PRKAR1A

Summary

PRKAR1A (protein kinase cAMP-dependent type I regulatory subunit alpha, HGNC:9388) is a protein-coding gene on chromosome 17q24.2, encoding cAMP-dependent protein kinase type I-alpha regulatory subunit (P10644). Regulatory subunit of the cAMP-dependent protein kinases involved in cAMP signaling in cells. It is a selective cancer dependency (DepMap: 15.8% of cell lines) and haploinsufficient (ClinGen: sufficient evidence).

cAMP is a signaling molecule important for a variety of cellular functions. cAMP exerts its effects by activating the cAMP-dependent protein kinase, which transduces the signal through phosphorylation of different target proteins. The inactive kinase holoenzyme is a tetramer composed of two regulatory and two catalytic subunits. cAMP causes the dissociation of the inactive holoenzyme into a dimer of regulatory subunits bound to four cAMP and two free monomeric catalytic subunits. Four different regulatory subunits and three catalytic subunits have been identified in humans. This gene encodes one of the regulatory subunits. This protein was found to be a tissue-specific extinguisher that down-regulates the expression of seven liver genes in hepatoma x fibroblast hybrids. Mutations in this gene cause Carney complex (CNC). This gene can fuse to the RET protooncogene by gene rearrangement and form the thyroid tumor-specific chimeric oncogene known as PTC2. A nonconventional nuclear localization sequence (NLS) has been found for this protein which suggests a role in DNA replication via the protein serving as a nuclear transport protein for the second subunit of the Replication Factor C (RFC40). Several alternatively spliced transcript variants encoding two different isoforms have been observed.

Source: NCBI Gene 5573 — RefSeq curated summary.

At a glance

• Gene–disease (curated): Carney complex, type 1 (Definitive, ClinGen) — +7 more curated relationships
• GWAS associations: 6
• Clinical variants (ClinVar): 1,339 total — 86 pathogenic, 29 likely-pathogenic
• Phenotypes (HPO): 244
• Druggable target: yes
• Cancer driver (intOGen): activating (oncogene-like) across 3 cancer types
• Cancer dependency (DepMap): dependent in 15.8% of screened cell lines
• Dosage sensitivity (ClinGen): haploinsufficiency sufficient evidence, triplosensitivity no evidence
• MANE Select transcript: NM_002734

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:9388
Approved symbol	PRKAR1A
Name	protein kinase cAMP-dependent type I regulatory subunit alpha
Location	17q24.2
Locus type	gene with protein product
Status	Approved
Aliases	CNC1
Ensembl gene	ENSG00000108946
Ensembl biotype	protein_coding
OMIM	188830
Entrez	5573

Gene structure

Transcript identifiers

Ensembl transcripts: 25 — 15 protein_coding, 6 retained_intron, 3 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined

ENST00000358598, ENST00000392710, ENST00000392711, ENST00000536854, ENST00000585427, ENST00000585460, ENST00000585608, ENST00000585815, ENST00000585907, ENST00000585981, ENST00000586397, ENST00000586541, ENST00000588178, ENST00000588188, ENST00000589017, ENST00000589228, ENST00000589309, ENST00000589480, ENST00000592194, ENST00000592800, ENST00000686019, ENST00000689501, ENST00000689625, ENST00000691392, ENST00000711037

RefSeq mRNA: 8 — MANE Select: NM_002734 NM_001276289, NM_001276290, NM_001278433, NM_001369389, NM_001369390, NM_002734, NM_212471, NM_212472

CCDS: CCDS11678, CCDS62307

Canonical transcript exons

ENST00000589228 — 11 exons

Exon	Start	End
ENSE00002808748	68530277	68533431
ENSE00003465268	68525754	68525912
ENSE00003489848	68529920	68530001
ENSE00003549891	68527840	68527900
ENSE00003635636	68524912	68524958
ENSE00003642606	68528870	68528991
ENSE00003703426	68515394	68515576
ENSE00003706655	68523725	68523816
ENSE00003709373	68522756	68522926
ENSE00003709612	68524016	68524077
ENSE00003899583	68512430	68512548

Expression profiles

Bgee: expression breadth ubiquitous, 295 present calls, max score 99.87.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 154.1208 / max 1722.4337, expressed in 1826 samples.

FANTOM5 promoters (12 alternative TSS)

Promoter ID	TPM avg	Samples expressed
162432	126.3982	1824
162433	13.3763	1775
162428	4.0883	1336
162429	3.4168	982
162443	2.8469	1261
162435	1.7081	967
162434	0.6802	406
162440	0.5038	206
162437	0.4499	162
162431	0.3278	175

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
mucosa of paranasal sinus	UBERON:0005030	99.87	gold quality
germinal epithelium of ovary	UBERON:0001304	99.83	gold quality
lateral nuclear group of thalamus	UBERON:0002736	99.72	gold quality
bronchial epithelial cell	CL:0002328	99.68	gold quality
epithelium of nasopharynx	UBERON:0001951	99.67	gold quality
adult organism	UBERON:0007023	99.62	gold quality
superficial temporal artery	UBERON:0001614	99.61	gold quality
choroid plexus epithelium	UBERON:0003911	99.61	gold quality
substantia nigra pars compacta	UBERON:0001965	99.58	gold quality
substantia nigra pars reticulata	UBERON:0001966	99.54	gold quality
caput epididymis	UBERON:0004358	99.53	gold quality
myocardium	UBERON:0002349	99.52	gold quality
parietal pleura	UBERON:0002400	99.51	gold quality
cardiac muscle of right atrium	UBERON:0003379	99.49	gold quality
lower lobe of lung	UBERON:0008949	99.49	gold quality
adrenal tissue	UBERON:0018303	99.49	gold quality
pleura	UBERON:0000977	99.47	gold quality
epithelium of bronchus	UBERON:0002031	99.47	gold quality
pons	UBERON:0000988	99.46	gold quality
bronchus	UBERON:0002185	99.45	gold quality
orbitofrontal cortex	UBERON:0004167	99.45	gold quality
visceral pleura	UBERON:0002401	99.44	gold quality
frontal pole	UBERON:0002795	99.44	gold quality
dorsal plus ventral thalamus	UBERON:0001897	99.43	gold quality
cauda epididymis	UBERON:0004360	99.43	gold quality
subthalamic nucleus	UBERON:0001906	99.42	gold quality
lateral globus pallidus	UBERON:0002476	99.41	gold quality
heart right ventricle	UBERON:0002080	99.40	gold quality
superior vestibular nucleus	UBERON:0007227	99.40	gold quality
postcentral gyrus	UBERON:0002581	99.37	gold quality

Single-cell (SCXA)

Detected in 8 experiment(s), a significant marker in 5.

