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

Gene ID: 51741, updated on 4-Dec-2019

Summary

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
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; 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

Genomic context

See WWOX in Genome Data Viewer
Location:
16q23.1-q23.2
Exon count:
10
Annotation release Status Assembly Chr Location
109.20190905 current GRCh38.p13 (GCF_000001405.39) 16 NC_000016.10 (78099654..79212667)
105 previous assembly GRCh37.p13 (GCF_000001405.25) 16 NC_000016.9 (78133310..79246567)

Chromosome 16 - NC_000016.10Genomic Context describing neighboring genes Neighboring gene uncharacterized LOC107984897 Neighboring gene leucine rich repeat containing 59 pseudogene Neighboring gene keratin 8 pseudogene 22 Neighboring gene WWOX antisense RNA 1 Neighboring gene Sharpr-MPRA regulatory region 4302 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 uncharacterized LOC112268165 Neighboring gene ribosomal protein S3 pseudogene 7 Neighboring gene uncharacterized LOC107984806 Neighboring gene RNA, 5S ribosomal pseudogene 431 Neighboring gene MAF bZIP transcription factor Neighboring gene uncharacterized LOC101928230

Genomic regions, transcripts, and products

Expression

  • 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

GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Phenotypes

Associated conditions

Description Tests
Epileptic encephalopathy, early infantile, 28
MedGen: C4015519 OMIM: 616211 GeneReviews: Not available
Compare labs
Malignant tumor of esophagus
MedGen: C0546837 OMIM: 133239 GeneReviews: Not available
Compare labs
Spinocerebellar ataxia, autosomal recessive 12
MedGen: C3280452 OMIM: 614322 GeneReviews: Not available
Compare labs

NHGRI GWAS Catalog

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

Pathways from BioSystems

  • Activation of the TFAP2 (AP-2) family of transcription factors, organism-specific biosystem (from REACTOME)
    Activation of the TFAP2 (AP-2) family of transcription factors, organism-specific biosystemThe helix-span-helix motif and the basic region of TFAP2 (AP-2) transcription factor family members TFAP2A, TFAP2B, TFAP2C, TFAP2D and TFAP2E enable dimerization and DNA binding. AP-2 dimers bind pal...
  • ErbB4 signaling events, organism-specific biosystem (from Pathway Interaction Database)
    ErbB4 signaling events, organism-specific biosystem
    ErbB4 signaling events
  • Gene Expression, organism-specific biosystem (from REACTOME)
    Gene Expression, organism-specific biosystemGene Expression covers the pathways by which genomic DNA is transcribed to yield RNA, the regulation of these transcription processes, and the pathways by which newly-made RNA Transcripts are process...
  • Generic Transcription Pathway, organism-specific biosystem (from REACTOME)
    Generic Transcription Pathway, organism-specific biosystemOVERVIEW OF TRANSCRIPTION REGULATION: Detailed studies of gene transcription regulation in a wide variety of eukaryotic systems has revealed the general principles and mechanisms by which cell- or t...
  • Negative regulation of activity of TFAP2 (AP-2) family transcription factors, organism-specific biosystem (from REACTOME)
    Negative regulation of activity of TFAP2 (AP-2) family transcription factors, organism-specific biosystemTranscriptional activity of TFAP2 (AP-2) transcription factor family homo- and heterodimers in inhibited by binding of KCTD1 or KCTD15 to the AP-2 transactivation domain (Ding et al. 2009, Zarelli an...
  • Nuclear signaling by ERBB4, organism-specific biosystem (from REACTOME)
    Nuclear signaling by ERBB4, organism-specific biosystemBesides signaling as a transmembrane receptor, ligand activated homodimers of ERBB4 JM-A isoforms (ERBB4 JM-A CYT1 and ERBB4 JM-A CYT2) undergo proteolytic cleavage by ADAM17 (TACE) in the juxtamembr...
  • Signal Transduction, organism-specific biosystem (from REACTOME)
    Signal Transduction, organism-specific biosystemSignal transduction is a process in which extracellular signals elicit changes in cell state and activity. Transmembrane receptors sense changes in the cellular environment by binding ligands, such a...
  • Signaling by ERBB4, organism-specific biosystem (from REACTOME)
    Signaling by ERBB4, organism-specific biosystemERBB4, also known as HER4, belongs to the ERBB family of receptors, which also includes ERBB1 (EGFR i.e. HER1), ERBB2 (HER2 i.e. NEU) and ERBB3 (HER3). Similar to EGFR, ERBB4 has an extracellular lig...
  • Transcriptional regulation by the AP-2 (TFAP2) family of transcription factors, organism-specific biosystem (from REACTOME)
    Transcriptional regulation by the AP-2 (TFAP2) family of transcription factors, organism-specific biosystemThe AP-2 (TFAP2) family of transcription factors includes five proteins in mammals: TFAP2A (AP-2 alpha), TFAP2B (AP-2 beta), TFAP2C (AP-2 gamma), TFAP2D (AP-2 delta) and TFAP2E (AP-2 epsilon). The AP...

Interactions

Products Interactant Other Gene Complex Source Pubs Description

General gene information

Markers

Homology

Gene Ontology Provided by GOA

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

General protein information

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)

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_001291997.2NP_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/Swiss-Prot
    Q9NZC7
    Conserved Domains (2) summary
    cd09809
    Location:11294
    human_WWOX_like_SDR_c-like; human WWOX (WW domain-containing oxidoreductase)-like, classical (c)-like SDRs
    PRK06196
    Location:2291
    PRK06196; oxidoreductase; Provisional
  2. NM_016373.4NP_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
    Q9NZC7
    Related
    ENSP00000457230.1, ENST00000566780.6
    Conserved Domains (2) summary
    cd09809
    Location:124407
    human_WWOX_like_SDR_c-like; human WWOX (WW domain-containing oxidoreductase)-like, classical (c)-like SDRs
    cd00201
    Location:1947
    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_130791.4NP_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, AW874692, DB035405
    Consensus CDS
    CCDS42197.1
    UniProtKB/Swiss-Prot
    Q9NZC7
    Related
    ENSP00000348119.3, ENST00000355860.7
    Conserved Domains (3) summary
    cd00201
    Location:6090
    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:1847
    WW; WW domain
    cl21454
    Location:124172
    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_120436.2 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, AW874692, BU157392, DB035405
    Related
    ENST00000563358.5

RefSeqs of Annotated Genomes: Homo sapiens Annotation Release 109.20190905

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

Reference GRCh38.p13 Primary Assembly

Genomic

  1. NC_000016.10 Reference GRCh38.p13 Primary Assembly

    Range
    78099654..79212667
    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.
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