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WWOX Gene

protein-coding   GIFtS: 66
GCID: GC16P078133

WW Domain Containing Oxidoreductase

(Previous name: WW domain-containing oxidoreductase)
  See WWOX-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
WW Domain Containing Oxidoreductase1 2     FRA16D2
FOR2 3 5     HHCMA562
WW Domain-Containing Oxidoreductase1 2     PRO01282
Fragile Site FRA16D Oxidoreductase2 3     SDR41C12
WOX12 3     Short Chain Dehydrogenase/Reductase Family 41C, Member 12
SCAR122 5     WW Domain-Containing Protein WWOX2
Member 11     EC 1.1.1.-3
Short Chain Dehydrogenase/Reductase Family 41C1     EC 1.1.18
D16S432E2     

External Ids:    HGNC: 127991   Entrez Gene: 517412   Ensembl: ENSG000001861537   OMIM: 6051315   UniProtKB: Q9NZC73   

Export aliases for WWOX gene to outside databases

Previous GC identifers: GC16P069063 GC16P079094 GC16P077872 GC16P077913 GC16P076691 GC16P063889


(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 WWOX Gene:
WW domain-containing proteins are found in all eukaryotes and play an important role in the regulation of a wide
variety of cellular functions such as protein degradation, transcription, and RNA splicing. This gene encodes a
protein which contains 2 WW domains and a short-chain dehydrogenase/reductase domain (SRD). The highest normal
expression of this gene is detected in hormonally regulated tissues such as testis, ovary, and prostate. This
expression pattern and the presence of an SRD domain suggest a role for this gene in steroid metabolism. The
encoded protein is more than 90% identical to the mouse protein, which is an essential mediator of tumor necrosis
factor-alpha-induced apoptosis, suggesting a similar, important role in apoptosis for the human protein. In
addition, there is evidence that this gene behaves as a suppressor of tumor growth. Alternative splicing of this
gene generates transcript variants that encode different isoforms. (provided by RefSeq, Jul 2008)

GeneCards Summary for WWOX Gene:
WWOX (WW domain containing oxidoreductase) is a protein-coding gene. Diseases associated with WWOX include spinocrebellar ataxia, autosomal recessive 12, and esophageal squamous cell carcinoma, somatic. GO annotations related to this gene include oxidoreductase activity and enzyme binding. An important paralog of this gene is ENSG00000258466.

UniProtKB/Swiss-Prot: WWOX_HUMAN, Q9NZC7
Function: Putative oxidoreductase. Acts as a tumor suppressor and plays a role in apoptosis. Required for normal
bone development (By similarity). May function synergistically with p53/TP53 to control genotoxic stress-induced
cell death. Plays a role in TGFB1 signaling and TGFB1-mediated cell death. May also play a role in tumor necrosis
factor (TNF)-mediated cell death. Inhibits Wnt signaling, probably by sequestering DVL2 in the cytoplasm

Gene Wiki entry for WWOX 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_000016.9  NT_010498.16  NC_018927.2  
Regulatory elements:
   Regulatory transcription factor binding sites in the WWOX gene promoter:
         AP-1   ATF-2   c-Jun   
         Other transcription factors

SwitchGear Promoter luciferase reporter plasmidWWOX promoter sequence
   Search Chromatin IP Primers for WWOX

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


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

Entrez Gene cytogenetic band: 16q23.3-q24.1   Ensembl cytogenetic band:  16q23.1   HGNC cytogenetic band: 16q23.3-q24.1

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

GeneLoc information about chromosome 16         GeneLoc Exon Structure

GeneLoc location for GC16P078133:  view genomic region     (about GC identifiers)

