Figure 2.

Missense mutations in RAS and RHO GTPases in cancer. Data were compiled for the 3 RAS proteins (HRAS, KRAS, and NRAS), RAC1, and RHOA for all cancers in cBioPortal (http://www.cbioportal.org/). Shown are those residues where 5 or more mutations have been identified. For RAS proteins, there are 3 hotspots for missense mutations (G12, G13, and Q61), leading to impaired intrinsic and RASGAP-stimulated GTP hydrolysis, and/or causing a fast cycling defect, favoring formation of RAS-GTP. For RAC1, the predominant mutation is at P29, causing a fast cycling defect that promotes the GTP-bound state. In contrast, the missense mutations found in RHOA do not favor formation of RHOA-GTP and instead lead to impaired interaction with effectors and/or regulators, resulting in dominant-negative mutant proteins.