PRKAR1B

Summary

PRKAR1B (protein kinase cAMP-dependent type I regulatory subunit beta, HGNC:9390) is a protein-coding gene on chromosome 7p22.3, encoding cAMP-dependent protein kinase type I-beta regulatory subunit (P31321). Regulatory subunit of the cAMP-dependent protein kinases involved in cAMP signaling in cells.

The protein encoded by this gene is a regulatory subunit of cyclic AMP-dependent protein kinase A (PKA), which is involved in the signaling pathway of the second messenger cAMP. Two regulatory and two catalytic subunits form the PKA holoenzyme, disbands after cAMP binding. The holoenzyme is involved in many cellular events, including ion transport, metabolism, and transcription. Several transcript variants encoding the same protein have been found for this gene.

Source: NCBI Gene 5575 — RefSeq curated summary.

At a glance

• Gene–disease (curated): Marbach-Schaaf neurodevelopmental syndrome (Strong, GenCC) — +1 more curated relationship
• GWAS associations: 10
• Clinical variants (ClinVar): 186 total — 4 pathogenic, 3 likely-pathogenic
• Phenotypes (HPO): 62
• Druggable target: yes
• MANE Select transcript: NM_001164760

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:9390
Approved symbol	PRKAR1B
Name	protein kinase cAMP-dependent type I regulatory subunit beta
Location	7p22.3
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000188191
Ensembl biotype	protein_coding
OMIM	176911
Entrez	5575

Gene structure

Transcript identifiers

Ensembl transcripts: 44 — 40 protein_coding, 4 protein_coding_CDS_not_defined

ENST00000360274, ENST00000400758, ENST00000403562, ENST00000406797, ENST00000414568, ENST00000417852, ENST00000430040, ENST00000456696, ENST00000478198, ENST00000488474, ENST00000537384, ENST00000544935, ENST00000703504, ENST00000703505, ENST00000852399, ENST00000852400, ENST00000852401, ENST00000852402, ENST00000852403, ENST00000852404, ENST00000852405, ENST00000852406, ENST00000852407, ENST00000852408, ENST00000852409, ENST00000852410, ENST00000852411, ENST00000852412, ENST00000852413, ENST00000912932, ENST00000912933, ENST00000912934, ENST00000912935, ENST00000912936, ENST00000912937, ENST00000972090, ENST00000972091, ENST00000972092, ENST00000972093, ENST00000972094, ENST00000972095, ENST00000972096, ENST00000972097, ENST00000972098

RefSeq mRNA: 6 — MANE Select: NM_001164760 NM_001164758, NM_001164759, NM_001164760, NM_001164761, NM_001164762, NM_002735

CCDS: CCDS34579

Canonical transcript exons

ENST00000537384 — 11 exons

Exon	Start	End
ENSE00003653279	711329	711527
ENSE00003843845	727210	727281
ENSE00003890654	549198	550602
ENSE00003890874	606193	606239
ENSE00003890939	551389	551470
ENSE00003891745	579256	579377
ENSE00003892516	596146	596304
ENSE00003893095	677229	677320
ENSE00003894505	584508	584568
ENSE00003896062	680556	680726
ENSE00003896230	607391	607452

Expression profiles

Bgee: expression breadth ubiquitous, 243 present calls, max score 99.14.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 16.2075 / max 748.0319, expressed in 1756 samples.

FANTOM5 promoters (11 alternative TSS)

Promoter ID	TPM avg	Samples expressed
82371	5.9830	1648
82368	5.0115	576
82362	2.2051	263
82372	1.8818	718
82367	0.4117	217
82361	0.2869	52
82363	0.1548	87
82360	0.0995	36
82369	0.0984	51
82359	0.0444	31

