Mutations in KCNC3 are responsible for SCA13. This gene is expressed heavily in Purkinje cells, as is the case for some other SCA subtypes, where it is believed to play an important role in facilitating high-frequency action potential firing. There are two known mutations in this gene associated with SCA13. The first mutation, R420H, is located in the voltage-sensing S4 segment of the channel. As this mutation neutralizes a site important for voltage sensing, it is not surprising that it results in non-conducting channels. Neurons expressing such channels are unable to follow high-frequency input with adequate fidelity. The second SCA13 associated mutation, F448L, results in functional channels that have altered kinetics. The voltage for half activation of these channels (V½) is shifted<unk> mV hyperpolarized compared to wild-type. Deactivation of these channels is also slowed drastically compared to wild-type. This results in neurons with longer after-hyperpolarizations and thus, a decreased maximal firing rate.
Spinocerebellar ataxia type-13
Spinocerebellar ataxia type 6
Spinocerebellar ataxia type 1
Autosomal recessive cerebellar ataxia type 1
Jokela type spinal muscular atrophy
Autosomal recessive spastic ataxia of Charlevoix-Saguenay
Friedreich's ataxia
Stratton Parker syndrome