PRKACB

Chr 1ADSomatic

protein kinase cAMP-activated catalytic subunit beta

Also known as: CAFD2, PKA C-beta, PKACB

NCBI Gene: 5567 ENSG00000142875 UniProt: P22694 OMIM: 176892

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.

GeneReviews OMIM ResearchSummary from RefSeq, OMIM, UniProt

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]

GeneReviews OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Cardioacrofacial dysplasia 2MIM #619143

ADSomatic

Clinical highlights

Gene–disease validity

Not independently assessedOMIM lists Cardioacrofacial dysplasia 2; no ClinGen or GenCC tier

Interpreting a novel variant

This gene is strongly intolerant of loss-of-function variation in the population, so LoF variants warrant close attention. No curated mechanism annotation is available — see the mechanism card for the computational prediction and its caveats.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.48

LOEUF

Multiple*

Mechanism· predicted

📖

GeneReview available — PRKACB

Authoritative clinical overview · Recommended first read

Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Moderate LoF intolerance

LoF Constraint?

0.48LOEUF

pLI 0.351

Z-score 3.35

OE 0.23 (0.12–0.48)

Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?

2.80Z-score

OE missense 0.45 (0.37–0.53)

90 obs / 202.2 exp

Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios?

LoF OE?0.23 (0.12–0.48)

0≤0.351.4

Missense OE?0.45 (0.37–0.53)

0≤0.61.4

Synonymous OE?0.95

0≤1.21.6

LoF obs/exp: 5 / 22.0Missense obs/exp: 90 / 202.2Syn Z: 0.35

Background carrier burden — how many people carry a rare variant somewhere in PRKACB?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 120

416 rare PASS variants

Rare truncating (LoF)

1 in 1,900

75 rare PASS variants

Rare synonymous (reference)

1 in 490

179 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for PRKACB. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 150	1 in 2,000
South Asian	~43k	1 in 440	1 in 1,400
Remaining (unassigned)	~30k	1 in 100	1 in 1,300
European (Finnish)	~27k	1 in 720	≈ 1 in 6,500
Admixed American	~22k	1 in 120	1 in 1,000
African / African American	~21k	1 in 240	1 in 1,500
East Asian	~20k	1 in 240	1 in 2,000
Ashkenazi Jewish	~13k	1 in 250	≈ 1 in 12,000
Middle Eastern	~2,884	1 in 190	≈ 1 in 940

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): 9 of 10 coding exons well covered in gnomAD exomes; exon 5 marginal. Genomes: all 10.? see exons ↓