Experiment	Marker?	Max mean expression
E-MTAB-8142	yes	45.98
E-CURD-112	yes	12.69
E-GEOD-130148	yes	8.03
E-MTAB-10137	yes	3.85
E-GEOD-70580	no	2121.24
E-CURD-10	no	729.80
E-MTAB-8271	no	257.79
E-ANND-3	no	0.00

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

2 targets.

Target	Regulation
CCL2	Repression
IL6	Repression

Upstream regulators (CollecTRI, top): E2F6, FOXC2, FOXD1, FOXD2, PATZ1

miRNA regulators (miRDB)

166 targeting PRKAR1A, 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-5011-5P	100.00	83.46	5820
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-4533	100.00	69.48	2758
HSA-MIR-200B-3P	100.00	73.31	2693
HSA-MIR-200C-3P	100.00	73.35	2685
HSA-MIR-429	100.00	73.44	2698
HSA-MIR-4476	100.00	68.18	2030
HSA-MIR-6876-5P	100.00	67.68	2126
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-150-5P	99.99	66.69	1976
HSA-MIR-196A-1-3P	99.99	72.15	2772
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-4482-3P	99.98	72.50	3147
HSA-MIR-499A-5P	99.98	70.79	1323
HSA-MIR-548P	99.98	72.25	3784
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-548N	99.98	71.94	4170
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-MIR-3658	99.96	73.87	4379
HSA-MIR-1468-3P	99.96	72.74	3797
HSA-MIR-5688	99.96	73.23	4504
HSA-MIR-495-3P	99.96	72.81	4197
HSA-MIR-9-3P	99.96	70.88	2068
HSA-MIR-96-5P	99.95	72.80	2140
HSA-MIR-545-3P	99.95	70.74	2783

Functional genomics

ClinGen dosage: haploinsufficiency 3 (sufficient evidence), triplosensitivity 0 (no evidence). ClinGen Gene Dosage Map DepMap (CRISPR cell-line fitness): dependent in 15.8% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 40)

• Formation of inactive cAMP-saturated holoenzyme of cAMP-dependent protein kinase under physiological conditions (PMID:11834733)
• Protein kinase A type I: a target for cancer therapy (PMID:11839645)
• mutations in the gene coding for PRKAR1A in Carney complex - review (PMID:12119264)
• The regulatory subunit type I-alpha of protein kinase A functions as a thyroid cancer tumor-suppressor gene. (PMID:12203783)
• germline and somatic mutations of the PRKAR1A gene in Cushing’s syndrome caused by sporadic primary pigmented nodular adrenocortical disease (PMID:12213893)
• Patients with Carney complex and primary pigmented nodular adrenocortical disease (PPNAD) reveals novel mutations and clues for pathophysiology: augmented PKA signaling is associated with adrenal tumorigenesis in PPNAD (PMID:12424709)
• PRKAR1A, one of the Carney complex genes, and its locus (17q22-24) are rarely altered in pituitary tumours outside the Carney complex (PMID:12471216)
• RIalpha and RIbeta homodimers as well as an RIalpha:RIbeta heterodimer and several of the mutants were able to bind to the R-binding domain of AKAP149/D-AKAP1 (PMID:12634056)
• (PRKAR1 alpha) has been discovered and found to be associated with a high risk of developing cardiac myxomas. (PMID:12752185)
• Reduced IL-10 secretion in common variable immunodeficiency patients seems to involve the cAMP-dependent protein kinase A type I system. (PMID:12759461)
• PRKAR1A activity in Carney complex cells is increased and it has a role in phosphorylation, cell metabolism and proliferation (PMID:12812976)
• PKA-RIbeta binds to merlin and may be involved in signaling with merlin in the cytoskeleton (PMID:12896975)
• PKA regulates ethanol-induced cAMP response element-mediated gene expression via activation of CREB-binding protein and inhibition of MAPK (PMID:15299023)
• PRKAR1A might function as a tumor suppressor gene (PMID:15331577)
• concluded that although PRKAR1A haploinsufficiency does predispose to tumorigenesis, distinct secondary genetic events are required for tumor formation (PMID:15371594)
• Low expression of R1A protein may favor cAMP-dependent proliferation of transformed somatotrophs. (PMID:15604292)
• evidence is presented for a novel interaction between RFC40 and the RIalpha subunit of PKA; findings indicate that modulation in the formation of the RFC40-RIa complex is associated with decreased cell survival (PMID:15655353)
• A nonconventional nuclear localization sequence (NLS) has been found for PRKAR1A. This suggests a new function for PRKAR1A as a nuclear transport protein for the second subunit of RFC40. (PMID:15846072)
• Mutation of the PRKAR1A gene may be associated with familial cardiac myxoma in Carney complex but may not be associated with sporadic cardiac myxoma. (PMID:15982496)
• Molecular genetic analysis demonstrated involvement of a mutation in the PRKAR1alpha gene. (PMID:16020889)
• switching of PKA isozyme can cause tumor cells to undergo phenotypic reversion of the malignancy [revoew] (PMID:16394127)
• Described simulations shed light on the mechanism by which PKA regulatory subunit RI alpha undergoes its dramatic conformational change upon binding to the C subunit. (PMID:16407073)
• cAMP signaling control is achieved by A-kinase anchoring proteins including type I PKA holoenzyme (PMID:16728392)
• Epac1 and cAMP-dependent protein kinase holoenzyme have similar cAMP affinity, but different cAMP domains (PMID:16728394)
• Haploinsufficiency at the protein kinase A RI alpha gene locus leads to fertility defects in male mice and men. (PMID:16728532)
• Phosphorylated-mTOR levels and mTOR activity were dramatically increased in HEK 293 cells with RIalpha levels reduced by siRNA. (PMID:16963469)
• Role of mutations in in primary pigmented nodular adrenocortical disease (Review) (PMID:17036196)
• Reviews genetic aspects of hereditary GH-secreting tumors and data from animal models resulting from the inactivation of the PRKAR1A tumor suppressor gene. (PMID:17047380)
• human cells with partially inactivated RIalpha levels have increased proliferation and survival. (PMID:17079485)
• Contrary to the classical model of PKA activation, elevated cAMP does not allow RIalpha and Calpha to diffuse far apart unless the pseudosubstrate inhibitor PKI or locally concentrated substrate is coexpressed (PMID:17884635)
• A high R1/R2 ratio favors the proliferation of well differentiated and hormone producing adrenocortical cells, while unbalanced expression of these subunits is not required for malignant transformation. (PMID:17904549)
• first immortalized cell line with naturally occurring PRKAR1A-inactivating mutation associated with tumor formation; data support hypothesis that balance between PKA-I & -II is critical for tumor induction &/or promotion in tissues with PRKAR1A mutations (PMID:18056771)
• Loss of expression of PRKAR1 offers a useful diagnostic test that helps to distinguish pigmented epithelioid melanocytoma from lesions that mimic it histologically. (PMID:18059235)
• Large PRKAR1A deletions may be responsible for Carney complex in patients that do not have PRKAR1A gene defects identifiable by sequencing. (PMID:18223213)
• data further corroborate the previous finding that altered PRKAR1A function, not only haploinsufficiency, is enough to elevate PKA activity which is apparently associated with tumorigenesis in tissues affected by Carney complex (PMID:18241045)
• BLM deficiency is associated with a relative excess of PRKAR1A in fibroblasts compared to other PKA subunits; PRKAR1A deficiency is associated with increased BLM protein in adrenal hyperplasias. (PMID:18401830)
• Wnt5a anti-apoptotic activity may be partially mediated by PKA-mediated phosphorylation of GSK-3beta and subsequent activation of the beta-catenin pathway. (PMID:18407462)
• Dysregulation of protein kinase A (PKA) activity, caused by loss of function mutations in PRKAR1A, is known to induce tumor formation in the inherited tumor syndrome Carney complex. (PMID:18413734)
• A PRKAR1A mutation is reported in individuals who were diagnosed with Carney complex after retrospective family screening. (PMID:18445140)
• A switch to type II PKA activity is not necessary for increased kinase activity or tumorigenesis. (PMID:18451138)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	prkar1aa	ENSDARG00000076128
danio_rerio	prkar1ab	ENSDARG00000101755
mus_musculus	Prkar1a	ENSMUSG00000020612
rattus_norvegicus	Prkar1a	ENSRNOG00000049876

