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NOX4 Gene

protein-coding   GIFtS: 63
GCID: GC11M089057

NADPH Oxidase 4

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(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
NADPH Oxidase 41 2     KOX-12 3
RENOX2 3 5     KOX2
Kidney Oxidase-12 3     EC 1.6.3.-3
Kidney Superoxide-Producing NADPH Oxidase2 3     EC 1.6.38
Renal NAD(P)H-Oxidase2 3     

External Ids:    HGNC: 78911   Entrez Gene: 505072   Ensembl: ENSG000000869917   OMIM: 6052615   UniProtKB: Q9NPH53   

Export aliases for NOX4 gene to outside databases

Previous GC identifers: GC11M091382 GC11M090606 GC11M089244 GC11M088747 GC11M088699 GC11M085294


(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 NOX4 Gene:
This gene encodes a member of the NOX-family of enzymes that functions as the catalytic subunit the NADPH oxidase
complex. The encoded protein is localized to non-phagocytic cells where it acts as an oxygen sensor and catalyzes
the reduction of molecular oxygen to various reactive oxygen species (ROS). The ROS generated by this protein
have been implicated in numerous biological functions including signal transduction, cell differentiation and
tumor cell growth. A pseudogene has been identified on the other arm of chromosome 11. Alternative splicing
results in multiple transcript variants.(provided by RefSeq, Jan 2009)

GeneCards Summary for NOX4 Gene:
NOX4 (NADPH oxidase 4) is a protein-coding gene. GO annotations related to this gene include heme binding and nucleotide binding. An important paralog of this gene is CYBB.

UniProtKB/Swiss-Prot: NOX4_HUMAN, Q9NPH5
Function: Constitutive NADPH oxidase which generates superoxide intracellularly upon formation of a complex with
CYBA/p22phox. Regulates signaling cascades probably through phosphatases inhibition. May function as an oxygen
sensor regulating the KCNK3/TASK-1 potassium channel and HIF1A activity. May regulate insulin signaling cascade.
May play a role in apoptosis, bone resorption and lipolysaccharide-mediated activation of NFKB. May produce
superoxide in the nucleus and play a role in regulating gene expression upon cell stimulation. Isoform 3 is not
functional. Isoform 4 displays an increased activity. Isoform 5 and isoform 6 display reduced activity

Gene Wiki entry for NOX4 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_000011.9  NT_033899.9  NC_018922.2  
Regulatory elements:
   Regulatory transcription factor binding sites in the NOX4 gene promoter:
         p53   AP-1   ATF-2   Nkx2-5   c-Jun   
         Other transcription factors

SwitchGear Promoter luciferase reporter plasmidNOX4 promoter sequence
   Search Chromatin IP Primers for NOX4

Epigenetics:
DNA Methylation CpG Assay Predesigned for Pyrosequencing in human, mouse, rat NOX4


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

Entrez Gene cytogenetic band: 11q14.2-q21   Ensembl cytogenetic band:  11q14.3   HGNC cytogenetic band: 11q14.2-q21

NOX4 Gene in genomic location: bands according to Ensembl, locations according to (and/or Entrez Gene and/or Ensembl if different)
NOX4 gene location

GeneLoc information about chromosome 11         GeneLoc Exon Structure

GeneLoc location for GC11M089057:  view genomic region     (about GC identifiers)

Start:
89,057,521 bp from pter      End:
89,322,779 bp from pter
Size:
265,259 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., and/or eBioscience,
Biochemical Assays by EMD Millipore, R&D Systems, OriGene, GenScript, Cell Signaling Technology, Enzo Life Sciences, Cloud-Clone Corp., and/or eBioscience, Antibodies by EMD Millipore, R&D Systems, Cell Signaling Technology, OriGene, Novus Biologicals, Thermo Fisher Scientific, LSBio, Abcam, Cloud-Clone Corp, and/or others.)
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UniProtKB/Swiss-Prot: NOX4_HUMAN, Q9NPH5 (See protein sequence)
Recommended Name: NADPH oxidase 4  
Size: 578 amino acids; 66932 Da
Subunit: Interacts with protein disulfide isomerase (By similarity). Interacts with, relocalizes and stabilizes
CYBA/p22phox. Interacts with TLR4
Developmental stage: Expressed in fetal kidney and fetal liver
Secondary accessions: A8K715 B7Z520 E7EMD7 Q5K3R4 Q5K3R5 Q5K3R6 Q5K3R8 Q7Z7G3 Q86V92
Alternative splicing: 9 isoforms:  Q9NPH5-1   Q9NPH5-2   Q9NPH5-3   Q9NPH5-4   Q9NPH5-5   Q9NPH5-6   Q9NPH5-7   Q9NPH5-8   
Q9NPH5-9   

