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Category Symbol Source: HGNC EntrezGene Ensembl GeneCards RNA genes CroW21

GIFtS
-

SCN5A Gene

protein-coding GIFtS: 65
GCID: GC03M038589

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

(Previous names: sodium channel, voltage-gated, type V, alpha (long QT syndrome...)
(Previous symbol: CMD1E)

Explore 51 diseases affiliated with
SCN5A via

MalaCards

our new
Human Malady Compendium

(According to ¹HGNC, ²Entrez Gene,
³UniProtKB/Swiss-Prot, ⁴UniProtKB/TrEMBL, ⁵OMIM, ⁶GeneLoc, ⁷Ensembl, ⁸DME, ⁹miRBase, and/or ¹⁰fRNAdb)
About This Section

Aliases
Sodium Channel, Voltage-Gated, Type V, Alpha Subunit¹ ²		IVF¹ ²
HH1¹ ² ³		Nav1.5¹ ²
CDCD2¹ ² ⁵		PFHB1¹ ²
CMD1E¹ ² ⁵		Sodium Channel Protein Cardiac Muscle Subunit Alpha² ³
HB1¹ ² ⁵		Voltage-Gated Sodium Channel Subunit Alpha Nav1.5² ³
LQT3¹ ² ⁵		VF1² ⁵
SSS1¹ ² ⁵		Sodium Channel, Voltage-Gated, Type V, Alpha (Long QT Syndrome 3)¹
CMPD2¹ ²		Cardiac Tetrodotoxin-Insensitive Voltage-Dependent Sodium Channel Alpha Subunit²
HB2¹ ²		Sodium Channel Protein Type 5 Subunit Alpha²
HBBD¹ ²		Sodium Channel Protein Type V Subunit Alpha³
ICCD¹ ²

External Ids:	HGNC: 10593¹	Entrez Gene: 6331²	Ensembl: ENSG00000183873⁷	OMIM: 600163⁵	UniProtKB: Q14524³

Export aliases for SCN5A gene to outside databases

Previous GC identifers: GC03U990070 GC03M038402 GC03M038550 GC03M038565

(According to Entrez Gene, Tocris Bioscience, Wikipedia's Gene Wiki, PharmGKB,
UniProtKB/Swiss-Prot, and/or UniProtKB/TrEMBL)
About This Section

Entrez Gene summary for SCN5A:

The protein encoded by this gene is an integral membrane protein and tetrodotoxin-resistant voltage-gated sodium

channel subunit. This protein is found primarily in cardiac muscle and is responsible for the initial upstroke of the

action potential in an electrocardiogram. Defects in this gene are a cause of long QT syndrome type 3 (LQT3), an

autosomal dominant cardiac disease. Alternative splicing results in several transcript variants encoding different

isoforms. (provided by RefSeq, Jul 2008)

UniProtKB/Swiss-Prot: SCN5A_HUMAN, Q14524

Function: This protein 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. It is a

tetrodotoxin-resistant Na(+) channel isoform. This channel is responsible for the initial upstroke of the action

potential. Channel inactivation is regulated by intracellular calcium levels

summary for SCN5A:

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 SCN5A (Nav1.5)

PharmGKB "VIP" summary for SCN5A

(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 69), Regulatory elements and Epigenetics data according to QIAGEN, SABiosciences, and/or SwitchGear Genomics)
About This Section

RefSeq DNA sequence:

NC_000003.11 NC_018914.1 NT_022517.18

Regulatory elements:

SABiosciences Regulatory transcription factor binding sites in the SCN5A gene promoter:
AP-2alpha isoform 3 AP-2alpha isoform 2 AP-2alpha AP-2alphaA
Other transcription factors

SwitchGear Promoter luciferase reporter plasmid: SCN5A promoter sequence

Search SABiosciences Chromatin IP Primers for SCN5A

Epigenetics:

QIAGEN PyroMark CpG Assay predesigned Pyrosequencing DNA Methylation assays in human, mouse, rat SCN5A

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

Entrez Gene cytogenetic band: 3p21 Ensembl cytogenetic band: 3p22.2 HGNC cytogenetic band: 3p21

SCN5A Gene in genomic location: bands according to Ensembl, locations according to (and/or Entrez Gene and/or Ensembl if different)
SCN5A gene location

GeneLoc information about chromosome 3 GeneLoc Exon Structure

GeneLoc location for GC03M038589: view genomic region (about GC identifiers)

Start:	38,589,548 bp from pter	End:	38,691,164 bp from pter
Size:	101,617 bases	Orientation:	minus strand

(According to ¹UniProtKB, HORDE, neXtProt, Ensembl, and/or Reactome, Modification sites according to ²PhosphoSitePlus, Specific Peptides from DME, Protein expression images according to data from SPIRE MOPED and PaxDb, 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, and/or Uscn,
Biochemical Assays by EMD Millipore, R&D Systems, OriGene, GenScript, Cell Signaling Technology, Enzo Life Sciences, and/or Uscn, Ontologies according to Gene Ontology Consortium 01 Mar 2013 and Entrez Gene, Antibodies by EMD Millipore, R&D Systems, GenScript, Cell Signaling Technology, OriGene, Novus Biologicals, Thermo Fisher Scientific, Abcam, and/or Uscn)
About This Section

