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GTPase HRas (HRas) binds GDP/GTP and possess intrinsic GTPase activity. HRas alternates between an inactive form bound to GDP and an active form bound to GTP. HRas is activated by a guanine nucleotide-exchange factor (GEF) and inactivated by a GTPase-activating protein (GAP). Defects in HRAS are the cause of Costello syndrome (COSTS), also known as faciocutaneoskeletal syndrome. Costello syndrome is a rare condition characterized by prenatally increased growth, postnatal growth deficiency, mental retardation, distinctive facial appearance, cardiovascular abnormalities (typically pulmonic stenosis, hypertrophic cardiomyopathy and/or atrial tachycardia), tumor predisposition, and skin and musculoskeletal abnormalities.