{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nSCN3B encodes the β3‐subunit of voltage‐gated sodium channels and plays a critical role in cardiac excitability. In the heart, mutations in SCN3B have been causally linked to arrhythmias such as atrial fibrillation, Brugada syndrome, and idiopathic ventricular fibrillation. For example, a mutation (A130V) in SCN3B was found to dramatically decrease sodium current density—acting in a dominant negative manner—and similar loss‐of‐function variants have been associated with sudden infant death syndrome and Brugada syndrome, underscoring the subunit’s importance in maintaining normal cardiac conduction and rhythm."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "6"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nFunctional analyses in heterologous systems reveal that SCN3B not only contributes structurally as part of the sodium channel complex but also modulates its electrophysiological properties. Experiments have shown that expression of mutant SCN3B can alter the sodium current density without markedly affecting channel activation or inactivation kinetics. Moreover, in neurons, β3 influences the voltage sensitivity and inactivation behavior of sodium channels, with its extracellular immunoglobulin‐like domain contributing to these effects."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}, {"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nStudies of SCN3B’s extracellular domain reveal distinct cell adhesion characteristics compared to other sodium channel β‐subunits. Although the β3 subunit can engage in trans homophilic binding via its Ig domain, it does not exhibit the same adhesive interactions (for example, with contactin or ankyrin) as observed for β1. This difference suggests that while SCN3B structurally supports channel function, its adhesive properties are uniquely tuned and may affect localization and interaction within the channel complex."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "8"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond its electrophysiological roles, SCN3B has been implicated in cellular signaling pathways mediated by p53. In response to DNA damage, p53 can upregulate SCN3B expression leading to apoptosis in certain cell types. In contrast, in liver cancer cells, overexpression of SCN3B promotes proliferation and inhibits apoptosis by facilitating p53 ubiquitination and degradation via stabilization of the p53/MDM2 complex. These findings indicate that SCN3B may serve dual, context‐dependent roles that are pro‐apoptotic in some settings while oncogenic in others."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "10"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nAlterations in SCN3B expression and sequence have also been associated with neurological disorders. Reduced hippocampal expression of SCN3B has been observed in certain temporal lobe epilepsy patients, which may contribute to altered neuronal excitability and epileptogenesis. Furthermore, specific single‐nucleotide polymorphisms in SCN3B have been linked to an increased risk of vertigo, suggesting that its function extends beyond cardiac and cancer biology to include roles in the central nervous system."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "12"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Morten S Olesen, Thomas Jespersen, Jonas B Nielsen, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Mutations in sodium channel β-subunit SCN3B are associated with early-onset lone atrial fibrillation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cardiovasc Res (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1093/cvr/cvq348"}], "href": "https://doi.org/10.1093/cvr/cvq348"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21051419"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21051419"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Pengyun Wang, Qinbo Yang, Xiaofen Wu, et al. 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