UniProtKB/Swiss-Prot: SCN5A_HUMAN, Q14524 (See protein sequence)

Recommended Name: Sodium channel protein type 5 subunit alpha

Size: 2016 amino acids; 226940 Da

Subunit: Interacts with the PDZ domain of the syntrophin SNTA1, SNTB1 and SNTB2 (By similarity). Interacts with NEDD4,

NEDD4L, WWP2 and GPD1L. Interacts with CALM. Interacts with FGF13; the interaction is direct and may regulate SNC5A

density at membranes and function

Subcellular location: Membrane; Multi-pass membrane protein

Miscellaneous: Na(+) channels in mammalian cardiac membrane have functional properties quite distinct from Na(+)

channels in nerve and skeletal muscle

4 PDB 3D structures from and Proteopedia for SCN5A:

2KBI (3D)

2L53 (3D)

4DCK (3D)

4DJC (3D)

Secondary accessions: A5H1P8 A6N922 A6N923 B2RTU0 E9PEF3 E9PEK2 E9PFW7 Q59H93 Q75RX9 Q75RY0 Q86UR3

Q8IZC9 Q96J69

Alternative splicing: 6 isoforms: Q14524-1 Q14524-2 Q14524-3 Q14524-4 Q14524-5 Q14524-6 (Very abundant isoform)

Explore the universe of human proteins at neXtProt for SCN5A: NX_Q14524

Post-translational modifications:

Regulated through phosphorylation by CaMK2D (By similarity)¹

Ubiquitinated by NEDD4L; which promotes its endocytosis. Does not seem to be ubiquitinated by NEDD4 or WWP2¹

View modification sites using PhosphoSitePlus²

View neXtProt modification sites for NX_Q14524

SCN5A Protein expression data from MOPED and PaxDb: About this image

REFSEQ proteins (6 alternative transcripts):

NP_000326.2 NP_001092874.1 NP_001092875.1 NP_001153632.1 NP_001153633.1 NP_932173.1

ENSEMBL proteins:

ENSP00000398962 ENSP00000398266 ENSP00000410257 ENSP00000328968 ENSP00000399524

ENSP00000403355 ENSP00000413996 ENSP00000333674 ENSP00000388797 ENSP00000397915

ENSP00000416634

Reactome Protein details: Q14524
Human Recombinant Protein Products:

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	Browse Proteins at Uscn

Gene Ontology (GO): 5/9 cellular component terms (GO ID links to tree view) (see all 9): About this table

GO ID	Qualified GO term	Evidence	PubMed IDs
GO:0001518	voltage-gated sodium channel complex	IDA	--
GO:0005783	endoplasmic reticulum	IDA	--
GO:0005886	plasma membrane	IDA	17060380
GO:0005901	colocalizes with caveola	TAS	17060380
GO:0009986	cell surface	IDA	19666841

SCN5A for ontologies About GeneDecksing

SCN5A Antibody Products:

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	Browse ELISAs and CLIAs at Uscn

(According to InterPro, ProtoNet, UniProtKB, and/or BLOCKS, Sets of similar genes according to GeneDecks)
About This Section

SCN5A for domains About GeneDecksing

5/6 InterPro domains/families (see all 6):

IPR001696 Na_channel_asu

IPR010526 Na_trans_assoc

IPR000048 IQ_motif_EF-hand-BS

IPR005821 Ion_trans_dom

IPR024583 DUF3451

Graphical View of Domain Structure for InterPro Entry Q14524

ProtoNet protein and cluster: Q14524

3 Blocks protein families:

IPB000048 IQ calmodulin-binding region

IPB001696 Voltage-gated Na+ channel alpha subunit signature

IPB008053 Voltage-gated Na+ channel alpha 5 subunit signature

UniProtKB/Swiss-Prot: SCN5A_HUMAN, Q14524

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. Nav1.5/SCN5A subfamily

Similarity: Contains 1 IQ domain

(According to ¹UniProtKB, Genatlas, LifeMap Discovery™, IUBMB, and/or ²DME, Human phenotypes from GenomeRNAi, Animal models from MGI Mar 06 2013,
bound targets from SABiosciences, miRNA Gene Targets from miRTarBase shRNA from OriGene, RNAi from EMD Millipore, siRNAs from OriGene, QIAGEN, microRNA from QIAGEN, Gene Editing from DNA2.0, Clones from EMD Millipore, OriGene, SwitchGear Genomics, GenScript, Sino Biological, DNA2.0, and Vector BioLabs, Cell Lines from GenScript, LifeMap BioReagents, In Situ Hybridization Assays from Advanced Cell Diagnostics, Ontologies according to Gene Ontology Consortium 01 Mar 2013 via Entrez Gene.)
About This Section

Function Summary:

UniProtKB/Swiss-Prot: SCN5A_HUMAN, Q14524

Function: This protein 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. It is a

tetrodotoxin-resistant Na(+) channel isoform. This channel is responsible for the initial upstroke of the action

potential. Channel inactivation is regulated by intracellular calcium levels

Genatlas biochemistry entry for SCN5A:

sodium voltage-gated channel,type V,alpha polypeptide,tetradotoxin-resistant,heart

