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SCN9A Gene

protein-coding   GIFtS: 64
GCID: GC02M167051

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

(Previous names: sodium channel, voltage-gated, type IX, alpha polypeptide)
  See 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 IX, Alpha Subunit1 2     FEB3B2 5
NENA2 3 5     GEFSP72 5
PN12 3 5     SFNP2 5
Sodium Channel, Voltage-Gated, Type IX, Alpha Polypeptide1 2     ETHA2
Neuroendocrine Sodium Channel2 3     NE-NA2
Peripheral Sodium Channel 12 3     Nav1.72
Sodium Channel Protein Type IX Subunit Alpha2 3     Sodium Channel Protein Type 9 Subunit Alpha2
Voltage-Gated Sodium Channel Subunit Alpha Nav1.72 3     Voltage-Gated Sodium Channel Alpha Subunit Nav1.72
hNE-Na2 3     

External Ids:    HGNC: 105971   Entrez Gene: 63352   Ensembl: ENSG000001694327   OMIM: 6034155   UniProtKB: Q158583   

Export aliases for SCN9A gene to outside databases

Previous GC identifers: GC02M165109 GC02M165596 GC02M167018 GC02M167257 GC02M166880 GC02M166763 GC02M158932


(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 SCN9A Gene:
This gene encodes a voltage-gated sodium channel which plays a significant role in nociception signaling.
Mutations in this gene have been associated with primary erythermalgia, channelopathy-associated insensitivity to
pain, and paroxysmal extreme pain disorder. (provided by RefSeq, Aug 2009)

GeneCards Summary for SCN9A Gene:
SCN9A (sodium channel, voltage-gated, type IX, alpha subunit) is a protein-coding gene. Diseases associated with SCN9A include scn9a-related dravet syndrome, and scn9a-related inherited erythromelalgia. GO annotations related to this gene include sodium ion binding and voltage-gated sodium channel activity. An important paralog of this gene is SCN5A.

UniProtKB/Swiss-Prot: SCN9A_HUMAN, Q15858
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. It is a
tetrodotoxin-sensitive Na(+) channel isoform. Plays a role in pain mechanisms, especially in the development of
inflammatory pain (By similarity)

summary for SCN9A 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 SCN9A (Nav1.7) 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:
NC_000002.12  NT_005403.18  NC_018913.2  
Regulatory elements:
   Regulatory transcription factor binding sites in the SCN9A gene promoter:
         Oct-B1   Sox5   oct-B3   POU3F2 (N-Oct-5b)   POU3F2 (N-Oct-5a)   POU3F2   MEF-2A   POU2F1   aMEF-2   
         Other transcription factors

SwitchGear Promoter luciferase reporter plasmidSCN9A promoter sequence
   Search Chromatin IP Primers for SCN9A

Epigenetics:
DNA Methylation CpG Assay Predesigned for Pyrosequencing in human, mouse, rat SCN9A


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

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

SCN9A Gene in genomic location: bands according to Ensembl, locations according to (and/or Entrez Gene and/or Ensembl if different)
SCN9A gene location

GeneLoc information about chromosome 2         GeneLoc Exon Structure

GeneLoc location for GC02M167051:  view genomic region     (about GC identifiers)

Start:
167,051,695 bp from pter      End:
167,232,503 bp from pter
Size:
180,809 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, and/or Cloud-Clone Corp.,
Biochemical Assays by EMD Millipore, R&D Systems, OriGene, GenScript, Cell Signaling Technology, Enzo Life Sciences, and/or Cloud-Clone Corp., Antibodies by EMD Millipore, R&D Systems, Cell Signaling Technology, OriGene, Novus Biologicals, Thermo Fisher Scientific, LSBio, Abcam, and/or Cloud-Clone Corp.)
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UniProtKB/Swiss-Prot: SCN9A_HUMAN, Q15858 (See protein sequence)
Recommended Name: Sodium channel protein type 9 subunit alpha  
Size: 1988 amino acids; 226372 Da
Subunit: The sodium channel consists of a large polypeptide and 2-3 smaller ones. This sequence represents a large
polypeptide. Interacts with NEDD4 and NEDD4L (By similarity)
Secondary accessions: A1BUH5 Q6B4R9 Q6B4S0 Q6B4S1 Q70HX1 Q70HX2 Q8WTU1 Q8WWN4
Alternative splicing: 3 isoforms:  Q15858-1   Q15858-2   Q15858-3   

