PRKAR1A Gene

The PRKAR1A gene (PRKAR1A is the acronym for Protein Kinase CAMP-Dependent Type I Regulatory Subunit Alpha) also referred to as the "Carney Compex Type 1 gene" or CNC1 gene, is a protein-coding gene located on chromosome 17q24.2. Several alternatively spliced transcript variants encoding two different isoforms have been observed.

The encoded protein, protein kinase A (PKA, also known as cAMP-dependent protein kinase) is involved in the regulation of lipid and glucose metabolism and is part of the signal transduction mechanism of certain GPCRs. PKA consists of two regulatory subunits and two catalytic subunits. PRKAR1A encodes one of the regulatory subunits.

cAMP causes dissociation of the inactive holoenzyme into a dimer of regulatory subunits bound to 4 cAMPs and 2 free monomeric catalytic subunits. This leads to activation of the protein kinase, which transmits the activation signal by phosphorylating various target proteins. Evidence shows that protein kinase A downregulates the expression of 7 liver genes in hepatoma x fibroblast hybrids.

Transfection of cells with PKA subunits resulted in changes in cell proliferation and cell cycle: a decrease in aneuploidy and G2/M in cells transfected with PRKAR1A and an increase in S-phase and aneuploidy in cells.

Mutations in the PRKAR1A gene cause Carney syndrome type 1 (also known as Carney complex). Furthermore, PRKAR1A can fuse with the RET protooncogene by gene rearrangement and form the thyroid tumor-specific chimeric oncogene PTC2.

Another disease associated with PRKAR1A is intracardiac myxoma.

1. Kamilaris CDC et al (2019) Carney Complex. Exp Clin Endocrinol Diabetes127:156-164
2. Saloustros E et al. (2017) Prkar1a gene knockout in the pancreas leads to neuroendocrine tumorigenesis. Endocr Relat Cancer 24:31-40.
3. Stratakis CA (2016) Carney complex: A familial lentiginosis predisposing to a variety of tumors. Rev Endocr Metab Disord 17: 367-371.