IUPHAR DATABASE | Voltage-gated sodium channels

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Na_v1.6

Family: Voltage-gated sodium channels

Contents:

Gene and Protein Information

Previous and Unofficial Names

Phenotypes, Alleles and Disease Models

Clinically-Relevant Mutations and Pathophysiology

Gene Expression and Pathophysiology

References

Gene and Protein Information
Species	TM	P Loops	AA	Chromosomal Location	Gene Symbol	Gene Name	Reference
Human	24	1	1980	12q13	SCN8A	sodium channel, voltage gated, type VIII, alpha subunit	1-2,16
Mouse	24	1	1978	15 F1	Scn8a	sodium channel, voltage-gated, type VIII, alpha	2,20
Rat	24	1	1978	7q36	Scn8a	sodium channel, voltage gated, type VIII, alpha subunit	4,18

Previous and Unofficial Names
NaCh6
PN4
CerIII
Nav1.6
MED
sodium channel, voltage gated, type VIII, alpha polypeptide
Na+ channel
peripheral nerve protein type 4
sodium channel 6
sodium channel protein type 8 subunit alpha
sodium channel protein type VIII subunit alpha
sodium channel voltage-gated type VIII alpha polypeptide
sodium channel, voltage-gated, type 8, alpha polypeptide
sodium channel, voltage-gated, type 8, alpha subunit
sodium channel, voltage-gated, type VIII, alpha
voltage-gated sodium channel subunit alpha Nav1.6
seal
motor end-plate disease
nmf2
ataxia 3
mnd-2
mnd2
nmf58
NMF335
nur14
AI853486
C630029C19Rik
dmu

Previous and Unofficial Names

NaCh6

PN4

CerIII

Nav1.6

MED

sodium channel, voltage gated, type VIII, alpha polypeptide

Na+ channel

peripheral nerve protein type 4

sodium channel 6

sodium channel protein type 8 subunit alpha

sodium channel protein type VIII subunit alpha

sodium channel voltage-gated type VIII alpha polypeptide

sodium channel, voltage-gated, type 8, alpha polypeptide

sodium channel, voltage-gated, type 8, alpha subunit

sodium channel, voltage-gated, type VIII, alpha

voltage-gated sodium channel subunit alpha Nav1.6

seal

motor end-plate disease

nmf2

ataxia 3

mnd-2

mnd2

nmf58

NMF335

nur14

AI853486

C630029C19Rik

dmu

Database Links
ChEMBL Target	18079 (Hs)
Ensembl	ENSG00000196876 (Hs), ENSMUSG00000023033 (Mm), ENSRNOG00000005309 (Rn)
Entrez Gene	6334 (Hs), 20273 (Mm), 29710 (Rn)
GeneCards	SCN8A (Hs)
GenitoUrinary Development Molecular Anatomy Project	Scn8a (Mm)
HomoloGene	7927 (Hs)
Human Protein Reference Database	09006 (Hs)
InterPro	Q9UQD0 (Hs), Q9WTU3 (Mm), O88420 (Rn)
KEGG Gene	hsa:6334 (Hs), mmu:20273 (Mm), rno:29710 (Rn)
OMIM	600702 (Hs)
PharmGKB Gene	PA35009 (Hs)
PhosphoSitePlus	Q9UQD0 (Hs), Q9WTU3 (Mm), O88420 (Rn)
Protein Ontology (PRO)	PRO:000002103 (Hs)
RefSeq Nucleotide	NM_014191 (Hs), NM_001077499 (Mm), NM_019266 (Rn)
RefSeq Protein	NP_055006 (Hs), NP_001070967 (Mm), NP_062139 (Rn)
TreeFam	ENSG00000196876 (Hs), ENSMUSG00000023033 (Mm), ENSRNOG00000005309 (Rn)
UniGene Hs.	436550 (Hs)
UniProt	Q9UQD0 (Hs), Q9WTU3 (Mm), O88420 (Rn)
Wikipedia	Na_v1.6
	Voltage-gated sodium channels

Search for 3D structures on the PDB
Search by keyword: Voltage-gated sodium channels Na_v1.6	Search by accession number: Q9WTU3, Q9UQD0, O88420

Associated Proteins

Heteromeric Pore-forming Subunits
Name	References
Not determined

Auxiliary Subunits
Name	References
β₄	24
β₃	13
β₂	5,8
β₁	7,12

Other Associated Proteins
Name	References
Not determined

Voltage Dependence

	V_0.5 (mV)	τ (msec)	Reference	Cell type	Species
Activation	-28.7	-	1	HEK 293 cells.	Human
Inactivation	-71.9	-	1	HEK 293 cells.	Human
Comments	Human channels expressed without β subunits.

	V_0.5 (mV)	τ (msec)	Reference	Cell type	Species
Activation	-18.7	0.1	6	Na_v1.8 null mouse DRG neurons.	Mouse
Inactivation	-64.1	1.0	6	Na_v1.8 null mouse DRG neurons.	Mouse
Comments	Mouse channel with a TTX-resistant mutation (Y371S), kinetics measured at -10mV.

	V_0.5 (mV)	τ (msec)	Reference	Cell type	Species
Activation	-8.5	-	20	Xenopus laevis oocyte	Mouse
Inactivation	-54.7	-	20	Xenopus laevis oocyte	Mouse
Comments	Mouse channel without β subunits.

