PRKACA

Summary

PRKACA (protein kinase cAMP-activated catalytic subunit alpha, HGNC:9380) is a protein-coding gene on chromosome 19p13.12, encoding cAMP-dependent protein kinase catalytic subunit alpha (P17612). Phosphorylates a large number of substrates in the cytoplasm and the nucleus.

This gene encodes one of the catalytic subunits of protein kinase A, which exists as a tetrameric holoenzyme with two regulatory subunits and two catalytic subunits, in its inactive form. 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. cAMP-dependent phosphorylation of proteins by protein kinase A is important to many cellular processes, including differentiation, proliferation, and apoptosis. Constitutive activation of this gene caused either by somatic mutations, or genomic duplications of regions that include this gene, have been associated with hyperplasias and adenomas of the adrenal cortex and are linked to corticotropin-independent Cushing’s syndrome. Alternative splicing results in multiple transcript variants encoding different isoforms. Tissue-specific isoforms that differ at the N-terminus have been described, and these isoforms may differ in the post-translational modifications that occur at the N-terminus of some isoforms.

Source: NCBI Gene 5566 — RefSeq curated summary.

At a glance

• Gene–disease (curated): cardioacrofacial dysplasia 1 (Strong, GenCC) — +2 more curated relationships
• Clinical variants (ClinVar): 79 total — 1 pathogenic
• Phenotypes (HPO): 83
• Druggable target: yes — 29 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_002730

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:9380
Approved symbol	PRKACA
Name	protein kinase cAMP-activated catalytic subunit alpha
Location	19p13.12
Locus type	gene with protein product
Status	Approved
Aliases	PKACa
Ensembl gene	ENSG00000072062
Ensembl biotype	protein_coding
OMIM	601639
Entrez	5566

Gene structure

Transcript identifiers

Ensembl transcripts: 17 — 13 protein_coding, 3 retained_intron, 1 nonsense_mediated_decay

ENST00000308677, ENST00000350356, ENST00000536649, ENST00000587372, ENST00000587533, ENST00000588209, ENST00000589284, ENST00000589994, ENST00000590853, ENST00000593092, ENST00000677951, ENST00000677971, ENST00000679067, ENST00000865237, ENST00000865238, ENST00000865239, ENST00000970385

RefSeq mRNA: 3 — MANE Select: NM_002730 NM_001304349, NM_002730, NM_207518

CCDS: CCDS12304, CCDS12305, CCDS92541

Canonical transcript exons

ENST00000308677 — 10 exons

Exon	Start	End
ENSE00001361389	14117502	14117762
ENSE00002862264	14091688	14093237
ENSE00003462126	14097579	14097674
ENSE00003483822	14093628	14093792
ENSE00003495407	14106760	14106888
ENSE00003501710	14097361	14097483
ENSE00003511814	14102816	14102914
ENSE00003565780	14097764	14097890
ENSE00003571973	14100826	14100908
ENSE00003674816	14107348	14107409

Expression profiles

Bgee: expression breadth ubiquitous, 143 present calls, max score 98.50.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 65.5473 / max 510.5482, expressed in 1824 samples.

FANTOM5 promoters (8 alternative TSS)

Promoter ID	TPM avg	Samples expressed
179614	60.0559	1824
179613	4.5668	1483
179608	0.4535	210
179612	0.3573	92
179609	0.0756	39
179611	0.0202	6
179610	0.0114	4
179607	0.0066	4

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
gastrocnemius	UBERON:0001388	98.50	gold quality
apex of heart	UBERON:0002098	98.40	gold quality
heart left ventricle	UBERON:0002084	98.36	gold quality
right atrium auricular region	UBERON:0006631	98.21	gold quality
muscle of leg	UBERON:0001383	98.13	gold quality
skeletal muscle tissue	UBERON:0001134	97.91	gold quality
hindlimb stylopod muscle	UBERON:0004252	97.83	gold quality
heart	UBERON:0000948	97.77	gold quality
left adrenal gland	UBERON:0001234	97.66	gold quality
left adrenal gland cortex	UBERON:0035825	97.64	gold quality
adrenal tissue	UBERON:0018303	97.63	gold quality
right adrenal gland cortex	UBERON:0035827	97.60	gold quality
right adrenal gland	UBERON:0001233	97.57	gold quality
adrenal gland	UBERON:0002369	97.55	gold quality
smooth muscle tissue	UBERON:0001135	97.20	gold quality
ovary	UBERON:0000992	97.18	gold quality
monocyte	CL:0000576	97.14	gold quality
right ovary	UBERON:0002118	97.12	gold quality
left ovary	UBERON:0002119	97.10	gold quality
leukocyte	CL:0000738	97.09	gold quality
superior frontal gyrus	UBERON:0002661	96.92	gold quality
primary visual cortex	UBERON:0002436	96.64	gold quality
prefrontal cortex	UBERON:0000451	96.49	gold quality
muscle tissue	UBERON:0002385	96.47	gold quality
adenohypophysis	UBERON:0002196	96.42	gold quality
hypothalamus	UBERON:0001898	96.40	gold quality
popliteal artery	UBERON:0002250	96.34	gold quality
tibial artery	UBERON:0007610	96.34	gold quality
frontal cortex	UBERON:0001870	96.28	gold quality
islet of Langerhans	UBERON:0000006	96.20	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	10.14
E-CURD-112	no	2.49

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): AP1, AR, ATF1, ATF2, ATF3, BCL11B, CEBPB, CEBPD, CEBPG, CREM, EGR4, ESR1, ETS2, ETV2, FOS, FOXH1, GATA3, GLI2, HNF4A, HSF1, HSF2, IRF6, JUNB, KAT5, MEF2D, MITF, MYB, MYC, MYF5, MYOD1, NCOA2, NCOA3, NFKB, NR4A2, NR5A1, NR5A2, PBX1, PHOX2A, POU1F1, PREB

miRNA regulators (miRDB)

89 targeting PRKACA, 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-4692	100.00	67.32	2066
HSA-MIR-4476	100.00	68.18	2030
HSA-MIR-6748-5P	100.00	65.81	1057
HSA-MIR-6876-5P	100.00	67.68	2126
HSA-MIR-6127	100.00	66.76	2188
HSA-MIR-6870-5P	99.99	68.55	2115
HSA-MIR-4514	99.99	67.10	1870
HSA-MIR-4482-3P	99.98	72.50	3147
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-5698	99.97	68.49	2029
HSA-MIR-4723-5P	99.97	68.70	2034
HSA-MIR-7111-5P	99.97	68.48	2062
HSA-MIR-2110	99.96	66.68	1930
HSA-MIR-6825-5P	99.96	69.81	3431
HSA-MIR-185-3P	99.95	67.01	1743
HSA-MIR-6835-3P	99.93	70.49	2904
HSA-MIR-3671	99.90	73.04	3897
HSA-MIR-4753-3P	99.90	71.03	3786
HSA-MIR-627-3P	99.90	71.42	3316
HSA-MIR-4492	99.87	68.25	3611
HSA-MIR-4447	99.85	67.81	2900
HSA-MIR-4728-5P	99.85	69.39	4718
HSA-MIR-1323	99.83	69.89	2471
HSA-MIR-6756-5P	99.82	67.97	2466
HSA-MIR-6785-5P	99.82	68.68	4428
HSA-MIR-6842-5P	99.80	67.54	1587
HSA-MIR-7110-5P	99.80	67.84	1712
HSA-MIR-3150A-3P	99.76	64.44	1640
HSA-MIR-6763-5P	99.76	64.68	1767
HSA-MIR-6794-5P	99.76	66.38	1048

Literature-anchored findings (GeneRIF, showing 40)

