PRKACB

Summary

PRKACB (protein kinase cAMP-activated catalytic subunit beta, HGNC:9381) is a protein-coding gene on chromosome 1p31.1, encoding cAMP-dependent protein kinase catalytic subunit beta (P22694). Mediates cAMP-dependent signaling triggered by receptor binding to GPCRs.

The protein encoded by this gene is a member of the serine/threonine protein kinase family. The encoded protein is a catalytic subunit of cAMP (cyclic AMP)-dependent protein kinase, which mediates signalling though cAMP. cAMP signaling is important to a number of processes, including cell proliferaton and differentiation. Multiple alternatively spliced transcript variants encoding distinct isoforms have been observed.

Source: NCBI Gene 5567 — RefSeq curated summary.

At a glance

• Gene–disease (curated): cardioacrofacial dysplasia 2 (Strong, GenCC) — +1 more curated relationship
• GWAS associations: 4
• Clinical variants (ClinVar): 80 total — 5 pathogenic, 1 likely-pathogenic
• Phenotypes (HPO): 73
• Druggable target: yes — 19 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_182948

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:9381
Approved symbol	PRKACB
Name	protein kinase cAMP-activated catalytic subunit beta
Location	1p31.1
Locus type	gene with protein product
Status	Approved
Aliases	PKACb
Ensembl gene	ENSG00000142875
Ensembl biotype	protein_coding
OMIM	176892
Entrez	5567

Gene structure

Transcript identifiers

Ensembl transcripts: 21 — 19 protein_coding, 2 protein_coding_CDS_not_defined

ENST00000370680, ENST00000370684, ENST00000370685, ENST00000370688, ENST00000370689, ENST00000394839, ENST00000413538, ENST00000417530, ENST00000432111, ENST00000436133, ENST00000446538, ENST00000450730, ENST00000467507, ENST00000470673, ENST00000610457, ENST00000610703, ENST00000614872, ENST00000892501, ENST00000892502, ENST00000892503, ENST00000892504

RefSeq mRNA: 30 — MANE Select: NM_182948 NM_001242857, NM_001242858, NM_001242859, NM_001242860, NM_001242861, NM_001242862, NM_001300915, NM_001300916, NM_001300917, NM_001375560, NM_001375561, NM_001375562, NM_001375563, NM_001375564, NM_001375565, NM_001375569, NM_001375571, NM_001375572, NM_001375573, NM_001375574, NM_001375575, NM_001375576, NM_001375577, NM_001375578, NM_001375579, NM_001375580, NM_001375581, NM_002731, NM_182948, NM_207578

CCDS: CCDS55609, CCDS55610, CCDS55611, CCDS691, CCDS692, CCDS693, CCDS72812, CCDS72813, CCDS72814, CCDS72815, CCDS72816

Canonical transcript exons

ENST00000370685 — 10 exons

Exon	Start	End
ENSE00001453304	84144271	84144548
ENSE00001453310	84235180	84238498
ENSE00001632964	84214153	84214317
ENSE00001730019	84202683	84202805
ENSE00003556692	84184037	84184135
ENSE00003559763	84182200	84182328
ENSE00003627109	84185100	84185182
ENSE00003650407	84179177	84179238
ENSE00003784231	84196616	84196742
ENSE00003791104	84197729	84197824

Expression profiles

Bgee: expression breadth ubiquitous, 293 present calls, max score 99.88.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 46.9896 / max 3545.3427, expressed in 1791 samples.

FANTOM5 promoters (25 alternative TSS)

Promoter ID	TPM avg	Samples expressed
3759	8.9177	616
3755	8.8859	1569
3760	8.5158	593
3769	4.6443	164
3756	4.3953	1285
3765	3.5439	165
3767	1.4089	145
3766	1.2361	127
3773	0.9533	102
3754	0.7469	429

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
endothelial cell	CL:0000115	99.88	gold quality
Brodmann (1909) area 23	UBERON:0013554	99.76	gold quality
parietal lobe	UBERON:0001872	99.66	gold quality
postcentral gyrus	UBERON:0002581	99.66	gold quality
middle temporal gyrus	UBERON:0002771	99.62	gold quality
entorhinal cortex	UBERON:0002728	99.61	gold quality
orbitofrontal cortex	UBERON:0004167	99.61	gold quality
pons	UBERON:0000988	99.56	gold quality
Brodmann (1909) area 46	UBERON:0006483	99.55	gold quality
superior vestibular nucleus	UBERON:0007227	99.49	gold quality
corpus callosum	UBERON:0002336	99.47	gold quality
substantia nigra pars compacta	UBERON:0001965	99.41	gold quality
substantia nigra pars reticulata	UBERON:0001966	99.35	gold quality
cortical plate	UBERON:0005343	99.35	gold quality
CA1 field of hippocampus	UBERON:0003881	99.34	gold quality
subthalamic nucleus	UBERON:0001906	99.32	gold quality
lateral globus pallidus	UBERON:0002476	99.30	gold quality
inferior vagus X ganglion	UBERON:0005363	99.30	gold quality
ventral tegmental area	UBERON:0002691	99.25	gold quality
lateral nuclear group of thalamus	UBERON:0002736	99.25	gold quality
dorsal plus ventral thalamus	UBERON:0001897	99.23	gold quality
medulla oblongata	UBERON:0001896	99.18	gold quality
occipital lobe	UBERON:0002021	99.14	gold quality
cranial nerve II	UBERON:0000941	99.11	gold quality
frontal pole	UBERON:0002795	99.01	gold quality
superior frontal gyrus	UBERON:0002661	98.99	gold quality
parotid gland	UBERON:0001831	98.96	gold quality
primary visual cortex	UBERON:0002436	98.95	gold quality
mucosa of sigmoid colon	UBERON:0004993	98.89	gold quality
colonic mucosa	UBERON:0000317	98.66	gold quality

Single-cell (SCXA)

Detected in 6 experiment(s), a significant marker in 5.