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		hsa-miR-520e hsa-miR-1307 hsa-miR-3146 hsa-miR-219-5p hsa-miR-374a hsa-miR-200b hsa-miR-3148 hsa-miR-761

		SwitchGear 3'UTR luciferase reporter plasmid: SCN5A 3' UTR sequence

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Gene Editing
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In Situ Assay
Products:

Advanced Cell Diagnostics RNAscope RNA in situ hybridization assays for SCN5A

Gene Ontology (GO): 5/8 molecular function terms (GO ID links to tree view) (see all 8): About this table

GO ID	Qualified GO term	Evidence	PubMed IDs
GO:0005248	voltage-gated sodium channel activity	IDA	19808477
GO:0005515	protein binding	IPI	18184654
GO:0005516	calmodulin binding	IPI	--
GO:0019899	enzyme binding	IPI	19666841
GO:0030506	ankyrin binding	IDA	15579534

SCN5A for ontologies About GeneDecksing

Animal Models:
9 MGI mutant phenotypes (inferred from 8 alleles) (MGI details for Scn5a):

behavior/neurological	cardiovascular system	cellular	embryogenesis	growth/size
mortality/aging	muscle	nervous system	normal

SCN5A for phenotypes About GeneDecksing

(Pathways according to EMD Millipore, R&D Systems, Cell Signaling Technology, KEGG, PharmGKB, BioSystems, Reactome, Tocris Bioscience, GeneGo (Thomson Reuters), QIAGEN, and/or UniProtKB, Sets of similar genes according to GeneDecks, Interaction Networks according to SABiosciences, 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 Mar 2013 via Entrez Gene).
About This Section

Unified GeneCards pathways - 5/8 super-pathways (see all 8) About this table

See pathways by source

Super-pathway

contained gene-specific pathways

Axon guidance

	Axon guidance	1.00			L1CAM interactions	0.39
	Developmental Biology	0.69

Activation of cAMP-Dependent PKA

	Activation of cAMP-Dependent PKA	1.00			PKA Signaling	0.56
	cAMP Pathway	0.77

Neuropathic Pain-Signaling in Dorsal Horn Neurons

	Neuropathic Pain-Signaling in Dorsal Horn Neurons	1.00			Cholera Infection	0.40
	Aldosterone Signaling in Epithelial Cells	0.47

Interaction between L1 and Ankyrins

Interaction between L1 and Ankyrins

1.00

Antiarrhythmic Pathway, Pharmacodynamics

Antiarrhythmic Pathway, Pharmacodynamics

1.00

Pathway sources
See GeneCards unified pathways
Show all pathways

1 EMD Millipore Pathway for SCN5A

Sodium channels and transporters- inward current

5/7 Downloadable PowerPoint Slides of QIAGEN Pathway Central Maps for SCN5A (see all 7)

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

1 BioSystems Pathway for SCN5A

SIDS Susceptibility Pathways

4 Reactome Pathways for SCN5A

	L1CAM interactions
	Developmental Biology
	Interaction between L1 and Ankyrins
	Axon guidance

1 PharmGKB Pathway for SCN5A

Antiarrhythmic Pathway, Pharmacodynamics

SCN5A for pathways About GeneDecksing

Interactions:

SABiosciences Gene Network Central^TM Interacting Genes and Proteins Network for SCN5A

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

5/74 Interacting proteins for SCN5A (Q14524^{1, 2, 3} ENSP00000328968⁴) via UniProtKB, MINT, STRING, and/or I2D (see all 74)

Interactant		Interaction Details
GeneCard	External ID(s)	Interaction Details
HIST1H4A	P62805³	I2D: score=1
HIST1H4B	P62805³	I2D: score=1
HIST1H4C	P62805³	I2D: score=1
HIST1H4D	P62805³	I2D: score=1
HIST1H4E	P62805³	I2D: score=1

About this table

Gene Ontology (GO): 5/30 biological process terms (GO ID links to tree view) (see all 30): About this table

GO ID	Qualified GO term	Evidence	PubMed IDs
GO:0002027	regulation of heart rate	IMP	18616619
GO:0003231	cardiac ventricle development	ISS	--
GO:0003360	brainstem development	ISS	--
GO:0006814	sodium ion transport	IDA	19074138
GO:0010765	positive regulation of sodium ion transport	IDA	18065446

SCN5A for ontologies About GeneDecksing

(Chemical Compounds according to UniProtKB, Enzo Life Sciences, EMD Millipore, Tocris Bioscience HMDB, BitterDB, and/or Novoseek, and Drugs according to DrugBank, Enzo Life Sciences, and/or PharmGKB, with drugs/clinical trials/news search links to CenterWatch)
About This Section

SCN5A for compounds About GeneDecksing

Browse Small Molecules at EMD Millipore

Browse drugs & compounds from Enzo Life Sciences

Compounds for SCN5A available from Tocris Bioscience About this table

Compound	Action	CAS #
Ralfinamide mesylate	Na+ channel blocker	[202825-45-4]
Vinpocetine	Na+ channel blocker	[42971-09-5]
QX 314 chloride	Na+ channel blocker	[5369-03-9]
Flecainide acetate	Cardiac Na+ channel blocker. Antiarrhythmic	[54143-56-5]
Tetrodotoxin citrate	Na+ channel blocker. Citrate salt of tetrodotoxin (Cat. No. 1078)	[18660-81-6]