• Protein kinase A enhances, whereas glycogen synthase kinase-3 beta inhibits, the activity of the exon 2-encoded transactivator domain of heterogeneous nuclear ribonucleoprotein D in a hierarchical fashion. (PMID:11903055)
• regulation of the membrane binding of PKCalpha (PMID:11997388)
• Katacalcin regulates human CD14+ PBMC migration via signaling events involving protein kinase A-dependent cAMP pathways. (PMID:12369791)
• cAMP-induced inhibition of P-selectin expression is, in large part, mediated through activation of PKA. (PMID:12574812)
• the effects of protein kinase A stimulation on sustained current in wild type and three disease-linked C-terminal mutant channels (D1790G, Y1795C, and Y1795H) (PMID:14500710)
• Merlin was phosphorylated by PKA in cells in which PAK activity was suppressed, indicating that the two kinases function independently. PKA can phosphorylate merlin at serine 518, promoting heterodimerization between merlin and ezrin (PMID:14981079)
• Inhibition of PKCalpha markedly inhibited IP3-induced activation of calcium the current. (PMID:15016832)
• PKACA is involved in extracellular (Ca2+) signalling mediated by the calcium sensing receptor. (PMID:15212956)
• repressor nuclear factor-kappaB p50/p50 binding to DNA depends on phosphorylation of Ser337 by the protein kinase A catalytic subunit (PMID:15642694)
• Protein kinase A regulates caspase-9 activation by Apaf-1 downstream of cytochrome c (PMID:15703181)
• a pseudopodial-located RhoA/ROCK/p38/NHE1 signal module is regulated by Protein Kinase A gating and then regulates invasion in breast cancer cell lines (PMID:15843433)
• claudin-3 phosphorylation by PKA may provide a mechanism for the disruption of tight junctions in ovarian cancer (PMID:15905176)
• A small but significant decrease in PKA, AKAP79, and PP2B in myometrial tissues from women in labor may contribute to a decrease in negative feedback on and enhancement of contractant signals at term (PMID:15914039)
• Protein kinase A-dependent phosphorylation of Lutheran/basal cell adhesion molecule glycoprotein regulates cell adhesion to laminin alpha5 (PMID:15975931)
• GCMa acetylation is mediated by CBP, which stimulates GCMa transcriptional activity through cyclic AMP/protein kinase A signaling (PMID:16166624)
• CTP synthetase is phosphorylated by protein kinase A (PMID:16179339)
• kinase inhibits the phosphatidylinositiol (3,4,5)-trisphosphate and Gbetagamma-mediated regulation of its activity (PMID:16301320)
• Results imply a hindered transduction of the protein kinase A phosphorylation signal from cardiac troponin I to troponin C. (PMID:16302972)
• analysis of a novel, noncanonical mechanism of modulation of beta-catenin signaling through direct phosphorylation of beta-catenin by PKA, promoting its interaction with CREB-binding protein (PMID:16476742)
• These observations suggest that in primary pulmonary fibroblasts, PKCalpha but not PKCdelta or PKCepsilon mediate the profibrotic effect of CCL18. (PMID:16601239)
• ATP binding specifically to the ATPC site in S2- InsP3R-1 controls the susceptibility of the receptor to protein kinase A-mediated phosphorylation (PMID:16621795)
• Results suggest that gravin maintains a signaling complex that includes protein kinase A and phosphodiesterase 4D. (PMID:16642035)
• transcriptomes associated with protein kinase A pathway was identified in human prostate cancer cells using Affymetrix GeneChip technology (PMID:16751804)
• Thus, PAR2 activates PKCepsilon and PKA in sensory neurons, and thereby sensitizes TRPV1 to cause thermal hyperalgesia. (PMID:16793902)
• analysis of a novel mechanism for the phosphorylation of MYPT3 by PKA and activation of the catalytic activity through direct interaction of a central region of MYPT3 with its N-terminal region (PMID:16920702)
• Results suggest involvement of AMP-activated protein kinase in the control of expression of both metabolic genes, UCP3 and GLUT4, in the skeletal muscle of mice and of human newborns. (PMID:16966355)
• STAT3 activation by G alpha(s) distinctively requires protein kinase A, JNK, and phosphatidylinositol 3-kinase (PMID:17008315)
• Data show that activation-dependent expression of matrix metalloproteinases in peripheral blood mononuclear cells involves protein kinase A. (PMID:17043752)
• activation of RankL gene expression by PKA- and gp130-inducers is mediated via common regulatory domains that also served to facilitate the activity of 1,25-(OH)2D3 (PMID:17053039)
• Rap1 mediates cyclic AMP-stimulated neurotensin secretion downstream of both Epac and protein kinase A signaling pathways (PMID:17068197)
• Opposite roles for the protein kinase A transgene are defined in the formation of initial memories and extinction memories, representing the first genetic evidence that protein kinases may be constraints for the extinction of fear. (PMID:17151273)
• LXRalpha is regulated not only by oxysterol derivatives but also by PKA-mediated phosphorylation, which suggests that nutritional regulation of SREBP-1c and lipogenesis could be regulated at least partially through modulation of LXR (PMID:17296605)
• These results indicate that the reactive oxygen species-mediated TNF-alpha-induced IL-8 transcription is regulated by NF-kappaB/RelA phosphorylation at the critical Ser(276) residue by PKAc, resulting in stable enhanceosome formation on target genes. (PMID:17317104)
• STAT-3 activation by DFMO is at least in part mediated through the PKA pathway (PMID:17333334)
• PTH induces an increased activity of the eNOS system through PKA and PKC pathways (PMID:17545677)
• Protein phosphorylation by PRKACA at Ser(637) results in clear alterations in Drp1 function and mitochondrial morphology. (PMID:17553808)
• cyclic AMP-dependent protein kinase regulates proteasome function through phosphorylation of Rpt6 (PMID:17565987)
• The anx 2-S100A10/CFTR complex is important for CFTR function across epithelia. (PMID:17581860)
• 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)
• PKA and VEGFR2 converge at the MEK/ERK1/2 pathway to protect serum starved neuronal cells from a caspase-dependent cell death. (PMID:17646929)

Cross-species orthologs

8 orthologs

Organism	Symbol	Gene ID
danio_rerio	prkacba	ENSDARG00000001782
danio_rerio	prkacab	ENSDARG00000016809
mus_musculus	Prkaca	ENSMUSG00000005469
rattus_norvegicus	Prkaca	ENSRNOG00000005257
drosophila_melanogaster	Pka-C2	FBGN0000274
drosophila_melanogaster	Pkg21D	FBGN0000442
drosophila_melanogaster	CG12069	FBGN0039796
caenorhabditis_elegans		WBGENE00001173

Paralogs (5): PRKG2 (ENSG00000138669), PRKACB (ENSG00000142875), PRKACG (ENSG00000165059), PRKX (ENSG00000183943), PRKG1 (ENSG00000185532)

Protein

Protein identifiers

cAMP-dependent protein kinase catalytic subunit alpha — P17612 (reviewed: P17612)

All UniProt accessions (9): P17612, A0A7I2V5J4, A0A7I2YQ82, A0A8V8TL59, B7Z708, K7EMV1, K7ENJ5, K7ERP6, Q15136

UniProt curated annotations — full annotation on UniProt →

Function. Phosphorylates a large number of substrates in the cytoplasm and the nucleus. Phosphorylates CDC25B, ABL1, NFKB1, CLDN3, histone H1.4 (H1-4), PSMC5/RPT6, PJA2, RYR2, RORA, SOX9, UHRF1 and VASP. 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. RORA is activated by phosphorylation. Required for glucose-mediated adipogenic differentiation increase and osteogenic differentiation inhibition from osteoblasts. Involved in chondrogenesis by mediating phosphorylation of SOX9. Involved in the regulation of platelets in response to thrombin and collagen; maintains circulating platelets in a resting state by phosphorylating proteins in numerous platelet inhibitory pathways when in complex with NF-kappa-B (NFKB1 and NFKB2) and I-kappa-B-alpha (NFKBIA), but thrombin and collagen disrupt these complexes and free active PRKACA stimulates platelets and leads to platelet aggregation by phosphorylating VASP. Prevents the antiproliferative and anti-invasive effects of alpha-difluoromethylornithine in breast cancer cells when activated. RYR2 channel activity is potentiated by phosphorylation in presence of luminal Ca(2+), leading to reduced amplitude and increased frequency of store overload-induced Ca(2+) release (SOICR) characterized by an increased rate of Ca(2+) release and propagation velocity of spontaneous Ca(2+) waves, despite reduced wave amplitude and resting cytosolic Ca(2+). PSMC5/RPT6 activation by phosphorylation stimulates proteasome. Negatively regulates tight junctions (TJs) in ovarian cancer cells via CLDN3 phosphorylation. NFKB1 phosphorylation promotes NF-kappa-B p50-p50 DNA binding. Required for phosphorylation of GLI transcription factors which inhibits them and prevents transcriptional activation of Hedgehog signaling pathway target genes. GLI transcription factor phosphorylation is inhibited by interaction of PRKACA with SMO which sequesters PRKACA at the cell membrane. Involved in embryonic development by down-regulating the Hedgehog (Hh) signaling pathway that determines embryo pattern formation and morphogenesis most probably through the regulation of OFD1 in ciliogenesis. Prevents meiosis resumption in prophase-arrested oocytes via CDC25B inactivation by phosphorylation. May also regulate rapid eye movement (REM) sleep in the pedunculopontine tegmental (PPT). Phosphorylates APOBEC3G and AICDA. Phosphorylates HSF1; this phosphorylation promotes HSF1 nuclear localization and transcriptional activity upon heat shock. Acts as a negative regulator of mTORC1 by mediating phosphorylation of RPTOR. Phosphorylates AKAP19. Phosphorylates and activates ABL1 in sperm flagellum to promote spermatozoa capacitation.

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. The cAMP-dependent protein kinase catalytic subunit binds PJA2. Both isoforms 1 and 2 forms activate cAMP-sensitive PKAI and PKAII holoenzymes by interacting with regulatory subunit (R) of PKA, PRKAR1A/PKR1 and PRKAR2A/PKR2, respectively. Interacts with PRKAR1A and PRKAR2B. Interacts with NFKB1, NFKB2 and NFKBIA in platelets; these interactions are disrupted by thrombin and collagen. Binds to ABL1 in spermatozoa and with CDC25B in oocytes. Interacts with APOBEC3G and AICDA. Interacts with RAB13; downstream effector of RAB13 involved in tight junction assembly. Found in a complex at least composed of MROH2B, PRKACA isoform 2 and TCP11. Interacts with MROH2B. Isoform 2 interacts with TCP11. Interacts with HSF1. Interacts with TBC1D31; in regulation of OFD1. Interacts in free form with SMO (via C-terminus); the interaction leads to sequestration of PRKACA at the membrane, preventing PRKACA-mediated phosphorylation of GLI transcription factors.

Subcellular location. Cytoplasm. Cell membrane. Membrane. Nucleus. Mitochondrion Cell projection. Cilium. Flagellum. Cytoplasmic vesicle. Secretory vesicle. Acrosome.

Tissue specificity. Isoform 1 is ubiquitous. Isoform 2 is sperm-specific and is enriched in pachytene spermatocytes but is not detected in round spermatids.

Post-translational modifications. Autophosphorylated. Phosphorylation is enhanced by vitamin K(2). Phosphorylated on threonine and serine residues. Phosphorylation on Thr-198 is required for full activity (PubMed:16765046, PubMed:20137943, PubMed:20481595, PubMed:20732331, PubMed:21774789, Ref.46). Phosphorylated at Tyr-331 by activated receptor tyrosine kinases EGFR and PDGFR; this increases catalytic efficiency. Asn-3 is partially deaminated to Asp-3 giving rise to 2 major isoelectric variants, called CB and CA respectively. When myristoylated, Ser-11 is autophosphorylated probably in conjunction with deamidation of Asn-3.

