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SCN4A Gene

protein-coding   GIFtS: 66
GCID: GC17M062015

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


(Previous symbol: HYKPP)
  See SCN4A-related diseases
at  

(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 IV, Alpha Subunit1 2     HYPP2 5
HYKPP1 2     NAC1A2 5
Sodium Channel Protein Skeletal Muscle Subunit Alpha2 3     Na(V)1.42
Sodium Channel Protein Type IV Subunit Alpha2 3     Nav1.42
Voltage-Gated Sodium Channel Subunit Alpha Nav1.42 3     Skeletal Muscle Voltage-Dependent Sodium Channel Type IV Alpha Subunit2
SkM12 3     Sodium Channel Protein Type 4 Subunit Alpha2
HOKPP22 5     

External Ids:    HGNC: 105911   Entrez Gene: 63292   Ensembl: ENSG000000073147   OMIM: 6039675   UniProtKB: P354993   

Export aliases for SCN4A gene to outside databases

Previous GC identifers: GC17M061653 GC17M064442 GC17M062356 GC17M062489 GC17M059369 GC17M057383


(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 SCN4A Gene:
Voltage-gated sodium channels are transmembrane glycoprotein complexes composed of a large alpha subunit with 24
transmembrane domains and one or more regulatory beta subunits. They are responsible for the generation and
propagation of action potentials in neurons and muscle. This gene encodes one member of the sodium channel alpha
subunit gene family. It is expressed in skeletal muscle, and mutations in this gene have been linked to several
myotonia and periodic paralysis disorders. (provided by RefSeq, Jul 2008)

GeneCards Summary for SCN4A Gene:
SCN4A (sodium channel, voltage-gated, type IV, alpha subunit) is a protein-coding gene. Diseases associated with SCN4A include hyperkalemic periodic paralysis type 2, and myasthenic syndrome, acetazolamide-responsive. GO annotations related to this gene include voltage-gated sodium channel activity. An important paralog of this gene is SCN5A.

UniProtKB/Swiss-Prot: SCN4A_HUMAN, P35499
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.
This sodium channel may be present in both denervated and innervated skeletal muscle

summary for SCN4A 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 SCN4A (Nav1.4) 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_000017.10  NT_010783.16  NC_018928.2  
Regulatory elements:
   Regulatory transcription factor binding sites in the SCN4A gene promoter:
         Tal-1   AML1a   p53   Pax-2   Pax-2a   STAT5A   E47   ATF6   RSRFC4   
         Other transcription factors

SwitchGear Promoter luciferase reporter plasmidSCN4A promoter sequence
   Search Chromatin IP Primers for SCN4A

Epigenetics:
DNA Methylation CpG Assay Predesigned for Pyrosequencing in human, mouse, rat SCN4A


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

Entrez Gene cytogenetic band: 17q23.3   Ensembl cytogenetic band:  17q23.3   HGNC cytogenetic band: 17q23.3

SCN4A Gene in genomic location: bands according to Ensembl, locations according to (and/or Entrez Gene and/or Ensembl if different)
SCN4A gene location

GeneLoc information about chromosome 17         GeneLoc Exon Structure

GeneLoc location for GC17M062015:  view genomic region     (about GC identifiers)

Start:
62,015,914 bp from pter      End:
62,050,278 bp from pter
Size:
34,365 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: SCN4A_HUMAN, P35499 (See protein sequence)
Recommended Name: Sodium channel protein type 4 subunit alpha  
Size: 1836 amino acids; 208061 Da
Subunit: Muscle sodium channels contain an alpha subunit and a smaller beta subunit. Interacts with the PDZ domain
of the syntrophin SNTA1, SNTB1 and SNTB2 (By similarity)
Secondary accessions: Q15478 Q16447 Q7Z6B1

Explore the universe of human proteins at neXtProt for SCN4A: NX_P35499

Explore proteomics data for SCN4A at MOPED

Post-translational modifications: 

  • Phosphorylation at Ser-1328 by PKC in a highly conserved cytoplasmic loop slows inactivation of the sodium channel
    and reduces peak sodium currents (By similarity)1
  • Glycosylation2 at Asn214, Asn288, Asn291, Asn297, Asn303, Asn315, Asn321, Asn333, Asn362, Asn1191,
                                 Asn1205
  • Modification sites at PhosphoSitePlus

  • See SCN4A Protein Expression from SPIRE MOPED, PaxDB, and MaxQB

    REFSEQ proteins: NP_000325.4  
    ENSEMBL proteins: 
     ENSP00000463963   ENSP00000396320  
    Reactome Protein details: P35499

    SCN4A Human Recombinant Protein Products:

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    Browse Sino Biological Recombinant Proteins
    Browse Sino Biological Cell Lysates
    Browse ProSpec Recombinant Proteins
    Browse Proteins at Cloud-Clone Corp.

