Calcium voltage-gated channel subunit alpha1 E (CACNA1E)

Calcium voltage-gated channel subunit alpha1 E (CACNA1E) encodes the pore-forming α1E subunit of the R-type (Cav2.3) voltage-dependent calcium channel, a high-voltage-activated ion channel predominantly expressed in the central nervous system, as well as other tissues such as the pancreas, retina, and kidney. This subunit enables rapid synaptic transmission and plays a central role in activities requiring calcium influx, including neuronal firing, synaptic plasticity, hormone and neurotransmitter secretion, gene expression, and insulin release. Pathogenic gain-of-function mutations in CACNA1E are implicated in developmental and epileptic encephalopathy type 69, manifesting as early-onset, refractory epilepsy with severe intellectual impairment, macrocephaly, and movement disorders. The channel is insensitive to dihydropyridine calcium channel blockers, but is blocked by the peptide SNX-482 and modulated by the antiepileptic drug topiramate, making it a target for precision therapies in genetic epilepsies

Other names

Cav2.3Voltage-dependent R-type calcium channel subunit alpha-1ECACH6CACNL1A6BIIBrain calcium channel IICalcium channel, L type, alpha-1 polypeptide, isoform 6Voltage-gated calcium channel subunit alpha Cav2.3DEE69EIEE69gm139

Blockers (e.g., SNX-482, topiramate) inhibit channel-mediated calcium influx, reducing neuronal excitability and abnormal neurotransmission associated with epilepsy