PRKACB

protein-coding

protein kinase cAMP-activated catalytic subunit beta, the group of AGC family kinases|Protein kinase A subunits

Gene summary

The protein encoded by this gene is a member of the serine/threonine protein kinase family. The encoded protein is a catalytic subunit of cAMP (cyclic AMP)-dependent protein kinase, which mediates signalling though cAMP. cAMP signaling is important to a number of processes, including cell proliferaton and differentiation. Multiple alternatively spliced transcript variants encoding distinct isoforms have been observed. [provided by RefSeq, Jul 2014]

MANE transcript

NM_182948.4

Inheritance

AR, AD

ClinVar variants

P:6U:48B:4

Top phenotype

Cardioacrofacial dysplasia 2

gnomAD constraint

pLI —, LoF o/e 0.23

Max pathogenic AF

—

Genomic locus

chr1:84,078,062-84,238,498

External References & Databases

Ensembl (ENSG00000142875)

Transcript & Mutation Effects

hg38 • Region Span ~160.4 kb

Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

Ellis-van Creveld syndromeSUPPORTIVE

Inheritance Pattern: AR

Disease ID:MONDO:0009162

Submitter: Orphanet

cardioacrofacial dysplasia 2MODERATE

Inheritance Pattern: AD

Disease ID:MONDO:0030877

Submitter: Ambry Genetics

cardioacrofacial dysplasia 2STRONG

Inheritance Pattern: AD

Disease ID:MONDO:0030877

Submitter: G2P

cardioacrofacial dysplasia 2STRONG

Inheritance Pattern: AD

Disease ID:MONDO:0030877

Submitter: Labcorp Genetics (formerly Invitae)

cardioacrofacial dysplasia 2STRONG

Inheritance Pattern: AD

Disease ID:MONDO:0030877

Submitter: PanelApp Australia

Clinical Genomic Database (CGD)

Cardioacrofacial dysplasia 2AD

Manifestation: Cardiovascular; Craniofacial; Dental; Musculoskeletal; Neurologic

Intervention: Cardiovascular

Rationale: Cardioacrofacial dysplasia 2 may include congenital cardiovascular anomalies (among other features), and awareness may allow prompt recognition and management of these issues

Comments: Mosaicism has been described in Cardioacrofacial dysplasia 2

Refs: 33058759

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to PRKACB variants in ClinVar

5 Conditions Cataloged

Inborn genetic diseasesTotal: 22

not providedTotal: 19

Cardioacrofacial dysplasia 2Total: 13

not specifiedTotal: 6

PRKACB-related disorderTotal: 5

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_182948.4. 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			3 clinvar	2 clinvar		5
missense	5 clinvar	1 clinvar	41 clinvar	2 clinvar		49
nonsense			1 clinvar			1
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			3 clinvar			3
Total	5	1	48	4	0	58

Highest pathogenic variant AF is 0.0000013811373

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 69 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_182948.4	RefSeq	NP_891993.1	10	MANE Select
ENST00000370685.7	Ensembl	ENSP00000359719.3	10	MANE Select
NM_001242857.3	RefSeq	NP_001229786.1	13	Standard
NM_001242858.3	RefSeq	NP_001229787.1	10	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Prion diseases - Homo sapiens (human)
Inflammatory mediator regulation of TRP channels - Homo sapiens (human)
Platelet activation - Homo sapiens (human)
Cortisol synthesis and secretion - Homo sapiens (human)
Relaxin signaling pathway - Homo sapiens (human)

Biological Process

neural tube closure
stimulatory C-type lectin receptor signaling pathway
renal water homeostasis
protein phosphorylation
signal transduction

Molecular Function

magnesium ion binding
protein serine/threonine kinase activity
cAMP-dependent protein kinase activity
protein binding
ATP binding

Cellular Component

nucleoplasm
centrosome
cytosol
plasma membrane
cAMP-dependent protein kinase complex

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000370685
Coding exons: 10
Length: 160437
Individuals with no LoFs: 125598
Homozygous LoFs: 0
Heterozygous LoFs: 8
Defined: 125606
p: 0.0000318

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	2.80	90	202	0.445	0.00000967	2614
Missense (PolyPhen)		16	65.811	0.24312		899
Synonymous	0.347	65	68.7	0.947	0.00000316	716
Loss of Function	3.35	5	22.0	0.228	0.00000107	285

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00013	0.00012	rare
Latino/Admixed American	0.000030	0.000029	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.000055	0.000054	rare
Finnish	0	0.0	absent
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: Mediates cAMP-dependent signaling triggered by receptor binding to GPCRs. PKA activation regulates diverse cellular processes such as cell proliferation, the cell cycle, differentiation and regulation of microtubule dynamics, chromatin condensation and decondensation, nuclear envelope disassembly and reassembly, as well as regulation of intracellular transport mechanisms and ion flux. Regulates the abundance of compartmentalized pools of its regulatory subunits through phosphorylation of PJA2 which binds and ubiquitinates these subunits, leading to their subsequent proteolysis (PubMed:12420224, PubMed:21423175). Phosphorylates GPKOW which regulates its ability to bind RNA (PubMed:21880142). {ECO:0000269|PubMed:12420224, ECO:0000269|PubMed:21423175, ECO:0000269|PubMed:21880142}.;

Recessive Scores

pRec: 0.341

Intolerance Scores

LoFtool: 0.434
RVIS EVS: -0.43
RVIS percentile EVS: 25.15

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.988

Gene Damage Prediction

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