     
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    antibodies-online antibodies for SCN4A (18 products) 

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    antibodies-online kits for SCN4A (7 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: Nav1.4
    Voltage-gated sodium channels

    Selected InterPro protein domains (see all 7):
     IPR028826 Na_channel_a4su_mammal-typ
     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 P35499

    ProtoNet protein and cluster: P35499

    3 Blocks protein domains:
    IPB000048 IQ calmodulin-binding region
    IPB001696 Voltage-gated Na+ channel alpha subunit signature
    IPB008052 Voltage-gated Na+ channel alpha 4 subunit signature


    UniProtKB/Swiss-Prot: SCN4A_HUMAN, P35499
    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. Nav1.4/SCN4A subfamily
    Similarity: Contains 1 IQ domain


    Find genes that share domains with SCN4A           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: SCN4A_HUMAN, P35499
    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.
    This sodium channel may be present in both denervated and innervated skeletal muscle

         Genatlas biochemistry entry for SCN4A:
    sodium voltage-gated channel,type IV,alpha polypeptide (see also GH@CR),adult muscle

         Gene Ontology (GO): 3 molecular function terms:    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0005216ion channel activity ----
    GO:0005248voltage-gated sodium channel activity IEA--
    GO:0005515protein binding ----
         
    Find genes that share ontologies with SCN4A           About GenesLikeMe


    Phenotypes:
         1 GenomeRNAi human phenotype for SCN4A:
     Synthetic lethal with Ras 

         5 MGI mutant phenotypes (inferred from 4 alleles(MGI details for Scn4a):
     behavior/neurological  growth/size/body  mortality/aging  muscle  no phenotypic analysis 

    Find genes that share phenotypes with SCN4A           About GenesLikeMe

    Animal Models:
         MGI mouse knock-out Scn4atm1Lex for SCN4A

       genOway: Develop your customized and physiologically relevant rodent model for SCN4A

    miRNA
    Products:
        
    miRTarBase miRNAs that target SCN4A:
    hsa-mir-335-5p (MIRT018528)

    Block miRNA regulation of human, mouse, rat SCN4A using miScript Target Protectors
    Selected qRT-PCR Assays for microRNAs that regulate SCN4A (see all 29):
    hsa-miR-2052 hsa-miR-3194-5p hsa-miR-19b-2* hsa-miR-520d-5p hsa-miR-486-3p hsa-miR-1205 hsa-miR-650 hsa-miR-3150a-3p
    SwitchGear 3'UTR luciferase reporter plasmidSCN4A 3' UTR sequence
    Inhib. RNA
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    Predesigned siRNA for gene silencing in human, mouse, rat SCN4A

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    Advanced Cell Diagnostics RNAscope RNA in situ hybridization assays for SCN4A


    (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
    SCN4A_HUMAN, P35499: Membrane; Multi-pass membrane protein
    Subcellular locations from COMPARTMENTS: 

    CompartmentConfidence
    plasma membrane4
    extracellular2
    nucleus1

    Gene Ontology (GO): 3 cellular component terms:    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0001518voltage-gated sodium channel complex IEA--
    GO:0005887integral component of plasma membrane TAS1659948
    GO:0016020membrane ----

    Find genes that share ontologies with SCN4A           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 SCN4A About   (see all 6)  
    See pathways by source

    SuperPathContained pathways About
    1L1CAM interactions
    Axon guidance0.63
    L1CAM interactions0.36
    Developmental Biology0.63
    2Activation of cAMP-Dependent PKA
    Activation of cAMP-Dependent PKA0.77
    PKA Signaling0.56
    cAMP Pathway0.77
    3Neuropathic Pain-Signaling in Dorsal Horn Neurons
    Neuropathic Pain-Signaling in Dorsal Horn Neurons0.47
    Cholera Infection0.40
    Aldosterone Signaling in Epithelial Cells0.47
    4G-Beta Gamma Signaling
    GHRH Signaling0.46
    5Sodium channels and transporters inward current
    Sodium channels and transporters inward current


