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

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; 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

Location:: 16q23.1-q23.2

Exon count:: 10

Annotation release	Status	Assembly	Chr	Location
RS_2023_10	current	GRCh38.p14 (GCF_000001405.40)	16	NC_000016.10 (78099654..79212667)
RS_2023_10	current	T2T-CHM13v2.0 (GCF_009914755.1)	16	NC_060940.1 (84155399..85268915)
105.20220307	previous assembly	GRCh37.p13 (GCF_000001405.25)	16	NC_000016.9 (78133551..79246564)

Chromosome 16 - NC_000016.10 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

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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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

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

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

RH119330 (e-PCR)
- UniSTS:133892

D16S3307 (e-PCR)
- UniSTS:14859

SHGC-142593 (e-PCR)
- UniSTS:171539

RH11464 (e-PCR)
- UniSTS:42517

RH120880 (e-PCR)
- UniSTS:137751

D16S3324 (e-PCR)
- UniSTS:52513

U48593 (e-PCR)
- UniSTS:66853

D16S2812 (e-PCR)
- UniSTS:153382

D16S684 (e-PCR)
- UniSTS:149289

RH70328 (e-PCR)
- UniSTS:60469

G59715 (e-PCR)
- UniSTS:137014

D16S2830 (e-PCR)
- UniSTS:153400

SHGC-152307 (e-PCR)
- UniSTS:177469

STS-AA010189 (e-PCR)
- UniSTS:45122

RH65187 (e-PCR)
- UniSTS:85059

G59732 (e-PCR)
- UniSTS:137030

D16S2957 (e-PCR)
- UniSTS:77134

G54637 (e-PCR)
- UniSTS:117838

D16S2854 (e-PCR)
- UniSTS:153424

D16S3049 (e-PCR), detects polymorphism
- UniSTS:46932

G15863 (e-PCR)
- UniSTS:57177

G29254 (e-PCR)
- UniSTS:26973

D16S516 (e-PCR)
- UniSTS:10334

D16S3344 (e-PCR)
- UniSTS:28257

D16S2571E (e-PCR)
- UniSTS:151653

G32522 (e-PCR)
- UniSTS:117107

A009G06 (e-PCR)
- UniSTS:13688

RH27913 (e-PCR)
- UniSTS:92030

SHGC-111352 (e-PCR)
- UniSTS:168319

D16S504 (e-PCR), detects polymorphism
- UniSTS:51585

G59680 (e-PCR)
- UniSTS:136834

D16S435E (e-PCR)
- UniSTS:12425

D16S518 (e-PCR), detects polymorphism
- UniSTS:53129

RH65206 (e-PCR)
- UniSTS:90250

RH122248 (e-PCR)
- UniSTS:134796

RH65299 (e-PCR)
- UniSTS:86166

SHGC-147374 (e-PCR)
- UniSTS:175777

SHGC-111467 (e-PCR)
- UniSTS:182947

D14S164 (e-PCR)
- UniSTS:148388

D16S2683 (e-PCR)
- UniSTS:153253

RH12208 (e-PCR)
- UniSTS:22182

STS-T69772 (e-PCR)
- UniSTS:16041

RH15657 (e-PCR)
- UniSTS:15530

D16S2694 (e-PCR)
- UniSTS:153264

SHGC-151189 (e-PCR)
- UniSTS:173495

SHGC-147929 (e-PCR)
- UniSTS:182968

G19118 (e-PCR)
- UniSTS:67776

A336YG9 (e-PCR)
- UniSTS:20419

SHGC-36289 (e-PCR)
- UniSTS:63432

RH118987 (e-PCR)
- UniSTS:138955

G43289 (e-PCR)
- UniSTS:94923

RH65116 (e-PCR)
- UniSTS:90060

D16S435E (e-PCR)
- UniSTS:147407

SHGC-60781 (e-PCR)
- UniSTS:72403

SHGC-155340 (e-PCR)
- UniSTS:182996

D16S3213 (e-PCR)
- UniSTS:25559

RH78191 (e-PCR)
- UniSTS:35548

SHGC-147192 (e-PCR)
- UniSTS:172766

D16S504 (e-PCR), detects polymorphism
- UniSTS:14303

D16S2742 (e-PCR)
- UniSTS:153312

SHGC-60733 (e-PCR)
- UniSTS:26340

RH69741 (e-PCR)
- UniSTS:52964

SHGC-147930 (e-PCR)
- UniSTS:176102

D16S3096 (e-PCR), detects polymorphism
- UniSTS:45798

D16S3029 (e-PCR), detects polymorphism
- UniSTS:17645

RH70047 (e-PCR)
- UniSTS:7160

AF007377 (e-PCR)
- UniSTS:13563

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables enzyme 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

EC 1.1.1.-

NP_057457.1

EC 1.1.1.-

NP_570607.1

EC 1.1.1.-

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

NG_011698.1 RefSeqGene

Range

5001..1118014

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

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
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 ...
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

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
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_2023_10

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

Reference GRCh38.p14 Primary Assembly

Genomic

NC_000016.10 Reference GRCh38.p14 Primary Assembly

Range

78099654..79212667

Download

GenBank, FASTA, Sequence Viewer (Graphics)

Alternate T2T-CHM13v2.0

Genomic

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

NM_018560.4: Suppressed sequence

Description

NM_018560.4: This RefSeq was permanently suppressed because it is a nonsense-mediated mRNA decay (NMD) candidate.
NM_130788.1: Suppressed sequence

Description

NM_130788.1: This RefSeq was permanently suppressed because it appears to be specific to a disease state.
NM_130790.1: Suppressed sequence

Description

NM_130790.1: This RefSeq was permanently suppressed because it appears to be specific to a disease state.
NM_130792.1: Suppressed sequence

Description

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