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SCN1A Gene

protein-coding GIFtS: 64
GCID: GC02M166809

Sodium Channel, Voltage-Gated, Type I, Alpha Subunit

(Previous name: febrile convulsions 3)
(Previous symbols: SCN1, FEB3)

See SCN1A-related diseases
at

MalaCards

(According to ¹HGNC, ²Entrez Gene,
³UniProtKB/Swiss-Prot, ⁴UniProtKB/TrEMBL, ⁵OMIM, ⁶GeneLoc, ⁷Ensembl, ⁸DME, ⁹miRBase, ¹⁰fRNAdb, ¹²H-InvDB, ¹³NCBI, ¹⁴NONCODE, and/or ¹⁵RNAdb)
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Aliases
Sodium Channel, Voltage-Gated, Type I, Alpha Subunit¹ ²		SMEI² ⁵
SCN1¹ ² ³		Febrile Convulsions 3¹
FEB3¹ ²		HBSCI²
Sodium Channel Protein Type I Subunit Alpha² ³		Nav1.1²
Voltage-Gated Sodium Channel Subunit Alpha Nav1.1² ³		Sodium Channel Protein Type 1 Subunit Alpha²
NAC1² ³		Sodium Channel Protein, Brain I Alpha Subunit²
EIEE6² ⁵		Sodium Channel Voltage Gated Type 1 Alpha Subunit²
FEB3A² ⁵		Sodium Channel, Voltage-Gated, Type I, Alpha Polypeptide²
FHM3² ⁵		Sodium Channel Protein Brain I Subunit Alpha³
GEFSP2² ⁵

External Ids:	HGNC: 10585¹	Entrez Gene: 6323²	Ensembl: ENSG00000144285⁷	OMIM: 182389⁵	UniProtKB: P35498³

Export aliases for SCN1A gene to outside databases

Previous GC identifers: GC02M164900 GC02M165387 GC02M167048 GC02M166671 GC02M166553 GC02M158727

(According to Entrez Gene, GeneCards, Tocris Bioscience, Wikipedia's Gene Wiki, PharmGKB,
UniProtKB/Swiss-Prot, and/or UniProtKB/TrEMBL)
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Entrez Gene summary for SCN1A Gene:

The vertebrate sodium channel is a voltage-gated ion channel essential for the generation and propagation of

action potentials, mainly in nerve and muscle. Voltage-sensitive sodium channels are heteromeric complexes

consisting of a large central pore-forming glycosylated alpha subunit, and two smaller auxiliary beta subunits.

This gene encodes the large alpha subunit, and mutations in this gene have been associated with several epilepsy,

convulsion and migraine disorders. Alternative splicing results in multiple transcript variants. The RefSeq

Project has decided to create four representative RefSeq records. Three of the transcript variants are supported

by experimental evidence and the fourth contains alternate 5' untranslated exons, the exact combination of which

have not been experimentally confirmed for the full-length transcript.(provided by RefSeq, Jan 2011)

GeneCards Summary for SCN1A Gene:

SCN1A (sodium channel, voltage-gated, type I, alpha subunit) is a protein-coding gene. Diseases associated with SCN1A include febrile seizures, familial, 3a, and scn1a-related seizure disorders. GO annotations related to this gene include voltage-gated sodium channel activity. An important paralog of this gene is SCN5A.

UniProtKB/Swiss-Prot: SCN1A_HUMAN, P35498

Function: Mediates the voltage-dependent sodium ion permeability of excitable membranes. Assuming opened or closed

conformations in response to the voltage difference across the membrane, the protein forms a sodium-selective

channel through which Na(+) ions may pass in accordance with their electrochemical gradient

summary for SCN1A Gene:

Voltage-gated sodium channels (NaV) are responsible for action potential initiation and propagation in

excitable cells, including nerve, muscle, and neuroendocrine cell types. They are also expressed at low

levels in non-excitable cells, where their physiological role is unclear. Structurally, Nav channels are

composed of one pore-forming alpha-subunit, which may be associated with either one or more beta-subunits.

alpha-subunits are composed for four homologous domains, each of which contains six transmembrane segments.

The fourth transmembrane loop (S4) acts as the 'voltage sensor' and is activated by changes in membrane

potential. S4 is also involved in channel gating.

Gene Wiki entry for SCN1A (Nav1.1) Gene

(According to GeneLoc and/or HGNC, and/or
Entrez Gene (NCBI build 37),
and/or miRBase,
Genomic Views according to UCSC (hg19) and Ensembl (release 75), Regulatory elements and Epigenetics data according to QIAGEN, and/or SwitchGear Genomics)
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RefSeq DNA sequence at NCBI GenBank:

NC_000002.11 NC_018913.2 NT_005403.18

Regulatory elements:

Regulatory transcription factor binding sites in the SCN1A gene promoter:
Oct-B1 oct-B3 oct-B2 AML1a Cdc5 E47 MEF-2A FOXJ2 (long isoform) FOXJ2 aMEF-2
Other transcription factors

SwitchGear Promoter luciferase reporter plasmid: SCN1A promoter sequence

Search Chromatin IP Primers for SCN1A

Epigenetics:

DNA Methylation CpG Assay Predesigned for Pyrosequencing in human, mouse, rat SCN1A

Genomic Location:
Genomic View: UCSC Golden Path with GeneCards custom track

Entrez Gene cytogenetic band: 2q24.3 Ensembl cytogenetic band: 2q24.3 HGNC cytogenetic band: 2q24.3

SCN1A Gene in genomic location: bands according to Ensembl, locations according to (and/or Entrez Gene and/or Ensembl if different)
SCN1A gene location

GeneLoc information about chromosome 2 GeneLoc Exon Structure

GeneLoc location for GC02M166809: view genomic region (about GC identifiers)