Activators

Key to terms and symbols

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Ligand					Sp.	Affinity	Units	Concentration range (M)	Holding voltage (mV)	Reference
β-scorpion toxin Cn2					Hs	-	-	3x10^-7 - 1x10^-8	-	19

Activator Comments

Several scorpion toxins have been reported as potential activators of Na_v1.6 (for example Β-scorpion toxin Tz1) [2888-2889]

Gating inhibitors

Key to terms and symbols

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Ligand	Sp.	Affinity	Units	Concentration range (M)	Holding voltage (mV)	Reference
ATX-II	Hs	6.7	pEC₅₀	-	-80.0	14
AFT-II	Hs	6.5	pEC₅₀	-	-80.0	14
Bc-III	Hs	6.0	pEC₅₀	-	-80.0	14

Gating Inhibitor Comments

α scorpion toxins have been reported to inhibit a variety of Na_V1.x ion channels including Na_V1.6 [9]

Pore Blockers

Key to terms and symbols

View all chemical structures

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Ligand	Sp.	Affinity	Units	Concentration range (M)	Holding voltage (mV)	Reference
tetrodotoxin	Rn	9.0	pIC₅₀	-	-130.0	4
tetrodotoxin	Mm	8.2	pIC₅₀	-	-60.0	20
4,9-anhydro-tetrodotoxin	Mm	7.8	pIC₅₀	-	-100.0	17

View species-specific pore blocker tables

Tissue Distribution

PNS: Dorsal root ganglia, nodes of Ranvier of sensory and motor axons.

Species:	Rat
Technique:	Immunohistochemistry
References:	3,18,21

CNS: Somato-dendritic distribution in output neurons of the cerebellum, cerebral cortex and hippocampus, Purkinje cells in the cerebellar granule cell layer, brainstem and spinal cord, astrocytes and Schwann cells, nodes of Ranvier.