Paralogs (4): PRKAR2B (ENSG00000005249), PRKAR2A (ENSG00000114302), CNBD1 (ENSG00000176571), PRKAR1B (ENSG00000188191)

Protein

Protein identifiers

cAMP-dependent protein kinase type I-alpha regulatory subunit — P10644 (reviewed: P10644)

Alternative names: Tissue-specific extinguisher 1

All UniProt accessions (13): P10644, B2R5T5, K7EIE5, K7EJ40, K7EK41, K7EKR1, K7EM13, K7EMU2, K7EMZ6, K7EPB2, K7EPR5, K7EQK3, X6RAV4

UniProt curated annotations — full annotation on UniProt →

Function. Regulatory subunit of the cAMP-dependent protein kinases involved in cAMP signaling in cells.

Subunit / interactions. The inactive holoenzyme is composed of two regulatory chains and two catalytic chains. Activation by cAMP releases the two active catalytic monomers and the regulatory dimer. Interacts with PRKACA and PRKACB. PRKAR1A also interacts with RFC2; the complex may be involved in cell survival. Interacts with AKAP4. Interacts with RARA; the interaction occurs in the presence of cAMP or FSH and regulates RARA transcriptional activity. Interacts with the phosphorylated form of PJA2. Interacts with CBFA2T3. Interacts with PRKX; regulates this cAMP-dependent protein kinase. Interacts with AKAP19; this interaction targets PRKAR1A to the plasma membrane. Interacts with AICDA. Interacts with PRRC1; resulting in PKA activation.

Subcellular location. Cell membrane.

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

Post-translational modifications. The pseudophosphorylation site binds to the substrate-binding region of the catalytic chain, resulting in the inhibition of its activity.

Disease relevance. Carney complex 1 (CNC1) [MIM:160980] CNC is a multiple neoplasia syndrome characterized by spotty skin pigmentation, cardiac and other myxomas, endocrine tumors, and psammomatous melanotic schwannomas. The disease is caused by variants affecting the gene represented in this entry. Intracardiac myxoma (INTMYX) [MIM:255960] Inheritance is autosomal recessive. The disease is caused by variants affecting the gene represented in this entry. Primary pigmented nodular adrenocortical disease 1 (PPNAD1) [MIM:610489] 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. Clinical manifestations of Cushing syndrome include facial and truncal obesity, abdominal striae, muscular weakness, osteoporosis, arterial hypertension, diabetes. PPNAD1 is most often diagnosed in patients with Carney complex, a multiple neoplasia syndrome. However it can also be observed in patients without other manifestations. The disease is caused by variants affecting the gene represented in this entry. Acrodysostosis 1, with or without hormone resistance (ACRDYS1) [MIM:101800] A form of skeletal dysplasia characterized by short stature, severe brachydactyly, facial dysostosis, and nasal hypoplasia. Affected individuals often have advanced bone age and obesity. Laboratory studies show resistance to multiple hormones, including parathyroid, thyrotropin, calcitonin, growth hormone-releasing hormone, and gonadotropin. However, not all patients show endocrine abnormalities. The disease is caused by variants affecting the gene represented in this entry.

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

Isoforms (2)

UniProt ID	Names	Canonical?
P10644-1	1	yes
P10644-2	2

RefSeq proteins (8): NP_001263218, NP_001263219, NP_001265362, NP_001356318, NP_001356319, NP_002725, NP_997636, NP_997637 (=MANE)

Domains & families (InterPro)

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

Pfam: PF00027, PF02197

UniProt features (68 total): sequence variant 18, binding site 16, modified residue 7, helix 7, mutagenesis site 6, strand 5, region of interest 2, disulfide bond 2, splice variant 2, chain 1, short sequence motif 1, turn 1

Structure

Experimental structures (PDB)

3 structures.

PDB	Method	Resolution (Å)
5KJZ	X-RAY DIFFRACTION	1.35
5KJX	X-RAY DIFFRACTION	1.9
5KJY	X-RAY DIFFRACTION	2

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P10644-F1	87.95	0.62

Functional residue map

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

Ligand- & substrate-binding residues (16): 260; 262; 325; 326; 327; 328; 335; 336; 373; 374; 201; 202 …

Post-translational modifications (7): 1, 3, 75, 77, 83, 101, 258

Disulfide bonds (2): 18, 39

Mutagenesis-validated functional residues (6):

Position	Phenotype
192	reduced affinity for camp and moderately increased affinity for cgmp.
212	reduced affinity for camp and approximately 50-fold increased affinity for cgmp.
315	negligible effect on affinity for camp and moderately increased affinity for cgmp.
316	reduced affinity for camp and approximately 4-fold increased affinity for cgmp.
336	negligible effect on affinity for camp and approximately 200-fold increased affinity for cgmp.
373	impairs response of pka to c-amp.