Experiment	Marker?	Max mean expression
E-MTAB-5061	yes	17.10
E-ANND-3	yes	10.05
E-GEOD-81608	yes	8.53
E-GEOD-81547	yes	6.30
E-GEOD-83139	yes	3.73
E-ENAD-27	no	3.21

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

183 targeting PRKACB, 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-3646	100.00	73.56	5283
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-5692B	100.00	71.32	2622
HSA-MIR-5692C	100.00	71.32	2622
HSA-MIR-429	100.00	73.44	2698
HSA-MIR-4668-3P	100.00	68.74	2635
HSA-MIR-574-5P	100.00	66.01	989
HSA-MIR-200B-3P	100.00	73.31	2693
HSA-MIR-200C-3P	100.00	73.35	2685
HSA-MIR-1252-5P	100.00	69.80	2774
HSA-LET-7A-3P	100.00	74.03	3932
HSA-LET-7B-3P	100.00	74.08	3913
HSA-LET-7F-1-3P	100.00	74.02	3928
HSA-MIR-98-3P	100.00	74.08	3907
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-568	99.98	69.86	2084
HSA-MIR-19A-3P	99.98	75.33	2762
HSA-MIR-19B-3P	99.98	75.44	2754
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-548P	99.98	72.25	3784
HSA-MIR-3617-3P	99.98	67.86	918
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-3065-5P	99.97	71.56	3281
HSA-MIR-590-3P	99.96	74.34	6478

Literature-anchored findings (GeneRIF, showing 32)

• c-MYC induces the activity of protein kinase A by inducing the transcription of the gene encoding the PKA catalytic subunit beta in multiple tissues, independent of cell proliferation by direct binding of c-MYC to promoter sequences. (PMID:12420224)
• Data describe the identification of a variant of the beta catalytic subunit of cyclic AMP-dependent protein kinase (PKACbeta) as a p75 neurotrophin receptor(NTR)-interacting protein, which phosphorylates p75(NTR) at Ser304. (PMID:12682012)
• there are abnormalities in [3H]cAMP binding and catalytic activity kinase A in brain of depressed suicide victims, which could be due to reduced expression of RIIbeta and Cbeta. (PMID:14744463)
• there is a PKA-Cbeta-mediated inhibitory mechanism of p73 function (PMID:15723830)
• Murine lymphoid tissues express a protein that is a homologue of human protein kinase c subunit beta2 (PMID:16889664)
• In conclusion, it seems that the Cbeta isoforms of PKA play different roles in proliferation and differentiation and could therefore be potential markers for prostate cancer progression. (PMID:16949795)
• Data provide the first evidence that Protein kinase C -beta play pivotal role in the regulation of AA production and cellular proliferation of human monocytoid MonoMac-6 cells. (PMID:17549442)
• Nuclear PKA C subunit co-locates with HA95 in splicing factor compartments and regulates pre-mRNA splicing, possibly through a cAMP-independent mechanism. (PMID:17594903)
• Recruitment of coactivator glucocorticoid receptor interacting protein 1 to an estrogen receptor transcription complex is regulated by the 3’,5’-cyclic adenosine 5’-monophosphate-dependent protein kinase. (PMID:18499756)
• 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)
• Report expression of protein kinase A and C subunits in post-mortem prefrontal cortex from persons with major depression and normal controls. (PMID:19573263)
• Results suggest that PKA can negatively regulate ERalpha, at least in part, through FoxH1. (PMID:19711044)
• Data show that Phosphorylation of The(197) in the activation loop on protein kinase A decreased the K(m) by approximately 15- and 7-fold for kemptide and ATP, respectively. (PMID:19965870)
• activated by podophyllotoxin (PMID:20033853)
• Data show that PI3K activation and PIP3 production lead to recruitment of the PKB/beta-arrestin/PDE4 complex to the membrane via the PKB PH domain, resulting in degradation of the TCR-induced cAMP pool and allowing full T-cell activation to proceed. (PMID:20086095)
• PGE(2)-induced CYP1B1 expression is mediated by ligand-independent activation of the ERalpha pathway as a result of the activation of ERK, Akt, and PKA in breast cancer cells. (PMID:20093341)
• The previously unknown small molecule inhibitor-dependent interaction of Cbeta1 with the cell cycle and apoptosis regulatory protein-1 was verified. (PMID:20564261)
• The gene polymorphism loci rs12132032 in PRKACB maybe a potential risk factor for anencephaly in Chinese population from Shanxi, while gender susceptibility may influence the correlation. (PMID:24294386)
• analysis of the mechanism underlying synergistic up-regulation of PDE4B2 via a cross-talk between PKA-Cbeta and p65 (PMID:25831493)
• Cbeta2 subunit of protein kinase A mRNA was up-regulated in prostate cancer and low expression of Cbeta2 mRNA in prostate cancer biopsies correlated with poor survival. (PMID:27838142)
• We identified fusions in PRKACA and PRKACB genes in pancreatic and biliary IOPNs, as well as in PDACs and pancreatic cyst fluid and bile duct cells from the same patients. These fusions might be used to identify patients at risk for IOPNs and their associated invasive carcinomas. (PMID:31678302)
• MicroRNA-384 Inhibits the Progression of Papillary Thyroid Cancer by Targeting PRKACB. (PMID:31998791)
• PRKACB variants in skeletal disease or adrenocortical hyperplasia: effects on protein kinase A. (PMID:33055300)
• Germline and Mosaic Variants in PRKACA and PRKACB Cause a Multiple Congenital Malformation Syndrome. (PMID:33058759)
• The conserved Tpk1 regulates non-homologous end joining double-strand break repair by phosphorylation of Nej1, a homolog of the human XLF. (PMID:34244791)
• Novel implications of a strictly monomorphic (GCC) repeat in the human PRKACB gene. (PMID:34667254)
• Expressing MLH1 in HCT116 cells increases cellular resistance to radiation by activating the PRKAC. (PMID:34787019)
• Investigation of -PRKACA/-PRKACB fusion genes in oncocytic tumors of the pancreatobiliary and other systems. (PMID:36152045)
• Gene Rearrangement and Expression of PRKACA and PRKACB Govern Morphobiology of Pancreatobiliary Oncocytic Neoplasms. (PMID:37871652)
• Dual-Specificity Phosphatase 4 Promotes Malignant Features in Colorectal Cancer Through Cyclic-AMP Response Element Binding Protein/Protein Kinase CAMP-Activated Catalytic Subunit Beta Activation. (PMID:38824257)
• PRKACA/PRKACB Fusions in Pancreatobiliary Intraductal Oncocytic Papillary Neoplasms Including Those With Atypical Morphology: An Analysis of 22 Cases Expanding Morphologic Spectrum. (PMID:38841868)