Species:	Rat
Technique:	Immunohistochemistry
References:	18,21,23

Phenotypes, Alleles and Disease Models

Mouse data from MGI

Click here to show/hide data

Allele	Composition & genetic background	Accession	Phenotype Id	Phenotype	Reference
Scn8a^med	Scn8a^med/Scn8a^med PCT	MGI:103169	MP:0005402	abnormal action potential	PMID: 4323310
Scn8a^dmu	Scn8a^dmu/Scn8a^dmu involves: C3H * C57BL/6	MGI:103169	MP:0010492	abnormal atrium endocardium morphology	PMID: 11532991
Scn8a^Clth	Scn8a^Clth/Scn8a^Clth involves: BALB/cAnN * C3H/HeH	MGI:103169	MP:0004924	abnormal behavior	PMID: 19737145
Scn8a⁺\|Scn8a^Clth	Scn8a^Clth/Scn8a⁺ involves: BALB/cAnN * C3H/HeH	MGI:103169	MP:0004924	abnormal behavior	PMID: 19737145
Scn8a^5J	Scn8a^5J/Scn8a^5J C57BL/6J-Scn8a<5J>/J	MGI:103169	MP:0002152	abnormal brain morphology
Scn8a^5J	Scn8a^5J/Scn8a^5J C57BL/6J-Scn8a<5J>/J	MGI:103169	MP:0000822	abnormal brain ventricle morphology
Scn8a^med-J\|Scnm1^tm1.1Mm	Scn8a^med-J/Scn8a^med-J,Scnm1^tm1.1Mm/Scnm1^tm1.1Mm involves: C57BL/6 * FVB * SJL * STOCK Krt71	MGI:103169 MGI:1341284	MP:0005621	abnormal cell physiology	PMID: 18791226
Scn8a^med-J\|Scnm1^s	Scn8a^med-J/Scn8a^med-J,Scnm1^s/Scnm1^s involves: C57BL/6J * STOCK Krt71	MGI:103169 MGI:1341284	MP:0005621	abnormal cell physiology	PMID: 18791226
Scn8a^7J	Scn8a^7J/Scn8a^7J involves: BALB/cByJ * C57BL/6J	MGI:103169	MP:0000872	abnormal cerebellum external granule cell layer morphology
Scn8a^med	Scn8a^med/Scn8a^med PCT	MGI:103169	MP:0002914	abnormal endplate potential	PMID: 4323310
Scn8a^dmu	Scn8a^dmu/Scn8a^dmu involves: C3H * C57BL/6 * C57BL/6J	MGI:103169	MP:0005551	abnormal eye electrophysiology	PMID: 15901786
Scn8a^dmu	Scn8a^dmu/Scn8a^dmu involves: C3H * C57BL/6 * DBA/2J	MGI:103169	MP:0005551	abnormal eye electrophysiology	PMID: 15901786
Scn8a^med	Scn8a^med/Scn8a^med involves: C3HeB/FeJ * DBA/2J	MGI:103169	MP:0005551	abnormal eye electrophysiology	PMID: 15901786
Scn8a^med-TgA4Bs	Scn8a^med-TgA4Bs/Scn8a^med-TgA4Bs B6.Cg-Scn8a	MGI:103169	MP:0005551	abnormal eye electrophysiology	PMID: 16822974
Scn8a^6J	Scn8a^6J/Scn8a^6J C57BL/6J-Scn8a<6J>/J	MGI:103169	MP:0001406	abnormal gait
Scn8a^med-jo2J	Scn8a^med-jo2J/Scn8a^med-jo2J B6(129S7)-Scn8a/J	MGI:103169	MP:0001406	abnormal gait
Scn8a^m1Btlr	Scn8a^m1Btlr/Scn8a^m1Btlr C57BL/6J-Scn8a	MGI:103169	MP:0001406	abnormal gait
Scn8a⁺\|Scn8a^m1Btlr	Scn8a^m1Btlr/Scn8a⁺ C57BL/6J-Scn8a	MGI:103169	MP:0001406	abnormal gait
Scn8a^med-J	Scn8a^med-J/Scn8a^med-J involves: STOCK Krt71	MGI:103169	MP:0001406	abnormal gait	PMID: 18791226
Scn8a^8J	Scn8a^8J/Scn8a^8J involves: C3HeB/FeJ * C57BL/6J	MGI:103169	MP:0001406	abnormal gait	PMID: 19254928
Scn8a^dmu	Scn8a^dmu/Scn8a^dmu involves: C3H * C57BL/6	MGI:103169	MP:0006113	abnormal heart septum morphology	PMID: 11532991
Scn8a^dmu	Scn8a^dmu/Scn8a^dmu involves: C3H * C57BL/6	MGI:103169	MP:0005294	abnormal heart ventricle morphology	PMID: 11532991
Scn8a^8J	Scn8a^8J/Scn8a^8J involves: C3HeB/FeJ * C57BL/6J	MGI:103169	MP:0001392	abnormal locomotor activity	PMID: 19254928
Scn8a^med	Scn8a^med/Scn8a^med PCT	MGI:103169	MP:0004835	abnormal miniature endplate potential	PMID: 4323310
Scn8a^med	Scn8a^med/Scn8a^med PCT	MGI:103169	MP:0002106	abnormal muscle physiology	PMID: 4323310
Scn8a^med	Scn8a^med/Scn8a^med PCT	MGI:103169	MP:0004142	abnormal muscle tone
Scn8a^med	Scn8a^med/Scn8a^med PCT	MGI:103169	MP:0005403	abnormal nerve conduction	PMID: 6127695
Scn8a^med-jo	Scn8a^med-jo/Scn8a^med-jo DBA/2WyDi-Scn8a	MGI:103169	MP:0002272	abnormal nervous system electrophysiology
Scn8a^med	Scn8a^med/Scn8a^med PCT	MGI:103169	MP:0001053	abnormal neuromuscular synapse morphology	PMID: 4315332
Scn8a^Clth	Scn8a^Clth/Scn8a^Clth involves: BALB/cAnN * C3H/HeH	MGI:103169	MP:0001492	abnormal pilomotor reflex	PMID: 19737145
Scn8a⁺\|Scn8a^Clth	Scn8a^Clth/Scn8a⁺ involves: BALB/cAnN * C3H/HeH	MGI:103169	MP:0001492	abnormal pilomotor reflex	PMID: 19737145
Scn8a⁺\|Scn8a^Clth	Scn8a^Clth/Scn8a⁺ involves: BALB/cAnN * C3H/HeH	MGI:103169	MP:0001485	abnormal pinna reflex	PMID: 19737145
Scn8a^7J	Scn8a^7J/Scn8a^7J involves: BALB/cByJ * C57BL/6J	MGI:103169	MP:0001504	abnormal posture
Scn8a^Clth	Scn8a^Clth/Scn8a^Clth involves: BALB/cAnN * C3H/HeH	MGI:103169	MP:0001961	abnormal reflex	PMID: 19737145
Scn8a⁺\|Scn8a^med	Scn8a^med/Scn8a⁺ C3Fe.Cg-Scn8a/J	MGI:103169	MP:0008840	abnormal spike wave discharge	PMID: 19254928
