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

Gene ID: 51741, updated on 2-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 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. Effect of the WWOX gene on the regulation of the cell cycle and apoptosis in human ovarian cancer stem cells. Yan H, et al. Mol Med Rep, 2015 Aug. PMID 25891642, Free PMC Article
  2. Evidences that the polymorphism Pro-282-Ala within the tumor suppressor gene WWOX is a new risk factor for differentiated thyroid carcinoma. Cancemi L, et al. Int J Cancer, 2011 Dec 15. PMID 21520031
  3. [Expression of WW domain containing oxidoreductase gene in cholangiocarcinoma and its effect on the biological behavior of cancer cell line RBE]. Huang Q, et al. Zhonghua Wai Ke Za Zhi, 2011 Apr 1. PMID 21612698
  4. Pc2-mediated SUMOylation of WWOX is essential for its suppression of DU145 prostate tumorigenesis. Choi HJ, et al. FEBS Lett, 2015 Dec 21. PMID 26592150
  5. Pleiotropic Functions of Tumor Suppressor WWOX in Normal and Cancer Cells. Abu-Remaileh M, et al. J Biol Chem, 2015 Dec 25. PMID 26499798, Free PMC Article

See all (324) 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
not available
Developmental and epileptic encephalopathy, 28
MedGen: C4015519 OMIM: 616211 GeneReviews: Not available
not available
Malignant tumor of esophagus
MedGen: C0546837 OMIM: 133239 GeneReviews: Not available
not available

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)

Genotypes

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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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

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