WT1 (Wilms tumor suppressor gene)

1999-10-01   Manfred Gessler  

Theodor-Boveri-Institut fuer Biowissenschaften, Lehrstuhl Physiol. Chemie I, Am Hubland, D-97074 Wuerzburg, Germany

Identity

HGNC
WT1
LOCATION
11p13
LOCUSID
7490
ALIAS
AWT1,GUD,NPHS4,WAGR,WIT-2,WT33
FUSION GENES
Show Gene Fusions

DNA/RNA

Description

10 exons spanning 48 kb of genomic DNA

Transcription

3 kb mRNA; four alternative splice forms: +/- exon 5 and alternative splice donor sites at exon 9

Proteins

Description

four major isoforms (429-449 aa) due to alternative splicing; there are eight minor isoforms resulting from different initiation sites (upstream CTG: 502-522 aa, downstream ATG: 303-323 aa)

Expression

kidney, spleen, mesothelia

Localisation

nuclear staining, either diffuse or in speckles, depending on isoform and mutations

Function

zinc finger transcription factor (4 C2H2-type fingers)

Homology

Sp1, Egr-1

Mutations

Germinal

various types of mutations, mostly affecting zinc fingers in exons 7-10. (WAGR syndrome, genito-urinary (GU) anomalies, Denys-Drash-syndrome, Frasier syndrome; see below)

Somatic

biallelic inactivation in Wilms tumors (

Implicated in

Entity name
Wilms tumor
Disease
nephroblastoma of childhood
Prognosis
good with treatment according to NWTS or SIOP
Cytogenetics
11p13 deletions/translocations can be seen in some cases
Oncogenesis
up to 15% of tumors show mainly biallelic inactivation of WT1 through deletion or mutatio
Entity name
desmoplastic small round cell tumor (DSRCT)
Prognosis
poor
Cytogenetics
translocations, t(11;22)(p13;q12)
Fusion protein
With EWS: EWS-WT; in frame fusion of EWS exons 1-7 and WT1 exons 8-10
Entity name
Denys-Drash syndrome (DDS)
Disease
defined by: mesangial sclerosis with kidney failure (age 2 yrs), gonadal dysgenesis, risk of Wilms tumors
Prognosis
kidney failure at age 0-5 years
Hybrid gene
dominant negative mutations, especially missense mutations within the zinc fingers (aa 394 Arg -> Trp) but very few nonsense mutations
Oncogenesis
high risk of Wilms tumor development
Entity name
Frasier syndrome
Disease
defined by: complete gonadal dysgenesis, focal glomerular sclerosis, gonadoblastoma; in karyotypic females the syndrome may be limited to focal glomerular sclerosis with regular gonadal development and function
Prognosis
kidney failure at age 10-30 years
Hybrid gene
heterozygous point mutations of alternative splice donor site in exon 9 with imbalance of WT1 isoform ratio
Oncogenesis
gonadoblatoma may occur within streak gonads

Article Bibliography

Pubmed IDLast YearTitleAuthors
83829381993The expression of the Wilms' tumour gene, WT1, in the developing mammalian embryo.Armstrong JF et al
93988521997Donor splice-site mutations in WT1 are responsible for Frasier syndrome.Barbaux S et al
86214951996A non-AUG translational initiation event generates novel WT1 isoforms.Bruening W et al
21543351990Isolation and characterization of a zinc finger polypeptide gene at the human chromosome 11 Wilms' tumor locus.Call KM et al
78626271995Characterization of the genomic breakpoint and chimeric transcripts in the EWS-WT1 gene fusion of desmoplastic small round cell tumor.Gerald WL et al
80195571994Infrequent mutation of the WT1 gene in 77 Wilms' Tumors.Gessler M et al
21547021990Homozygous deletion in Wilms tumours of a zinc-finger gene identified by chromosome jumping.Gessler M et al
16587871991Alternative splicing and genomic structure of the Wilms tumor gene WT1.Haber DA et al
94994251998Frasier syndrome is caused by defective alternative splicing of WT1 leading to an altered ratio of WT1 +/-KTS splice isoforms.Klamt B et al
77365911995Subnuclear localization of WT1 in splicing or transcription factor domains is regulated by alternative splicing.Larsson SH et al
90905241997A clinical overview of WT1 gene mutations.Little M et al
16552841991Germline mutations in the Wilms' tumor suppressor gene are associated with abnormal urogenital development in Denys-Drash syndrome.Pelletier J et al
22442091990Binding of the Wilms' tumor locus zinc finger protein to the EGR-1 consensus sequence.Rauscher FJ 3rd et al
104385241999Internal translation initiation generates novel WT1 protein isoforms with distinct biological properties.Scharnhorst V et al
81709461994Fine structure analysis of the WT1 gene in sporadic Wilms tumors.Varanasi R et al

Other Information

Locus ID:

NCBI: 7490
MIM: 607102
HGNC: 12796
Ensembl: ENSG00000184937

Variants:

dbSNP: 7490
ClinVar: 7490
TCGA: ENSG00000184937
COSMIC: WT1

RNA/Proteins

Gene IDTranscript IDUniprot
ENSG00000184937ENST00000332351J3KNN9
ENSG00000184937ENST00000379077H0Y3F0
ENSG00000184937ENST00000379079P19544
ENSG00000184937ENST00000448076H0Y7K5
ENSG00000184937ENST00000452863A0A0A0MT54
ENSG00000184937ENST00000527882H0YED9
ENSG00000184937ENST00000530998P19544
ENSG00000184937ENST00000639563A0A1W2PQQ0
ENSG00000184937ENST00000640146A0A1W2PR07
ENSG00000184937ENST00000651459A0A494C0I9