Explore the universe of human proteins at neXtProt for NOX4: NX_Q9NPH5

Explore proteomics data for NOX4 at MOPED

Post-translational modifications: 

  • Isoform 3 and isoform 4 are N-glycosylated. Isoform 4 glycosylation is required for its proper function1
  • Glycosylation2 at Asn133, Asn230
  • Modification sites at PhosphoSitePlus
  • 3 DME Specific Peptides for NOX4 (Q9NPH5)
     GIGVTPF  DTHPPGCISLN  TICIFSGVHVAAHLVNALNFSVNYSE 


    See NOX4 Protein Expression from SPIRE MOPED, PaxDB, and MaxQB

    REFSEQ proteins (3 alternative transcripts): 
    NP_001137308.1  NP_001137309.1  NP_058627.1  

    ENSEMBL proteins: 
     ENSP00000344747   ENSP00000436892   ENSP00000436716   ENSP00000263317   ENSP00000434924  
     ENSP00000433797   ENSP00000436093   ENSP00000436970   ENSP00000435039   ENSP00000365146  
     ENSP00000435474   ENSP00000376961   ENSP00000405705   ENSP00000412446   ENSP00000440172  
     ENSP00000439373  

    NOX4 Human Recombinant Protein Products:

    Browse Purified and Recombinant Proteins at EMD Millipore
    Browse R&D Systems for human recombinant proteins
    Browse recombinant and purified proteins available from Enzo Life Sciences
    Browse OriGene full length recombinant human proteins expressed in human HEK293 cells
    OriGene Protein Over-expression Lysate for NOX4
    OriGene Custom MassSpec
    OriGene Custom Protein Services for NOX4
    GenScript Custom Purified and Recombinant Proteins Services for NOX4
    Novus Biologicals NOX4 Proteins
    Novus Biologicals NOX4 Lysate
    Browse Sino Biological Recombinant Proteins
    Browse Sino Biological Cell Lysates
    Browse ProSpec Recombinant Proteins
    Cloud-Clone Corp. Proteins for NOX4

     
    Search eBioscience for Proteins for NOX4 

    NOX4 Antibody Products:

    EMD Millipore Mono- and Polyclonal Antibodies for the study of NOX4
    R&D Systems Antibodies for NOX4
    OriGene Antibodies for NOX4
    OriGene Custom Antibody Services for NOX4
    Novus Biologicals NOX4 Antibodies
    Abcam antibodies for NOX4
    Cloud-Clone Corp. Antibodies for NOX4
    ThermoFisher Antibody for NOX4
    LSBio Antibodies in human, mouse, rat for NOX4

    NOX4 Assay Products:

    Browse Kits and Assays available from EMD Millipore
    OriGene Custom Assay Services for NOX4
    Browse R&D Systems for biochemical assays
    GenScript Custom Assay Services for NOX4
    Browse Enzo Life Sciences for kits & assays
    Cloud-Clone Corp. ELISAs for NOX4
    Cloud-Clone Corp. CLIAs for NOX4
    Search eBioscience for ELISAs for NOX4 


    (According to HGNC, IUPHAR, InterPro, ProtoNet, UniProtKB, and/or BLOCKS, Sets of similar genes according to GeneDecks)
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    Selected InterPro protein domains (see all 6):
     IPR017927 Fd_Rdtase_FAD-bd
     IPR000778 Cyt_b245_heavy_chain
     IPR013130 Fe3_Rdtase_TM_dom
     IPR013121 Fe_red_NAD-bd_6
     IPR013112 FAD-bd_8

