The SCN7A/Nax gene encodes sodium channel protein type 7 subunit alpha (SCN7A), forming Nax channel that is considered as a descendant of the voltage-gated sodium channel, although it is not regulated by the membrane voltage. Like another alpha subunit of sodium channel proteins, SCN7A contains 4 internal repeats, each with 5 hydrophobic segments (S1, S2, S3, S5, S6) and one positively charged segment (S4). This sodium channel protein has some atypical characteristics; the similarity between the human and mouse proteins is lower compared to other orthologous sodium channel pairs. Also, the S4 segments, which sense voltage changes, have fewer arginine and lysine residues and fewer positive charged residues compared with other sodium channels.
|Basic Information of SCN7A|
|Protein Name||Sodium channel protein type 7 subunit alpha|
|Aliases||Putative voltage-gated sodium channel subunit alpha Nax, Sodium channel protein cardiac and skeletal muscle subunit alpha, Sodium channel protein type VII subunit alpha|
|Organism||Homo sapiens (Human)|
SCN7A was originally thought to be a glial sodium channel, however, in situ studies reveals that SCN7A/Nax is expressed in lung, uterus, heart, neurons and nonmyelinating Schwann cells in the peripheral nervous system. Recent experimental data indicate that the channel serves as a sodium-level sensor of the body fluid, and controls the Na-intake behavior by changing the excitability of neurons. In a large-scale gene-expression study in a rat model of temporal lobe epilepsy, a persistent increased SCN7A/Nax expression in neuron and reactive astroglia is revealed, which supports the possible involvement of this channel in the epileptogenic process. Normokalemic Periodic Paralysis is also associated with SCN7A.
Fig.1 Each of the four homologous domains makes up one subunit of the voltage-gated sodium channel.
This article finds that the enhanced expression of SCN7A/Nax channel within a distinct subpopulation of DRG neurons contributes to bone cancer pain by increasing the excitability of these neurons.
This article suggests that SNP rs7565062 of SCN7A is significantly associated with EH and the allele T of rs7565062 or the related haplotype G-A-T may be a genetic risk factor for EH in the Northern Han Chinese population.
This article suggests that SCN7A/Na(x) expression may be associated with temporal lobe epilepsy in rat and human hippocampus.
This article identifies several biomarkers including SCN7A in fixed colorectal carcinoma samples.
This article suggests that the mechanisms involved in systemic and central Na+ sensing are specific to each rodent species, because of the difference in NaX expression pattern and in NaX-expressing cell types.
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