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SCNN1A Gene

protein-coding   GIFtS: 68
GCID: GC12M006456

Sodium Channel, Non-Voltage-Gated 1 Alpha Subunit

(Previous names: sodium channel, nonvoltage-gated 1 alpha, sodium channel,...)
(Previous symbol: SCNN1)
  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, Non-Voltage-Gated 1 Alpha Subunit1 2     Alpha ENaC-22
SCNN11 2 3     alpha-ENaC2
Sodium Channel, Nonvoltage-Gated 1 Alpha1 2     alpha-NaCH2
Epithelial Na(+) Channel Subunit Alpha2 3     Amiloride-Sensitive Epithelial Sodium Channel Alpha Subunit2
Nonvoltage-Gated Sodium Channel 1 Subunit Alpha2 3     Amiloride-Sensitive Sodium Channel Subunit Alpha2
SCNEA2 3     Amiloride-Sensitive Sodium Channel Subunit Alpha 22
BESC22 5     Nasal Epithelial Sodium Channel Alpha Subunit2
Sodium Channel, Non-Voltage-Gated 1 Alpha1     Alpha-ENaC3
ENaCa2     Alpha-NaCH3
ENaCalpha2     ENaCA3

External Ids:    HGNC: 105991   Entrez Gene: 63372   Ensembl: ENSG000001113197   OMIM: 6002285   UniProtKB: P370883   

Export aliases for SCNN1A gene to outside databases

Previous GC identifers: GC12M006310 GC12M006430 GC12M006326


(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 SCNN1A Gene:
Nonvoltage-gated, amiloride-sensitive, sodium channels control fluid and electrolyte transport across epithelia in
many organs. These channels are heteromeric complexes consisting of 3 subunits: alpha, beta, and gamma. This gene
encodes the alpha subunit, and mutations in this gene have been associated with pseudohypoaldosteronism type 1
(PHA1), a rare salt wasting disease resulting from target organ unresponsiveness to mineralocorticoids.
Alternatively spliced transcript variants encoding different isoforms have been described for this gene.
(provided by RefSeq, Apr 2009)

GeneCards Summary for SCNN1A Gene:
SCNN1A (sodium channel, non-voltage-gated 1 alpha subunit) is a protein-coding gene. Diseases associated with SCNN1A include pseudohypoaldosteronism type 1, and bronchiectasis with or without elevated sweat chloride 2. GO annotations related to this gene include actin binding and ligand-gated sodium channel activity. An important paralog of this gene is SCNN1B.

UniProtKB/Swiss-Prot: SCNNA_HUMAN, P37088
Function: Sodium permeable non-voltage-sensitive ion channel inhibited by the diuretic amiloride. Mediates the
electrodiffusion of the luminal sodium (and water, which follows osmotically) through the apical membrane of
epithelial cells. Plays an essential role in electrolyte and blood pressure homeostasis, but also in airway
surface liquid homeostasis, which is important for proper clearance of mucus. Controls the reabsorption of sodium
in kidney, colon, lung and sweat glands. Also plays a role in taste perception

Gene Wiki entry for SCNN1A 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_000012.12  NC_018923.2  NT_009759.17  
Regulatory elements:
   Regulatory transcription factor binding sites in the SCNN1A gene promoter:
         AhR   GR   AP-1   ATF-2   GR-beta   POU3F2   Chx10   GR-alpha   c-Jun   NF-kappaB1   
         Other transcription factors

SwitchGear Promoter luciferase reporter plasmids (see all 4): SCNN1A promoter sequence
   Search Chromatin IP Primers for SCNN1A

Epigenetics:
DNA Methylation CpG Assay Predesigned for Pyrosequencing in human, mouse, rat SCNN1A


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

Entrez Gene cytogenetic band: 12p13   Ensembl cytogenetic band:  12p13.31   HGNC cytogenetic band: 12p13

SCNN1A Gene in genomic location: bands according to Ensembl, locations according to (and/or Entrez Gene and/or Ensembl if different)
SCNN1A gene location

