Scn9a Gene

The sodium channel-coding SCN9a gene located on chromosome 2q24.3 encodes a voltage-gated sodium channel that is enriched in nociceptive and sympathetic neurons of the peripheral nervous system (Michiels et al. 2005). The SCN9a gene contains 26 exons (Michiels et al. 2005). SCN9a is also expressed in subcortical structures of the CNS (McDermott et al. 2019). Furthermore, this sodium channel is expressed in smooth muscle cells of the bronchial system and in pulmonary and coronary arteries.

Numerous mutations with different and predominantly autosomal dominant inherited phenotypes have been described:

• Primary Erythermalgia (Familial Erythermalgia) OMIM:133020
• Epilepsy, generalized, with febrile seizures plus, type 7; OMIM: 613863
• Febrile seizures, familial, 3B; OMIM: 613863
• HSAN2D, autosomal recessive; OMIM: 243000, autosomal recessive inheritance.
• Insensitivity to pain, congenital; OMIM: 243000, autosomal recessive inheritance.
• Paroxysmal extreme pain disorder; OMIM:167400
• Small fiber neuropathy; OMIM:133020

1. Cox J et al (2006) An SCN9A channelopathy causes congenital inability to experience pain. Nature 444: 894-898
2. Cummins T R ett al.(2004) Electrophysiological properties of mutant Na(v)1.7 sodium channels in a painful inherited neuropathy. J Neurosci 24: 8232-8236
3. Goldberg Y P et al (2007) Loss-of-function mutations in the Na(v)1.7 gene underlie congenital indifference to pain in multiple human populations. Clin Genet71: 311-319.
4. McDermott L A et al (2019) Defining the functional role of NaV1.7 in human nociception. Neuron 101: 905-919
5. Michiels JJ et al (2005) Autosomal dominant erythermalgia associated with a novel mutation in the voltage-gated sodium channel alpha-subunit Nav1.7. Arch Neurol 62:1587-1590.