PIK3CA and Venous malformation: Moreover, somatic mutations in the tyrosine kinase with immunoglobulin and EGF homology domains 2 (TIE2) gene, which promote PI3K activation, have been observed in > 50% of patients with venous malformations, whereas approximately 20% harbor phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA) mutations [54].