SCN2A sodium voltage-gated channel alpha subunit 2 [Homo sapiens (human)] - Gene

Summary

Official Symbol: SCN2Aprovided by HGNC
Official Full Name: sodium voltage-gated channel alpha subunit 2provided by HGNC
Primary source: HGNC:HGNC:10588
See related: Ensembl:ENSG00000136531 MIM:182390; AllianceGenome:HGNC:10588
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: EA9; HBA; NAC2; BFIC3; BFIS3; BFNIS; DEE11; HBSCI; EIEE11; HBSCII; Nav1.2; SCN2A1; SCN2A2; Na(v)1.2
Summary: Voltage-gated sodium channels are transmembrane glycoprotein complexes composed of a large alpha subunit with four repeat domains, each of which is composed of six membrane-spanning segments, and one or more regulatory beta subunits. Voltage-gated sodium channels function in the generation and propagation of action potentials in neurons and muscle. This gene encodes one member of the sodium channel alpha subunit gene family. Allelic variants of this gene are associated with seizure disorders and autism spectrum disorder. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Nov 2016]
Expression: Biased expression in brain (RPKM 20.5) and kidney (RPKM 1.1) See more
Orthologs: all
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Genomic context

Location:: 2q24.3

Exon count:: 31

Annotation release	Status	Assembly	Chr	Location
RS_2023_10	current	GRCh38.p14 (GCF_000001405.40)	2	NC_000002.12 (165239414..165392304)
RS_2023_10	current	T2T-CHM13v2.0 (GCF_009914755.1)	2	NC_060926.1 (165696714..165849575)
105.20220307	previous assembly	GRCh37.p13 (GCF_000001405.25)	2	NC_000002.11 (166095924..166248814)

Chromosome 2 - NC_000002.12 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

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?

Pathogenic gating pore current conducted by autism-related mutations in the NaV1.2 brain sodium channel.
Title: Pathogenic gating pore current conducted by autism-related mutations in the Na(V)1.2 brain sodium channel.
Distinctive In Vitro Phenotypes in iPSC-Derived Neurons From Patients With Gain- and Loss-of-Function SCN2A Developmental and Epileptic Encephalopathy.
Title: Distinctive In Vitro Phenotypes in iPSC-Derived Neurons From Patients With Gain- and Loss-of-Function SCN2A Developmental and Epileptic Encephalopathy.
Exome sequencing of ATP1A3-negative cases of alternating hemiplegia of childhood reveals SCN2A as a novel causative gene.
Title: Exome sequencing of ATP1A3-negative cases of alternating hemiplegia of childhood reveals SCN2A as a novel causative gene.
Epilepsy-associated SCN2A (NaV1.2) variants exhibit diverse and complex functional properties.
Title: Epilepsy-associated SCN2A (NaV1.2) variants exhibit diverse and complex functional properties.
Missense mutations in the membrane domain of PRRT2 affect its interaction with Nav1.2 voltage-gated sodium channels.
Title: Missense mutations in the membrane domain of PRRT2 affect its interaction with Nav1.2 voltage-gated sodium channels.
Pathogenic SCN2A variants cause early-stage dysfunction in patient-derived neurons.
Title: Pathogenic SCN2A variants cause early-stage dysfunction in patient-derived neurons.
A Push-Pull Mechanism Between PRRT2 and beta4-subunit Differentially Regulates Membrane Exposure and Biophysical Properties of NaV1.2 Sodium Channels.
Title: A Push-Pull Mechanism Between PRRT2 and β4-subunit Differentially Regulates Membrane Exposure and Biophysical Properties of NaV1.2 Sodium Channels.
Association of sodium voltage-gated channel genes polymorphisms with epilepsy risk and prognosis in the Saudi population.
Title: Association of sodium voltage-gated channel genes polymorphisms with epilepsy risk and prognosis in the Saudi population.
Functional correlates of clinical phenotype and severity in recurrent SCN2A variants.
Title: Functional correlates of clinical phenotype and severity in recurrent SCN2A variants.
Role of SCN2A c.56G/A Gene Polymorphism in Egyptian Children with Genetic Epilepsy with Febrile Seizure Plus.
Title: Role of SCN2A c.56G/A Gene Polymorphism in Egyptian Children with Genetic Epilepsy with Febrile Seizure Plus.

