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WT1 Wilms tumor 1 [ Homo sapiens (human) ]

Gene ID: 7490, updated on 9-Dec-2018

Summary

Official Symbol
WT1provided by HGNC
Official Full Name
Wilms tumor 1provided by HGNC
Primary source
HGNC:HGNC:12796
See related
Ensembl:ENSG00000184937 MIM:607102
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
GUD; AWT1; WAGR; WT33; NPHS4; WIT-2
Summary
This gene encodes a transcription factor that contains four zinc-finger motifs at the C-terminus and a proline/glutamine-rich DNA-binding domain at the N-terminus. It has an essential role in the normal development of the urogenital system, and it is mutated in a small subset of patients with Wilms tumor. This gene exhibits complex tissue-specific and polymorphic imprinting pattern, with biallelic, and monoallelic expression from the maternal and paternal alleles in different tissues. Multiple transcript variants have been described. In several variants, there is evidence for the use of a non-AUG (CUG) translation initiation codon upstream of, and in-frame with the first AUG. Authors of PMID:7926762 also provide evidence that WT1 mRNA undergoes RNA editing in human and rat, and that this process is tissue-restricted and developmentally regulated. [provided by RefSeq, Mar 2015]
Expression
Biased expression in endometrium (RPKM 27.6), testis (RPKM 17.6) and 4 other tissues See more
Orthologs

Genomic context

See WT1 in Genome Data Viewer
Location:
11p13
Exon count:
11
Annotation release Status Assembly Chr Location
109 current GRCh38.p12 (GCF_000001405.38) 11 NC_000011.10 (32387775..32435539, complement)
105 previous assembly GRCh37.p13 (GCF_000001405.25) 11 NC_000011.9 (32408789..32457104, complement)

Chromosome 11 - NC_000011.10Genomic Context describing neighboring genes Neighboring gene HCNE2 enhancer upstream of PAX6 Neighboring gene WT1 3' enhancer Neighboring gene WT1 intron 3 regulatory region Neighboring gene WT1/WT1-AS bi-directional promoter region Neighboring gene WT1 antisense RNA Neighboring gene protein GVQW2-like Neighboring gene heterogeneous nuclear ribonucleoprotein A3 pseudogene 9 Neighboring gene eukaryotic translation initiation factor 3 subunit M

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 Jun 15 11:32:44 2016

Bibliography

GeneRIFs: Gene References Into FunctionsWhat's a GeneRIF?

Phenotypes

Professional guidelines

Description
Professional guideline
ACMG 2013

The ACMG recommends that laboratories performing clinical sequencing seek and report mutations in WT1 that are pathogenic or expected to be pathogenic.

GuidelinePubMed

Associated conditions

Description Tests
Aniridia 1
MedGen: C0344542 OMIM: 106210 GeneReviews: PAX6-Related Aniridia
Compare labs
Diffuse mesangial sclerosis
MedGen: C0268747 OMIM: 256370 GeneReviews: Not available
Compare labs
Drash syndrome
MedGen: C0950121 OMIM: 194080 GeneReviews: Not available
Compare labs
Frasier syndrome
MedGen: C0950122 OMIM: 136680 GeneReviews: Not available
Compare labs
Meacham syndrome
MedGen: C1837026 OMIM: 608978 GeneReviews: Not available
Compare labs
Mesothelioma, malignant
MedGen: C0345967 OMIM: 156240 GeneReviews: Not available
Compare labs
Wilms tumor 1 Compare labs
Wilms tumor, aniridia, genitourinary anomalies, and mental retardation syndrome
MedGen: C0206115 OMIM: 194072 GeneReviews: PAX6-Related Aniridia
Compare labs

Copy number response

Description
Copy number response
Triplosensitivity

No evidence available (Last evaluated (2012-07-06)

ClinGen Genome Curation Page
Haploinsufficency

Sufficient evidence for dosage pathogenicity (Last evaluated (2012-07-06)

ClinGen Genome Curation Page

NHGRI GWAS Catalog

Description
Common variants at 11p13 are associated with susceptibility to tuberculosis.
NHGRI GWA Catalog
Genome-wide association study of ancestry-specific TB risk in the South African Coloured population.
NHGRI GWA Catalog

HIV-1 interactions

Replication interactions

Interaction Pubs
Screening in Jurkat T-cells with a short-hairpin-RNA (shRNA) library identifies Wilms tumor 1 (WT1) is important for HIV-1 replication. shRNA against WT1 exhibits a decrease on LTR-driven beta-gal transcription compared to control PubMed