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
Brodmann (1909) area 10	UBERON:0013541	99.14	gold quality
right frontal lobe	UBERON:0002810	98.90	gold quality
cingulate cortex	UBERON:0003027	98.40	gold quality
anterior cingulate cortex	UBERON:0009835	98.39	gold quality
prefrontal cortex	UBERON:0000451	98.29	gold quality
frontal pole	UBERON:0002795	98.22	gold quality
Brodmann (1909) area 9	UBERON:0013540	97.94	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	97.83	gold quality
frontal cortex	UBERON:0001870	97.55	gold quality
neocortex	UBERON:0001950	97.35	gold quality
amygdala	UBERON:0001876	97.29	gold quality
nucleus accumbens	UBERON:0001882	97.13	gold quality
right hemisphere of cerebellum	UBERON:0014890	97.07	gold quality
cerebellar hemisphere	UBERON:0002245	96.87	gold quality
cerebellar cortex	UBERON:0002129	96.85	gold quality
cerebral cortex	UBERON:0000956	96.36	gold quality
hypothalamus	UBERON:0001898	96.36	gold quality
lateral nuclear group of thalamus	UBERON:0002736	96.32	gold quality
cerebellum	UBERON:0002037	95.99	gold quality
telencephalon	UBERON:0001893	95.88	gold quality
cortical plate	UBERON:0005343	95.59	gold quality
forebrain	UBERON:0001890	95.40	gold quality
paraflocculus	UBERON:0005351	95.40	gold quality
brain	UBERON:0000955	95.11	gold quality
caudate nucleus	UBERON:0001873	95.06	gold quality
putamen	UBERON:0001874	95.06	gold quality
Brodmann (1909) area 46	UBERON:0006483	95.02	gold quality
temporal lobe	UBERON:0001871	95.01	gold quality
central nervous system	UBERON:0001017	94.99	gold quality
Ammon’s horn	UBERON:0001954	94.52	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	3.87

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

52 targeting PRKAR1B, 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-6825-5P	99.96	69.81	3431
HSA-MIR-185-3P	99.95	67.01	1743
HSA-MIR-4447	99.85	67.81	2900
HSA-MIR-6756-5P	99.82	67.97	2466
HSA-MIR-6763-5P	99.76	64.68	1767
HSA-MIR-3150A-3P	99.76	64.44	1640
HSA-MIR-4729	99.69	72.18	4233
HSA-MIR-6766-5P	99.68	67.70	2325
HSA-MIR-3175	99.65	66.30	2031
HSA-MIR-6132	99.60	65.83	1554
HSA-MIR-6836-5P	99.60	65.62	1538
HSA-MIR-4761-5P	99.51	66.69	804
HSA-MIR-486-3P	99.51	66.82	1901
HSA-MIR-1207-5P	99.49	69.11	2983
HSA-MIR-4688	99.48	64.68	828
HSA-MIR-6743-5P	99.48	63.60	721
HSA-MIR-6722-3P	99.45	67.62	1919
HSA-MIR-4284	99.36	65.25	1293
HSA-MIR-155-5P	99.35	70.16	1509
HSA-MIR-4505	99.27	67.81	2678
HSA-MIR-149-5P	99.25	67.16	1315
HSA-MIR-642A-3P	99.23	67.67	1258
HSA-MIR-642B-3P	99.23	67.67	1258
HSA-MIR-5787	99.22	67.86	2628
HSA-MIR-4263	99.18	69.25	2236
HSA-MIR-6510-5P	99.14	66.59	1081
HSA-MIR-491-5P	99.13	65.98	1468
HSA-MIR-4763-3P	99.10	67.83	2649
HSA-MIR-1909-3P	99.03	66.56	1662
HSA-MIR-331-3P	98.76	64.91	793

Literature-anchored findings (GeneRIF, showing 7)

• The paired-like homeodomain protein, Arix, mediates protein kinase A-stimulated dopamine beta-hydroxylase gene transcription through its phosphorylation status (PMID:11943777)
• 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)
• This study demonistrated that PRKAR1B mutation associated with a new neurodegenerative disorder with unique pathology. (PMID:24722252)
• No pathogenic PRKAR1B mutations were found in early onset familial dementia patients in a Dutch cohort. (PMID:25108559)
• Genomic and sequence variants of protein kinase A regulatory subunit type 1beta (PRKAR1B) in patients with adrenocortical disease and Cushing syndrome. (PMID:32895490)
• Variants in PRKAR1B cause a neurodevelopmental disorder with autism spectrum disorder, apraxia, and insensitivity to pain. (PMID:33833410)
• EIF4A3-induced circular RNA PRKAR1B promotes osteosarcoma progression by miR-361-3p-mediated induction of FZD4 expression. (PMID:34716310)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	prkar1b	ENSDARG00000103800
mus_musculus	Prkar1b	ENSMUSG00000025855
rattus_norvegicus	Prkar1b	ENSRNOG00000028733
drosophila_melanogaster	Pka-R1	FBGN0259243
caenorhabditis_elegans		WBGENE00002190

Paralogs (4): PRKAR2B (ENSG00000005249), PRKAR1A (ENSG00000108946), PRKAR2A (ENSG00000114302), CNBD1 (ENSG00000176571)

Protein

Protein identifiers

cAMP-dependent protein kinase type I-beta regulatory subunit — P31321 (reviewed: P31321)

All UniProt accessions (6): C9IZL8, C9J4C2, C9JR00, C9JSK5, P31321, H7BYW5

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 PRKX; regulates this cAMP-dependent protein kinase. Interacts with AKAP19; this interaction targets PRKAR1B to the plasma membrane.