Scn8a⁺\|Scn8a^med-jo	Scn8a^med-jo/Scn8a⁺ B6.D2-Scn8a/J	MGI:103169	MP:0008840	abnormal spike wave discharge	PMID: 19254928
Scn1a⁺\|Scn1a^tm1Wac\|Scn8a⁺\|Scn8a^med-jo	Scn1a^tm1Wac/Scn1a⁺,Scn8a^med-jo/Scn8a⁺ involves: 129 * C57BL/6J * DBA/2WyDi * FVB/NJ	MGI:103169 MGI:98246	MP:0008840	abnormal spike wave discharge	PMID: 17881658
Scn8a^8J	Scn8a^8J/Scn8a^8J involves: C3HeB/FeJ * C57BL/6J	MGI:103169	MP:0008840	abnormal spike wave discharge	PMID: 19254928
Scn8a⁺\|Scn8a^8J	Scn8a^8J/Scn8a⁺ involves: C3HeB/FeJ * C57BL/6J	MGI:103169	MP:0008840	abnormal spike wave discharge	PMID: 19254928
Scn8a^7J	Scn8a^7J/Scn8a^7J involves: BALB/cByJ * C57BL/6J	MGI:103169	MP:0003993	abnormal ventral spinal root morphology
Scn8a^med	Scn8a^med/Scn8a^med PCT	MGI:103169	MP:0003491	abnormal voluntary movement
Scn8a^dmu\|Scn8a^med	Scn8a^dmu/Scn8a^med involves: C3H * C3HeB/Fe * C57BL/6	MGI:103169	MP:0003491	abnormal voluntary movement	PMID: 11532991
Scn8a⁺\|Scn8a^Clth	Scn8a^Clth/Scn8a⁺ involves: BALB/cAnN * C3H/HeH	MGI:103169	MP:0006358	absent pinna reflex	PMID: 19737145
Scn8a^med-J\|Scnm1^s	Scn8a^med-J/Scn8a^med-J,Scnm1^s/Scnm1^s involves: C57BL/6J	MGI:103169 MGI:1341284	MP:0001393	ataxia	PMID: 12374766
Scn8a^tm1Mm\|Tg(Zp3-cre)3Mrt	Scn8a^tm1Mm/Scn8a^tm1Mm,Tg(Zp3-cre)3Mrt/? involves: 129S1/Sv * 129X1/SvJ * C57BL/6J	MGI:103169 MGI:2176051	MP:0001393	ataxia	PMID: 15286995
Scn8a^7J	Scn8a^7J/Scn8a^7J involves: BALB/cByJ * C57BL/6J	MGI:103169	MP:0001393	ataxia
Scn8a^med-J	Scn8a^med-J/Scn8a^med-J involves: STOCK Krt71	MGI:103169	MP:0001393	ataxia	PMID: 18791226
Scn8a^nur14	Scn8a^nur14/Scn8a^nur14 C57BL/6J-Scn8a	MGI:103169	MP:0001393	ataxia	PMID: 19261867
Scn8a^med-TgA4Bs\|Scn8a^nur14	Scn8a^med-TgA4Bs/Scn8a^nur14 involves: C3H * C57BL/6J	MGI:103169	MP:0001393	ataxia	PMID: 19261867
Scn8a^med-jo2J	Scn8a^med-jo2J/Scn8a^med-jo2J B6(129S7)-Scn8a/J	MGI:103169	MP:0005405	axon degeneration
Scn8a^med-jo2J	Scn8a^med-jo2J/Scn8a^med-jo2J B6(129S7)-Scn8a/J	MGI:103169	MP:0004709	cervical vertebrae degeneration
Scn8a^4J	Scn8a^4J/Scn8a^4J C57BL/6J-Scn8a<4J>/J	MGI:103169	MP:0001265	decreased body size
Scn8a^8J	Scn8a^8J/Scn8a^8J involves: C3HeB/FeJ * C57BL/6J	MGI:103169	MP:0001265	decreased body size	PMID: 19254928
Scn8a^6J	Scn8a^6J/Scn8a^6J C57BL/6J-Scn8a<6J>/J	MGI:103169	MP:0001262	decreased body weight
Scn8a^dmu	Scn8a^dmu/Scn8a^dmu involves: C3H * C57BL/6	MGI:103169	MP:0001262	decreased body weight	PMID: 11532991
Scn8a^med-TgA4Bs	Scn8a^med-TgA4Bs/Scn8a^med-TgA4Bs involves: C3H * C57BL/6J	MGI:103169	MP:0001262	decreased body weight	PMID: 7601440
Scn8a^Clth	Scn8a^Clth/Scn8a^Clth involves: BALB/cAnN * C3H/HeH	MGI:103169	MP:0001262	decreased body weight	PMID: 19737145
Scn8a⁺\|Scn8a^Clth	Scn8a^Clth/Scn8a⁺ involves: BALB/cAnN * C3H/HeH	MGI:103169	MP:0001262	decreased body weight	PMID: 19737145
Scn8a^med-jo2J	Scn8a^med-jo2J/Scn8a^med-jo2J B6(129S7)-Scn8a/J	MGI:103169	MP:0004765	decreased brainstem auditory evoked potential
Scn8a^Clth	Scn8a^Clth/Scn8a^Clth involves: BALB/cAnN * C3H/HeH	MGI:103169	MP:0004765	decreased brainstem auditory evoked potential	PMID: 19737145
Scn8a⁺\|Scn8a^Clth	Scn8a^Clth/Scn8a⁺ involves: BALB/cAnN * C3H/HeH	MGI:103169	MP:0004765	decreased brainstem auditory evoked potential	PMID: 19737145
Scn8a^5J	Scn8a^5J/Scn8a^5J C57BL/6J-Scn8a<5J>/J	MGI:103169	MP:0008924	decreased cerebellar granule cell number
Scn8a^Clth	Scn8a^Clth/Scn8a^Clth involves: BALB/cAnN * C3H/HeH	MGI:103169	MP:0000880	decreased Purkinje cell number	PMID: 19737145
Scn8a^7J	Scn8a^7J/Scn8a^7J involves: BALB/cByJ * C57BL/6J	MGI:103169	MP:0009400	decreased skeletal muscle fiber size
Scn8a^Clth	Scn8a^Clth/Scn8a^Clth involves: BALB/cAnN * C3H/HeH	MGI:103169	MP:0001489	decreased startle reflex	PMID: 19737145
Scn8a⁺\|Scn8a^Clth	Scn8a^Clth/Scn8a⁺ involves: BALB/cAnN * C3H/HeH	MGI:103169	MP:0001489	decreased startle reflex	PMID: 19737145
Scn8a⁺\|Scn8a^med	Scn8a^med/Scn8a⁺ C3Fe.Cg-Scn8a/J	MGI:103169	MP:0002887	decreased susceptibility to pharmacologically induced seizures	PMID: 17881658
Scn8a⁺\|Scn8a^med-jo	Scn8a^med-jo/Scn8a⁺ B6.D2-Scn8a/J	MGI:103169	MP:0002887	decreased susceptibility to pharmacologically induced seizures	PMID: 17881658
Scn8a^med	Scn8a^med/Scn8a^med PCT	MGI:103169	MP:0000921	demyelination	PMID: 6127695 6319212
