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    WWOX WW domain containing oxidoreductase [ Homo sapiens (human) ]

    Gene ID: 51741, updated on 26-Nov-2024

    Summary

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    Official Symbol
    WWOXprovided by HGNC
    Official Full Name
    WW domain containing oxidoreductaseprovided by HGNC
    Primary source
    HGNC:HGNC:12799
    See related
    Ensembl:ENSG00000186153 MIM:605131; AllianceGenome:HGNC:12799
    Gene type
    protein coding
    RefSeq status
    REVIEWED
    Organism
    Homo sapiens
    Lineage
    Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
    Also known as
    FOR; WOX1; DEE28; EIEE28; FRA16D; SCAR12; HHCMA56; PRO0128; SDR41C1; D16S432E
    Summary
    This gene encodes a member of the short-chain dehydrogenases/reductases (SDR) protein family. This gene spans the FRA16D common chromosomal fragile site and appears to function as a tumor suppressor gene. Expression of the encoded protein is able to induce apoptosis, while defects in this gene are associated with multiple types of cancer. Disruption of this gene is also associated with autosomal recessive spinocerebellar ataxia 12. Disruption of a similar gene in mouse results in impaired steroidogenesis, additionally suggesting a metabolic function for the protein. Alternative splicing results in multiple transcript variants. [provided by RefSeq, May 2014]
    Expression
    Ubiquitous expression in thyroid (RPKM 4.4), kidney (RPKM 2.1) and 25 other tissues See more
    Orthologs
    mouse all
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    Genomic context

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    See WWOX in Genome Data Viewer
    Location:
    16q23.1-q23.2
    Exon count:
    10
    Annotation release Status Assembly Chr Location
    RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 16 NC_000016.10 (78099654..79212667)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 16 NC_060940.1 (84155399..85268915)
    RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 16 NC_000016.9 (78133551..79246564)

    Chromosome 16 - NC_000016.10Genomic Context describing neighboring genes Neighboring gene uncharacterized LOC107984897 Neighboring gene Neanderthal introgressed variant-containing enhancer experimental_45663 Neighboring gene leucine rich repeat containing 59 pseudogene Neighboring gene Neanderthal introgressed variant-containing enhancer experimental_45737 Neighboring gene Neanderthal introgressed variant-containing enhancer experimental_45804 Neighboring gene Neanderthal introgressed variant-containing enhancer experimental_45838 Neighboring gene H3K27ac hESC enhancer GRCh37_chr16:78133785-78134284 Neighboring gene Neanderthal introgressed variant-containing enhancer experimental_45974 Neighboring gene Neanderthal introgressed variant-containing enhancer experimental_45980 Neighboring gene keratin 8 pseudogene 22 Neighboring gene Neanderthal introgressed variant-containing enhancer experimental_46047 Neighboring gene Sharpr-MPRA regulatory region 1447 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr16:78247857-78248356 Neighboring gene Sharpr-MPRA regulatory region 10407 Neighboring gene Neanderthal introgressed variant-containing enhancer experimental_46108 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr16:78337176-78337676 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr16:78337677-78338177 Neighboring gene OCT4-NANOG hESC enhancer GRCh37_chr16:78345064-78345644 Neighboring gene NANOG hESC enhancer GRCh37_chr16:78347375-78347876 Neighboring gene WWOX antisense RNA 1 Neighboring gene Neanderthal introgressed variant-containing enhancer experimental_46172 Neighboring gene Neanderthal introgressed variant-containing enhancer experimental_46191 Neighboring gene Neanderthal introgressed variant-containing enhancer experimental_46196 Neighboring gene OCT4-NANOG hESC enhancer GRCh37_chr16:78405950-78406582 Neighboring gene OCT4-NANOG hESC enhancer GRCh37_chr16:78455072-78455805 Neighboring gene Sharpr-MPRA regulatory region 4302 Neighboring gene Neanderthal introgressed variant-containing enhancer experimental_46257 Neighboring gene uncharacterized LOC124903728 Neighboring gene uncharacterized LOC124903730 Neighboring gene VISTA enhancer hs12 Neighboring gene LSM3 homolog, U6 small nuclear RNA and mRNA degradation associated pseudogene 5 Neighboring gene uncharacterized LOC105371354 Neighboring gene NANOG hESC enhancer GRCh37_chr16:78645793-78646336 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 11155 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 7736 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 11156 Neighboring gene uncharacterized LOC112268165 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 11157 Neighboring gene ribosomal protein S3 pseudogene 7 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr16:79001468-79001968 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr16:79001969-79002469 Neighboring gene BRD4-independent group 4 enhancer GRCh37_chr16:79009787-79010986 Neighboring gene Sharpr-MPRA regulatory region 10194 Neighboring gene OCT4-NANOG hESC enhancer GRCh37_chr16:79087270-79087965 Neighboring gene NANOG hESC enhancer GRCh37_chr16:79111232-79111752 Neighboring gene uncharacterized LOC107984806 Neighboring gene H3K27ac hESC enhancer GRCh37_chr16:79203711-79204283 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr16:79321285-79321785 Neighboring gene OCT4-NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr16:79332665-79333313 Neighboring gene OCT4-NANOG-H3K27ac hESC enhancer GRCh37_chr16:79333314-79333961 Neighboring gene RNA, 5S ribosomal pseudogene 431 Neighboring gene OCT4-NANOG hESC enhancer GRCh37_chr16:79362104-79362979 Neighboring gene MPRA-validated peak2651 silencer Neighboring gene MAF bZIP transcription factor Neighboring gene ReSE screen-validated silencer GRCh37_chr16:79516400-79516610 Neighboring gene uncharacterized LOC124903729