Function

Pathways and Gene Ontology

Reactome pathways

52 pathways

ID	Pathway
R-HSA-163615	PKA activation
R-HSA-164378	PKA activation in glucagon signalling
R-HSA-180024	DARPP-32 events
R-HSA-381676	Glucagon-like Peptide-1 (GLP1) regulates insulin secretion
R-HSA-432040	Vasopressin regulates renal water homeostasis via Aquaporins
R-HSA-442720	CREB1 phosphorylation through the activation of Adenylate Cyclase
R-HSA-5610787	Hedgehog ‘off’ state
R-HSA-9634597	GPER1 signaling
R-HSA-9660821	ADORA2B mediated anti-inflammatory cytokines production
R-HSA-9664323	FCGR3A-mediated IL10 synthesis
R-HSA-9700645	ALK mutants bind TKIs
R-HSA-9725370	Signaling by ALK fusions and activated point mutants
R-HSA-983231	Factors involved in megakaryocyte development and platelet production
R-HSA-9856530	High laminar flow shear stress activates signaling by PIEZO1 and PECAM1:CDH5:KDR in endothelial cells
R-HSA-109582	Hemostasis
R-HSA-111885	Opioid Signalling
R-HSA-111931	PKA-mediated phosphorylation of CREB
R-HSA-111933	Calmodulin induced events
R-HSA-111996	Ca-dependent events
R-HSA-111997	CaM pathway
R-HSA-112040	G-protein mediated events
R-HSA-112043	PLC beta mediated events
R-HSA-112314	Neurotransmitter receptors and postsynaptic signal transmission
R-HSA-112315	Transmission across Chemical Synapses
R-HSA-112316	Neuronal System
R-HSA-1430728	Metabolism
R-HSA-1489509	DAG and IP3 signaling
R-HSA-162582	Signal Transduction
R-HSA-163359	Glucagon signaling in metabolic regulation
R-HSA-163685	Integration of energy metabolism

MSigDB gene sets: 983 (showing top): MORF_MTA1, WAMUNYOKOLI_OVARIAN_CANCER_LMP_DN, GOBP_REGULATION_OF_CELL_ACTIVATION, GOBP_RESPONSE_TO_NITROGEN_COMPOUND, GOBP_REGULATION_OF_LEUKOCYTE_PROLIFERATION, GOBP_REGULATION_OF_INFLAMMATORY_RESPONSE_TO_ANTIGENIC_STIMULUS, GOBP_MUSCLE_TISSUE_DEVELOPMENT, MORF_MBD4, GOBP_REGULATION_OF_PHOSPHORYLATION, GOBP_INFLAMMATORY_RESPONSE, GOBP_FORMATION_OF_PRIMARY_GERM_LAYER, GOBP_NEGATIVE_REGULATION_OF_LEUKOCYTE_PROLIFERATION, GOBP_RESPONSE_TO_FLUID_SHEAR_STRESS, GOBP_CELLULAR_RESPONSE_TO_FLUID_SHEAR_STRESS, GOZGIT_ESR1_TARGETS_DN

GO Biological Process (17): mesoderm formation (GO:0001707), negative regulation of inflammatory response to antigenic stimulus (GO:0002862), renal water homeostasis (GO:0003091), regulation of transcription by RNA polymerase II (GO:0006357), adenylate cyclase-activating G protein-coupled receptor signaling pathway (GO:0007189), chemical synaptic transmission (GO:0007268), negative regulation of gene expression (GO:0010629), positive regulation of insulin secretion (GO:0032024), intracellular signal transduction (GO:0035556), sarcomere organization (GO:0045214), negative regulation of activated T cell proliferation (GO:0046007), cardiac muscle cell proliferation (GO:0060038), cellular response to glucagon stimulus (GO:0071377), vascular endothelial cell response to laminar fluid shear stress (GO:0097700), negative regulation of cAMP/PKA signal transduction (GO:0141162), regulation of protein phosphorylation (GO:0001932), heart development (GO:0007507)

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

GO Cellular Component (17): cytoplasm (GO:0005737), multivesicular body (GO:0005771), centrosome (GO:0005813), cytosol (GO:0005829), plasma membrane (GO:0005886), cAMP-dependent protein kinase complex (GO:0005952), membrane (GO:0016020), nucleotide-activated protein kinase complex (GO:0031588), neuromuscular junction (GO:0031594), protein-containing complex (GO:0032991), plasma membrane raft (GO:0044853), ciliary base (GO:0097546), glutamatergic synapse (GO:0098978), sperm head-tail coupling apparatus (GO:0120212), immunological synapse (GO:0001772), axoneme (GO:0005930), synapse (GO:0045202)

Reactome top-level categories

Rollup of top-18 pathways:

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

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	7
intracellular anatomical structure	2
cAMP-dependent protein kinase activity	2
intracellular protein-containing complex	2
synapse	2
plasma membrane	2
formation of primary germ layer	1
mesoderm morphogenesis	1
inflammatory response to antigenic stimulus	1
regulation of inflammatory response to antigenic stimulus	1
negative regulation of inflammatory response	1
negative regulation of immune response	1
renal system process	1
multicellular organismal-level water homeostasis	1
regulation of DNA-templated transcription	1
transcription by RNA polymerase II	1
adenylate cyclase-modulating G protein-coupled receptor signaling pathway	1
adenylate cyclase activator activity	1
anterograde trans-synaptic signaling	1
gene expression	1
regulation of gene expression	1
negative regulation of macromolecule biosynthetic process	1
insulin secretion	1
positive regulation of protein secretion	1
regulation of insulin secretion	1
positive regulation of peptide hormone secretion	1
signal transduction	1
myofibril assembly	1
actomyosin structure organization	1
negative regulation of T cell proliferation	1
regulation of activated T cell proliferation	1
activated T cell proliferation	1
striated muscle cell proliferation	1
cardiac muscle tissue growth	1
response to glucagon	1
cellular response to peptide hormone stimulus	1
cellular response to laminar fluid shear stress	1
vascular endothelial cell response to fluid shear stress	1
cAMP/PKA signal transduction	1
regulation of cAMP/PKA signal transduction	1

