Costello syndrome is encoded by HRAS (11p15.5) and KRAS (12p12.1), and gain-of-function mutations influencing p.Gly13 or p.Gly12 may cause germline activation of HRAS, and thereby lead to dysregulation of the Ras-Raf-MEK-ERK signaling pathway (20, 85, 86). The gene discussed is HRAS; the disease is Costello syndrome.