    Find genes that share SuperPaths with SCN4A           About GenesLikeMe

    Pathways by source                                                                                                                                                                 See SuperPaths
    Show all pathways

    Selected Downloadable PowerPoint Slides of GeneGlobe Pathway Central Maps for SCN4A (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 SCN4A
        Interaction between L1 and Ankyrins


        Custom Pathway & Disease-focused RT2 Profiler PCR Arrays for SCN4A
    Interactions:

        GeneGlobe Interaction Network for SCN4A

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

    Selected Interacting proteins for SCN4A (P354993 ENSP000003963204) via UniProtKB, MINT, STRING, and/or I2D (see all 35)
    InteractantInteraction Details
    GeneCardExternal ID(s)
    CALM1P621583I2D: score=3 
    CALM2P621583I2D: score=3 
    CALM3P621583I2D: score=3 
    SNTA1Q134243, ENSP000002173814I2D: score=3 STRING: ENSP00000217381
    SLC9A3R1O147453, ENSP000002626134I2D: score=1 STRING: ENSP00000262613
    About this table

    Gene Ontology (GO): 5 biological process terms:    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0006811ion transport ----
    GO:0006814sodium ion transport TAS10218481
    GO:0006936muscle contraction TAS1338909
    GO:0035725sodium ion transmembrane transport TAS10218481
    GO:0055085transmembrane transport ----

    Find genes that share ontologies with SCN4A           About GenesLikeMe



    (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 SCN4A available from Tocris Bioscience    About this table
    CompoundAction CAS #
    Phrixotoxin 3 Potent modulator of NaV1.2, NaV1.3 and NaV1.5 channels [880886-00-0]
    QX 314 chlorideNa+ channel blocker[5369-03-9]
    VeratridineVoltage-gated Na+ channel opener[71-62-5]
    TetrodotoxinNa+ channel blocker[4368-28-9]
    Tetrodotoxin citrateNa+ channel blocker. Citrate salt of tetrodotoxin (Cat. No. 1078)[18660-81-6]

    1 HMDB Compound for SCN4A    About this table
    CompoundSynonyms CAS #PubMed Ids
    SodiumSodium (see all 2)7440-23-5--

    4 DrugBank Compounds for SCN4A    About this table
    CompoundSynonyms CAS #TypeActionsPubMed Ids
    ZonisamideZonisamida [Spanish] (see all 2)68291-97-4targetinhibitor20025128 14704463 19557119 18433351 20001433 15511691 19948168
    DiclofenacDiclofenac Acid (see all 4)15307-86-5targetinhibitor15574747 15032643 15824190
    FlecainideFlecainida [INN-Spanish] (see all 2)54143-55-4targetinhibitor14608015
    Propofol2,6-Diisopropylphenol (see all 2)2078-54-8targetinhibitor18574460

    9 IUPHAR Ligands for SCN4A (Nav1.4)    About this table
    LigandTypeActionAffinityPubmed IDs
    tetrodotoxin
    Pore BlockerAntagonist7.68058462
    AFT-II
    Gating inhibitorAntagonist7.515169781
    ATX-II
    Gating inhibitorAntagonist7 - 7.315169781 8660409
    Bc-III
    Gating inhibitorAntagonist6.115169781
    mu-conotoxin GIIIA
    Pore BlockerAntagonist5.98058462
    mexilitine
    Pore BlockerAntagonist3.414608007
    veratridine
    ActivatorNone3.4--
    saxitoxin
    Channel blockerNone3.4--
    batrachotoxin
    ActivatorNone3.4--

    Selected Novoseek inferred chemical compound relationships for SCN4A gene (see all 13)    About this table
    Compound   -log (P-Val)   Hits   PubMed IDs for Articles with Shared Sentences (# sentences)
    sodium 81.5 95 14557559 (3), 9508059 (2), 18203179 (2), 8044656 (2) (see all 75)
    acetazolamide 71.9 1 11353725 (1)
    potassium 58.8 7 15596759 (2), 12414843 (1), 8242056 (1), 17917308 (1) (see all 6)
    chloride 44.2 3 9196902 (1), 18337730 (1), 19966974 (1)
    valine 42.3 4 16624558 (1), 10218481 (1), 11294924 (1), 20445432 (1)
    dihydropyridine 34.8 7 8395939 (3), 12536108 (1)
    methionine 34.8 4 9392583 (1), 16624558 (1), 10218481 (1), 12933953 (1)
    histidine 31.4 1 15185439 (1)
    succinylcholine 27.4 1 7741283 (1)
    arginine 22.9 2 17591984 (1), 15185439 (1)

