SCN8A sodium voltage-gated channel alpha subunit 8 [Homo sapiens (human)] - Gene

Summary

Official Symbol: SCN8Aprovided by HGNC
Official Full Name: sodium voltage-gated channel alpha subunit 8provided by HGNC
Primary source: HGNC:HGNC:10596
See related: Ensembl:ENSG00000196876 MIM:600702; AllianceGenome:HGNC:10596
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: MED; PN4; CIAT; BFIS5; DEE13; NaCh6; CERIII; EIEE13; MYOCL2; Nav1.6
Summary: This gene encodes a member of the sodium channel alpha subunit gene family. The encoded protein forms the ion pore region of the voltage-gated sodium channel. This protein is essential for the rapid membrane depolarization that occurs during the formation of the action potential in excitable neurons. Mutations in this gene are associated with cognitive disability, pancerebellar atrophy and ataxia. Alternate splicing results in multiple transcript variants.[provided by RefSeq, May 2010]
Expression: Biased expression in brain (RPKM 8.0), testis (RPKM 1.0) and 2 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 12q13.13

Exon count:: 28

Annotation release	Status	Assembly	Chr	Location
RS_2023_10	current	GRCh38.p14 (GCF_000001405.40)	12	NC_000012.12 (51591233..51812864)
RS_2023_10	current	T2T-CHM13v2.0 (GCF_009914755.1)	12	NC_060936.1 (51554795..51776384)
105.20220307	previous assembly	GRCh37.p13 (GCF_000001405.25)	12	NC_000012.11 (51985017..52206648)

Chromosome 12 - NC_000012.12 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: HPA RNA-seq normal tissues
Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
BioProject: PRJEB4337
Publication: PMID 24309898
Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

[Clinical features and genetic analysis of five children with epilepsies due to variants of SCN8A gene].
Title: [Clinical features and genetic analysis of five children with epilepsies due to variants of SCN8A gene].
Coupling of Slack and NaV1.6 sensitizes Slack to quinidine blockade and guides anti-seizure strategy development.
Title: Coupling of Slack and Na(V)1.6 sensitizes Slack to quinidine blockade and guides anti-seizure strategy development.
Expanding the genotype-phenotype spectrum in SCN8A-related disorders.
Title: Expanding the genotype-phenotype spectrum in SCN8A-related disorders.
Clinical severity is correlated with age at seizure onset and biophysical properties of recurrent gain of function variants associated with SCN8A-related epilepsy.
Title: Clinical severity is correlated with age at seizure onset and biophysical properties of recurrent gain of function variants associated with SCN8A-related epilepsy.
Genotype-phenotype correlations in SCN8A-related disorders reveal prognostic and therapeutic implications.
Title: Genotype-phenotype correlations in SCN8A-related disorders reveal prognostic and therapeutic implications.
Nav1.6 promotes the progression of human follicular thyroid carcinoma cells via JAK-STAT signaling pathway.
Title: Nav1.6 promotes the progression of human follicular thyroid carcinoma cells via JAK-STAT signaling pathway.
Commonalities and distinctions between two neurodevelopmental disorder subtypes associated with SCN2A and SCN8A variants and literature review.
Title: Commonalities and distinctions between two neurodevelopmental disorder subtypes associated with SCN2A and SCN8A variants and literature review.
A SCN8A variant associated with severe early onset epilepsy and developmental delay: Loss- or gain-of-function?
Title: A SCN8A variant associated with severe early onset epilepsy and developmental delay: Loss- or gain-of-function?
Spontaneous seizures and elevated seizure susceptibility in response to somatic mutation of sodium channel Scn8a in the mouse.
Title: Spontaneous seizures and elevated seizure susceptibility in response to somatic mutation of sodium channel Scn8a in the mouse.
SCN8A Epilepsy, Developmental Encephalopathy, and Related Disorders.
Title: SCN8A Epilepsy, Developmental Encephalopathy, and Related Disorders.

