Mutations in sodium-channel gene SCN9A cause a spectrum of human genetic pain disorders

J Clin Invest. 2007 Dec;117(12):3603-9. doi: 10.1172/JCI33297.


The voltage-gated sodium-channel type IX alpha subunit, known as Na(v)1.7 and encoded by the gene SCN9A, is located in peripheral neurons and plays an important role in action potential production in these cells. Recent genetic studies have identified Na(v)1.7 dysfunction in three different human pain disorders. Gain-of-function missense mutations in Na(v)1.7 have been shown to cause primary erythermalgia and paroxysmal extreme pain disorder, while nonsense mutations in Na(v)1.7 result in loss of Na(v)1.7 function and a condition known as channelopathy-associated insensitivity to pain, a rare disorder in which affected individuals are unable to feel physical pain. This review highlights these recent developments and discusses the critical role of Na(v)1.7 in pain sensation in humans.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Action Potentials / genetics*
  • Humans
  • Mutation, Missense*
  • NAV1.7 Voltage-Gated Sodium Channel
  • Neurons / metabolism
  • Neurons / pathology
  • Pain / genetics*
  • Pain / metabolism
  • Pain Insensitivity, Congenital / genetics*
  • Pain Insensitivity, Congenital / metabolism
  • Pain Insensitivity, Congenital / pathology
  • Peripheral Nerves / metabolism
  • Peripheral Nerves / pathology
  • Sodium Channels / genetics*
  • Sodium Channels / metabolism


  • NAV1.7 Voltage-Gated Sodium Channel
  • SCN9A protein, human
  • Sodium Channels