Protein interactions

Protein Gene Interaction Pubs
Nef nef Podocyte-specific expression of HIV-1 Nef induces loss of synaptopodin and WT1, and expression of Ki-67 in podocytes, which is essential for the dedifferentiation and proliferation of podocytes in HIV-associated nephropathy PubMed

Go to the HIV-1, Human Interaction Database

Pathways from BioSystems

Interactions

Products Interactant Other Gene Complex Source Pubs Description

General gene information

Markers

Homology

Gene Ontology Provided by GOA

Function Evidence Code Pubs
C2H2 zinc finger domain binding IPI
Inferred from Physical Interaction
more info
PubMed 
DNA-binding transcription activator activity, RNA polymerase II-specific IDA
Inferred from Direct Assay
more info
PubMed 
DNA-binding transcription activator activity, RNA polymerase II-specific ISS
Inferred from Sequence or Structural Similarity
more info
 
DNA-binding transcription factor activity ISS
Inferred from Sequence or Structural Similarity
more info
 
DNA-binding transcription factor activity NAS
Non-traceable Author Statement
more info
PubMed 
DNA-binding transcription factor activity, RNA polymerase II-specific IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
DNA-binding transcription factor activity, RNA polymerase II-specific ISA
Inferred from Sequence Alignment
more info
 
DNA-binding transcription factor activity, RNA polymerase II-specific ISM
Inferred from Sequence Model
more info
PubMed 
DNA-binding transcription factor activity, RNA polymerase II-specific NAS
Non-traceable Author Statement
more info
PubMed 
RNA binding IEA
Inferred from Electronic Annotation
more info
 
double-stranded methylated DNA binding IDA
Inferred from Direct Assay
more info
PubMed 
hemi-methylated DNA-binding IDA
Inferred from Direct Assay
more info
PubMed 
protein binding IPI
Inferred from Physical Interaction
more info
PubMed 
sequence-specific DNA binding IDA
Inferred from Direct Assay
more info
PubMed 
transcription regulatory region DNA binding IDA
Inferred from Direct Assay
more info
PubMed 
zinc ion binding IDA
Inferred from Direct Assay
more info
PubMed 
Process Evidence Code Pubs
RNA splicing ISS
Inferred from Sequence or Structural Similarity
more info
 
adrenal cortex formation ISS
Inferred from Sequence or Structural Similarity
more info
 
adrenal gland development IGI
Inferred from Genetic Interaction
more info
PubMed 
branching involved in ureteric bud morphogenesis IGI
Inferred from Genetic Interaction
more info
PubMed 
camera-type eye development ISS
Inferred from Sequence or Structural Similarity
more info
 
cardiac muscle cell fate commitment ISS
Inferred from Sequence or Structural Similarity
more info
 
cellular response to cAMP IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
cellular response to cAMP IEP
Inferred from Expression Pattern
more info
PubMed 
cellular response to gonadotropin stimulus IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
cellular response to gonadotropin stimulus IDA
Inferred from Direct Assay
more info
PubMed 
diaphragm development ISS
Inferred from Sequence or Structural Similarity
more info
 
epithelial cell differentiation ISS
Inferred from Sequence or Structural Similarity
more info
 
germ cell development ISS
Inferred from Sequence or Structural Similarity
more info
 
glomerular basement membrane development IMP
Inferred from Mutant Phenotype
more info
PubMed 
glomerular visceral epithelial cell differentiation IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
glomerular visceral epithelial cell differentiation ISS
Inferred from Sequence or Structural Similarity
more info
 
glomerulus development IGI
Inferred from Genetic Interaction
more info
PubMed 
gonad development ISS
Inferred from Sequence or Structural Similarity
more info
 
heart development IGI
Inferred from Genetic Interaction
more info
PubMed 
kidney development IGI
Inferred from Genetic Interaction
more info
PubMed 
male genitalia development ISS
Inferred from Sequence or Structural Similarity
more info
 
male gonad development IEP
Inferred from Expression Pattern
more info
PubMed 
mesenchymal to epithelial transition ISS
Inferred from Sequence or Structural Similarity
more info
 
metanephric S-shaped body morphogenesis IGI
Inferred from Genetic Interaction
more info
PubMed 
metanephric epithelium development IEP
Inferred from Expression Pattern
more info
PubMed 
metanephric mesenchyme development ISS
Inferred from Sequence or Structural Similarity
more info
 
