Property Summary

NCBI Gene PubMed Count 47
PubMed Score 279.45
PubTator Score 115.06

Knowledge Summary

Patent (17,384)

TINX Plot

  Disease (8)

Disease Target Count Z-score Confidence
Carcinoma 2147 0.0 1.0
Disease Target Count Z-score Confidence
Motor neuron disease 39 0.0 1.0
Disease Target Count Z-score Confidence
Intellectual disability 573 3.294 1.6
Disease Target Count Z-score Confidence
Dystonia 77 3.661 1.8

Expression

  Differential Expression (16)

Disease log2 FC p
malignant mesothelioma -2.700 1.7e-06
astrocytic glioma -1.700 3.5e-03
posterior fossa group A ependymoma -2.800 5.2e-22
oligodendroglioma -1.300 2.0e-15
psoriasis -1.500 3.3e-03
glioblastoma -2.900 5.2e-07
medulloblastoma -2.600 3.4e-10
atypical teratoid / rhabdoid tumor -3.200 2.8e-17
medulloblastoma, large-cell -3.000 1.8e-07
primitive neuroectodermal tumor -2.300 2.9e-07
primary pancreatic ductal adenocarcinoma -1.015 3.6e-02
intraductal papillary-mucinous adenoma (... 3.100 1.0e-03
adult high grade glioma -2.700 9.1e-07
pilocytic astrocytoma -2.600 5.2e-12
subependymal giant cell astrocytoma -2.140 4.3e-02
lung carcinoma 3.100 7.6e-55

Gene RIF (33)

PMID Text
26974309 the calpain-dependent cleavage of Nav1.6 channels expressed in human embryonic kidney (HEK) 293 cells caused the upregulation of I(NaP)
26677014 Our study establishes SCN8A as a novel gene in which a recurrent mutation causes BFIS/ICCA, expanding the clinical-genetic spectrum of combined epileptic and dyskinetic syndromes.
26182346 Human Nav1.6 channels generate larger resurgent currents than human Nav1.1 channels, but the SCN4B-derived Navbeta4 peptide does not protect either isoform from use-dependent reduction.
25818041 Epileptic encephalopathy related to mutations in the SCN8A genes.
25804238 Expression profiling of SCN8A and NDUFC2 genes in colorectal carcinoma is reported. There was no NDUFC2 differential expression in colorectal carcinoma.
25785782 The results of this study suggested that SCN8A mutation cause early onset epilepsy and intellectual disability.
25725044 These data strengthen previous findings linking gain-of-function mutations of SCN8A with EIEE and demonstrate the importance of functional testing in establishing the pathogenicity of de novo mutations.
25659151 identified the PI3K/Akt pathway, the cell-cycle regulator Wee1 kinase, and protein kinase C (PKC) as prospective regulatory nodes of neuronal excitability through modulation of the FGF14:Nav1.6 complex.
25568300 SCN8A encephalopathy presents in infancy with multiple seizure types.
24888894 SCN8A mutations can cause variable phenotypes, most of which can be diagnosed as unclassified early onset epileptic encephalopathies, and rarely as malignant migrating partial seizures in infancy.
24874546 Data support the contribution of gain-of-function mutations of Nav1.6 (de novo variant p.Thr767Ile) that increase excitatory pyramidal neuron excitability
23640885 inhibition of GSK3 reduces the assembly of the FGF14.Nav channel complex, modifies FGF14-dependent regulation of Na(+) currents, and induces dissociation and subcellular redistribution of the native FGF14.Nav channel complex in hippocampal neurons.
