Sodium voltage-gated channel alpha subunit 8 pre-messenger RNA (SCN8A pre-mRNA)

SCN8A pre-mRNA is the primary RNA transcript of the SCN8A gene, which encodes the alpha subunit of the voltage-gated sodium channel Nav1.6 [UniProt Q9UQD0]. This channel is a critical component of the neuronal machinery, primarily localized at the axon initial segment and nodes of Ranvier, where it facilitates the initiation and rapid propagation of action potentials [OMIM 600702]. Mutations in the SCN8A gene, particularly gain-of-function variants, are a known cause of severe neurological disorders, including Developmental and Epileptic Encephalopathy 13 (DEE13) and various forms of refractory epilepsy [Lenk et al., 2020]. Therapeutic strategies targeting the pre-mRNA, such as antisense oligonucleotides (ASOs), aim to modulate the expression of Nav1.6 by inducing RNase H-mediated degradation of the transcript or altering its splicing patterns [Praxis Precision Medicines]. By reducing the abundance of overactive sodium channels, these therapies seek to restore normal neuronal excitability and provide a precision medicine approach for patients with SCN8A-related disorders who are often resistant to conventional anti-seizure medications.

Other names

Sodium channel protein type 8 subunit alpha pre-mRNANav1.6 pre-mRNASCN8A transcriptVoltage-gated sodium channel type VIII alpha subunit pre-mRNA

Antisense oligonucleotide (ASO) mediated knockdown or splicing modulation to reduce the expression of the Nav1.6 protein in cases of gain-of-function mutations [Lenk et al., 2020].