PRKAR1B

protein kinase cAMP-dependent type I regulatory subunit beta, the group of Protein kinase A subunits

Basic information

Region (hg38): 7:549196-727650

Links

ENSG00000188191 ∙ NCBI:5575 ∙ OMIM:176911 ∙ HGNC:9390 ∙ Uniprot:P31321 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• PRKAR1B-related neurodegenerative dementia with intermediate filaments (Supportive), mode of inheritance: AD
• Marbach-Schaaf neurodevelopmental syndrome (Strong), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Marbach-Schaaf neurodevelopmental syndrome	AD	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Craniofacial; Neurologic	33833410

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the PRKAR1B gene.

• Primary ciliary dyskinesia (123 variants)
• not provided (48 variants)
• Inborn genetic diseases (29 variants)
• Marbach-Schaaf neurodevelopmental syndrome (5 variants)
• not specified (5 variants)
• Primary ciliary dyskinesia 18 (2 variants)
• PRKAR1B-related neurodevelopmental disorder (1 variants)
• PRKAR1B-related condition (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the PRKAR1B gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			1	7	9	17
missense		2	24	1	1	28
nonsense		1				1
start loss			1			1
frameshift			1			1
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region	1		1	2	2	6
non coding	6		65	58	7	136
Total	6	3	92	66	17

Highest pathogenic variant AF is 0.0000135

Variants in PRKAR1B

This is a list of pathogenic ClinVar variants found in the PRKAR1B region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
7-550434-A-C		Marbach-Schaaf neurodevelopmental syndrome	Uncertain significance (Mar 22, 2022)
7-550447-T-C		not specified	Uncertain significance (Nov 02, 2023)
7-550481-G-T			Likely benign (Apr 25, 2018)
7-550511-G-A		not specified • PRKAR1B-related disorder	Benign (Aug 02, 2019)
7-550542-A-AG			Uncertain significance (Mar 18, 2022)
7-550559-G-A		PRKAR1B-related disorder	Benign/Likely benign (Nov 11, 2019)
7-550561-C-T		not specified	Uncertain significance (Aug 04, 2022)
7-550562-A-G		not specified • PRKAR1B-related disorder	Benign (Mar 05, 2019)
7-550568-C-T			Benign (May 13, 2018)
7-550572-C-T			Uncertain significance (Jan 01, 2022)
7-550573-G-A		PRKAR1B-related neurodevelopmental disorder • Marbach-Schaaf neurodevelopmental syndrome	Pathogenic/Likely pathogenic (Feb 01, 2024)
7-550578-C-T		PRKAR1B-related disorder	Likely benign (Nov 03, 2023)
7-550592-T-C		not specified • PRKAR1B-related disorder	Benign (Aug 02, 2019)
7-550607-G-C			Uncertain significance (Nov 11, 2022)
7-550610-T-G		not specified • PRKAR1B-related disorder	Benign (Aug 02, 2019)
7-551390-G-A		PRKAR1B-related disorder	Likely benign (Dec 31, 2019)
7-551419-C-T		PRKAR1B-related disorder	Uncertain significance (Feb 18, 2023)
7-551425-C-T		not specified	Uncertain significance (Jun 23, 2023)
7-551426-G-A			Benign (Dec 31, 2019)
7-551429-C-T			Benign (Dec 31, 2019)
7-551445-C-T			Likely pathogenic (Mar 13, 2023)
7-551448-C-T		not specified	Uncertain significance (Dec 16, 2022)
7-551449-G-A		Marbach-Schaaf neurodevelopmental syndrome	Uncertain significance (Apr 04, 2024)
7-551459-G-A			Benign (Dec 31, 2019)
7-551465-G-A			Benign (Jan 19, 2018)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
PRKAR1B	protein_coding	protein_coding	ENST00000406797	10	178454

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.179	0.820	125741	0	7	125748	0.0000278

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	2.08	171	267	0.641	0.0000188	2466
Missense in Polyphen		53	106.76	0.49644		901
Synonymous	-0.615	125	117	1.07	0.00000900	754
Loss of Function	3.05	5	19.5	0.256	8.31e-7	229