Explore the universe of human proteins at neXtProt for SCN9A: NX_Q15858

Explore proteomics data for SCN9A at MOPED

Post-translational modifications: 

  • Ubiquitinated by NEDD4L; which may promote its endocytosis. Does not seem to be ubiquitinated by NEDD4 (By
    similarity)1
  • Phosphorylation at Ser-1490 by PKC in a highly conserved cytoplasmic loop slows inactivation of the sodium channel
    and reduces peak sodium currents (By similarity)1
  • Glycosylation2 at Asn209, Asn283, Asn1352, Asn1366, Asn1375
  • Modification sites at PhosphoSitePlus

  • See SCN9A Protein Expression from SPIRE MOPED, PaxDB, and MaxQB

    REFSEQ proteins: NP_002968.1  
    ENSEMBL proteins: 
     ENSP00000386306   ENSP00000386330   ENSP00000413212   ENSP00000393141   ENSP00000364536  
     ENSP00000304748  
    Reactome Protein details: Q15858

    SCN9A Human Recombinant Protein Products:

    Browse Purified and Recombinant Proteins at EMD Millipore
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    Browse OriGene Protein Over-expression Lysates
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    Novus Biologicals SCN9A Protein
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    Browse Sino Biological Cell Lysates
    Browse ProSpec Recombinant Proteins
    Browse Proteins at Cloud-Clone Corp.

    SCN9A Antibody Products:

    EMD Millipore Mono- and Polyclonal Antibodies for the study of SCN9A
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    SCN9A Assay Products:

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    GenScript Custom Assay Services for SCN9A
    Browse Enzo Life Sciences for kits & assays
    Browse ELISAs at Cloud-Clone Corp.
    Browse CLIAs at Cloud-Clone Corp.


    (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: Nav1.7
    Voltage-gated sodium channels

    Selected InterPro protein domains (see all 7):
     IPR010526 Na_trans_assoc
     IPR028803 SCN9A
     IPR005821 Ion_trans_dom
     IPR027359 Channel_four-helix_dom
     IPR001696 Na_channel_asu

    Graphical View of Domain Structure for InterPro Entry Q15858

    ProtoNet protein and cluster: Q15858

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


    UniProtKB/Swiss-Prot: SCN9A_HUMAN, Q15858
    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. Nav1.7/SCN9A subfamily
    Similarity: Contains 1 IQ domain


    SCN9A for domains           About GeneDecksing


    (According to 1UniProtKB, Genatlas, LifeMap Discovery™, IUBMB, and/or 2DME, Human phenotypes from GenomeRNAi, Animal models from MGI Mar 06 2013, inGenious Targeting Laboratory, 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, and Vector BioLabs, Cell Lines from GenScript, ESI BIO, In Situ Hybridization Assays from Advanced Cell Diagnostics, Ontologies according to Gene Ontology Consortium 01 Apr 2014 via Entrez Gene.)
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    Molecular Function:

         UniProtKB/Swiss-Prot Summary: SCN9A_HUMAN, Q15858
    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. It is a
    tetrodotoxin-sensitive Na(+) channel isoform. Plays a role in pain mechanisms, especially in the development of
    inflammatory pain (By similarity)

         Genatlas biochemistry entry for SCN9A:
    sodium channel voltage-gated,type IX,alpha polypeptide,tetradotoxin sensitive,solely expressed in neuroendocrine
    cells

         Gene Ontology (GO): 4 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 ----
    GO:0031402sodium ion binding IEA--
         
    SCN9A for ontologies           About GeneDecksing


    Phenotypes:
         5 MGI mutant phenotypes (inferred from 5 alleles(MGI details for Scn9a):
     behavior/neurological  integument  mortality/aging  nervous system  normal 