    Genomic regions, transcripts, and products

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    Go to nucleotide: Graphics FASTA GenBank

    Expression

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    • Project title: HPA RNA-seq normal tissues
    • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
    • BioProject: PRJEB4337
    • Publication: PMID 24309898
    • Analysis date: Wed Apr 4 07:08:55 2018

    Bibliography

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    Related articles in PubMed

    1. WWOX induces apoptosis and inhibits proliferation in cervical cancer and cell lines. Qu J, et al. Int J Mol Med, 2013 May. PMID 23525362
    2. Diverse effect of WWOX overexpression in HT29 and SW480 colon cancer cell lines. Nowakowska M, et al. Tumour Biol, 2014 Sep. PMID 24938873, Free PMC Article
    3. Methylation status of WWOX gene promoter CpG islands in epithelial ovarian cancer and its clinical significance. Yan H, et al. Biomed Rep, 2013 May. PMID 24648952, Free PMC Article
    4. Association study of a functional copy number variation in the WWOX gene with risk of gliomas among Chinese people. Yu K, et al. Int J Cancer, 2014 Oct 1. PMID 24585490
    5. Common Chromosomal Fragile Site Gene WWOX in Metabolic Disorders and Tumors. Li J, et al. Int J Biol Sci, 2014. PMID 24520212, Free PMC Article

