The reference OMIM entry for this protein is 139320

Gnas complex locus; gnas
Gnas1 gene, formerly; gnas1, formerly guanine nucleotide-binding protein, alpha-stimulating activity polypeptide 1, included; gnas1, included
Gs, alpha subunit, included
Stimulatory g protein, included
Adenylate cycla

DESCRIPTION

GNAS is a complex imprinted locus that produces multiple transcripts through the use of alternative promoters and alternative splicing. The most well-characterized transcript derived from GNAS, Gs-alpha, encodes the alpha subunit of the stimulatory guanine nucleotide-binding protein (G protein). Gs-alpha is expressed biallelically in nearly all tissues and plays essential roles in a multitude of physiologic processes. Other transcripts produced by GNAS are expressed exclusively from either the paternal or the maternal GNAS allele (Bastepe and Juppner, 2005).

CLONING

- Overview of Transcripts Produced by GNAS The GNAS locus is imprinted and encodes 4 main transcripts, Gs-alpha, XLAS, NESP55, and the A/B transcript, as well as an antisense GNAS transcript (GNASAS; 610540). The 4 main transcripts are produced through the use of alternative promoters and splicing of 4 unique first exons onto the shared exons 2 through 13. Gs-alpha is ubiquitously expressed and encodes a protein that stimulates adenylyl cyclase when activated by an agonist-occupied G protein-coupled receptor, thereby generating the second messenger cAMP. Gs-alpha is biallelically expressed except in a small number of tissues, including renal proximal tubules, thyroid, gonads, and pituitary, where it is predominantly expressed from the maternal GNAS allele. XLAS is a large variant of Gs-alpha that is expressed exclusively from the paternal GNAS allele, primarily in neuroendocrine tissues and the nervous system. The XLAS and Gs-alpha proteins are identical over their C-terminal portions, but they have distinct N termini. NESP55 is exclusively expressed from the maternal GNAS allele and encodes a chromogranin (see 118910)-like neuroendocrine secretory protein that, due to a stop codon in its unique first exon, shares no amino acid sequence with Gs-alpha. The A/B transcript, which uses the alternative first exon A/B (also referred to as exon 1A or 1-prime), and the antisense GNAS transcript, which consists of exons that do not overlap with any other GNAS exons, are ubiquitously expressed noncoding transcripts that are derived exclusively from the paternal GNAS allele. Consistent with their parent-specific expression, the promoters of the XLAS, NESP55, A/B, and antisense transcripts are within differentially methylated regions (DMRs), and in each case the nonmethylated promoter drives expression. In contrast, the promoter for Gs-alpha lacks methylation and is biallelically active in most tissues (Bastepe and Juppner, 2005). - Gs-Alpha Transcript Using oligonucleotide probes for recombinants that code for alpha subunits of G signal transduction proteins, Bray et al. (1986) screened human brain cDNA libraries and identified 11 clones corresponding to 4 species of Gs-alpha cDNA. One of the clones was predicted to encode a 384-amino acid protein with homology to the bovine and rat Gs-alpha proteins. The 4 clones differed in nucleotide sequence in the region that codes for amino acid residues 71 to 88. Two forms corresponded to proteins with molecular masses of 52 and 45 kD. The authors suggested alternative splicing of a single precursor mRNA. - A/B Transcript Ishikawa et al. (1990) reported a Gs-alpha mRNA that uses a different promoter and exon, which they termed exon 1-prime (later termed exon 1A or A/B) that is located 2.5 kb upstream of GNAS exon 1. Exon 1-prime does not contribute an in-frame ATG, and thus its mRNA may encode a truncated form o ... More on the omim web site

Subscribe to this protein entry history

Nov. 17, 2018: Protein entry updated
Automatic update: OMIM entry 139320 was added.

Oct. 19, 2018: Additional information
Initial protein addition to the database. This entry was referenced in Bryk and co-workers. (2017).