SCN8A

SCN8A is a gene that encodes the alpha subunit of the voltage-gated sodium channel, Nav1.6. This channel is primarily found in the neurons of the central nervous system and plays a crucial role in the propagation of action potentials in neurons. Mutations in the SCN8A gene have been associated with a variety of neurological disorders, including epilepsy, intellectual disability, and movement disorders.

Structure

The SCN8A gene is located on the short (p) arm of chromosome 12 at position 13. The encoded protein, Nav1.6, is a large, complex molecule composed of four homologous domains (I-IV), each containing six transmembrane segments (S1-S6). The S4 segment in each domain acts as a voltage sensor, while the pore-forming loop between S5 and S6 is responsible for sodium ion selectivity and conductance.

Function

Nav1.6 channels are primarily expressed in the axon initial segment and nodes of Ranvier in neurons, where they play a critical role in the initiation and propagation of action potentials. They are also involved in the regulation of neuronal excitability and synaptic transmission.

Clinical significance

Mutations in the SCN8A gene can lead to a variety of neurological disorders. These include:

• SCN8A encephalopathy: This severe condition is characterized by early-onset epileptic seizures, intellectual disability, and movement disorders. It is caused by de novo (new) mutations in the SCN8A gene.

• Early infantile epileptic encephalopathy 13 (EIEE13): This is a severe form of epilepsy that begins in infancy. Affected individuals have frequent seizures and severe intellectual disability.

• Intellectual disability, autosomal dominant 16 (MRD16): This condition is characterized by mild to moderate intellectual disability, often accompanied by seizures.

See also

• Voltage-gated ion channel
• Sodium channelopathy

References

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