Scn8a sodium voltage-gated channel alpha subunit 8 [Rattus norvegicus (Norway rat)] - Gene

Summary

Official Symbol: Scn8aprovided by RGD
Official Full Name: sodium voltage-gated channel alpha subunit 8provided by RGD
Primary source: RGD:3638
See related: Ensembl:ENSRNOG00000005309 AllianceGenome:RGD:3638
Gene type: protein coding
RefSeq status: PROVISIONAL
Organism: Rattus norvegicus
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; Murinae; Rattus
Summary: Enables sodium ion binding activity and voltage-gated sodium channel activity. Involved in nervous system development; neuronal action potential; and sodium ion transport. Located in axon initial segment; node of Ranvier; and plasma membrane. Is integral component of membrane. Part of voltage-gated sodium channel complex. Is active in glutamatergic synapse and parallel fiber to Purkinje cell synapse. Is integral component of postsynaptic density membrane and integral component of presynaptic active zone membrane. Biomarker of congestive heart failure. Human ortholog(s) of this gene implicated in benign familial neonatal epilepsy and developmental and epileptic encephalopathy 13. Orthologous to human SCN8A (sodium voltage-gated channel alpha subunit 8). [provided by Alliance of Genome Resources, Apr 2022]
Expression: Biased expression in Brain (RPKM 284.3), Testes (RPKM 17.1) and 2 other tissues See more
Orthologs: human mouse all
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Genomic context

Location:: 7q36

Exon count:: 31

Annotation release	Status	Assembly	Chr	Location
RS_2024_02	current	GRCr8 (GCF_036323735.1)	7	NC_086025.1 (133860901..134034809)
RS_2023_06	previous assembly	mRatBN7.2 (GCF_015227675.2)	7	NC_051342.1 (131982152..132156075)
106	previous assembly	Rnor_6.0 (GCF_000001895.5)	7	NC_005106.4 (142575629..142683659)

Chromosome 7 - NC_086025.1 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

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Expression

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See details

Project title: A rat RNA-Seq transcriptomic BodyMap across 11 organs and 4 developmental stages
Description: 320 RNA samples isolated from 11 organs (adrenal gland, brain, heart, kidney, liver, lung, muscle, spleen, thymus, and testes or uterus) from both sexes of Fischer 344 rats across four developmental stages (2-, 6-, 21-, and 104-weeks-old)
BioProject: PRJNA238328
Publication: PMID 24510058
Analysis date: Mon Jun 6 17:44:12 2016

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Increased expression of Nav1.6 of reactive astrocytes in the globus pallidus is closely associated with motor deficits in a model of Parkinson's disease.
Title: Increased expression of Nav1.6 of reactive astrocytes in the globus pallidus is closely associated with motor deficits in a model of Parkinson's disease.
Upregulation of Nav1.6 Mediated by the p38 MAPK Pathway in the Dorsal Root Ganglia Contributes to Cancer-Induced Bone Pain in Rats.
Title: Upregulation of Na(v)1.6 Mediated by the p38 MAPK Pathway in the Dorsal Root Ganglia Contributes to Cancer-Induced Bone Pain in Rats.
Study found that knockdown of either NaV1.6 or NaVbeta4 reduced pain behaviors and sensory neuron hyperexcitability in the chronic compression dorsal rook ganglia model of low back pain.
Title: Role of Na(V)1.6 and Na(V)β4 Sodium Channel Subunits in a Rat Model of Low Back Pain Induced by Compression of the Dorsal Root Ganglia.
To clarify the exact expression patterns of Nav1.6 during epileptogenesis, we examined the expression of Nav1.6 at protein and mRNA levels in two distinct models of temporal lobe epilepsy including a post-status epilepticus model induced by kainic acid intrahippocampal injection and a kindling model evoked by pentylenetetrazole.
Title: Remarkable alterations of Nav1.6 in reactive astrogliosis during epileptogenesis.
Data strongly suggest that voltage-gated sodium channel subunit alpha Nav1.6 ( Nav1.6) plays an indispensable role in the peripheral pain hypersensitivity induced by BmK I.
Title: Local knockdown of Nav1.6 relieves pain behaviors induced by BmK I.
Study provides insight into the dynamics of Nav1.6 on the cell surface and raises new questions such as how somatic localization and function are linked and how localized regulation of these channels may influence overall neuronal physiology.
Title: Single-Molecule Imaging of Nav1.6 on the Surface of Hippocampal Neurons Reveals Somatic Nanoclusters.
The data support a model where ankyrinG-binding is required for preferential Nav1.6 insertion into the axon initial segment plasma membrane during development.
Title: Preferential targeting of Nav1.6 voltage-gated Na+ Channels to the axon initial segment during development.
Results highlight the relative importance of abnormal sensory neuron spontaneous activity in establishing both pain behaviors and sympathetic sprouting, and suggest that the NaV1.6 isoform may have value as a therapeutic target
Title: Local knockdown of the NaV1.6 sodium channel reduces pain behaviors, sensory neuron excitability, and sympathetic sprouting in rat models of neuropathic pain.
This study demonistrated that Knockdown of sodium channel NaV1.6 blocks mechanical pain and abnormal bursting activity of afferent neurons in inflamed sensory ganglia in rats.
Title: Knockdown of sodium channel NaV1.6 blocks mechanical pain and abnormal bursting activity of afferent neurons in inflamed sensory ganglia.
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.
Title: The fibroblast growth factor 14·voltage-gated sodium channel complex is a new target of glycogen synthase kinase 3 (GSK3).

