GNAS is a GTPase that is activated upon ligand binding of a G-protein coupled receptor, and is involved in mediating hormone response. Hotspot mutations impair GTPase activity, resulting in constitutive pathway activation and are common in a variety of tumor types. Simple variants in GNAS are seen in about 3% of all tumors. They are seen in 71% of pseudomyxoma peritonei tumors, 30% of pituitary tumors, and 14% of pancreatic tumors, where they can be diagnostic. Variants in GNAS are also seen in 15% of bone tumors, 14% of pancreas tumors, and 4% of colorectal and adrenal tumors.