Disease relevance of SCN8A

• The human homologue, SCN8A, maps to chromosome 12q13 and is a candidate gene for inherited neurodegenerative disease [1].
• The voltage-gated sodium channel SCN8A is associated with inherited neurological disorders in the mouse that include ataxia, dystonia, severe muscle weakness, and paralysis [2].
• The spastic paraplegia SPG10 locus: narrowing of critical region and exclusion of sodium channel gene SCN8A as a candidate [3].
• Molecular changes in neurons in multiple sclerosis: altered axonal expression of Nav1.2 and Nav1.6 sodium channels and Na+/Ca2+ exchanger [4].

Psychiatry related information on SCN8A

• Heterozygosity for a protein truncation mutation of sodium channel SCN8A in a patient with cerebellar atrophy, ataxia, and mental retardation [5].

High impact information on SCN8A

• Our results demonstrate the molecular identities of the sodium channels expressed along demyelinated and degenerating axons in MS and suggest that coexpression of Nav1.6 and Na+/Ca2+ exchanger is associated with axonal degeneration in MS [4].
• This new model suggests that SCN8A on chromosome 12q13 and SCNM1 on chromosome 1p21-1q21 may contribute to human inherited dystonia [6].
• This region harbors the type II keratin gene cluster, and potential candidate genes include SCN8A and HOXC genes [7].
• Alternative splicing of human transcripts for a subset of the genes that are expressed in dorsal root ganglia, SCN8A (Na(v)1.6), SCN9A (Na(v)1.7), and SCN11A (Na(v)1.9) was characterized in detail [8].
• Alternative splicing of the sodium channel SCN8A predicts a truncated two-domain protein in fetal brain and non-neuronal cells [9].

Biological context of SCN8A

• Consistent down-regulation of all transcripts was observed, as well as significant changes in the splicing patterns of SCN8A and SCN9A [8].
• Exon organization, coding sequence, physical mapping, and polymorphic intragenic markers for the human neuronal sodium channel gene SCN8A [2].
• The SCN8A protein is evolutionarily conserved, with 98.5% amino acid sequence identity between human and mouse [2].
• The polymorphic (CA)n microsatellite marker D12S2211, with PIC = 0.68, was isolated from intron 10C of SCN8A [2].
• Suicide attempt and basic mechanisms in neural conduction: relationships to the SCN8A and VAMP4 genes [10].

Anatomical context of SCN8A

• The voltage-gated sodium channel alpha subunit SCN8A is one of the most abundant sodium channels in neurons from brain and spinal cord [9].
• In this study, we explored whether ankyrin-G has a role in modifying gating properties of the neuronal Nav1.6 channel that is predominantly localized at nodes of Ranvier and initial segments [11].
• The somato-dendritic localization of Nav1.1 and Nav1.6 in Purkinje cells suggests that these isoforms are involved in the integration of synaptic input [12].
• Deep cerebellar nuclei neurons expressed Nav1.1 and Nav1.6 as well as Nabeta1 [12].
• Bergmann glia expressed Nav1.6, but not granule cell layer astrocytes [12].

Associations of SCN8A with chemical compounds

• The substitution of S553 with alanine within L1 of the Nav1.6 channel prevents p38-mediated reduction of Nav1.6 current density [13].

Other interactions of SCN8A

• Calmodulin binds to the C terminus of sodium channels Nav1.4 and Nav1.6 and differentially modulates their functional properties [14].

Analytical, diagnostic and therapeutic context of SCN8A

• Sequence analysis shows that Nav1.6 contains a putative MAP kinase-recognition module in the cytoplasmic loop (L1), which joins domains 1 and 2 [13].
• In situ hybridization and immunolocalization studies demonstrated that granule cells predominantly express Nav1.2, Nav1.6, Nabeta1, and Nabeta2 [12].

References