GNAS is a complex locus located on the telomeric end of chromosome 20q. At least five distinct promoters reside in this locus, leading to biallelically, paternally, and/or maternally expressed transcripts from both the sense and antisense strands. Expression from this locus is tightly regulated by epigenetic mechanisms and cis-acting regulatory elements, including non-coding RNA molecules. GNAS encodes Gsα, one of the subunits of the heterotrimeric stimulatory G protein, which is essential for the actions of numerous agonists. Several human disorders are caused by heterozygous mutations that affect Gsα expression and/or activity, and consistent with the tissue-specific paternal silencing of Gsα expression, these disorders are inherited in a parent-of-origin specific manner. In contrast to Gsα, the roles of most of the other GNAS products remain unknown at the cellular and molecular level, even though the biological significance of these products are clear from gene knockout studies. Depending on their parental origin, mutations that affect the Gsα transcript also disrupt some of the additional GNAS transcripts, such as XLαs. It is likely that the disruption of these additional gene products or alterations
