GNAS complex locus

GNAS complex locus, also known as GNAS, is a is_associated_with::protein which in humans is encoded by the GNAS is_associated_with::gene. The protein encoded by this gene is the stimulatory G-protein alpha subunit (Gs-α), a key component of many is_associated_with::signal transduction pathways.

Gene
This gene locus has a highly complex imprinted expression pattern. It gives rise to maternally, paternally, and biallelically expressed transcripts that are derived from four alternative promoters and 5' exons. Some transcripts contains a differentially methylated region (DMR) at their 5' exons, and this DMR is commonly found in imprinted genes and correlates with transcript expression. An antisense transcript exists, and this antisense transcript and one of the transcripts are paternally expressed, produce noncoding RNAs, and may regulate imprinting in this region. In addition, one of the transcripts contains a second overlapping ORF, which encodes a structurally unrelated protein.

The GNAS locus is imprinted and encodes 5 main transcripts:


 * Gs-α
 * XLAS
 * NESP55
 * A/B transcript
 * antisense GNAS transcript

Protein
Alternative splicing of downstream exons is also observed, which results in different forms of the stimulatory G-protein alpha subunit (Gs-α), a key element of the classical signal transduction pathway linking receptor-ligand interactions with the activation of is_associated_with::adenylyl cyclase and a variety of cellular responses. Multiple transcript variants have been found for this gene, but the full-length nature and/or biological validity of some variants have not been determined.

Clinical significance
Deficiencies are associated with:
 * is_associated_with::Albright hereditary osteodystrophy
 * is_associated_with::pseudohypoparathyroidism type Ia
 * is_associated_with::pseudohypoparathyroidism type Ib
 * is_associated_with::pseudopseudohypoparathyroidism
 * is_associated_with::McCune-Albright syndrome

Mutations in this gene also result in progressive osseus heteroplasia, is_associated_with::polyostotic fibrous dysplasia of bone, and some pituitary tumors.

Interactions
GNAS complex locus has been shown to interact with is_associated_with::RIC8A.