    2 PharmGKB related drug/compound annotations for SCN4A gene    About this table
    Drug/compound PharmGKB Annotation
    flecainideCA  
    mexiletineCA  



    Find genes that share compounds with SCN4A           About GenesLikeMe



    (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 SCN4A gene: 
    NM_000334.4  

    Unigene Cluster for SCN4A:

    Sodium channel, voltage-gated, type IV, alpha subunit
    Hs.46038  [show with all ESTs]
    Unigene Representative Sequence: M81758
    4 Ensembl transcripts including schematic representations, and UCSC links where relevant:
    ENST00000578147 ENST00000584310 ENST00000581514 ENST00000435607(uc002jds.1)

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    Additional mRNA sequence: 

    AY212253.1 M81758.1 

    3 DOTS entries:

    DT.205582  DT.120934850  DT.102822636 

    Selected AceView cDNA sequences (see all 207):

    CR618467 BX280250 CR623737 AL559878 CR591997 CR606875 CR617922 S79249 
    CA415356 BX336723 AU105583 BG755705 CR608074 CR599571 BM924097 AU099391 
    AY212253 BM920096 CR592092 X83539 BI836408 AI239619 BG392020 BE514442 

    GeneLoc Exon Structure

    5 Alternative Splicing Database (ASD) splice patterns (SP) for SCN4A    About this scheme

    ExUns: 1 ^ 2 ^ 3 ^ 4 ^ 5 ^ 6 ^ 7 ^ 8 ^ 9 ^ 10 ^ 11a · 11b ^ 12a · 12b ^ 13 ^ 14a · 14b ^ 15a · 15b ^ 16 ^ 17a · 17b ^ 18a · 18b ^ 19a · 19b ^
    SP1:                                                              -                                         -                                                   
    SP2:                                                                                                                                                            
    SP3:                                                                                                        -           -     -     -     -                     
    SP4:                                                                                                                                                            
    SP5:                                                                                                                                                            

    ExUns: 20 ^ 21 ^ 22 ^ 23 ^ 24
    SP1:                              
    SP2:                              
    SP3:                              
    SP4:                              
    SP5:                              


    ECgene alternative splicing isoforms for SCN4A

    (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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    SCN4A expression in normal human tissues (normalized intensities)
    See probesets specificity/sensitivity at GeneAnnot
    About this imageBioGPS <intensity>2/3
    CGAP TAG: GCCTCAGCCC
    SCN4A Expression
    About this image

    SCN4A Protein expression data from MOPED1, PaxDb2 and MaxQB3    About this image

    SCN4A Protein Expression

    SOURCE GeneReport for Unigene cluster: Hs.46038
        Custom PCR Arrays for SCN4A
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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 SCN4A gene from Selected species (see all 11)    About this table
    Organism Taxonomic
    classification
    Gene Description Human
    Similarity
    Orthology
    Type
    Details
    mouse
    (Mus musculus)
    Mammalia Scn4a1 , 5 sodium channel, voltage-gated, type IV, alpha1, 5 88.54(n)1
    92.45(a)1
      11 (68.91 cM)5
    1108801  NM_133199.21  NP_573462.21 
     1063185925 
    chicken
    (Gallus gallus)
    Aves SCN4A1 sodium channel, voltage-gated, type IV, alpha subunit 79.03(n)
    81.76(a)
      771297  XM_004948509.1  XP_004948566.1 
    lizard
    (Anolis carolinensis)
    Reptilia SCN4A6
    sodium channel, voltage-gated, type IV, alpha subu...
    73(a)
    1 ↔ 1
    6(63462911-63564233)
    tropical clawed frog
    (Xenopus tropicalis)
    Amphibia LOC1004923711 sodium channel protein type 4 subunit alpha-like 69.93(n)
    78.22(a)
      100492371  XM_002933041.2  XP_002933087.2 
    zebrafish
    (Danio rerio)
    Actinopterygii scn4aa1 sodium channel, voltage-gated, type IV, alpha, a 69.94(n)
    74.37(a)
      572442  NM_001039825.1  NP_001034914.1 