GeneLoc information about chromosome 12         GeneLoc Exon Structure

GeneLoc location for GC12M006456:  view genomic region     (about GC identifiers)

Start:
6,456,009 bp from pter      End:
6,486,896 bp from pter
Size:
30,888 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: SCNNA_HUMAN, P37088 (See protein sequence)
Recommended Name: Amiloride-sensitive sodium channel subunit alpha  
Size: 669 amino acids; 75704 Da
Subunit: Probable heterotrimer containing one alpha, one beta and one gamma subunit. A delta subunit can replace
the alpha subunit. Interacts with the WW domains of NEDD4, NEDD4L, WWP1 and WWP2. Interacts with the full length
immature form of PCSK9 (pro-PCSK9)
Sequence caution: Sequence=AAH06526.2; Type=Erroneous initiation; Note=Translation N-terminally shortened;
1 PDB 3D structure from and Proteopedia for SCNN1A:
2M3O (3D)    
Secondary accessions: A5X2U9 B4E2Q5 C5HTZ0 O43271 Q6GSQ6 Q9UM64
Alternative splicing: 6 isoforms:  P37088-1   P37088-2   P37088-3   P37088-4   P37088-5   P37088-6   (No experimental confirmation available)

Explore the universe of human proteins at neXtProt for SCNN1A: NX_P37088

Explore proteomics data for SCNN1A at MOPED

Post-translational modifications: 

  • Ubiquitinated; this targets individual subunits for endocytosis and proteasome-mediated degradation (By
    similarity)1
  • ENaC cleavage by furin, and subsequently by prostasin (PRSS8), leads to a stepwise increase in the open
    probability of the channel as a result of release of the alpha and gamma subunit inhibitory tracts, respectively.
    Interaction of ENaC subunit SCNN1B with BPIFA1 protects ENaC against proteolytic activation1
  • Glycosylation2 at Asn232, Asn293, Asn312, Asn397, Asn511
  • Modification sites at PhosphoSitePlus

  • See SCNN1A Protein Expression from SPIRE MOPED, PaxDB, and MaxQB

    REFSEQ proteins (3 alternative transcripts): 
    NP_001029.1  NP_001153047.1  NP_001153048.1  

    ENSEMBL proteins: 
     ENSP00000353292   ENSP00000440876   ENSP00000228916   ENSP00000380166   ENSP00000345028  
     ENSP00000438739   ENSP00000443434   ENSP00000351825  
    Reactome Protein details: P37088

    SCNN1A Human Recombinant Protein Products:

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    OriGene Protein Over-expression Lysate for SCNN1A
    OriGene Custom MassSpec
    OriGene Custom Protein Services for SCNN1A
    GenScript Custom Purified and Recombinant Proteins Services for SCNN1A
    Novus Biologicals SCNN1A Lysate
    Browse Sino Biological Recombinant Proteins
    Browse Sino Biological Cell Lysates
    Browse ProSpec Recombinant Proteins
    Browse Proteins at Cloud-Clone Corp.

    SCNN1A Antibody Products:

    EMD Millipore Mono- and Polyclonal Antibodies for the study of SCNN1A
    Browse R&D Systems for Antibodies
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    Novus Biologicals SCNN1A Antibodies
    Abcam antibodies for SCNN1A (Q6GSQ6, P37088)
    Browse Antibodies at Cloud-Clone Corp.
    ThermoFisher Antibody for SCNN1A
    LSBio Antibodies in human, mouse, rat for SCNN1A

    SCNN1A Assay Products:

    Browse Kits and Assays available from EMD Millipore
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    GenScript Custom Assay Services for SCNN1A
    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:
    SCNN: Ion channels / Sodium channel, nonvoltage-gated
    SC: Sodium channels

    IUPHAR Guide to PHARMACOLOGY protein family classification: ENaC alpha
    Epithelial sodium channels (ENaC)

