SCN9A and erythromelalgia: The NaV1.7-W1538R mutation, located in the S2 helix of the voltage sensing domain of the channel’s domain IV (VSD4), causes a hyperpolarizing shift in the voltage-dependence of activation of NaV1.7 channels and has been implicated in the pathology of both inherited erythromelalgia (Cregg et al., 2013) and small fiber neuropathy (Eijkenboom et al., 2019).