Submit: New GeneRIF Correction See all GeneRIFs (19)

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

AU049240 (e-PCR)
- UniSTS:145688

Scn3a (e-PCR), detects polymorphism
- UniSTS:516640

Scn4a (e-PCR), detects polymorphism
- UniSTS:516642

BE103200 (e-PCR)
- UniSTS:244773

Scn8a (e-PCR), detects polymorphism
- UniSTS:516646

AU049825 (e-PCR)
- UniSTS:146271

Scn1a (e-PCR), detects polymorphism
- UniSTS:463471

G64248 (e-PCR)
- UniSTS:166786

SHGC-58494 (e-PCR)
- UniSTS:94368

SCN8A_3459 (e-PCR)
- UniSTS:462513

Gene Ontology Provided by RGD

Function	Evidence Code	Pubs
enables ATP binding	IEA Inferred from Electronic Annotation more info
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables sodium ion binding	IDA Inferred from Direct Assay more info	PubMed
enables sodium ion binding	IEA Inferred from Electronic Annotation more info
enables sodium ion binding	ISO Inferred from Sequence Orthology more info
enables voltage-gated sodium channel activity	IBA Inferred from Biological aspect of Ancestor more info
enables voltage-gated sodium channel activity	IC Inferred by Curator more info	PubMed
enables voltage-gated sodium channel activity	IDA Inferred from Direct Assay more info	PubMed
enables voltage-gated sodium channel activity	IEA Inferred from Electronic Annotation more info
enables voltage-gated sodium channel activity	IMP Inferred from Mutant Phenotype more info	PubMed
enables voltage-gated sodium channel activity	ISO Inferred from Sequence Orthology more info

Process	Evidence Code	Pubs
acts_upstream_of_or_within adult walking behavior	ISO Inferred from Sequence Orthology more info
acts_upstream_of_or_within locomotory behavior	ISO Inferred from Sequence Orthology more info
involved_in membrane depolarization during action potential	IBA Inferred from Biological aspect of Ancestor more info
acts_upstream_of_or_within muscle organ development	ISO Inferred from Sequence Orthology more info
involved_in myelination	IEP Inferred from Expression Pattern more info	PubMed
acts_upstream_of_or_within nerve development	ISO Inferred from Sequence Orthology more info
involved_in neuronal action potential	IBA Inferred from Biological aspect of Ancestor more info
involved_in neuronal action potential	IDA Inferred from Direct Assay more info	PubMed
involved_in neuronal action potential	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in optic nerve development	IEP Inferred from Expression Pattern more info	PubMed
involved_in peripheral nervous system development	IEP Inferred from Expression Pattern more info	PubMed
acts_upstream_of_or_within response to toxic substance	ISO Inferred from Sequence Orthology more info
acts_upstream_of_or_within sensory perception of sound	ISO Inferred from Sequence Orthology more info
involved_in sodium ion transmembrane transport	IBA Inferred from Biological aspect of Ancestor more info
involved_in sodium ion transmembrane transport	IEA Inferred from Electronic Annotation more info
involved_in sodium ion transport	IDA Inferred from Direct Assay more info	PubMed