Disease relevance. Primary pigmented nodular adrenocortical disease 4 (PPNAD4) [MIM:615830] A rare bilateral adrenal defect causing ACTH-independent Cushing syndrome. Macroscopic appearance of the adrenals is characteristic with small pigmented micronodules observed in the cortex. Adrenal glands show overall normal size and weight, and multiple small yellow-to-dark brown nodules surrounded by a cortex with a uniform appearance. Microscopically, there are moderate diffuse cortical hyperplasia with mostly nonpigmented nodules, multiple capsular deficits and massive circumscribed and infiltrating extra-adrenal cortical excrescences with micronodules. Clinical manifestations of Cushing syndrome include facial and truncal obesity, abdominal striae, muscular weakness, osteoporosis, arterial hypertension, diabetes. The disease is caused by variants affecting the gene represented in this entry. Cardioacrofacial dysplasia 1 (CAFD1) [MIM:619142] 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. The disease is caused by variants affecting the gene represented in this entry.

Activity regulation. Allosterically activated by various compounds, including ATP. Activated by cAMP; the nucleotide acts as a dynamic and allosteric activator by coupling the two lobes of apo PKA, enhancing the enzyme dynamics synchronously and priming it for catalysis. Inhibited by H89 (N-[2-[[3-(4-Bromophenyl)-2-propenyl]amino]ethyl]-5-isoquinolinesulfonamide), spiroindoline, azole-based inhibitors, (3s)-amino-aminomethylbenzamide analogs, ARC-1032 (6-{[(2S,3S,4R,5R)-5-(6-amino-9H-purin-9-yl)-3,4-dihydroxyoxolan-2-yl]formamido}-N-[(1R)-4-carbamimidamido-1-carbamoylbutyl]hexanamide), ARC-1034 (6-{[(2S,3S,4R,5R)-5-(6-amino-9H-purin-9-yl)-3,4-dihydroxyoxolan-2-yl]formamido}-N-[(1R)-4-carbamimidamido-1-{[(1R)-4-carbamimidamido-1-carbamoylbutyl]carbamoyl}butyl]hexanamide), ARC-582, ARC-902 (Adc-6-aminohexanoic acid-(D-Arg)(6)-NH(2)), ARC-1012 ((2R)-6-amino-2-(6-{[(2S,3S,4R,5R)-5-(6-amino-9H-purin-9-yl)-3,4-dihydroxyoxolan-2-yl]formamido}hexanamido)-N-(5-{[(1R)-4-carbamimidamido-1-{[(1R)-4-carbamimidamido-1-carbamoylbutyl]carbamoyl}butyl]carbamoyl}pentyl)hexanamide) and ARC-1039 (6-{[(2S,3S,4R,5R)-5-(6-amino-9H-purin-9-yl)-3,4-dihydroxyoxolan-2-yl]formamido}-N-[(1R)-1-[(5-{[(1R)-4-carbamimidamido-1-{[(1R)-4-carbamimidamido-1-carbamoylbutyl]carbamoyl}butyl]carbamoyl}pentyl)carbamoyl]ethyl]he xanamide).

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

Isoforms (2)

UniProt ID	Names	Canonical?
P17612-1	1, C-alpha-1	yes
P17612-2	2, C-alpha-2, C-alpha-S, C(s)

RefSeq proteins (3): NP_001291278, NP_002721, NP_997401 (=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 (68 total): helix 19, mutagenesis site 10, strand 10, modified residue 8, sequence variant 5, turn 5, binding site 4, domain 2, initiator methionine 1, chain 1, lipid moiety-binding region 1, splice variant 1, active site 1

Structure

Experimental structures (PDB)

54 structures, top 30 by resolution.

PDB	Method	Resolution (Å)
4WB8	X-RAY DIFFRACTION	1.55
3OVV	X-RAY DIFFRACTION	1.58
3POO	X-RAY DIFFRACTION	1.6
4WB5	X-RAY DIFFRACTION	1.64
6QJ7	X-RAY DIFFRACTION	1.69
3AMA	X-RAY DIFFRACTION	1.75
4UJ1	X-RAY DIFFRACTION	1.77
5IZJ	X-RAY DIFFRACTION	1.85
4UJ9	X-RAY DIFFRACTION	1.87
3OWP	X-RAY DIFFRACTION	1.88
6FRX	X-RAY DIFFRACTION	1.88
5BX6	X-RAY DIFFRACTION	1.89
5BX7	X-RAY DIFFRACTION	1.89
3L9M	X-RAY DIFFRACTION	1.9
4WB7	X-RAY DIFFRACTION	1.9
4UJA	X-RAY DIFFRACTION	1.93
4UJB	X-RAY DIFFRACTION	1.95
3VQH	X-RAY DIFFRACTION	1.95
3AGM	X-RAY DIFFRACTION	2
3L9L	X-RAY DIFFRACTION	2
3L9N	X-RAY DIFFRACTION	2
3NX8	X-RAY DIFFRACTION	2
3OOG	X-RAY DIFFRACTION	2
4UJ2	X-RAY DIFFRACTION	2.02
3P0M	X-RAY DIFFRACTION	2.03
5N23	X-RAY DIFFRACTION	2.09
3AGL	X-RAY DIFFRACTION	2.1
4AE6	X-RAY DIFFRACTION	2.1
4WB6	X-RAY DIFFRACTION	2.1
5IZF	X-RAY DIFFRACTION	2.1

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P17612-F1	95.92	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 (4): 50–58; 73; 122–128; 169–172

Post-translational modifications (9): 11, 49, 140, 196, 198, 331, 339, 2, 3

Mutagenesis-validated functional residues (10):

Position	Phenotype
48	enhanced basal kinase activity; when associated with q-96, l-121, a-124, k-182 and a-184.
96	enhanced basal kinase activity; when associated with r-48, l-121, a-124, k-182 and a-184.
121	enhanced basal kinase activity; when associated with r-48, q-96, a-124, k-182 and a-184.
124	enhanced basal kinase activity; when associated with r-48, q-96, l-121, k-182 and a-184.
182	enhanced basal kinase activity; when associated with r-48, q-96, l-121, a-124 and a-184.
184	enhanced basal kinase activity; when associated with r-48, q-96, l-121, a-124 and k-182.
195	no phosphorylation.
201	no phosphorylation.
202	no phosphorylation.
205	loss of allosteric regulation.

Function

Pathways and Gene Ontology

Reactome pathways

113 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-2565942	Regulation of PLK1 Activity at G2/M Transition
R-HSA-380259	Loss of Nlp from mitotic centrosomes
R-HSA-380270	Recruitment of mitotic centrosome proteins and complexes
R-HSA-380284	Loss of proteins required for interphase microtubule organization from the centrosome
R-HSA-380320	Recruitment of NuMA to mitotic centrosomes
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-512988	Interleukin-3, Interleukin-5 and GM-CSF signaling
R-HSA-5578775	Ion homeostasis
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-5620912	Anchoring of the basal body to the plasma membrane
R-HSA-5621575	CD209 (DC-SIGN) signaling
R-HSA-5687128	MAPK6/MAPK4 signaling
R-HSA-8853659	RET signaling
R-HSA-8854518	AURKA Activation by TPX2
R-HSA-8963896	HDL assembly
R-HSA-9010642	ROBO receptors bind AKAP5

MSigDB gene sets: 985 (showing top): PID_SHP2_PATHWAY, REACTOME_TRIGLYCERIDE_CATABOLISM, GOBP_MORPHOGENESIS_OF_AN_EPITHELIUM, PID_HDAC_CLASSI_PATHWAY, MYAATNNNNNNNGGC_UNKNOWN, GOBP_RESPONSE_TO_NITROGEN_COMPOUND, GOBP_EMBRYO_DEVELOPMENT_ENDING_IN_BIRTH_OR_EGG_HATCHING, GOBP_EPITHELIUM_DEVELOPMENT, GOBP_REGULATION_OF_AUTOPHAGY, GOBP_NUCLEOSIDE_DIPHOSPHATE_METABOLIC_PROCESS, REACTOME_INNATE_IMMUNE_SYSTEM, MYOGENIN_Q6, GOBP_POSITIVE_REGULATION_OF_ENDOCYTOSIS, GOBP_REGULATION_OF_CALCIUM_MEDIATED_SIGNALING, GOBP_REGULATION_OF_MICROTUBULE_BASED_PROCESS

GO Biological Process (53): mesoderm formation (GO:0001707), neural tube closure (GO:0001843), regulation of heart rate (GO:0002027), renal water homeostasis (GO:0003091), mRNA processing (GO:0006397), protein export from nucleus (GO:0006611), adenylate cyclase-activating G protein-coupled receptor signaling pathway (GO:0007189), adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway (GO:0007193), regulation of cardiac muscle contraction by regulation of the release of sequestered calcium ion (GO:0010881), regulation of macroautophagy (GO:0016241), cytokine-mediated signaling pathway (GO:0019221), dorsal/ventral neural tube patterning (GO:0021904), intracellular potassium ion homeostasis (GO:0030007), positive regulation of insulin secretion (GO:0032024), negative regulation of interleukin-2 production (GO:0032703), high-density lipoprotein particle assembly (GO:0034380), cellular response to heat (GO:0034605), mitochondrial protein catabolic process (GO:0035694), positive regulation of cholesterol biosynthetic process (GO:0045542), regulation of osteoblast differentiation (GO:0045667), positive regulation of gluconeogenesis (GO:0045722), negative regulation of smoothened signaling pathway (GO:0045879), positive regulation of protein export from nucleus (GO:0046827), sperm capacitation (GO:0048240), positive regulation of phagocytosis (GO:0050766), positive regulation of calcium-mediated signaling (GO:0050850), regulation of cell cycle (GO:0051726), regulation of cardiac muscle contraction (GO:0055117), regulation of proteasomal protein catabolic process (GO:0061136), cellular response to cold (GO:0070417), regulation of microtubule cytoskeleton organization (GO:0070507), regulation of protein processing (GO:0070613), cellular response to glucose stimulus (GO:0071333), cellular response to parathyroid hormone stimulus (GO:0071374), cellular response to glucagon stimulus (GO:0071377), cellular response to epinephrine stimulus (GO:0071872), cell communication by electrical coupling involved in cardiac conduction (GO:0086064), vascular endothelial cell response to laminar fluid shear stress (GO:0097700), postsynaptic modulation of chemical synaptic transmission (GO:0099170), negative regulation of protein localization to chromatin (GO:0120186)