Start:
78,133,310 bp from pter      End:
79,246,564 bp from pter
Size:
1,113,255 bases      Orientation:
plus 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: WWOX_HUMAN, Q9NZC7 (See protein sequence)
Recommended Name: WW domain-containing oxidoreductase  
Size: 414 amino acids; 46677 Da
Subunit: Interacts with TP53, p73/TP73 and MAPK8. Interacts with MAPT/TAU, RUNX2 and HYAL2 (By similarity). Forms
a ternary complex with TP53 and MDM2. Interacts with ERBB4, LITAF and WBP1. Interacts with DVL1, DVL2 and DVL3.
May interact with FAM189B and SCOTIN. Interacts with TNK2. Interacts with TMEM207
Sequence caution: Sequence=AAP94227.1; Type=Frameshift; Positions=362;
1 PDB 3D structure from and Proteopedia for WWOX:
1WMV (3D)    
Secondary accessions: A8K323 Q5MYT5 Q96KM3 Q96RF2 Q9BTT8 Q9NPC9 Q9NRF4 Q9NRF5 Q9NRF6 Q9NRK1
Q9NZC5
Alternative splicing: 7 isoforms:  Q9NZC7-1   Q9NZC7-2   Q9NZC7-3   Q9NZC7-4   Q9NZC7-5   Q9NZC7-6   Q9NZC7-7   (Variant in position: 182:K->E (found in a primary colorectal tumor and tumor cells))

Explore the universe of human proteins at neXtProt for WWOX: NX_Q9NZC7

Explore proteomics data for WWOX at MOPED

Post-translational modifications: 

  • Phosphorylated upon genotoxic stress. Phosphorylation of Tyr-33 regulates interaction with TP53, TP73 and MAPK8.
    May also regulate proapoptotic activity. Phosphorylation by TNK2 is associated with polyubiquitination and
    degradation1
  • Ubiquitinated when phosphorylated by TNK2, leading to its degradation1
  • Ubiquitination2 at Lys100, Lys274
  • Modification sites at PhosphoSitePlus
  • Selected DME Specific Peptides for WWOX (Q9NZC7) (see all 9)
     GGMYFNNC  LVQLLQDVL  DGLETTFQV  VVSSESHRFT 


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

    REFSEQ proteins (3 alternative transcripts): 
    NP_057457.1  NP_570607.1  NP_570859.1  

    ENSEMBL proteins: 
     ENSP00000457230   ENSP00000454788   ENSP00000384238   ENSP00000384495   ENSP00000445210  
     ENSP00000454331   ENSP00000454485   ENSP00000348119   ENSP00000386161  
    Reactome Protein details: Q9NZC7

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

     
    Search eBioscience for Proteins for WWOX 

    WWOX Antibody Products:

    EMD Millipore Mono- and Polyclonal Antibodies for the study of WWOX
    R&D Systems Antibodies for WWOX
    Cell Signaling Technology (CST) Antibodies for WWOX 
    OriGene Antibodies for WWOX
    OriGene Custom Antibody Services for WWOX
    Novus Biologicals WWOX Antibodies
    Abcam antibodies for WWOX (Q9NZCZ, Q9NZC7)
    Cloud-Clone Corp. Antibodies for WWOX
    ThermoFisher Antibody for WWOX
    LSBio Antibodies in human, mouse, rat for WWOX

    WWOX Assay Products:

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


    (According to HGNC, IUPHAR, InterPro, ProtoNet, UniProtKB, and/or BLOCKS, Sets of similar genes according to GeneDecks)
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    HGNC Gene Families:
    SDRC2: Short chain dehydrogenase/reductase superfamily / Classical SDR fold cluster 2

    4 InterPro protein domains:
     IPR002347 Glc/ribitol_DH
     IPR002198 DH_sc/Rdtase_SDR
     IPR001202 WW_dom
     IPR016040 NAD(P)-bd_dom

    Graphical View of Domain Structure for InterPro Entry Q9NZC7

    ProtoNet protein and cluster: Q9NZC7

    2 Blocks protein domains:
    IPB002198 Short-chain dehydrogenase/reductase SDR
    IPB002347 Glucose/ribitol dehydrogenase family signature


    UniProtKB/Swiss-Prot: WWOX_HUMAN, Q9NZC7
    Domain: The WW 1 domain mediates interaction with TP53, and probably TP73, TFAP2C, LITAF and WBP1
    Similarity: Belongs to the short-chain dehydrogenases/reductases (SDR) family
    Similarity: Contains 2 WW domains


