However, even though the activation of PI3K signaling often results in proliferative venous malformations, the increase in RAS/MAPK/ERK activity often induces non-proliferative arterial-venous malformations which is in agreement with the bell-shaped response to mitogenic/VEGF/ERK signaling [6] discussed above. The gene discussed is MAPK1; the disease is Venous malformation.