The human GNAS locus maps to the telomeric end of the long arm of chromosome 20 (20q13.2-20q13.3) [10-12], while its mouse ortholog is located in distal chromosome 2 [13, 14]. GNAS in humans and mice appear structurally and functionally similar to one and other. This locus has multiple promoters and differentially methylated regions (DMR) and gives rise to non-coding RNA molecules and transcripts that encode functional proteins (Fig. 1). Furthermore, nearly all GNAS products show parent-of-origin specific expression. Among the multiple products derived from GNAS, the best characterized protein is the α-subunit of the heterotrimeric stimulatory G protein (Gsα), which has at least five variants that result from alternative pre-mRNA splicing. Derived from distinct promoters are at least four different additional GNAS products, including the neuroendocrine secretory protein 55 (NESP55), the extra-large variant of Gsα (XLαs), the A/B transcript, and the GNAS antisense transcript. Most of these additional transcripts also undergo alternative splicing and, thus, have different variants.