    See all (325) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. Mechanistic Investigation of WWOX Function in NF-kB-Induced Skin Inflammation in Psoriasis.
      Title: Mechanistic Investigation of WWOX Function in NF-kB-Induced Skin Inflammation in Psoriasis.
    2. Remote modulation of WWOX by an intronic variant associated with survival of Chinese gastric cancer patients.
      Title: Remote modulation of WWOX by an intronic variant associated with survival of Chinese gastric cancer patients.
    3. Identification of compound heterozygous deletion of the WWOX gene in WOREE syndrome.
      Title: Identification of compound heterozygous deletion of the WWOX gene in WOREE syndrome.
    4. Loss of fragile WWOX gene leads to senescence escape and genome instability.
      Title: Loss of fragile WWOX gene leads to senescence escape and genome instability.
    5. WWOX binds MERIT40 and modulates its function in homologous recombination, implications in breast cancer.
      Title: WWOX binds MERIT40 and modulates its function in homologous recombination, implications in breast cancer.
    6. WWOX Polymorphisms as Predictors of the Biochemical Recurrence of Localized Prostate Cancer after Radical Prostatectomy.
      Title: WWOX Polymorphisms as Predictors of the Biochemical Recurrence of Localized Prostate Cancer after Radical Prostatectomy.
    7. Neurological Disorders Associated with WWOX Germline Mutations-A Comprehensive Overview.
      Title: Neurological Disorders Associated with WWOX Germline Mutations-A Comprehensive Overview.
    8. WWOX Modulates ROS-Dependent Senescence in Bladder Cancer.
      Title: WWOX Modulates ROS-Dependent Senescence in Bladder Cancer.
    9. Loss of tumor suppressor WWOX accelerates pancreatic cancer development through promotion of TGFbeta/BMP2 signaling.
      Title: Loss of tumor suppressor WWOX accelerates pancreatic cancer development through promotion of TGFβ/BMP2 signaling.
    10. WWOX and metabolic regulation in normal and pathological conditions.
      Title: WWOX and metabolic regulation in normal and pathological conditions.
    Submit: New GeneRIF Correction See all GeneRIFs (238)

    Phenotypes

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    Find tests for this gene in the NIH Genetic Testing Registry (GTR)

    Review eQTL and phenotype association data in this region using PheGenI

    Associated conditions

    Description Tests
    Autosomal recessive spinocerebellar ataxia 12
    MedGen: C3280452 OMIM: 614322 GeneReviews: Not available
    		Compare labs
    Developmental and epileptic encephalopathy, 28
    MedGen: C4015519 OMIM: 616211 GeneReviews: Not available
    		Compare labs
    Malignant tumor of esophagus
    MedGen: C0546837 OMIM: 133239 GeneReviews: Not available
    		Compare labs

    EBI GWAS Catalog

    Description
    A genome-wide association study on obesity and obesity-related traits.
    EBI GWAS Catalog
    Common genetic variants associated with cognitive performance identified using the proxy-phenotype method.
    EBI GWAS Catalog
    Genetic variants associated with cardiac structure and function: a meta-analysis and replication of genome-wide association data.
    EBI GWAS Catalog
    Genetic variants associated with disordered eating.
    EBI GWAS Catalog
    Genetic Variants Associated with Serum Thyroid Stimulating Hormone (TSH) Levels in European Americans and African Americans from the eMERGE Network.
    EBI GWAS Catalog
    Genome-wide association analysis identifies six new loci associated with forced vital capacity.
    EBI GWAS Catalog
    Genome-wide association and large-scale follow up identifies 16 new loci influencing lung function.
    EBI GWAS Catalog
    Genome-wide association study of bipolar disorder accounting for effect of body mass index identifies a new risk allele in TCF7L2.
    EBI GWAS Catalog
    Genome-wide association study of d-amphetamine response in healthy volunteers identifies putative associations, including cadherin 13 (CDH13).
    EBI GWAS Catalog
    Genome-wide association study of monoamine metabolite levels in human cerebrospinal fluid.
    EBI GWAS Catalog
    Genome-wide joint meta-analysis of SNP and SNP-by-smoking interaction identifies novel loci for pulmonary function.
    EBI GWAS Catalog
    Genome-wide pharmacogenomic study of neurocognition as an indicator of antipsychotic treatment response in schizophrenia.
    EBI GWAS Catalog
    Meta-analysis of genome-wide association studies identifies eight new loci for type 2 diabetes in east Asians.
    EBI GWAS Catalog
    Radiation pharmacogenomics: a genome-wide association approach to identify radiation response biomarkers using human lymphoblastoid cell lines.
    EBI GWAS Catalog