    Find genes that share domains with WWOX           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: WWOX_HUMAN, Q9NZC7
    Function: Putative oxidoreductase. Acts as a tumor suppressor and plays a role in apoptosis. Required for normal
    bone development (By similarity). May function synergistically with p53/TP53 to control genotoxic stress-induced
    cell death. Plays a role in TGFB1 signaling and TGFB1-mediated cell death. May also play a role in tumor necrosis
    factor (TNF)-mediated cell death. Inhibits Wnt signaling, probably by sequestering DVL2 in the cytoplasm

         Enzyme Numbers (IUBMB): EC 1.1.12 EC 1.1.1.-1

         Gene Ontology (GO): Selected molecular function terms (see all 6):    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0005515protein binding IPI15064722
    GO:0016491oxidoreductase activity TAS10786676
    GO:0019899enzyme binding IPI19366691
    GO:0046983protein dimerization activity TAS10786676
    GO:0048037cofactor binding TAS10786676
         
    Find genes that share ontologies with WWOX           About GenesLikeMe


    Phenotypes:
         5 GenomeRNAi human phenotypes for WWOX:
     Decreased viability with cispl  Increased cell death HMECs cel  Increased cell death in breast  Increased cilium length after  
     Increased gamma-H2AX phosphory 

         13 MGI mutant phenotypes (inferred from 6 alleles(MGI details for Wwox):
     cellular  endocrine/exocrine gland  growth/size/body  hematopoietic system  homeostasis/metabolism 
     immune system  liver/biliary system  mortality/aging  nervous system  no phenotypic analysis 
     reproductive system  skeleton  tumorigenesis 

    Find genes that share phenotypes with WWOX           About GenesLikeMe

    Animal Models:
         MGI mouse knock-outs for WWOX: Wwoxtm1.1Mald Wwoxtm2.1Ria

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

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

    miRNA
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    Block miRNA regulation of human, mouse, rat WWOX using miScript Target Protectors
    8 qRT-PCR Assays for microRNAs that regulate WWOX:
    hsa-miR-498 hsa-miR-3164 hsa-miR-3938 hsa-miR-134 hsa-miR-3118 hsa-miR-4323 hsa-miR-2116 hsa-miR-758
    SwitchGear 3'UTR luciferase reporter plasmidWWOX 3' UTR sequence
    Inhib. RNA
    Products:
        
    OriGene RNAi products in human, mouse, rat for WWOX
    Predesigned siRNA for gene silencing in human, mouse, rat WWOX

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

    Clone
    Products:
         
    OriGene clones in human, mouse for WWOX (see all 16)
    OriGene ORF clones in mouse, rat for WWOX
    OriGene custom cloning services - gene synthesis, subcloning, mutagenesis, variant library, vector shuttling
    GenScript: all cDNA clones in your preferred vector (see all 3): WWOX (NM_130791)
    Browse Sino Biological Human cDNA Clones
    DNA2.0 Custom Codon Optimized Gene Synthesis Service for WWOX
    Vector BioLabs ready-to-use adenovirus/AAV for human, mouse, rat WWOX

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

     
    Advanced Cell Diagnostics RNAscope RNA in situ hybridization assays for WWOX

    Flow Cytometry
    Products:
       

     
    eBioscience FlowRNA Probe Sets ( VA6-13773) for WWOX 


    (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
    WWOX_HUMAN, Q9NZC7: Cytoplasm. Nucleus. Mitochondrion. Golgi apparatus. Note=Partially localizes to the
    mitochondria. Translocates to the nucleus upon genotoxic stress or TNF stimulation (By similarity). Translocates
    to the nucleus in response to TGFB1. Isoform 5 and isoform 6 may localize in the nucleus
    Subcellular locations from COMPARTMENTS: 

    CompartmentConfidence
    golgi apparatus5
    mitochondrion5
    nucleus5
    cytosol4

    Gene Ontology (GO): Selected cellular component terms (see all 7):    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0005634nucleus IDA19366691
    GO:0005737cytoplasm TAS10786676
    GO:0005739mitochondrion ISS--
    GO:0005794Golgi apparatus IDA15064722
    GO:0005829cytosol TAS--