Start:	166,845,670 bp from pter	End:	167,005,642 bp from pter
Size:	159,973 bases	Orientation:	minus strand

(According to ¹UniProtKB, HORDE, ²neXtProt, Ensembl, and/or Reactome, Modification sites according to PhosphoSitePlus, Specific Peptides from DME, RefSeq according to NCBI, PDB rendering according to OCA and/or Proteopedia, Recombinant Proteins from EMD Millipore, R&D Systems, GenScript, Enzo Life Sciences, OriGene, Novus Biologicals, Sino Biological, ProSpec, Cloud-Clone Corp., eBioscience, and/or antibodies-online,
Biochemical Assays by EMD Millipore, R&D Systems, OriGene, GenScript, Cell Signaling Technology, Enzo Life Sciences, Cloud-Clone Corp., eBioscience, and/or antibodies-online, Antibodies by EMD Millipore, R&D Systems, Cell Signaling Technology, OriGene, Novus Biologicals, Thermo Fisher Scientific, Abcam, Cloud-Clone Corp, antibodies-online, and/or others.)
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UniProtKB/Swiss-Prot: SCN1A_HUMAN, P35498 (See protein sequence)

Recommended Name: Sodium channel protein type 1 subunit alpha

Size: 2009 amino acids; 228972 Da

Subunit: The sodium channel consists of a large polypeptide and 2-3 smaller ones. This sequence represents a large

polypeptide. Interacts with FGF13; may regulate SCN1A activity

Secondary accessions: E9PG49 Q16172 Q585T7 Q8IUJ6 Q96LA3 Q9C008

Alternative splicing: 3 isoforms: P35498-1 P35498-2 P35498-3

Explore the universe of human proteins at neXtProt for SCN1A: NX_P35498

Explore proteomics data for SCN1A at MOPED

Post-translational modifications:

Phosphorylation at Ser-1516 by PKC in a highly conserved cytoplasmic loop slows inactivation of the sodium channel

and reduces peak sodium currents (By similarity)¹

Glycosylation² at Asn211, Asn284, Asn295, Asn301, Asn306, Asn338, Asn1378, Asn1392, Asn1403

Modification sites at PhosphoSitePlus

See SCN1A Protein Expression from SPIRE MOPED, PaxDB, and MaxQB

REFSEQ proteins (4 alternative transcripts):

NP_001159435.1 NP_001159436.1 NP_008851.3 NP_001189364.1

ENSEMBL proteins:

ENSP00000303540 ENSP00000364554 ENSP00000386312 ENSP00000407030

Reactome Protein details: P35498

SCN1A Human Recombinant Protein Products:

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	Browse ProSpec Recombinant Proteins
	Browse Proteins at Cloud-Clone Corp.
	Search eBioscience for Proteins for SCN1A
	antibodies-online proteins for SCN1A (2 products)
	antibodies-online peptides for SCN1A

SCN1A Antibody Products:

	EMD Millipore Mono- and Polyclonal Antibodies for the study of SCN1A
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	Novus Biologicals SCN1A Antibodies
	Search for Antibodies for SCN1A at Abcam
	Browse Antibodies at Cloud-Clone Corp.
	ThermoFisher Antibodies for SCN1A
	antibodies-online antibodies for SCN1A (47 products)

SCN1A Assay Products:

	Browse Kits and Assays available from EMD Millipore
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	GenScript Custom Assay Services for SCN1A
	Browse Enzo Life Sciences for kits & assays
	Browse ELISAs at Cloud-Clone Corp. Browse CLIAs at Cloud-Clone Corp.
	Search eBioscience for ELISAs for SCN1A
	antibodies-online kits for SCN1A (4 products)

(According to HGNC, IUPHAR, InterPro, ProtoNet, UniProtKB, and/or BLOCKS, Sets of similar genes according to GeneDecks)
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HGNC Gene Families:

SC: Sodium channels

SCN: Voltage-gated ion channels / Sodium channels

IUPHAR Guide to PHARMACOLOGY protein family classification: Na_v1.1

Voltage-gated sodium channels

Selected InterPro protein domains (see all 7):

IPR008051 Na_channel_a1su

IPR010526 Na_trans_assoc

IPR005821 Ion_trans_dom

IPR027359 Channel_four-helix_dom

IPR001696 Na_channel_asu

Graphical View of Domain Structure for InterPro Entry P35498

ProtoNet protein and cluster: P35498

4 Blocks protein domains:

IPB000048 IQ calmodulin-binding region

IPB000100 Bacterial ribonuclease P protein

IPB001696 Voltage-gated Na+ channel alpha subunit signature

IPB008051 Voltage-gated Na+ channel alpha 1 subunit signature

UniProtKB/Swiss-Prot: SCN1A_HUMAN, P35498

Domain: The sequence contains 4 internal repeats, each with 5 hydrophobic segments (S1,S2,S3,S5,S6) and one

positively charged segment (S4). Segments S4 are probably the voltage-sensors and are characterized by a series

of positively charged amino acids at every third position

Similarity: Belongs to the sodium channel (TC 1.A.1.10) family. Nav1.1/SCN1A subfamily

Similarity: Contains 1 IQ domain

Find genes that share domains with SCN1A About GenesLikeMe

(According to ¹UniProtKB, Genatlas, LifeMap Discovery™, IUBMB, and/or ²DME, Human phenotypes from GenomeRNAi, Animal models from MGI Mar 06 2013, genOway,
transcription factor targeting from QIAGEN and/or HOMER, miRNA Gene Targets from miRTarBase, shRNA from OriGene, siRNAs from OriGene, QIAGEN, microRNA from QIAGEN, SwitchGear Genomics, Gene Editing from DNA2.0, Clones from OriGene, GenScript, Sino Biological, DNA2.0, Vector BioLabs and/or Addgene, Cell Lines from GenScript, ESI BIO, In Situ Hybridization Assays from Advanced Cell Diagnostics, Flow cytometry from eBioscience, Ontologies according to Gene Ontology Consortium 01 Apr 2014 via Entrez Gene.)
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Molecular Function:

UniProtKB/Swiss-Prot Summary: SCN1A_HUMAN, P35498

Function: Mediates the voltage-dependent sodium ion permeability of excitable membranes. Assuming opened or closed

conformations in response to the voltage difference across the membrane, the protein forms a sodium-selective

channel through which Na(+) ions may pass in accordance with their electrochemical gradient

Genatlas biochemistry entry for SCN1A:

sodium voltage-gated channel,type I,alpha polypeptide,expressed in brain

Gene Ontology (GO): 2 molecular function terms: About this table

GO ID	Qualified GO term	Evidence	PubMed IDs
GO:0005216	ion channel activity	--	--
GO:0005248	voltage-gated sodium channel activity	NAS	10742094

Find genes that share ontologies with SCN1A About GenesLikeMe

Phenotypes:
2 GenomeRNAi human phenotypes for SCN1A:

Elongated cells

Synthetic lethal with c-Myc af

6 MGI mutant phenotypes (inferred from 8 alleles) (MGI details for Scn1a):

behavior/neurological	growth/size/body	mortality/aging	nervous system	normal
reproductive system

Find genes that share phenotypes with SCN1A About GenesLikeMe

Animal Models:
MGI mouse knock-outs for SCN1A: Scn1a^tm1Kea Scn1a^tm2.2Kzy Scn1a^tm1Kzy Scn1a^tm1Wac

genOway: Develop your customized and physiologically relevant rodent model for SCN1A

miRNA Products:		miRTarBase miRNAs that target SCN1A: hsa-mir-93-3p (MIRT038738)

		Block miRNA regulation of human, mouse, rat SCN1A using miScript Target Protectors
		Selected qRT-PCR Assays for microRNAs that regulate SCN1A (see all 75):
		hsa-miR-548j hsa-miR-100* hsa-miR-3607-3p hsa-miR-106a hsa-miR-30d hsa-miR-371-5p hsa-miR-519a hsa-miR-30a

		SwitchGear 3'UTR luciferase reporter plasmid: SCN1A 3' UTR sequence

Inhib. RNA Products:		OriGene RNAi products in human, mouse, rat for SCN1A
		Predesigned siRNA for gene silencing in human, mouse, rat SCN1A

Gene Editing
Products:

DNA2.0 Custom Protein Engineering Service for SCN1A

Clone Products:		OriGene clones in human, mouse for SCN1A (see all 14) OriGene ORF clones in mouse, rat for SCN1A OriGene custom cloning services - gene synthesis, subcloning, mutagenesis, variant library, vector shuttling
		GenScript: all cDNA clones in your preferred vector (see all 4): SCN1A (NM_001202435)
		Browse Sino Biological Human cDNA Clones
		DNA2.0 Custom Codon Optimized Gene Synthesis Service for SCN1A
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Cell Line Products:		GenScript Custom overexpressing Cell Line Services for SCN1A
		Browse ESI BIO Cell Lines and PureStem Progenitors for SCN1A

In Situ Assay
Products:

Advanced Cell Diagnostics RNAscope RNA in situ hybridization assays for SCN1A

(According to UniProtKB, COMPARTMENTS Subcellular localization database, Ontologies according to Gene Ontology Consortium 01 Apr 2014 via Entrez Gene.)
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Subcellular locations from UniProtKB/Swiss-Prot

SCN1A_HUMAN, P35498: Membrane; Multi-pass membrane protein

Subcellular locations from COMPARTMENTS:

Compartment	Confidence
plasma membrane	3
cytoskeleton	1
mitochondrion	1

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Gene Ontology (GO): Selected cellular component terms (see all 11): About this table

GO ID	Qualified GO term	Evidence	PubMed IDs
GO:0001518	voltage-gated sodium channel complex	IEA	--
GO:0014704	intercalated disc	IEA	--
GO:0016020	membrane	--	--
GO:0016021	integral component of membrane	--	--
GO:0030018	Z disc	ISS	--

Find genes that share ontologies with SCN1A About GenesLikeMe

(SuperPaths according to PathCards, Pathways according to R&D Systems, Cell Signaling Technology, KEGG, PharmGKB, BioSystems, Sino Biological, Reactome, Tocris Bioscience, GeneGo (Thomson Reuters), QIAGEN, and/or UniProtKB, Sets of similar genes according to GeneDecks, Interaction Networks according to QIAGEN, and/or STRING, Interactions according to ¹UniProtKB, ²MINT, ³I2D, and/or ⁴STRING, with links to IntAct and Ensembl, Ontologies according to Gene Ontology Consortium 01 Apr 2014 via Entrez Gene).
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SuperPaths for SCN1A About (see all 6)

See pathways by source

Powered
by

SuperPath

Contained pathways About

L1CAM interactions

	Axon guidance	0.63			L1CAM interactions	0.36
	Developmental Biology	0.63

Activation of cAMP-Dependent PKA

	Activation of cAMP-Dependent PKA	0.77			PKA Signaling	0.56
	cAMP Pathway	0.77

Neuropathic Pain-Signaling in Dorsal Horn Neurons

	Neuropathic Pain-Signaling in Dorsal Horn Neurons	0.47			Cholera Infection	0.40
	Aldosterone Signaling in Epithelial Cells	0.47

G-Beta Gamma Signaling

GHRH Signaling

0.46

Circadian entrainment

Dopaminergic synapse

0.37

Find genes that share SuperPaths with SCN1A About GenesLikeMe

Pathways by source See SuperPaths
Show all pathways

Selected Downloadable PowerPoint Slides of GeneGlobe Pathway Central Maps for SCN1A (see all 7)

