Jarecki et al. have shown that Nav1.7/I1461T, leading to paroxysmal extreme pain disorder, shifted activation and deactivation when expressed in different splice variants [31], while another study reported that familial hemiplegic migraine-1 missense mutations attribute different effects on the gating properties of various splice variants of the voltage-gated calcium channel Cav2.1 [45]. The gene discussed is SCN9A; the disease is paroxysmal extreme pain disorder.