    Find genes that share ontologies with WWOX           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 WWOX About   (see all 7)  
    See pathways by source

    SuperPathContained pathways About
    1PI-3K cascade
    Signaling by ERBB40.66
    2Signaling by GPCR
    Signal Transduction0.58
    3Cell Cycle / Checkpoint Control
    Cell Cycle / Checkpoint Control0.32
    4Selected targets of ESR1
    Selected targets of ESR1
    5Nuclear signaling by ERBB4
    Nuclear signaling by ERBB4


    Find genes that share SuperPaths with WWOX           About GenesLikeMe

    Pathways by source                                                                                                                                                                 See SuperPaths
    Show all pathways


    2 Cell Signaling Technology (CST) Pathways for WWOX
        Apoptosis and Autophagy
    Cell Cycle / Checkpoint Control

    1 BioSystems Pathway for WWOX
        ErbB4 signaling events

    1 Reactome Pathway for WWOX
        Nuclear signaling by ERBB4


        Pathway & Disease-focused RT2 Profiler PCR Array including WWOX: 
              Oncogenes & Tumor Suppressor Genes in human mouse rat

    Interactions:

        GeneGlobe Interaction Network for WWOX

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

    Selected Interacting proteins for WWOX (Q9NZC71, 2, 3 ENSP000003861614) via UniProtKB, MINT, STRING, and/or I2D (see all 54)
    InteractantInteraction Details
    GeneCardExternal ID(s)
    TP73O153502, 3, ENSP000003675454MINT-60129 MINT-60098 MINT-60104 MINT-60132 MINT-60099 MINT-60101 MINT-60131 MINT-60103 MINT-60106 MINT-60130 MINT-60102 MINT-60128 MINT-60105 MINT-60100 I2D: score=2 STRING: ENSP00000367545
    TP53P046372, 3, ENSP000002693054MINT-61317 MINT-61316 MINT-61314 MINT-61311 I2D: score=5 STRING: ENSP00000269305
    CPSF6Q166302, 3, ENSP000003917744MINT-72773 I2D: score=4 STRING: ENSP00000391774
    CPSF1Q105702, 3, ENSP000003393534MINT-72769 I2D: score=3 STRING: ENSP00000339353
    CPSF2Q9P2I02, 3, ENSP000002988754MINT-72770 I2D: score=3 STRING: ENSP00000298875
    About this table

    Gene Ontology (GO): Selected biological process terms (see all 15):    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0001649osteoblast differentiation IEA--
    GO:0006915apoptotic process ----
    GO:0008152metabolic process ----
    GO:0008202steroid metabolic process TAS10786676
    GO:0016055Wnt signaling pathway IEA--

    Find genes that share ontologies with WWOX           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 WWOX

    3 Novoseek inferred chemical compound relationships for WWOX gene    About this table
    Compound   -log (P-Val)   Hits   PubMed IDs for Articles with Shared Sentences (# sentences)
    steroid 20.3 6 10786676 (1), 15073846 (1), 15580310 (1), 16360296 (1) (see all 6)
    estrogen 20 9 15580310 (2), 15692750 (2), 17142102 (1), 19130459 (1)
    tyrosine 0 8 16288044 (5), 15070730 (1)



    Find genes that share compounds with WWOX           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 WWOX gene (7 alternative transcripts): 
    NM_016373.2  NM_130791.2  NM_130844.2  NM_018560.4  NM_130788.1  NM_130790.1  NM_130792.1  

    Unigene Cluster for WWOX:

    WW domain containing oxidoreductase
    Hs.461453  [show with all ESTs]
    Unigene Representative Sequence: NM_016373
    16 Ensembl transcripts including schematic representations, and UCSC links where relevant:
    ENST00000566780(uc002ffj.2 uc002ffk.3 uc010vnk.2 uc002ffl.3 uc010che.3)
    ENST00000569332 ENST00000402655 ENST00000406884 ENST00000539474 ENST00000562214
    ENST00000566662 ENST00000569818(uc002ffi.2) ENST00000355860 ENST00000408984
    ENST00000565562 ENST00000561846 ENST00000563358 ENST00000562639 ENST00000565791
    ENST00000566103
    miRNA
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    8 qRT-PCR Assays for microRNAs that regulate WWOX:
    hsa-miR-498 hsa-miR-3164 hsa-miR-3938 hsa-miR-134 hsa-miR-3118 hsa-miR-4323 hsa-miR-2116 hsa-miR-758
    SwitchGear 3'UTR luciferase reporter plasmidWWOX 3' UTR sequence
    Inhib. RNA
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    Predesigned siRNA for gene silencing in human, mouse, rat WWOX
    Clone
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    OriGene custom cloning services - gene synthesis, subcloning, mutagenesis, variant library, vector shuttling
    GenScript: all cDNA clones in your preferred vector (see all 3): WWOX (NM_130791)
    DNA2.0 Custom Codon Optimized Gene Synthesis Service for WWOX
    Vector BioLabs ready-to-use adenovirus/AAV for human, mouse, rat WWOX
    Primer
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    OriGene qSTAR qPCR primer pairs in human, mouse for WWOX
    Pre-validated RT2 qPCR Primer Assay in human, mouse, rat WWOX
      QuantiTect SYBR Green Assays in human, mouse, rat WWOX
      QuantiFast Probe-based Assays in human, mouse, rat WWOX
    Flow Cytometry
    Products:
       

     
    eBioscience FlowRNA Probe Sets ( VA6-13773) for WWOX 

    Additional mRNA sequence: 

    AF187015.1 AF211943.1 AF227527.1 AF227528.1 AF227529.1 AF239665.1 AF395123.1 AF395124.1 
    AK027626.1 AK290438.1 AK291300.1 AK298322.1 AY256821.1 BC003184.1 BT007445.1 

    15 DOTS entries:

    DT.92430580  DT.100792310  DT.201551  DT.40127884  DT.100697287  DT.95162670  DT.100792311  DT.110793 
    DT.95162673  DT.100649780  DT.65284359  DT.120725701  DT.95143769  DT.97804917  DT.99980695 

    Selected AceView cDNA sequences (see all 79):

    NM_130844 CK819992 BE221974 AI433889 BM273297 BF222068 BM787303 BQ723239 
    BF446303 NM_130791 AA970231 BF509356 BG256580 BI913753 AI218009 AI570665 
    BM917671 BE867819 BE266312 BX421793 BU157392 CB961492 AW874690 AI266744 

    GeneLoc Exon Structure

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

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


    ECgene alternative splicing isoforms for WWOX

    (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)
    About This Section

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


    WWOX expression in embryonic tissues and stem cells    About this table
    Data from LifeMap, the Embryonic Development and Stem Cells Database
     selected tissues (see all 2) fully expand
     
     Skeletal Muscle (Muscoskeletal System)    fully expand to see all 2 entries
             Muscle Progenitor Cells Mandibular Arch Muscles
     
     Blood (Hematopoietic System)
             Mature B-Cells Peripheral Blood
    WWOX Protein expression data from MOPED1, PaxDb2 and MaxQB3    About this image

    WWOX Protein Expression

    SOURCE GeneReport for Unigene cluster: Hs.461453

    UniProtKB/Swiss-Prot: WWOX_HUMAN, Q9NZC7
    Tissue specificity: Widely expressed. Strongly expressed in testis, prostate, and ovary. Overexpressed in cancer
    cell lines. Isoform 5 and isoform 6 may only be expressed in tumor cell lines

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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 eukaryotes.