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. Marbach-Schaaf neurodevelopmental syndrome (MASNS) [MIM:619680] An autosomal dominant neurodevelopmental disorder characterized by global developmental delay, speech delay, behavioral abnormalities, hypotonia, and movement disorders including dyspraxia, apraxia, and clumsiness. More variable features include high pain tolerance, sleep disturbances, and variable non-specific dysmorphic features. The disease is caused by variants affecting the gene represented in this entry.

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

RefSeq proteins (6): NP_001158230, NP_001158231, NP_001158232, NP_001158233, NP_001158234, NP_002726 (=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
IPR042818	RIbeta_DD	Domain
IPR050503	cAMP-dep_PK_reg_su-like	Family

Pfam: PF00027, PF02197

UniProt features (27 total): binding site 6, modified residue 6, sequence variant 3, helix 3, disulfide bond 2, region of interest 2, initiator methionine 1, chain 1, sequence conflict 1, turn 1, short sequence motif 1

Structure

Experimental structures (PDB)

3 structures.

PDB	Method	Resolution (Å)
4F9K	X-RAY DIFFRACTION	2.8
4DIN	X-RAY DIFFRACTION	3.7
9O7V	X-RAY DIFFRACTION	3.7

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P31321-F1	87.24	0.60

Functional residue map

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

Ligand- & substrate-binding residues (6): 335; 137–254; 202; 211; 255–381; 326

Post-translational modifications (6): 3, 21, 77, 83, 85, 97

Disulfide bonds (2): 18, 39

Function

Pathways and Gene Ontology

Reactome pathways

48 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-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
R-HSA-1643685	Disease
R-HSA-372790	Signaling by GPCR

MSigDB gene sets: 415 (showing top): GOBP_RESPONSE_TO_NITROGEN_COMPOUND, GOBP_REGULATION_OF_INFLAMMATORY_RESPONSE_TO_ANTIGENIC_STIMULUS, GOBP_COGNITION, GOBP_BEHAVIOR, GOBP_REGULATION_OF_PHOSPHORYLATION, GOBP_INFLAMMATORY_RESPONSE, GOBP_RESPONSE_TO_FLUID_SHEAR_STRESS, GOBP_CELLULAR_RESPONSE_TO_FLUID_SHEAR_STRESS, GOBP_REGULATION_OF_TRANSFERASE_ACTIVITY, GOBP_VESICLE_MEDIATED_TRANSPORT, REACTOME_GLUCAGON_SIGNALING_IN_METABOLIC_REGULATION, GOBP_CELLULAR_RESPONSE_TO_OXYGEN_CONTAINING_COMPOUND, BIOCARTA_NOS1_PATHWAY, BIOCARTA_SHH_PATHWAY, chr7p22

GO Biological Process (14): negative regulation of inflammatory response to antigenic stimulus (GO:0002862), renal water homeostasis (GO:0003091), adenylate cyclase-activating G protein-coupled receptor signaling pathway (GO:0007189), chemical synaptic transmission (GO:0007268), learning or memory (GO:0007611), cellular response to glucagon stimulus (GO:0071377), vascular endothelial cell response to laminar fluid shear stress (GO:0097700), regulation of synaptic vesicle cycle (GO:0098693), negative regulation of cAMP/PKA signal transduction (GO:0141162), positive regulation of long-term synaptic potentiation (GO:1900273), positive regulation of fear response (GO:1903367), positive regulation of excitatory postsynaptic potential (GO:2000463), regulation of protein phosphorylation (GO:0001932), modulation of chemical synaptic transmission (GO:0050804)

GO Molecular Function (6): cAMP-dependent protein kinase inhibitor activity (GO:0004862), cAMP-dependent protein kinase regulator activity (GO:0008603), cAMP binding (GO:0030552), protein kinase A catalytic subunit binding (GO:0034236), nucleotide binding (GO:0000166), protein binding (GO:0005515)

GO Cellular Component (12): cytoplasm (GO:0005737), multivesicular body (GO:0005771), cytosol (GO:0005829), plasma membrane (GO:0005886), cAMP-dependent protein kinase complex (GO:0005952), ciliary base (GO:0097546), Schaffer collateral - CA1 synapse (GO:0098685), hippocampal mossy fiber to CA3 synapse (GO:0098686), postsynapse (GO:0098794), glutamatergic synapse (GO:0098978), membrane (GO:0016020), synapse (GO:0045202)

Reactome top-level categories

Rollup of top-18 pathways:

Category	Pathways
Opioid Signalling	2
Anti-inflammatory response favouring Leishmania parasite infection	2
PKA-mediated phosphorylation of CREB	1
Glucagon signaling in metabolic regulation	1
Regulation of insulin secretion	1
Aquaporin-mediated transport	1
Post NMDA receptor activation events	1
Signaling by Hedgehog	1
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
PLC beta mediated events	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	5
synapse	3
cAMP-dependent protein kinase activity	2
inflammatory response to antigenic stimulus	1
regulation of inflammatory response to antigenic stimulus	1
negative regulation of inflammatory response	1
negative regulation of immune response	1
renal system process	1
multicellular organismal-level water homeostasis	1
adenylate cyclase-modulating G protein-coupled receptor signaling pathway	1
adenylate cyclase activator activity	1
anterograde trans-synaptic signaling	1
behavior	1
cognition	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
regulation of vesicle-mediated transport	1
synaptic vesicle cycle	1
cAMP/PKA signal transduction	1
regulation of cAMP/PKA signal transduction	1
negative regulation of intracellular signal transduction	1
positive regulation of synaptic transmission	1
long-term synaptic potentiation	1
regulation of long-term synaptic potentiation	1
fear response	1
positive regulation of response to stimulus	1
positive regulation of multicellular organismal process	1
regulation of fear response	1
positive regulation of signal transduction	1
excitatory postsynaptic potential	1
modulation of excitatory postsynaptic potential	1
protein phosphorylation	1
regulation of protein modification process	1
regulation of phosphorylation	1
chemical synaptic transmission	1
regulation of trans-synaptic signaling	1
cAMP-dependent protein kinase regulator activity	1
protein serine/threonine kinase inhibitor activity	1

Protein interactions and networks

STRING

2304 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PRKAR1B	CMYA5	Q8N3K9	757
PRKAR1B	PRKACB	P22694	738
PRKAR1B	PRKACG	P22612	722
PRKAR1B	PRKACA	P17612	701
PRKAR1B	PRKAR2A	P13861	506
PRKAR1B	FASN	P49327	493
PRKAR1B	DTNBP1	Q96EV8	492
PRKAR1B	PRKAR2B	P31323	487
PRKAR1B	WRN	Q14191	484
PRKAR1B	ACACA	Q13085	468
PRKAR1B	BMERB1	Q96MC5	448
PRKAR1B	MEF2A	Q02078	441
PRKAR1B	RPS6KB1	P23443	438
PRKAR1B	RPS6KA1	Q15418	434
PRKAR1B	PRKAG1	P54619	429

IntAct

340 interactions, top by confidence:

A	B	Type	Score
PRKACA	PRKAR1B	psi-mi:“MI:0915”(physical association)	0.890
PRKAR1A	PRKAR1B	psi-mi:“MI:0915”(physical association)	0.800
VAPB	FAM83G	psi-mi:“MI:0914”(association)	0.730
	PRKAR1A	psi-mi:“MI:0914”(association)	0.700
GUCA1A	PRKAR1B	psi-mi:“MI:0915”(physical association)	0.560
PRKAR1B	SAP30BP	psi-mi:“MI:0915”(physical association)	0.560
PRKAR1B	SHC3	psi-mi:“MI:0915”(physical association)	0.560
PRKAR1B	GNL3L	psi-mi:“MI:0915”(physical association)	0.560
PRKAR1B	DACH1	psi-mi:“MI:0915”(physical association)	0.560
PRKAR1B	GLIS2	psi-mi:“MI:0915”(physical association)	0.560
PRKAR1B	LENG1	psi-mi:“MI:0915”(physical association)	0.560
PRKAR1B	GPKOW	psi-mi:“MI:0915”(physical association)	0.560
ZNF35	PRKAR1B	psi-mi:“MI:0915”(physical association)	0.560
PRKAR1B	SMG9	psi-mi:“MI:0915”(physical association)	0.560
PRKAR1B	IGFN1	psi-mi:“MI:0915”(physical association)	0.560
PRKAR1B	ZNF410	psi-mi:“MI:0915”(physical association)	0.560
CDKN1A	PRKAR1B	psi-mi:“MI:0915”(physical association)	0.560
PRKAR1B	ZNF329	psi-mi:“MI:0915”(physical association)	0.560
PRKAR1B	SH2D4A	psi-mi:“MI:0915”(physical association)	0.560
PRKAR1B	CDC37	psi-mi:“MI:0915”(physical association)	0.560
PRKAR1B	RUNX1T1	psi-mi:“MI:0915”(physical association)	0.560
PRKAR1B	FAM161A	psi-mi:“MI:0915”(physical association)	0.560
PRKAR1B	AKAP14	psi-mi:“MI:0915”(physical association)	0.560
PRKAR1B	ZNF177	psi-mi:“MI:0915”(physical association)	0.560
PRKAR1B	DNAAF19	psi-mi:“MI:0915”(physical association)	0.560
PRKAR1B	EEF2KMT	psi-mi:“MI:0915”(physical association)	0.560
PRKAR1B	BOD1L2	psi-mi:“MI:0915”(physical association)	0.560
PRKAR1B	VEZF1	psi-mi:“MI:0915”(physical association)	0.560
AKAP7	PRKAR1B	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (221): PRKAR1B (Affinity Capture-MS), PRKAR1B (Affinity Capture-MS), PRKAR1B (Affinity Capture-MS), PRKAR1B (Affinity Capture-MS), PRKAR1B (Affinity Capture-MS), PRKAR1B (Affinity Capture-MS), PRKAR1B (Affinity Capture-MS), PRKAR1B (Affinity Capture-MS), PRKAR1B (Affinity Capture-MS), PRKAR1B (Affinity Capture-MS), PRKAR1B (Two-hybrid), AKAP1 (Two-hybrid), PRKAR1B (Affinity Capture-MS), PRKAR1B (Affinity Capture-MS), PRKAR1B (Affinity Capture-MS)