	Cholera Infection
	Neuropathic Pain-Signaling in Dorsal Horn Neurons
	PKA Signaling
	cAMP Pathway
	Aldosterone Signaling in Epithelial Cells

1 Reactome Pathway for SCN1A

Interaction between L1 and Ankyrins

1 Kegg Pathway (Kegg details for SCN1A):

Dopaminergic synapse

Pathway & Disease-focused RT² Profiler PCR Array including SCN1A:

Neuronal Ion Channels in human mouse rat

Interactions:

Search GeneGlobe Interaction Network for SCN1A

STRING Interaction Network Preview (showing 5 interactants - click image to see 25)

Selected Interacting proteins for SCN1A (P35498³ ENSP00000364554⁴) via UniProtKB, MINT, STRING, and/or I2D (see all 33)

Interactant		Interaction Details
GeneCard	External ID(s)	Interaction Details
CALM1	P62158³	I2D: score=1
CALM2	P62158³	I2D: score=1
CALM3	P62158³	I2D: score=1
ESR2	Q92731³, ENSP00000343925⁴	I2D: score=1 STRING: ENSP00000343925
SNTA1	Q13424³, ENSP00000217381⁴	I2D: score=1 STRING: ENSP00000217381

About this table

Gene Ontology (GO): Selected biological process terms (see all 10): About this table

GO ID	Qualified GO term	Evidence	PubMed IDs
GO:0001508	action potential	--	--
GO:0006811	ion transport	--	--
GO:0006814	sodium ion transport	NAS	10742094
GO:0007628	adult walking behavior	IEA	--
GO:0019227	neuronal action potential propagation	IEA	--

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(Chemical Compounds according to UniProtKB, Enzo Life Sciences, EMD Millipore, Tocris Bioscience, ApexBio, HMDB, BitterDB, and/or Novoseek, Ligands according to IUPHAR, and Drugs according to DrugBank, Enzo Life Sciences, and/or PharmGKB)
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Browse Small Molecules at EMD Millipore

Browse drugs & compounds from Enzo Life Sciences

Browse compounds at ApexBio

Compounds for SCN1A available from Tocris Bioscience About this table

Compound	Action	CAS #
Phrixotoxin 3	Potent modulator of NaV1.2, NaV1.3 and NaV1.5 channels	[880886-00-0]
QX 314 chloride	Na+ channel blocker	[5369-03-9]
Veratridine	Voltage-gated Na+ channel opener	[71-62-5]
Tetrodotoxin	Na+ channel blocker	[4368-28-9]
Tetrodotoxin citrate	Na+ channel blocker. Citrate salt of tetrodotoxin (Cat. No. 1078)	[18660-81-6]

2 HMDB Compounds for SCN1A About this table

Compound	Synonyms	CAS #	PubMed Ids
Sodium	Sodium (see all 2)	7440-23-5	--
Topiramate	Epitomax (see all 5)	97240-79-4	--

8 DrugBank Compounds for SCN1A About this table

Compound	Synonyms	CAS #	Type	Actions	PubMed Ids
Zonisamide	Zonisamida [Spanish] (see all 2)	68291-97-4	target	inhibitor	20025128 14704463 19557119 11752352 18433351 20001433 15511691 19948168
Permethrin	--	52645-53-1	target	inhibitor	19766671 19960691 14651650 19171193 20881019
Topiramate	Tipiramate [French] (see all 3)	97240-79-4	target	inhibitor	15526956 15508261 17621480 12861512 11948006
Phenacemide	Carbamide phenylacetate (see all 5)	63-98-9	target	inhibitor	17139284 3959032 11752352 17016423
Phenytoin	5,5-diphenylhydantoin (see all 13)	57-41-0	target	inhibitor	15805193 17001291 20298965
Phenazopyridine	--	94-78-0	target	inhibitor	20976818 8799190
Dronedarone	--	141626-36-0	target	inhibitor	12890054
Nitrazepam	1, 3-Dihydro-7-nitro-5-phenyl-2H-1,4-benzodiazepin-2-one (see all 8)	146-22-5	target	other/unknown	2450203

7 IUPHAR Ligands for SCN1A (Na_v1.1) About this table

Ligand	Type	Action	Affinity	Pubmed IDs
ATX-II	Gating inhibitor	Antagonist	8.2	15169781
Bc-III	Gating inhibitor	Antagonist	6.5	15169781
AFT-II	Gating inhibitor	Antagonist	6.4	15169781
saxitoxin	Channel blocker	None	6.4	--
veratridine	Activator	None	6.4	--
batrachotoxin	Activator	None	6.4	--
tetrodotoxin	Channel blocker	None	6.4	--

5 Novoseek inferred chemical compound relationships for SCN1A gene About this table

Compound	-log (P-Val)	Hits	PubMed IDs for Articles with Shared Sentences (# sentences)
sodium	80.2	92	17054685 (3), 12566275 (2), 14672992 (2), 17544618 (2) (see all 71)
phenytoin	36.5	6	17001291 (3), 19087113 (1), 15805193 (1), 18489610 (1)
lamotrigine	30.3	3	20037572 (2), 19087113 (1)
carbamazepine	16.3	2	18489610 (3), 19087113 (1), 17001291 (1), 18554361 (1) (see all 5)
potassium	8.38	2	11579435 (1)