    Orthologs for WWOX gene from Selected species (see all 18)    About this table
    Organism Taxonomic
    classification
    Gene Description Human
    Similarity
    Orthology
    Type
    Details
    mouse
    (Mus musculus)
    Mammalia Wwox1 , 5 WW domain-containing oxidoreductase1, 5 85.79(n)1
    93.95(a)1
      8 (60.99 cM)5
    807071  NM_019573.31  NP_062519.21 
     1144396555 
    chicken
    (Gallus gallus)
    Aves WWOX1 WW domain containing oxidoreductase 77.81(n)
    83.16(a)
      415801  NM_001030574.1  NP_001025745.1 
    lizard
    (Anolis carolinensis)
    Reptilia WWOX6
    WW domain containing oxidoreductase
    80(a)
    1 ↔ 1
    GL343446.1(108385-271765)
    African clawed frog
    (Xenopus laevis)
    Amphibia BG345567.12   -- 80.72(n)    BG345567.1 
    zebrafish
    (Danio rerio)
    Actinopterygii zgc559752 similar to WW domain containing oxidoreductase 73.97(n)   393887  BC044560.1 
    fruit fly
    (Drosophila melanogaster)
    Insecta CG72213
    Wwox1
    oxidoreductase, acting on CH-OH group
    of donors3
    WW domain containing oxidoreductase1
    49(a)3
    55.27(n)1
    50.63(a)1
      28D53
    340901  NM_135327.31  NP_609171.11 
    worm
    (Caenorhabditis elegans)
    Secernentea K10H10.61 , 3 Alcohol/other dehydrogenases, short
    chain type3
    K10H10.61
    36(a)
    (best of 4)3
    44.48(n)1
    37.79(a)1
      II(14498950-14500572)3
    1872851  NM_064611.11  NP_497012.11 
    baker's yeast
    (Saccharomyces cerevisiae)
    Saccharomycetes ENV96
    Protein proposed to be involved in vacuolar functi...
    25(a)
    1 → many
    XV(795801-796793) YOR246C
    rice
    (Oryza sativa)
    Liliopsida Os04g02911001 Os04g0291100 45.92(n)
    42.31(a)
      4335398  NM_001058926.1  NP_001052391.1 


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

    (Paralogs according to 1HomoloGene,
    2Ensembl, and 3SIMAP, Pseudogenes according to 4Pseudogene.org Build 68)
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    Paralogs for WWOX gene
    ENSG000002584662  DHRS122  DHRSX2  RDH122  DHRS132  RDH142  RDH132  RDH112  
    6 SIMAP similar genes for WWOX using alignment to 3 protein entries:     WWOX_HUMAN (see all proteins):
    RDH12    RDH11    RDH13    RDH14    HHCMA56    WWC2

    Find genes that share paralogs with WWOX           About GenesLikeMe



    (SNPs/Variants according to the 1NCBI SNP Database, 2Ensembl, 3PupaSUITE, 4UniProtKB, and DNA2.0, Linkage Disequilibrium by HapMap, Structural Variations(CNVs/InDels/Inversions) from the Database of Genomic Variants, Mutations from the Human Gene Mutation Database (HGMD), the Human Cytochrome P450 Allele Nomenclature Database, and the Locus Specific Mutation Databases (LSDB), Blood group antigen gene mutations by BGMUT, Resequencing Primers, Cancer Mutation PCR Arrays and Assays, and Copy Number PCR Arrays from QIAGEN)
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    Selected SNPs for WWOX (see all 44975)    About this table                                 

    Genomic DataTranscription Related DataAllele Frequencies
    SNP IDValidClinical
    significance
    Chr 16 posSequence#AA
    Chg
    TypeMore#Allele
    freq
    PopTotal
    sample
    More
    ----------
    rs1147553641,2,,4
    C,FA Burkitt lymphoma cell line4 --79156133(+) CAGCAC/GCACTG 4 T S mis11Minor allele frequency- G:0.03WA 118
    rs1413610801,2,,4
    C,FA primary colorectal tumor4 --79156159(+) AGGGCC/TGGGAT 4 R W mis11Minor allele frequency- T:0.01EU 1287
    rs735728381,2,,4
    C,FA cervical carcinoma cell line4 --79473710(+) CCCACG/ACGGGG 2 /H /R mis16Minor allele frequency- A:0.01WA CSA EU 1449
    rs599615641,2
    C,F--63887899(+) ATATTG/ACCCAG 3 -- us2k11Minor allele frequency- A:0.50WA 2
    rs18626901,2
    C,A--63887955(-) GCACTT/ATGGGA 3 -- us2k14Minor allele frequency- A:0.00NA WA CSA 7
    rs1137007771,2
    C,F--63887963(+) TGCTGG/AGATTA 3 -- us2k11Minor allele frequency- A:0.50NA 2
    rs2003354391,2
    --63894555(+) AAAAA-/ACACACG 2 -- int10--------
    rs720483271,2
    C--63894558(+) AAACA-/CAC   
       GCACG
    CACGC
    2 -- int10--------
    rs1126146971,2
    C--63894587(+) CACATACAC/-  
            