    ENSEMBL Gene Tree for SCN4A (if available)
    TreeFam Gene Tree for SCN4A (if available)

    (Paralogs according to 1HomoloGene,
    2Ensembl, and 3SIMAP, Pseudogenes according to 4Pseudogene.org Build 68)
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    Paralogs for SCN4A gene
    SCN5A2  SCN9A2  CACNA1D2  SCN7A2  CACNA1I2  CACNA1F2  CACNA1G2  SCN8A2  
    SCN10A2  SCN3A2  SCN2A2  CACNA1S2  CACNA1C2  CACNA1H2  SCN11A2  SCN1A2  
    Selected SIMAP similar genes for SCN4A using alignment to 4 protein entries:     SCN4A_HUMAN (see all proteins) (see all similar genes):
    SCN1A    SCN3A    SCN2A    SCN5A    SCN8A    SCN10A
    SCN2A2    SCN9A    SCN11A    SCN7A    TPCN1    CACNA1I
    CACNA1A    CACNA1H    CACNA1E    CACNA1C    CACNA1B    CACNA1F

    Find genes that share paralogs with SCN4A           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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    Selected SNPs for SCN4A (see all 1129)    About this table                                 

    Genomic DataTranscription Related DataAllele Frequencies
    SNP IDValidClinical
    significance
    Chr 17 posSequence#AA
    Chg
    TypeMore#Allele
    freq
    PopTotal
    sample
    More
    ----------
    rs620708841,2,,4
    C,FPeriodic paralysis normokalemic (NKPP)4 non-pathogenic163052348(+) GAAGAC/TGGTGA 2 I V mis12Minor allele frequency- T:0.01EA EU 711
    VAR_0652304
    Myotonia SCN4A-related (MYOSCN4A)4--see VAR_0652302 R W mis40--------
    VAR_0549464
    Myotonia SCN4A-related (MYOSCN4A)4--see VAR_0549462 I N mis40--------
    VAR_0177924
    Periodic paralysis hypokalemic 2 (HOKPP2)4--see VAR_0177922 P S mis40--------
    VAR_0549364
    Paramyotonia congenita of von Eulenburg (PMC)4--see VAR_0549362 Q K mis40--------
    VAR_0223414
    Paramyotonia congenita of von Eulenburg (PMC)4--see VAR_0223412 A D mis40--------
    VAR_0549474
    Paramyotonia congenita of von Eulenburg (PMC)4--see VAR_0549472 L P mis40--------
    VAR_0015674
    Paramyotonia congenita of von Eulenburg (PMC)4--see VAR_0015672 G A mis40--------
    VAR_0549354
    Periodic paralysis hypokalemic 2 (HOKPP2)4--see VAR_0549352 R W mis40--------
    VAR_0549444
    Periodic paralysis hypokalemic 2 (HOKPP2)4--see VAR_0549442 R H mis40--------

    HapMap Linkage Disequilibrium report for SCN4A (62015914 - 62050278 bp)

    Structural Variations
         Database of Genomic Variants (DGV) 7 variations for SCN4A:    About this table    
    Variant IDTypeSubtypePubMed ID
    esv999259CNV Loss20482838
    nsv908684CNV Loss21882294
    nsv908685CNV Loss21882294
    nsv820272CNV Loss19587683
    nsv833511CNV Loss17160897
    nsv470596CNV Loss18288195
    nsv517272CNV Gain+Loss19592680

    Human Gene Mutation Database (HGMD): SCN4A
    Locus Specific Mutation Databases (LSDB): SCN4A

    Site Specific Mutation Identification with PCR Assays
    SeqTarget long-range PCR primers for resequencing SCN4A
    DNA2.0 Custom Variant and Variant Library Synthesis for SCN4A