Submit: New GeneRIF Correction See all GeneRIFs (76)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Associated conditions

Description	Tests
Cognitive impairment with or without cerebellar ataxia MedGen: C3280415 OMIM: 614306 GeneReviews: SCN8A-Related Epilepsy and/or Neurodevelopmental Disorders	Compare labs
Developmental and epileptic encephalopathy, 13 MedGen: C3281191 OMIM: 614558 GeneReviews: SCN8A-Related Epilepsy and/or Neurodevelopmental Disorders	Compare labs
Myoclonus, familial, 2 MedGen: C5193056 OMIM: 618364 GeneReviews: Not available	Compare labs
Seizures, benign familial infantile, 5 MedGen: C4310728 OMIM: 617080 GeneReviews: SCN8A-Related Epilepsy and/or Neurodevelopmental Disorders	Compare labs

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

D12S347 (e-PCR), detects polymorphism
- UniSTS:83463

RH78513 (e-PCR)
- UniSTS:47641

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

D12S1968 (e-PCR)
- UniSTS:12863

SHGC-31178 (e-PCR)
- UniSTS:4676

A006S01 (e-PCR)
- UniSTS:18010

G64248 (e-PCR)
- UniSTS:166786

D12S1546 (e-PCR)
- UniSTS:13965

D12S347 (e-PCR), detects polymorphism
- UniSTS:39063

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

SCN8A_3459 (e-PCR)
- UniSTS:462513

WI-15800 (e-PCR)
- UniSTS:4796

RH92945 (e-PCR)
- UniSTS:86209

G54251 (e-PCR)
- UniSTS:109518

G54253 (e-PCR)
- UniSTS:109520

G43469 (e-PCR)
- UniSTS:94950

G64234 (e-PCR)
- UniSTS:166904

RH11256 (e-PCR)
- UniSTS:43512

Gene Ontology Provided by GOA

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 voltage-gated sodium channel activity	IBA Inferred from Biological aspect of Ancestor more info
enables voltage-gated sodium channel activity	IDA Inferred from Direct Assay more info	PubMed
enables voltage-gated sodium channel activity	IMP Inferred from Mutant Phenotype more info	PubMed
enables voltage-gated sodium channel activity	NAS Non-traceable Author Statement more info	PubMed

Process	Evidence Code	Pubs
involved_in cardiac muscle cell action potential involved in contraction	IBA Inferred from Biological aspect of Ancestor more info
involved_in myelination	ISS Inferred from Sequence or Structural Similarity more info
involved_in nervous system development	TAS Traceable Author Statement more info	PubMed
involved_in neuronal action potential	IEA Inferred from Electronic Annotation more info
involved_in optic nerve development	IEA Inferred from Electronic Annotation more info
involved_in peripheral nervous system development	ISS Inferred from Sequence or Structural Similarity more info
involved_in sodium ion transmembrane transport	IBA Inferred from Biological aspect of Ancestor more info
involved_in sodium ion transport	NAS Non-traceable Author Statement more info	PubMed

Component	Evidence Code	Pubs
located_in Z disc	ISS Inferred from Sequence or Structural Similarity more info
located_in axon	ISS Inferred from Sequence or Structural Similarity more info
located_in axon initial segment	ISS Inferred from Sequence or Structural Similarity more info
located_in cell junction	IDA Inferred from Direct Assay more info
located_in cytoplasmic vesicle	IEA Inferred from Electronic Annotation more info
located_in glutamatergic synapse	IEA Inferred from Electronic Annotation more info
located_in membrane	TAS Traceable Author Statement more info	PubMed
located_in node of Ranvier	ISS Inferred from Sequence or Structural Similarity more info
located_in parallel fiber to Purkinje cell synapse	IEA Inferred from Electronic Annotation more info
located_in plasma membrane	IDA Inferred from Direct Assay more info
located_in postsynaptic density membrane	IEA Inferred from Electronic Annotation more info
located_in presynaptic active zone membrane	IEA Inferred from Electronic Annotation 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	IC Inferred by Curator more info	PubMed
part_of voltage-gated sodium channel complex	IDA Inferred from Direct Assay more info	PubMed

General protein information

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Preferred Names: sodium channel protein type 8 subunit alpha

Names: hNa6/Scn8a voltage-gated sodium channel; sodium channel, voltage gated, type VIII, alpha subunit; voltage-gated sodium channel subunit alpha Nav1.6; voltage-gated sodium channel type VIII alpha protein

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.

Genomic

NG_021180.3 RefSeqGene

Range

6276..227907

Download

GenBank, FASTA, Sequence Viewer (Graphics), LRG_1389

mRNA and Protein(s)

NM_001177984.3 → NP_001171455.1 sodium channel protein type 8 subunit alpha isoform 2

See identical proteins and their annotated locations for NP_001171455.1

Status: REVIEWED

Description

Transcript Variant: This variant (2) lacks an in-frame exon in the coding region, compared to variant 1. The encoded isoform (2) is shorter than isoform 1. Isoforms 2 and 4 are the same length but differ in their sequence.