Scn8a^med-J\|Scnm1^s	Scn8a^med-J/Scn8a^med-J,Scnm1^s/Scnm1^s involves: C57BL/6J	MGI:103169 MGI:1341284	MP:0005323	dystonia	PMID: 12374766
Scn8a^med-J	Scn8a^med-J/Scn8a^med-J involves: STOCK Krt71	MGI:103169	MP:0005323	dystonia	PMID: 18791226
Scn8a^dmu	Scn8a^dmu/Scn8a^dmu involves: C3H * C57BL/6	MGI:103169	MP:0000752	dystrophic muscle	PMID: 11532991
Scn8a^dmu\|Scn8a^med	Scn8a^dmu/Scn8a^med involves: C3H * C3HeB/Fe * C57BL/6	MGI:103169	MP:0000752	dystrophic muscle	PMID: 11532991
Scn8a^Clth	Scn8a^Clth/Scn8a^Clth involves: BALB/cAnN * C3H/HeH	MGI:103169	MP:0009779	enhanced behavioral response to anesthetic	PMID: 19737145
Scn8a^7J	Scn8a^7J/Scn8a^7J involves: BALB/cByJ * C57BL/6J	MGI:103169	MP:0005307	head tossing
Scn8a^med	Scn8a^med/Scn8a^med PCT	MGI:103169	MP:0000755	hindlimb paralysis
Scn8a^4J	Scn8a^4J/Scn8a^4J C57BL/6J-Scn8a<4J>/J	MGI:103169	MP:0000755	hindlimb paralysis
Scn8a^5J	Scn8a^5J/Scn8a^5J C57BL/6J-Scn8a<5J>/J	MGI:103169	MP:0000755	hindlimb paralysis
Scn8a^nur14	Scn8a^nur14/Scn8a^nur14 involves: C57BL/6J	MGI:103169	MP:0000755	hindlimb paralysis	PMID: 12955145
Scn8a^tm1Mm\|Tg(Zp3-cre)3Mrt	Scn8a^tm1Mm/Scn8a^tm1Mm,Tg(Zp3-cre)3Mrt/? involves: 129S1/Sv * 129X1/SvJ * C57BL/6J	MGI:103169 MGI:2176051	MP:0000755	hindlimb paralysis	PMID: 15286995
Scn8a^med-J\|Scnm1^tm1.1Mm	Scn8a^med-J/Scn8a^med-J,Scnm1^tm1.1Mm/Scnm1^tm1.1Mm involves: C57BL/6 * FVB * SJL * STOCK Krt71	MGI:103169 MGI:1341284	MP:0000755	hindlimb paralysis	PMID: 18791226
Scn8a^dmu	Scn8a^dmu/Scn8a^dmu involves: C3H * C57BL/6	MGI:103169	MP:0000755	hindlimb paralysis	PMID: 11532991
Scn8a^dmu\|Scn8a^med	Scn8a^dmu/Scn8a^med involves: C3H * C3HeB/Fe * C57BL/6	MGI:103169	MP:0000755	hindlimb paralysis	PMID: 11532991
Scn8a^med-TgA4Bs	Scn8a^med-TgA4Bs/Scn8a^med-TgA4Bs involves: C3H * C57BL/6J	MGI:103169	MP:0000755	hindlimb paralysis	PMID: 7601440
Scn8a^nur14	Scn8a^nur14/Scn8a^nur14 C57BL/6J-Scn8a	MGI:103169	MP:0000755	hindlimb paralysis	PMID: 19261867
Scn8a^Clth	Scn8a^Clth/Scn8a^Clth involves: BALB/cAnN * C3H/HeH	MGI:103169	MP:0001505	hunched posture	PMID: 19737145
Scn8a⁺\|Scn8a^Clth	Scn8a^Clth/Scn8a⁺ involves: BALB/cAnN * C3H/HeH	MGI:103169	MP:0001505	hunched posture	PMID: 19737145
Scn8a^5J	Scn8a^5J/Scn8a^5J C57BL/6J-Scn8a<5J>/J	MGI:103169	MP:0001891	hydroencephaly
Scn8a^med-TgA4Bs	Scn8a^med-TgA4Bs/Scn8a^med-TgA4Bs involves: C3H * C57BL/6J	MGI:103169	MP:0001525	impaired balance	PMID: 7601440
Scn8a^Clth	Scn8a^Clth/Scn8a^Clth involves: BALB/cAnN * C3H/HeH	MGI:103169	MP:0001405	impaired coordination	PMID: 19737145
Scn8a^Clth	Scn8a^Clth/Scn8a^Clth involves: BALB/cAnN * C3H/HeH	MGI:103169	MP:0006325	impaired hearing	PMID: 19737145
Scn8a⁺\|Scn8a^Clth	Scn8a^Clth/Scn8a⁺ involves: BALB/cAnN * C3H/HeH	MGI:103169	MP:0006325	impaired hearing	PMID: 19737145
Scn8a^med-jo	Scn8a^med-jo/Scn8a^med-jo DBA/2WyDi-Scn8a	MGI:103169	MP:0001524	impaired limb coordination
Scn8a^Clth	Scn8a^Clth/Scn8a^Clth involves: BALB/cAnN * C3H/HeH	MGI:103169	MP:0001363	increased anxiety-related response	PMID: 19737145
Scn8a^7J	Scn8a^7J/Scn8a^7J involves: BALB/cByJ * C57BL/6J	MGI:103169	MP:0001513	limb grasping
Scn8a^med-TgA4Bs	Scn8a^med-TgA4Bs/Scn8a^med-TgA4Bs involves: C3H * C57BL/6J	MGI:103169	MP:0001513	limb grasping	PMID: 7601440
Scn8a^dmu	Scn8a^dmu/Scn8a^dmu involves: C3H * C57BL/6	MGI:103169	MP:0000749	muscle degeneration	PMID: 11532991
Scn8a^med-J\|Scnm1^s	Scn8a^med-J/Scn8a^med-J,Scnm1^s/Scnm1^s involves: C57BL/6J * STOCK Krt71	MGI:103169 MGI:1341284	MP:0000747	muscle weakness	PMID: 18791226
Scn8a^med	Scn8a^med/Scn8a^med PCT	MGI:103169	MP:0002269	muscular atrophy	PMID: 4315332
Scn8a^6J	Scn8a^6J/Scn8a^6J C57BL/6J-Scn8a<6J>/J	MGI:103169	MP:0002269	muscular atrophy	PMID: 15170223
Scn8a^med-J\|Scnm1^s	Scn8a^med-J/Scn8a^med-J,Scnm1^s/Scnm1^s involves: C57BL/6J	MGI:103169 MGI:1341284	MP:0002269	muscular atrophy	PMID: 12374766
Scn8a^med-TgA4Bs	Scn8a^med-TgA4Bs/Scn8a^med-TgA4Bs involves: C3H * C57BL/6J	MGI:103169	MP:0002269	muscular atrophy	PMID: 7601440
Scn8a^dmu	Scn8a^dmu/Scn8a^dmu involves: C3H * C57BL/6	MGI:103169	MP:0004566	myocardial fiber degeneration	PMID: 11532991
Scn8a^7J	Scn8a^7J/Scn8a^7J involves: BALB/cByJ * C57BL/6J	MGI:103169	MP:0000243	myoclonus
Scn8a^7J	Scn8a^7J/Scn8a^7J involves: BALB/cByJ * C57BL/6J	MGI:103169	MP:0000751	myopathy
Scn8a^med-jo2J	Scn8a^med-jo2J/Scn8a^med-jo2J B6(129S7)-Scn8a/J	MGI:103169	MP:0002687	oligozoospermia