    3 InterPro protein domains:
     IPR004724 EnaC
     IPR020903 Na+channel_ASC_CS
     IPR001873 Na+channel_ASC

    Graphical View of Domain Structure for InterPro Entry P37088

    ProtoNet protein and cluster: P37088

    1 Blocks protein domain: IPB001873 Na+ channel

    UniProtKB/Swiss-Prot: SCNNA_HUMAN, P37088
    Similarity: Belongs to the amiloride-sensitive sodium channel (TC 1.A.6) family. SCNN1A subfamily


    SCNN1A 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: SCNNA_HUMAN, P37088
    Function: Sodium permeable non-voltage-sensitive ion channel inhibited by the diuretic amiloride. Mediates the
    electrodiffusion of the luminal sodium (and water, which follows osmotically) through the apical membrane of
    epithelial cells. Plays an essential role in electrolyte and blood pressure homeostasis, but also in airway
    surface liquid homeostasis, which is important for proper clearance of mucus. Controls the reabsorption of sodium
    in kidney, colon, lung and sweat glands. Also plays a role in taste perception
    Enzyme regulation: Activated by WNK1, WNK2, WNK3 and WNK4 (By similarity)
    Induction: By aldosterone

         Genatlas biochemistry entry for SCNN1A:
    epithelial amiloride-sensitive sodium channel,non-voltage gated in the luminal membrane of the collecting tubule
    of kidney,(NHE4-PEN),subunit alpha

         Gene Ontology (GO): 5 molecular function terms:    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0003779actin binding IEA--
    GO:0005272sodium channel activity ----
    GO:0005515protein binding IPI11244092
    GO:0015280contributes to ligand-gated sodium channel activity IDA--
    GO:0050699WW domain binding IPI10642508
         
    SCNN1A for ontologies           About GeneDecksing


    Phenotypes:
         7 MGI mutant phenotypes (inferred from 4 alleles(MGI details for Scnn1a):
     behavior/neurological  growth/size/body  homeostasis/metabolism  mortality/aging  normal 
     renal/urinary system  respiratory system 

    SCNN1A for phenotypes           About GeneDecksing

    Animal Models:
         MGI mouse knock-outs for SCNN1A: Scnn1atm1.2Hum Scnn1atm1Rss

       inGenious Targeting Laboratory: Let us create your new Knockout/Knockin mouse model for SCNN1A
       inGenious Targeting Laboratory: Contact us about creating complex and humanized mouse models for SCNN1A

       genOway customized KO model: permanent, tissue-specific or time-controlled inactivation for SCNN1A
       genOway customized Knockin model: humanization, point mutation, expression monitoring, etc. for SCNN1A

    miRNA
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    Selected qRT-PCR Assays for microRNAs that regulate SCNN1A (see all 15):
    hsa-miR-4303 hsa-miR-647 hsa-miR-3140-3p hsa-miR-502-5p hsa-miR-640 hsa-miR-24-1* hsa-miR-1285 hsa-miR-3179
    SwitchGear 3'UTR luciferase reporter plasmidSCNN1A 3' UTR sequence
    Inhib. RNA
    Products:
        
    OriGene RNAi products in human, mouse, rat for SCNN1A
    Predesigned siRNA for gene silencing in human, mouse, rat SCNN1A

    Gene Editing
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    Clone
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    GenScript: all cDNA clones in your preferred vector (see all 3): SCNN1A (NM_001038)
    Browse Sino Biological Human cDNA Clones
    DNA2.0 Custom Codon Optimized Gene Synthesis Service for SCNN1A
    Vector BioLabs ready-to-use adenovirus/AAV for human, mouse, rat SCNN1A

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    Advanced Cell Diagnostics RNAscope RNA in situ hybridization assays for SCNN1A


    (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
    SCNNA_HUMAN, P37088: Apical cell membrane; Multi-pass membrane protein. Note=Apical membrane of epithelial cells
    Subcellular locations from COMPARTMENTS: 

    CompartmentConfidence
    plasma membrane5
    cytoskeleton2
    cytosol1
    extracellular1
    nucleus1
    peroxisome1

    Gene Ontology (GO): Selected cellular component terms (see all 10):    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0005829cytosol IEA--
    GO:0005886plasma membrane TAS--
    GO:0005887integral component of plasma membrane IDA--
    GO:0009897external side of plasma membrane IEA--
    GO:0016020membrane ----

