PRKAR1B

protein-coding

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

Gene summary

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. [provided by RefSeq, Aug 2015]

MANE transcript

NM_001164760.2

Inheritance

ClinVar variants

P:10U:119B:36

Top phenotype

Marbach-Schaaf neurodevelopmental syndrome

gnomAD constraint

pLI —, LoF o/e 0.26

Max pathogenic AF

—

Genomic locus

chr7:549,197-727,650

External References & Databases

Ensembl (ENSG00000188191)

Transcript & Mutation Effects

hg38 • Region Span ~178.5 kb

Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

Marbach-Schaaf neurodevelopmental syndromeSTRONG

Inheritance Pattern: AD

Disease ID:MONDO:0859214

Submitter: Labcorp Genetics (formerly Invitae)

Marbach-Schaaf neurodevelopmental syndromeSTRONG

Inheritance Pattern: AD

Disease ID:MONDO:0859214

Submitter: PanelApp Australia

PRKAR1B-related neurodegenerative dementia with intermediate filamentsSUPPORTIVE

Inheritance Pattern: AD

Disease ID:MONDO:0018475

Submitter: Orphanet

Clinical Genomic Database (CGD)

Marbach-Schaaf neurodevelopmental syndromeAD

Manifestation: Craniofacial; Neurologic

Intervention: General

Rationale: 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

Refs: 33833410

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to PRKAR1B variants in ClinVar

9 Conditions Cataloged

Primary ciliary dyskinesiaTotal: 162

not providedTotal: 111

not specifiedTotal: 88

PRKAR1B-related disorderTotal: 27

Marbach-Schaaf neurodevelopmental syndromeTotal: 15

DNAAF5-related disorderTotal: 5

Primary ciliary dyskinesia 18Total: 2

Paediatric disordersTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001164760.2. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous			1 clinvar	23 clinvar	5 clinvar	29
missense	3 clinvar	5 clinvar	105 clinvar	7 clinvar	1 clinvar	121
nonsense		1 clinvar	3 clinvar			4
start loss			1 clinvar			1
frameshift			6 clinvar			6
splice donor/acceptor (+/-2bp)	1 clinvar		3 clinvar			4
Total	4	6	119	30	6	165

Highest pathogenic variant AF is 0.000015214397

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 103 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001164760.2	RefSeq	NP_001158232.1	10	MANE Select
ENST00000537384.6	Ensembl	ENSP00000440449.1	10	MANE Select
NM_001164758.2	RefSeq	NP_001158230.1	10	Standard
NM_001164759.1	RefSeq	NP_001158231.1	10	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Insulin signaling pathway - Homo sapiens (human)
miRs in Muscle Cell Differentiation
Myometrial Relaxation and Contraction Pathways
G Protein Signaling Pathways
Lipid Metabolism Pathway

Biological Process

renal water homeostasis
protein phosphorylation
blood coagulation
learning or memory
cGMP-mediated signaling

Molecular Function

cAMP-dependent protein kinase inhibitor activity
protein binding
cAMP-dependent protein kinase regulator activity
cAMP binding
protein kinase A catalytic subunit binding

Cellular Component

cytosol
plasma membrane
cAMP-dependent protein kinase complex
ciliary base
Schaffer collateral - CA1 synapse

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000406797
Coding exons: 10
Length: 178454
Individuals with no LoFs: 125741
Homozygous LoFs: 0
Heterozygous LoFs: 7
Defined: 125748
p: 0.0000278

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	2.08	171	267	0.641	0.0000188	2466
Missense (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

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00012	0.00012	rare
Latino/Admixed American	0	0.0	absent
Ashkenazi Jewish	0	0.0	absent
East Asian	0	0.0	absent
Finnish	0.000046	0.000046	rare
European (Non-Finnish)	0.000036	0.000035	rare
South Asian	0	0.0	absent
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Regulatory subunit of the cAMP-dependent protein kinases involved in cAMP signaling in cells. {ECO:0000269|PubMed:20819953}.;

Intolerance Scores

LoFtool: 0.0564
RVIS EVS: -1.11
RVIS percentile EVS: 6.78

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.859

Gene Damage Prediction

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