Gene: PRKAR1A

Alternate names for this Gene: ACRDYS1|ADOHR|CAR|CNC|CNC1|PKR1|PPNAD1|PRKAR1|TSE1

Gene Summary: cAMP is a signaling molecule important for a variety of cellular functions. cAMP exerts its effects by activating the cAMP-dependent protein kinase, which transduces the signal through phosphorylation of different target proteins. The inactive kinase holoenzyme is a tetramer composed of two regulatory and two catalytic subunits. cAMP causes the dissociation of the inactive holoenzyme into a dimer of regulatory subunits bound to four cAMP and two free monomeric catalytic subunits. Four different regulatory subunits and three catalytic subunits have been identified in humans. This gene encodes one of the regulatory subunits. This protein was found to be a tissue-specific extinguisher that down-regulates the expression of seven liver genes in hepatoma x fibroblast hybrids. Mutations in this gene cause Carney complex (CNC). This gene can fuse to the RET protooncogene by gene rearrangement and form the thyroid tumor-specific chimeric oncogene known as PTC2. A nonconventional nuclear localization sequence (NLS) has been found for this protein which suggests a role in DNA replication via the protein serving as a nuclear transport protein for the second subunit of the Replication Factor C (RFC40). Several alternatively spliced transcript variants encoding two different isoforms have been observed.

Gene is located in Chromosome: 17

Location in Chromosome : 17q24.2

Description of this Gene: protein kinase cAMP-dependent type I regulatory subunit alpha

Type of Gene: protein-coding

rs1555814719 in PRKAR1A gene and ACRODYSOSTOSIS 1 WITH OR WITHOUT HORMONE RESISTANCE PMID 22723333 2012 PRKAR1A mutation affecting cAMP-mediated G protein-coupled receptor signaling in a patient with acrodysostosis and hormone resistance.

PMID 26405036 2015 Functional Characterization of PRKAR1A Mutations Reveals a Unique Molecular Mechanism Causing Acrodysostosis but Multiple Mechanisms Causing Carney Complex.

PMID 23425300 2013 Novel mutations of the PRKAR1A gene in patients with acrodysostosis.

PMID 22464252 2012 Exome sequencing identifies PDE4D mutations in acrodysostosis.

PMID 22464250 2012 Exome sequencing identifies PDE4D mutations as another cause of acrodysostosis.

PMID 21651393 2011 Recurrent PRKAR1A mutation in acrodysostosis with hormone resistance.

PMID 23043190 2012 PRKAR1A and PDE4D mutations cause acrodysostosis but two distinct syndromes with or without GPCR-signaling hormone resistance.

rs727503379 in PRKAR1A gene and Carney Complex PMID 10974026 2000 Mutations in the protein kinase A R1alpha regulatory subunit cause familial cardiac myxomas and Carney complex.

rs137853303 in PRKAR1A gene and Carney Complex, Type 1 PMID 18241045 2008 In vitro functional studies of naturally occurring pathogenic PRKAR1A mutations that are not subject to nonsense mRNA decay.

PMID 15371594 2004 Comparative PRKAR1A genotype-phenotype analyses in humans with Carney complex and prkar1a haploinsufficient mice.

PMID 22785148 2012 An unusual presentation of Carney complex with diffuse primary pigmented nodular adrenocortical disease on one adrenal gland and a nonpigmented adrenocortical adenoma and focal primary pigmented nodular adrenocortical disease on the other.

PMID 26405036 2015 Functional Characterization of PRKAR1A Mutations Reveals a Unique Molecular Mechanism Causing Acrodysostosis but Multiple Mechanisms Causing Carney Complex.

PMID 25394175 2015 A practice guideline from the American College of Medical Genetics and Genomics and the National Society of Genetic Counselors: referral indications for cancer predisposition assessment.

PMID 23323113 2012 Novel Mutation in PRKAR1A in Carney Complex.

PMID 11115848 2000 Genetic heterogeneity and spectrum of mutations of the PRKAR1A gene in patients with the carney complex.

PMID 19293268 2009 Mutations in regulatory subunit type 1A of cyclic adenosine 5'-monophosphate-dependent protein kinase (PRKAR1A): phenotype analysis in 353 patients and 80 different genotypes.

PMID 20358582 2010 Mutations and polymorphisms in the gene encoding regulatory subunit type 1-alpha of protein kinase A (PRKAR1A): an update.

PMID 18056771 2008 An immortalized human cell line bearing a PRKAR1A-inactivating mutation: effects of overexpression of the wild-type Allele and other protein kinase A subunits.

PMID 22259056 2012 Activation of cyclic AMP signaling leads to different pathway alterations in lesions of the adrenal cortex caused by germline PRKAR1A defects versus those due to somatic GNAS mutations.

PMID 22341669 2012 Recurrent left atrial myxomas in Carney complex: a genetic cause of multiple strokes that can be prevented.

rs35359468 in PRKAR1A gene and Reticulocyte count (procedure) PMID 27863252 2016 The Allelic Landscape of Human Blood Cell Trait Variation and Links to Common Complex Disease.