SCN8A
Domain
The sequence contains 4 internal repeats, each with 5 hydrophobic segments (S1, S2, S3, S5, S6) and one positively charged segment (S4). Segments S4 are probably the voltage-sensors and are characterized by a series of positively charged amino acids at every third position.
Function
Pore-forming subunit of a voltage-gated sodium channel complex assuming opened or closed conformations in response to the voltage difference across membranes and through which sodium ions selectively pass along their electrochemical gradient (PubMed:24874546, PubMed:25239001, PubMed:25725044, PubMed:26900580, PubMed:29726066, PubMed:33245860, PubMed:36696443, PubMed:36823201). Contributes to neuronal excitability by regulating action potential threshold and propagation (PubMed:24874546, PubMed:25239001, PubMed:25725044, PubMed:26900580, PubMed:29726066, PubMed:33245860, PubMed:36696443, PubMed:36823201).
Isoform 5
More specifically expressed in non-neuronal cells, could play a role in sodium release from intracellular compartments and participate in the control of podosomes formation and macrophages adhesion and movement.
Involvement in disease
Cognitive impairment with or without cerebellar ataxia
CIAT
A disorder characterized by markedly delayed cognitive and motor development, attention deficit disorder, and cerebellar ataxia. Features include bilateral esophoria, strabismatic amblyopia, unsustained gaze evoked nystagmus on horizontal gaze, ataxic gait, dysmetria in the upper limbs and dysarthria, with normal strength, tone, and reflexes.
None
The disease is caused by variants affecting the gene represented in this entry.
Developmental and epileptic encephalopathy 13
DEE13
A form of epilepsy characterized by frequent tonic seizures or spasms beginning in infancy with a specific EEG finding of suppression-burst patterns, characterized by high-voltage bursts alternating with almost flat suppression phases. Patients may progress to West syndrome, which is characterized by tonic spasms with clustering, arrest of psychomotor development, and hypsarrhythmia on EEG. DEE13 is a severe form consisting of early-onset seizures, features of autism, intellectual disability, ataxia, and sudden unexplained death in epilepsy.
None
The disease is caused by variants affecting the gene represented in this entry.
Seizures, benign familial infantile, 5
BFIS5
A form of benign familial infantile epilepsy, a neurologic disorder characterized by afebrile seizures occurring in clusters during the first year of life, without neurologic sequelae. BFIS5 inheritance is autosomal dominant.
None
The disease is caused by variants affecting the gene represented in this entry.
Myoclonus, familial, 2
MYOCL2
An autosomal dominant neurologic disorder characterized by upper limb isolated myoclonus without seizures or cognitive impairment. MYOCL2 is a non-progressive disease with onset in the first decade of life.
None
The disease may be caused by variants affecting the gene represented in this entry.
Post-translational modifications
May be ubiquitinated by NEDD4L; which would promote its endocytosis.
Phosphorylation at Ser-1497 by PKC in a highly conserved cytoplasmic loop slows inactivation of the sodium channel and reduces peak sodium currents.
Sequence Similarities
Belongs to the sodium channel (TC 1.A.1.10) family. Nav1.6/SCN8A subfamily.
Tissue Specificity
Expressed in the hippocampus with increased expression in epileptic tissue compared to normal adjacent tissue (at protein level) (PubMed:28842554).
Isoform 5
Expressed in non-neuronal tissues, such as monocytes/macrophages.
Cellular localization
- Cell membrane
- Multi-pass membrane protein
- Cell projection
- Axon
- Mainly localizes to the axon initial segment.
- Isoform 5
- Cytoplasmic vesicle
- Cell projection
- Podosome
Alternative names
MED, SCN8A, Sodium channel protein type 8 subunit alpha, Sodium channel protein type VIII subunit alpha, Voltage-gated sodium channel subunit alpha Nav1.6