2 HMDB Compounds for SCN5A About this table

Compound	Synonyms	CAS #	PubMed Ids
Sodium	Sodium (see all 2)	7440-23-5	--
Verapamil	Akilen (see all 107)	52-53-9	--

10/29 DrugBank Compounds for SCN5A (see all 29) About this table

Compound	Synonyms	CAS #	Type	Actions	PubMed Ids
Flecainide	Flecainida [INN-Spanish] (see all 2)	54143-55-4	target	inhibitor	10758053 10617684 15272045 10961955 12601084 11752352 11196553 11535580 11307783
Quinidine	--	56-54-2	target	inhibitor	16138883 16972995 17023504 9476974 17556186 11752352 15877619 20685573
Quinidine barbiturate	--	--	target	inhibitor	16138883 16972995 17023504 9476974 17556186 11752352 15877619 20685573
Mexiletine	Mexiletina [INN-Spanish] (see all 4)	31828-71-4	target	inhibitor	12650887 16168489 12123767 12604879 12676070 11752352 11196553
Zonisamide	Zonisamida [Spanish] (see all 2)	68291-97-4	target	inhibitor	20025128 14704463 19557119 18433351 20001433 15511691 19948168
Ajmaline	--	4360-12-7	target	inhibitor	20022821 18599870 20174578 6088360 20870038 21126620
Dibucaine	--	85-79-0	target	inhibitor	9742684 17139284 11752352 17016423 12354567 8798723
Indecainide	9-(3-(Isopropylamino)propyl)-9-fluorenylcarboxamid (see all 6)	74517-78-5	target	inhibitor	17139284 2688391 6206315 11752352 17016423 2476626
Lidocaine	Dilocaine (see all 2)	137-58-6	target	inhibitor	16686685 17016511 20585544 19088384 16840798 17445919
Procainamide	--	51-06-9	target	inhibitor	11155778 11752352 10662748 11839626 10443304 11225790

10/22 Novoseek chemical compound relationships for SCN5A gene (see all 22) About this table

Compound	-log (P-Val)	Hits	PubMed IDs for Articles with Shared Sentences (# sentences)
sodium	87	288	18436145 (4), 14753626 (3), 18591664 (3), 20042427 (3) (see all 99)
ajmaline	83.4	5	15520322 (1), 20022821 (1), 15028074 (1), 10662748 (1) (see all 5)
mexiletine	83.1	9	17698727 (2), 9556090 (1), 18071303 (1), 18060054 (1) (see all 6)
flecainide	82	13	11333173 (4), 10758053 (2), 11535580 (1), 18071303 (1) (see all 8)
pilsicainide	78.6	2	17916151 (1)
lidocaine	51.1	16	8785328 (4), 18599870 (2), 1309946 (1), 10758053 (1) (see all 10)
potassium	49.9	23	8873679 (2), 10613047 (2), 9570196 (1), 11259355 (1) (see all 15)
procainamide	46.7	1	10662748 (1)
cisapride	34.1	1	16301357 (1)
tetrodotoxin	29.5	7	1309946 (2), 9694861 (1), 1375397 (1)

Search CenterWatch for drugs/clinical trials and news about SCN5A

(Secondary structures according to fRNAdb,
GenBank/EMBL/DDBJ Accessions according to
Unigene (Build 235 Homo sapiens; Mar 10 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,
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Tagged/untagged cDNA clones from OriGene, SwitchGear Genomics, GenScript, DNA2.0, Vector BioLabs, Primers from OriGene, SABiosciences, and/or QIAGEN )
About This Section

REFSEQ mRNAs for SCN5A gene (6 alternative transcripts):

NM_000335.4 NM_001099404.1 NM_001099405.1 NM_001160160.1 NM_001160161.1 NM_198056.2

Unigene Cluster for SCN5A:

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

Hs.517898 [show with all ESTs]

Unigene Representative Sequence: NM_198056

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

ENST00000414099 ENST00000423572(uc021wvn.1 uc021wvo.1) ENST00000413689(uc021wvi.1 uc021wvk.1 uc021wvp.1 uc021wvs.1 uc021wvt.1)

ENST00000333535 ENST00000455624(uc021wvw.1) ENST00000450102(uc010hhl.1)

ENST00000449557 ENST00000464652 ENST00000491944 ENST00000476683 ENST00000327956(uc021wvx.1)

ENST00000451551(uc021wvj.1 uc021wvl.1 uc021wvu.1) ENST00000443581(uc021wvq.1 uc021wvr.1)

ENST00000425664(uc021wvm.1 uc021wvv.1)

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		SwitchGear 3'UTR luciferase reporter plasmid: SCN5A 3' UTR sequence

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Additional cDNA sequence:

AB158469.2 AB158470.2 AB208866.1 AF482988.1 AJ310886.1 AJ310887.1 AJ310888.1 AJ310889.1

AJ310890.1 AJ310891.1 AJ310892.1 AJ310893.1 AJ310894.1 AJ310895.1 AJ310896.1 AY038064.1

AY148488.1 BC051374.1 BC140813.1 BC144621.1 EF092292.1 EF092293.1 EF092294.1 EF092295.1

EF629346.1 EF629347.1

5 DOTS entries:

DT.100745286 DT.75174024 DT.99955208 DT.120884034 DT.100697400

24/27 AceView cDNA sequences (see all 27):

AJ310889 AF482988 AJ310886 AJ310891 AJ310893 AJ310887 AJ310890 NM_000335

AJ310896 AJ310888 AY148488 NM_198056 BM917024 AJ310895 AB158470 BU845010

BC051374 M77235 AB158469 AY038064 AJ310892 BU846317 AJ310894 BE391214

GeneLoc Exon Structure

5 Alternative Splicing Database (ASD) splice patterns (SP) for SCN5A About this scheme

ExUns:	1	^	2a	·	2b	^	3a	·	3b	^	4a	·	4b	^	5	^	6a	·	6b	·	6c	^	7	^	8
SP1:									-
SP2:																	-						-
SP3:																	-		-		-
SP4:															-		-						-
SP5:

ECgene alternative splicing isoforms for SCN5A

(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™, plus additional links to Genevestigator, and/or SOURCE, and/or BioGPS, and/or UniProtKB,
PCR Arrays from SABiosciences, Primers from OriGene, SABiosciences, and/or QIAGEN, In Situ Hybridization Assays from Advanced Cell Diagnostics)
About This Section

SCN5A expression in normal human tissues (normalized intensities)
See probesets specificity/sensitivity at GeneAnnot
About this imageBioGPS
CGAP TAG: --

About this image

SCN5A expression in embryonic tissues and stem cells

Expression by the Database of Embryonic development, Stem cell research, and Regenerative medicine About this table

3 LifeMap In Vivo Development Anatomical Compartments/Cells

Tissue

Anatomical Compartment

Cell

Category (developmental path)

Bone

Cartilage

Head Mesenchyme

Expression:

Positive

Negative

Selective marker

Experimental details:

Curated

Microarrays

In-situ hybridization

Stem Cell Differentiation: 2 LifeMap Cells

Name

Category

Early cardiomyocytes (Differentiation of c...)

Floating colonies of cardiomyocytes (Differentiation of c...)

See SCN5A Protein Expression from SPIRE MOPED and PaxDB
Genevestigator expression for SCN5A

SOURCE GeneReport for Unigene cluster: Hs.517898

UniProtKB/Swiss-Prot: SCN5A_HUMAN, Q14524

Tissue specificity: Found in jejunal circular smooth muscle cells (at protein level). Expressed in human atrial and

ventricular cardiac muscle but not in adult skeletal muscle, brain, myometrium, liver, or spleen. Isoform 4 is

expressed in brain

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In Situ
Assay Products:

Advanced Cell Diagnostics RNAscope RNA in situ hybridization assays for SCN5A

(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)
About This Section

This gene was present in the common ancestor of animals.

Orthologs for SCN5A gene from 4/18 species (see all 18) About this table

Organism	Taxonomic classification	Gene	Description	Human Similarity	Orthology Type	Details
chicken (Gallus gallus)	Aves	SCN5A¹	sodium channel, voltage-gated, type V, alpha subunit	72(n) 77.66(a)		395947 XM_001232817.2 XP_001232818.2
lizard (Anolis carolinensis)	Reptilia	SCN5A⁶	--	70(a)	1 ↔ 1	GL343530.1(7284-146192)
zebrafish (Danio rerio)	Actinopterygii	scn12ab¹	sodium channel, voltage gated, type XII, alpha b	67.66(n) 68.43(a)		566868 NM_001045123.1 NP_001038588.1
fruit fly (Drosophila melanogaster)	Insecta	NaCP60E³	sodium ion transport voltage-gated sodium channel	63(a) (best of 2)		60E5 --

ENSEMBL Gene Tree for SCN5A (if available)
TreeFam Gene Tree for SCN5A (if available)

(Paralogs according to ¹HomoloGene,
²Ensembl, and ³SIMAP, Pseudogenes according to ⁴Pseudogene.org Build 68)
About This Section

Paralogs for SCN5A gene

CACNA1A² SCN9A² CACNA1D² CACNA1I² SCN7A² CACNA1F² SCN8A² CACNA1G²

SCN10A² SCN3A² CACNA1E² SCN2A² CACNA1S² CACNA1C² CACNA1H² SCN11A²

SCN4A² SCN1A² CACNA1B²

18/25 SIMAP similar genes for SCN5A using alignment to 17 protein entries: SCN5A_HUMAN (see all proteins) (see all similar genes):

SCN1A SCN2A SCN10A SCN3A SCN9A SCN4A

CACNA1F SCN8A SCN2A2 SCN11A CACNA1A CACNA1I

CACNA1S CACNA1G CACNA1B CACNA1C CACNA1D TPCN1

SCN5A for paralogs About GeneDecksing

(SNPs/Variants according to the ¹NCBI SNP Database, ²Ensembl, ³PupaSUITE, UniProtKB, 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) and the Locus Specific Mutation Databases (LSDB), Blood group antigen gene mutations by BGMUT, Resequencing Primers from QIAGEN, Cancer Mutation PCR Arrays and Assays and Copy Number PCR Arrays from SABiosciences)
About This Section