    SCNN1A 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 SCNN1A About   (see all 12)                                                                                              See pathways by source

    SuperPathContained pathways About
    1Activation of cAMP-Dependent PKA
    Activation of cAMP-Dependent PKA0.77
    PKA Signaling0.56
    cAMP Pathway0.77
    2Neuropathic Pain-Signaling in Dorsal Horn Neurons
    Neuropathic Pain-Signaling in Dorsal Horn Neurons0.47
    Cholera Infection0.40
    Aldosterone Signaling in Epithelial Cells0.47
    3Ion channel transport
    Ion channel transport0.58
    Stimuli-sensing channels0.58
    4Transport of glucose and other sugars, bile salts and organic acids, metal ions and amine compounds
    Transmembrane transport of small molecules0.47
    5G-Beta Gamma Signaling
    GHRH Signaling0.46

    Pathways by source                                                                                                                                                                 See SuperPaths
    Show all pathways

    Selected Downloadable PowerPoint Slides of GeneGlobe Pathway Central Maps for SCNN1A (see all 7)
        Cholera Infection
    Neuropathic Pain-Signaling in Dorsal Horn Neurons
    PKA Signaling
    cAMP Pathway
    Aldosterone Signaling in Epithelial Cells

    2 GeneGo (Thomson Reuters) Pathways for SCNN1A
        CFTR-dependent regulation of ion channels in Airway Epithelium (norm and CF)
    NO-dependent CFTR activation (normal and CF)

    1 Reactome Pathway for SCNN1A
        Stimuli-sensing channels

    1 PharmGKB Pathway for SCNN1A
        Diuretics Pathway, Pharmacodynamics

    2 Kegg Pathways  (Kegg details for SCNN1A):
        Taste transduction
    Aldosterone-regulated sodium reabsorption


    SCNN1A for pathways           About GeneDecksing

        Pathway & Disease-focused RT2 Profiler PCR Array including SCNN1A: 
              Hypertension in human mouse rat

    Interactions:

        GeneGlobe Interaction Network for SCNN1A

    STRING Interaction Network Preview (showing 5 interactants - click image to see 21)

    Selected Interacting proteins for SCNN1A (P370882, 3 ENSP000002289164) via UniProtKB, MINT, STRING, and/or I2D (see all 21)
    InteractantInteraction Details
    GeneCardExternal ID(s)
    NEDD4P469342, 3, ENSP000003455304MINT-14025 MINT-16750 I2D: score=4 STRING: ENSP00000345530
    SNX3O604933, ENSP000002300854I2D: score=2 STRING: ENSP00000230085
    UBE2IP632793, ENSP000003248974I2D: score=2 STRING: ENSP00000324897
    USP10Q146943, ENSP000002194734I2D: score=2 STRING: ENSP00000219473
    WWP2O003083, ENSP000003482834I2D: score=2 STRING: ENSP00000348283
    About this table

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

    GO IDQualified GO termEvidencePubMed IDs
    GO:0006814sodium ion transport TAS8589714
    GO:0007588excretion TAS8589714
    GO:0034220ion transmembrane transport TAS--
    GO:0035725sodium ion transmembrane transport IDA--
    GO:0050878regulation of body fluid levels ----

    SCNN1A 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 

    Browse Tocris compounds for SCNN1A (SCNNA)

    2 HMDB Compounds for SCNN1A    About this table
    CompoundSynonyms CAS #PubMed Ids
    SodiumSodium (see all 2)7440-23-5--
    Triamterene6-Phenyl-2,4,7-triaminopteridine (see all 25)396-01-0--

    2 DrugBank Compounds for SCNN1A    About this table
    CompoundSynonyms CAS #TypeActionsPubMed Ids
    Triamterene-- 396-01-0targetinhibitor17139284 8772124 11752352 17016423 11509829
    AmilorideAmilorida [INN-Spanish] (see all 6)2016-88-8targetinhibitor15084585 11752352 12928313 17556672