GO Molecular Function (19): magnesium ion binding (GO:0000287), protein serine/threonine kinase activity (GO:0004674), cAMP-dependent protein kinase activity (GO:0004691), protein serine/threonine/tyrosine kinase activity (GO:0004712), ATP binding (GO:0005524), potassium channel inhibitor activity (GO:0019870), protein kinase binding (GO:0019901), protein domain specific binding (GO:0019904), manganese ion binding (GO:0030145), ubiquitin protein ligase binding (GO:0031625), protein kinase A regulatory subunit binding (GO:0034237), channel activator activity (GO:0099103), protein serine kinase activity (GO:0106310), histone H1-4S35 kinase activity (GO:0140198), nucleotide binding (GO:0000166), protein kinase activity (GO:0004672), protein binding (GO:0005515), kinase activity (GO:0016301), transferase activity (GO:0016740)

GO Cellular Component (28): acrosomal vesicle (GO:0001669), nucleus (GO:0005634), nucleoplasm (GO:0005654), cytoplasm (GO:0005737), mitochondrial matrix (GO:0005759), centrosome (GO:0005813), cytosol (GO:0005829), plasma membrane (GO:0005886), cAMP-dependent protein kinase complex (GO:0005952), nuclear speck (GO:0016607), nucleotide-activated protein kinase complex (GO:0031588), neuromuscular junction (GO:0031594), calcium channel complex (GO:0034704), sperm flagellum (GO:0036126), plasma membrane raft (GO:0044853), perinuclear region of cytoplasm (GO:0048471), extracellular exosome (GO:0070062), sperm midpiece (GO:0097225), ciliary base (GO:0097546), postsynapse (GO:0098794), glutamatergic synapse (GO:0098978), mitochondrion (GO:0005739), cilium (GO:0005929), axoneme (GO:0005930), membrane (GO:0016020), cytoplasmic vesicle (GO:0031410), motile cilium (GO:0031514), cell projection (GO:0042995)

Reactome top-level categories

Rollup of top-18 pathways:

Category	Pathways
Integration of energy metabolism	2
Centrosome maturation	2
Calmodulin induced events	1
Triglyceride metabolism	1
PKA-mediated phosphorylation of CREB	1
Glucagon signaling in metabolic regulation	1
Opioid Signalling	1
G2/M Transition	1
Loss of proteins required for interphase microtubule organization from the centrosome	1
Mitotic Prometaphase	1
Regulation of insulin secretion	1
Adaptive Immune System	1
Aquaporin-mediated transport	1
Signaling by VEGF	1
Post NMDA receptor activation events	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	7
protein kinase activity	3
adenylate cyclase-modulating G protein-coupled receptor signaling pathway	2
mitochondrion	2
cytoplasm	2
intracellular protein-containing complex	2
synapse	2
formation of primary germ layer	1
mesoderm morphogenesis	1
primary neural tube formation	1
tube closure	1
regulation of heart contraction	1
regulation of biological quality	1
renal system process	1
multicellular organismal-level water homeostasis	1
RNA processing	1
mRNA metabolic process	1
intracellular protein transport	1
nuclear export	1
adenylate cyclase activator activity	1
adenylate cyclase inhibitor activity	1
regulation of release of sequestered calcium ion into cytosol by sarcoplasmic reticulum	1
regulation of cardiac muscle contraction by calcium ion signaling	1
regulation of autophagy	1
macroautophagy	1
cell surface receptor signaling pathway	1
cellular response to cytokine stimulus	1
dorsal/ventral pattern formation	1
neural tube patterning	1
intracellular monoatomic cation homeostasis	1
potassium ion homeostasis	1
insulin secretion	1
positive regulation of protein secretion	1
regulation of insulin secretion	1
positive regulation of peptide hormone secretion	1
negative regulation of cytokine production	1
interleukin-2 production	1
regulation of interleukin-2 production	1
plasma lipoprotein particle assembly	1
response to heat	1

Protein interactions and networks

STRING

7104 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PRKACA	AKAP1	Q92667	998
PRKACA	AKAP12	Q02952	989
PRKACA	AKAP5	P24588	985
PRKACA	EZR	P15311	983
PRKACA	RAPGEF3	O95398	974
PRKACA	CALML3	P27482	971
PRKACA	CALML4	Q96GE6	971
PRKACA	CALML5	Q9NZT1	971
PRKACA	CALM1	P02593	970
PRKACA	CALML6	Q8TD86	969
PRKACA	RAPGEF4	Q8WZA2	968
PRKACA	AKAP9	Q99996	968
PRKACA	PRKAR1A	P10644	955
PRKACA	AKAP6	Q13023	951
PRKACA	ADCY5	O95622	951

IntAct

494 interactions, top by confidence:

A	B	Type	Score
PRKACA	PRKAR2B	psi-mi:“MI:0915”(physical association)	0.960
PRKACA	PRKAR2B	psi-mi:“MI:0407”(direct interaction)	0.960
PRKAR1A	PRKACA	psi-mi:“MI:0915”(physical association)	0.960
PRKACA	PRKAR1A	psi-mi:“MI:0407”(direct interaction)	0.960
PRKACA	PRKAR1A	psi-mi:“MI:0915”(physical association)	0.960
PRKAR2B	PRKACA	psi-mi:“MI:0915”(physical association)	0.960
PRKACA	PRKAR1A	psi-mi:“MI:2364”(proximity)	0.960
PRKAR2B	PRKACA	psi-mi:“MI:2364”(proximity)	0.960
PRKACA	PRKAR1B	psi-mi:“MI:0915”(physical association)	0.890
	PRKAR1A	psi-mi:“MI:0217”(phosphorylation reaction)	0.700
HSP90AA1	PRKACA	psi-mi:“MI:0915”(physical association)	0.670
MAPK7	PFDN6	psi-mi:“MI:0914”(association)	0.640
AICDA	PRKAR1A	psi-mi:“MI:0914”(association)	0.620
	PRKAR2A	psi-mi:“MI:0217”(phosphorylation reaction)	0.590
Gnao1	PRKACA	psi-mi:“MI:0915”(physical association)	0.590
Gnao1	PRKACA	psi-mi:“MI:0407”(direct interaction)	0.590
Gnao1	PRKACA	psi-mi:“MI:0914”(association)	0.590
PRKACA	PKIB	psi-mi:“MI:0915”(physical association)	0.560
PRKACA	AVPI1	psi-mi:“MI:0915”(physical association)	0.560
AKT1	PRKACA	psi-mi:“MI:0915”(physical association)	0.560
PRKACA	APBB2	psi-mi:“MI:0915”(physical association)	0.560
BDNF	PRKACA	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (672): MAPT (Biochemical Activity), PRKACA (Affinity Capture-RNA), PRKACA (Affinity Capture-RNA), PDE3A (Biochemical Activity), TOM22 (Biochemical Activity), PRKACA (Affinity Capture-MS), PRKACA (Two-hybrid), PRKACA (Affinity Capture-MS), PRKACA (Affinity Capture-MS), PRKACA (Affinity Capture-MS), PRKACA (Co-fractionation), PRKAR2A (Co-fractionation), RPE (Co-fractionation), USP20 (Biochemical Activity), PRKACA (Two-hybrid)

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

200 interactions.

A	Effect	B	Mechanism
PRKACA	down-regulates	RXRA	phosphorylation
PRKACA	“up-regulates activity”	CSK	phosphorylation
PRKACA	“down-regulates activity”	CIITA	phosphorylation
PRKACA	“down-regulates activity”	RGS10	phosphorylation
PRKACA	“up-regulates activity”	ITGA4	phosphorylation
PRKACA	“up-regulates activity”	ETV5	phosphorylation
PRKACA	“down-regulates activity”	PIN1	phosphorylation
PRKACA	up-regulates	NOS3	phosphorylation
PRKACA	up-regulates	SRC	phosphorylation
PRKACA	up-regulates	HNRNPD	phosphorylation
PRKACA	down-regulates	CAPN2	phosphorylation
PRKACA	up-regulates	KDELR1	phosphorylation
PRKACA	up-regulates	SUFU	phosphorylation
PRKACA	down-regulates	HDAC8	phosphorylation
PRKACA	“up-regulates activity”	PRKAR2B	phosphorylation
PRKACA	up-regulates	ESR1	phosphorylation
PRKACA	up-regulates	FLNA	phosphorylation
PRKACA	down-regulates	AKAP13	phosphorylation
PRKACA	down-regulates	HRH1	phosphorylation
PRKACA	down-regulates	NEDD4L	phosphorylation
PRKACA	up-regulates	AKAP13	phosphorylation
PRKACA	up-regulates	NCOA3	phosphorylation
PRKACA	down-regulates	CASP9	phosphorylation
PRKACA	“up-regulates activity”	TNNI3	phosphorylation
PRKACA	up-regulates	SOX9	phosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 127 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
Response of endothelial cells to shear stress	6	20.7×	1e-04
Cellular responses to mechanical stimuli	6	17.9×	1e-04
Glucagon-like Peptide-1 (GLP1) regulates insulin secretion	5	15.3×	9e-04
Loss of Nlp from mitotic centrosomes	7	12.8×	1e-04
Loss of proteins required for interphase microtubule organization from the centrosome	7	12.8×	1e-04
Regulation of insulin secretion	5	12.6×	2e-03
AURKA Activation by TPX2	7	12.2×	2e-04
Regulation of PLK1 Activity at G2/M Transition	8	11.7×	1e-04

GO biological processes:

GO term	Partners	Fold	FDR
vascular endothelial cell response to laminar fluid shear stress	5	33.3×	4e-04
learning	5	12.8×	6e-03
protein stabilization	10	6.1×	3e-03
proteasome-mediated ubiquitin-dependent protein catabolic process	10	4.7×	6e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	41
Likely benign	14
Benign	3

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
162471	NM_002730.4(PRKACA):c.597_599dup (p.Leu199_Cys200insTrp)	Pathogenic

SpliceAI

1307 predictions. Top by Δscore:

