Sodium channel protein type 8 subunit alpha

SCN8A encodes the pore-forming alpha subunit of a voltage-gated sodium channel that controls neuronal excitability by regulating action potential threshold and propagation (UniProt: Q9UQD0). The protein functions as a selective conduit for sodium ions across cell membranes in response to membrane voltage changes, with additional roles in non-neuronal cells in podosomes and macrophage adhesion.

SCN8A is expressed in the nervous system and associated with multiple neurodevelopmental and epileptic disorders (UniProt: Q9UQD0). Mutations cause Developmental and Epileptic Encephalopathy 13 (DEE13), characterized by early-onset seizures, autism features, intellectual disability, and ataxia; benign familial infantile seizures; cognitive impairment with cerebellar ataxia; and familial myoclonus.

In Alzheimer's disease, SCN8A is downregulated in post-mortem AD brain compared to age-matched controls (mean log2FC −0.40), as measured by tandem mass tag proteomics across multiple subcellular fractions (Chaparral AD proteomics). This reduced expression may reflect impaired neuronal ion channel function in AD pathology.