SCN9A

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There are multiple known variants in the 1988 amino acid sodium channel protein type 9 subunit alpha protein due to mutations in the encoding gene SCN9A at 2q24.3 which cause:

  • Primary erythromelalgia, PERYTHM
    • An autosomal dominant disease with recurrent episodes of severe pain associated with redness and warmth in the feet or hands
    • At least 8 different mutations scattered through the peptide can cause
      • The VAR_064609 variant from leucine to phenylalanine (L869F, p.Leu869Phe, L858F on processed molecule) is cold sensitive allowing easy treatment
  • Congenital loss of sensation (congenital indifference to pain autosomal recessive, CIPAR, channelopathy-associated insensitivity to pain)
  • Paroxysmal extreme pain disorder (PEPD)
    • Episodes of burning pain in the rectal, ocular, and mandibular areas that may be accompanied by autonomic change such as skin flushing
    • At least 8 different mutations towards the end of the peptide
  • Generalised epilepsy with febrile seizures plus type 7 (GEFS+7)
  • Familial febrile convulsions type 3B (FEB3B)

This protein is the α-subunit of the tetrodotoxin-sensitive voltage-gated sodium channel NaV1.7. There are several isoforms from alternative splicing:

  1. Isoform 1 is expressed preferentially in the central and peripheral nervous system
  2. Isoform 2 is expressed preferentially in the dorsal root ganglions
  3. Isoform 3

Some of the specific mutations will be heat sensitive (so cold treatment can work) and specific drugs are in development which may result in general treatment for some pain syndromes[1]

References

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