Protein interactions and networks

STRING

2844 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PRKAR1A	PRKACA	P17612	955
PRKAR1A	PDE11A	Q9HCR9	917
PRKAR1A	PRKACB	P22694	915
PRKAR1A	PRKACG	P22612	910
PRKAR1A	PDE8B	O95263	843
PRKAR1A	GNAS	Q5JWF2	828
PRKAR1A	MYH8	P13535	807
PRKAR1A	RET	P07949	758
PRKAR1A	PTCH2	Q9Y6C5	752
PRKAR1A	TAT	P17735	737
PRKAR1A	POMC	P01189	730
PRKAR1A	NUMA1	Q14980	708
PRKAR1A	MEN1	O00255	682
PRKAR1A	ARMC5	Q96C12	663
PRKAR1A	NCOA4	Q13772	641

IntAct

298 interactions, top by confidence:

A	B	Type	Score
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
PRKACA	PRKAR1A	psi-mi:“MI:2364”(proximity)	0.960
PRKAR1A	PRKAR1B	psi-mi:“MI:0915”(physical association)	0.800
C2orf88	PRKAR1A	psi-mi:“MI:0915”(physical association)	0.740
PRKAR1A	C2orf88	psi-mi:“MI:0915”(physical association)	0.740
VAPB	FAM83G	psi-mi:“MI:0914”(association)	0.730
PRKACA	VAPB	psi-mi:“MI:0914”(association)	0.730
	PRKAR1A	psi-mi:“MI:0914”(association)	0.700
	PRKAR1A	psi-mi:“MI:0217”(phosphorylation reaction)	0.700
	PRKAR1A	psi-mi:“MI:0915”(physical association)	0.700
MAPK7	PFDN6	psi-mi:“MI:0914”(association)	0.640
AICDA	PRKAR1A	psi-mi:“MI:0915”(physical association)	0.620
AICDA	PRKAR1A	psi-mi:“MI:0914”(association)	0.620
PLEKHF2	PRKAR1A	psi-mi:“MI:0915”(physical association)	0.620
GABARAPL1	IPO5	psi-mi:“MI:0914”(association)	0.590
PRKAR1A	DPB3	psi-mi:“MI:0915”(physical association)	0.560
TCD1	PRKAR1A	psi-mi:“MI:0915”(physical association)	0.560
DPB3	PRKAR1A	psi-mi:“MI:0915”(physical association)	0.560
PRKAR1A	TCD1	psi-mi:“MI:0915”(physical association)	0.560
AKAP7	PRKAR1A	psi-mi:“MI:0915”(physical association)	0.560
PRKAR1A	RSPH3	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (444): PRKAR1A (Two-hybrid), PRKAR1A (Affinity Capture-MS), PRKAR1A (Affinity Capture-MS), PRKAR1A (Biochemical Activity), PRKAR1A (Affinity Capture-MS), MTOR (Affinity Capture-Western), PRKAR1A (Affinity Capture-Western), PRKAR1A (Affinity Capture-MS), PRKAR1B (Affinity Capture-MS), AKAP11 (Affinity Capture-MS), STOML2 (Affinity Capture-MS), PRKACA (Affinity Capture-MS), PRKACG (Affinity Capture-MS), PRKACB (Affinity Capture-MS), PALM2-AKAP2 (Affinity Capture-MS)

ESM2 similar proteins: C9WPN6, F1QGW6, O14787, O77676, P00514, P00516, P07802, P09456, P0C605, P10644, P11233, P12849, P20461, P31321, P35250, P41091, P49136, P53033, P61964, P62482, P62483, P63320, P63321, P63322, P81377, P81795, Q05B83, Q13303, Q13976, Q27955, Q2KHU8, Q2KIG2, Q2VIR3, Q3SYU7, Q498M4, Q5I0F6, Q5M786, Q5R797, Q5REL1, Q5ZM91

Diamond homologs: A0R3F9, A8X6H1, O05581, O14448, O59922, O76360, P00514, P00516, P05987, P07278, P07802, P09456, P0C605, P10644, P12849, P16905, P30625, P31319, P31320, P31321, P36600, P49605, P81377, P81900, P9WM60, P9WM61, Q01386, Q13237, Q13976, Q5I0F6, Q5REL1, Q5ZM91, Q61410, Q64595, Q6BZG7, Q6C2X0, Q6CPK7, Q75AM2, Q86ZN7, Q8TF77

SIGNOR signaling

11 interactions.

A	Effect	B	Mechanism
CDK2	up-regulates	PRKAR1A	phosphorylation
PDE4DIP	up-regulates	PRKAR1A	binding
CyclinE/CDK2	up-regulates	PRKAR1A	phosphorylation
PRKAR1A	“down-regulates activity”	PRKACA	binding
PRKAR1A	“down-regulates activity”	PRKACB	binding
“3’,5’-cyclic AMP”	“down-regulates activity”	PRKAR1A	“chemical inhibition”
FOXD2	“up-regulates quantity by expression”	PRKAR1A	“transcriptional regulation”
PJA2	“down-regulates quantity by destabilization”	PRKAR1A	polyubiquitination
CyclinY/CDK16	“up-regulates activity”	PRKAR1A	phosphorylation
CDK16	“up-regulates activity”	PRKAR1A	phosphorylation
PRKG1	“up-regulates activity”	PRKAR1A	phosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 143 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
PKA activation in glucagon signalling	5	36.5×	2e-05
PKA activation	5	34.5×	3e-05
PKA-mediated phosphorylation of CREB	5	31.0×	3e-05
DARPP-32 events	5	25.9×	5e-05
Calmodulin induced events	6	24.8×	2e-05
CaM pathway	6	24.8×	2e-05
Ca-dependent events	6	24.0×	2e-05
Anti-inflammatory response favouring Leishmania parasite infection	5	21.4×	1e-04

GO biological processes:

GO term	Partners	Fold	FDR
vascular endothelial cell response to laminar fluid shear stress	5	31.1×	2e-04
renal water homeostasis	5	21.6×	5e-04
autophagosome maturation	6	17.9×	3e-04
mitophagy	6	16.2×	4e-04
positive regulation of protein ubiquitination	7	12.7×	3e-04
positive regulation of cell differentiation	5	11.3×	7e-03
positive regulation of proteasomal ubiquitin-dependent protein catabolic process	6	10.7×	3e-03
protein phosphorylation	17	9.8×	2e-09

Disease & clinical

Cancer significance

From intOGen — cancer-driver classification: activating (oncogene-like) across 3 cancer types — ACC, MBL, PAST.