Scn8a^med-J\|Scnm1^s	Scn8a^med-J/Scn8a^med-J,Scnm1^s/Scnm1^s involves: C57BL/6J	MGI:103169 MGI:1341284	MP:0000753	paralysis	PMID: 12374766
Scn8a^7J	Scn8a^7J/Scn8a^7J involves: BALB/cByJ * C57BL/6J	MGI:103169	MP:0000958	peripheral nervous system degeneration
Scn8a^med	Scn8a^med/Scn8a^med PCT	MGI:103169	MP:0002082	postnatal lethality	PMID: 4315332
Scn8a^nur14	Scn8a^nur14/Scn8a^nur14 involves: C57BL/6J	MGI:103169	MP:0002082	postnatal lethality	PMID: 12955145
Scn8a^med-jo2J	Scn8a^med-jo2J/Scn8a^med-jo2J B6(129S7)-Scn8a/J	MGI:103169	MP:0002082	postnatal lethality
Scn8a^med-J\|Scnm1^I112T	Scn8a^med-J/Scn8a^med-J,Scnm1^I112T/Scnm1^I112T involves: C57BL/6 * STOCK Krt71	MGI:103169 MGI:1341284	MP:0002082	postnatal lethality	PMID: 18791226
Scn8a^dmu\|Scn8a^med	Scn8a^dmu/Scn8a^med involves: C3H * C3HeB/Fe * C57BL/6	MGI:103169	MP:0002082	postnatal lethality	PMID: 11532991
Scn1a^tm1Wac\|Scn8a⁺\|Scn8a^med-jo	Scn1a^tm1Wac/Scn1a^tm1Wac,Scn8a^med-jo/Scn8a⁺ involves: 129 * C57BL/6J * DBA/2WyDi * FVB/NJ	MGI:103169 MGI:98246	MP:0002082	postnatal lethality	PMID: 17881658
Scn8a^8J	Scn8a^8J/Scn8a^8J involves: C3HeB/FeJ * C57BL/6J	MGI:103169	MP:0002082	postnatal lethality	PMID: 19254928
Scn8a^med-TgA4Bs\|Scn8a^nur14	Scn8a^med-TgA4Bs/Scn8a^nur14 involves: C3H * C57BL/6J	MGI:103169	MP:0002082	postnatal lethality	PMID: 19261867
Scn8a^4J	Scn8a^4J/Scn8a^4J C57BL/6J-Scn8a<4J>/J	MGI:103169	MP:0002083	premature death
Scn8a^5J	Scn8a^5J/Scn8a^5J C57BL/6J-Scn8a<5J>/J	MGI:103169	MP:0002083	premature death
Scn8a^6J	Scn8a^6J/Scn8a^6J C57BL/6J-Scn8a<6J>/J	MGI:103169	MP:0002083	premature death
Scn8a^med-J\|Scnm1^s	Scn8a^med-J/Scn8a^med-J,Scnm1^s/Scnm1^s involves: C57BL/6J	MGI:103169 MGI:1341284	MP:0002083	premature death	PMID: 12374766
Scn8a^tm1Mm\|Tg(Zp3-cre)3Mrt	Scn8a^tm1Mm/Scn8a^tm1Mm,Tg(Zp3-cre)3Mrt/? involves: 129S1/Sv * 129X1/SvJ * C57BL/6J	MGI:103169 MGI:2176051	MP:0002083	premature death	PMID: 15286995
Scn8a^med-J\|Scnm1^tm1.1Mm	Scn8a^med-J/Scn8a^med-J,Scnm1^tm1.1Mm/Scnm1^tm1.1Mm involves: C57BL/6 * FVB * SJL * STOCK Krt71	MGI:103169 MGI:1341284	MP:0002083	premature death	PMID: 18791226
Scn8a^med-J\|Scnm1^s	Scn8a^med-J/Scn8a^med-J,Scnm1^s/Scnm1^s involves: C57BL/6J * STOCK Krt71	MGI:103169 MGI:1341284	MP:0002083	premature death	PMID: 18791226
Scn8a^dmu	Scn8a^dmu/Scn8a^dmu involves: C3H * C57BL/6	MGI:103169	MP:0002083	premature death	PMID: 11532991
Scn8a^med-TgA4Bs	Scn8a^med-TgA4Bs/Scn8a^med-TgA4Bs involves: C3H * C57BL/6J	MGI:103169	MP:0002083	premature death	PMID: 7601440
Scn8a^8J	Scn8a^8J/Scn8a^8J involves: C3HeB/FeJ * C57BL/6J	MGI:103169	MP:0002083	premature death	PMID: 19254928
Scn8a^nur14	Scn8a^nur14/Scn8a^nur14 C57BL/6J-Scn8a	MGI:103169	MP:0002083	premature death	PMID: 19261867
Scn8a^med	Scn8a^med/Scn8a^med PCT	MGI:103169	MP:0000748	progressive muscle weakness	PMID: 4315332
Scn8a^med-jo2J	Scn8a^med-jo2J/Scn8a^med-jo2J B6(129S7)-Scn8a/J	MGI:103169	MP:0000876	Purkinje cell degeneration
Scn8a^med-jo	Scn8a^med-jo/Scn8a^med-jo DBA/2WyDi-Scn8a	MGI:103169	MP:0000876	Purkinje cell degeneration
Scn8a^dmu	Scn8a^dmu/Scn8a^dmu involves: C3H * C57BL/6	MGI:103169	MP:0001954	respiratory distress	PMID: 11532991
Scn8a^dmu	Scn8a^dmu/Scn8a^dmu involves: C3H * C57BL/6	MGI:103169	MP:0003852	skeletal muscle necrosis	PMID: 11532991
Scn8a^Clth	Scn8a^Clth/Scn8a^Clth involves: BALB/cAnN * C3H/HeH	MGI:103169	MP:0000852	small cerebellum	PMID: 19737145
Scn8a^med-jo2J	Scn8a^med-jo2J/Scn8a^med-jo2J B6(129S7)-Scn8a/J	MGI:103169	MP:0000745	tremors
Scn8a^m1Btlr	Scn8a^m1Btlr/Scn8a^m1Btlr C57BL/6J-Scn8a	MGI:103169	MP:0000745	tremors
Scn8a⁺\|Scn8a^m1Btlr	Scn8a^m1Btlr/Scn8a⁺ C57BL/6J-Scn8a	MGI:103169	MP:0000745	tremors
Scn8a^med-J	Scn8a^med-J/Scn8a^med-J involves: STOCK Krt71	MGI:103169	MP:0000745	tremors	PMID: 18791226
Scn8a^med-jo	Scn8a^med-jo/Scn8a^med-jo DBA/2WyDi-Scn8a	MGI:103169	MP:0000745	tremors
Scn8a^nur14	Scn8a^nur14/Scn8a^nur14 C57BL/6J-Scn8a	MGI:103169	MP:0000745	tremors	PMID: 19261867
Scn8a^med-TgA4Bs\|Scn8a^nur14	Scn8a^med-TgA4Bs/Scn8a^nur14 involves: C3H * C57BL/6J	MGI:103169	MP:0000745	tremors	PMID: 19261867
Scn8a^Clth	Scn8a^Clth/Scn8a^Clth involves: BALB/cAnN * C3H/HeH	MGI:103169	MP:0000745	tremors	PMID: 19737145
Scn8a⁺\|Scn8a^Clth	Scn8a^Clth/Scn8a⁺ involves: BALB/cAnN * C3H/HeH	MGI:103169	MP:0000745	tremors	PMID: 19737145