Submit: New GeneRIF Correction See all GeneRIFs (111)

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
Developmental and epileptic encephalopathy, 11 MedGen: C3150987 OMIM: 613721 GeneReviews: Not available	Compare labs
Episodic ataxia, type 9 MedGen: C5394520 OMIM: 618924 GeneReviews: Not available	Compare labs
SCN2A-related generalized epilepsy with febrile seizures plus MedGen: CN120574 GeneReviews: Not available	Compare labs
Seizures, benign familial infantile, 3 MedGen: C1843140 OMIM: 607745 GeneReviews: Not available	Compare labs

Copy number response

Description
Copy number response Triplosensitivity No evidence available (Last evaluated 2020-04-22) ClinGen Genome Curation Page Haploinsufficency Sufficient evidence for dosage pathogenicity (Last evaluated 2020-04-22) ClinGen Genome Curation PagePubMed

EBI GWAS Catalog

Description
Common variants associated with general and MMR vaccine-related febrile seizures. EBI GWAS Catalog EBI GWAS CatalogPubMed
Genome-wide association study of chronic periodontitis in a general German population. EBI GWAS Catalog EBI GWAS CatalogPubMed

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

D2S2330 (e-PCR), detects polymorphism
- UniSTS:16131

SHGC-79014 (e-PCR)
- UniSTS:101392

D2S399 (e-PCR), detects polymorphism
- UniSTS:24339

Scn1a (e-PCR), detects polymorphism
- UniSTS:516635

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

WI-18792 (e-PCR)
- UniSTS:64336

SHGC-3738 (e-PCR)
- UniSTS:92756

SHGC-82894 (e-PCR)
- UniSTS:96087

D2S124 (e-PCR), detects polymorphism
- UniSTS:64108

SHGC-105580 (e-PCR)
- UniSTS:169336

RH47377 (e-PCR)
- UniSTS:79517

SHGC-30518 (e-PCR)
- UniSTS:41135

RH45814 (e-PCR)
- UniSTS:12984

SHGC-53406 (e-PCR)
- UniSTS:12985

SCN2A2_3453 (e-PCR)
- UniSTS:471750

RH79255 (e-PCR)
- UniSTS:39161

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables calmodulin binding	IMP Inferred from Mutant Phenotype 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	ISS Inferred from Sequence or Structural Similarity more info

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 cellular response to hypoxia	ISS Inferred from Sequence or Structural Similarity more info
involved_in dentate gyrus development	IEA Inferred from Electronic Annotation more info
involved_in determination of adult lifespan	IEA Inferred from Electronic Annotation more info
acts_upstream_of_or_within intrinsic apoptotic signaling pathway in response to osmotic stress	ISS Inferred from Sequence or Structural Similarity more info
involved_in memory	ISS Inferred from Sequence or Structural Similarity more info
involved_in myelination	ISS Inferred from Sequence or Structural Similarity more info
involved_in nerve development	IEA Inferred from Electronic Annotation more info
acts_upstream_of_or_within nervous system development	ISS Inferred from Sequence or Structural Similarity more info
acts_upstream_of_or_within neuron apoptotic process	ISS Inferred from Sequence or Structural Similarity more info
involved_in neuronal action potential	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in neuronal action potential	ISS Inferred from Sequence or Structural Similarity more info
involved_in sodium ion transmembrane transport	IBA Inferred from Biological aspect of Ancestor more info
acts_upstream_of_or_within sodium ion transport	ISS Inferred from Sequence or Structural Similarity more info

Component	Evidence Code	Pubs
located_in T-tubule	IEA Inferred from Electronic Annotation more info
located_in axon	TAS Traceable Author Statement more info	PubMed
located_in glutamatergic synapse	IEA Inferred from Electronic Annotation more info
located_in intercalated disc	IEA Inferred from Electronic Annotation more info
located_in membrane	ISS Inferred from Sequence or Structural Similarity more info
located_in node of Ranvier	ISS Inferred from Sequence or Structural Similarity more info
located_in paranode region of axon	IEA Inferred from Electronic Annotation more info
is_active_in plasma membrane	IDA Inferred from Direct Assay more info	PubMed
located_in plasma membrane	ISS Inferred from Sequence or Structural Similarity more info
located_in presynaptic 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	ISS Inferred from Sequence or Structural Similarity more info

General protein information

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Preferred Names: sodium channel protein type 2 subunit alpha

Names: sodium channel protein brain II subunit alpha; sodium channel protein type II subunit alpha; sodium channel protein, brain type 2 alpha subunit; sodium channel, voltage-gated, type II, alpha 1 polypeptide; sodium channel, voltage-gated, type II, alpha 2 polypeptide; sodium channel, voltage-gated, type II, alpha subunit; voltage-gated sodium channel subtype II; voltage-gated sodium channel subunit alpha Nav1.2; voltage-gated sodium channel type II alpha subunit