    SCN9A for phenotypes           About GeneDecksing

    Animal Models:
         MGI mouse knock-out Scn9atm1.1Jnw for SCN9A

       inGenious Targeting Laboratory: Let us create your new Knockout/Knockin mouse model for SCN9A
       inGenious Targeting Laboratory: Contact us about creating complex and humanized mouse models for SCN9A

       genOway customized KO model: permanent, tissue-specific or time-controlled inactivation for SCN9A
       genOway customized Knockin model: humanization, point mutation, expression monitoring, etc. for SCN9A

    miRNA
    Products:
        
    miRTarBase miRNAs that target SCN9A:
    hsa-mir-335-5p (MIRT018700)

    Block miRNA regulation of human, mouse, rat SCN9A using miScript Target Protectors
    Selected qRT-PCR Assays for microRNAs that regulate SCN9A (see all 53):
    hsa-miR-411* hsa-miR-4317 hsa-miR-100* hsa-miR-3607-3p hsa-miR-379* hsa-miR-376b hsa-miR-429 hsa-miR-513a-5p
    SwitchGear 3'UTR luciferase reporter plasmidSCN9A 3' UTR sequence
    Inhib. RNA
    Products:
        
    OriGene RNAi products in human, mouse, rat for SCN9A
    Predesigned siRNA for gene silencing in human, mouse, rat SCN9A

    Gene Editing
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    Clone
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    Browse Sino Biological Human cDNA Clones
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    Cell Line
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    Browse ESI BIO Cell Lines and PureStem Progenitors for SCN9A 
    In Situ Assay
    Products:
       

     
    Advanced Cell Diagnostics RNAscope RNA in situ hybridization assays for SCN9A


    (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
    SCN9A_HUMAN, Q15858: Membrane; Multi-pass membrane protein. Note=In neurite terminals (By similarity)
    Subcellular locations from COMPARTMENTS: 

    CompartmentConfidence
    plasma membrane3
    endoplasmic reticulum1

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

    GO IDQualified GO termEvidencePubMed IDs
    GO:0001518voltage-gated sodium channel complex IEA--
    GO:0016020membrane ----
    GO:0016021integral component of membrane ----

    SCN9A for ontologies           About GeneDecksing


    (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 SCN9A About   (see all 7)                                                                                              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
    5Synaptic transmission ion currents
    Synaptic transmission ion currents

    Pathways by source                                                                                                                                                                 See SuperPaths
    Show all pathways

    Selected Downloadable PowerPoint Slides of GeneGlobe Pathway Central Maps for SCN9A (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 SCN9A
        Interaction between L1 and Ankyrins



    SCN9A for pathways           About GeneDecksing

        Pathway & Disease-focused RT2 Profiler PCR Array including SCN9A: 
              Neuronal Ion Channels in human mouse rat

    Interactions:

        GeneGlobe Interaction Network for SCN9A

    STRING Interaction Network Preview (showing 5 interactants - click image to see 23)

    Selected Interacting proteins for SCN9A (Q158583 ENSP000003863064) via UniProtKB, MINT, STRING, and/or I2D (see all 26)
    InteractantInteraction Details
    GeneCardExternal ID(s)
    CALM1P621583I2D: score=1 
    CALM2P621583I2D: score=1 
    CALM3P621583I2D: score=1 
    SCN10AENSP000003906004STRING: ENSP00000390600
    SCN11AENSP000003075994STRING: ENSP00000307599
    About this table

    Gene Ontology (GO): Selected biological process terms (see all 9):    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0006811ion transport ----
    GO:0006814sodium ion transport TAS7720699
    GO:0006954inflammatory response IEA--
    GO:0009636response to toxic substance IEA--
    GO:0009791post-embryonic development IEA--

    SCN9A for ontologies           About GeneDecksing



    (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 SCN9A 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 SCN9A    About this table
    CompoundSynonyms CAS #PubMed Ids
    SodiumSodium (see all 2)7440-23-5--

    5 DrugBank Compounds for SCN9A    About this table
    CompoundSynonyms CAS #TypeActionsPubMed Ids
    ZonisamideZonisamida [Spanish] (see all 2)68291-97-4targetinhibitor20025128 14704463 19557119 18433351 20001433 15511691 19948168
    LidocaineDilocaine (see all 2)137-58-6targetinhibitor17430993 20585544 19088384
    Ranolazine(-)-Ranolazine (see all 3)142387-99-3targetinhibitor11752352 19077543
    RufinamideCGP 33101 (see all 4)106308-44-5targetmodulator23221868
    LacosamideErlosamide (see all 4)175481-36-4target----