22365152 Discovered a de novo heterozygous missense mutation (c.5302A>G [p.Asn1768Asp]) in the voltage-gated sodium-channel gene SCN8A in the proband.
21630263 We conclude that Na(V) 1.6 is upregulated in CaC and could serve as a novel molecular marker for the metastatic behavior of this carcinoma.
21562192 The beta-subunits differentially regulate the expression and gating of Nav1.8 and Nav1.6 in dorsal root ganglion neurons.
21156207 Genetic variants of the SCN8A voltage-gated ion channel influence not only the phenotype of mice carrying the SCN1A mutation but also the seizure frequency.
20632842 Our findings suggest that the SCN8A gene may be involved in the susceptibility to suicidal behavior among psychiatric disorder patients in the Han Chinese population.
20632842 Observational study of gene-disease association. (HuGE Navigator)
20600647 Results show no significant difference in the size or immunofluorescence staining intensity of Na(v)1.6 nodal accumulations located at either typical or atypical nodal sites within axons in normal samples when compared to painful samples.
20483028 An important mechanism of electroacupuncture therapy is its regulation of Nav1.6 and Nav1.1 expression after ischemia.
20421839 Significant up-regulation of mRNA and protein for Nav1.6 is observed in rat hippocampal neurons following fluid percussion traumatic brain injury in an animal trial.
20379614 Clinical trial of gene-disease association and gene-environment interaction. (HuGE Navigator)
20204400 Using the whole-cell configuration of the patch-clamp technique, we investigated the Na(v)1.6 transient and persistent currents in HEK-293 cells.
19352218 Observational study of gene-disease association. (HuGE Navigator)
19136557 a variant of NaV1.6 participates in the control of podosome and invadopodia formation and suggest that intracellular sodium release mediated by NaV1.6 may regulate cellular invasion of macrophages and melanoma cells.
18812204 he results of this study indicate that SCN8A may be a potential susceptibility gene for bipolar disorder in the Han Chinese population.
18812204 Observational study of gene-disease association. (HuGE Navigator)
18718804 The data of this study suggested that mutations of SCN8A are unlikely to be a major cause of autosomal dominant essential tremor in Caucasian patients.
18718804 Observational study of gene-disease association. (HuGE Navigator)
17881658 results demonstrate that genetic interactions can alter seizure severity and support the hypothesis that genetic modifiers contribute to the clinical variability observed in severe myoclonic epilepsy of infancy
17805013 Different mechanisms underlie axonal degeneration in acute and chronic multiple sclerosis, with axonal injury at sites of coexpression of Nav1.6 and sodium-calcium exchanger in acute lesions but independent of coexpression in chronic lesions.
16775201 Mmbrane-binding domain of ankyrin-G is critical for reducing the persistent sodium current of Nav1.6.
16702217 Beta-scorpion toxin enhance channel activation, which could make it a model drug to replace deep brain stimulation of the subthalamic nucleus in patients with Parkinson disease.