Variant	Effect	Δscore
19:14093624:CCA:C	donor_loss	1.0000
19:14093625:CACCT:C	donor_loss	1.0000
19:14093626:ACCTT:A	donor_gain	1.0000
19:14093627:C:CA	donor_loss	1.0000
19:14093627:CCTT:C	donor_gain	1.0000
19:14093627:CCTTC:C	donor_gain	1.0000
19:14093630:T:A	donor_gain	1.0000
19:14093793:CTGGA:C	acceptor_loss	1.0000
19:14097577:A:AC	donor_gain	1.0000
19:14097578:C:CC	donor_gain	1.0000
19:14097578:CTTTG:C	donor_gain	1.0000
19:14097612:A:AC	donor_gain	1.0000
19:14097613:G:C	donor_gain	1.0000
19:14097675:CT:C	acceptor_loss	1.0000
19:14097676:T:C	acceptor_loss	1.0000
19:14097759:GGCAC:G	donor_loss	1.0000
19:14097760:GCAC:G	donor_loss	1.0000
19:14097761:CACC:C	donor_loss	1.0000
19:14097762:ACCTG:A	donor_loss	1.0000
19:14097763:CCTGA:C	donor_loss	1.0000
19:14097772:AGC:A	donor_gain	1.0000
19:14097886:GCTCA:G	acceptor_gain	1.0000
19:14097887:CTCA:C	acceptor_gain	1.0000
19:14097887:CTCAC:C	acceptor_gain	1.0000
19:14097888:TCA:T	acceptor_gain	1.0000
19:14097888:TCACT:T	acceptor_gain	1.0000
19:14097889:CA:C	acceptor_gain	1.0000
19:14097889:CAC:C	acceptor_gain	1.0000
19:14097891:C:CC	acceptor_gain	1.0000
19:14097894:A:AC	acceptor_gain	1.0000

AlphaMissense

2345 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
19:14093184:A:C	F328L	1.000
19:14093184:A:T	F328L	1.000
19:14093186:A:G	F328L	1.000
19:14093669:A:G	W297R	1.000
19:14093669:A:T	W297R	1.000
19:14093710:C:T	G283E	1.000
19:14093717:G:T	R281S	1.000
19:14097409:G:C	F239L	1.000
19:14097409:G:T	F239L	1.000
19:14097411:A:G	F239L	1.000
19:14097413:G:T	P238H	1.000
19:14097422:C:T	G235D	1.000
19:14097443:A:G	L228P	1.000
19:14097449:C:T	G226E	1.000
19:14097450:C:A	G226W	1.000
19:14097450:C:G	G226R	1.000
19:14097450:C:T	G226R	1.000
19:14097457:C:A	W223C	1.000
19:14097457:C:G	W223C	1.000
19:14097459:A:G	W223R	1.000
19:14097459:A:T	W223R	1.000
19:14097462:A:G	W222R	1.000
19:14097462:A:T	W222R	1.000
19:14097464:T:A	D221V	1.000
19:14097464:T:G	D221A	1.000
19:14097465:C:G	D221H	1.000
19:14097482:C:T	G215D	1.000
19:14097483:C:G	G215R	1.000
19:14097589:A:T	I211N	1.000
19:14097598:G:T	P208H	1.000

dbSNP variants (sampled 300 via entrez): RS1000168486 (19:14111592 A>G), RS1000221865 (19:14109328 C>CA), RS1000407026 (19:14098114 C>T), RS1000443253 (19:14105110 T>A,C), RS1000823222 (19:14108911 A>G), RS1000862872 (19:14099569 G>T), RS1000965181 (19:14094047 A>G), RS1000981700 (19:14099256 C>T), RS1000993660 (19:14105441 G>A), RS1001013911 (19:14099058 G>A,C,T), RS1001046905 (19:14106492 A>G), RS1001059075 (19:14113768 C>A,T), RS1001321515 (19:14103954 G>A), RS1001421730 (19:14117680 A>C), RS1001434887 (19:14093105 C>G,T)

Disease associations

OMIM: gene MIM:601639 | disease phenotypes: MIM:615830, MIM:619142

GenCC curated gene-disease

Disease	Classification	Inheritance
cardioacrofacial dysplasia 1	Strong	Autosomal dominant
Ellis-van Creveld syndrome	Supportive	Autosomal recessive
pigmented nodular adrenocortical disease, primary, 4	Limited	Unknown

Mondo (5): neurodevelopmental disorder (MONDO:0700092), pigmented nodular adrenocortical disease, primary, 4 (MONDO:0014359), cardioacrofacial dysplasia 1 (MONDO:0030876), ACTH-independent adrenal Cushing syndrome, somatic (MONDO:0800377), Ellis-van Creveld syndrome (MONDO:0009162)

Orphanet (1): OBSOLETE: Primary pigmented nodular adrenocortical disease (Orphanet:189439)

HPO phenotypes

83 total (30 of 83 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:0000322	Short philtrum
HP:0000327	Hypoplasia of the maxilla
HP:0000486	Strabismus
HP:0000668	Hypodontia
HP:0000684	Delayed eruption of teeth
HP:0000691	Microdontia
HP:0000698	Conical tooth
HP:0000699	Diastema
HP:0000712	Emotional lability
HP:0000716	Depression
HP:0000774	Narrow chest
HP:0000819	Diabetes mellitus
HP:0000822	Hypertension
HP:0000924	Abnormality of the skeletal system
HP:0000938	Osteopenia
HP:0000939	Osteoporosis
HP:0000978	Bruising susceptibility

GWAS associations

0 associations (top):

MeSH disease descriptors (2)

Descriptor	Name	Tree numbers
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
D065886	Neurodevelopmental Disorders	F03.625

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (2): CHEMBL2094138 (PROTEIN FAMILY), CHEMBL4101 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

29 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 77,540 (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
CHEMBL1171837	PONATINIB	4	8,955
CHEMBL2105759	BARICITINIB	4	6,741
CHEMBL2325741	CAPIVASERTIB	4	2,157
CHEMBL608533	MIDOSTAURIN	4	7,259
CHEMBL38380	FASUDIL	3	11,953
CHEMBL2219422	AFURESERTIB	3	1,467
CHEMBL223360	LINIFANIB	3	3,925
CHEMBL300138	ENZASTAURIN	3	3,209
CHEMBL483158	ALISERTIB	3	2,305
CHEMBL603469	LESTAURTINIB	3
CHEMBL91829	RUBOXISTAURIN	3	77
CHEMBL574737	UCN-01	2	2,217
CHEMBL575448	BMS-754807	2	406
CHEMBL6246	ELLAGIC ACID	2	23,148
CHEMBL1667969	SAR-407899 FREE BASE	2	157
CHEMBL1967878	CENISERTIB	2	358
CHEMBL3137336	UPROSERTIB	2	1,624
CHEMBL3545396	BMS-690514	2	567
CHEMBL460702	BMS-777607	2	253
CHEMBL475251	R-406	2	762
CHEMBL495727	AT-9283	2
CHEMBL1084546	PF-00562271	1
CHEMBL3128043	PF-03758309	1
CHEMBL3544960	AT-13148	1
CHEMBL482967	CYC-116	1
CHEMBL49120	PD-0166285	1
CHEMBL494089	GSK-690693	1
CHEMBL571948	Y-39983	1
CHEMBL574738	AST-487	1

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 (4 total), top 4:

Ligand	Action	Affinity	Parameter
GSK690693	Inhibition	7.72	pKd
H-89	Inhibition	7.32	pKi
aplithianine A	Inhibition	7.08	pIC50
ripasudil	Inhibition	5.68	pIC50

Binding affinities (BindingDB)