    5 Novoseek inferred chemical compound relationships for SCNN1A gene    About this table
    Compound   -log (P-Val)   Hits   PubMed IDs for Articles with Shared Sentences (# sentences)
    sodium 70.4 18 10419459 (1), 19017867 (1), 8617496 (1), 10722699 (1) (see all 10)
    thiazide 48.7 1 14596636 (1)
    actinomycin d 41.8 2 11266509 (1)
    dexamethasone 36 1 11266509 (1)
    nacl 6.42 2 8617496 (1)



    SCNN1A 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 SCNN1A gene (3 alternative transcripts): 
    NM_001038.5  NM_001159575.1  NM_001159576.1  

    Unigene Cluster for SCNN1A:

    Sodium channel, non-voltage-gated 1 alpha subunit
    Hs.591047  [show with all ESTs]
    Unigene Representative Sequence: AK172792
    Selected Ensembl transcripts including schematic representations, and UCSC links where relevant (see all 24):
    ENST00000360168(uc001qnw.3 uc010sfb.2) ENST00000540037(uc001qnv.3)
    ENST00000228916(uc001qnx.3) ENST00000396966 ENST00000338748 ENST00000543768
    ENST00000539953 ENST00000457871 ENST00000366131 ENST00000539030 ENST00000538979
    ENST00000541249 ENST00000542966 ENST00000536087 ENST00000544882 ENST00000536176
    ENST00000543585 ENST00000536788
    miRNA
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    Selected qRT-PCR Assays for microRNAs that regulate SCNN1A (see all 15):
    hsa-miR-4303 hsa-miR-647 hsa-miR-3140-3p hsa-miR-502-5p hsa-miR-640 hsa-miR-24-1* hsa-miR-1285 hsa-miR-3179
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      QuantiTect SYBR Green Assays in human, mouse, rat SCNN1A
      QuantiFast Probe-based Assays in human, mouse, rat SCNN1A

    Additional mRNA sequence: 

    AK025536.1 AK172792.1 AK304379.1 AY365119.1 BC006526.2 BC037417.1 BC062613.1 DQ402522.1 
    X76180.1 

    21 DOTS entries:

    DT.452748  DT.92434940  DT.100680671  DT.92044705  DT.100782830  DT.91967789  DT.101984086  DT.97868354 
    DT.95201531  DT.92434939  DT.95256681  DT.100782831  DT.121189413  DT.91688475  DT.95256668  DT.95256682 
    DT.121189257  DT.95256669  DT.95256679  DT.91691051  DT.95137577 

    Selected AceView cDNA sequences (see all 197):

    AI699795 CD675158 AW080449 BF038512 CA395982 CK903500 X76180 BC006526 
    BU163535 BQ689113 AA477114 AU125381 BC062613 AI276391 AW247908 BQ690364 
    BQ690483 AA477362 BQ689552 BM839133 AA630143 AU124465 BU174404 AI261669 

    GeneLoc Exon Structure

    Selected Alternative Splicing Database (ASD) splice patterns (SP) for SCNN1A (see all 12)    About this scheme

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

    ExUns: 18a · 18b
    SP1:            
    SP2:            
    SP3:            
    SP4:            
    SP5:            


    ECgene alternative splicing isoforms for SCNN1A

    (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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    SCNN1A expression in normal human tissues (normalized intensities)      SCNN1A embryonic expression: see
    See probesets specificity/sensitivity at GeneAnnot
    About this imageBioGPS <intensity>2/3
    CGAP TAG: --
    SCNN1A Expression
    About this image


    SCNN1A expression in embryonic tissues and stem cells    About this table
    Data from LifeMap, the Embryonic Development and Stem Cells Database
     selected tissues (see all 9) fully expand
     
     Inner Cell Mass (Early Embryonic Tissues)    fully expand to see all 4 entries
             Human embryonic stem cells (family)
     
     Lung (Respiratory System)
             Alveolar type II cells
     
     Kidney (Urinary System)
             Principal Cells Renal Collecting Duct System
     