    (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: 603967   
    OMIM disorders: 170500  168300  608390  614198  613345  
    UniProtKB/Swiss-Prot: SCN4A_HUMAN, P35499
  • Paramyotonia congenita of von Eulenburg (PMC) [MIM:168300]: An autosomal dominant channelopathy
    characterized by myotonia, increased by exposure to cold, intermittent flaccid paresis, not necessarily dependent
    on cold or myotonia, lability of serum potassium, non-progressive nature and lack of atrophy or hypertrophy of
    muscles. In some patients, myotonia is not increased by cold exposure (paramyotonia without cold paralysis).
    Patients may have a combination phenotype of PMC and HYPP. Note=The disease is caused by mutations affecting the
    gene represented in this entry
  • Periodic paralysis hypokalemic 2 (HOKPP2) [MIM:613345]: An autosomal dominant disorder manifested by
    episodic flaccid generalized muscle weakness associated with falls of serum potassium levels. Note=The disease is
    caused by mutations affecting the gene represented in this entry
  • Periodic paralysis hyperkalemic (HYPP) [MIM:170500]: An autosomal dominant channelopathy characterized by
    episodic flaccid generalized muscle weakness associated with high levels of serum potassium. Concurrence of
    myotonia is found in HYPP patients. Note=The disease is caused by mutations affecting the gene represented in
    this entry
  • Periodic paralysis normokalemic (NKPP) [MIM:170500]: A disorder closely related to hyperkalemic periodic
    paralysis, but marked by a lack of alterations in potassium levels during attacks of muscle weakness. Note=The
    disease is caused by mutations affecting the gene represented in this entry
  • Myotonia SCN4A-related (MYOSCN4A) [MIM:608390]: A phenotypically highly variable myotonia aggravated by
    potassium loading, and sometimes by cold. Myotonia is characterized by sustained muscle tensing that prevents
    muscles from relaxing normally. It causes muscle stiffness that can interfere with movement. In some people the
    stiffness is very mild, while in other cases it may be severe enough to interfere with walking, running, and
    other activities of daily life. Myotonia SCN4A-related includes myotonia permanens and myotonia fluctuans. In
    myotonia permanens, the myotonia is generalized and there is a hypertrophy of the muscle, particularly in the
    neck and the shoulder. Attacks of severe muscle stiffness of the thoracic muscles may be life threatening due to
    impaired ventilation. In myotonia fluctuans, the muscle stiffness may fluctuate from day to day, provoked by
    exercise. Note=The disease is caused by mutations affecting the gene represented in this entry
  • Myasthenic syndrome, congenital, acetazolamide-responsive (CMSAR) [MIM:614198]: A congenital myasthenic
    syndrome associated with fatigable generalized weakness and recurrent attacks of respiratory and bulbar paralysis
    since birth. The fatigable weakness involves lid-elevator, external ocular, facial, limb and truncal muscles and
    an decremental response of the compound muscle action potential on repetitive stimulation. Note=The disease is
    caused by mutations affecting the gene represented in this entry

  • 20 diseases for SCN4A:    
    About MalaCards
    hyperkalemic periodic paralysis type 2    myasthenic syndrome, acetazolamide-responsive    hyperkalemic periodic paralysis type 1    congenital myasthenic syndrome
    myotonia congenita, atypical, acetazolamide-responsive    scn4a-related congenital myasthenic syndrome    normokalemic periodic paralysis    hypokalemic periodic paralysis
    hyperkalemic periodic paralysis    potassium aggravated myotonia    paramyotonia congenita    hypokalemic periodic paralysis type 2
    hypokalemic periodic paralysis type 1    myotonia    malignant hyperthermia susceptibility    periodic paralyses
    malignant hyperthermia    thyrotoxic periodic paralysis    myasthenic syndrome, congenital, with pre- and postsynaptic defects    muscular dystrophy-dystroglycanopathy

    3 diseases from the University of Copenhagen DISEASES database for SCN4A:
    Myopathy     Idiopathic generalized epilepsy     Malignant hyperthermia

    Find genes that share disorders with SCN4A           About GenesLikeMe

    Selected Novoseek inferred disease relationships for SCN4A gene (see all 13)    About this table