Clinical variants and AI predictions

ClinVar

1339 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	86
Likely pathogenic	29
Uncertain significance	578
Likely benign	519
Benign	43

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1069150	NM_002734.5(PRKAR1A):c.330_338dup (p.Tyr113Ter)	Pathogenic
1074600	NM_002734.5(PRKAR1A):c.340del (p.Val114fs)	Pathogenic
1075863	NM_002734.5(PRKAR1A):c.590dup (p.Gly198fs)	Pathogenic
1203139	NM_002734.5(PRKAR1A):c.499C>T (p.Gln167Ter)	Pathogenic
1253843	NM_002734.5(PRKAR1A):c.957del (p.Pro320fs)	Pathogenic
12662	NM_002734.5(PRKAR1A):c.491_492del (p.Val164fs)	Pathogenic
12663	NM_002734.5(PRKAR1A):c.786_787delinsCT (p.Trp262_Glu263delinsCysTer)	Pathogenic
12665	NM_002734.5(PRKAR1A):c.618_621del (p.Ile206fs)	Pathogenic
12667	NM_002734.5(PRKAR1A):c.761_762del (p.Ser254fs)	Pathogenic
12669	NM_002734.5(PRKAR1A):c.1A>G (p.Met1Val)	Pathogenic
12671	PRKAR1A, 16-BP DEL	Pathogenic
12672	NM_002734.5(PRKAR1A):c.708+1G>T	Pathogenic
12673	NM_002734.5(PRKAR1A):c.892-1G>A	Pathogenic
1352652	NM_002734.5(PRKAR1A):c.190_203del (p.Gln64fs)	Pathogenic
1368681	NM_002734.5(PRKAR1A):c.718dup (p.Leu240fs)	Pathogenic
1377787	NM_002734.5(PRKAR1A):c.479del (p.Ala160fs)	Pathogenic
1393898	NM_002734.5(PRKAR1A):c.97del (p.Asp33fs)	Pathogenic
1399779	NM_002734.5(PRKAR1A):c.502+1G>C	Pathogenic
1421058	NM_002734.5(PRKAR1A):c.440+1G>A	Pathogenic
1451227	NM_002734.5(PRKAR1A):c.545dup (p.Asp183fs)	Pathogenic
1452556	NM_002734.5(PRKAR1A):c.926_930del (p.Asn309fs)	Pathogenic
1456695	NM_002734.5(PRKAR1A):c.629del (p.Pro210fs)	Pathogenic
164995	NM_002734.5(PRKAR1A):c.623del (p.Gly208fs)	Pathogenic
1732024	NM_002734.3(PRKAR1A):c.349delG	Pathogenic
2017377	NM_002734.5(PRKAR1A):c.877T>A (p.Phe293Ile)	Pathogenic
2018571	NM_002734.5(PRKAR1A):c.502+2T>G	Pathogenic
2021392	NM_002734.5(PRKAR1A):c.786G>A (p.Trp262Ter)	Pathogenic
2033429	NM_002734.5(PRKAR1A):c.763_766del (p.Ser254_Ile255insTer)	Pathogenic
2135778	NM_002734.5(PRKAR1A):c.787G>T (p.Glu263Ter)	Pathogenic
2424526	NC_000017.10:g.(?66518887)(66519967_?)del	Pathogenic

SpliceAI

3316 predictions. Top by Δscore:

Variant	Effect	Δscore
17:68515389:CGCA:C	acceptor_loss	1.0000
17:68515389:CGCAG:C	acceptor_gain	1.0000
17:68515391:CAG:C	acceptor_gain	1.0000
17:68515392:A:AG	acceptor_gain	1.0000
17:68515392:A:C	acceptor_loss	1.0000
17:68515392:AGA:A	acceptor_gain	1.0000
17:68515393:G:C	acceptor_loss	1.0000
17:68515393:G:GG	acceptor_gain	1.0000
17:68515393:GA:G	acceptor_gain	1.0000
17:68515393:GAG:G	acceptor_gain	1.0000
17:68515393:GAGA:G	acceptor_gain	1.0000
17:68515393:GAGAA:G	acceptor_gain	1.0000
17:68522750:TTTCA:T	acceptor_loss	1.0000
17:68522751:TTCAG:T	acceptor_loss	1.0000
17:68522754:A:AC	acceptor_loss	1.0000
17:68522754:A:AG	acceptor_gain	1.0000
17:68522754:AGGAG:A	acceptor_gain	1.0000
17:68522755:G:GG	acceptor_gain	1.0000
17:68522755:GGAGG:G	acceptor_gain	1.0000
17:68522923:AAAG:A	donor_loss	1.0000
17:68522924:AAG:A	donor_loss	1.0000
17:68522925:AG:A	donor_loss	1.0000
17:68522926:GGTAG:G	donor_loss	1.0000
17:68522927:GT:G	donor_loss	1.0000
17:68522928:T:A	donor_loss	1.0000
17:68523720:TCTA:T	acceptor_loss	1.0000
17:68523721:CTAG:C	acceptor_loss	1.0000
17:68523722:TAG:T	acceptor_loss	1.0000
17:68523723:A:AG	acceptor_gain	1.0000
17:68523723:A:G	acceptor_loss	1.0000

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000022114 (17:68417229 C>T), RS1000047717 (17:68442560 G>T), RS1000051175 (17:68533730 T>C), RS1000054925 (17:68417610 C>A), RS1000056885 (17:68484780 C>T), RS1000074772 (17:68449412 C>T), RS1000077975 (17:68465728 C>T), RS1000119279 (17:68517152 T>C), RS1000145471 (17:68448061 C>T), RS1000147185 (17:68509909 C>A), RS1000166201 (17:68467655 C>G), RS1000167453 (17:68425684 A>G), RS1000180879 (17:68549251 T>C), RS1000185319 (17:68549443 G>A), RS1000186029 (17:68490698 G>C)

Disease associations

OMIM: gene MIM:188830 | disease phenotypes: MIM:160980, MIM:101800, MIM:255960, MIM:610489, MIM:610193, MIM:204690, MIM:614253, MIM:155255

GenCC curated gene-disease

Disease	Classification	Inheritance
Acrodysostosis 1 with or without hormone resistance	Definitive	Autosomal dominant
Carney complex, type 1	Definitive	Autosomal dominant
acrodysostosis with multiple hormone resistance	Definitive	Autosomal dominant
pigmented nodular adrenocortical disease, primary, 1	Strong	Autosomal dominant
familial atrial myxoma	Strong	Autosomal dominant
Carney complex	Supportive	Autosomal dominant
primary pigmented nodular adrenocortical disease	Supportive	Autosomal dominant
acrodysostosis	Supportive	Autosomal dominant

ClinGen Gene-Disease Validity (1)