    Graphical View of Domain Structure for InterPro Entry Q9NPH5

    ProtoNet protein and cluster: Q9NPH5

    2 Blocks protein domains:
    IPB000778 Cytochrome B-245 heavy chain signature
    IPB013130 Ferric reductase-like transmembrane component


    UniProtKB/Swiss-Prot: NOX4_HUMAN, Q9NPH5
    Similarity: Contains 1 FAD-binding FR-type domain
    Similarity: Contains 1 ferric oxidoreductase domain


    Find genes that share domains with NOX4           About GenesLikeMe


    (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, 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: NOX4_HUMAN, Q9NPH5
    Function: Constitutive NADPH oxidase which generates superoxide intracellularly upon formation of a complex with
    CYBA/p22phox. Regulates signaling cascades probably through phosphatases inhibition. May function as an oxygen
    sensor regulating the KCNK3/TASK-1 potassium channel and HIF1A activity. May regulate insulin signaling cascade.
    May play a role in apoptosis, bone resorption and lipolysaccharide-mediated activation of NFKB. May produce
    superoxide in the nucleus and play a role in regulating gene expression upon cell stimulation. Isoform 3 is not
    functional. Isoform 4 displays an increased activity. Isoform 5 and isoform 6 display reduced activity
    Enzyme regulation: Inhibited by plumbagin (By similarity). Activated by phorbol 12-myristate 13-acetate (PMA).
    Activated by insulin. Inhibited by diphenylene iodonium
    Induction: By 7-ketocholesterol (at protein level)

         Enzyme Numbers (IUBMB): EC 1.6.32 EC 1.6.3.-1

         Gene Ontology (GO): Selected molecular function terms (see all 11):    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0000166nucleotide binding TAS10869423
    GO:0005515protein binding ----
    GO:0009055electron carrier activity TAS10869423
    GO:0016174NAD(P)H oxidase activity TAS10869423
    GO:0016175superoxide-generating NADPH oxidase activity IEA--
         
    Find genes that share ontologies with NOX4           About GenesLikeMe


    Phenotypes:
         2 GenomeRNAi human phenotypes for NOX4:
     Decreased cell number and incr  Increased HPV18 LCR reporter a 

         10 MGI mutant phenotypes (inferred from 5 alleles(MGI details for Nox4):
     cardiovascular system  cellular  growth/size/body  homeostasis/metabolism  mortality/aging 
     muscle  nervous system  no phenotypic analysis  renal/urinary system  respiratory system 

    Find genes that share phenotypes with NOX4           About GenesLikeMe

    Animal Models:
         MGI mouse knock-outs for NOX4: Nox4tm1.1Ams Nox4tm1.1Hwsc Nox4tm1Kkr

       inGenious Targeting Laboratory: Let us create your new Knockout/Knockin mouse model for NOX4
       inGenious Targeting Laboratory: Contact us about creating complex and humanized mouse models for NOX4

       genOway customized KO model: permanent, tissue-specific or time-controlled inactivation for NOX4
       genOway customized Knockin model: humanization, point mutation, expression monitoring, etc. for NOX4

    miRNA
    Products:
        
    miRTarBase miRNAs that target NOX4:
    hsa-mir-148b-3p (MIRT019477)

    Block miRNA regulation of human, mouse, rat NOX4 using miScript Target Protectors
    Selected qRT-PCR Assays for microRNAs that regulate NOX4 (see all 40):
    hsa-miR-4254 hsa-miR-25 hsa-miR-16-1* hsa-miR-9 hsa-miR-4325 hsa-miR-532-5p hsa-miR-3116 hsa-miR-92b
    SwitchGear 3'UTR luciferase reporter plasmidNOX4 3' UTR sequence
    Inhib. RNA
    Products:
        
    OriGene RNAi products in human, mouse, rat for NOX4
    Predesigned siRNA for gene silencing in human, mouse, rat NOX4