    Variation

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    See variants in ClinVar

    See studies and variants in dbVar

    See Variation Viewer (GRCh37.p13)

    See Variation Viewer (GRCh38)

    Pathways from PubChem

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    Interactions

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    Products Interactant Other Gene Complex Source Pubs Description

    General gene information

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    Markers

    Homology

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    enables enzyme binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    enables identical protein binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    enables oxidoreductase activity NAS
    Non-traceable Author Statement
    more info
    		 PubMed 
    enables protein binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    contributes_to transcription coactivator activity ISS
    Inferred from Sequence or Structural Similarity
    more info
    		 PubMed 
    Process Evidence Code Pubs
    involved_in Wnt signaling pathway IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in cellular response to transforming growth factor beta stimulus IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in extrinsic apoptotic signaling pathway IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in intrinsic apoptotic signaling pathway by p53 class mediator IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in negative regulation of Wnt signaling pathway IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in osteoblast differentiation IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in positive regulation of extrinsic apoptotic signaling pathway ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    involved_in positive regulation of extrinsic apoptotic signaling pathway in absence of ligand IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in positive regulation of transcription by RNA polymerase II ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    involved_in skeletal system morphogenesis ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    Component Evidence Code Pubs
    located_in Golgi apparatus IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    part_of RNA polymerase II transcription regulator complex ISS
    Inferred from Sequence or Structural Similarity
    more info
    		 PubMed 
    located_in cytoplasm IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    located_in cytosol IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    located_in cytosol TAS
    Traceable Author Statement
    more info
    		  
    located_in lysosome IEA
    Inferred from Electronic Annotation
    more info
    		  
    colocalizes_with microvillus IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    located_in mitochondrion ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    located_in nucleus IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    colocalizes_with plasma membrane IDA
    Inferred from Direct Assay
    more info
    		 PubMed 

    General protein information

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    Preferred Names
    WW domain-containing oxidoreductase
    Names
    WW domain-containing protein WWOX
    fragile site FRA16D oxidoreductase
    short chain dehydrogenase/reductase family 41C member 1
    NP_001278926.1
    NP_057457.1
    NP_570607.1

    NCBI Reference Sequences (RefSeq)

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    NEW Try the new Transcript table

    RefSeqs maintained independently of Annotated Genomes

    These reference sequences exist independently of genome builds. Explain

    These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

    Genomic

    1. NG_011698.1 RefSeqGene

      Range
      5001..1118014
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. NM_001291997.2 → NP_001278926.1  WW domain-containing oxidoreductase isoform 4

      Status: REVIEWED

      Description
      Transcript Variant: This variant (4) differs in its 5' UTR and uses a downstream start codon, compared to variant 1. The encoded isoform (4) has a shorter N-terminus, compared to isoform 1.
      Source sequence(s)
      AF211943
      UniProtKB/TrEMBL
      B4DPG3
      Conserved Domains (2) summary
      cd09809
      Location:11 → 294
      human_WWOX_like_SDR_c-like; human WWOX (WW domain-containing oxidoreductase)-like, classical (c)-like SDRs
      PRK06196
      Location:2 → 291
      PRK06196; oxidoreductase; Provisional

    2. NM_016373.4 → NP_057457.1  WW domain-containing oxidoreductase isoform 1

      See identical proteins and their annotated locations for NP_057457.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (1) represents the longest transcript and encodes the longest isoform (1).
      Source sequence(s)
      AF211943
      Consensus CDS
      CCDS42196.1
      UniProtKB/Swiss-Prot
      A8K323, Q5MYT5, Q96KM3, Q96RF2, Q9BTT8, Q9NPC9, Q9NRF4, Q9NRF5, Q9NRF6, Q9NRK1, Q9NZC5, Q9NZC7
      UniProtKB/TrEMBL
      A0A411HBC7, A8K5I5, B3KNJ9
      Related
      ENSP00000457230.1, ENST00000566780.6
      Conserved Domains (2) summary
      cd09809
      Location:124 → 407
      human_WWOX_like_SDR_c-like; human WWOX (WW domain-containing oxidoreductase)-like, classical (c)-like SDRs
      cd00201
      Location:19 → 47
      WW; Two conserved tryptophans domain; also known as the WWP or rsp5 domain; around 40 amino acids; functions as an interaction module in a diverse set of signalling proteins; binds specific proline-rich sequences but at low affinities compared to other ...

