SCN9A

About SCN9A

SCN9A on chromosome 2q24.3 encodes Nav1.7, a voltage gated sodium channel highly expressed in pain sensing nociceptor neurons and sympathetic neurons, where it amplifies small depolarizations and sets the threshold for firing. Gain of function variants cause inherited erythromelalgia, sometimes called man on fire syndrome, with episodes of burning pain and redness in the hands and feet triggered by warmth or exercise, as well as paroxysmal extreme pain disorder and some forms of small fiber neuropathy. Loss of function variants on both copies cause congenital insensitivity to pain, in which affected individuals feel no physical pain but have otherwise largely normal sensation, apart from a loss of the sense of smell. Without pain as a warning, they suffer repeated injuries such as biting injuries to the tongue and lips, fractures, and burns. A key 2006 study of families in northern Pakistan, including a boy who performed street feats without feeling pain, linked this condition to SCN9A. These discoveries identified Nav1.7 as a promising target for non opioid painkillers, although selective Nav1.7 inhibitors have so far proved difficult to develop. SCN9A variants also influence pain sensitivity in the general population.