GNAS gene

The GNAS gene, also called GNAS1 gene, (GNAS is the acronym for: "Guanine Nucleotide binding protein, Alpha Stimulating activity polypeptide". Guanine Nucleotide-Binding Protein G(S) Subunit Alpha) is a protein coding gene located on chromosome 20q13.32. Its major product is the heterotrimeric G protein alpha subunit Gs-alpha, a key component of the G protein-coupled receptor-gated adenylyl cyclase signal transduction pathways.

Diseases associated with GNAS include:

• Mccune-Albright syndrome (In this, GNAS mutations are found to cause constitutive Gsα signal transduction. The clinical features of this disease depend largely on the parental allelic origin of the GNAS mutation, reflecting tissue-specific paternal Gsα silencing).
• and
• Pseudohypoparathyroidism, type Ia.

Associated pathways include ADORA2B-mediated production of anti-inflammatory cytokines and the GPCR pathway.

The locus localized on chromosome 20q13.32 shows a highly complex imprinted expression pattern. It gives rise to maternally, paternally and biallelic expressed transcripts. Some transcripts contain a differentially methylated region (DMR) at their 5' exons, which is often found in imprinted genes and correlates with transcript expression. An antisense transcript is produced by an overlapping locus on the opposite strand. One of the transcripts produced by this locus and the antisense transcript are paternally expressed noncoding RNAs that could regulate imprinting in this region. In addition, one of the transcripts contains a second overlapping ORF encoding a structurally unrelated protein - Alex.

Note: Guanine nucleotide-binding proteins(G-proteins) act as transducers in numerous signaling pathways controlled by G-protein-coupled receptors (GPCRs). Signal transduction involves the activation of adenyl cyclases, resulting in an increase in the signaling molecule cAMP. Signal transduction involves activation of adenylyl cyclases, resulting in an increase in the signaling molecule cAMP (Gao X et al. (2007). GNAS acts downstream of several GPCRs, including beta-adrenergic receptors. Stimulates the Ras signaling pathway via RAPGEF2 (Pak Y et al. 2002).

1. Farfel Z et al (1996) Pseudohypoparathyroidism, a novel mutation in the betagamma-contact region of Gsalpha impairs receptor stimulation. J Biol Chem 271:19653-5.
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 22:7942-52.
4. Spencer T et al (2019) The Clinical Spectrum of McCune-Albright Syndrome and Its Management. Horm Res Paediatr 92:347-356.