SCN9A

SCN9A encodes the pore-forming alpha subunit of Nav1.7, a tetrodotoxin-sensitive voltage-gated sodium channel. It is a single large polypeptide (~1977 aa) with the canonical Nav architecture of four internal homologous repeats (domains I-IV), each containing six transmembrane segments (S1-S6); the S4 segments are the voltage sensors and the S5-S6 re-entrant loops form the Na+-selective pore. The channel is functional on its own as a multi-pass plasma membrane protein and is modulated by auxiliary beta subunits (SCN1B, SCN2B, SCN3B, SCN4B). On membrane depolarization the channel opens and selectively conducts Na+ down its electrochemical gradient, mediating the rising (depolarizing) phase of the action potential. Nav1.7 is strongly expressed in peripheral sensory neurons, most notably small-diameter nociceptive dorsal root ganglion neurons, and in sympathetic ganglion neurons; in nociceptors it localizes to the soma membrane, axons, axon/nerve terminals, and nodes of Ranvier, where it acts as a threshold/amplifier channel that boosts subthreshold depolarizations and sets the gain for action potential firing. Loss-of-function mutations cause complete congenital inability to perceive pain, while gain-of-function mutations cause inherited erythromelalgia and paroxysmal extreme pain disorder, establishing Nav1.7 as an essential, non-redundant determinant of human pain sensation.

Disorders

Relationship is the entry's genetic[].relationship_type. untyped means the entry has a genetic record for the gene but does not type it; its free-text association is shown instead.

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• nociceptor_sodium_channel_excitability via Congenital Insensitivity to Pain, Primary Erythermalgia