Cross-species orthologs

8 orthologs

Organism	Symbol	Gene ID
danio_rerio	prkacba	ENSDARG00000001782
danio_rerio	prkacab	ENSDARG00000016809
mus_musculus	Prkacb	ENSMUSG00000005034
rattus_norvegicus	Prkacb	ENSRNOG00000004978
drosophila_melanogaster	Pka-C2	FBGN0000274
drosophila_melanogaster	Pkg21D	FBGN0000442
drosophila_melanogaster	CG12069	FBGN0039796
caenorhabditis_elegans		WBGENE00001173

Paralogs (5): PRKACA (ENSG00000072062), PRKG2 (ENSG00000138669), PRKACG (ENSG00000165059), PRKX (ENSG00000183943), PRKG1 (ENSG00000185532)

Protein

Protein identifiers

cAMP-dependent protein kinase catalytic subunit beta — P22694 (reviewed: P22694)

All UniProt accessions (10): P22694, A0A087WVC4, B1APF7, B1APF8, B1APF9, B1APG0, B1APG1, B1APG2, B1APG3, B2RB89

UniProt curated annotations — full annotation on UniProt →

Function. Mediates cAMP-dependent signaling triggered by receptor binding to GPCRs. PKA activation regulates diverse cellular processes such as cell proliferation, the cell cycle, differentiation and regulation of microtubule dynamics, chromatin condensation and decondensation, nuclear envelope disassembly and reassembly, as well as regulation of intracellular transport mechanisms and ion flux. Regulates the abundance of compartmentalized pools of its regulatory subunits through phosphorylation of PJA2 which binds and ubiquitinates these subunits, leading to their subsequent proteolysis. Phosphorylates GPKOW which regulates its ability to bind RNA. Acts as a negative regulator of mTORC1 by mediating phosphorylation of RPTOR.

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. Interacts with PRKAR1A and PRKAR2B. The cAMP-dependent protein kinase catalytic subunit binds PJA2. Interacts with GPKOW.

Subcellular location. Cytoplasm. Cell membrane. Membrane. Nucleus.

Tissue specificity. Isoform 1 is most abundant in the brain, with low level expression in kidney. Isoform 2 is predominantly expressed in thymus, spleen and kidney. Isoform 3 and isoform 4 are only expressed in the brain.

Post-translational modifications. Asn-3 is partially deaminated to Asp giving rise to 2 major isoelectric variants, called CB and CA respectively.

Disease relevance. Cardioacrofacial dysplasia 2 (CAFD2) [MIM:619143] An autosomal dominant disease characterized by dysmorphic facial features, congenital cardiac defects, primarily common atrium or atrioventricular septal defect, and limb anomalies, including short limbs, brachydactyly and postaxial polydactyly. CAFD2 patients may show developmental delay of variable severity, intellectual disability, autistic features and focal seizures. The disease is caused by variants affecting the gene represented in this entry.

Activity regulation. Activated by cAMP.

Miscellaneous. Incomplete sequence. Incomplete sequence. Incomplete sequence.