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

Disease	Classification	Inheritance
Carney complex, type 1	Definitive	AD

Mondo (13): Carney complex, type 1 (MONDO:0008057), hereditary neoplastic syndrome (MONDO:0015356), Acrodysostosis 1 with or without hormone resistance (MONDO:0007044), familial atrial myxoma (MONDO:0009719), pigmented nodular adrenocortical disease, primary, 1 (MONDO:0012509), arrhythmogenic right ventricular dysplasia 10 (MONDO:0012434), Carney complex (MONDO:0015285), amelogenesis imperfecta type 1G (MONDO:0008771), endocrine pancreas disorder (MONDO:0001933), medulloblastoma (MONDO:0007959), (MONDO:0017240), primary pigmented nodular adrenocortical disease (MONDO:0015999), acrodysostosis (MONDO:0019797)

Orphanet (8): Carney complex (Orphanet:1359), Inherited cancer-predisposing syndrome (Orphanet:140162), OBSOLETE: Acrodysostosis with multiple hormone resistance (Orphanet:280651), OBSOLETE: Primary pigmented nodular adrenocortical disease (Orphanet:189439), Familial atrial myxoma (Orphanet:615), Enamel-renal syndrome (Orphanet:1031), Amelogenesis imperfecta-gingival hyperplasia syndrome (Orphanet:171836), Medulloblastoma (Orphanet:616)

HPO phenotypes

244 total (30 of 244 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000008	Abnormal morphology of female internal genitalia
HP:0000028	Cryptorchidism
HP:0000053	Macroorchidism
HP:0000055	Abnormal female external genitalia morphology
HP:0000080	Abnormality of reproductive system physiology
HP:0000098	Tall stature
HP:0000122	Unilateral renal agenesis
HP:0000135	Hypogonadism
HP:0000138	Ovarian cyst
HP:0000194	Open mouth
HP:0000199	Tongue nodules
HP:0000212	Gingival overgrowth
HP:0000225	Gingival bleeding
HP:0000238	Hydrocephalus
HP:0000248	Brachycephaly
HP:0000286	Epicanthus
HP:0000303	Mandibular prognathia
HP:0000311	Round face
HP:0000316	Hypertelorism
HP:0000327	Hypoplasia of the maxilla
HP:0000365	Hearing impairment
HP:0000421	Epistaxis
HP:0000431	Wide nasal bridge
HP:0000455	Broad nasal tip
HP:0000457	Depressed nasal ridge
HP:0000463	Anteverted nares
HP:0000486	Strabismus
HP:0000506	Telecanthus
HP:0000635	Blue irides

GWAS associations

6 associations (top):

Study	Trait	p-value
GCST008058_46	Estimated glomerular filtration rate	2.000000e-10
GCST008059_193	Estimated glomerular filtration rate	1.000000e-09
GCST008759_20	Intake of total sugars	4.000000e-06
GCST010866_157	Coronary artery disease	5.000000e-10
GCST010989_274	Body size at age 10	1.000000e-08
GCST90011900_151	Serum alkaline phosphatase levels	4.000000e-12

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0010158	sugar consumption measurement
EFO:0009819	comparative body size at age 10, self-reported
EFO:0004533	alkaline phosphatase measurement

MeSH disease descriptors (8)

Descriptor	Name	Tree numbers
D056733	Carney Complex	C04.557.450.565.550.312; C04.588.894.309.500; C14.280.459.500; C16.131.077.229; C16.131.831.108
D008527	Medulloblastoma	C04.557.465.625.600.380.515; C04.557.465.625.600.590.500; C04.557.470.670.380.515; C04.557.470.670.590.500; C04.557.580.625.600.380.515; C04.557.580.625.600.590.500
D009386	Neoplastic Syndromes, Hereditary	C04.700; C16.320.700
C538179	Acrodysostosis (supp.)
C538241	Amelogenesis imperfecta nephrocalcinosis (supp.)
C565707	Arrhythmogenic Right Ventricular Dysplasia, Familial, 10 (supp.)
C538262	Atrial myxoma, familial (supp.)
C566469	Pigmented Nodular Adrenocortical Disease, Primary, 1 (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4928 (SINGLE PROTEIN)

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

GtoPdb / IUPHAR curated pharmacology

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

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

Binding affinities (BindingDB)

1 measured of 1 human assays (1 total across all organisms); most potent 1 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value
8-[Fluo]-cAMP	KD	7.32 nM

PubChem BioAssay actives

5 with measured affinity, of 23 total; 1 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-[6-amino-9-(7-hydroxy-2-oxido-2-oxo-4a,6,7,7a-tetrahydro-4H-furo[3,2-d][1,3,2]dioxaphosphinin-6-yl)purin-8-yl]sulfanylethylcarbamothioylamino]-2-(3-hydroxy-6-oxoxanthen-9-yl)benzoic acid	1802504: 8-[Fluo]-cAMP Fluorescence Polarization Binding Assay from Article 10.1021/acs.biochem.6b01152: “Electrostatic Interactions as Mediators in the Allosteric Activation of Protein Kinase A RIa.”	kd	0.0067	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	decreases methylation, affects expression, decreases expression	4
Tretinoin	affects cotreatment, increases expression	3
Cadmium Chloride	increases abundance, increases expression, decreases expression	3
bisphenol A	affects expression, decreases expression	2
trichostatin A	affects cotreatment, increases expression	2
Cadmium	increases abundance, increases expression, decreases expression	2
Aflatoxin B1	affects cotreatment, increases expression, increases methylation	2
FR900359	decreases phosphorylation	1
bisphenol F	increases expression	1
triphenyl phosphate	affects expression	1
alpha-pinene	decreases expression, increases oxidation, increases abundance, affects cotreatment	1
tetrahydropalmatine	decreases expression	1
methylparaben	decreases expression	1
sodium arsenite	affects cotreatment, increases expression	1
ochratoxin A	increases expression	1
coumarin	increases phosphorylation	1
cupric oxide	decreases phosphorylation	1
1-nitropyrene	increases expression	1
quinoline	increases expression	1
methacrylaldehyde	affects cotreatment, decreases expression, increases oxidation, increases abundance	1
di-n-butylphosphoric acid	affects expression	1
perfluorooctane sulfonic acid	decreases expression	1
azoxystrobin	decreases expression	1
deguelin	decreases expression	1
fenpyroximate	decreases expression	1
4-chloro-N-((4-(1,1-dimethylethyl)phenyl)methyl)-3-ethyl-1-methyl-1H-pyrazole-5-carboxamide	decreases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
nutlin 3	affects cotreatment, increases secretion	1
ICG 001	decreases expression	1
bisphenol B	increases expression	1

