While other mutations have been described involving the external pore forming loop of Kir2.1,[7] mutations in KCNJ2 impairing channel interactions with phosphatidylinositol 4,5-bisphosphonate (PIP2) are thought to play a significant role as pathogenic mechanism in ATS.[25]  PIP2 is a membrane-bound second messenger which activates Kir2.1, among other inward-rectifiers, and promotes an open-channel position [5]. This evidence concerns the gene KCNJ2 and Andersen-Tawil syndrome.