This signaling cascade flows through the pathway, together with the proteins positively and negatively controlling the cascade; signaling upregulation in RASopathies like NS results from enhanced activity of RAS proteins (i.e., HRAS, KRAS, NRAS, MRAS, RRAS, RRAS2, and RIT1), upstream positive signal transducers and regulators (i.e., SHP2, SOS1, and SOS2), proteins favoring transmission of RAS signaling to downstream transducers (i.e., MRAS, SHOC2, and PPP1CB), and tiers of the MAPK cascade (i.e., BRAF, RAF1, MAP2K1, MAP2K2, and MAPK1) [16]. The gene discussed is PTPN11; the disease is RASopathy.