Clinically-Relevant Mutations and Pathophysiology

Disease:	Severe Epileptic Encephalopathy
OMIM:	308350, 614558
Orphanet:	1934
Role:	Increased persistent current, incomplete inactivation, depolarizing shift in the voltage-dependence of steady-state fast inactivation
References:	22

Click column headers to sort

Type	Species	Molecular location	Description	Reference
Missense	Human	N1768D		22

Disease:	Motor Endplate Disease
Role:	Early onset progressive paralysis of hind limbs, severe muscle atrophy, degeneration of cerebellar Purkinje cells and juvenile lethality.
References:	2

Click column headers to sort

Type	Species	Molecular location	Description	Reference
Intragenic deletion	Mouse	-		2

Disease:	Cerebellar ataxia
Comments:	This mutation is responsible for cerebellar ataxia in the mouse mutant jolting.
References:	10

Click column headers to sort

Type	Species	Molecular location	Description	Reference
Missense	Mouse	A1071T		10

Gene Expression and Pathophysiology

Single point mutation A1071T

Tissue or cell type:	Cerebellar Purkinje neurons
Pathophysiology:	Cerebellar ataxia
Species:	Mouse
Technique:
References:	10

Knock-out mice and two single point mutations A1071T and V929F

Tissue or cell type:	Neurons
Pathophysiology:	Mutant mice demonstrated spike-wave discharges indicative of absence epilepsy
Species:	Mouse
Technique:	Gene knockout
References:	15

Intragenic deletion causing complete loss of expression

Tissue or cell type:	Neurons
Pathophysiology:	Early onset progressive paralysis of hind limbs, severe muscle atrophy, degeneration of cerebellar Purkinje cells and juvenile lethality
Species:	Mouse
Technique:
References:	2

Knock-out mice and a single point mutation A1071T

Tissue or cell type:	Neurons
Pathophysiology:	Both types of mutant mice were more resistant to flurothyl- and kainic acid-induced seizures than wild-type mice
Species:	Mouse
Technique:	Gene knockout
References:	11

REFERENCES

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1. Burbidge, SA; Dale, TJ; Powell, AJ; Whitaker, WR; Xie, XM; Romanos, MA; Clare, JJ. (2002) Molecular cloning, distribution and functional analysis of the NA(V)1.6. Voltage-gated sodium channel from human brain. Brain Res. Mol. Brain Res., 103 (1-2): 80-90. [PMID:12106694]

2. Burgess, DL; Kohrman, DC; Galt, J; Plummer, NW; Jones, JM; Spear, B; Meisler, MH. (1995) Mutation of a new sodium channel gene, Scn8a, in the mouse mutant 'motor endplate disease'. Nat. Genet., 10 (4): 461-5. [PMID:7670495]

3. Caldwell, JH; Schaller, KL; Lasher, RS; Peles, E; Levinson, SR. (2000) Sodium channel Na(v)1.6 is localized at nodes of ranvier, dendrites, and synapses. Proc. Natl. Acad. Sci. U.S.A., 97 (10): 5616-20. [PMID:10779552]

4. Dietrich, PS; McGivern, JG; Delgado, SG; Koch, BD; Eglen, RM; Hunter, JC; Sangameswaran, L. (1998) Functional analysis of a voltage-gated sodium channel and its splice variant from rat dorsal root ganglia. J. Neurochem., 70 (6): 2262-72. [PMID:9603190]

5. Eubanks, J; Srinivasan, J; Dinulos, MB; Disteche, CM; Catterall, WA. (1997) Structure and chromosomal localization of the beta2 subunit of the human brain sodium channel. Neuroreport, 8 (12): 2775-9. [PMID:9295116]

6. Herzog, RI; Cummins, TR; Ghassemi, F; Dib-Hajj, SD; Waxman, SG. (2003) Distinct repriming and closed-state inactivation kinetics of Nav1.6 and Nav1.7 sodium channels in mouse spinal sensory neurons. J. Physiol. (Lond.), 551 (Pt 3): 741-50. [PMID:12843211]

7. Isom, LL; De Jongh, KS; Patton, DE; Reber, BF; Offord, J; Charbonneau, H; Walsh, K; Goldin, AL; Catterall, WA. (1992) Primary structure and functional expression of the beta 1 subunit of the rat brain sodium channel. Science, 256 (5058): 839-42. [PMID:1375395]

8. Isom, LL; Ragsdale, DS; De Jongh, KS; Westenbroek, RE; Reber, BF; Scheuer, T; Catterall, WA. (1995) Structure and function of the beta 2 subunit of brain sodium channels, a transmembrane glycoprotein with a CAM motif. Cell, 83 (3): 433-42. [PMID:8521473]

9. Kahn, R; Karbat, I; Ilan, N; Cohen, L; Sokolov, S; Catterall, WA; Gordon, D; Gurevitz, M. (2009) MOLECULAR REQUIREMENTS FOR RECOGNITION OF BRAIN VOLTAGE-GATED SODIUM CHANNELS BY SCORPION ALPHA-TOXINS. J. Biol. Chem., . [PMID:19509294]