     Epithelial Cells
             Principal Cells Renal Collecting Duct System
     
     Blood (Hematopoietic System)
             Monocytes Peripheral Blood
    SCNN1A Protein expression data from MOPED1, PaxDb2 and MaxQB3    About this image

    SCNN1A Protein Expression

    SOURCE GeneReport for Unigene cluster: Hs.591047

    UniProtKB/Swiss-Prot: SCNNA_HUMAN, P37088
    Tissue specificity: Highly expressed in kidney and lung. Detected at intermediate levels in pancreas and liver,
    and at low levels in heart and placenta. Isoform 1 and isoform 2 predominate in all tissues. Expression of
    isoform 3, isoform 4 and isoform 5 is very low or not detectable, except in lung and heart

        Pathway & Disease-focused RT2 Profiler PCR Array including SCNN1A: 
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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 animals.

    Orthologs for SCNN1A gene from Selected species (see all 12)    About this table
    Organism Taxonomic
    classification
    Gene Description Human
    Similarity
    Orthology
    Type
    Details
    mouse
    (Mus musculus)
    Mammalia Scnn1a1 , 5 sodium channel, nonvoltage-gated 1 alpha1, 5 83.28(n)1
    83.48(a)1
      6 (59.32 cM)5
    202761  NM_011324.21  NP_035454.21 
     1253206595 
    chicken
    (Gallus gallus)
    Aves SCNN1A1 sodium channel, non-voltage-gated 1 alpha subunit 66.28(n)
    64.61(a)
      396050  NM_205145.2  NP_990476.2 
    lizard
    (Anolis carolinensis)
    Reptilia SCNN1A6
    sodium channel, non-voltage-gated 1 alpha subunit
    59(a)
    1 ↔ 1
    GL343381.1(503093-544128)
    African clawed frog
    (Xenopus laevis)
    Amphibia alphaxENaC2 epithelial sodium channel alpha subunit 76.65(n)    U23535.1 
    worm
    (Caenorhabditis elegans)
    Secernentea unc-1053 Amiloride-sensitive sodium channel 30(a)
    (best of 5)
      II(8117189-8122268)   --


    ENSEMBL Gene Tree for SCNN1A (if available)
    TreeFam Gene Tree for SCNN1A (if available)

    (Paralogs according to 1HomoloGene,
    2Ensembl, and 3SIMAP, Pseudogenes according to 4Pseudogene.org Build 68)
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    Paralogs for SCNN1A gene
    SCNN1B2  ASIC32  SCNN1G2  ASIC42  SCNN1D2  ASIC22  ASIC52  ASIC12  
    3 SIMAP similar genes for SCNN1A using alignment to 9 protein entries:     SCNNA_HUMAN (see all proteins):
    SCNN1D    SCNN1G    SCNN1B

    SCNN1A for paralogs           About GeneDecksing


    1 Pseudogenes.org Pseudogene for SCNN1A
    PGOHUM00000258611


    (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 SCNN1A (see all 922)    About this table    
    Genomic DataTranscription Related DataAllele Frequencies
    SNP IDValidClinical
    significance
    Chr 12 posSequence#AA
    Chg
    TypeMore#Allele
    freq
    PopTotal
    sample
    More
    ----------
    rs617598611,2,,4
    CBronchiectasis with or without elevated sweat chloride 2 (BESC2)4 pathogenic16414364(-) ACCCCA/GTCAGC 6 I V mis10--------
    VAR_0265184
    Pseudohypoaldosteronism 1, autosomal recessive (PHA1B)4--see VAR_0265182 G C mis40--------
    VAR_0158344
    Pseudohypoaldosteronism 1, autosomal recessive (PHA1B)4--see VAR_0158342 S L mis40--------
    rs1378526341,2
    Cpathogenic16388950(-) TATCGC/TGACAG 6 R * stg10--------
    rs57429121,2,,4
    C,F,Hpathogenic16389153(-) CACGAT/CGGCCC 6 /R /W mis119Minor allele frequency- C:0.02NS NA EA EU 9866
    rs617598601,2
    Cpathogenic16414463(-) ACAACC/TGCATG 6 R C mis10--------
    rs1939207731,2
    Cuntested16395255(-) CCTCCA/GTCAGC 6 I V mis10--------
    rs116083201,2
    C,F,H--6386351(+) TGAGCC/ATCATC 3 -- ds50015Minor allele frequency- A:0.00NS EA NA 420
    rs116083221,2
    C,F,H--6386379(+) GACAGA/C/TTGATG 3 -- ds50017NS EA NA 552
    rs726575281,2
    C,F--6386412(+) ATTGCC/TGCCAG 3 -- ds50011Minor allele frequency- T:0.00NS 1118

