Activating mutations in the TIE2 receptor or the downstream signal transducer PIK3CA [p110α catalytic subunit of phosphatidylinositide-3 kinase (PI3K)] cause human venous malformations (VMs) [28–32] while loss-of-function TIE2 mutations result in glaucoma. The gene discussed is TEK; the disease is Venous malformation.