Structure-based assessment of disease-related mutations in human voltage-gated sodium channels

Weiyun Huang, Minhao Liu, S. Frank Yan, Nieng Yan

Research output: Contribution to journalReview articlepeer-review

65 Scopus citations


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 Cav1.1 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.

Original languageAmerican English
Pages (from-to)401-438
Number of pages38
JournalProtein and Cell
Issue number6
StatePublished - Jun 1 2017

ASJC Scopus subject areas

  • Drug Discovery
  • Biochemistry
  • Biotechnology
  • Cell Biology


  • Na channels
  • Na1.7
  • channelopathy
  • pain
  • structure modeling


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