SNP ID	Valid	Clinical significance	Chr 3 pos	Sequence	#	AA Chg	Type	More	#	Allele freq	Pop	Total sample	More
Genomic Data					Transcription Related Data				Allele Frequencies
				--	--	--		--	--
rs41258454^1,2	C,	non-pathogenic	93874921(+)	`TGCCCG/AGGCCA`	6	--	int¹		6		NS	964
rs41311123^1,2	C,F,	non-pathogenic	93891386(+)	`CCGGCA/C/TCCCAC`	18	G	syn¹		7		NS EU	1475
rs45620037^1,2	C,	pathogenic	93837732(-)	`ACGCAC/TCTTCC`	8	T I	mis¹ int¹		5		NS NA	496
rs45471994^1,2	C	pathogenic	93837767(-)	`TATCAG/ATCATT`	8	/I /V	mis¹ int¹		5		NS NA	494
rs137854608^1,2	C	pathogenic	93841743(-)	`CCGACA/GGCTTG`	12	S G	mis¹		0	--	--	--	--
rs137854606^1,2	C	pathogenic	93847467(-)	`CCCGTG/TGCCTC`	12	G C	mis¹		0	--	--	--	--
rs1805124^1,2	C,F,A,H,	pathogenic	93847600(-)	`CCACCA/GCACAT`	12	H R	mis¹ ese³		35		NA NS EA WA CSA EU	4979
rs137854611^1,2	C	pathogenic	93853742(-)	`CATGGA/C/TGCTGG`	18	E A V	mis¹		0	--	--	--	--
rs137854609^1,2	C	pathogenic	93870395(-)	`TTGCCA/G/TCCCAG`	18	T A S	mis¹		0	--	--	--	--
rs137854617^1,2	C	pathogenic	93870563(-)	`TGGCCA/GAGTCA`	12	K E	mis¹		0	--	--	--	--

HapMap Linkage Disequilibrium report for SCN5A (38589548 - 38691164 bp)
Structural Variations (Copy Number Variations, Insertions/Deletions, Inversions)
Database of Genomic Variants (DGV): 5 variations for SCN5A
5 CNVs: 79745 36146 59139 91282 91281
Human Gene Mutation Database (HGMD): SCN5A

Locus Specific Mutation Databases (LSDB): SCN5A

SABiosciences Cancer Mutation PCR Assays

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DNA2.0 Custom Variant and Variant Library Synthesis for SCN5A

(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.)
About This Section

SCN5A for disorders           About GeneDecksing

OMIM gene information: 600163
OMIM disorders: 603830  601144  113900  603829  608567  601154  272120
UniProtKB/Swiss-Prot: SCN5A_HUMAN, Q14524

Defects in SCN5A are a cause of progressive familial heart block type 1A (PFHB1A) [MIM:113900]; also known as

Lenegre-Lev disease or progressive cardiac conduction defect (PCCD). PFHB1A is an autosomal dominant cardiac bundle

branch disorder that may progress to complete heart block. PFHB1A is characterized by progressive alteration of

cardiac conduction through the His-Purkinje system with right or left bundle branch block and widening of QRS

complexes, leading to complete atrioventricular block and causing syncope and sudden death

Defects in SCN5A are the cause of long QT syndrome type 3 (LQT3) [MIM:603830]. Long QT syndromes are heart

disorders characterized by a prolonged QT interval on the ECG and polymorphic ventricular arrhythmias. They cause

syncope and sudden death in response to exercise or emotional stress. LQT3 inheritance is an autosomal dominant

Defects in SCN5A are the cause of Brugada syndrome type 1 (BRGDA1) [MIM:601144]. An autosomal dominant

tachyarrhythmia characterized by right bundle branch block and ST segment elevation on an electrocardiogram (ECG). It

can cause the ventricles to beat so fast that the blood is prevented from circulating efficiently in the body. When

this situation occurs (called ventricular fibrillation), the individual will faint and may die in a few minutes if the

heart is not reset

Defects in SCN5A are the cause of sick sinus syndrome type 1 (SSS1) [MIM:608567]. The term 'sick sinus

syndrome' encompasses a variety of conditions caused by sinus node dysfunction. The most common clinical

manifestations are syncope, presyncope, dizziness, and fatigue. Electrocardiogram typically shows sinus bradycardia,

sinus arrest, and/or sinoatrial block. Episodes of atrial tachycardias coexisting with sinus bradycardia

('tachycardia-bradycardia syndrome') are also common in this disorder. SSS occurs most often in the elderly associated

with underlying heart disease or previous cardiac surgery, but can also occur in the fetus, infant, or child without

heart disease or other contributing factors, in which case it is considered to be a congenital disorder

Defects in SCN5A are the cause of familial paroxysmal ventricular fibrillation type 1 (VF1) [MIM:603829]. A

cardiac arrhythmia marked by fibrillary contractions of the ventricular muscle due to rapid repetitive excitation of

myocardial fibers without coordinated contraction of the ventricle and by absence of atrial activity

