SCN2A
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
Mediates the voltage-dependent sodium ion permeability of excitable membranes. Assuming opened or closed conformations in response to the voltage difference across the membrane, the protein forms a sodium-selective channel through which Na(+) ions may pass in accordance with their electrochemical gradient (PubMed:1325650, PubMed:17021166, PubMed:28256214, PubMed:29844171). Implicated in the regulation of hippocampal replay occurring within sharp wave ripples (SPW-R) important for memory (By similarity).
Involvement in disease
Seizures, benign familial infantile, 3
BFIS3
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. BFIS3 inheritance is autosomal dominant.
None
The disease is caused by variants affecting the gene represented in this entry.
Developmental and epileptic encephalopathy 11
DEE11
An autosomal dominant seizure disorder characterized by neonatal or infantile onset of refractory seizures with resultant delayed neurologic development and persistent neurologic abnormalities. Patients may progress to West syndrome, which is characterized by tonic spasms with clustering, arrest of psychomotor development, and hypsarrhythmia on EEG.
None
The disease is caused by variants affecting the gene represented in this entry.
Defects in SCN2A are associated with genetic epilepsy with febrile seizures plus (GEFS+), a familial autosomal dominant epilepsy syndrome, a clinical subset of febrile seizures, characterized by frequent episodes after 6 years of age and various types of subsequent epilepsy.
Defects in SCN2A are associated with autism spectrum disorders (ASD). It seems that mutations resulting in sodium channel gain of function and increased neuron excitability lead to infantile seizures, whereas variants resulting in sodium channel loss of function and decrease neuron excitability are associated with ASD.
Episodic ataxia 9
EA9
An autosomal dominant neurologic disorder characterized by episodic ataxia manifesting in the first years of life, early-onset seizures, difficulty walking, dizziness, slurred speech, headache, vomiting, and pain. The duration of ataxic episodes is heterogeneous. Most patients show episodes lasting minutes to maximum several hours, but periods lasting days up to weeks have been reported. Some patients have mildly delayed development with speech delay and/or autistic features or mildly impaired intellectual development.
None
The disease is 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-1506 by PKC in a highly conserved cytoplasmic loop slows inactivation of the sodium channel and reduces peak sodium currents.
Sumoylated at Lys-38. Sumoylation is induced by hypoxia, increases voltage-gated sodium current and mediates the early response to acute hypoxia in neurons. Sumoylated SCN2A is located at the cell membrane.
Sequence Similarities
Belongs to the sodium channel (TC 1.A.1.10) family. Nav1.2/SCN2A subfamily.
Cellular localization
- Cell membrane
- Multi-pass membrane protein
Alternative names
HBA, NAC2, SCN2A1, SCN2A2, SCN2A, Sodium channel protein type 2 subunit alpha, HBSC II, Sodium channel protein brain II subunit alpha, Sodium channel protein type II subunit alpha, Voltage-gated sodium channel subunit alpha Nav1.2