Voltage-gated sodium (Nav) channels are essential for the rapid upstroke of action potentials and the propagation of electrical signals in nerves and muscles.Defects of Nav channels are associated with a variety of channelopathies.More than 1000 disease-related mutations have been identified in Nav channels,with Nav1.1 and Nav1.5 each harboring more than 400 mutations.Nav channels represent major targets for a wide array of neurotoxins and drugs.Atomic structures of Nav channels are required to understand their function and disease mechanisms.The recently determined atomic structure of the rabbit voltage-gated calcium (Cav)channel Car1.1 provides a template for homology-based structural modeling of the evolutionarily related Nav channels.In this Resource article,we summarized all the reported disease-related mutations in human Nav channels,generated a homologous model of human Nav1.7,and structurally mapped disease-associated mutations.Before the determination of structures of human Nav channels,the analysis presented here serves as the base framework for mechanistic investigation of Nav channelopathies and for potential structure-based drug discovery.