    Gene Editing
    Products:
    DNA2.0 Custom Protein Engineering Service for NOX4

    Clone
    Products:
         
    OriGene clones in human, mouse for NOX4 (see all 19)
    OriGene ORF clones in mouse, rat for NOX4
    OriGene custom cloning services - gene synthesis, subcloning, mutagenesis, variant library, vector shuttling
    GenScript: all cDNA clones in your preferred vector (see all 3): NOX4 (NM_001143837)
    Sino Biological Human cDNA Clone for NOX4
    DNA2.0 Custom Codon Optimized Gene Synthesis Service for NOX4
    Vector BioLabs ready-to-use adenovirus/AAV for human, mouse, rat NOX4

    Cell Line
    Products:
         
    GenScript Custom overexpressing Cell Line Services for NOX4
    Browse ESI BIO Cell Lines and PureStem Progenitors for NOX4 
    In Situ Assay
    Products:
       

     
    Advanced Cell Diagnostics RNAscope RNA in situ hybridization assays for NOX4


    (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
    NOX4_HUMAN, Q9NPH5: Endoplasmic reticulum membrane; Multi-pass membrane protein. Cell membrane; Multi-pass
    membrane protein (Probable). Cell junction, focal adhesion (Probable). Nucleus (Probable). Note=May localize to
    plasma membrane and focal adhesions. According to PubMed:15927447, may also localize to the nucleus
    Subcellular locations from COMPARTMENTS: 

    CompartmentConfidence
    endoplasmic reticulum5
    plasma membrane5
    nucleus4
    extracellular2
    mitochondrion2
    cytoskeleton1

    Gene Ontology (GO): Selected cellular component terms (see all 9):    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0005634nucleus IEA--
    GO:0005739mitochondrion IEA--
    GO:0005789endoplasmic reticulum membrane IEA--
    GO:0005925focal adhesion IEA--
    GO:0016021integral component of membrane TAS10869423

    Find genes that share ontologies with NOX4           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 NOX4 About   (see all 6)  
    See pathways by source

    SuperPathContained pathways About
    1Apoptotic Pathways in Synovial Fibroblasts
    Rac1 Pathway0.65
    2PAK Pathway
    Antioxidant Action of Vitamin-C0.56
    3Human Embryonic Stem Cell Pluripotency
    Factors Promoting Cardiogenesis in Vertebrates0.50
    4Spinal Cord Injury
    Spinal Cord Injury
    5Signaling events mediated by PTP1B
    Signaling events mediated by PTP1B

    3 Downloadable PowerPoint Slides of GeneGlobe Pathway Central Maps for NOX4
        Rac1 Pathway
    Factors Promoting Cardiogenesis in Vertebrates
    Antioxidant Action of Vitamin-C

    3 BioSystems Pathways for NOX4
        Oxidative Stress
    Spinal Cord Injury
    Signaling events mediated by PTP1B



        Pathway & Disease-focused RT2 Profiler PCR Arrays including NOX4: 
              Nephrotoxicity in human mouse rat
              Oxidative Stress in human mouse rat
              Nitric Oxide Signaling Pathway in human mouse rat
              Cellular Senescence in human mouse rat
              Necrosis in human mouse rat

    Interactions:

        GeneGlobe Interaction Network for NOX4

    STRING Interaction Network Preview (showing 2 interactants - click image to see more details)

    3 Interacting proteins for NOX4 (Q9NPH53 ENSP000002633174) via UniProtKB, MINT, STRING, and/or I2D
    InteractantInteraction Details
    GeneCardExternal ID(s)
    TLR4O002063, ENSP000003630894I2D: score=2 STRING: ENSP00000363089
    CYBAP134983I2D: score=1 
    PTPN1ENSP000003606834STRING: ENSP00000360683
    About this table

    Gene Ontology (GO): Selected biological process terms (see all 25):    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0000902cell morphogenesis ISS10869423
    GO:0001666response to hypoxia IEA--
    GO:0006801superoxide metabolic process ----
    GO:0006954inflammatory response TAS10869423
    GO:0007568aging ----

    Find genes that share ontologies with NOX4           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 