2 PharmGKB related drug/compound annotations for SCN1A gene About this table

Drug/compound	PharmGKB Annotation
carbamazepine	CA
phenytoin	CA

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(Secondary structures according to fRNAdb,
GenBank/EMBL/DDBJ Accessions according to
Unigene (Build 236 Homo sapiens; Apr 25 2013) or GenBank,
RefSeq according to Entrez Gene,
DOTS (version 10), and/or AceView, transcript ids from Ensembl with links to UCSC,
exon structure from GeneLoc, alternative splicing isoforms according to ASD and/or ECgene,
siRNAs from OriGene, QIAGEN, shRNA from OriGene, microRNA from QIAGEN, SwitchGear Genomics,
Tagged/untagged cDNA clones from OriGene, GenScript, DNA2.0, Vector BioLabs, and/or Addgene, Primers from OriGene, and/or QIAGEN, Flow cytometry from eBioscience )
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REFSEQ mRNAs for SCN1A gene (4 alternative transcripts):

NM_001165963.1 NM_001165964.1 NM_006920.4 NM_001202435.1

Unigene Cluster for SCN1A:

Sodium channel, voltage-gated, type I, alpha subunit

Hs.22654 [show with all ESTs]

Unigene Representative Sequence: NM_001202435

7 Ensembl transcripts including schematic representations, and UCSC links where relevant:

ENST00000303395 ENST00000375405 ENST00000409050 ENST00000473295 ENST00000491429

ENST00000507401 ENST00000423058(uc010fpk.3 uc021vsb.1 uc002udo.4)

miRNA Products:		Block miRNA regulation of human, mouse, rat SCN1A using miScript Target Protectors
		Selected qRT-PCR Assays for microRNAs that regulate SCN1A (see all 75):
		hsa-miR-548j hsa-miR-100* hsa-miR-3607-3p hsa-miR-106a hsa-miR-30d hsa-miR-371-5p hsa-miR-519a hsa-miR-30a

		SwitchGear 3'UTR luciferase reporter plasmid: SCN1A 3' UTR sequence

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		Predesigned siRNA for gene silencing in human, mouse, rat SCN1A

Clone Products:		OriGene clones in human, mouse for SCN1A (see all 14) OriGene ORF clones in mouse, rat for SCN1A OriGene custom cloning services - gene synthesis, subcloning, mutagenesis, variant library, vector shuttling
		GenScript: all cDNA clones in your preferred vector (see all 4): SCN1A (NM_001202435)
		DNA2.0 Custom Codon Optimized Gene Synthesis Service for SCN1A
		Search Vector BioLabs for ready-to-use adenovirus/AAV for human, mouse, rat SCN1A

Primer Products:		OriGene qSTAR qPCR primer pairs in human, mouse for SCN1A
		Pre-validated RT² qPCR Primer Assay in human, mouse, rat SCN1A
		QuantiTect SYBR Green Assays in human, mouse, rat SCN1A
		QuantiFast Probe-based Assays in human, mouse, rat SCN1A

Additional mRNA sequence:

AB093548.1 AB093549.1 AB098335.1 AK094487.1 AK293759.1 AK294900.1 AY043484.1 HQ726795.1

HQ726796.1 HQ726798.1 HQ726799.1 M91803.1 X65362.1

4 DOTS entries:

DT.211707 DT.100012777 DT.100735345 DT.97774887

Selected AceView cDNA sequences (see all 32):

BX116162 AA297746 AB093548 BM718214 F03961 AB093549 AB098335 X65362

BX507999 AY043484 F04010 BX477644 AK094487 AL565167 AF225985 NM_006920

BX432053 AL533359 AL707423 M91803 F07763 BI667397 F07703 BP359985

GeneLoc Exon Structure

(RNA expression data according to H-InvDB, NONCODE, miRBase, and RNAdb, Expression images according to data from BioGPS, Illumina Human BodyMap, and CGAP SAGE, Sets of similar genes according to GeneDecks, in vivo and in vitro expression data from LifeMap Discovery™, Protein expression images according to data from SPIRE ¹MOPED, ²PaxDb, and ³MaxQB, plus additional links to SOURCE, and/or BioGPS, and/or UniProtKB,
PCR Arrays from QIAGEN, Primers from OriGene, and/or QIAGEN, In Situ Hybridization Assays from Advanced Cell Diagnostics)
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SCN1A expression in normal human tissues (normalized intensities)
See probesets specificity/sensitivity at GeneAnnot
About this imageBioGPS <intensity>^2/3
CGAP TAG: CTGGAAAATG

About this image

SCN1A expression in embryonic tissues and stem cells About this table

Data from LifeMap, the Embryonic Development and Stem Cells Database


Brain (Nervous System)
Oligodendrocyte Precursor Cells Forebrain White Matter

SCN1A Protein expression data from MOPED¹, PaxDb² and MaxQB³:

About this image

SCN1A Protein Expression

SOURCE GeneReport for Unigene cluster: Hs.22654

Pathway & Disease-focused RT² Profiler PCR Array including SCN1A:

Neuronal Ion Channels in human mouse rat

Primer Products:		OriGene qSTAR qPCR primer pairs in human, mouse for SCN1A
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(Orthologs according to ^1,2HomoloGene (²older version, for species not in ¹newer version), ³euGenes, ⁴SGD , ⁵MGI Mar 06 2013, with possible further links to Flybase and/or WormBase, and/or ⁶Ensembl pan taxonomic compara , Gene Trees according to Ensembl and TreeFam)
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This gene was present in the common ancestor of chordates.