127 measured of 168 human assays (172 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
CHEMBL5196521	KI	0.007 nM
ARC-3429	KD	0.019 nM
CHEMBL5179794	KI	0.023 nM
ARC-3430	KD	0.1 nM
Staurosporine	KD	1.7 nM
D0157	IC50	4 nM	US-20250299772: METHOD FOR GENERATION OF CHEMICAL DERIVATIVES AGAINST TARGET PROTEIN TO BUILD AI DRUG PLATFORM
CHEMBL5172486	KI	4.2 nM
CHEMBL5188777	IC50	5.6 nM
DM009	IC50	7 nM	US-20250299772: METHOD FOR GENERATION OF CHEMICAL DERIVATIVES AGAINST TARGET PROTEIN TO BUILD AI DRUG PLATFORM
D1011	IC50	8 nM	US-20250299772: METHOD FOR GENERATION OF CHEMICAL DERIVATIVES AGAINST TARGET PROTEIN TO BUILD AI DRUG PLATFORM
4-(4-Fluorophenyl)-2-(4-hydroxyphenyl)-5-(4-pyridyl)-1H-imidazole	KD	9.8 nM
DM010	IC50	10 nM	US-20250299772: METHOD FOR GENERATION OF CHEMICAL DERIVATIVES AGAINST TARGET PROTEIN TO BUILD AI DRUG PLATFORM
ARC-3384	KD	11 nM
D0101	IC50	13 nM	US-20250299772: METHOD FOR GENERATION OF CHEMICAL DERIVATIVES AGAINST TARGET PROTEIN TO BUILD AI DRUG PLATFORM
D0011	IC50	13 nM	US-20250299772: METHOD FOR GENERATION OF CHEMICAL DERIVATIVES AGAINST TARGET PROTEIN TO BUILD AI DRUG PLATFORM
(1R)-1-[3-fluoro-4-[(1-hydroxy-7-methyl-3H-2,1-benzoxaborol-6-yl)oxy]phenyl]ethanamine	IC50	13.9 nM	US-9493490: Boron-containing small molecules
ARC-3380	KD	14.9 nM
D1008	IC50	19 nM	US-20250299772: METHOD FOR GENERATION OF CHEMICAL DERIVATIVES AGAINST TARGET PROTEIN TO BUILD AI DRUG PLATFORM
D0139	IC50	22 nM	US-20250299772: METHOD FOR GENERATION OF CHEMICAL DERIVATIVES AGAINST TARGET PROTEIN TO BUILD AI DRUG PLATFORM
CHEMBL5201435	IC50	24 nM
D0054	IC50	26 nM	US-20250299772: METHOD FOR GENERATION OF CHEMICAL DERIVATIVES AGAINST TARGET PROTEIN TO BUILD AI DRUG PLATFORM
D0069	IC50	30 nM	US-20250299772: METHOD FOR GENERATION OF CHEMICAL DERIVATIVES AGAINST TARGET PROTEIN TO BUILD AI DRUG PLATFORM
D1010	IC50	31 nM	US-20250299772: METHOD FOR GENERATION OF CHEMICAL DERIVATIVES AGAINST TARGET PROTEIN TO BUILD AI DRUG PLATFORM
D0137	IC50	40 nM	US-20250299772: METHOD FOR GENERATION OF CHEMICAL DERIVATIVES AGAINST TARGET PROTEIN TO BUILD AI DRUG PLATFORM
5-(1,4-diazepan-1-ylsulfonyl)isoquinoline	KD	50 nM	US-11198680: Rho kinase inhibitor BA-1049 (R) and active metabolites thereof
[3-chloro-4-[(1-hydroxy-7-propan-2-yl-3H-2,1-benzoxaborol-6-yl)oxy]phenyl]methanamine	IC50	59.6 nM	US-9493490: Boron-containing small molecules
D0025	IC50	62 nM	US-20250299772: METHOD FOR GENERATION OF CHEMICAL DERIVATIVES AGAINST TARGET PROTEIN TO BUILD AI DRUG PLATFORM
D0135	IC50	63 nM	US-20250299772: METHOD FOR GENERATION OF CHEMICAL DERIVATIVES AGAINST TARGET PROTEIN TO BUILD AI DRUG PLATFORM
1-(5-Isoquinolinesulfonyl)-2-methylpiperazine	IC50	100 nM
D0065	IC50	119 nM	US-20250299772: METHOD FOR GENERATION OF CHEMICAL DERIVATIVES AGAINST TARGET PROTEIN TO BUILD AI DRUG PLATFORM
D0083	IC50	129 nM	US-20250299772: METHOD FOR GENERATION OF CHEMICAL DERIVATIVES AGAINST TARGET PROTEIN TO BUILD AI DRUG PLATFORM
PKC-412	KD	190 nM
CHEMBL5174274	IC50	400 nM
MLS000033148	IC50	415 nM
(4Z)-4-(2-amino-5-oxo-3,5-dihydro-4H-imidazol-4-ylidene)-4,5,6,7-tetrahydropyrrolo[2,3-c]azepin-8(1H)-one	IC50	420 nM
4-[3-(1H-1,3-benzodiazol-2-yl)-1H-indazol-6-yl]-2-methoxyphenol	IC50	443 nM
1-[4-(3-amino-1H-indazol-4-yl)phenyl]-3-(2-fluoro-5-methyl-phenyl)urea	KD	450 nM
3-(2-furanylmethyl)-8-methoxy-5H-pyrimido[5,4-b]indol-4-one	IC50	464 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
4-[4-[2-(4-chloranylphenoxy)ethyl]piperazin-1-yl]thieno[2,3-d]pyrimidine	IC50	711 nM
1-Phenyl-2-(5-pyridin-4-yl-4H-[1,2,4]triazol-3-ylsulfanyl)-ethanone	IC50	765 nM
CHEMBL5189362	IC50	790 nM
3-(pyridin-4-yl)-1H-indole	IC50	800 nM
MLS000065710	IC50	1130 nM
CHEMBL5174535	IC50	1200 nM
6-(1-piperidinyl)-7H-purine	IC50	1400 nM
1-[4-[(4-ethyl-1-piperazinyl)methyl]-3-(trifluoromethyl)phenyl]-3-[4-[[6-(methylamino)-4-pyrimidinyl]oxy]phenyl]urea	KD	1400 nM
N-[4-(1H-pyrazol-4-yl)phenyl]-2,3-dihydro-1,4-benzodioxine-2-carboxamide	IC50	1410 nM
6-(1-azepanyl)-7H-purine	IC50	1490 nM
3-({5,6-diphenyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl}amino)propane-1,2-diol	IC50	1500 nM

ChEMBL bioactivities

816 potent at pChembl≥5 of 923 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
10.72	Kd	0.019	nM	CHEMBL5201435
10.64	Ki	0.023	nM	CHEMBL5179794
10.38	Kd	0.042	nM	CHEMBL5185265
10.00	IC50	0.1	nM	CHEMBL213618
10.00	Kd	0.1	nM	CHEMBL5183651
9.30	Kd	0.5	nM	CHEMBL524516
9.20	Kd	0.63	nM	CHEMBL5189362
9.20	Ki	0.63	nM	CHEMBL5174535
9.15	IC50	0.7	nM	STAUROSPORINE
9.10	Ki	0.7943	nM	CHEMBL1980995
9.05	IC50	0.9	nM	STAUROSPORINE
9.03	IC50	0.935	nM	STAUROSPORINE
9.00	IC50	1	nM	CHEMBL207544
8.96	IC50	1.1	nM	CHEMBL3613610
8.90	Ki	1.259	nM	CHEMBL1980407
8.80	IC50	1.58	nM	STAUROSPORINE
8.74	Kd	1.8	nM	CHEMBL498924
8.68	IC50	2.1	nM	CHEMBL383264
8.66	IC50	2.2	nM	CHEMBL3613609
8.64	IC50	2.3	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
8.50	Ki	3.162	nM	CHEMBL1870106
8.50	Ki	3.162	nM	CHEMBL1994438
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
8.41	Kd	3.9	nM	BALANOL
8.41	IC50	3.9	nM	BALANOL
8.40	Ki	4	nM	CHEMBL436718
8.40	IC50	4	nM	BALANOL
8.40	IC50	4	nM	STAUROSPORINE
8.40	Ki	3.981	nM	CHEMBL2000271
8.40	Ki	3.981	nM	CHEMBL1983315
8.40	Ki	3.981	nM	CHEMBL1968930
8.38	Kd	4.2	nM	CHEMBL5179913
8.38	Ki	4.2	nM	CHEMBL5172486
8.33	Ki	4.7	nM	BALANOL
8.31	IC50	4.9	nM	CHEMBL1077376
8.30	IC50	5	nM	CHEMBL378963
8.30	IC50	5	nM	CHEMBL226625
8.30	IC50	5	nM	GF-109203
8.30	Ki	5.012	nM	CHEMBL1976240
8.30	Ki	5.012	nM	CHEMBL1970903
8.29	IC50	5.1	nM	CHEMBL3613611
8.28	IC50	5.3	nM	CHEMBL413460
8.27	IC50	5.4	nM	CHEMBL3613603