    ACACA
    2 -- int11Minor allele frequency- -:0.50CSA 2
    rs1126707071,2
    C--63894590(+) ATACAC/TACACA 2 -- int10--------

    HapMap Linkage Disequilibrium report for WWOX (78133310 - 78383310 bp, first 250kb of WWOX)

    Structural Variations
         Database of Genomic Variants (DGV) Selected variations for WWOX (see all 123):    About this table    
    Variant IDTypeSubtypePubMed ID
    esv2714756CNV Deletion23290073
    esv2714750CNV Deletion23290073
    esv2714748CNV Deletion23290073
    esv2570625CNV Deletion19546169
    esv2714747CNV Deletion23290073
    esv1604147CNV Deletion17803354
    esv2714755CNV Deletion23290073
    esv2662103CNV Deletion23128226
    esv2674405CNV Deletion23128226
    nsv820565CNV Deletion20802225

    Human Gene Mutation Database (HGMD): WWOX
    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: 605131   
    OMIM disorders: 133239  614322  
    UniProtKB/Swiss-Prot: WWOX_HUMAN, Q9NZC7
  • Note=Defects in WWOX may be involved in several cancer types. The gene spans the second most common
    chromosomal fragile site (FRA16D) which is frequently altered in cancers. Alteration of the expression and
    expression of some isoforms is associated with cancers. However, it is still unclear if alteration of WWOX is
    directly implicated in cancerogenesis or if it corresponds to a secondary effect
  • Esophageal cancer (ESCR) [MIM:133239]: A malignancy of the esophagus. The most common types are
    esophageal squamous cell carcinoma and adenocarcinoma. Cancer of the esophagus remains a devastating disease
    because it is usually not detected until it has progressed to an advanced incurable stage. Note=The disease may
    be caused by mutations affecting the gene represented in this entry

  • 4 diseases for WWOX:    
    About MalaCards
    spinocrebellar ataxia, autosomal recessive 12    esophageal squamous cell carcinoma, somatic    46xy sex reversal 3    esophageal squamous cell carcinoma


    Find genes that share disorders with WWOX           About GenesLikeMe

    Selected Novoseek inferred disease relationships for WWOX gene (see all 16)    About this table

    Disease   -log (P-Val)   Hits   PubMed IDs for Articles with Shared Sentences (# sentences)
    fragile sites chromosome 78.9 1 15044096 (1)
    cancer 53.1 44 17360458 (3), 19609013 (2), 16360296 (2), 17163164 (2) (see all 28)
    tumors 50.9 163 17575124 (5), 15073125 (4), 15982416 (4), 16288044 (4) (see all 48)
    hematopoietic malignancies 46.6 1 15168591 (1)
    allelic loss 44.3 2 16378185 (1), 11719429 (1)
    breast carcinoma 42.5 9 15692750 (3), 15073846 (2), 16061658 (1)
    breast cancer 37.2 37 16360296 (5), 10786676 (3), 11719429 (3), 19130459 (3) (see all 13)
    primary tumor 34 2 15073125 (2)
    carcinoma squamous cell 33 6 16115915 (2), 11956080 (1), 18061530 (1)
    epithelial tumor 28.2 1 15044096 (1)

    Genetic Association Database (GAD): WWOX
    Human Genome Epidemiology (HuGE) Navigator: WWOX (10 documents)

    Export disorders for WWOX 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 WWOX gene, integrated from 10 sources (see all 198):
    (articles sorted by number of sources associating them with WWOX)
        Utopia: connect your pdf to the dynamic
    world of online information