AA Sequence

MAARLLAPPGPDSFKPFTPESLANIERRIAESKLKKPPKADGSHREDDEDSKPKPNSDLEAGKSLPFIYG      1 - 70
DIPQGLVAVPLEDFDPYYLTQKTFVVLNRGKTLFRFSATPALYILSPFNLIRRIAIKILIHSVFSMIIMC     71 - 140
TILTNCVFMTFSNPPDWSKNVEYTFTGIYTFESLVKIIARGFCIDGFTFLRDPWNWLDFSVIMMAYITEF    141 - 210
VNLGNVSALRTFRVLRALKTISVIPGLKTIVGALIQSVKKLSDVMILTVFCLSVFALIGLQLFMGNLRNK    211 - 280
CVVWPINFNESYLENGTKGFDWEEYINNKTNFYTVPGMLEPLLCGNSSDAGQCPEGYQCMKAGRNPNYGY    281 - 350
TSFDTFSWAFLALFRLMTQDYWENLYQLTLRAAGKTYMIFFVLVIFVGSFYLVNLILAVVAMAYEEQNQA    351 - 420
TLEEAEQKEAEFKAMLEQLKKQQEEAQAAAMATSAGTVSEDAIEEEGEEGGGSPRSSSEISKLSSKSAKE    421 - 490
RRNRRKKRKQKELSEGEEKGDPEKVFKSESEDGMRRKAFRLPDNRIGRKFSIMNQSLLSIPGSPFLSRHN    491 - 560
SKSSIFSFRGPGRFRDPGSENEFADDEHSTVEESEGRRDSLFIPIRARERRSSYSGYSGYSQGSRSSRIF    561 - 630
PSLRRSVKRNSTVDCNGVVSLIGGPGSHIGGRLLPEATTEVEIKKKGPGSLLVSMDQLASYGRKDRINSI    631 - 700
MSVVTNTLVEELEESQRKCPPCWYKFANTFLIWECHPYWIKLKEIVNLIVMDPFVDLAITICIVLNTLFM    701 - 770
AMEHHPMTPQFEHVLAVGNLVFTGIFTAEMFLKLIAMDPYYYFQEGWNIFDGFIVSLSLMELSLADVEGL    771 - 840
SVLRSFRLLRVFKLAKSWPTLNMLIKIIGNSVGALGNLTLVLAIIVFIFAVVGMQLFGKSYKECVCKINQ    841 - 910
DCELPRWHMHDFFHSFLIVFRVLCGEWIETMWDCMEVAGQAMCLIVFMMVMVIGNLVVLNLFLALLLSSF    911 - 980
SADNLAATDDDGEMNNLQISVIRIKKGVAWTKLKVHAFMQAHFKQREADEVKPLDELYEKKANCIANHTG    981 - 1050
ADIHRNGDFQKNGNGTTSGIGSSVEKYIIDEDHMSFINNPNLTVRVPIAVGESDFENLNTEDVSSESDPE   1051 - 1120
GSKDKLDDTSSSEGSTIDIKPEVEEVPVEQPEEYLDPDACFTEGCVQRFKCCQVNIEEGLGKSWWILRKT   1121 - 1190
CFLIVEHNWFETFIIFMILLSSGALAFEDIYIEQRKTIRTILEYADKVFTYIFILEMLLKWTAYGFVKFF   1191 - 1260
TNAWCWLDFLIVAVSLVSLIANALGYSELGAIKSLRTLRALRPLRALSRFEGMRVVVNALVGAIPSIMNV   1261 - 1330
LLVCLIFWLIFSIMGVNLFAGKYHYCFNETSEIRFEIEDVNNKTECEKLMEGNNTEIRWKNVKINFDNVG   1331 - 1400
AGYLALLQVATFKGWMDIMYAAVDSRKPDEQPKYEDNIYMYIYFVIFIIFGSFFTLNLFIGVIIDNFNQQ   1401 - 1470
KKKFGGQDIFMTEEQKKYYNAMKKLGSKKPQKPIPRPLNKIQGIVFDFVTQQAFDIVIMMLICLNMVTMM   1471 - 1540
VETDTQSKQMENILYWINLVFVIFFTCECVLKMFALRHYYFTIGWNIFDFVVVILSIVGMFLADIIEKYF   1541 - 1610
VSPTLFRVIRLARIGRILRLIKGAKGIRTLLFALMMSLPALFNIGLLLFLVMFIFSIFGMSNFAYVKHEA   1611 - 1680
GIDDMFNFETFGNSMICLFQITTSAGWDGLLLPILNRPPDCSLDKEHPGSGFKGDCGNPSVGIFFFVSYI   1681 - 1750
IISFLIVVNMYIAIILENFSVATEESADPLSEDDFETFYEIWEKFDPDATQFIEYCKLADFADALEHPLR   1751 - 1820
VPKPNTIELIAMDLPMVSGDRIHCLDILFAFTKRVLGDSGELDILRQQMEERFVASNPSKVSYEPITTTL   1821 - 1890
RRKQEEVSAVVLQRAYRGHLARRGFICKKTTSNKLENGGTHREKKESTPSTASLPSYDSVTKPEKEKQQR   1891 - 1960
AEEGRRERAKRQKEVRESKC                                                     1961 - 1980
//

Text Mined References (50)