    HapMap Linkage Disequilibrium report for SCNN1A (6456009 - 6486896 bp)

    Structural Variations
         Database of Genomic Variants (DGV) 4 variations for SCNN1A:    About this table    
    Variant IDTypeSubtypePubMed ID
    esv2745469CNV Deletion23290073
    esv2479244CNV Insertion19546169
    esv34325CNV Gain17911159
    dgv453e1CNV Complex17122850

    Human Gene Mutation Database (HGMD): SCNN1A
    Locus Specific Mutation Databases (LSDB): SCNN1A

    Site Specific Mutation Identification with PCR Assays
    SeqTarget long-range PCR primers for resequencing SCNN1A
    DNA2.0 Custom Variant and Variant Library Synthesis for SCNN1A

    (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: 600228   
    OMIM disorders: 264350  613021  
    UniProtKB/Swiss-Prot: SCNNA_HUMAN, P37088
  • Pseudohypoaldosteronism 1, autosomal recessive (PHA1B) [MIM:264350]: A rare salt wasting disease
    resulting from target organ unresponsiveness to mineralocorticoids. PHA1B is a severe form involving multiple
    organ systems, and characterized by an often fulminant presentation in the neonatal period with dehydration,
    hyponatremia, hyperkalemia, metabolic acidosis, failure to thrive and weight loss. Note=The disease is caused by
    mutations affecting the gene represented in this entry. The degree of channel function impairment differentially
    affects the renin-aldosterone system and urinary Na/K ratios, resulting in distinct genotype-phenotype
    relationships in PHA1 patients. Loss-of-function mutations are associated with a severe clinical course and
    age-dependent hyperactivation of the renin-aldosterone system. This feature is not observed in patients with
    missense mutations that reduce but do not eliminate channel function. Markedly reduced channel activity results
    in impaired linear growth and delayed puberty (PubMed:18634878)
  • Bronchiectasis with or without elevated sweat chloride 2 (BESC2) [MIM:613021]: A debilitating respiratory
    disease characterized by chronic, abnormal dilatation of the bronchi and other cystic fibrosis-like symptoms in
    the absence of known causes of bronchiectasis (cystic fibrosis, autoimmune diseases, ciliary dyskinesia, common
    variable immunodeficiency, foreign body obstruction). Clinical features include sub-normal lung function,
    sinopulmonary infections, chronic productive cough, excessive sputum production, and elevated sweat chloride in
    some cases. Note=The disease is caused by mutations affecting the gene represented in this entry

  • Selected diseases for SCNN1A (see all 38):    About MalaCards
    pseudohypoaldosteronism type 1    bronchiectasis with or without elevated sweat chloride 2    pseudohypoaldosteronism    autosomal recessive pseudohypoaldosteronism type 1
    bronchiectasis    bronchiectasis with or without elevated sweat chloride 1, modifier of    liddle syndrome    pseudohypoaldosteronism type ii
    endolymphatic hydrops    pulmonary edema    familial hypercholesterolemia    cerebral palsy
    venous thromboembolism    metabolic acidosis    respiratory failure    thromboembolism
    common variable immunodeficiency    hypercholesterolemia    migraine    hyperparathyroidism

    3 diseases from the University of Copenhagen DISEASES database for SCNN1A:
    Pseudohypoaldosteronism     Liddle syndrome     Hypertension

