PKIA

protein-coding

cAMP-dependent protein kinase inhibitor alpha

Gene summary

The protein encoded by this gene is a member of the cAMP-dependent protein kinase (PKA) inhibitor family. This protein was demonstrated to interact with and inhibit the activities of both C alpha and C beta catalytic subunits of the PKA. Alternatively spliced transcript variants encoding the same protein have been reported. [provided by RefSeq, Jul 2008]

Previous symbols:

PRKACN1

MANE transcript

NM_006823.4

Inheritance

—

ClinVar variants

U:4

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.52

Max pathogenic AF

—

Genomic locus

chr8:78,516,340-78,605,267

External References & Databases

Ensembl (ENSG00000171033)

Transcript & Mutation Effects

hg38 • Region Span ~88.9 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to PKIA variants in ClinVar

1 Conditions Cataloged

not specifiedTotal: 3

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_006823.4. 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						0
missense			3 clinvar			3
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			1 clinvar			1
Total	0	0	4	0	0	4

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 60 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_006823.4	RefSeq	NP_006814.1	2	MANE Select
ENST00000396418.7	Ensembl	ENSP00000379696.2	2	MANE Select
NM_181839.3	RefSeq	NP_862822.1	2	Standard
ENST00000352966.10	Ensembl	ENSP00000336552.5	2	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Alcoholism - Homo sapiens (human)
Myometrial Relaxation and Contraction Pathways
Calcium Regulation in the Cardiac Cell

Biological Process

negative regulation of transcription by RNA polymerase II
regulation of G2/M transition of mitotic cell cycle
negative regulation of protein import into nucleus
negative regulation of cAMP-dependent protein kinase activity

Molecular Function

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

Cellular Component

nucleus
cytoplasm

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000396418
Coding exons: 2
Length: 89129
Individuals with no LoFs: 0
Homozygous LoFs: 0
Heterozygous LoFs: 0
Defined: 0
p: 0.00

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.788	24	37.6	0.638	0.00000165	490
Missense (PolyPhen)		7	13.326	0.52528		178
Synonymous	0.977	9	13.6	0.663	5.81e-7	148
Loss of Function	0.617	1	1.92	0.520	7.86e-8	32

Population LoF Frequency

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

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Extremely potent competitive inhibitor of cAMP-dependent protein kinase activity, this protein interacts with the catalytic subunit of the enzyme after the cAMP-induced dissociation of its regulatory chains.;

Recessive Scores

pRec: 0.156

Intolerance Scores

RVIS EVS: 0.19
RVIS percentile EVS: 66.32

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.781

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Low	Low	Low
Primary Immunodeficiency	Low	Low	Low
Cancer	Low	Low	Low