Mapping the mutation hotspots in VSDs of Na _v channels. The annotated disease-associated mutations from UniProt are mapped along the MSA of VSDs in nine human Na_v channels. (A–C) The number of mutations at the equivalent position in four VSDs (A), the number of phenotypes in VSD_I (B), and that in VSD_II (C) are used to demonstrate the mutation hotspots. (B and C) Pathogenic missense mutations are colored according to GoF (green bars), LoF (red), mixed (yellow), and uncertain (black) effects. Hotspots are labeled in this figure with either the order of gating charges (A) or residue IDs from Na_v1.5 (B and C).