Sodium voltage-gated channel alpha subunit 8 (SCN8A) (SCN8A)

The mutant SCN8A genomic DNA protospacer refers to a specific sequence within the Sodium voltage-gated channel alpha subunit 8 gene that harbors a pathogenic mutation, typically a single nucleotide substitution. SCN8A encodes the Nav1.6 protein, a critical voltage-gated sodium channel responsible for the initiation and propagation of action potentials in the central and peripheral nervous systems (UniProt P35498). Pathogenic gain-of-function mutations in SCN8A are a primary cause of Early Infantile Epileptic Encephalopathy type 13 (EIEE13), characterized by severe, refractory seizures and developmental delay (PubMed: 23023331). By targeting the protospacer containing the pathogenic adenine, therapeutic strategies such as Adenine Base Editors (ABEs) can precisely convert the mutant adenine back to the wild-type guanine without inducing double-strand breaks (PubMed: 29072295). This approach aims to restore normal Nav1.6 function and alleviate the neuronal hyperexcitability associated with the disease. Current research focuses on optimizing guide RNA specificity and delivery mechanisms to ensure safe and effective gene correction in affected neuronal populations (PubMed: 31605454).

Other names

Nav1.6Sodium channel protein type 8 subunit alphaEIEE13BFIS5CerlPN4SCN8A protospacer

Adenine base editing to convert pathogenic adenine to guanine, restoring the wild-type DNA sequence and normalizing Nav1.6 channel function.