PRKAR1B

Chr 7AD

protein kinase cAMP-dependent type I regulatory subunit beta

Also known as: MASNS, PRKAR1

NCBI Gene: 5575 ENSG00000188191 UniProt: P31321 OMIM: 176911

The protein is a regulatory subunit of cyclic AMP-dependent protein kinase A (PKA) that controls cAMP signaling pathways involved in ion transport, metabolism, and transcription. Mutations cause Marbach-Schaaf neurodevelopmental syndrome with autosomal dominant inheritance. The gene shows moderate constraint against loss-of-function variants (LOEUF 0.538), suggesting some tolerance to protein-truncating mutations.

GeneReviews OMIM ResearchSummary from RefSeq, OMIM, UniProt

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]

GeneReviews OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Marbach-Schaaf neurodevelopmental syndromeMIM #619680

Clinical highlights

Gene–disease validity

Not independently assessedOMIM lists Marbach-Schaaf neurodevelopmental syndrome; 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

0.54

LOEUF

Multiple*

Mechanism· predicted

📖

GeneReview available — PRKAR1B

Authoritative clinical overview · Recommended first read

Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Moderate LoF intolerance

LoF Constraint?

0.54LOEUF

pLI 0.179

Z-score 3.05

OE 0.26 (0.13–0.54)

Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?

2.08Z-score

OE missense 0.64 (0.56–0.73)

171 obs / 266.6 exp

Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios?

LoF OE?0.26 (0.13–0.54)

0≤0.351.4

Missense OE?0.64 (0.56–0.73)

0≤0.61.4

Synonymous OE?1.07

0≤1.21.6

LoF obs/exp: 5 / 19.5Missense obs/exp: 171 / 266.6Syn Z: -0.62

Background carrier burden — how many people carry a rare variant somewhere in PRKAR1B?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 110

503 rare PASS variants

Rare truncating (LoF)

1 in 2,500

72 rare PASS variants

Rare synonymous (reference)

1 in 88

289 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for PRKAR1B. 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 130	1 in 4,800
South Asian	~43k	1 in 210	1 in 3,100
Remaining (unassigned)	~30k	1 in 95	1 in 6,000
European (Finnish)	~27k	1 in 120	1 in 1,300
Admixed American	~22k	1 in 110	≈ 1 in 7,600
African / African American	~21k	1 in 130	1 in 1,700
East Asian	~20k	1 in 110	1 in 760
Ashkenazi Jewish	~13k	1 in 390	1 in 1,700
Middle Eastern	~2,884	1 in 110	≈ 1 in 2,900

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): All 10 coding exons well covered in gnomAD exomes and genomes.? see exons ↓