10. Kohrman, DC; Smith, MR; Goldin, AL; Harris, J; Meisler, MH. (1996) A missense mutation in the sodium channel Scn8a is responsible for cerebellar ataxia in the mouse mutant jolting. J. Neurosci., 16 (19): 5993-9. [PMID:8815882]

11. Martin, MS; Tang, B; Papale, LA; Yu, FH; Catterall, WA; Escayg, A. (2007) The voltage-gated sodium channel Scn8a is a genetic modifier of severe myoclonic epilepsy of infancy. Hum. Mol. Genet., 16 (23): 2892-9. [PMID:17881658]

12. McClatchey, AI; Cannon, SC; Slaugenhaupt, SA; Gusella, JF. (1993) The cloning and expression of a sodium channel beta 1-subunit cDNA from human brain. Hum. Mol. Genet., 2 (6): 745-9. [PMID:8394762]

13. Morgan, K; Stevens, EB; Shah, B; Cox, PJ; Dixon, AK; Lee, K; Pinnock, RD; Hughes, J; Richardson, PJ; Mizuguchi, K; Jackson, AP. (2000) beta 3: an additional auxiliary subunit of the voltage-sensitive sodium channel that modulates channel gating with distinct kinetics. Proc. Natl. Acad. Sci. U.S.A., 97 (5): 2308-13. [PMID:10688874]

14. Oliveira, JS; Redaelli, E; Zaharenko, AJ; Cassulini, RR; Konno, K; Pimenta, DC; Freitas, JC; Clare, JJ; Wanke, E. (2004) Binding specificity of sea anemone toxins to Nav 1.1-1.6 sodium channels: unexpected contributions from differences in the IV/S3-S4 outer loop. J. Biol. Chem., 279 (32): 33323-35. [PMID:15169781]

15. Papale, LA; Beyer, B; Jones, JM; Sharkey, LM; Tufik, S; Epstein, M; Letts, VA; Meisler, MH; Frankel, WN; Escayg, A. (2009) Heterozygous mutations of the voltage-gated sodium channel SCN8A are associated with spike-wave discharges and absence epilepsy in mice. Hum. Mol. Genet., 18 (9): 1633-41. [PMID:19254928]

16. Plummer, NW; Galt, J; Jones, JM; Burgess, DL; Sprunger, LK; Kohrman, DC; Meisler, MH. (1998) Exon organization, coding sequence, physical mapping, and polymorphic intragenic markers for the human neuronal sodium channel gene SCN8A. Genomics, 54 (2): 287-96. [PMID:9828131]

17. Rosker, C; Lohberger, B; Hofer, D; Steinecker, B; Quasthoff, S; Schreibmayer, W. (2007) The TTX metabolite 4,9-anhydro-TTX is a highly specific blocker of the Na(v1.6) voltage-dependent sodium channel. Am. J. Physiol., Cell Physiol., 293 (2): C783-9. [PMID:17522141]

18. Schaller, KL; Krzemien, DM; Yarowsky, PJ; Krueger, BK; Caldwell, JH. (1995) A novel, abundant sodium channel expressed in neurons and glia. J. Neurosci., 15 (5 Pt 1): 3231-42. [PMID:7751906]

19. Schiavon, E; Sacco, T; Cassulini, RR; Gurrola, G; Tempia, F; Possani, LD; Wanke, E. (2006) Resurgent current and voltage sensor trapping enhanced activation by a beta-scorpion toxin solely in Nav1.6 channel. Significance in mice Purkinje neurons. J. Biol. Chem., 281 (29): 20326-37. [PMID:16702217]

20. Smith, MR; Smith, RD; Plummer, NW; Meisler, MH; Goldin, AL. (1998) Functional analysis of the mouse Scn8a sodium channel. J. Neurosci., 18 (16): 6093-102. [PMID:9698304]

21. Tzoumaka, E; Tischler, AC; Sangameswaran, L; Eglen, RM; Hunter, JC; Novakovic, SD. (2000) Differential distribution of the tetrodotoxin-sensitive rPN4/NaCh6/Scn8a sodium channel in the nervous system. J. Neurosci. Res., 60 (1): 37-44. [PMID:10723066]

22. Veeramah, KR; O'Brien, JE; Meisler, MH; Cheng, X; Dib-Hajj, SD; Waxman, SG; Talwar, D; Girirajan, S; Eichler, EE; Restifo, LL; et al.. (2012) De novo pathogenic SCN8A mutation identified by whole-genome sequencing of a family quartet affected by infantile epileptic encephalopathy and SUDEP. Am. J. Hum. Genet., 90 (3): 502-10. [PMID:22365152]

23. Whitaker, W; Faull, R; Waldvogel, H; Plumpton, C; Burbidge, S; Emson, P; Clare, J. (1999) Localization of the type VI voltage-gated sodium channel protein in human CNS. Neuroreport, 10 (17): 3703-9. [PMID:10619670]

24. Yu, FH; Westenbroek, RE; Silos-Santiago, I; McCormick, KA; Lawson, D; Ge, P; Ferriera, H; Lilly, J; DiStefano, PS; Catterall, WA; Scheuer, T; Curtis, R. (2003) Sodium channel beta4, a new disulfide-linked auxiliary subunit with similarity to beta2. J. Neurosci., 23 (20): 7577-85. [PMID:12930796]

To cite this database page, please use the following:

William A. Catterall, Alan L. Goldin, Stephen G. Waxman.
Voltage-gated sodium channels: Na_v1.6. Last modified on 04/01/2013. Accessed on 22/05/2013. IUPHAR database (IUPHAR-DB), http://www.iuphar-db.org/DATABASE/ObjectDisplayForward?objectId=583.

Voltage-gated sodium channels
	Introduction
	Contributors
	References
	Na_v1.1
	Na_v1.2
	Na_v1.3
	Na_v1.4
	Na_v1.5
	Na_v1.6
	Na_v1.7
	Na_v1.8
	Na_v1.9