1
testosterone enanthate	affects expression	1
triphenyl phosphate	affects expression	1
alpha-pinene	affects cotreatment, increases oxidation, increases abundance	1
deoxynivalenol	increases expression	1
o,p’-DDT	increases expression	1
cobaltous chloride	decreases expression	1
nivalenol	increases expression	1
methacrylaldehyde	affects cotreatment, increases oxidation, increases abundance	1
8-cyclopentyl-1,3-dimethylxanthine	increases phosphorylation	1
cobalt oxide	increases expression	1
N-(2-(4-bromocinnamylamino)ethyl)-5-isoquinolinesulfonamide	decreases reaction, increases phosphorylation, decreases phosphorylation	1
2,3,5-(triglutathion-S-yl)hydroquinone	increases ADP-ribosylation	1
nutlin 3	affects cotreatment, increases secretion	1
bisphenol B	increases expression	1
abrine	decreases expression	1
dorsomorphin	increases expression, affects cotreatment	1
bisphenol S	increases expression	1
LDN 193189	affects cotreatment, increases expression	1
bisphenol AF	increases expression	1
Acetaminophen	decreases expression	1
Acrolein	increases oxidation, increases abundance, affects cotreatment	1

ChEMBL screening assays

4 unique, capped per target: 4 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL3991841	Binding	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 ma	The target landscape of clinical kinase drugs. — Science

Cellosaurus cell lines

1 cell lines: 1 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B2C4	Abcam HeLa PRKAR2A KO	Cancer cell line	Female

Clinical trials (associated diseases)

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