negative regulation of apoptotic process IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
negative regulation of apoptotic process IGI
Inferred from Genetic Interaction
more info
PubMed 
negative regulation of cell growth IDA
Inferred from Direct Assay
more info
PubMed 
negative regulation of cell proliferation IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
negative regulation of cell proliferation IDA
Inferred from Direct Assay
more info
PubMed 
negative regulation of female gonad development ISS
Inferred from Sequence or Structural Similarity
more info
 
negative regulation of metanephric glomerular mesangial cell proliferation ISS
Inferred from Sequence or Structural Similarity
more info
 
negative regulation of transcription by RNA polymerase II IDA
Inferred from Direct Assay
more info
PubMed 
negative regulation of transcription by RNA polymerase II IMP
Inferred from Mutant Phenotype
more info
PubMed 
negative regulation of transcription, DNA-templated IDA
Inferred from Direct Assay
more info
PubMed 
positive regulation of DNA methylation IMP
Inferred from Mutant Phenotype
more info
PubMed 
positive regulation of gene expression IMP
Inferred from Mutant Phenotype
more info
PubMed 
positive regulation of heart growth ISS
Inferred from Sequence or Structural Similarity
more info
 
positive regulation of male gonad development ISS
Inferred from Sequence or Structural Similarity
more info
 
positive regulation of metanephric ureteric bud development ISS
Inferred from Sequence or Structural Similarity
more info
 
positive regulation of pri-miRNA transcription by RNA polymerase II IMP
Inferred from Mutant Phenotype
more info
PubMed 
positive regulation of transcription by RNA polymerase II IDA
Inferred from Direct Assay
more info
PubMed 
positive regulation of transcription, DNA-templated IDA
Inferred from Direct Assay
more info
PubMed 
positive regulation of transcription, DNA-templated IGI
Inferred from Genetic Interaction
more info
PubMed 
posterior mesonephric tubule development ISS
Inferred from Sequence or Structural Similarity
more info
 
regulation of animal organ formation ISS
Inferred from Sequence or Structural Similarity
more info
 
regulation of transcription by RNA polymerase II IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
regulation of transcription by RNA polymerase II ISS
Inferred from Sequence or Structural Similarity
more info
 
regulation of transcription, DNA-templated ISS
Inferred from Sequence or Structural Similarity
more info
 
regulation of transcription, DNA-templated NAS
Non-traceable Author Statement
more info
PubMed 
sex determination IDA
Inferred from Direct Assay
more info
PubMed 
thorax and anterior abdomen determination ISS
Inferred from Sequence or Structural Similarity
more info
 
tissue development ISS
Inferred from Sequence or Structural Similarity
more info
 
ureteric bud development ISS
Inferred from Sequence or Structural Similarity
more info
 
vasculogenesis ISS
Inferred from Sequence or Structural Similarity
more info
 
visceral serous pericardium development IGI
Inferred from Genetic Interaction
more info
PubMed 
Component Evidence Code Pubs
cytoplasm ISS
Inferred from Sequence or Structural Similarity
more info
 
cytosol IDA
Inferred from Direct Assay
more info
 
nuclear speck IDA
Inferred from Direct Assay
more info
PubMed 
nucleolus IEA
Inferred from Electronic Annotation
more info
 
nucleoplasm IDA
Inferred from Direct Assay
more info
 
nucleus IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
nucleus IDA
Inferred from Direct Assay
more info
PubMed 

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_009272.1 RefSeqGene

    Range
    5001..52767
    Download
    GenBank, FASTA, Sequence Viewer (Graphics), LRG_525

mRNA and Protein(s)

  1. NM_000378.5NP_000369.4  Wilms tumor protein isoform A

    Status: REVIEWED

    Description
    Transcript Variant: This variant (A) lacks an alternate in-frame exon and uses an alternate, in-frame splice site in the 3' coding region, compared to variant D. This results in a shorter protein (isoform A), compared to isoform D. It initiates translation from a non-AUG (CUG) site, and also from a downstream, in-frame AUG.
    Source sequence(s)
    AB971668, AK093168, BC046461, M30393, X51630
    Consensus CDS
    CCDS44561.1
    Related
    ENSP00000415516.3, ENST00000452863.7
    Conserved Domains (3) summary
    COG5048
    Location:437495
    COG5048; FOG: Zn-finger [General function prediction only]
    sd00017
    Location:384403
    ZF_C2H2; C2H2 Zn finger [structural motif]
    pfam02165
    Location:74377
    WT1; Wilm's tumor protein
  2. NM_001198551.1NP_001185480.1  Wilms tumor protein isoform E