    SCNN1A for disorders           About GeneDecksing

    2 Novoseek inferred disease relationships for SCNN1A gene    About this table

    Disease   -log (P-Val)   Hits   PubMed IDs for Articles with Shared Sentences (# sentences)
    pseudohypoaldosteronism 91.5 3 20064610 (1), 12530930 (1), 16207733 (1)
    liddles syndrome 87.9 3 20064610 (1), 12530930 (1), 16207733 (1)

    Genetic Association Database (GAD): SCNN1A
    Human Genome Epidemiology (HuGE) Navigator: SCNN1A (35 documents)

    Export disorders for SCNN1A 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 SCNN1A gene, integrated from 10 sources (see all 201):
    (articles sorted by number of sources associating them with SCNN1A)
        Utopia: connect your pdf to the dynamic
    world of online information

    1. The alpha-subunit of the epithelial sodium channel is an aldosterone- induced transcript in mammalian collecting ducts, and this transcriptional response is mediated via distinct cis-elements in the 5'-flanking region of the gene. (PubMed id 11266509)1, 2, 9 Mick V.E....Thomas C.P. (Mol. Endocrinol. 2001)
    2. Hormonal regulation and genomic organization of the human amiloride- sensitive epithelial sodium channel alpha subunit gene. (PubMed id 10447117)1, 2, 9 Chow Y.H.... Hu J. (Pediatr. Res. 1999)
    3. Cloning and functional studies of splice variants of the alpha- subunit of the amiloride-sensitive Na+ channel. (PubMed id 9575806)1, 2, 9 Tucker J.K.... Oh Y. (Am. J. Physiol. 1998)
    4. Genetic analysis of Rwandan patients with cystic fibrosis-like symptoms: identification of novel cystic fibrosis transmembrane conductance regulator and epithelial sodium channel gene variants. (PubMed id 19017867)1, 4, 9 Mutesa L.... Bours V. (Chest 2009)
    5. Risk of meningioma and common variation in genes related to innate immunity. (PubMed id 20406964)1, 4 Rajaraman P....Inskip P.D. (amp 2010)
    6. Polymorphisms in innate immunity genes and risk of childhood leukemia. (PubMed id 20438785)1, 4 Han S....Kang D. (Hum. Immunol. 2010)
    7. L-type voltage-dependent calcium channel alpha subunit 1C is a novel candidate gene associated with secondary hyperparathyroidism: an application of haplotype-based analysis for multiple linked single nucleotide polymorphisms. (PubMed id 20424473)1, 4 Yokoyama K....Hosoya T. (Nephron Clin Pract 2010)
    8. Pharmacogenetic association of hypertension candidate genes with fasting glucose in the GenHAT Study. (PubMed id 20577119)1, 4 Irvin M.R....Arnett D.K. (J. Hypertens. 2010)
    9. Variation at the NFATC2 locus increases the risk of thiazolidinedione-induced edema in the Diabetes REduction Assessment with ramipril and rosiglitazone Medication (DREAM) study. (PubMed id 20628086)1, 4 Bailey S.D....Anand S. (Diabetes Care 2010)
    10. Independent predictive roles of eotaxin Ala23Thr, paraoxonase 2 Ser311Cys and beta-adrenergic receptor Trp64Arg polymorphisms on cardiac disease in Type 2 Diabetes--an 8-year prospective cohort analysis of 1297 patients. (PubMed id 20536507)1, 4 Wang Y....Chan J.C. (Diabet. Med. 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: 6337 HGNC: 10599 AceView: SCNN1A Ensembl:ENSG00000111319 euGenes: HUgn6337
    ECgene: SCNN1A Kegg: 6337 H-InvDB: SCNN1A

    (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 SCNN1A Pharmacogenomics, SNPs, Pathways
    GeneReviewshttp://www.ncbi.nlm.nih.gov/books/NBK1116/?term=SCNN1A[genesymbol]

    (Patent information from GeneIP,
    Licensable technologies from WIS Yeda, Salk, Tufts,
    IP news from LifeMap Sciences, Inc.)
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    Patent Information for SCNN1A gene:
    Search GeneIP for patents involving SCNN1A

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



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