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000123	0.000123
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.0000465	0.0000462
European (Non-Finnish)	0.0000365	0.0000352
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Regulatory subunit of the cAMP-dependent protein kinases involved in cAMP signaling in cells. {ECO:0000269|PubMed:20819953}.
• Pathway: Insulin signaling pathway - Homo sapiens (human);miRs in Muscle Cell Differentiation;Myometrial Relaxation and Contraction Pathways;G Protein Signaling Pathways;Lipid Metabolism Pathway;Liver steatosis AOP;Calcium Regulation in the Cardiac Cell;Sudden Infant Death Syndrome (SIDS) Susceptibility Pathways;Signaling by GPCR;Signal Transduction;mechanism of gene regulation by peroxisome proliferators via ppara;phospholipase c-epsilon pathway;gata3 participate in activating the th2 cytokine genes expression;repression of pain sensation by the transcriptional regulator dream;transcription factor creb and its extracellular signals;regulation of ck1/cdk5 by type 1 glutamate receptors;nitric oxide signaling pathway;stathmin and breast cancer resistance to antimicrotubule agents;cystic fibrosis transmembrane conductance regulator (cftr) and beta 2 adrenergic receptor (b2ar) pathway;regulation of bad phosphorylation;transcription regulation by methyltransferase of carm1;activation of csk by camp-dependent protein kinase inhibits signaling through the t cell receptor;mcalpain and friends in cell motility;chrebp regulation by carbohydrates and camp;signaling pathway from g-protein families;how progesterone initiates the oocyte maturation;attenuation of gpcr signaling;activation of camp-dependent protein kinase pka;Glucagon signaling in metabolic regulation;GPCR Dopamine D1like receptor;Factors involved in megakaryocyte development and platelet production;GPCR Adenosine A2A receptor;GPCR signaling-cholera toxin;Hedgehog;Metabolism;PKA activation;PKA-mediated phosphorylation of CREB;Calmodulin induced events;CaM pathway;Transport of small molecules;Glucagon-like Peptide-1 (GLP1) regulates insulin secretion;Regulation of insulin secretion;actions of nitric oxide in the heart;Hedgehog ,off, state;DARPP-32 events;IL-7 signaling;GPCR signaling-G alpha s PKA and ERK;Signaling by Hedgehog;TGF_beta_Receptor;Hemostasis;DAG and IP3 signaling;JAK STAT pathway and regulation;EPO signaling;Ca-dependent events;PLC beta mediated events;G-protein mediated events;Opioid Signalling;G alpha (i) signalling events;PKA activation in glucagon signalling;Vasopressin regulates renal water homeostasis via Aquaporins;Aquaporin-mediated transport;Integration of energy metabolism;VEGF;GPCR downstream signalling;Intracellular signaling by second messengers;Alpha4 beta1 integrin signaling events (Consensus)

Intolerance Scores

• loftool: 0.0564
• rvis_EVS: -1.11
• rvis_percentile_EVS: 6.78

Haploinsufficiency Scores

• hipred: Y
• hipred_score: 0.763
• ghis: 0.625

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.859

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Prkar1b
• Phenotype: behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); immune system phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan)

Gene ontology

• Biological process: renal water homeostasis;protein phosphorylation;blood coagulation;learning or memory;cGMP-mediated signaling;activation of protein kinase A activity;modulation of chemical synaptic transmission;cellular response to glucagon stimulus;regulation of synaptic vesicle cycle;negative regulation of cAMP-dependent protein kinase activity
• Cellular component: cytosol;plasma membrane;cAMP-dependent protein kinase complex;ciliary base;Schaffer collateral - CA1 synapse;hippocampal mossy fiber to CA3 synapse;glutamatergic synapse
• Molecular function: cAMP-dependent protein kinase inhibitor activity;protein binding;cAMP-dependent protein kinase regulator activity;cAMP binding;protein kinase A catalytic subunit binding;3',5'-cyclic-GMP phosphodiesterase activity