    Disease   -log (P-Val)   Hits   PubMed IDs for Articles with Shared Sentences (# sentences)
    paramyotonia congenita 98.1 27 1315122 (2), 8044656 (2), 8580427 (2), 9196904 (2) (see all 22)
    hypokalemic periodic paralysis 95.9 12 19118277 (2), 14557559 (2), 15072700 (2), 18203179 (1) (see all 8)
    hyperkalemic periodic paralysis 95.5 18 9508059 (2), 1315122 (2), 8044656 (2), 9436446 (2) (see all 13)
    periodic paralysis 95.4 19 10366610 (2), 17898326 (1), 9703181 (1), 20076800 (1) (see all 16)
    normokalemic periodic paralysis 94.5 7 15583983 (2), 19065518 (2), 14990128 (1), 15596759 (1) (see all 5)
    myotonia congenita 88.8 1 19840739 (1)
    paralysis 71.4 8 8580427 (2), 9392583 (1), 14557559 (1), 10369308 (1) (see all 5)
    myopathy 71 9 14617673 (1), 8044656 (1), 10930446 (1), 19290024 (1) (see all 7)
    neuromuscular diseases 58.9 1 1315122 (1)
    hypokalemia 54.4 1 15185439 (1)

    GeneTests: SCN4A
    GeneReviews: SCN4A
    Genetic Association Database (GAD): SCN4A
    Human Genome Epidemiology (HuGE) Navigator: SCN4A (3 documents)

    Export disorders for SCN4A 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 SCN4A gene, integrated from 10 sources (see all 188):
    (articles sorted by number of sources associating them with SCN4A)
        Utopia: connect your pdf to the dynamic
    world of online information

    1. Identification of a mutation in the gene causing hyperkalemic periodic paralysis. (PubMed id 1659948)1, 2, 3, 9 Ptacek L.J.... Leppert M.F. (Cell 1991)
    2. In tandem analysis of CLCN1 and SCN4A greatly enhances mutation detection in families with non-dystrophic myotonia. (PubMed id 18337730)1, 4, 9 Trip J....Ginjaar I.B. (Eur. J. Hum. Genet. 2008)
    3. A novel founder SCN4A mutation causes painful cold-induced myotonia in French-Canadians. (PubMed id 17998485)1, 2, 9 Rossignol E.... Brais B. (Neurology 2007)
    4. Tubular aggregates in paralysis periodica paramyotonica with T704M mutation of SCN4A. (PubMed id 19077043)1, 2, 9 Luan X.... Yuan Y. (Neuropathology 2009)
    5. Absence of ion channels CACN1AS and SCN4A mutations in thyrotoxic hypokalemic periodic paralysis. (PubMed id 15072700)1, 4, 9 Ng W.Y....Cheah J.S. (Thyroid 2004)
    6. Paramyotonia congenita without paralysis on exposure to cold: a novel mutation in the SCN4A gene (Val1293Ile). (PubMed id 8580427)1, 2, 9 Koch M.C.... Ricker K. (NeuroReport 1995)
    7. Voltage sensor charge loss accounts for most cases of hypokalemic periodic paralysis. (PubMed id 19118277)1, 2, 9 Matthews E....Hanna M.G. (Neurology 2009)
    8. What causes paramyotonia in the United Kingdom? Common and new SCN4A mutations revealed. (PubMed id 18166706)1, 2, 9 Matthews E.... Hanna M.G. (Neurology 2008)
    9. Mutations of sodium channel alpha-subunit genes in Chinese patients with normokalemic periodic paralysis. (PubMed id 18046642)1, 2, 9 Xiuhai G.... Yanling M. (Cell. Mol. Neurobiol. 2008)
    10. New mutations of SCN4A cause a potassium-sensitive normokalemic periodic paralysis. (PubMed id 15596759)1, 2, 9 Vicart S.... Fontaine B. (Neurology 2004)

    (in PubMed, OMIM, and NCBI Bookshelf)
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     ANDOR
    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: 6329 HGNC: 10591 AceView: SCN4AandCD79B Ensembl:ENSG00000007314 euGenes: HUgn6329
    ECgene: SCN4A H-InvDB: SCN4A

    (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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    NameDescription
    PharmGKB entry for SCN4A Pharmacogenomics, SNPs, Pathways
    GeneReviewshttp://www.ncbi.nlm.nih.gov/books/NBK1116/?term=SCN4A[genesymbol]
    Wikipedia http://en.wikipedia.org/wiki/SCN4A

    (Patent information from GeneIP,
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    IP news from LifeMap Sciences, Inc.)
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    Patent Information for SCN4A gene:
    Search GeneIP for patents involving SCN4A

    GeneCards and IP:
    Japan Patent Office Licenses GeneCards     European Patent Office Licenses GeneCards     Improving the IP Search



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