    8 IUPHAR Ligands for SCN9A (Nav1.7)    About this table
    LigandTypeActionAffinityPubmed IDs
    XEN907
    Pore BlockerInhibition8.5221570288
    tetrodotoxin
    Pore BlockerAntagonist7.67720699
    N-Me-aminopyrimidinone 9
    Gating inhibitorInhibition7.122209205
    pyrrolopyrimidine 48
    Pore BlockerInhibition6.9622318156
    Cd2+
    Pore BlockerAntagonist37720699
    veratridine
    ActivatorNone3--
    saxitoxin
    Channel blockerNone3--
    batrachotoxin
    ActivatorNone3--

    3 Novoseek inferred chemical compound relationships for SCN9A gene    About this table
    Compound   -log (P-Val)   Hits   PubMed IDs for Articles with Shared Sentences (# sentences)
    sodium 73.2 39 9169448 (3), 17167479 (2), 14985375 (2), 18347287 (2) (see all 24)
    carrageenan 44 1 15030943 (1)
    tetrodotoxin 26.6 2 9169448 (2)



    SCN9A for compounds           About GeneDecksing



    (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,
    Conferences by KenesGroup, 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, Primers from OriGene, and/or QIAGEN )
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    REFSEQ mRNAs for SCN9A gene: 
    NM_002977.3  

    Unigene Cluster for SCN9A:

    Sodium channel, voltage-gated, type IX, alpha subunit
    Hs.439145  [show with all ESTs]
    Unigene Representative Sequence: NM_002977
    7 Ensembl transcripts including schematic representations, and UCSC links where relevant:
    ENST00000409672(uc010fpl.3) ENST00000409435(uc002udr.1) ENST00000454569
    ENST00000452182 ENST00000472119 ENST00000375387(uc002uds.1 uc002udt.1)
    ENST00000303354
    miRNA
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    hsa-miR-411* hsa-miR-4317 hsa-miR-100* hsa-miR-3607-3p hsa-miR-379* hsa-miR-376b hsa-miR-429 hsa-miR-513a-5p
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    Inhib. RNA
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      QuantiFast Probe-based Assays in human, mouse, rat SCN9A

    Additional mRNA sequence: 

    AJ277393.1 AJ310882.1 AJ310883.1 AJ310897.1 AK307549.1 AY682084.1 AY682085.1 AY682086.1 
    BC113079.1 BC113080.1 DQ857292.1 X82835.1 

    6 DOTS entries:

    DT.203056  DT.310741  DT.120960101  DT.100740641  DT.75152923  DT.92420091 

    Selected AceView cDNA sequences (see all 26):

    BX100638 BG253038 CB146297 AJ310882 NM_002977 AJ277393 AJ310897 AJ310883 
    BM993170 X82835 AA298508 BX409895 BX409894 AL517958 AI091722 CK005041 
    AY682086 AY682084 AY682085 BG483641 AL517957 AA620400 BG227970 BG183871 

    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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    SCN9A expression in normal human tissues (normalized intensities)      SCN9A embryonic expression: see
    See probesets specificity/sensitivity at GeneAnnot
    About this imageBioGPS <intensity>2/3
    CGAP TAG: --
    SCN9A Expression
    About this image


    SCN9A expression in embryonic tissues and stem cells    About this table
    Data from LifeMap, the Embryonic Development and Stem Cells Database
     
     Bone (Muscoskeletal System)    fully expand to see all 2 entries
             Zeugopod Growth Plate
    SCN9A Protein expression data from MOPED1, PaxDb2 and MaxQB3    About this image

    SCN9A Protein Expression

    SOURCE GeneReport for Unigene cluster: Hs.439145

    UniProtKB/Swiss-Prot: SCN9A_HUMAN, Q15858
    Tissue specificity: Expressed strongly in dorsal root ganglion, with only minor levels elsewhere in the body,
    smooth muscle cells, MTC cell line and C-cell carcinoma. Isoform 1 is expressed preferentially in the central and
    peripheral nervous system. Isoform 2 is expressed preferentially in the dorsal root ganglion