Orthologs for SCN1A gene from Selected species (see all 11) About this table

Organism	Taxonomic classification	Gene	Description	Human Similarity	Orthology Type	Details
mouse (Mus musculus)	Mammalia	Scn1a^{1 , 5}	sodium channel, voltage-gated, type I, alpha^{1, 5}	90.44(n)¹ 98.15(a)¹		2 (39.13 cM)⁵ 20265¹ NM_018733.2¹ NP_061203.2¹ 66270781⁵
chicken (Gallus gallus)	Aves	SCN1A¹	sodium channel, voltage-gated, type I, alpha subunit	83.09(n) 91.2(a)		771555 XM_003641586.2 XP_003641634.1
lizard (Anolis carolinensis)	Reptilia	SCN1A⁶	sodium channel, voltage-gated, type I, alpha subun...	89(a)	1 ↔ 1	GL343214.1(901340-1055970)
tropical clawed frog (Xenopus tropicalis)	Amphibia	BX735435.1²	--	76.51(n)		BX735435.1
zebrafish (Danio rerio)	Actinopterygii	scn1lab⁶	sodium channel, voltage-gated, type I like, alpha ...	78(a)	1 → many	6(10158986-10231330) ENSDARG00000062744

ENSEMBL Gene Tree for SCN1A (if available)
TreeFam Gene Tree for SCN1A (if available)

(Paralogs according to ¹HomoloGene,
²Ensembl, and ³SIMAP, Pseudogenes according to ⁴Pseudogene.org Build 68)
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Paralogs for SCN1A gene

SCN5A² SCN9A² CACNA1D² SCN7A² CACNA1I² CACNA1F² CACNA1G² SCN8A²

SCN10A² SCN3A² SCN2A² CACNA1S² CACNA1C² CACNA1H² SCN11A² SCN4A²

17 SIMAP similar genes for SCN1A using alignment to 6 protein entries: SCN1A_HUMAN (see all proteins):

SCN2A SCN2A2 SCN3A SCN9A SCN4A SCN5A

SCN8A SCN10A CACNA1D SCN11A CACNA1H SCN7A

CACNA1A CACNA1B TPCN1 CACNA1E CACNA1C

Find genes that share paralogs with SCN1A About GenesLikeMe

(SNPs/Variants according to the ¹NCBI SNP Database, ²Ensembl, ³PupaSUITE, ⁴UniProtKB, and DNA2.0, Linkage Disequilibrium by HapMap, Structural Variations(CNVs/InDels/Inversions) from the Database of Genomic Variants, Mutations from the Human Gene Mutation Database (HGMD), the Human Cytochrome P450 Allele Nomenclature Database, and the Locus Specific Mutation Databases (LSDB), Blood group antigen gene mutations by BGMUT, Resequencing Primers, Cancer Mutation PCR Arrays and Assays, and Copy Number PCR Arrays from QIAGEN)
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SNP ID	Valid	Clinical significance	Chr 2 pos	Sequence	#	AA Chg	Type	More	#	Allele freq	Pop	Total sample	More
Genomic Data					Transcription Related Data				Allele Frequencies
				--	--	--		--	--
rs121918629^1,2,,4	C	Intractable childhood epilepsy with generalized tonic-clonic seizures (ICEGTC)⁴ pathogenic¹	166245737(-)	`TGAGAC/TCTTTG`	8	T I	mis¹		0	--	--	--	--
rs121918744^1,2,,4	C	Generalized epilepsy with febrile seizures plus 2 (GEFS+2)⁴ untested¹	166245809(-)	`CTACGA/C/TCATCT`	12	D A V	mis¹		0	--	--	--	--
rs121917922^1,2,,4	C	Severe myoclonic epilepsy in infancy (SMEI)⁴ untested¹	166245890(-)	`CCGCAC/G/TGCTGC`	12	T R M	mis¹		0	--	--	--	--
rs121917955^1,2,,4	C	Generalized epilepsy with febrile seizures plus 2 (GEFS+2)⁴ pathogenic¹	166245895(-)	`GGGATC/GCGCAC`	8	I M	mis¹		0	--	--	--	--
rs121918622^1,2,,4	C	Severe myoclonic epilepsy in infancy (SMEI)⁴ pathogenic¹	166245920(-)	`CCTACA/GTCTGA`	8	H R	mis¹		0	--	--	--	--
rs121918630^1,2,,4	C	Intractable childhood epilepsy with generalized tonic-clonic seizures (ICEGTC)⁴ pathogenic¹	166247758(-)	`TTGTGG/TTTGTC`	8	V F	mis¹		0	--	--	--	--
rs121918742^1,2,,4	C	Severe myoclonic epilepsy in infancy (SMEI)⁴ untested¹	166247832(-)	`TACTGA/GAGAGT`	8	E G	mis¹		0	--	--	--	--
rs121918632^1,2,,4	C	Migraine, familial hemiplegic, 3 (FHM3)⁴ pathogenic¹	166249686(-)	`ACATCC/TTTATG`	8	L F	mis¹		0	--	--	--	--
rs121918633^1,2,,4	C	Migraine, familial hemiplegic, 3 (FHM3)⁴ pathogenic¹	166251634(-)	`CAGCAC/GAAAAA`	8	H Q	mis¹		0	--	--	--	--
rs121918628^1,2,,4	C	Migraine, familial hemiplegic, 3 (FHM3)⁴ pathogenic¹	166251636(-)	`ACCAGA/CAGAAA`	8	K Q	mis¹		0	--	--	--	--

HapMap Linkage Disequilibrium report for SCN1A (166845670 - 167005642 bp)

Structural Variations
Database of Genomic Variants (DGV) 10 variations for SCN1A: About this table

Variant ID	Type	Subtype	PubMed ID
esv2721078	CNV	Deletion	23290073
esv2721076	CNV	Deletion	23290073
esv2357676	CNV	Deletion	18987734
esv2721077	CNV	Deletion	23290073
esv2721079	CNV	Deletion	23290073
esv2721080	CNV	Deletion	23290073
nsv459936	CNV	Loss	19166990
dgv63n17	CNV	Loss	16327808
dgv4355n71	CNV	Gain	21882294
nsv834445	CNV	Gain+Loss	17160897