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

Isoforms (10)

UniProt ID	Names	Canonical?
P22694-1	1, Beta1	yes
P22694-2	2, Beta2
P22694-3	3, Beta3
P22694-4	4, Beta4
P22694-5	5, Beta4ab
P22694-6	6, Beta4abc
P22694-7	7
P22694-8	8
P22694-9	9
P22694-10	10

RefSeq proteins (30): NP_001229786, NP_001229787, NP_001229788, NP_001229789, NP_001229790, NP_001229791, NP_001287844, NP_001287845, NP_001287846, NP_001362489, NP_001362490, NP_001362491, NP_001362492, NP_001362493, NP_001362494, NP_001362498, NP_001362500, NP_001362501, NP_001362502, NP_001362503, NP_001362504, NP_001362505, NP_001362506, NP_001362507, NP_001362508, NP_001362509, NP_001362510, NP_002722, NP_891993, NP_997461 (=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 (38 total): splice variant 12, modified residue 8, sequence variant 5, sequence conflict 5, domain 2, binding site 2, initiator methionine 1, chain 1, lipid moiety-binding region 1, active site 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P22694-F1	95.61	0.95

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 (9): 140, 198, 322, 331, 339, 2, 3, 11, 69

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: 767 (showing top): REACTOME_TRIGLYCERIDE_CATABOLISM, GOBP_MORPHOGENESIS_OF_AN_EPITHELIUM, GCACCTT_MIR18A_MIR18B, GOBP_EMBRYO_DEVELOPMENT_ENDING_IN_BIRTH_OR_EGG_HATCHING, GOBP_EPITHELIUM_DEVELOPMENT, REACTOME_INNATE_IMMUNE_SYSTEM, GGTGTGT_MIR329, KEGG_HEDGEHOG_SIGNALING_PATHWAY, REACTOME_ADAPTIVE_IMMUNE_SYSTEM, GOBP_RESPONSE_TO_FLUID_SHEAR_STRESS, KEGG_MAPK_SIGNALING_PATHWAY, MODULE_45, GOBP_INSULIN_SECRETION, GOBP_CELLULAR_RESPONSE_TO_FLUID_SHEAR_STRESS, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN

GO Biological Process (15): neural tube closure (GO:0001843), renal water homeostasis (GO:0003091), protein phosphorylation (GO:0006468), signal transduction (GO:0007165), adenylate cyclase-modulating G protein-coupled receptor signaling pathway (GO:0007188), adenylate cyclase-activating G protein-coupled receptor signaling pathway (GO:0007189), dorsal/ventral neural tube patterning (GO:0021904), positive regulation of insulin secretion (GO:0032024), high-density lipoprotein particle assembly (GO:0034380), negative regulation of smoothened signaling pathway (GO:0045879), regulation of protein processing (GO:0070613), vascular endothelial cell response to laminar fluid shear stress (GO:0097700), negative regulation of TORC1 signaling (GO:1904262), cellular response to nutrient levels (GO:0031669), TORC1 signaling (GO:0038202)

GO Molecular Function (12): magnesium ion binding (GO:0000287), protein serine/threonine kinase activity (GO:0004674), cAMP-dependent protein kinase activity (GO:0004691), ATP binding (GO:0005524), potassium channel inhibitor activity (GO:0019870), ubiquitin protein ligase binding (GO:0031625), 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 (10): nucleus (GO:0005634), nucleoplasm (GO:0005654), centrosome (GO:0005813), cytosol (GO:0005829), plasma membrane (GO:0005886), cAMP-dependent protein kinase complex (GO:0005952), extracellular exosome (GO:0070062), ciliary base (GO:0097546), cytoplasm (GO:0005737), membrane (GO:0016020)

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	5
cellular response to stimulus	2
protein kinase activity	2
primary neural tube formation	1
tube closure	1
renal system process	1
multicellular organismal-level water homeostasis	1
phosphorylation	1
protein modification process	1
cell communication	1
cellular process	1
signaling	1
regulation of cellular process	1
adenylate cyclase activity	1
G protein-coupled receptor signaling pathway	1
adenylate cyclase-modulating G protein-coupled receptor signaling pathway	1
adenylate cyclase activator activity	1
dorsal/ventral pattern formation	1
neural tube patterning	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
smoothened signaling pathway	1
regulation of smoothened signaling pathway	1
negative regulation of signal transduction	1
protein processing	1
regulation of proteolysis	1
regulation of protein maturation	1
cellular response to laminar fluid shear stress	1
vascular endothelial cell response to fluid shear stress	1
negative regulation of TOR signaling	1
TORC1 signaling	1
regulation of TORC1 signaling	1
response to nutrient levels	1
TOR signaling	1
metal ion binding	1
cyclic nucleotide-dependent protein kinase activity	1
cAMP binding	1

Protein interactions and networks

STRING

6952 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PRKACB	AKAP1	Q92667	998
PRKACB	AKAP12	Q02952	989
PRKACB	AKAP5	P24588	985
PRKACB	EZR	P15311	983
PRKACB	CALML3	P27482	971
PRKACB	CALML4	Q96GE6	971
PRKACB	CALML5	Q9NZT1	971
PRKACB	CALM1	P02593	970
PRKACB	RAPGEF3	O95398	970
PRKACB	CALML6	Q8TD86	969
PRKACB	AKAP9	Q99996	967
PRKACB	RAPGEF4	Q8WZA2	967
PRKACB	CREB1	P16220	958
PRKACB	AKAP6	Q13023	951
PRKACB	SUFU	Q9UMX1	929