PubChem BioAssay actives

384 with measured affinity, of 3498 total; 50 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
N-[(2S)-1-[[(2R)-1-[[(2R)-1-amino-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-6-[[(2R)-5-(diaminomethylideneamino)-2-[[9-oxo-9-[4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)piperazin-1-yl]nonanoyl]amino]pentanoyl]amino]-1-oxohexan-2-yl]-N’-[(2S,3S)-1-[(3-fluoro-2-oxopropyl)amino]-3-methyl-1-oxopentan-2-yl]butanediamide	1886673: Covalent inhibition of human recombinant PKAC-alpha assessed as inhibition constant	ki	<0.0001	uM
4-[3-[[(5R)-6-amino-5-[[(2R)-2-[[(2R)-2-[[(2R)-2-[[(2R)-2-[[(2R)-2-[[(2R)-2-[[(2R)-2-[6-[[5-(2-aminopyrimidin-4-yl)selenophene-2-carbonyl]amino]hexanoylamino]propanoyl]amino]-5-carbamimidamidopentanoyl]amino]-5-carbamimidamidopentanoyl]amino]-5-carbamimidamidopentanoyl]amino]-5-carbamimidamidopentanoyl]amino]-5-carbamimidamidopentanoyl]amino]-5-carbamimidamidopentanoyl]amino]-6-oxohexyl]-methylamino]-6-dimethylazaniumylidenexanthen-9-yl]-3-carboxybenzoate	1846298: Displacement of mAb(D38C6)-BTN from human recombinant PKAc alpha incubated for 15 mins by microplate reader assay	kd	<0.0001	uM
N-[(2S)-1-[[(2R)-1-[[(2R)-1-amino-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-6-[[(2R)-5-(diaminomethylideneamino)-2-[[9-oxo-9-[4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)piperazin-1-yl]nonanoyl]amino]pentanoyl]amino]-1-oxohexan-2-yl]-N’-[(2S,3S)-3-methyl-1-oxo-1-(2-oxopropylamino)pentan-2-yl]butanediamide	1886660: Displacement of ARC-1063 fluorescent probe from recombinant human PKAC-alpha assessed as dissociation equilibrium constant preincubated for 1 hr followed by photoluminescent probe addition by time-gated luminescence intensity based assay	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,3S,4R,5R)-N-[6-[[(2R)-6-amino-1-[[6-[[(2R)-1-[[(2R)-1-[[(2R)-1-[[(2R)-1-amino-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-6-oxohexyl]amino]-1-oxohexan-2-yl]amino]-6-oxohexyl]-5-(6-aminopurin-9-yl)-3,4-dihydroxyoxolane-2-carboxamide	412084: Binding affinity to PKA catalytic subunit alpha by fluorescence polarization assay	kd	0.0005	uM
(2S,3S,4R,5R)-N-[6-[[(2R)-6-amino-1-[[6-[[(2R)-1-[[(2R)-1-[[(2R)-1-[[(2R)-1-[[(2R)-1-[[(2R)-1-amino-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-6-oxohexyl]amino]-1-oxohexan-2-yl]amino]-6-oxohexyl]-5-(6-aminopurin-9-yl)-3,4-dihydroxyoxolane-2-carboxamide	412084: Binding affinity to PKA catalytic subunit alpha by fluorescence polarization assay	kd	0.0005	uM
N-[(2S)-1-[[(2R)-1-amino-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-6-[[(2R)-5-(diaminomethylideneamino)-2-[[9-oxo-9-[4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)piperazin-1-yl]nonanoyl]amino]pentanoyl]amino]-1-oxohexan-2-yl]-N’-[(2S,3S)-1-[(3-fluoro-2-oxopropyl)amino]-3-methyl-1-oxopentan-2-yl]butanediamide	1886673: Covalent inhibition of human recombinant PKAC-alpha assessed as inhibition constant	ki	0.0006	uM
N-[(2S)-1-[[(2R)-1-amino-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-6-[[(2R)-5-(diaminomethylideneamino)-2-[[9-oxo-9-[4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)piperazin-1-yl]nonanoyl]amino]pentanoyl]amino]-1-oxohexan-2-yl]-N’-[(2S,3S)-3-methyl-1-oxo-1-(2-oxopropylamino)pentan-2-yl]butanediamide	1886660: Displacement of ARC-1063 fluorescent probe from recombinant human PKAC-alpha assessed as dissociation equilibrium constant preincubated for 1 hr followed by photoluminescent probe addition by time-gated luminescence intensity based assay	kd	0.0006	uM
(2S,3R,4R,6R)-3-methoxy-2-methyl-4-(methylamino)-29-oxa-1,7,17-triazaoctacyclo[12.12.2.12,6.07,28.08,13.015,19.020,27.021,26]nonacosa-8,10,12,14,19,21,23,25,27-nonaen-16-one	1941062: Inhibition of PKA (unknown origin)	ic50	0.0007	uM
methyl 3-[[4-(aminomethyl)-1-(5-methyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl)piperidine-4-carbonyl]amino]benzoate	1244620: Inhibition of PKA (unknown origin) by radiometric assay	ic50	0.0010	uM
methyl 3-[[1-(5-cyano-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-4-[(dimethylamino)methyl]piperidine-4-carbonyl]amino]benzoate	1244620: Inhibition of PKA (unknown origin) by radiometric assay	ic50	0.0010	uM
methyl 3-[[4-[(dimethylamino)methyl]-1-(5-fluoro-7H-pyrrolo[2,3-d]pyrimidin-4-yl)piperidine-4-carbonyl]amino]benzoate	1244620: Inhibition of PKA (unknown origin) by radiometric assay	ic50	0.0010	uM
(2S)-1-[(6-ethynyl-5-isoquinolin-6-yl-3-pyridinyl)oxy]-3-(1H-indol-3-yl)propan-2-amine	265591: Inhibition of PKA at 5 uM ATP	ic50	0.0010	uM
[3-[[4-(aminomethyl)-1-(5-methyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl)piperidine-4-carbonyl]amino]phenyl] N,N-dimethylcarbamate	1244620: Inhibition of PKA (unknown origin) by radiometric assay	ic50	0.0010	uM
methyl 3-[[4-[(dimethylamino)methyl]-1-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)piperidine-4-carbonyl]amino]benzoate	1244620: Inhibition of PKA (unknown origin) by radiometric assay	ic50	0.0011	uM
(1S,3R,4R)-N-[6-[[(2R)-1-[[6-[[(2R)-1-[[(2R)-1-amino-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-6-oxohexyl]amino]-1-oxopropan-2-yl]amino]-6-oxohexyl]-3-(6-aminopurin-9-yl)-4-hydroxycyclopentane-1-carboxamide	412084: Binding affinity to PKA catalytic subunit alpha by fluorescence polarization assay	kd	0.0018	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
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]-3-hydroxybenzoic acid	1315723: Binding affinity to PKAalpha (unknown origin) using Lys-Arg-Thr-Leu-Arg-Arg as substrate after 8 mins in presence of [gamma-32P]ATP by liquid scintillation spectrometry	kd	0.0039	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
(2R)-4-[[(5S)-6-[[(2S)-1-[[(2S)-5-amino-1-[[(2S)-1-[[(2S)-1-[[(2R)-1-amino-6-[[3-carboxy-4-[3-(dimethylamino)-6-dimethylazaniumylidenexanthen-9-yl]benzoyl]amino]-1-oxohexan-2-yl]amino]-1-oxopropan-2-yl]amino]-3-hydroxy-1-oxobutan-2-yl]amino]-1,5-dioxopentan-2-yl]amino]-5-[[amino(azaniumylidene)methyl]amino]-1-oxopentan-2-yl]amino]-5-[[(2S)-5-[[amino(azaniumylidene)methyl]amino]-2-[[(2S)-2-azaniumylpropanoyl]amino]pentanoyl]amino]-6-oxohexyl]amino]-2-[6-[[(2S,3S,4R,5R)-5-(4-amino-5-iodopyrrolo[2,3-d]pyrimidin-7-yl)-3,4-dihydroxyoxolane-2-carbonyl]amino]hexanoylamino]-4-oxobutanoate	1802698: Equilibrium Binding/Displacement Assay with Fluorescence Anisotropy from Article 10.1002/cbic.201600697: “Slowly on, Slowly off: Bisubstrate-Analogue Conjugates of 5-Iodotubercidin and Histone H3 Peptide Targeting Protein Kinase Haspin.”	kd	0.0041	uM
N-[(2S)-1-amino-6-[[(2R)-5-(diaminomethylideneamino)-2-[[9-oxo-9-[4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)piperazin-1-yl]nonanoyl]amino]pentanoyl]amino]-1-oxohexan-2-yl]-N’-[(2S,3S)-1-[(3-fluoro-2-oxopropyl)amino]-3-methyl-1-oxopentan-2-yl]butanediamide	1886673: Covalent inhibition of human recombinant PKAC-alpha assessed as inhibition constant	ki	0.0042	uM
N-[(2S)-1-amino-6-[[(2R)-5-(diaminomethylideneamino)-2-[[9-oxo-9-[4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)piperazin-1-yl]nonanoyl]amino]pentanoyl]amino]-1-oxohexan-2-yl]-N’-[(2S,3S)-3-methyl-1-oxo-1-(2-oxopropylamino)pentan-2-yl]butanediamide	1886660: Displacement of ARC-1063 fluorescent probe from recombinant human PKAC-alpha assessed as dissociation equilibrium constant preincubated for 1 hr followed by photoluminescent probe addition by time-gated luminescence intensity based assay	kd	0.0042	uM
N-[6-[[(2R)-6-amino-1-[[6-[[(2R)-5-(diaminomethylideneamino)-1-[[(2R)-5-(diaminomethylideneamino)-1-[[(2R)-5-(diaminomethylideneamino)-1-[[(2R)-5-(diaminomethylideneamino)-1-[[(2R)-5-(diaminomethylideneamino)-1-[[(2R)-5-(diaminomethylideneamino)-1-[[(2S)-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]-1-oxohexan-2-yl]amino]-6-oxohexyl]-5-(2-aminopyrimidin-4-yl)thiophene-2-carboxamide	471402: Inhibition of PKACalpha in presence of 1000 uM ATP	ic50	0.0049	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
3-[1-[3-(dimethylamino)propyl]indol-3-yl]-4-(1H-indol-3-yl)pyrrole-2,5-dione	2000131: Inhibition of human PKAC-alpha	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
(2S,3S,4R,5R)-5-(6-aminopurin-9-yl)-N-[6-[[(2R)-5-(diaminomethylideneamino)-1-[[(2R)-5-(diaminomethylideneamino)-1-[[(2R)-5-(diaminomethylideneamino)-1-[[(2R)-5-(diaminomethylideneamino)-1-[[(2R)-5-(diaminomethylideneamino)-1-[[(2R)-5-(diaminomethylideneamino)-1-[6-[2-(isoquinolin-5-ylsulfonylamino)ethylamino]hexanoylamino]-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]-3,4-dihydroxyoxolane-2-carboxamide	273774: Inhibitory potency towards human cAPK C alpha in the presence of 100 uM ATP and 30 uM TAMRA-kemptide	ic50	0.0053	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
N-[6-[[(2R)-6-amino-1-[[6-[[(2R)-1-[[(2R)-1-[[(2R)-1-[[(2R)-1-[[(2R)-1-[[(2R)-1-amino-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-6-oxohexyl]amino]-1-oxohexan-2-yl]amino]-6-oxohexyl]-5-(2-aminopyrimidin-4-yl)thiophene-2-carboxamide	471402: Inhibition of PKACalpha in presence of 1000 uM ATP	ic50	0.0055	uM
N-[(2S)-1-[[(2R)-1-[[(2R)-1-[[(2R)-1-amino-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-6-[[(2R)-5-(diaminomethylideneamino)-2-[[9-oxo-9-[4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)piperazin-1-yl]nonanoyl]amino]pentanoyl]amino]-1-oxohexan-2-yl]-N’-[(2S,3S)-3-methyl-1-oxo-1-(2-oxopropylamino)pentan-2-yl]butanediamide	1886659: Inhibition of ARC-1063 fluorescent probe binding to recombinant human PKAC-alpha incubated for 1 hr by time-gated luminescence intensity based displacement assay	ic50	0.0056	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,3S,4R,5R)-N-[6-[[(2R)-1-[[6-[[(2R)-1-[[(2R)-1-amino-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-6-oxohexyl]amino]-1-oxopropan-2-yl]amino]-6-oxohexyl]-5-(6-aminopurin-9-yl)-3,4-dihydroxyoxolane-2-carboxamide	412084: Binding affinity to PKA catalytic subunit alpha by fluorescence polarization assay	kd	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
(2S,3S,4R,5R)-N-[6-[[(2R)-6-amino-1-[[6-[[(2R)-1-[[(2R)-1-amino-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-6-oxohexyl]amino]-1-oxohexan-2-yl]amino]-6-oxohexyl]-5-(6-aminopurin-9-yl)-3,4-dihydroxyoxolane-2-carboxamide	412084: Binding affinity to PKA catalytic subunit alpha by fluorescence polarization assay	kd	0.0076	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,3S,4R,5R)-N-[6-[[(2R)-1-[[(2R)-1-[[(2R)-1-[[(2R)-1-[[(2R)-1-[[(2R)-1-amino-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-6-oxohexyl]-5-(6-aminopurin-9-yl)-3,4-dihydroxyoxolane-2-carboxamide	273774: Inhibitory potency towards human cAPK C alpha in the presence of 100 uM ATP and 30 uM TAMRA-kemptide	ic50	0.0083	uM
(2S,3S,4R,5R)-N-[6-[[(2R)-6-amino-1-[[6-[[(2S)-1-[[(2S)-1-amino-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-6-oxohexyl]amino]-1-oxohexan-2-yl]amino]-6-oxohexyl]-5-(6-aminopurin-9-yl)-3,4-dihydroxyoxolane-2-carboxamide	412084: Binding affinity to PKA catalytic subunit alpha by fluorescence polarization assay	kd	0.0087	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
(2S,3S,4R,5R)-N-[6-[[(2R)-6-amino-1-[[8-[[(2R)-1-[[(2R)-1-amino-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-8-oxooctyl]amino]-1-oxohexan-2-yl]amino]-6-oxohexyl]-5-(6-aminopurin-9-yl)-3,4-dihydroxyoxolane-2-carboxamide	412084: Binding affinity to PKA catalytic subunit alpha by fluorescence polarization assay	kd	0.0095	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	decreases expression, increases expression	3
Caffeine	decreases activity, decreases reaction, decreases expression, decreases phosphorylation	3
Cisplatin	decreases expression, increases expression, decreases response to substance, increases phosphorylation	3
bisphenol A	increases expression, affects binding	2
mercuric bromide	increases expression, affects cotreatment	2
belinostat	affects cotreatment, increases expression	2
Resveratrol	affects cotreatment, affects reaction, increases expression, increases degradation, increases reaction	2
Panobinostat	affects cotreatment, increases expression	2
Benzo(a)pyrene	affects methylation	2
Colforsin	increases activity, decreases activity, decreases reaction	2
Phenylmercuric Acetate	affects cotreatment, increases expression	2
Valproic Acid	increases expression, increases methylation	2
aristolochic acid I	increases expression	1
FR900359	increases phosphorylation	1
bisphenol F	increases expression	1
ammonium 2,3,3,3-tetrafluoro-2-(heptafluoropropoxy)-propanoate	affects cotreatment, affects expression	1
moringin	affects cotreatment, decreases expression	1
oxyphylla A	affects cotreatment, increases phosphorylation	1
dicrotophos	increases expression	1
tylophorine	increases expression	1
daidzein	affects cotreatment, decreases expression	1
triphenyl phosphate	affects expression	1
daidzin	decreases expression, affects cotreatment	1
o,p’-DDT	increases activity	1
11-nor-delta(9)-tetrahydrocannabinol-9-carboxylic acid	affects methylation, increases abundance	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
cobaltous chloride	decreases expression	1
perfluorooctanoic acid	affects cotreatment, affects expression	1
sulindac sulfide	increases expression	1
ochratoxin A	increases acetylation, increases expression	1