Source sequence(s)

AB027567, AC013421, AC025097, AC068987, BX112779

Consensus CDS

CCDS53794.1

UniProtKB/Swiss-Prot

Q9UQD0

Related

ENSP00000440360.1, ENST00000545061.5

Conserved Domains (6) summary

smart00015
Location:1853 → 1874

IQ; Calmodulin-binding motif

cd13433
Location:1424 → 1476

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

pfam00520
Location:1481 → 1735

Ion_trans; Ion transport protein

pfam06512
Location:991 → 1192

Na_trans_assoc; Sodium ion transport-associated

pfam11933
Location:502 → 688

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

pfam16905
Location:1739 → 1802

GPHH; Voltage-dependent L-type calcium channel, IQ-associated
NM_001330260.2 → NP_001317189.1 sodium channel protein type 8 subunit alpha isoform 3

Status: REVIEWED

Description

Transcript Variant: This variant (3) contains an alternate in-frame exon in the 5' coding region, compared to variant 1. Isoforms 1 and 3 are the same length but differ in their sequence.

Source sequence(s)

AC013421, AC025097, AC068987, AC140060

Consensus CDS

CCDS81692.1

UniProtKB/Swiss-Prot

Q9UQD0

UniProtKB/TrEMBL

Q6B4S4

Related

ENSP00000487583.2, ENST00000627620.5

Conserved Domains (6) summary

smart00015
Location:1894 → 1915

IQ; Calmodulin-binding motif

cd13433
Location:1465 → 1517

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

pfam00520
Location:1197 → 1473

Ion_trans; Ion transport protein

pfam06512
Location:991 → 1192

Na_trans_assoc; Sodium ion transport-associated

pfam11933
Location:504 → 702

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

pfam16905
Location:1788 → 1835

GPHH; Voltage-dependent L-type calcium channel, IQ-associated
NM_001369788.1 → NP_001356717.1 sodium channel protein type 8 subunit alpha isoform 4

Status: REVIEWED

Description

Transcript Variant: Isoforms 2 and 4 are the same length but differ in their sequence.

Source sequence(s)

AC013421, AC025097, AC068987, AC140060

Consensus CDS

CCDS91697.1

UniProtKB/TrEMBL

A0A590UK43

Related

ENSP00000499691.1, ENST00000668547.1

Conserved Domains (6) summary

smart00015
Location:1853 → 1874

IQ; Calmodulin-binding motif

cd13433
Location:1424 → 1476

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

pfam00520
Location:1481 → 1735

Ion_trans; Ion transport protein

pfam06512
Location:991 → 1192

Na_trans_assoc; Sodium ion transport-associated

pfam11933
Location:502 → 692

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

pfam16905
Location:1739 → 1802

GPHH; Voltage-dependent L-type calcium channel, IQ-associated
NM_014191.4 → NP_055006.1 sodium channel protein type 8 subunit alpha isoform 1

See identical proteins and their annotated locations for NP_055006.1

Status: REVIEWED

Description

Transcript Variant: This variant (1) represents the longer transcript and encodes the longest isoform (1). Isoforms 1 and 3 are the same length but differ in their sequence.

Source sequence(s)

AB027567, AC013421, AC025097, AC068987

Consensus CDS

CCDS44891.1

UniProtKB/Swiss-Prot

B9VWG8, O95788, Q9NYX2, Q9UPB2, Q9UQD0

Related

ENSP00000346534.4, ENST00000354534.11

Conserved Domains (6) summary

smart00015
Location:1894 → 1915

IQ; Calmodulin-binding motif

cd13433
Location:1465 → 1517

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

pfam00520
Location:1197 → 1473

Ion_trans; Ion transport protein

pfam06512
Location:991 → 1192

Na_trans_assoc; Sodium ion transport-associated

pfam11933
Location:502 → 688

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

pfam16905
Location:1780 → 1843

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

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2023_10

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

Reference GRCh38.p14 Primary Assembly

Genomic

NC_000012.12 Reference GRCh38.p14 Primary Assembly

Range

51591233..51812864

Download

GenBank, FASTA, Sequence Viewer (Graphics)

Alternate T2T-CHM13v2.0

Genomic

NC_060936.1 Alternate T2T-CHM13v2.0

Range

51554795..51776384

Download

GenBank, FASTA, Sequence Viewer (Graphics)

Suppressed Reference Sequence(s)

The following Reference Sequences have been suppressed. Explain

NM_175894.2: Suppressed sequence

Description

NM_175894.2: This RefSeq was suppressed temporarily based on the calculation that the annotated protein was shorter than a protein or proteins from a putative ortholog.