IntAct

128 interactions, top by confidence:

A	B	Type	Score
GSK3A	AXIN1	psi-mi:“MI:0914”(association)	0.800
PRKACB	PRKAR1A	psi-mi:“MI:0914”(association)	0.790
DYNLL1	BLTP3B	psi-mi:“MI:0914”(association)	0.730
PRKACA	VAPB	psi-mi:“MI:0914”(association)	0.730
VAPB	FAM83G	psi-mi:“MI:0914”(association)	0.730
DYNLL2	BLTP3B	psi-mi:“MI:0914”(association)	0.640
VAPA	FAM83G	psi-mi:“MI:0914”(association)	0.640
VAPA	PITPNM1	psi-mi:“MI:0914”(association)	0.640
APPBP2	PRKACB	psi-mi:“MI:0915”(physical association)	0.560
PRKACB	APPBP2	psi-mi:“MI:0915”(physical association)	0.560
PRKACB	PKIA	psi-mi:“MI:0915”(physical association)	0.560
PRKACB	AVPI1	psi-mi:“MI:0915”(physical association)	0.560
APP	PRKACB	psi-mi:“MI:0915”(physical association)	0.560
PRKACB	HSP90AB1	psi-mi:“MI:0915”(physical association)	0.560
PRKCZ	IPO5	psi-mi:“MI:0914”(association)	0.530
PICK1	ILVBL	psi-mi:“MI:0914”(association)	0.530
RABGGTB	PIPSL	psi-mi:“MI:0914”(association)	0.530
MLF1	NDC80	psi-mi:“MI:0914”(association)	0.530
BMP1	TLL1	psi-mi:“MI:0914”(association)	0.530
PKIG	TYMS	psi-mi:“MI:0914”(association)	0.530

BioGRID (320): PRKACB (Two-hybrid), APPBP2 (Two-hybrid), PRKACB (Affinity Capture-MS), PRKACB (Affinity Capture-MS), PRKACB (Affinity Capture-MS), PRKACB (Affinity Capture-MS), PRKACB (Affinity Capture-MS), PRKACB (Affinity Capture-MS), PRKACB (Affinity Capture-MS), PRKACB (Affinity Capture-MS), PRKACB (Affinity Capture-MS), PRKACB (Affinity Capture-MS), PRKACB (Affinity Capture-MS), PRKACB (Affinity Capture-MS), PRKACB (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

21 interactions.

A	Effect	B	Mechanism
PRKACB	up-regulates	MYBPC3	phosphorylation
PRKAR1A	“down-regulates activity”	PRKACB	binding
PRKAR1B	“down-regulates activity”	PRKACB	binding
PRKAR2A	“down-regulates activity”	PRKACB	binding
PRKAR2B	“down-regulates activity”	PRKACB	binding
PRKACB	“down-regulates activity”	TENT2	phosphorylation
PRKACB	“down-regulates activity”	PHKA2	phosphorylation
PRKACB	“down-regulates activity”	PHKA1	phosphorylation
PRKACB	down-regulates	BAD	phosphorylation
PRKACB	up-regulates	NGFR	phosphorylation
3-(1-methyl-3-indolyl)-4-[1-[1-(2-pyridinylmethyl)-4-piperidinyl]-3-indolyl]pyrrole-2,5-dione	“down-regulates activity”	PRKACB	“chemical inhibition”
Ruboxistaurin	“down-regulates activity”	PRKACB	“chemical inhibition”
PRKACB	“up-regulates activity”	GPKOW	phosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 157 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	6	37.0×	2e-06
PKA activation	6	34.9×	2e-06
PKA-mediated phosphorylation of CREB	6	31.4×	2e-06
DARPP-32 events	6	26.2×	5e-06
Anti-inflammatory response favouring Leishmania parasite infection	6	21.7×	1e-05
Leishmania parasite growth and survival	6	21.7×	1e-05
Calmodulin induced events	6	20.9×	1e-05
CaM pathway	6	20.9×	1e-05

GO biological processes:

GO term	Partners	Fold	FDR
vascular endothelial cell response to laminar fluid shear stress	6	31.9×	3e-05
cellular response to glucagon stimulus	5	30.5×	2e-04
renal water homeostasis	6	22.2×	2e-04
negative regulation of inflammatory response to antigenic stimulus	5	21.8×	7e-04
negative regulation of cAMP/PKA signal transduction	5	21.8×	7e-04
regulation of microtubule cytoskeleton organization	5	19.7×	1e-03
positive regulation of protein import into nucleus	5	15.3×	3e-03
negative regulation of gene expression	10	5.0×	4e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	5
Likely pathogenic	1
Uncertain significance	41
Likely benign	8
Benign	1

Top pathogenic / likely-pathogenic (6)