ESM2 similar proteins: A0A1L8EV45, C9WPN6, F1QGW6, F6RQL9, O73723, O77676, P00516, P0C605, P20461, P23258, P23330, P31321, P32392, P35250, P41091, P53033, P61157, P61158, P62482, P62483, P81795, P83887, P83888, Q05B83, Q0VCD2, Q13126, Q13303, Q13976, Q27955, Q2KHU8, Q2KJ81, Q2VIR3, Q32KM1, Q4V7C7, Q5R797, Q5R8R1, Q5ZHS1, Q5ZMS3, Q641P0, Q641W4

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

4 interactions.

A	Effect	B	Mechanism
PRKAR1B	“down-regulates activity”	PRKACA	binding
PRKAR1B	“down-regulates activity”	PRKACB	binding
“3’,5’-cyclic AMP”	“down-regulates activity”	PRKAR1B	“chemical inhibition”
PJA2	“down-regulates quantity by destabilization”	PRKAR1B	polyubiquitination

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 115 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	51.7×	9e-06
PKA activation	5	48.8×	9e-06
PKA-mediated phosphorylation of CREB	5	43.9×	1e-05
DARPP-32 events	5	36.6×	3e-05
Anti-inflammatory response favouring Leishmania parasite infection	5	30.3×	4e-05
Leishmania parasite growth and survival	5	30.3×	4e-05
Calmodulin induced events	5	29.3×	4e-05
CaM pathway	5	29.3×	4e-05

GO biological processes:

GO term	Partners	Fold	FDR
vascular endothelial cell response to laminar fluid shear stress	5	36.3×	2e-04
renal water homeostasis	5	25.3×	6e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	4
Likely pathogenic	3
Uncertain significance	106
Likely benign	27
Benign	15

Top pathogenic / likely-pathogenic (7)

Variant ID	HGVS	Classification
1329089	NM_001164760.2(PRKAR1B):c.500_501inv (p.Gln167Leu)	Pathogenic
2099042	NM_017802.4(DNAAF5):c.517_521dup (p.Leu175fs)	Pathogenic
3344452	NM_001164760.2(PRKAR1B):c.904G>A (p.Val302Met)	Pathogenic
941234	NM_017802.4(DNAAF5):c.246del (p.Arg83fs)	Pathogenic
1802230	NM_001164760.2(PRKAR1B):c.570G>A (p.Trp190Ter)	Likely pathogenic
2444586	NM_001164760.2(PRKAR1B):c.917G>A (p.Arg306Gln)	Likely pathogenic
3349891	NM_001164760.2(PRKAR1B):c.926A>C (p.Asn309Thr)	Likely pathogenic

SpliceAI

4246 predictions. Top by Δscore:

Variant	Effect	Δscore
7:550598:CTCCC:C	acceptor_gain	1.0000
7:550599:TCCC:T	acceptor_gain	1.0000
7:550600:CCC:C	acceptor_gain	1.0000
7:550600:CCCC:C	acceptor_gain	1.0000
7:550601:CC:C	acceptor_gain	1.0000
7:550601:CCC:C	acceptor_gain	1.0000
7:550602:CC:C	acceptor_gain	1.0000
7:550602:CCTG:C	acceptor_loss	1.0000
7:550603:C:CC	acceptor_gain	1.0000
7:550604:T:G	acceptor_loss	1.0000
7:551383:ACTC:A	donor_loss	1.0000
7:551384:CT:C	donor_loss	1.0000
7:551385:TCA:T	donor_loss	1.0000
7:551386:C:CG	donor_loss	1.0000
7:551387:A:AC	donor_gain	1.0000
7:551387:A:C	donor_loss	1.0000
7:551388:C:CC	donor_gain	1.0000
7:551466:GTGCC:G	acceptor_gain	1.0000
7:551467:TGCC:T	acceptor_gain	1.0000
7:551468:GCC:G	acceptor_gain	1.0000
7:551469:CC:C	acceptor_gain	1.0000
7:551469:CCC:C	acceptor_gain	1.0000
7:551469:CCCTG:C	acceptor_loss	1.0000
7:551470:CC:C	acceptor_gain	1.0000
7:551471:C:CC	acceptor_gain	1.0000
7:551472:T:A	acceptor_loss	1.0000
7:579254:A:AT	donor_loss	1.0000
7:579254:ACCT:A	donor_gain	1.0000
7:579255:C:A	donor_loss	1.0000
7:579255:CCT:C	donor_gain	1.0000

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000020798 (7:717858 C>CCCT), RS1000033060 (7:618851 C>G), RS1000036084 (7:561126 CACACAA>C), RS1000064263 (7:653693 G>C,T), RS1000066040 (7:648418 C>A,T), RS1000094680 (7:699220 G>A,T), RS1000107333 (7:615381 C>T), RS1000114608 (7:687304 A>C), RS1000122338 (7:727238 G>A), RS1000131981 (7:682057 A>G), RS1000135594 (7:633784 A>G), RS1000139067 (7:564712 C>T), RS1000149461 (7:585558 G>A,T), RS1000156338 (7:689138 CAG>C), RS1000187741 (7:690407 C>A,T)

Disease associations

OMIM: gene MIM:176911 | disease phenotypes: MIM:619680, MIM:244400, MIM:614874, MIM:610805

GenCC curated gene-disease

Disease	Classification	Inheritance
Marbach-Schaaf neurodevelopmental syndrome	Strong	Autosomal dominant
PRKAR1B-related neurodegenerative dementia with intermediate filaments	Supportive	Autosomal dominant

Mondo (6): Marbach-Schaaf neurodevelopmental syndrome (MONDO:0859214), primary ciliary dyskinesia (MONDO:0016575), congenital heart disease (MONDO:0005453), primary ciliary dyskinesia 18 (MONDO:0013940), congenital anomaly of kidney and urinary tract (MONDO:0019719), PRKAR1B-related neurodegenerative dementia with intermediate filaments (MONDO:0018475)

Orphanet (3): Marbach-Schaaf neurodevelopmental syndrome (Orphanet:692173), Primary ciliary dyskinesia (Orphanet:244), Renal or urinary tract malformation (Orphanet:93545)

HPO phenotypes

62 total (30 of 62 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000176	Submucous cleft hard palate
HP:0000219	Thin upper lip vermilion
HP:0000252	Microcephaly
HP:0000286	Epicanthus
HP:0000311	Round face
HP:0000341	Narrow forehead
HP:0000358	Posteriorly rotated ears
HP:0000403	Recurrent otitis media
HP:0000455	Broad nasal tip
HP:0000473	Torticollis
HP:0000483	Astigmatism
HP:0000565	Esotropia
HP:0000582	Upslanted palpebral fissure
HP:0000601	Hypotelorism
HP:0000718	Aggressive behavior
HP:0000719	Inappropriate behavior
HP:0000726	Dementia
HP:0000729	Autistic behavior
HP:0000736	Short attention span
HP:0000739	Anxiety
HP:0000741	Apathy
HP:0000750	Delayed speech and language development
HP:0001156	Brachydactyly
HP:0001182	Tapered finger
HP:0001250	Seizure
HP:0001263	Global developmental delay
HP:0001300	Parkinsonism
HP:0001319	Neonatal hypotonia
HP:0001337	Tremor

GWAS associations

10 associations (top):

Study	Trait	p-value
GCST004601_94	Red blood cell count	4.000000e-12
GCST004604_117	Hematocrit	8.000000e-14
GCST004615_43	Hemoglobin concentration	4.000000e-12
GCST007385_32	Plasma free amino acid levels	3.000000e-08
GCST007385_5	Plasma free amino acid levels	7.000000e-09
GCST010989_115	Body size at age 10	9.000000e-09
GCST012490_551	Femur bone mineral density x serum urate levels interaction	6.000000e-09
GCST90002383_470	Hematocrit	2.000000e-24
GCST90002384_70	Hemoglobin	4.000000e-23
GCST90002403_190	Red blood cell count	2.000000e-23