ChEMBL screening assays

606 unique, capped per target: 598 binding, 7 functional, 1 admet

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1052130	Binding	Percent residual PKA activity in the presence of 10uM inhibitor	Biochemical and three-dimensional-structural study of the specific inhibition of protein kinase CK2 by [5-oxo-5,6-dihydroindolo-(1,2-a)quinazolin-7-yl]acetic acid (IQA). — Biochem J
CHEMBL630618	Functional	Activation of cAMP dependent protein kinase (PKA)	Bioactivatable derivatives of 8-substituted cAMP-analogues — Bioorg Med Chem Lett
CHEMBL4424901	ADMET	Inhibition of full length human untagged PKAalpha expressed in Escherichia coli BL21 (DE3) pLysS cells using Kemptide as substrate	Optimization of an azetidine series as inhibitors of colony stimulating factor-1 receptor (CSF-1R) Type II to lead to the clinical candidate JTE-952. — 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_D1Q3	Abcam K-562 PRKACA KO	Cancer cell line	Female
CVCL_D2LP	Abcam Raji PRKACA KO	Cancer cell line	Male
CVCL_D7YD	Ubigene A-549 PRKACA KO	Cancer cell line	Male
CVCL_D9PG	Ubigene HEK293 PRKACA KO	Transformed cell line	Female
CVCL_TG70	HAP1 PRKACA (-) 1	Cancer cell line	Male
CVCL_TG71	HAP1 PRKACA (-) 2	Cancer cell line	Male
CVCL_WQ39	Abcam Jurkat PRKACA KO	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT04586348	PHASE4	UNKNOWN	Prenatal Iodine Supplementation and Early Childhood Neurodevelopment
NCT04873115	PHASE4	UNKNOWN	Double-blind, Placebo-controlled, Randomized Clinical Trial Comparing the Efficacy and Safety of Sialanar Plus orAl rehabiLitation Against Placebo Plus Oral Rehabilitation for chIldren and Adolescents With seVere Sialorrhoea and Neurodisabilties,
NCT02559102	PHASE3	COMPLETED	Dexmedetomidine Sedation Versus General Anaesthesia for Inguinal Hernia Surgery in Infants
NCT02757079	PHASE3	COMPLETED	Study of the Efficacy and Safety of NPC-15 for Sleep Disorders of Children With Neurodevelopmental Disorders
NCT06915480	PHASE3	RECRUITING	Reducing Missed Appointments
NCT07377032	PHASE3	RECRUITING	TAP-GRIN: Interventional Study on Patients With GRIN-related Neurodevelopmental Disorders
NCT02909959	PHASE2	COMPLETED	Sulforaphane for the Treatment of Young Men With Autism Spectrum Disorder
NCT06081348	PHASE2	RECRUITING	Sertraline vs. Placebo in the Treatment of Anxiety in Children and AdoLescents With NeurodevelopMental Disorders
NCT06352372	PHASE2	COMPLETED	Safety and Efficacy of tPBM for Epileptiform Activity in Autism
NCT05436639	PHASE2	COMPLETED	SPI-62 as a Treatment for Hypercortisolism Related to a Benign Adrenal Tumor
NCT00503191	PHASE1	COMPLETED	NeuroModulation Technique Treatment of Autism
NCT04475848	PHASE1	COMPLETED	A Study to Investigate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics and Food Effect of RO6953958 in Healthy Participants
NCT06300398	PHASE1	COMPLETED	IAMA-6 Oral Dose Study in Healthy Adults
NCT01783041	PHASE2/PHASE3	COMPLETED	Effect of Early L-Carnitine Supplementation on Neurodevelopmental Outcomes in Very Preterm Infants
NCT05767385	PHASE2/PHASE3	RECRUITING	Fetal Cerebrovascular Autoregulation in Congenital Heart Disease and Association With Neonatal Neurobehavior
NCT05675098	EARLY_PHASE1	NOT_YET_RECRUITING	Central Nervous System Stimulants and Physical Function in Children With Cerebral Palsy
NCT00783783	Not specified	COMPLETED	CYP2D6 Pharmacogenetics in Risperidone-Treated Children
NCT01778504	Not specified	RECRUITING	Studying Childhood-onset Behavioral, Psychiatric, and Developmental Disorders
NCT01850784	Not specified	UNKNOWN	High Energy Formula Feeding in Infants With Congenital Heart Disease
NCT01922791	Not specified	COMPLETED	Nutrition and Pregnancy Intervention Study
NCT01942525	Not specified	UNKNOWN	Influence of Intrauterine Growth Restriction on Amplitude-integrated EEG in Preterm Infants
NCT02003170	Not specified	COMPLETED	Etiology and Early Diagnosis of Neurodevelopmental Disorders
NCT02118649	Not specified	ACTIVE_NOT_RECRUITING	Enhancing Behavior and Brain Response to Visual Targets Using a Computer Game
NCT02557191	Not specified	TERMINATED	Biomarkers, Neurodevelopment and Preterm Infants
NCT02690675	Not specified	COMPLETED	Iron Supplement Effect on Child Development
NCT02694003	Not specified	COMPLETED	Better Nights, Better Days for Children With Neurodevelopment Disorders
NCT02792894	Not specified	COMPLETED	Family Networks (FaNs) for Children With Developmental Disorders and Delays
NCT02871674	Not specified	UNKNOWN	Good Night Project: Behavioural Sleep Interventions for Children With ADHD: A Randomised Controlled Trial
NCT02887157	Not specified	COMPLETED	Analyzing Retinal Microanatomy in ROP
NCT02898298	Not specified	COMPLETED	Positive Emotion Regulation Training in Children, Adolescents and Young Adults With and Without Developmental Disorder
NCT02912780	Not specified	UNKNOWN	Introduction of Microsystems in a Level 3 Neonatal Intensive Care Unit
NCT03023293	Not specified	COMPLETED	n-3 PUFAs, Irisin and Maternal Glucose Metabolism From Pregnancy to Postpartum
NCT03023644	Not specified	COMPLETED	Improving Neurodevelopmental Outcomes in Children With Congenital Heart Disease: An Intervention Study
NCT03032991	Not specified	UNKNOWN	Early Biomarkers of Neurodevelopment in Offspring of Diabetic Mothers
NCT03088189	Not specified	TERMINATED	Effect of Parental Peri-conceptional Vitamin B12 Supplementation on Infant Neurocognitive Development in Offspring
NCT03096028	Not specified	COMPLETED	Developmental Origins of Mental Health Disorders
NCT03148782	Not specified	COMPLETED	Brain Plasticity Underlying Acquisition of New Organizational Skills in Children-R61 Phase
NCT03172104	Not specified	COMPLETED	Neurobehavioural Development of Infants Born <30 Weeks Gestational Age Between Birth and Five Years of Age
NCT03222375	Not specified	RECRUITING	SQUED™ Series 28.1 Home-use and Treatment of Autowave Reverberator of Autism
NCT03229928	Not specified	COMPLETED	Clinical Testing of a Real-Time Behavior Measurement Tool: Measuring Outcomes for CHAnge