        Pathway & Disease-focused RT2 Profiler PCR Array including SCN9A: 
              Neuronal Ion Channels in human mouse rat

    Primer
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    OriGene qSTAR qPCR primer pairs in human, mouse for SCN9A
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    QuantiFast Probe-based Assays in human, mouse, rat SCN9A
    In Situ
    Assay Products:
     

     
    Advanced Cell Diagnostics RNAscope RNA in situ hybridization assays for SCN9A

    (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 SCN9A gene from Selected species (see all 12)    About this table
    Organism Taxonomic
    classification
    Gene Description Human
    Similarity
    Orthology
    Type
    Details
    mouse
    (Mus musculus)
    Mammalia Scn9a1 , 5 sodium channel, voltage-gated, type IX, alpha1, 5 86.37(n)1
    92.04(a)1
      2 (39.13 cM)5
    202741  NM_018852.21  NP_061340.21 
     664800805 
    chicken
    (Gallus gallus)
    Aves SCN9A1 sodium channel, voltage-gated, type IX, alpha subunit 75.3(n)
    76.2(a)
      395946  XM_004942783.1  XP_004942840.1 
    lizard
    (Anolis carolinensis)
    Reptilia SCN9A6
    sodium channel, voltage-gated, type IX, alpha subu...
    73(a)
    1 ↔ 1
    GL343214.1(737315-867044)
    tropical clawed frog
    (Xenopus tropicalis)
    Amphibia scn2a1 sodium channel, voltage-gated, type II, alpha subunit 71.83(n)
    72.88(a)
      100486750  XM_002939270.2  XP_002939316.2 
    zebrafish
    (Danio rerio)
    Actinopterygii scn1lab6
    sodium channel, voltage-gated, type I like, alpha ...
    73(a)
    1 → many
    6(10158986-10231330) ENSDARG00000062744


    ENSEMBL Gene Tree for SCN9A (if available)
    TreeFam Gene Tree for SCN9A (if available)

    (Paralogs according to 1HomoloGene,
    2Ensembl, and 3SIMAP, Pseudogenes according to 4Pseudogene.org Build 68)
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    Paralogs for SCN9A gene
    SCN5A2  CACNA1D2  SCN7A2  CACNA1I2  CACNA1F2  CACNA1G2  SCN8A2  SCN10A2  
    SCN3A2  SCN2A2  CACNA1S2  CACNA1C2  CACNA1H2  SCN11A2  SCN4A2  SCN1A2  
    15 SIMAP similar genes for SCN9A using alignment to 7 protein entries:     SCN9A_HUMAN (see all proteins):
    SCN3A    SCN1A    SCN2A    SCN2A2    SCN8A    SCN5A
    SCN4A    SCN10A    TPCN1    SCN7A    SCN11A    CACNA1B
    CACNA1C    CACNA1E    CACNA1I

    SCN9A for paralogs           About GeneDecksing


    1 Pseudogenes.org Pseudogene for SCN9A
    PGOHUM00000240414


    (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 SCN9A (see all 4593)    About this table    
    Genomic DataTranscription Related DataAllele Frequencies
    SNP IDValidClinical
    significance
    Chr 2 posSequence#AA
    Chg
    TypeMore#Allele
    freq
    PopTotal
    sample
    More
    ----------
    rs1219089101,2,,4
    CParoxysmal extreme pain disorder (PEPD)4 pathogenic1166526332(-) CCTTAC/TGTGAA 2 R C mis10--------
    rs1219089191,2,,4
    CGeneralized epilepsy with febrile seizures plus 7 (GEFS+7)4 pathogenic1166535387(-) ACACAA/GGAAAA 2 K R mis10--------
    VAR_0646014
    Primary erythermalgia (PERYTHM)4--see VAR_0646012 E K mis40--------
    VAR_0320214
    Paroxysmal extreme pain disorder (PEPD)4--see VAR_0320212 F V mis40--------
    VAR_0320174
    Paroxysmal extreme pain disorder (PEPD)4--see VAR_0320172 V F mis40--------
    VAR_0645964
    Febrile seizures, familial, 3B (FEB3B)4--see VAR_0645962 I V mis40--------
    VAR_0320184
    Paroxysmal extreme pain disorder (PEPD)4--see VAR_0320182 V F mis40--------
    VAR_0646044
    Generalized epilepsy with febrile seizures plus 7 (GEFS+7)4--see VAR_0646042 N Y mis40--------
    VAR_0320194
    Primary erythermalgia (PERYTHM)4--see VAR_0320192 F V mis40--------
    VAR_0199484
    Primary erythermalgia (PERYTHM)4--see VAR_0199482 L H mis40--------