    3. NM_130791.5 → NP_570607.1  WW domain-containing oxidoreductase isoform 2

      See identical proteins and their annotated locations for NP_570607.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (2) lacks several exons and uses an alternate 3'-terminal exon, compared to variant 1. The encoded isoform (2) has a shorter and distinct C-terminus, compared to isoform 1.
      Source sequence(s)
      AF187015, DB035405
      Consensus CDS
      CCDS42197.1
      UniProtKB/TrEMBL
      A0A411HBF5
      Related
      ENSP00000348119.3, ENST00000355860.7
      Conserved Domains (3) summary
      cd00201
      Location:60 → 90
      WW; Two conserved tryptophans domain; also known as the WWP or rsp5 domain; around 40 amino acids; functions as an interaction module in a diverse set of signalling proteins; binds specific proline-rich sequences but at low affinities compared to other ...
      pfam00397
      Location:18 → 47
      WW; WW domain
      cl21454
      Location:124 → 172
      NADB_Rossmann; Rossmann-fold NAD(P)(+)-binding proteins

    RNA

    1. NR_120435.2 RNA Sequence

      Status: REVIEWED

      Description
      Transcript Variant: This variant (3) is intronless and extends past a splice site that is used in variant 1. This variant is represented as non-coding because the predicted protein does not meet RefSeq quality criteria.
      Source sequence(s)
      AF227529, AW874693, DB035405
      Related
      ENST00000569818.1

    2. NR_120436.3 RNA Sequence

      Status: REVIEWED

      Description
      Transcript Variant: This variant (5) uses an alternate splice site in the 5'-terminal exon, lacks several exons, and uses an alternate 3'-terminal exon, compared to variant 1. This variant is represented as non-coding because the predicted protein does not meet RefSeq quality criteria.
      Source sequence(s)
      AF187015, BU157392, DB035405
      Related
      ENST00000563358.5

    RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2024_08

    The following sections contain reference sequences that belong to a specific genome build. Explain

    Reference GRCh38.p14 Primary Assembly

    Genomic

    1. NC_000016.10 Reference GRCh38.p14 Primary Assembly

      Range
      78099654..79212667
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060940.1 Alternate T2T-CHM13v2.0

      Range
      84155399..85268915
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    Suppressed Reference Sequence(s)

    The following Reference Sequences have been suppressed. Explain

    1. NM_018560.4: Suppressed sequence

      Description
      NM_018560.4: This RefSeq was permanently suppressed because it is a nonsense-mediated mRNA decay (NMD) candidate.

    2. NM_130788.1: Suppressed sequence

      Description
      NM_130788.1: This RefSeq was permanently suppressed because it appears to be specific to a disease state.

    3. NM_130790.1: Suppressed sequence

      Description
      NM_130790.1: This RefSeq was permanently suppressed because it appears to be specific to a disease state.

    4. NM_130792.1: Suppressed sequence

      Description
      NM_130792.1: This RefSeq was permanently suppressed because it appears to be specific to a disease state.

    5. NM_130844.2: Suppressed sequence

      Description
      NM_130844.2: This RefSeq was permanently suppressed because currently there is support for the transcript but not for the protein.
    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    Q9NZC7.1 GenPept UniProtKB/Swiss-Prot:Q9NZC7

    Gene LinkOut

    The following LinkOut resources are supplied by external providers. These providers are responsible for maintaining the links.

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