Interestingly, germline mutations identified in leukocytes from patients with the RASopathy cardio-facio-cutaneous syndrome23, 24 include two MAP2K1 mutations (p.G128V/p.Y130C) in the catalytic core, and putatively activating mutations in the negative regulatory region of MAP2K1 (p.F53S) or MAP2K2 (p.F57V, analogous to MAP2K1 p.F53). Here, MAP2K2 is linked to RASopathy.