    HapMap Linkage Disequilibrium report for SCN9A (167051695 - 167232503 bp)

    Structural Variations
         Database of Genomic Variants (DGV) Selected variations for SCN9A (see all 11):    About this table    
    Variant IDTypeSubtypePubMed ID
    esv2721082CNV Deletion23290073
    esv2127014CNV Deletion18987734
    esv1764654CNV Deletion17803354
    esv2721083CNV Deletion23290073
    esv2666983CNV Deletion23128226
    esv2658860CNV Deletion23128226
    nsv507046CNV Insertion20534489
    esv23265CNV Loss19812545
    nsv834448CNV Loss17160897
    nsv459937CNV Loss19166990

    Human Gene Mutation Database (HGMD): SCN9A
    Site Specific Mutation Identification with PCR Assays
    SeqTarget long-range PCR primers for resequencing SCN9A
    DNA2.0 Custom Variant and Variant Library Synthesis for SCN9A

    (in which this Gene is Involved, According to MalaCards, OMIM, UniProtKB, the University of Copenhagen DISEASES database, Conferences by KenesGroup, Novoseek, Genatlas, GeneTests, GAD, HuGE Navigator, and/or TGDB.)
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    OMIM gene information: 603415   
    OMIM disorders: 133020  243000  167400  613863  607208  
    UniProtKB/Swiss-Prot: SCN9A_HUMAN, Q15858
  • Primary erythermalgia (PERYTHM) [MIM:133020]: Autosomal dominant disease characterized by recurrent
    episodes of severe pain associated with redness and warmth in the feet or hands. Note=The disease is caused by
    mutations affecting the gene represented in this entry
  • Congenital indifference to pain autosomal recessive (CIPAR) [MIM:243000]: A disorder characterized by
    congenital inability to perceive any form of pain, in any part of the body. All other sensory modalities are
    preserved and the peripheral and central nervous systems are apparently intact. Patients perceive the sensations
    of touch, warm and cold temperature, proprioception, tickle and pressure, but not painful stimuli. There is no
    evidence of a motor or sensory neuropathy, either axonal or demyelinating. Note=The disease is caused by
    mutations affecting the gene represented in this entry
  • Paroxysmal extreme pain disorder (PEPD) [MIM:167400]: Autosomal dominant paroxysmal disorder of pain and
    autonomic dysfunction. The distinctive features are paroxysmal episodes of burning pain in the rectal, ocular,
    and mandibular areas accompanied by autonomic manifestations such as skin flushing. Note=The disease is caused by
    mutations affecting the gene represented in this entry
  • Generalized epilepsy with febrile seizures plus 7 (GEFS+7) [MIM:613863]: 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
  • Febrile seizures, familial, 3B (FEB3B) [MIM:613863]: 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 SCN9A (see all 43):    About MalaCards
    scn9a-related dravet syndrome    scn9a-related inherited erythromelalgia    congenital indifference to pain, autosomal recessive    erythromelalgia
    pain disorder    epilepsy, generalized, with febrile seizures plus, type 7    small fiber neuropathy    dravet syndrome, modifier of
    scn9a-related generalized epilepsy with febrile seizures plus    hereditary sensory neuropathy    familial febrile seizures 3b    paroxysmal extreme pain disorder
    scn1a-related seizure disorders    dravet syndrome    generalized epilepsy with febrile seizures plus    epilepsy, generalized, with febrile seizures plus, type 3
    hereditary sensory and autonomic neuropathy type ii    seizure disorder    burning mouth syndrome    febrile seizures

