Relevance to Autism

Variants in the KCNT1 gene co-segregated with disease in three families with autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE) with major comorbidites of intellectual disability and psychiatric features (Heron et al., 2012). Furthermore, de novo variants in KCNT1 were identified in sporadic cases with nocturnal frontal lobe epilepsy (NFLE) and malignant migrating partial seizures of infancy (MMPSI) (Heron et al., 2012; Barcia et al., 2012). FMRP, the protein encoded by the syndromic ASD gene FMR1, binds to the C-terminus of the potassium channel encoded by KCNT1 to activate the channel (PMID 20512134).

Molecular Function

Potassium channels represent the most complex class of voltage-gated ion channels from both functional and structural standpoints. Their diverse functions include regulating neurotransmitter release, heart rate, insulin secretion, neuronal excitability, epithelial electrolyte transport, smooth muscle contraction, and cell volume. This gene encodes a sodium-activated potassium channel subunit which is thought to function in ion conductance and developmental signaling pathways. Mutations in this gene cause the early-onset epileptic disorders, malignant migrating partial seizures of infancy and autosomal dominant nocturnal frontal lobe epilepsy.

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