Calcium voltage-gated channel subunit alpha1 C pre-mRNA exon 8A region (CACNA1C exon 8A)

The Calcium voltage-gated channel subunit alpha1 C (CACNA1C) pre-mRNA exon 8A region is a critical regulatory segment of the gene encoding the pore-forming subunit of the Cav1.2 L-type calcium channel (Splawski et al., 2004). This region undergoes mutually exclusive splicing with exon 8, where exon 8A is the predominant isoform in the heart and brain during early development (Diebold et al., 2002). A specific G406R mutation within exon 8A leads to Timothy Syndrome, a multi-system disorder characterized by lethal cardiac arrhythmias and autism spectrum phenotypes due to impaired channel inactivation (Splawski et al., 2004). Therapeutic targeting of this pre-mRNA region utilizes antisense oligonucleotides (ASOs) to modulate splicing, effectively switching the expression from the mutated exon 8A to the functional, wild-type exon 8 (Song et al., 2024). This splice-switching approach aims to restore normal electrophysiological properties in affected tissues like the myocardium and neurons (Panagiotakos et al., 2015).

Other names

CACNA1C exon 8.1Cav1.2 exon 8ATimothy Syndrome mutation locusCACNA1C alternative exon 8

Splicing modulation to induce exon skipping of the mutated exon 8A and promote inclusion of the alternative wild-type exon 8 (Song et al., 2024).