In humans, three RAS genes encode four distinct isoforms: HRAS, NRAS, and the two splice variants of KRAS gene, KRAS4a and KRAS4b, containing exons 4a and 4b, respectively. All four RAS isoforms contain identical residues in the first half of the GTPase domain (G-domain) and they share 82% sequence identity in the second half of the G-domain. The last 19–20 amino acids located at the C-terminal end exhibit significant sequence diversity among RAS isoforms and constitute the “hypervariable region (HVR)”. Unlike the other RAS isoforms, KRAS4b is not palmitoylated and contains a polybasic region (shown in blue color). In the figure, G-domains are shown in ribbon representation and membrane anchored farnesyl and palmitoyl lipid chains are shown in orange and green color.