Human Gene Mutation Database (HGMD): SCN1A

Site Specific Mutation Identification with PCR Assays

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(in which this Gene is Involved, According to MalaCards, OMIM, UniProtKB, the University of Copenhagen DISEASES database, Novoseek, Genatlas, GeneTests, GAD, HuGE Navigator, and/or TGDB.)
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OMIM gene information: 182389
OMIM disorders: 604403 607208 609634
UniProtKB/Swiss-Prot: SCN1A_HUMAN, P35498

Generalized epilepsy with febrile seizures plus 2 (GEFS+2) [MIM:604403]: A rare autosomal dominant,

familial condition with incomplete penetrance and large intrafamilial variability. Patients display febrile

seizures persisting sometimes beyond the age of 6 years and/or a variety of afebrile seizure types. This disease

combines febrile seizures, generalized seizures often precipitated by fever at age 6 years or more, and partial

seizures, with a variable degree of severity. Note=The disease is caused by mutations affecting the gene

represented in this entry

Severe myoclonic epilepsy in infancy (SMEI) [MIM:607208]: A rare disorder characterized by generalized

tonic, clonic, and tonic-clonic seizures that are initially induced by fever and begin during the first year of

life. Later, patients also manifest other seizure types, including absence, myoclonic, and simple and complex

partial seizures. Psychomotor development delay is observed around the second year of life. Some patients

manifest a borderline disease phenotype and do not necessarily fulfill all diagnostic criteria for core SMEI.

SMEI is considered to be the most severe phenotype within the spectrum of generalized epilepsies with febrile

seizures-plus. Note=The disease is caused by mutations affecting the gene represented in this entry

Intractable childhood epilepsy with generalized tonic-clonic seizures (ICEGTC) [MIM:607208]: A disorder

characterized by generalized tonic-clonic seizures beginning usually in infancy and induced by fever. Seizures

are associated with subsequent mental decline, as well as ataxia or hypotonia. ICEGTC is similar to SMEI, except

for the absence of myoclonic seizures. Note=The disease is caused by mutations affecting the gene represented in

this entry

Migraine, familial hemiplegic, 3 (FHM3) [MIM:609634]: A subtype of migraine associated with transient

blindness in some families. Migraine is a disabling symptom complex of periodic headaches, usually temporal and

unilateral. Headaches are often accompanied by irritability, nausea, vomiting and photophobia, preceded by

constriction of the cranial arteries. The two major subtypes are common migraine (migraine without aura) and

classic migraine (migraine with aura). Classic migraine is characterized by recurrent attacks of reversible

neurological symptoms (aura) that precede or accompany the headache. Aura may include a combination of sensory

disturbances, such as blurred vision, hallucinations, vertigo, numbness and difficulty in concentrating and

speaking. Note=The disease is caused by mutations affecting the gene represented in this entry

Febrile seizures, familial, 3A (FEB3A) [MIM:604403]: Seizures associated with febrile episodes in

childhood without any evidence of intracranial infection or defined pathologic or traumatic cause. It is a common

condition, affecting 2-5% of children aged 3 months to 5 years. The majority are simple febrile seizures

(generally defined as generalized onset, single seizures with a duration of less than 30 minutes). Complex

febrile seizures are characterized by focal onset, duration greater than 30 minutes, and/or more than one seizure

in a 24 hour period. The likelihood of developing epilepsy following simple febrile seizures is low. Complex

febrile seizures are associated with a moderately increased incidence of epilepsy. Note=The disease is caused by

mutations affecting the gene represented in this entry

Selected diseases for SCN1A (see all 27):
About MalaCards

febrile seizures, familial, 3a scn1a-related seizure disorders myoclonic astatic epilepsy myoclonic epilepsy of infancy

epilepsy with generalized tonic-clonic seizures lennox-gastaut syndrome dravet syndrome epilepsy, generalized, with febrile seizures plus, type 2

familial hemiplegic migraine type 3 familial hemiplegic migraine migraine hemiplegic migraine

malignant migrating partial seizures of infancy temporal lobe epilepsy generalized epilepsy with febrile seizures plus epilepsy, generalized, with febrile seizures plus, type 1

epilepsy syndrome febrile infection-related epilepsy syndrome sporadic hemiplegic migraine febrile seizures

1 inferred disease relationship from the University of Copenhagen DISEASES database for SCN1A:

Brain disease

Find genes that share disorders with SCN1A About GenesLikeMe

Selected Novoseek inferred disease relationships for SCN1A gene (see all 19) About this table

Disease	-log (P-Val)	Hits	PubMed IDs for Articles with Shared Sentences (# sentences)
dravet syndrome	98.4	43	19673951 (3), 19087113 (2), 19763161 (2), 18076640 (2) (see all 23)
epilepsies myoclonic	97	62	16458823 (3), 17030758 (3), 12821740 (2), 18479393 (2) (see all 45)
epilepsy generalized	95.6	40	11254445 (2), 14738422 (2), 19339291 (2), 11579434 (1) (see all 35)
seizures febrile	95.4	66	19292758 (4), 11254445 (3), 12742596 (2), 15087100 (2) (see all 48)
hemiplegic migraine familial	91	9	19332696 (2), 18357670 (1), 19673951 (1), 18451712 (1) (see all 8)
myoclonic seizure	84.7	1	17507202 (1)
epilepsy	83.5	95	19586930 (3), 17561957 (3), 18413471 (3), 19666879 (3) (see all 53)
seizure febrile simple	79.4	2	17565594 (1), 16326807 (1)
familial benign neonatal convulsions	76.4	2	17181426 (1), 11579435 (1)
myoclonic astatic epilepsy	76.2	2	15944908 (2)

GeneTests: SCN1A
GeneReviews: SCN1A
Genetic Association Database (GAD): SCN1A
Human Genome Epidemiology (HuGE) Navigator: SCN1A (31 documents)

