PRKACB
Chr 1ADSomaticprotein kinase cAMP-activated catalytic subunit beta
Also known as: CAFD2, PKA C-beta, PKACB
The protein is a catalytic subunit of cAMP-dependent protein kinase that mediates cAMP signaling to regulate cellular processes including proliferation, differentiation, cell cycle progression, and intracellular transport. Mutations cause cardioacrofacial dysplasia 2, which follows autosomal dominant inheritance with somatic mosaicism reported. The gene is moderately constrained against loss-of-function variants (LOEUF 0.479), and the condition affects cardiac and craniofacial development.
Primary Disease Associations & Inheritance
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Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
More LoF-intolerant than ~75% of genes
Moderately missense-constrained (top ~2.5%)
This gene has evidence for multiple mechanisms of pathogenicity (dominant-negative and gain-of-function). Both the Badonyi & Marsh prediction and the broader genomic evidence point to dominant-negative as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.
Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.
Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.
ClinVar Variant Classifications
100 submitted variants in ClinVar
Classification Summary
Curated Variants Distribution
Classified variants from ClinVar · 5 ACMG categories
| Classification | LoF | Missense + Inframe | Non-coding | Synonymous | Total |
|---|---|---|---|---|---|
Pathogenic | 0 | 5 | 14 | 0 | 19 |
Likely Pathogenic | 0 | 1 | 2 | 0 | 3 |
VUS | 1 | 36 | 7 | 0 | 44 |
Likely Benign | 0 | 2 | 4 | 2 | 8 |
Benign | 0 | 0 | 1 | 0 | 1 |
Conflicting | — | 1 | |||
| Total | 1 | 44 | 28 | 2 | 76 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
PRKACB · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
External Resources
Links to major genomics databases and tools
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
No active trials found for this gene.
Search ClinicalTrials.gov →External Resources
Links to major genomics databases and tools