Variant ID	HGVS	Classification
1805125	NM_182948.4(PRKACB):c.404A>T (p.His135Leu)	Pathogenic
989456	NM_182948.4(PRKACB):c.844G>C (p.Gly282Arg)	Pathogenic
989457	NM_182948.4(PRKACB):c.302C>T (p.Ser101Leu)	Pathogenic
989458	NM_182948.4(PRKACB):c.404A>G (p.His135Arg)	Pathogenic
989459	NM_182948.4(PRKACB):c.403C>A (p.His135Asn)	Pathogenic
4291969	NM_182948.4(PRKACB):c.997A>G (p.Lys333Glu)	Likely pathogenic

SpliceAI

1514 predictions. Top by Δscore:

Variant	Effect	Δscore
1:84179161:ATAT:A	acceptor_gain	1.0000
1:84179162:T:G	acceptor_gain	1.0000
1:84179163:A:AG	acceptor_gain	1.0000
1:84179163:AT:A	acceptor_gain	1.0000
1:84179164:T:G	acceptor_gain	1.0000
1:84179164:T:TA	acceptor_gain	1.0000
1:84179168:T:G	acceptor_gain	1.0000
1:84179169:A:AG	acceptor_gain	1.0000
1:84179175:A:AG	acceptor_gain	1.0000
1:84179176:G:GG	acceptor_gain	1.0000
1:84179176:GT:G	acceptor_gain	1.0000
1:84179235:TCAGG:T	donor_loss	1.0000
1:84179236:CAGG:C	donor_loss	1.0000
1:84179238:GGTAA:G	donor_loss	1.0000
1:84179239:G:A	donor_loss	1.0000
1:84179240:T:A	donor_loss	1.0000
1:84182185:T:G	acceptor_gain	1.0000
1:84182185:T:TA	acceptor_gain	1.0000
1:84182188:A:AG	acceptor_gain	1.0000
1:84182189:T:G	acceptor_gain	1.0000
1:84182192:A:AG	acceptor_gain	1.0000
1:84182193:C:G	acceptor_gain	1.0000
1:84182194:A:AG	acceptor_gain	1.0000
1:84182195:T:G	acceptor_gain	1.0000
1:84182196:A:AG	acceptor_gain	1.0000
1:84182196:ATAG:A	acceptor_loss	1.0000
1:84182197:T:G	acceptor_gain	1.0000
1:84182197:TAGA:T	acceptor_loss	1.0000
1:84182198:A:AG	acceptor_gain	1.0000
1:84182199:G:GT	acceptor_gain	1.0000

AlphaMissense

2636 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:84182240:T:A	L50H	1.000
1:84182242:G:A	G51R	1.000
1:84182242:G:C	G51R	1.000
1:84182243:G:A	G51E	1.000
1:84182248:G:C	G53R	1.000
1:84182248:G:T	G53C	1.000
1:84182249:G:A	G53D	1.000
1:84182254:T:A	F55I	1.000
1:84182254:T:C	F55L	1.000
1:84182256:T:A	F55L	1.000
1:84182256:T:G	F55L	1.000
1:84182257:G:A	G56R	1.000
1:84182257:G:C	G56R	1.000
1:84182258:G:A	G56E	1.000
1:84182258:G:T	G56V	1.000
1:84182303:C:A	A71D	1.000
1:84182308:A:C	K73Q	1.000
1:84182308:A:G	K73E	1.000
1:84182310:G:C	K73N	1.000
1:84182310:G:T	K73N	1.000
1:84184074:A:T	E92V	1.000
1:84184075:G:C	E92D	1.000
1:84184075:G:T	E92D	1.000
1:84185140:G:A	G126E	1.000
1:84185143:G:A	G127D	1.000
1:84185143:G:T	G127V	1.000
1:84185151:T:C	F130L	1.000
1:84185152:T:G	F130C	1.000
1:84185153:T:A	F130L	1.000
1:84185153:T:G	F130L	1.000

dbSNP variants (sampled 300 via entrez): RS1000002928 (1:84090159 C>T), RS1000030582 (1:84097999 T>A), RS1000042051 (1:84209649 AG>A), RS1000042172 (1:84179633 C>G,T), RS1000042238 (1:84128016 T>C,G), RS1000057750 (1:84118972 A>T), RS1000066672 (1:84174021 T>G), RS1000098774 (1:84142488 A>G), RS1000101108 (1:84102774 C>A,G), RS1000111463 (1:84213412 A>G), RS1000113130 (1:84189946 C>A,G), RS1000125429 (1:84188928 T>C), RS1000200159 (1:84236058 G>A,T), RS1000210055 (1:84093057 G>A), RS1000227186 (1:84212199 C>T)

Disease associations

OMIM: gene MIM:176892 | disease phenotypes: MIM:619143

GenCC curated gene-disease

Disease	Classification	Inheritance
cardioacrofacial dysplasia 2	Strong	Autosomal dominant
Ellis-van Creveld syndrome	Supportive	Autosomal recessive

Mondo (3): cardioacrofacial dysplasia 2 (MONDO:0030877), breast ductal adenocarcinoma (MONDO:0005590), Ellis-van Creveld syndrome (MONDO:0009162)

Orphanet (0):