Export disorders for SCN1A gene to outside databases

(in PubMed. Associations of this gene to articles via ¹Entrez Gene, ²UniProtKB/Swiss-Prot, ³HGNC, ⁴GAD, ⁵PharmGKB, ⁶HMDB, ⁷DrugBank, ⁸UniProtKB/TrEMBL, ⁹ Novoseek, and/or ¹⁰fRNAdb)
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PubMed articles for SCN1A gene, integrated from 10 sources (see all 323):
(articles sorted by number of sources associating them with SCN1A)

Utopia: connect your pdf to the dynamic
world of online information

Spectrum of SCN1A mutations in severe myoclonic epilepsy of infancy. (PubMed id 12821740)^{1, 2, 4, 9} Nabbout R....Zara F. (Neurology 2003)
A novel SCN1A mutation associated with generalized epilepsy with febrile seizures plus -- and prevalence of variants in patients with epilepsy. (PubMed id 11254445)^{1, 2, 4, 9} Escayg A.... Meisler M.H. (Am. J. Hum. Genet. 2001)
Localization of a putative human brain sodium channel gene (SCN1A) to chromosome band 2q24. (PubMed id 8062593)^{1, 2, 3, 9} Malo M.S.... Ingram V.M. (Cytogenet. Cell Genet. 1994)
The spectrum of SCN1A-related infantile epileptic encephalopathies. (PubMed id 17347258)^{1, 2, 4, 9} Harkin L.A.... Scheffer I.E. (Brain 2007)
A common polymorphism in the SCN1A gene associates with phenytoin serum levels at maintenance dose. (PubMed id 17001291)^{1, 4, 7, 9} Tate S.K....Liou H.H. (Pharmacogenet. Genomics 2006)
Mutations of neuronal voltage-gated Na+ channel alpha 1 subunit gene SCN1A in core severe myoclonic epilepsy in infancy (SMEI) and in borderline SMEI (SMEB). (PubMed id 14738421)^{1, 2, 4, 9} Fukuma G.... Hirose S. (Epilepsia 2004)
Differential role of sodium channels SCN1A and SCN2A gene polymorphisms with epilepsy and multiple drug resistance in the north Indian population. (PubMed id 19694741)^{1, 2, 4} Lakhan R.... Mittal B. (Br. J. Clin. Pharmacol. 2009)
Physicochemical property changes of amino acid residues that accompany missense mutations in SCN1A affect epilepsy phenotype severity. (PubMed id 19586930)^{1, 4, 9} Kanai K....Kaneko S. (J. Med. Genet. 2009)
Cryptogenic epileptic syndromes related to SCN1A: twelve novel mutations identified. (PubMed id 18413471)^{1, 2, 9} Zucca C.... Bassi M.T. (Arch. Neurol. 2008)
Novel SCN1A mutations in Indonesian patients with severe myoclonic epilepsy in infancy. (PubMed id 19563458)^{1, 2, 9} Herini E.S.... Nishio H. (Pediatr. Int. 2010)

(in PubMed, OMIM, and NCBI Bookshelf)
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		AND	OR
Aliases
Disorders
Free Text

Query String		PubMed OMIM NCBI Bookshelf
	(Note: In FireFox, select the above section and copy using Ctrl-C)

(According to Entrez Gene, HGNC, AceView, euGenes, Ensembl, miRBase, ECgene, Kegg, and/or H-InvDB)
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Entrez Gene: 6323	HGNC: 10585	AceView: SCN1A	Ensembl:ENSG00000144285	euGenes: HUgn6323
ECgene: SCN1A	Kegg: 6323	H-InvDB: SCN1A

(According to HUGE)
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(According to PharmGKB, ATLAS, HORDE, IMGT, LEIDEN, UniProtKB/Swiss-Prot, UniProtKB/TrEMBL, and/or others, e.g. Wikipedia and GeneReviews, via UniProtKB/Swiss-Prot)
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Name	Description
PharmGKB entry for SCN1A	Pharmacogenomics, SNPs, Pathways
GeneReviews	http://www.ncbi.nlm.nih.gov/books/NBK1116/?term=SCN1A[genesymbol]

Intellectual Property for SCN1A gene
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Patent Information for SCN1A gene:
Search GeneIP for patents involving SCN1A

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SCN1A Gene

Sodium Channel, Voltage-Gated, Type I, Alpha Subunit

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SCN1A (Gene Symbol)
Sodium Channel, Voltage-Gated, Type I, Alpha Subunit
SCN1
FEB3
Sodium Channel Protein Type I Subunit Alpha
Voltage-Gated Sodium Channel Subunit Alpha Nav1.1
NAC1
EIEE6
FEB3A
FHM3
GEFSP2
SMEI
Febrile Convulsions 3
HBSCI
Nav1.1
Sodium Channel Protein Type 1 Subunit Alpha
Sodium Channel Protein, Brain I Alpha Subunit
Sodium Channel Voltage Gated Type 1 Alpha Subunit
Sodium Channel, Voltage-Gated, Type I, Alpha Polypeptide
Sodium Channel Protein Brain I Subunit Alpha

Migraine hemiplegic
Myoclonic Epilepsy Juvenile
Migraine
EPILEPSY, IDIOPATHIC GENERALIZED
Epilepsy
Familial Hemiplegic Migraine
Epilepsies Myoclonic
MYOCLONIC SEIZURE
psychiatric disorder
Epilepsy Frontal Lobe
Myoclonic Astatic Epilepsy
Hemiplegic Migraine Familial
Seizures Febrile
SCN1A-Related Seizure Disorders
Epilepsy Generalized
ENCEPHALOPATHY
Familial Benign Neonatal Convulsions
Seizure Febrile Simple
DRAVET SYNDROME
LENNOX-GASTAUT SYNDROME
Epilepsies Partial

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SCN1A Gene

Sodium Channel, Voltage-Gated, Type I, Alpha Subunit

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