GNAS gene

The GNAS gene (GNAS stands for Guanine Nucleotide-Binding Protein G(S) Subunit Alpha Isoforms Short Complex Locus) is a protein-coding gene located on chromosome 20q13.32. Several transcript variants encoding different isoforms have been found for this gene.

The GNAS gene encodes the stimulatory G protein alpha subunit. This is a key element of the classical signal transduction pathway linking receptor-ligand interactions with adenylyl cyclase activation and a variety of cellular responses.

The GNAS gene exhibits a highly complex imprinted expression pattern. Evidence is provided for alternative splicing of downstream exons, resulting in different forms of the stimulatory G protein alpha subunit.

GNAS stimulates the Ras signaling pathway via RAPGEF2 (Pak Y et al. 2002).

Guanine nucleotide-binding proteins (G-proteins) act as transducers in numerous signaling pathways controlled by G-protein-coupled receptors (GPCRs). Signal transduction involves activation of adenylyl cyclases, leading to an increase in the signaling molecule cAMP.

Furthermore, guanine nucleotide-binding proteins (G-proteins) act as transducers in numerous signaling pathways controlled by G-protein-coupled receptors (GPCRs) (Gao X et al. 2007).

Signal transduction involves activation of adenylyl cyclases, resulting in an increase in the signaling molecule cAMP (Farfel Z et al. 1996).

Diseases associated with GNAS include:

• Mccune-Albright syndrome
• and
• Pseudohypoparathyroidism, type Ia.

1. Farfel Z et al (1996) Pseudohypoparathyroidism, a novel mutation in the betagamma-contact region of Gsalpha impairs receptor stimulation. J Biol Chem 271:19653-1965.
2. Gao X et al. (2007) Conditional stimulation of type V and VI adenylyl cyclases by G protein betagamma subunits. J Biol Chem 282:294-302.
3. Pak Y et al (2002) Direct binding of the beta1 adrenergic receptor to the cyclic AMP-dependent guanine nucleotide exchange factor CNrasGEF leads to Ras activation. Mol Cell Biol 22:7942-7952.