PRKAR1B

Chr 7

protein kinase cAMP-dependent type I regulatory subunit beta

Also known as: MASNS, PRKAR1

NCBI Gene: 5575ENSG00000188191UniProt: P31321

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]

Primary Disease Associations & Inheritance

UniProtMarbach-Schaaf neurodevelopmental syndrome
83
ClinVar variants
5
Pathogenic / LP
0.18
pLI score
0
Active trials
Clinical Summary— PRKAR1B
⚡
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.26) despite low pLI — interpret in context.
📋
ClinVar Variants
5 Pathogenic / Likely Pathogenic· 60 VUS of 83 total submissions
Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Moderate LoF intolerance
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
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?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
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?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.26 (0.13–0.54)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.64 (0.56–0.73)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.07
0≤1.21.6
LoF obs/exp: 5 / 19.5Missense obs/exp: 171 / 266.6Syn Z: -0.62

ClinVar Variant Classifications

83 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic5
VUS60
Likely Benign17
Benign1
5
Pathogenic
60
VUS
17
Likely Benign
1
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
2
0
3
0
5
Likely Pathogenic
0
0
0
0
0
VUS
0
55
5
0
60
Likely Benign
0
0
3
14
17
Benign
0
0
0
1
1
Total255111583

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

PRKAR1B · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Gene2Phenotype Curations

PRKAR1B-related developmental disorder

moderate
ADUndeterminedAltered Gene Product Structure
Dev. Disorders
G2P ↗
missense variantinframe deletioninframe insertion

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype

OMIM

No OMIM entries found.

📖
GeneReview available — PRKAR1B
Authoritative clinical overview · NCBI Bookshelf · Recommended first read
Open GeneReview ↗
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
A mutation in the PRKAR1B gene drives pathological mechanisms of neurodegeneration across species.
Benjamin-Zukerman T et al.·Brain
2024Functional
Genomic and sequence variants of protein kinase A regulatory subunit type 1β (PRKAR1B) in patients with adrenocortical disease and Cushing syndrome.
Drougat L et al.·Genet Med
2021Cohort
Variants in PRKAR1B cause a neurodevelopmental disorder with autism spectrum disorder, apraxia, and insensitivity to pain.
Marbach F et al.·Genet Med
2021
PRKAR1B mutation associated with a new neurodegenerative disorder with unique pathology.
Wong TH et al.·Brain
2014
Mutation frequency of PRKAR1B and the major familial dementia genes in a Dutch early onset dementia cohort.
Cohn-Hokke PE et al.·J Neurol
2014Cohort
Phenotypic characterization of seven individuals with Marbach-Schaaf neurodevelopmental syndrome.
Marbach F et al.·Am J Med Genet A
2022
PRKAR1B as an oncogenic biomarker for diagnostic and prognostic stratification of tumor immunity, proliferation, and migration in head and neck squamous cell carcinoma.
Zhao P et al.·Front Immunol
2026
Expansion of the Phenotypic and Genotypic Spectrum for PRKAR1B -Related Marbach-Schaaf Neurodevelopmental Syndrome: A Case Series.
Burkart S et al.·Clin Genet
2026Case report
A Novel PRKAR1B-BRAF Fusion in Gastrointestinal Stromal Tumor Guides Adjuvant Treatment Decision-Making During Pregnancy.
Charo LM et al.·J Natl Compr Canc Netw
2018Case report
Identification of Methylation Signatures and Rules for Sarcoma Subtypes by Machine Learning Methods.
Ren J et al.·Biomed Res Int
2022
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools