Gain-of-function mutations in the human SCN11A-encoded voltage-gated Na(+) channel NaV1.9 cause severe pain disorders ranging from neuropathic pain to congenital pain insensitivity.
Heterozygous mutations in TRPA1, which encodes the transient receptor potential cation channel, can cause familial episodic pain syndromes, and variants of genes coding for the voltage-gated sodium channels Nav1.8 (SCN10A) and Nav1.9 (SCN11A) lead to small-fibre neuropathy and congenital insensitivity to pain, respectively.