    1. WWOX, a novel WW domain-containing protein mapping to human chromosome 16q23.3-24.1, a region frequently affected in breast cancer. (PubMed id 10786676)1, 2, 3, 9 Bednarek A.K....Aldaz C.M. (Cancer Res. 2000)
    2. Common chromosomal fragile site FRA16D sequence: identification of the FOR gene spanning FRA16D and homozygous deletions and translocation breakpoints in cancer cells. (PubMed id 10861292)1, 2, 3, 9 Ried K.... Richards R.I. (Hum. Mol. Genet. 2000)
    3. The tumor suppressor gene WWOX at FRA16D is involved in pancreatic carcinogenesis. (PubMed id 15073125)1, 2, 9 Kuroki T.... Croce C.M. (Clin. Cancer Res. 2004)
    4. Physical and functional interactions between the Wwox tumor suppressor protein and the AP-2gamma transcription factor. (PubMed id 15548692)1, 2, 9 Aqeilan R.I....Croce C.M. (Cancer Res. 2004)
    5. WWOX, the FRA16D gene, behaves as a suppressor of tumor growth. (PubMed id 11719429)1, 2, 9 Bednarek A.K.... Aldaz C.M. (Cancer Res. 2001)
    6. WW domain-containing proteins, WWOX and YAP, compete for interaction with ErbB-4 and modulate its transcriptional function. (PubMed id 16061658)1, 2, 9 Aqeilan R.I.... Croce C.M. (Cancer Res. 2005)
    7. Frequent downregulation and loss of WWOX gene expression in human hepatocellular carcinoma. (PubMed id 15266310)1, 2, 9 Park S.-W....Aldaz C.M. (Br. J. Cancer 2004)
    8. Activated tyrosine kinase Ack1 promotes prostate tumorigenesis: role of Ack1 in polyubiquitination of tumor suppressor Wwox. (PubMed id 16288044)1, 2, 9 Mahajan N.P.... Earp H.S. (Cancer Res. 2005)
    9. Loss of WWOX expression in gastric carcinoma. (PubMed id 15131042)1, 2, 9 Aqeilan R.I.... Croce C.M. (Clin. Cancer Res. 2004)
    10. Functional association between Wwox tumor suppressor protein and p73, a p53 homolog. (PubMed id 15070730)1, 2, 9 Aqeilan R.I.... Croce C.M. (Proc. Natl. Acad. Sci. U.S.A. 2004)

    (in PubMed, OMIM, and NCBI Bookshelf)
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     ANDOR
    Aliases
    Disorders
    Free Text  

      Query String
    PubMed
    OMIM
    NCBI Bookshelf
      (Note: In FireFox, select the above section and copy using Ctrl-C)

    (According to Entrez Gene, HGNC, AceView, euGenes, Ensembl, miRBase, ECgene, Kegg, and/or H-InvDB)
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    Entrez Gene: 51741 HGNC: 12799 AceView: WWOX Ensembl:ENSG00000186153 euGenes: HUgn51741
    ECgene: WWOX H-InvDB: WWOX

    (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 WWOX Pharmacogenomics, SNPs, Pathways
    ATLAS Chromosomes in Cancer entry for WWOX 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 WWOX gene:
    Search GeneIP for patents involving WWOX

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



    (Antibodies, recombinant proteins, and assays from EMD Millipore, R&D Systems, OriGene, QIAGEN, GenScript, Cell Signaling Technology, Novus Biologicals, Sino Biological, Enzo Life Sciences, Abcam, ProSpec, Cloud-Clone Corp., Thermo Fisher Scientific, LSBio, eBioscience, and/or others, Gene Editing from DNA2.0. Clones from OriGene, GenScript, Sino Biological, DNA2.0, SwitchGear Genomics, Vector BioLabs, Addgene, Cell lines from GenScript, and ESI BIO, Flow cytometery from eBioscience, PCR Arrays from QIAGEN, Drugs and/or compounds from EMD Millipore, Tocris Bioscience, Enzo Life Sciences, and/or ApexBio, In Situ Hybridization Assays from
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