EFO canonical traits (8, from GWAS)

EFO ID	Trait name
EFO:0004305	erythrocyte count
EFO:0004348	hematocrit
EFO:0004509	hemoglobin measurement
EFO:0005134	amino acid measurement
EFO:0008534	tryptophan measurement
EFO:0009769	histidine measurement
EFO:0009819	comparative body size at age 10, self-reported
EFO:0004531	urate measurement

MeSH disease descriptors (4)

Descriptor	Name	Tree numbers
D002925	Ciliary Motility Disorders	C08.200; C09.150; C16.131.077.245.500; C16.320.184.500
D006330	Heart Defects, Congenital	C14.240.400; C14.280.400; C16.131.240.400
D007619	Kartagener Syndrome	C08.127.384.500; C08.200.531; C08.695.501; C09.150.531; C14.240.400.280.500; C14.280.400.280.500; C16.131.077.245.500.531; C16.131.240.400.280.500; C16.131.740.501; C16.131.810.250.500; C16.320.184.500.531; C16.320.480
C566906	Cakut (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL2320 (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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	decreases expression, increases expression	3
Benzo(a)pyrene	decreases expression, increases methylation, affects methylation	2
Tetrachlorodibenzodioxin	affects expression, increases expression	2
Tobacco Smoke Pollution	affects expression, decreases methylation	2
Aflatoxin B1	decreases expression, increases methylation	2
Particulate Matter	decreases reaction, increases expression, increases abundance	2
methyleugenol	decreases expression	1
triphenyl phosphate	affects expression	1
bisphenol A	affects cotreatment, decreases methylation	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
benzo(e)pyrene	increases methylation	1
potassium chromate(VI)	increases expression	1
aflatoxin B2	increases methylation	1
coumarin	increases phosphorylation	1
di-n-butylphosphoric acid	affects expression	1
perfluorooctane sulfonic acid	increases expression	1
CGP 52608	affects binding, increases reaction	1
2-palmitoylglycerol	increases expression	1
ICG 001	decreases expression	1
2-methyl-2H-pyrazole-3-carboxylic acid (2-methyl-4-o-tolylazophenyl)amide	decreases reaction, increases expression	1
jinfukang	increases expression	1
4-(4-((5-(4,5-dimethyl-2-nitrophenyl)-2-furanyl)methylene)-4,5-dihydro-3-methyl-5-oxo-1H-pyrazol-1-yl)benzoic acid	decreases expression	1
Temozolomide	increases expression	1
Arsenic Trioxide	decreases expression	1
Fulvestrant	affects cotreatment, decreases methylation	1
Air Pollutants	increases abundance, increases expression	1
Arsenic	affects methylation	1
Vehicle Emissions	decreases reaction, increases expression	1
Caffeine	decreases phosphorylation	1
Cisplatin	decreases expression	1

ChEMBL screening assays

1 unique, capped per target: 1 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL4188745	Binding	Binding affinity to recombinant human full length PKA-R1beta 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

