Sodium channel regulatory subunit beta-3

SCN3B encodes sodium channel regulatory subunit beta-3, an accessory protein that modulates voltage-gated sodium channel function. The protein directly regulates multiple Nav channels including SCN2A/Nav1.2, SCN5A/Nav1.5, SCN10A/Nav1.8, and potentially SCN7A/Nav2.1, influencing their localization, gating properties, and inactivation kinetics (UniProt: Q9NY72). These regulatory functions are essential for proper electrical signal propagation in excitable tissues.

SCN3B is primarily implicated in cardiac pathophysiology, with UniProt-curated associations to Brugada syndrome 7 and familial atrial fibrillation. Both conditions reflect impaired sodium channel activity and abnormal cardiac electrical signaling. While the protein's expression and function are best characterized in cardiac tissue, sodium channels and their regulators are also present in neuronal populations.

SCN3B is downregulated in Alzheimer's disease brain tissue. Analysis of post-mortem AD brain versus age-matched controls using TMT-labeled quantitative proteomics across four subcellular fractions (P2, P3, S2, S3) revealed reduced SCN3B abundance with a mean log2 fold-change of −0.513 (Chaparral AD proteomics). The functional significance of this reduction in AD neurodegeneration remains to be established.