Defects in SCN5A may be a cause of sudden infant death syndrome (SIDS) [MIM:272120]. SIDS is the sudden death

of an infant younger than 1 year that remains unexplained after a thorough case investigation, including performance

of a complete autopsy, examination of the death scene, and review of clinical history. Pathophysiologic mechanisms for

SIDS may include respiratory dysfunction, cardiac dysrhythmias, cardiorespiratory instability, and inborn errors of

metabolism, but definitive pathogenic mechanisms precipitating an infant sudden death remain elusive. Long QT

syndromes-associated mutations can be responsible for some of SIDS cases

Defects in SCN5A may be a cause of familial atrial standstill (FAS) [MIM:108770]. Atrial standstill is an

extremely rare arrhythmia, characterized by the absence of electrical and mechanical activity in the atria.

Electrocardiographically, it is characterized by bradycardia, the absence of P waves, and a junctional narrow complex

escape rhythm

Defects in SCN5A are the cause of cardiomyopathy dilated type 1E (CMD1E) [MIM:601154]; also known as dilated

cardiomyopathy with conduction disorder and arrhythmia or dilated cardiomyopathy with conduction defect 2. Dilated

cardiomyopathy is a disorder characterized by ventricular dilation and impaired systolic function, resulting in

congestive heart failure and arrhythmia. Patients are at risk of premature death

Defects in SCN5A are the cause of familial atrial fibrillation type 10 (ATFB10) [MIM:614022]. ATFB10 is a

familial form of atrial fibrillation, a common sustained cardiac rhythm disturbance. Atrial fibrillation is

characterized by disorganized atrial electrical activity and ineffective atrial contraction promoting blood stasis in

the atria and reduces ventricular filling. It can result in palpitations, syncope, thromboembolic stroke, and

congestive heart failure

20/51 diseases for SCN5A (see all 51): About MalaCards

long qt syndrome long qt syndrome 3 right bundle branch block sudden infant death syndrome

heart block, progressive, type ia arrhythmogenic right ventricular dysplasia heart block, nonprogressive progressive familial heart block type 1a

ventricular fibrillation heart block ventricular fibrillation, familial, 1 left ventricular noncompaction

sick sinus syndrome atrial fibrillation hemiplegic migraine resting heart rate

long qt syndrome 2 supravalvular aortic stenosis brugada syndrome familial hemiplegic migraine

8 diseases from the University of Copenhagen DISEASES database for SCN5A:

Brugada syndrome Long QT syndrome Right bundle branch block Sick sinus syndrome

Sudden infant death syndrome Congenital heart block Dilated cardiomyopathy Familial atrial fibrillation

10/39 Novoseek disease relationships for SCN5A gene (see all 39) About this table

Disease	-log (P-Val)	Hits	PubMed IDs for Articles with Shared Sentences (# sentences)
brugada syndrome	98	265	17227473 (7), 16325048 (5), 19100032 (5), 11748104 (4) (see all 99)
long qt syndrome	94.9	69	8521555 (2), 19083750 (2), 14654377 (2), 10200053 (1) (see all 57)
long qt syndrome 3	91	6	16707561 (1), 18408010 (1), 19041666 (1), 17110414 (1) (see all 5)
ventricular fibrillation, idiopathic	90.9	16	10940383 (2), 12693506 (1), 14985827 (1), 20042427 (1) (see all 15)
death sudden cardiac	85.7	13	19377070 (2), 15890323 (1), 16132053 (1), 16943925 (1) (see all 10)
death sudden	85.3	29	10590249 (2), 18361072 (2), 11289718 (1), 16707561 (1) (see all 25)
arrhythmia	83.8	92	18368697 (5), 18708744 (2), 15123648 (2), 19027780 (2) (see all 57)
romano-ward syndrome	82.6	3	18752142 (1), 10973849 (1), 10508990 (1)
defect conduction	81.9	23	11748104 (3), 16707561 (2), 16643399 (2), 17897635 (2) (see all 14)
right bundle branch block	80.9	3	16943925 (1), 10940383 (1), 10662748 (1)

GeneTests: SCN5A

Brugada Syndrome

Dilated Cardiomyopathy

Romano-Ward Syndrome

Genetic Association Database (GAD): SCN5A
Human Genome Epidemiology (HuGE) Navigator: SCN5A (101 documents)

Export disorders for SCN5A 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)
About This Section

PubMed articles for SCN5A gene, integrated from 9 sources (see all 638):
(articles sorted by number of sources associating them with SCN5A)