    Browse Tocris compounds for NOX4

    3 HMDB Compounds for NOX4    About this table
    CompoundSynonyms CAS #PubMed Ids
    FAD1H-Purin-6-amine flavin dinucleotide (see all 21)146-14-5--
    Heme(protoporphyrinato)iron (see all 19)14875-96-8--
    NADPH2'-(dihydrogen phosphate) 5'-(trihydrogen pyrophosphate) Adenosine 5'-ester with 1,4-dihydro-1-b-D-ribofuranosylnicotinamide (see all 23)53-57-6--

    Selected Novoseek inferred chemical compound relationships for NOX4 gene (see all 13)    About this table
    Compound   -log (P-Val)   Hits   PubMed IDs for Articles with Shared Sentences (# sentences)
    nadph 89.8 120 16025326 (4), 11032835 (3), 19540572 (3), 15322091 (3) (see all 75)
    diphenyleneiodonium 81.1 3 11032835 (1), 18206249 (1), 16227320 (1)
    apocynin 78.3 2 17501721 (1), 18092937 (1)
    superoxide 69.2 37 19671250 (5), 11032835 (3), 10869423 (2), 15322091 (2) (see all 22)
    oxygen 69.1 39 18783311 (4), 17259440 (1), 19812163 (1), 10869423 (1) (see all 26)
    7-ketocholesterol 61.8 6 15572675 (2), 17448905 (1), 19157829 (1)
    n acetylcysteine 48.5 4 18783311 (1), 18206249 (1), 18092937 (1)
    h2o2 42.9 1 18849343 (1)
    8-isoprostane 38.5 1 17259440 (1)
    nitric oxide 35.9 3 19074681 (1), 19129694 (1)



    Find genes that share compounds with NOX4           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 NOX4 gene (3 alternative transcripts): 
    NM_001143836.1  NM_001143837.1  NM_016931.3  

    Unigene Cluster for NOX4:

    NADPH oxidase 4
    Hs.371036  [show with all ESTs]
    Unigene Representative Sequence: NM_001143837
    18 Ensembl transcripts including schematic representations, and UCSC links where relevant:
    ENST00000343727 ENST00000534731 ENST00000525196 ENST00000263317(uc009yvs.1)
    ENST00000532825 ENST00000527956 ENST00000524473 ENST00000527626 ENST00000528341
    ENST00000531342 ENST00000375979 ENST00000529343 ENST00000525278 ENST00000393282(uc001pcy.3)
    ENST00000413594 ENST00000424319(uc009yvr.3 uc010rtv.2 uc009yvq.3)
    ENST00000535633(uc001pcu.3 uc001pcw.3 uc001pcx.3 uc001pct.3 uc001pcv.3 uc009yvo.3 uc010rtu.2 uc009yvp.3)
    ENST00000542487
    miRNA
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    Block miRNA regulation of human, mouse, rat NOX4 using miScript Target Protectors
    Selected qRT-PCR Assays for microRNAs that regulate NOX4 (see all 40):
    hsa-miR-4254 hsa-miR-25 hsa-miR-16-1* hsa-miR-9 hsa-miR-4325 hsa-miR-532-5p hsa-miR-3116 hsa-miR-92b
    SwitchGear 3'UTR luciferase reporter plasmidNOX4 3' UTR sequence
    Inhib. RNA
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    Predesigned siRNA for gene silencing in human, mouse, rat NOX4
    Clone
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    OriGene ORF clones in mouse, rat for NOX4
    OriGene custom cloning services - gene synthesis, subcloning, mutagenesis, variant library, vector shuttling
    GenScript: all cDNA clones in your preferred vector (see all 3): NOX4 (NM_001143837)
    DNA2.0 Custom Codon Optimized Gene Synthesis Service for NOX4
    Vector BioLabs ready-to-use adenovirus/AAV for human, mouse, rat NOX4
    Primer
    Products:
        