    3 diseases from the University of Copenhagen DISEASES database for SCN9A:
    Erythromelalgia     Pain disorder     Neuropathy

    SCN9A for disorders           About GeneDecksing

    2 Novoseek inferred disease relationships for SCN9A gene    About this table

    Disease   -log (P-Val)   Hits   PubMed IDs for Articles with Shared Sentences (# sentences)
    erythromelalgia 95 20 14985375 (3), 18347287 (3), 20146699 (2), 15314237 (1) (see all 12)
    prostate cancer 18.2 2 16088330 (1), 18596065 (1)

    GeneTests: SCN9A
    GeneReviews: SCN9A
    Genetic Association Database (GAD): SCN9A
    Human Genome Epidemiology (HuGE) Navigator: SCN9A (6 documents)

    Export disorders for SCN9A 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 SCN9A gene, integrated from 10 sources (see all 136):
    (articles sorted by number of sources associating them with SCN9A)
        Utopia: connect your pdf to the dynamic
    world of online information

    1. A role of SCN9A in human epilepsies, as a cause of febrile seizures and as a potential modifier of Dravet syndrome. (PubMed id 19763161)1, 2, 4, 9 Singh N.A.... Leppert M.F. (PLoS Genet. 2009)
    2. Structure and functional expression of a new member of the tetrodotoxin-sensitive voltage-activated sodium channel family from human neuroendocrine cells. (PubMed id 7720699)1, 2, 3, 9 Klugbauer N.... Hofmann F. (EMBO J. 1995)
    3. Association analysis of SCN9A gene variants with borderline personality disorder. (PubMed id 18439623)1, 4, 9 TadiA8 A....Dahmen N. (J Psychiatr Res 2008)
    4. An SCN9A channelopathy causes congenital inability to experience pain. (PubMed id 17167479)1, 2, 9 Cox J.J.... Woods C.G. (Nature 2006)
    5. Mutations in SCN9A, encoding a sodium channel alpha subunit, in patients with primary erythermalgia. (PubMed id 14985375)1, 2, 9 Yang Y.... Shen Y. (J. Med. Genet. 2004)
    6. A novel tetrodotoxin-sensitive, voltage-gated sodium channel expressed in rat and human dorsal root ganglia. (PubMed id 9169448)1, 2, 9 Sangameswaran L.... Hunter J.C. (J. Biol. Chem. 1997)
    7. Pain perception is altered by a nucleotide polymorphism in SCN9A. (PubMed id 20212137)1, 4, 9 Reimann F....Woods C.G. (Proc. Natl. Acad. Sci. U.S.A. 2010)
    8. Electrophysiological properties of mutant Nav1.7 sodium channels in a painful inherited neuropathy. (PubMed id 15385606)1, 2, 9 Cummins T.R.... Waxman S.G. (J. Neurosci. 2004)
    9. Autosomal dominant erythermalgia associated with a novel mutation in the voltage-gated sodium channel alpha subunit Nav1.7. (PubMed id 16216943)1, 2, 9 Michiels J.J.... Drenth J.P.H. (Arch. Neurol. 2005)
    10. Congenital insensitivity to pain: novel SCN9A missense and in-frame deletion mutations. (PubMed id 20635406)1, 2 Cox J.J....Parvari R. (Hum. Mutat. 2010)

    (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: 6335 HGNC: 10597 AceView: SCN9A Ensembl:ENSG00000169432 euGenes: HUgn6335
    ECgene: SCN9A H-InvDB: SCN9A

    (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 SCN9A Pharmacogenomics, SNPs, Pathways
    GeneReviewshttp://www.ncbi.nlm.nih.gov/books/NBK1116/?term=SCN9A[genesymbol]
    Wikipedia http://en.wikipedia.org/wiki/SCN9A
    Protein Spotlighthttp://web.expasy.org/spotlight/back_issues/102

    (Patent information from GeneIP,
    Licensable technologies from WIS Yeda, Salk, Tufts,
    IP news from LifeMap Sciences, Inc.)
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    Patent Information for SCN9A gene:
    Search GeneIP for patents involving SCN9A

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



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