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

Genetic analysis of the cardiac sodium channel gene SCN5A in Koreans with Brugada syndrome. (PubMed id 15338453)^{1, 2, 4, 9} Shin D.-J.... Yoon S.K. (2004)
Congenital sick sinus syndrome caused by recessive mutations in the cardiac sodium channel gene (SCN5A). (PubMed id 14523039)^{1, 2, 4, 9} Benson D.W.... George A.L. Jr. (2003)
Allelic variants in long-QT disease genes in patients with drug- associated torsades de pointes. (PubMed id 11997281)^{1, 2, 4, 9} Yang P.... Roden D.M. (2002)
Double SCN5A mutation underlying asymptomatic Brugada syndrome. (PubMed id 15851320)^{1, 2, 4, 9} Yokoi H.... Tsutsui H. (2005)
SCN5A mutation associated with dilated cardiomyopathy, conduction disorder, and arrhythmia. (PubMed id 15466643)^{1, 2, 3, 9} McNair W.P....Mestroni L. (2004)
SCN5A mutations associated with an inherited cardiac arrhythmia, long QT syndrome. (PubMed id 7889574)^{1, 2, 4, 9} Wang Q.... Keating M.T. (1995)
Compendium of cardiac channel mutations in 541 consecutive unrelated patients referred for long QT syndrome genetic testing. (PubMed id 15840476)^{1, 2, 4} Tester D.J....Ackerman M.J. (2005)
Genotype-phenotype relationship in Brugada syndrome: electrocardiographic features differentiate SCN5A-related patients from non-SCN5A-related patients. (PubMed id 12106943)^{1, 2, 4} Smits J.P.P.... Wilde A.A.M. (2002)
Human SCN5A gene mutations alter cardiac sodium channel kinetics and are associated with the Brugada syndrome. (PubMed id 10690282)^{1, 2, 4} Rook M.B.... Wilde A.A.M. (1999)
SCN5A variants in Japanese patients with left ventricular noncompaction and arrhythmia. (PubMed id 18368697)^{1, 2, 9} Shan L....Towbin J.A. (2008)

(in PubMed, OMIM, and NCBI Bookshelf)
About This Section

		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)
About This Section

Entrez Gene: 6331	HGNC: 10593	AceView: SCN5A	Ensembl:ENSG00000183873	euGenes: HUgn6331
ECgene: SCN5A	H-InvDB: SCN5A

(According to HUGE)
About This Section

(According to PharmGKB, ATLAS, HORDE, IMGT, LEIDEN, UniProtKB/Swiss-Prot, and/or UniProtKB/TrEMBL,
Wikipedia and/or GeneReviews via UniProtKB/Swiss-Prot)
About This Section

Name	Description
PharmGKB entry for SCN5A	Pharmacogenomics, SNPs, Pathways
GeneReviews	http://www.ncbi.nlm.nih.gov/sites/GeneTests/lab/gene/SCN5A

Intellectual Property for SCN5A gene
(Patent information from GeneIP, Licensable technologies from WIS Yeda, Salk, Tufts, IP news from LifeMap Sciences, Inc.)

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Patent Information for SCN5A gene:
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GeneCards and IP:
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SCN5A Gene

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

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SCN5A (Gene Symbol)
Sodium Channel, Voltage-Gated, Type V, Alpha Subunit
HH1
CDCD2
CMD1E
HB1
LQT3
SSS1
CMPD2
HB2
HBBD
ICCD
IVF
Nav1.5
PFHB1
Sodium Channel Protein Cardiac Muscle Subunit Alpha
Voltage-Gated Sodium Channel Subunit Alpha Nav1.5
VF1
Sodium Channel, Voltage-Gated, Type V, Alpha (Long QT Syndrome 3)
Cardiac Tetrodotoxin-Insensitive Voltage-Dependent Sodium Channel Alpha Subunit
Sodium Channel Protein Type 5 Subunit Alpha
Sodium Channel Protein Type V Subunit Alpha

Torsades de Pointes
Genetic Susceptibility
Right bundle branch block
Conduction Abnormalities
SINUS ARREST
Death Sudden Cardiac
Long QT Syndrome
VENTRICULAR FIBRILLATION, IDIOPATHIC
Tachyarrhythmia
VENTRICULAR ARRHYTHMIA
Atrial Fibrillation
Sudden infant death syndrome
Bradycardia
Arrhythmogenic Right Ventricular Dysplasia
DEFECT CONDUCTION
LONG QT SYNDROME 3
Ischemia
BRUGADA SYNDROME
HEART FAILURE
Tachycardia Ventricular
Cardiomyopathy
Coronary Artery Disease
BUNDLE BRANCH BLOCK
Shock
Death Sudden
Heart Diseases
Atrioventricular Block
Arrhythmia
VENTRICULAR TACHYARRHYTHMIA
ATRIAL FIBRILLATION, FAMILIAL
Romano-Ward Syndrome
Sick Sinus Syndrome
Cardiovascular Diseases
genetic disorder
Dilated Cardiomyopathy
FIBRILLATION
Cardiac Arrest
Ventricular Fibrillation
Tachycardia

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SCN5A Gene

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

Aliasesfor SCN5A gene

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Proteinsfor SCN5A gene

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Expression for SCN5A gene

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Aliases
for SCN5A gene

Summaries
for SCN5A gene

Genomic Views
for SCN5A gene

Proteins
for SCN5A gene

Protein Domains /
Families
for SCN5A gene

Function
for SCN5A gene

Pathways & Interactions
for SCN5A gene

Drugs & Compounds
for SCN5A gene

Transcripts
for SCN5A gene

Expression
for SCN5A gene

Orthologs
for SCN5A gene

Paralogs
for SCN5A gene

Genomic Variants
for SCN5A gene

Disorders / Diseases
for SCN5A gene

Publications
for SCN5A gene

Intellectual Property
for SCN5A gene

Products
for SCN5A gene