2 cell lines: 1 cancer cell line, 1 induced pluripotent stem cell

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

Cellosaurus	Name	Category	Sex
CVCL_B2C3	Abcam HeLa PRKAR1B KO	Cancer cell line	Female
CVCL_E4Q5	KOLF2.1J PRKAR1B 0.2kbdel DEL/DEL	Induced pluripotent stem cell	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00668824	PHASE4	UNKNOWN	Improved Diagnosis of Congenital Heart Disease by Magnetic Resonance Imaging Using Vasovist
NCT01368705	PHASE4	COMPLETED	Nitrogen Balance in Infants After Post Cardiothoracic Surgery
NCT01619982	PHASE4	COMPLETED	Pre-operative Prophylaxis With Vancomycin and Cefazolin in Pediatric Cardiovascular Surgery Patients
NCT02122679	PHASE4	WITHDRAWN	Tranexamic Acid Effect on Platelet Aggregation Following Infant Cardiopulmonary Bypass
NCT02527811	PHASE4	UNKNOWN	Ulinastatin Injection in in Pediatric Patients Undergoing Open Heart Surgery
NCT03014700	PHASE4	COMPLETED	Fibrinogen Concentrate vs Cryoprecipitate
NCT03408340	PHASE4	TERMINATED	Paravertebral Nerve Blocks in Neonates
NCT03630796	PHASE4	UNKNOWN	Effect of Sevoflurane in Postoperative Troponin I Levels in Children Undergoing Congenital Heart Defects Surgery
NCT03667703	PHASE4	COMPLETED	Stress Ulcer Prophylaxis Versus Placebo in Critically Ill Infants With Congenital Heart Disease
NCT04453761	PHASE4	UNKNOWN	Thiamine Influenced on Substrate Energy Effectiveness in Indonesian Children Undergoing Cardiopulmonary Bypass
NCT06668389	PHASE4	RECRUITING	Sodium-Glucose Cotransporter 2 Inhibitors for Repaired Tetralogy of Fallot Patients for Enhancement of Cardio-Pulmonary Status Trial
NCT07499154	PHASE4	NOT_YET_RECRUITING	Perioperative Lidocaine for Lung Protection in Infants Undergoing Cardiac Surgery
NCT00000470	PHASE3	COMPLETED	Infant Heart Surgery: Central Nervous System Sequelae of Circulatory Arrest
NCT00000494	PHASE3	COMPLETED	Management of Patent Ductus in Premature Infants
NCT01134302	PHASE3	UNKNOWN	Hybrid Versus Norwood Management Strategies in Infants Undergoing Single Ventricle Palliation
NCT01607983	PHASE3	WITHDRAWN	Effects of Pulmonary Vasodilation Upon VA Coupling in Fontan Patients
NCT01662011	PHASE3	UNKNOWN	Application of Neurally Adjusted Ventilatory Assist to Children After Congenital Cardiac Surgery
NCT02320669	PHASE3	COMPLETED	Phase 3 Triiodothyronine Supplementation for Infants After Cardiopulmonary Bypass
NCT02615262	PHASE3	COMPLETED	Intraoperative Dexamethasone in Pediatric Cardiac Surgery
NCT03153137	PHASE3	COMPLETED	Clinical Study Assessing the Efficacy and Safety of Macitentan in Fontan-palliated Subjects
NCT03154476	PHASE3	COMPLETED	Role of Sildenafil for Fontan Associated Liver Disease (SiFALD) Study
NCT04536194	PHASE3	COMPLETED	Dopamine Versus Norepinephrine Under General Anesthesia
NCT04702373	PHASE3	ACTIVE_NOT_RECRUITING	Training in Exercise Activities and Motion for Growth (TEAM 4 Growth) RCT
NCT05049590	PHASE3	COMPLETED	Acute Normovolemic Hemodilution in Complex Cardiac Surgery
NCT06406517	PHASE3	UNKNOWN	Comparative Effectiveness of Gadopiclenol for Evaluation of Adult Congenital Heart Anatomy and Hemodynamics
NCT06693674	PHASE3	RECRUITING	Effect of Sacubitril-Valsartan on Cardiac Structure and Function
NCT06955260	PHASE3	NOT_YET_RECRUITING	SGLT2 Inhibition With Empagliflozin in Fontan Circulatory Failure
NCT02871778	PHASE2	COMPLETED	Clearing Lungs With ENaC Inhibition in Primary Ciliary Dyskinesia
NCT07318974	PHASE2	ACTIVE_NOT_RECRUITING	Melatonin Therapy for Improving ICSI Outcomes in Women With Diminished Ovarian Reserve
NCT00115375	PHASE2	COMPLETED	Platelet Aggregation Inhibition in Children on Clopidogrel (PICOLO)
NCT00350220	PHASE2	COMPLETED	Transfusion Strategies in Pediatric Cardiothoracic Surgery
NCT00374088	PHASE2	COMPLETED	N-Acetylcysteine in Neonatal Congenital Heart Surgery (INACT Study)
NCT00538785	PHASE2	COMPLETED	A Study to Evaluate MEDI-524 In Children With Hemodynamically Significant Congenital Heart Disease
NCT00770705	PHASE2	WITHDRAWN	Parenteral Phenoxybenzamine During Congenital Heart Disease Surgery
NCT00919945	PHASE2	TERMINATED	Impact of Early Enteral Feeding on Splanchnic Blood Flow After Surgery for Critical Heart Disease in the Newborn
NCT01063712	PHASE2	COMPLETED	Safety and Effectiveness of the Device Nit-Occlud® PDA-R
NCT01069510	PHASE2	COMPLETED	Spironolactone in Adult Congenital Heart Disease
NCT01189981	PHASE2	COMPLETED	Effect of eHealth Encouragements to Intensive Exercise in Adolescents With Congenital Heart Disease
NCT01330433	PHASE2	COMPLETED	Effects of CoSeal on Bleeding & Adhesions in Pediatric Heart Surgery
NCT01662037	PHASE2	COMPLETED	Bosentan Therapy in Children With Functional Single Ventricle