Expression (GTEx)

0
50
100
150
Adipose - Subcutaneous
Adipose - Visceral
Adrenal Gland
Artery - Aorta
Artery - Tibial
Bladder
Brain - Amygdala
Brain - Anterior cingulate cortex
Brain - Caudate
Brain - Cerebellar Hemisphere
Brain - Cerebellum
Brain - Cortex
Brain - Frontal Cortex
Brain - Hippocampus
Brain - Hypothalamus
Brain - Nucleus accumbens
Brain - Putamen
Brain - Spinal cord
Brain - Substantia nigra
Breast - Mammary Tissue
Cells - Cultured fibroblasts
Cells - EBV - transformed lymphocytes
Cervix - Ectocervix
Cervix - Endocervix
Colon - Sigmoid
Colon - Transverse
Esophagus - Gastroesophageal Junction
Esophagus - Mucosa
Esophagus - Muscularis
Fallopian Tube
Heart - Atrial Appendage
Heart - Left Ventricle
Kidney - Cortex
Kidney - Medulla
Liver
Lung
Minor Salivary Gland
Muscle - Skeletal
Nerve - Tibial
Ovary
Pancreas
Pituitary
Prostate
Skin - Not Sun Exposed
Skin - Sun Exposed
Small Intestine - Terminal Ileum
Spleen
Stomach
Testis
Thyroid
Uterus
Vagina
Whole Blood

Pathways

PathwaySourceExternal ID
Transcriptional misregulation in cancerKEGGko05202
Transcriptional misregulation in cancerKEGGhsa05202

Protein levels (Protein atlas)

Not detected
Low
Medium
High
cerebral cortex
cerebellum
hippocampus
caudate
thyroid gland
parathyroid gland
adrenal gland
nasopharynx
bronchus
lung
oral mucosa
salivary gland
esophagus
stomach 1
stomach 2
duodenum
small intestine
colon
rectum
liver
gallbladder
pancreas
kidney
urinary bladder
testis
epididymis
seminal vesicle
prostate
vagina
ovary
fallopian tube
endometrium 1
endometrium 2
cervix, uterine
placenta
breast
heart muscle
smooth muscle
skeletal muscle
soft tissue 1
soft tissue 2
adipose tissue
skin 1
skin 2
appendix
spleen
lymph node
tonsil
bone marrow

PharmGKB

Entity IDNameTypeEvidenceAssociationPKPDPMIDs
PA445084Wilms TumorDiseaseDataAnnotation, Literature, MultilinkAnnotationassociated23788249

References

Pubmed IDYearTitleCitations
381581262024EWSR1::WT1 Fusions in Neoplasms Other Than Conventional Desmoplastic Small Round Cell Tumor: Three Tumors Occurring Outside the Female Genital Tract.0
382191852024Familial focal segmental glomerulosclerosis associated with a WT1 gene missense mutation: A case report.0
383003832024WT1 and TP53 as valuable diagnostic biomarkers for relapse after hematopoietic stem cell transplantation in acute myeloid leukemia.0
383838422024MAP4K4 and WT1 mediate SOX6-induced cellular senescence by synergistically activating the ATF2-TGFβ2-Smad2/3 signaling pathway in cervical cancer.0
384231832024Inhibition of transcriptional coactivator YAP Impairs the expression and function of transcription factor WT1 in diabetic podocyte injury.0
385884092024Comprehensive Transcriptomic Analysis of EWSR1::WT1 Targets Identifies CDK4/6 Inhibitors as an Effective Therapy for Desmoplastic Small Round Cell Tumors.0
386421532024Overexpression of WT1 in all molecular subtypes of breast cancer and its impact on survival: exploring oncogenic and tumor suppressor roles of distinct WT1 isoforms.0
387459482024Homeobox regulator Wilms Tumour 1 is displaced by androgen receptor at cis-regulatory elements in the endometrium of PCOS patients.0
381581262024EWSR1::WT1 Fusions in Neoplasms Other Than Conventional Desmoplastic Small Round Cell Tumor: Three Tumors Occurring Outside the Female Genital Tract.0
382191852024Familial focal segmental glomerulosclerosis associated with a WT1 gene missense mutation: A case report.0
383003832024WT1 and TP53 as valuable diagnostic biomarkers for relapse after hematopoietic stem cell transplantation in acute myeloid leukemia.0
383838422024MAP4K4 and WT1 mediate SOX6-induced cellular senescence by synergistically activating the ATF2-TGFβ2-Smad2/3 signaling pathway in cervical cancer.0
384231832024Inhibition of transcriptional coactivator YAP Impairs the expression and function of transcription factor WT1 in diabetic podocyte injury.0
385884092024Comprehensive Transcriptomic Analysis of EWSR1::WT1 Targets Identifies CDK4/6 Inhibitors as an Effective Therapy for Desmoplastic Small Round Cell Tumors.0
386421532024Overexpression of WT1 in all molecular subtypes of breast cancer and its impact on survival: exploring oncogenic and tumor suppressor roles of distinct WT1 isoforms.0

Citation

Manfred Gessler

WT1 (Wilms tumor suppressor gene)

Atlas Genet Cytogenet Oncol Haematol. 1999-10-01

Online version: http://atlasgeneticsoncology.org/gene/78/css/cancer-prone-explorer/js/_common.js