Component	Evidence Code	Pubs
located_in Z disc	ISO Inferred from Sequence Orthology more info
is_active_in axon	IBA Inferred from Biological aspect of Ancestor more info
located_in axon	IDA Inferred from Direct Assay more info	PubMed
located_in axon initial segment	IDA Inferred from Direct Assay more info	PubMed
located_in cell junction	IEA Inferred from Electronic Annotation more info
located_in cell junction	ISO Inferred from Sequence Orthology more info
located_in dendrite	ISO Inferred from Sequence Orthology more info
is_active_in glutamatergic synapse	IDA Inferred from Direct Assay more info	PubMed
located_in membrane	ISO Inferred from Sequence Orthology more info
located_in neuronal cell body	ISO Inferred from Sequence Orthology more info
located_in node of Ranvier	IDA Inferred from Direct Assay more info	PubMed
located_in node of Ranvier	ISO Inferred from Sequence Orthology more info
is_active_in parallel fiber to Purkinje cell synapse	IDA Inferred from Direct Assay more info	PubMed
located_in plasma membrane	ISO Inferred from Sequence Orthology more info
is_active_in postsynaptic density membrane	IDA Inferred from Direct Assay more info	PubMed
is_active_in presynaptic active zone membrane	IDA Inferred from Direct Assay more info	PubMed
part_of sodium channel complex	ISO Inferred from Sequence Orthology more info
part_of voltage-gated sodium channel complex	IBA Inferred from Biological aspect of Ancestor more info
part_of voltage-gated sodium channel complex	IDA Inferred from Direct Assay more info	PubMed
part_of voltage-gated sodium channel complex	IEA Inferred from Electronic Annotation more info
part_of voltage-gated sodium channel complex	ISO Inferred from Sequence Orthology more info

General protein information

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Preferred Names: sodium channel protein type 8 subunit alpha

Names: Na+ channel; PN4; naCh6; peripheral nerve protein type 4; sodium channel 6; sodium channel protein type VIII subunit alpha; sodium channel, voltage gated, type VIII, alpha subunit; sodium channel, voltage-gated, type 8, alpha polypeptide; sodium channel, voltage-gated, type 8, alpha subunit; sodium channel, voltage-gated, type VIII, alpha polypeptide; voltage-gated sodium channel subunit alpha Nav1.6

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

mRNA and Protein(s)

NM_019266.3 → NP_062139.2 sodium channel protein type 8 subunit alpha

See identical proteins and their annotated locations for NP_062139.2

Status: PROVISIONAL

Source sequence(s)

JAXUCZ010000007

UniProtKB/Swiss-Prot

O88420, O88421

UniProtKB/TrEMBL

A6KCM2

Related

ENSRNOP00000075703.2, ENSRNOT00000080923.2

Conserved Domains (6) summary

smart00015
Location:1892 → 1913

IQ; Calmodulin-binding motif

cd13433
Location:1463 → 1515

Na_channel_gate; Inactivation gate of the voltage-gated sodium channel alpha subunits

pfam00520
Location:1195 → 1471

Ion_trans; Ion transport protein

pfam06512
Location:989 → 1190

Na_trans_assoc; Sodium ion transport-associated

pfam11933
Location:504 → 700

Na_trans_cytopl; Cytoplasmic domain of voltage-gated Na+ ion channel

pfam16905
Location:1786 → 1833

GPHH; Voltage-dependent L-type calcium channel, IQ-associated

RefSeqs of Annotated Genomes: GCF_036323735.1-RS_2024_02

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCr8

Genomic

NC_086025.1 Reference GRCr8

Range

133860901..134034809

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_063263132.1 → XP_063119202.1 sodium channel protein type 8 subunit alpha isoform X1

UniProtKB/Swiss-Prot

O88420, O88421
XM_063263131.1 → XP_063119201.1 sodium channel protein type 8 subunit alpha isoform X2

UniProtKB/TrEMBL

F1LMH2
XM_063263134.1 → XP_063119204.1 sodium channel protein type 8 subunit alpha isoform X4

UniProtKB/TrEMBL

A0A8I5ZX68
XM_063263130.1 → XP_063119200.1 sodium channel protein type 8 subunit alpha isoform X1

UniProtKB/Swiss-Prot

O88420, O88421
XM_063263133.1 → XP_063119203.1 sodium channel protein type 8 subunit alpha isoform X3
XM_063263137.1 → XP_063119207.1 sodium channel protein type 8 subunit alpha isoform X6
XM_063263135.1 → XP_063119205.1 sodium channel protein type 8 subunit alpha isoform X5