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_008143.1 RefSeqGene

Range

5013..157903

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_001040142.2 → NP_001035232.1 sodium channel protein type 2 subunit alpha isoform 1

See identical proteins and their annotated locations for NP_001035232.1

Status: REVIEWED

Source sequence(s)

AC011303, BP199510, BP311214, BU729783, DA232976, M94055

Consensus CDS

CCDS33314.1

UniProtKB/Swiss-Prot

A6NC14, A6NIQ5, Q14472, Q53T77, Q99250, Q9BZC9, Q9BZD0

UniProtKB/TrEMBL

A0A1B0GWA6

Related

ENSP00000364586.2, ENST00000375437.7

Conserved Domains (5) summary

cd13433
Location:1474 → 1526

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

pfam00520
Location:1207 → 1482

Ion_trans; Ion transport protein

pfam06512
Location:997 → 1203

Na_trans_assoc; Sodium ion transport-associated

pfam11933
Location:514 → 709

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

pfam16905
Location:1798 → 1845

GPHH; Voltage-dependent L-type calcium channel, IQ-associated
NM_001040143.2 → NP_001035233.1 sodium channel protein type 2 subunit alpha isoform 2

See identical proteins and their annotated locations for NP_001035233.1

Status: REVIEWED

Source sequence(s)

AC011303, AC013438

Consensus CDS

CCDS33313.1

UniProtKB/TrEMBL

A0A1B0GWA6

Related

ENSP00000490107.1, ENST00000636071.2

Conserved Domains (5) summary

cd13433
Location:1474 → 1526

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

pfam00520
Location:1207 → 1482

Ion_trans; Ion transport protein

pfam06512
Location:997 → 1203

Na_trans_assoc; Sodium ion transport-associated

pfam11933
Location:514 → 709

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

pfam16905
Location:1798 → 1845

GPHH; Voltage-dependent L-type calcium channel, IQ-associated
NM_001371246.1 → NP_001358175.1 sodium channel protein type 2 subunit alpha isoform 2

Status: REVIEWED

Source sequence(s)

AC011303, AC013438

Consensus CDS

CCDS33313.1

UniProtKB/TrEMBL

A0A1B0GWA6

Related

ENSP00000486885.1, ENST00000631182.3

Conserved Domains (5) summary

cd13433
Location:1474 → 1526

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

pfam00520
Location:1207 → 1482

Ion_trans; Ion transport protein

pfam06512
Location:997 → 1203

Na_trans_assoc; Sodium ion transport-associated

pfam11933
Location:514 → 709

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

pfam16905
Location:1798 → 1845

GPHH; Voltage-dependent L-type calcium channel, IQ-associated
NM_001371247.1 → NP_001358176.1 sodium channel protein type 2 subunit alpha isoform 1

Status: REVIEWED

Source sequence(s)

AC011303, AC013438

Consensus CDS

CCDS33314.1

UniProtKB/Swiss-Prot

A6NC14, A6NIQ5, Q14472, Q53T77, Q99250, Q9BZC9, Q9BZD0

UniProtKB/TrEMBL

A0A1B0GWA6

Related

ENSP00000490866.1, ENST00000637266.2

Conserved Domains (5) summary

cd13433
Location:1474 → 1526

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

pfam00520
Location:1207 → 1482

Ion_trans; Ion transport protein

pfam06512
Location:997 → 1203

Na_trans_assoc; Sodium ion transport-associated

pfam11933
Location:514 → 709

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

pfam16905
Location:1798 → 1845

GPHH; Voltage-dependent L-type calcium channel, IQ-associated
NM_021007.3 → NP_066287.2 sodium channel protein type 2 subunit alpha isoform 1

See identical proteins and their annotated locations for NP_066287.2

Status: REVIEWED

Source sequence(s)

AC011303

Consensus CDS

CCDS33314.1

UniProtKB/Swiss-Prot

A6NC14, A6NIQ5, Q14472, Q53T77, Q99250, Q9BZC9, Q9BZD0

UniProtKB/TrEMBL

A0A1B0GWA6

Related

ENSP00000283256.6, ENST00000283256.10

Conserved Domains (5) summary

cd13433
Location:1474 → 1526

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

pfam00520
Location:1207 → 1482

Ion_trans; Ion transport protein

pfam06512
Location:997 → 1203

Na_trans_assoc; Sodium ion transport-associated

pfam11933
Location:514 → 709

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

pfam16905
Location:1798 → 1845

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