    OriGene qPCR primer pairs and template standards for NOX4
    OriGene qSTAR qPCR primer pairs in human, mouse for NOX4
    Pre-validated RT2 qPCR Primer Assay in human, mouse, rat NOX4
      QuantiTect SYBR Green Assays in human, mouse, rat NOX4
      QuantiFast Probe-based Assays in human, mouse, rat NOX4

    Additional mRNA sequence: 

    AB041035.1 AF254621.1 AF261943.1 AJ704726.1 AJ704727.1 AJ704728.1 AJ704729.1 AK057189.1 
    AK291830.1 AK298323.1 AK298328.1 AK298357.1 AK298376.1 AK311381.1 AK311389.1 AY288918.1 
    BC040105.1 BC051371.1 NR_026571.1 

    8 DOTS entries:

    DT.408129  DT.120737878  DT.100754298  DT.40128676  DT.75145131  DT.120737898  DT.92419790  DT.120737886 

    Selected AceView cDNA sequences (see all 50):

    BP376400 BX282690 AF261943 AY288918 AI253120 BM693080 AB041035 BU730205 
    NM_016931 AA456001 AW024435 AA919129 AI241222 AI624542 BC040105 AI433445 
    CD517592 AI935422 AI885681 AW418588 BI763068 CB963821 AI284575 AK057189 

    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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    NOX4 expression in normal human tissues (normalized intensities)
    See probesets specificity/sensitivity at GeneAnnot
    About this imageBioGPS <intensity>2/3
    CGAP TAG: CACTGAATTC
    NOX4 Expression
    About this image


    NOX4 expression in embryonic tissues and stem cells    About this table
    Data from LifeMap, the Embryonic Development and Stem Cells Database
     selected tissues (see all 7) fully expand
     
     Endothelium (Cardiovascular System)    fully expand to see all 3 entries
             Endothelial Cells Blood Brain Barrier
             Human umbilical vein endothelial cells (HUVEC)
     
     Inner Cell Mass (Early Embryonic Tissues)    fully expand to see all 2 entries
             Line H9 (Naive)
     
     Skeletal Muscle (Muscoskeletal System)    fully expand to see all 2 entries
             Myoblasts Mandibular Arch Muscles
     
     Brain (Nervous System)    fully expand to see all 2 entries
             Endothelial Cells Blood Brain Barrier
     
     Heart (Cardiovascular System)
             Heart Tube
    NOX4 Protein expression data from MOPED1, PaxDb2 and MaxQB3    About this image

    NOX4 Protein Expression

    SOURCE GeneReport for Unigene cluster: Hs.371036

    UniProtKB/Swiss-Prot: NOX4_HUMAN, Q9NPH5
    Tissue specificity: Expressed by distal tubular cells in kidney cortex and in endothelial cells (at protein
    level). Widely expressed. Strongly expressed in kidney and to a lower extent in heart, adipocytes, hepatoma,
    endothelial cells, skeletal muscle, brain, several brain tumor cell lines and airway epithelial cells

        Pathway & Disease-focused RT2 Profiler PCR Arrays including NOX4: 
              Nephrotoxicity in human mouse rat
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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 NOX4 gene from Selected species (see all 13)    About this table
    Organism Taxonomic
    classification
    Gene Description Human
    Similarity
    Orthology
    Type
    Details
    mouse
    (Mus musculus)
    Mammalia Nox41 , 5 NADPH oxidase 41, 5 86.97(n)1
    90.83(a)1
      7 (48.96 cM)5
    504901  NM_015760.51  NP_056575.11 
     872460965 
    chicken
    (Gallus gallus)
    Aves NOX41 NADPH oxidase 4 77.14(n)
    79.72(a)
      419012  NM_001101829.1  NP_001095299.1 
    lizard
    (Anolis carolinensis)
    Reptilia NOX46
    NADPH oxidase 4
    76(a)
    1 ↔ 1
    3(198898784-199031843)
    tropical clawed frog
    (Xenopus tropicalis)
    Amphibia nox41 NADPH oxidase 4 67.71(n)
    67.19(a)
      101733537  XM_004912170.1  XP_004912227.1 
    zebrafish
    (Danio rerio)
    Actinopterygii CABZ01079296.16
    NOX4 (1 of 2)6
    NADPH oxidase 4
    68(a)
    67(a)
    1 ↔ many
    1 ↔ many
    15(42646544-42659914) ENSDARG00000088285
    15(42601596-42607151) ENSDARG00000087563
    mosquito
    (Anopheles gambiae)
    Insecta AgaP_AGAP0037721 AgaP_AGAP003772 44.59(n)
    33.4(a)
      1271506  XM_310312.7  XP_310312.7 