    See identical proteins and their annotated locations for NP_001185480.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (E) differs in the 5' UTR, lacks a portion of the 5' coding region, and initiates translation at an alternate start codon, compared to variant D. This variant also uses an alternate, in-frame splice site in the 3' coding region, compared to variant D. The encoded isoform (E) has a distinct N-terminus and is shorter than isoform D.
    Source sequence(s)
    AK093168, BC032861, BC046461, BG718348, M30393
    Consensus CDS
    CCDS55751.1
    UniProtKB/Swiss-Prot
    P19544
    UniProtKB/TrEMBL
    Q6PI38
    Related
    ENSP00000368370.2, ENST00000379079.6
    Conserved Domains (4) summary
    COG5048
    Location:237295
    COG5048; FOG: Zn-finger [General function prediction only]
    sd00017
    Location:184203
    ZF_C2H2; C2H2 Zn finger [structural motif]
    pfam02165
    Location:3177
    WT1; Wilm's tumour protein
    pfam13465
    Location:226250
    zf-H2C2_2; Zinc-finger double domain
  3. NM_001198552.1NP_001185481.1  Wilms tumor protein isoform F

    See identical proteins and their annotated locations for NP_001185481.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (F) differs in the 5' UTR, lacks a portion of the 5' coding region, and initiates translation at an alternate start codon, compared to variant D. This variant also lacks an alternate, in-frame exon compared to variant D. The encoded isoform (F) has a distinct N-terminus and is shorter than isoform D.
    Source sequence(s)
    AK093168, BC046461, BG718348, M30393
    Consensus CDS
    CCDS55750.1
    UniProtKB/Swiss-Prot
    P19544
    UniProtKB/TrEMBL
    Q6PI38
    Related
    ENSP00000435307.1, ENST00000530998.5
    Conserved Domains (4) summary
    COG5048
    Location:152280
    COG5048; FOG: Zn-finger [General function prediction only]
    sd00017
    Location:167186
    ZF_C2H2; C2H2 Zn finger [structural motif]
    pfam02165
    Location:3160
    WT1; Wilm's tumour protein
    pfam13465
    Location:209233
    zf-H2C2_2; Zinc-finger double domain
  4. NM_024424.4NP_077742.3  Wilms tumor protein isoform B

    Status: REVIEWED

    Description
    Transcript Variant: This variant (B) uses an alternate, in-frame splice site in the 3' coding region, compared to variant D. This results in a shorter protein (isoform B), compared to isoform D. It initiates translation from a non-AUG (CUG) site, and also from a downstream, in-frame AUG.
    Source sequence(s)
    AB971668, AK093168, AK291736, BC046461, M30393, X51630
    Consensus CDS
    CCDS44562.1
    Related
    ENSP00000413452.3, ENST00000448076.7
    Conserved Domains (3) summary
    COG5048
    Location:454512
    COG5048; FOG: Zn-finger [General function prediction only]
    sd00017
    Location:401420
    ZF_C2H2; C2H2 Zn finger [structural motif]
    pfam02165
    Location:74394
    WT1; Wilm's tumor protein
  5. NM_024426.5NP_077744.4  Wilms tumor protein isoform D

    Status: REVIEWED

    Description
    Transcript Variant: This variant (D) represents the longest transcript and encodes the longest isoform (D). It initiates translation from a non-AUG (CUG) site, and also from a downstream, in-frame AUG.
    Source sequence(s)
    AB971668, AK093168, BC046461, M30393, X51630
    Consensus CDS
    CCDS7878.2
    Related
    ENSP00000331327.3, ENST00000332351.7
    Conserved Domains (3) summary
    COG5048
    Location:386514
    COG5048; FOG: Zn-finger [General function prediction only]
    sd00017
    Location:401420
    ZF_C2H2; C2H2 Zn finger [structural motif]
    pfam02165
    Location:74394
    WT1; Wilm's tumor protein

RefSeqs of Annotated Genomes: Homo sapiens Annotation Release 109 details...Open this link in a new tab

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

Reference GRCh38.p12 Primary Assembly

Genomic

  1. NC_000011.10 Reference GRCh38.p12 Primary Assembly

    Range
    32387775..32435539 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

Suppressed Reference Sequence(s)

The following Reference Sequences have been suppressed. Explain

  1. NM_024425.2: Suppressed sequence

    Description
    NM_024425.2: This RefSeq was permanently suppressed because currently there is insufficient support for the transcript and the protein.
Support Center