ChEMBL screening assays

2 unique, capped per target: 2 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL4188744	Binding	Binding affinity to recombinant human full length PKA-R1alpha expressed in Escherichia coli BL21 DE3-RIL cells assessed as reduction in interaction with AKAP at 20 nM by fluorescence polarization analysis	Investigating PKA-RII specificity using analogs of the PKA:AKAP peptide inhibitor STAD-2. — Bioorg Med Chem

Cellosaurus cell lines

5 cell lines: 4 cancer cell line, 1 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B8N3	Abcam HCT 116 PRKAR1A KO	Cancer cell line	Male
CVCL_B9QC	Abcam A-549 PRKAR1A KO	Cancer cell line	Male
CVCL_D2H2	Abcam MCF-7 PRKAR1A KO	Cancer cell line	Female
CVCL_IM65	OVCAR-8 RIA	Cancer cell line	Female
CVCL_S899	CAR47	Transformed cell line	Female

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT01536717	PHASE4	SUSPENDED	Comparison of the Local Anaesthetics Articaine and Bupivacaine in Treatment of Acute Sternum Pain After Heart Surgery
NCT02875314	PHASE4	ACTIVE_NOT_RECRUITING	HeadStart4: Newly Diagnosed Children (<10 y/o) With Medulloblastoma and Other CNS Embryonal Tumors
NCT04081701	PHASE4	RECRUITING	68-Ga DOTATATE PET/MRI in the Diagnosis and Management of Somatostatin Receptor Positive CNS Tumors.
NCT00085735	PHASE3	COMPLETED	Comparison of Radiation Therapy Regimens in Combination With Chemotherapy in Treating Young Patients With Newly Diagnosed Standard-Risk Medulloblastoma
NCT00336024	PHASE3	COMPLETED	Combination Chemotherapy Followed By Peripheral Stem Cell Transplant in Treating Young Patients With Newly Diagnosed Supratentorial Primitive Neuroectodermal Tumors or High-Risk Medulloblastoma
NCT00392327	PHASE3	ACTIVE_NOT_RECRUITING	Chemotherapy and Radiation Therapy in Treating Young Patients With Newly Diagnosed, Previously Untreated, High-Risk Medulloblastoma/PNET
NCT01351870	PHASE3	COMPLETED	Hyperfractionated Versus Conventionally Fractionated Radiotherapy in Standard Risk Medulloblastoma (PNET4)
NCT07291102	PHASE3	NOT_YET_RECRUITING	Comparison of Neurocognitive Outcome in Two Standard Regimen for Treatment of Low-risk Medulloblastoma
NCT01560260	PHASE2	COMPLETED	Linsitinib in Treating Patients With Gastrointestinal Stromal Tumors
NCT02468193	PHASE2	COMPLETED	Study of Efficacy and Safety of Osilodrostat in Cushing’s Syndrome
NCT00031590	PHASE2	TERMINATED	Low-Dose Radiation and Combination Chemotherapy Following Surgery in Children With Newly Diagnosed Medulloblastoma
NCT00180791	PHASE2	UNKNOWN	High Risk Primitive Neuroectodermal (PNET) Brain Tumors in Childhood
NCT00180947	PHASE2	UNKNOWN	Study of Vinorelbine and Cyclofosfamide Among Patients With Refractory Tumours or in Relapse
NCT00404495	PHASE2	COMPLETED	Combination of Irinotecan and Temozolomide in Children With Brain Tumors.
NCT00407433	PHASE2	COMPLETED	Clinical Studies of Gemcitabine-Oxaliplatin
NCT00520936	PHASE2	COMPLETED	A Study of Pemetrexed in Children With Recurrent Cancer
NCT00601003	PHASE2	COMPLETED	Study of Nifurtimox to Treat Refractory or Relapsed Neuroblastoma or Medulloblastoma
NCT00840047	PHASE2	ACTIVE_NOT_RECRUITING	Methionine PET/CT Studies In Patients With Cancer
NCT01217437	PHASE2	COMPLETED	Temozolomide and Irinotecan Hydrochloride With or Without Bevacizumab in Treating Young Patients With Recurrent or Refractory Medulloblastoma or CNS Primitive Neuroectodermal Tumors
NCT01326104	PHASE2	COMPLETED	Vaccine Immunotherapy for Recurrent Medulloblastoma and Primitive Neuroectodermal Tumor
NCT01356290	PHASE2	RECRUITING	Antiangiogenic Therapy for Children With Recurrent Medulloblastoma, Ependymoma, ATRT and Rare CNS Tumors
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NCT02624388	PHASE2	TERMINATED	Study of Genistein in Pediatric Oncology Patients (UVA-Gen001)
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NCT03173950	PHASE2	COMPLETED	Immune Checkpoint Inhibitor Nivolumab in People With Recurrent Select Rare CNS Cancers
NCT03210714	PHASE2	ACTIVE_NOT_RECRUITING	Erdafitinib in Treating Patients With Relapsed or Refractory Advanced Solid Tumors, Non-Hodgkin Lymphoma, or Histiocytic Disorders With FGFR Mutations (A Pediatric MATCH Treatment Trial)
NCT03213652	PHASE2	ACTIVE_NOT_RECRUITING	Ensartinib in Treating Patients With Relapsed or Refractory Advanced Solid Tumors, Non-Hodgkin Lymphoma, or Histiocytic Disorders With ALK or ROS1 Genomic Alterations (A Pediatric MATCH Treatment Trial)
NCT03213665	PHASE2	COMPLETED	Tazemetostat in Treating Patients With Relapsed or Refractory Advanced Solid Tumors, Non-Hodgkin Lymphoma, or Histiocytic Disorders With EZH2, SMARCB1, or SMARCA4 Gene Mutations (A Pediatric MATCH Treatment Trial)
NCT03213678	PHASE2	COMPLETED	Samotolisib in Treating Patients With Relapsed or Refractory Advanced Solid Tumors, Non-Hodgkin Lymphoma, or Histiocytic Disorders With TSC or PI3K/MTOR Mutations (A Pediatric MATCH Treatment Trial)
NCT03213704	PHASE2	ACTIVE_NOT_RECRUITING	Larotrectinib in Treating Patients With Relapsed or Refractory Advanced Solid Tumors, Non-Hodgkin Lymphoma, or Histiocytic Disorders With NTRK Fusions (A Pediatric MATCH Treatment Trial)
NCT03233204	PHASE2	COMPLETED	Olaparib in Treating Patients With Relapsed or Refractory Advanced Solid Tumors, Non-Hodgkin Lymphoma, or Histiocytic Disorders With Defects in DNA Damage Repair Genes (A Pediatric MATCH Treatment Trial)