    ENSEMBL Gene Tree for NOX4 (if available)
    TreeFam Gene Tree for NOX4 (if available)

    (Paralogs according to 1HomoloGene,
    2Ensembl, and 3SIMAP, Pseudogenes according to 4Pseudogene.org Build 68)
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    Paralogs for NOX4 gene
    CYBB2  NOX12  NOX32  DUOX22  DUOX12  NOX52  
    3 SIMAP similar genes for NOX4 using alignment to 6 protein entries:     NOX4_HUMAN (see all proteins):
    CYBB    NOX1    NOX3

    Find genes that share paralogs with NOX4           About GenesLikeMe


    1 Pseudogenes.org Pseudogene for NOX4
    PGOHUM00000242685


    (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 NOX4 (see all 5734)    About this table                                 

    Genomic DataTranscription Related DataAllele Frequencies
    SNP IDValidClinical
    significance
    Chr 11 posSequence#AA
    Chg
    TypeMore#Allele
    freq
    PopTotal
    sample
    More
    ----------
    rs341400211,2
    C--89057108(-) GTCTC-/A/AAA 
            
    AAAAA
    7 -- ds5001 cds11NA 2
    rs37509241,2
    C--89057109(-) TGTCTC/GAAAAA 4 -- ds50010--------
    rs37509231,2
    C--89057130(-) CCTGGC/AAACAG 4 -- ds50013Minor allele frequency- A:0.00NA CSA 5
    rs1859487901,2
    --89057151(+) AGTGCA/CGTGGC 4 -- ds50010--------
    rs1457396551,2
    --89057164(+) AATCTC/TGGCTC 4 -- ds50010--------
    rs1891919111,2
    C--89057243(+) CTATAA/GGCACC 4 -- ds50010--------
    rs1818971571,2
    --89057347(+) CTACCC/TGCCTC 4 -- ds50010--------
    rs38292291,2
    C,F--89057348(-) CGAGGC/TGGGTA 4 -- ds50012Minor allele frequency- T:0.50NA 4
    rs1858877711,2
    --89057385(+) TGTGAA/GCCACC 4 -- ds50010--------
    rs1909557201,2
    --89057534(+) TTAACA/GTTTAT 4 -- ut31 nc-transcript-variant0--------

    HapMap Linkage Disequilibrium report for NOX4 (89057521 - 89307521 bp, first 250kb of NOX4)

    Structural Variations
         Database of Genomic Variants (DGV) Selected variations for NOX4 (see all 14):    About this table    
    Variant IDTypeSubtypePubMed ID
    esv1095170CNV Deletion17803354
    esv272386CNV Insertion20981092
    esv267878CNV Insertion20981092
    esv269866CNV Insertion20981092
    nsv898089CNV Loss21882294
    dgv1254n71CNV Loss21882294
    nsv898090CNV Loss21882294
    dgv165n27CNV Loss19166990
    nsv468785CNV Gain19166990
    nsv898088CNV Gain21882294

    Site Specific Mutation Identification with PCR Assays
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    (in which this Gene is Involved, According to MalaCards, OMIM, UniProtKB, the University of Copenhagen DISEASES database, Novoseek, Genatlas, GeneTests, GAD, HuGE Navigator, and/or TGDB.)
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    OMIM gene information: 605261    OMIM disorders: --

    3 diseases from the University of Copenhagen DISEASES database for NOX4:
    Hypertension     Atherosclerosis     Diabetes mellitus

