PRKAR1A
Protein Kinase cAMP-Dependent Type I Regulatory Subunit Alpha
Gene Information Card
| Symbol | PRKAR1A |
|---|---|
| Full Name | Protein Kinase cAMP-Dependent Type I Regulatory Subunit Alpha |
| Gene Type | Protein coding |
| Chromosomal Location | 17q24.2 |
| NCBI Gene ID | 5573 ncbi.nlm.nih.gov/gene/5573 |
| Ensembl ID | ENSG00000108946 |
| UniProt ID | P10644 |
| OMIM ID | 188830 |
| HGNC ID | 9388 |
| Aliases | PRKAR1, TSE1, CNC, CAR, PKR1, ADOHR |
Description
PRKAR1A encodes the type I alpha regulatory subunit of cAMP-dependent protein kinase (PKA). This subunit binds cAMP and regulates PKA activity, playing a critical role in signal transduction pathways controlling cell growth, differentiation, and metabolism. Loss-of-function mutations in PRKAR1A are associated with Carney complex, a familial multiple neoplasia syndrome.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Carney complex (CNC) | Loss-of-function mutations lead to dysregulated PKA activity and tumorigenesis | OMIM #160980 |
| Primary pigmented nodular adrenocortical disease (PPNAD) | Inactivating mutations cause adrenal hyperplasia and Cushing syndrome | OMIM #610489 |
| Acrodysostosis | Dominant-negative mutations impair cAMP signaling | OMIM #101800 |
| Thyroid adenoma | Somatic mutations contribute to PKA activation | COSMIC |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 12.5 | Medium |
| Heart | 10.2 | Medium |
| Adrenal gland | 8.9 | Medium |
| Testis | 7.3 | Low |
| Thyroid | 6.1 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK293 | 15.0 | High expression |
| HeLa | 12.3 | High expression |
| MCF7 | 9.8 | Medium expression |
| A549 | 7.5 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.491_492delTG | Frameshift deletion | Rare | Loss of function, Carney complex |
| c.709C>T (p.Arg237*) | Nonsense | Rare | Premature truncation, Carney complex |
| c.1A>G (p.Met1?) | Missense | Rare | Initiation codon loss, Carney complex |
| c.892G>A (p.Gly298Arg) | Missense | Rare | Dominant-negative, acrodysostosis |
Mutation functional classification
Loss of Function (LOF)
Most Carney complex mutations result in haploinsufficiency or complete loss of regulatory subunit function, leading to increased PKA activity.
Gain of Function (GOF)
Not commonly described; gain-of-function is not a typical mechanism for PRKAR1A.
Dominant Negative (DN)
Mutations in the cAMP-binding domains (e.g., p.Gly298Arg) can act as dominant-negative, impairing holoenzyme formation and causing acrodysostosis.
View complete mutation data：
Gene Ontology (GO)
| • cAMP-dependent protein kinase regulator activity (GO:0008605) | • protein kinase A catalytic subunit binding (GO:0043422) |
| • cAMP binding (GO:0030552) | • regulation of protein kinase A signaling (GO:0010737) |
Pathways
• cAMP/PKA signaling pathway (Reactome R-HSA-163615)
• PKA-mediated phosphorylation (Reactome R-HSA-111933)
Protein Summary
The PRKAR1A protein (P10644) is a 381-amino acid regulatory subunit of PKA type I. It contains two cAMP-binding domains and an N-terminal dimerization/docking domain. Upon cAMP binding, the regulatory subunit releases the catalytic subunits, enabling phosphorylation of downstream targets. The protein is ubiquitously expressed and is critical for hormonal signaling.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| PRKAR1A (p.N332K) Point Mutation in HAP1 Cell Line | EDC03584 | Human | 5573 | Details Get a Quote |
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