HPO phenotypes

73 total (30 of 73 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000008	Abnormal morphology of female internal genitalia
HP:0000028	Cryptorchidism
HP:0000039	Epispadias
HP:0000047	Hypospadias
HP:0000069	Abnormality of the ureter
HP:0000072	Hydroureter
HP:0000077	Abnormality of the kidney
HP:0000164	Abnormality of the dentition
HP:0000190	Abnormal oral frenulum morphology
HP:0000191	Accessory oral frenulum
HP:0000233	Thin vermilion border
HP:0000276	Long face
HP:0000303	Mandibular prognathia
HP:0000316	Hypertelorism
HP:0000322	Short philtrum
HP:0000337	Broad forehead
HP:0000486	Strabismus
HP:0000668	Hypodontia
HP:0000684	Delayed eruption of teeth
HP:0000691	Microdontia
HP:0000698	Conical tooth
HP:0000774	Narrow chest
HP:0000924	Abnormality of the skeletal system
HP:0001156	Brachydactyly
HP:0001161	Hand polydactyly
HP:0001162	Postaxial hand polydactyly
HP:0001217	Clubbing
HP:0001231	Abnormal fingernail morphology
HP:0001241	Capitate-hamate fusion

GWAS associations

4 associations (top):

Study	Trait	p-value
GCST001690_1	Breast cancer (male)	1.000000e-06
GCST009391_1681	Metabolite levels	7.000000e-07
GCST012490_412	Femur bone mineral density x serum urate levels interaction	2.000000e-08
GCST012490_641	Femur bone mineral density x serum urate levels interaction	4.000000e-09

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0010343	cholesteryl ester 18:0 measurement
EFO:0004531	urate measurement

MeSH disease descriptors (2)

Descriptor	Name	Tree numbers
D018270	Carcinoma, Ductal, Breast	C04.557.470.200.025.232.500; C04.557.470.615.132.500; C04.588.180.390; C17.800.090.500.390
D004613	Ellis-Van Creveld Syndrome	C05.116.099.708.327; C16.131.077.350.398; C16.131.831.350.398; C16.320.850.250.398; C17.800.804.350.398; C17.800.827.250.398

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (2): CHEMBL2094138 (PROTEIN FAMILY), CHEMBL2918 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

19 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 60,401 (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
CHEMBL2325741	CAPIVASERTIB	4	2,157
CHEMBL5416410	DASATINIB	4	655
CHEMBL608533	MIDOSTAURIN	4	7,259
CHEMBL38380	FASUDIL	3	11,953
CHEMBL2219422	AFURESERTIB	3	1,467
CHEMBL300138	ENZASTAURIN	3	3,209
CHEMBL603469	LESTAURTINIB	3
CHEMBL91829	RUBOXISTAURIN	3	77
CHEMBL574737	UCN-01	2	2,217
CHEMBL575448	BMS-754807	2	406
CHEMBL6246	ELLAGIC ACID	2	23,148
CHEMBL3137336	UPROSERTIB	2	1,624
CHEMBL3545396	BMS-690514	2	567
CHEMBL475251	R-406	2	762
CHEMBL495727	AT-9283	2	1,376
CHEMBL3128043	PF-03758309	1	233
CHEMBL3544960	AT-13148	1	779
CHEMBL494089	GSK-690693	1	2,061
CHEMBL574738	AST-487	1	451

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

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

Ligand	Action	Affinity	Parameter
GSK690693	Inhibition	7.89	pKd
staurosporine	Inhibition	7.48	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
4-(4-Fluorophenyl)-2-(4-hydroxyphenyl)-5-(4-pyridyl)-1H-imidazole	KD	9.8 nM
PKC-412	KD	190 nM
(18S)-18-[(dimethylamino)methyl]-17-oxa-4,14,21-triazahexacyclo[19.6.1.1^{7,14}.0^{2,6}.0^{8,13}.0^{22,27}]nonacosa-1(28),2(6),7(29),8(13),9,11,22(27),23,25-nonaene-3,5-dione	KD	700 nM
1-[4-[(4-ethyl-1-piperazinyl)methyl]-3-(trifluoromethyl)phenyl]-3-[4-[[6-(methylamino)-4-pyrimidinyl]oxy]phenyl]urea	KD	1400 nM

ChEMBL bioactivities

284 potent at pChembl≥5 of 348 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
10.89	Kd	0.013	nM	CHEMBL5190946
10.00	IC50	0.1	nM	CHEMBL213618
10.00	Kd	0.1	nM	CHEMBL5183651
9.22	IC50	0.603	nM	STAUROSPORINE
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
8.92	IC50	1.2	nM	STAUROSPORINE
8.68	IC50	2.1	nM	CHEMBL383264
8.66	IC50	2.2	nM	CHEMBL3613609
8.64	IC50	2.28	nM	STAUROSPORINE
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
8.49	Kd	3.212	nM	CHEMBL5653589
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
8.17	IC50	6.8	nM	CHEMBL226148
8.17	ED50	6.79	nM	CHEMBL5653589
8.15	IC50	7	nM	CHEMBL3613604
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
7.89	Kd	13	nM	GSK-690693
7.85	Kd	14	nM	AT-13148
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

PubChem BioAssay actives

223 with measured affinity, of 1338 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
5-(2-aminopyrimidin-4-yl)-N-[6-[[1-[[6-[[5-carbamimidamido-1-[[5-carbamimidamido-1-[[5-carbamimidamido-1-[[5-carbamimidamido-1-[[5-carbamimidamido-1-[[5-carbamimidamido-1-[(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]amino]-6-oxohexyl]amino]-3-(1H-indol-3-yl)-1-oxopropan-2-yl]amino]-6-oxohexyl]selenophene-2-carboxamide	1846299: Binding affinity to human wild-type PKAc beta assessed as dissociation constant	kd	<0.0001	uM
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	1715214: Inhibition of human PKAcb using KEAKEKRQEQIAKRRRLSSLRASTSKSGGSQK as substrate by [gamma-33P]-ATP assay	ic50	0.0006	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
(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
(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
4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2149071: Binding affinity to human PRKACB incubated for 45 mins by Kinobead based pull down assay	kd	0.0032	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
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
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	624882: Binding constant for PKAC-beta kinase domain	kd	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-[(2S)-1-amino-3-(3,4-difluorophenyl)propan-2-yl]-5-chloro-4-(4-chloro-1-methylpyrazol-5-yl)furan-2-carboxamide	1425124: 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	0.0490	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, decreases expression, affects methylation, increases expression	8
trichostatin A	affects cotreatment, decreases expression	4
butyraldehyde	decreases expression, increases methylation	2
pentanal	decreases expression, increases methylation	2
Benzo(a)pyrene	decreases expression, increases mutagenesis	2
Ethinyl Estradiol	affects expression, affects reaction, decreases expression, decreases phosphorylation	2
Colforsin	decreases reaction, increases expression, affects cotreatment, increases response to substance, affects binding (+1 more)	2
Phenylmercuric Acetate	affects cotreatment, decreases expression	2
aristolochic acid I	decreases expression	1
FR900359	increases phosphorylation	1
ammonium 2,3,3,3-tetrafluoro-2-(heptafluoropropoxy)-propanoate	affects cotreatment, affects expression	1
testosterone enanthate	affects expression	1
oxybenzone	increases expression	1
triphenyl phosphate	affects expression	1
propionaldehyde	increases methylation	1
bisphenol A	decreases expression	1
nonanal	increases methylation	1
n-hexanal	increases methylation	1
2,4,5,2’,4’,5’-hexachlorobiphenyl	increases expression, decreases reaction	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
sodium arsenite	increases expression	1
tetrabromobisphenol A	decreases expression	1
perfluorooctanoic acid	affects cotreatment, affects expression	1
doxifluridine	decreases response to substance	1
2,2’,3’,4,4’,5-hexachlorobiphenyl	affects expression	1
coumarin	increases phosphorylation	1
caprylic aldehyde	increases methylation	1
1-UFT protocol	decreases response to substance	1
kemptide	increases phosphorylation	1
heptanal	increases methylation	1

ChEMBL screening assays

391 unique, capped per target: 385 binding, 6 functional

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

Cellosaurus cell lines

7 cell lines: 6 cancer cell line, 1 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B2C2	Abcam HeLa PRKACB KO	Cancer cell line	Female
CVCL_D7YE	Ubigene A-549 PRKACB KO	Cancer cell line	Male
CVCL_D8TU	Ubigene HCT 116 PRKACB KO	Cancer cell line	Male
CVCL_D9PH	Ubigene HEK293 PRKACB KO	Transformed cell line	Female
CVCL_E0LS	Ubigene HeLa PRKACB KO	Cancer cell line	Female
CVCL_TG72	HAP1 PRKACB (-) 1	Cancer cell line	Male
CVCL_TG73	HAP1 PRKACB (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT03414970	PHASE3	ACTIVE_NOT_RECRUITING	Hypofractionated Radiation Therapy After Mastectomy in Preventing Recurrence in Patients With Stage IIa-IIIa Breast Cancer
NCT00461344	PHASE2	TERMINATED	Docetaxel + Doxorubicin as Neoadjuvant Chemotherapy in Patients With Breast Cancer
NCT07499999	PHASE2	NOT_YET_RECRUITING	Randomized Double-Blind Phase II Trial of Baby Exemestane Versus Baby Tamoxifen in Post-Menopausal Women at High Risk for Breast Cancer
NCT00637364	PHASE1/PHASE2	SUSPENDED	High Intensity Focused Ultrasound Tumor Treatment for Pancreatic Cancer Pain
NCT02779855	PHASE1/PHASE2	COMPLETED	Talimogene Laherparepvec in Combination With Neoadjuvant Chemotherapy in Triple Negative Breast Cancer
NCT01753908	EARLY_PHASE1	COMPLETED	Broccoli Sprout Extract in Treating Patients With Breast Cancer
NCT01796041	EARLY_PHASE1	COMPLETED	Intraoperative Imaging of Breast Cancer With Indocyanine Green
NCT01208974	Not specified	ACTIVE_NOT_RECRUITING	Nipple-Areola Complex (NAC) Irradiation After Nipple-Sparing Mastectomy and Reconstruction
NCT01875198	Not specified	TERMINATED	Oncologic Impact of Splenectomy-omitting Radical Pancreatectomy in Well-selected Left-sided Pancreatic Cancer
NCT03543397	Not specified	UNKNOWN	MRI in Ductal Carcinoma in Situ (DCIS)
NCT03834532	Not specified	COMPLETED	Living Well After Breast Surgery