PMID Year Title
27210545 2016 Autosomal dominant SCN8A mutation with an unusually mild phenotype.
26974309 2016 Cleavage of Na(+) channels by calpain increases persistent Na(+) current and promotes spasticity after spinal cord injury.
26900580 2016 Pathogenic mechanism of recurrent mutations of SCN8A in epileptic encephalopathy.
26677014 2016 Benign infantile seizures and paroxysmal dyskinesia caused by an SCN8A mutation.
26182346 2015 Human Nav1.6 Channels Generate Larger Resurgent Currents than Human Nav1.1 Channels, but the Nav?4 Peptide Does Not Protect Either Isoform from Use-Dependent Reduction.
25818041 2015 Diagnostic yield of genetic testing in epileptic encephalopathy in childhood.
25804238 2015 Expression profiling of SCN8A and NDUFC2 genes in colorectal carcinoma.
25785782 2015 SCN8A mutations in Chinese children with early onset epilepsy and intellectual disability.
25725044 2015 De novo gain-of-function and loss-of-function mutations of SCN8A in patients with intellectual disabilities and epilepsy.
25659151 2015 Identifying a kinase network regulating FGF14:Nav1.6 complex assembly using split-luciferase complementation.
25568300 2015 The phenotypic spectrum of SCN8A encephalopathy.
25239001 2014 Characterization of a de novo SCN8A mutation in a patient with epileptic encephalopathy.
24888894 2014 Early onset epileptic encephalopathy caused by de novo SCN8A mutations.
24874546 2014 A novel de novo mutation of SCN8A (Nav1.6) with enhanced channel activation in a child with epileptic encephalopathy.
24352161 2014 De novo SCN8A mutation identified by whole-exome sequencing in a boy with neonatal epileptic encephalopathy, multiple congenital anomalies, and movement disorders.
23640885 2013 The fibroblast growth factor 14·voltage-gated sodium channel complex is a new target of glycogen synthase kinase 3 (GSK3).
22365152 2012 De novo pathogenic SCN8A mutation identified by whole-genome sequencing of a family quartet affected by infantile epileptic encephalopathy and SUDEP.
21630263 2012 Overexpression of NaV 1.6 channels is associated with the invasion capacity of human cervical cancer.
21562192 2011 Regulation of Nav1.6 and Nav1.8 peripheral nerve Na+ channels by auxiliary ?-subunits.
21156207 2011 Neuronal voltage-gated ion channels are genetic modifiers of generalized epilepsy with febrile seizures plus.
21078353 2011 Addition of positive charges at the C-terminal peptide region of CssII, a mammalian scorpion peptide toxin, improves its affinity for sodium channels Nav1.6.
20632842 2010 Genetic polymorphisms in the SCN8A gene are associated with suicidal behavior in psychiatric disorders in the Chinese population.
20600647 2010 Pulpitis increases the proportion of atypical nodes of Ranvier in human dental pulp axons without a change in Nav1.6 sodium channel expression.
20483028 2010 Effect of electroacupuncture therapy on the expression of Na(v)1.1 and Na(v)1.6 in rat after acute cerebral ischemia.
20421839 2010 The up-regulation of voltage-gated sodium channel Nav1.6 expression following fluid percussion traumatic brain injury in rats.
20379614 Personalized smoking cessation: interactions between nicotine dose, dependence and quit-success genotype score.
20351042 2010 Sodium channel gene family: epilepsy mutations, gene interactions and modifier effects.
20204400 2010 Biophysical characterisation of the persistent sodium current of the Nav1.6 neuronal sodium channel: a single-channel analysis.
19352218 2009 Candidate gene analysis in an on-going genome-wide association study of attention-deficit hyperactivity disorder: suggestive association signals in ADRA1A.
19136557 2009 Regulation of podosome formation in macrophages by a splice variant of the sodium channel SCN8A.
18812204 2008 SCN8A as a novel candidate gene associated with bipolar disorder in the Han Chinese population.
18718804 2009 Evaluation of SCN8A as a candidate gene for autosomal dominant essential tremor.
17881658 2007 The voltage-gated sodium channel Scn8a is a genetic modifier of severe myoclonic epilepsy of infancy.
17805013 2007 Sodium channel expression within chronic multiple sclerosis plaques.
16775201 2006 Ankyrin-G regulates inactivation gating of the neuronal sodium channel, Nav1.6.
16702217 2006 Resurgent current and voltage sensor trapping enhanced activation by a beta-scorpion toxin solely in Nav1.6 channel. Significance in mice Purkinje neurons.
16541075 2006 The finished DNA sequence of human chromosome 12.
16382098 2005 International Union of Pharmacology. XLVII. Nomenclature and structure-function relationships of voltage-gated sodium channels.
16236810 2006 Heterozygosity for a protein truncation mutation of sodium channel SCN8A in a patient with cerebellar atrophy, ataxia, and mental retardation.
16014723 2005 Voltage-gated sodium channel Nav1.6 is modulated by p38 mitogen-activated protein kinase.
15676283 2005 Multiple transcripts of sodium channel SCN8A (Na(V)1.6) with alternative 5'- and 3'-untranslated regions and initial characterization of the SCN8A promoter.
15302875 2004 Expression of alternatively spliced sodium channel alpha-subunit genes. Unique splicing patterns are observed in dorsal root ganglia.
15282281 2004 Fibroblast growth factor homologous factor 2B: association with Nav1.6 and selective colocalization at nodes of Ranvier of dorsal root axons.
14702039 2004 Complete sequencing and characterization of 21,243 full-length human cDNAs.
10779552 2000 Sodium channel Na(v)1.6 is localized at nodes of ranvier, dendrites, and synapses.
10066808 1999 Activation of Go-proteins by membrane depolarization traced by in situ photoaffinity labeling of galphao-proteins with [alpha32P]GTP-azidoanilide.
9828131 1998 Exon organization, coding sequence, physical mapping, and polymorphic intragenic markers for the human neuronal sodium channel gene SCN8A.
9295353 1997 Alternative splicing of the sodium channel SCN8A predicts a truncated two-domain protein in fetal brain and non-neuronal cells.
8635876 1996 Isolation of genes differentially expressed in human primary myoblasts and embryonal rhabdomyosarcoma.
7670495 1995 Mutation of a new sodium channel gene, Scn8a, in the mouse mutant 'motor endplate disease'.