    Find genes that share disorders with NOX4           About GenesLikeMe

    8 Novoseek inferred disease relationships for NOX4 gene    About this table

    Disease   -log (P-Val)   Hits   PubMed IDs for Articles with Shared Sentences (# sentences)
    vascular diseases 44.1 1 14678249 (1)
    hypertension pulmonary 28.9 1 17585072 (1)
    atherosclerosis 18.8 1 15572675 (1)
    insulin resistance 7.75 2 17553579 (1)
    tumors 6.87 9 16230378 (2), 18467643 (1), 18508317 (1), 19074681 (1) (see all 6)
    renal disease 2.3 1 19430333 (1)
    pancreatic cancer 0.145 3 15155719 (2), 16532036 (1)
    heart failure 0 2 18387435 (1), 16179589 (1)

    Genetic Association Database (GAD): NOX4
    Human Genome Epidemiology (HuGE) Navigator: NOX4 (12 documents)

    Export disorders for NOX4 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 NOX4 gene, integrated from 10 sources (see all 217):
    (articles sorted by number of sources associating them with NOX4)
        Utopia: connect your pdf to the dynamic
    world of online information

    1. Nox4 is critical for hypoxia-inducible factor 2-alpha transcriptional activity in von Hippel-Lindau-deficient renal cell carcinoma. (PubMed id 16230378)1, 2, 9 Maranchie J.K. and Zhan Y. (Cancer Res. 2005)
    2. Identification of renox, an NAD(P)H oxidase in kidney. (PubMed id 10869423)1, 2, 9 Geiszt M.... Leto T.L. (Proc. Natl. Acad. Sci. U.S.A. 2000)
    3. Identification of novel Nox4 splice variants with impact on ROS levels in A549 cells. (PubMed id 15721269)1, 2, 9 Goyal P.... Haenze J. (Biochem. Biophys. Res. Commun. 2005)
    4. NAD(P)H oxidase 4 mediates transforming growth factor-beta1-induced differentiation of cardiac fibroblasts into myofibroblasts. (PubMed id 16179589)1, 2, 9 Cucoranu I.... Sorescu D. (Circ. Res. 2005)
    5. NAD(P)H oxidase Nox-4 mediates 7-ketocholesterol-induced endoplasmic reticulum stress and apoptosis in human aortic smooth muscle cells. (PubMed id 15572675)1, 2, 9 Pedruzzi E.... Ogier-Denis E. (Mol. Cell. Biol. 2004)
    6. A novel superoxide-producing NAD(P)H oxidase in kidney. (PubMed id 11032835)1, 2, 9 Shiose A.... Sumimoto H. (J. Biol. Chem. 2001)
    7. The NAD(P)H oxidase homolog Nox4 modulates insulin-stimulated generation of H2O2 and plays an integral role in insulin signal transduction. (PubMed id 14966267)1, 2, 9 Mahadev K.... Goldstein B.J. (Mol. Cell. Biol. 2004)
    8. Reactive oxygen species produced by NAD(P)H oxidase inhibit apoptosis in pancreatic cancer cells. (PubMed id 15155719)1, 2, 9 Vaquero E.C....Gukovskaya A.S. (J. Biol. Chem. 2004)
    9. Genetic risk factors for hepatopulmonary syndrome in patients with advanced liver disease. (PubMed id 20346360)1, 4 Roberts K.E....Fallon M.B. (Gastroenterology 2010)
    10. Personalized smoking cessation: interactions between nicotine dose, dependence and quit-success genotype score. (PubMed id 20379614)1, 4 Rose J.E....Uhl G.R. (Mol. 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: 50507 HGNC: 7891 AceView: NOX4 Ensembl:ENSG00000086991 euGenes: HUgn50507
    ECgene: NOX4 H-InvDB: NOX4

    (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 NOX4 Pharmacogenomics, SNPs, Pathways
    ATLAS Chromosomes in Cancer entry for NOX4 Genetics and Cytogenetics in Oncology and Haematology

    (Patent information from GeneIP,
    Licensable technologies from WIS Yeda, Salk, Tufts,
    IP news from LifeMap Sciences, Inc.)
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    Patent Information for NOX4 gene:
    Search GeneIP for patents involving NOX4

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



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