WT1 (Wilms' tumor suppressor gene)

Identity

HGNC	WT1
Location	11p13
Location_base_pair	Starts at 32365901 and ends at 32413663 bp from pter ( according to hg18-Mar_2006).
Local_order	Cen-RAG1/2-CAT-CD59-WT1-RCN-PAX6-FSHB-tel

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

Protein

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 (<15%) and some mesotheliomas and granulosa cell tumors

Implicated in

Entity	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	desmoplastic small round cell tumor (DSRCT)
Prognosis	poor
Cytogenetics	translocations, t(11;22)(p13;q12)
Abnormal Protein	With EWS: EWS-WT; in frame fusion of EWS exons 1-7 and WT1 exons 8-10
Entity	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/Mutated 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	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/Mutated 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

External links

	Nomenclature
HGNC	WT1   12796
Entrez_Gene	WT1  7490  Wilms tumor 1
	Cards
Atlas	WT1ID78
GeneCards	WT1
Ensembl	ENSG00000184937 [Gene_View]  WT1 [Vega]
Genatlas	WT1
	Genomic and cartography
GoldenPath	WT1  -  11p13   chr11:32365901-32413663 -  11p13   [Description]    (hg18-Mar_2006)
Ensembl	WT1 - 11p13 [CytoView]
NCBI	Mapview
OMIM	136680 Disease map [OMIM]
OMIM	194070 Disease map [OMIM]
OMIM	194072 Disease map [OMIM]
OMIM	194080 Disease map [OMIM]
OMIM	256370 Disease map [OMIM]
OMIM	607102 Disease map [OMIM]
HomoloGene	WT1
	Gene and transcription
Genbank	AK093168 [ ENTREZ ]
Genbank	AK291736 [ ENTREZ ]
Genbank	BC032861 [ ENTREZ ]
Genbank	BC046461 [ ENTREZ ]
Genbank	M30393 [ ENTREZ ]
RefSeq	NM_000378 [ SRS ]    NM_000378 [ ENTREZ ]
RefSeq	NM_024424 [ SRS ]    NM_024424 [ ENTREZ ]
RefSeq	NM_024425 [ SRS ]    NM_024425 [ ENTREZ ]
RefSeq	NM_024426 [ SRS ]    NM_024426 [ ENTREZ ]
RefSeq	AC_000054 [ SRS ]    AC_000054 [ ENTREZ ]
RefSeq	AC_000143 [ SRS ]    AC_000143 [ ENTREZ ]
RefSeq	NC_000011 [ SRS ]    NC_000011 [ ENTREZ ]
RefSeq	NT_009237 [ SRS ]    NT_009237 [ ENTREZ ]
RefSeq	NW_001838022 [ SRS ]    NW_001838022 [ ENTREZ ]
RefSeq	NW_925006 [ SRS ]    NW_925006 [ ENTREZ ]
CCDS	WT1 CCDS - NCBI
AceView	WT1 AceView - NCBI
Unigene	Hs.591980 [ SRS ]    Hs.591980 [ NCBI ]
Fast-db	4548 (alternative variants)
	Protein : pattern, domain, 3D structure
SwissProt	P19544 [ SRS]    P19544 [ EXPASY ]     P19544 [ INTERPRO ]     P19544 [ UNIPROT ] P19544 [ VarSplice FASTA ]
Prosite	PS00028 ZINC_FINGER_C2H2_1 [ SRS ]    PS00028 ZINC_FINGER_C2H2_1 [ Expasy ]
Prosite	PS50157 ZINC_FINGER_C2H2_2 [ SRS ]    PS50157 ZINC_FINGER_C2H2_2 [ Expasy ]
Interpro	IPR000976 Wilms_tumour [ SRS ]    IPR000976 Wilms_tumour [ EBI ]
Interpro	IPR007087 Znf_C2H2 [ SRS ]    IPR007087 Znf_C2H2 [ EBI ]
Interpro	IPR015880 Znf_C2H2-like [ SRS ]    IPR015880 Znf_C2H2-like [ EBI ]
Interpro	IPR013087 Znf_C2H2/integrase_DNA-bd [ SRS ]    IPR013087 Znf_C2H2/integrase_DNA-bd [ EBI ]
CluSTr	P19544
Pfam	PF02165 WT1 [ SRS ]    PF02165 WT1 [ Sanger ]    pfam02165 [ NCBI-CDD ]
Pfam	PF00096 zf-C2H2 [ SRS ]    PF00096 zf-C2H2 [ Sanger ]    pfam00096 [ NCBI-CDD ]
Smart	SM00355 ZnF_C2H2 [EMBL]
Prodom	PD000003 Znf_C2H2[INRA-Toulouse]
Prodom	P19544 WT1_HUMAN [ Domain structure ]   P19544 WT1_HUMAN  [ sequences sharing at least 1 domain ]
Blocks	P19544
PDB	1LU6 [ SRS ]    1LU6 [ PdbSum ],   1LU6 [ IMB ]   1LU6 [ RSDB ]
PDB	1XF7 [ SRS ]    1XF7 [ PdbSum ],   1XF7 [ IMB ]   1XF7 [ RSDB ]
PDB	2G7T [ SRS ]    2G7T [ PdbSum ],   2G7T [ IMB ]   2G7T [ RSDB ]
PDB	2G7V [ SRS ]    2G7V [ PdbSum ],   2G7V [ IMB ]   2G7V [ RSDB ]
PDB	2G7W [ SRS ]    2G7W [ PdbSum ],   2G7W [ IMB ]   2G7W [ RSDB ]
PDB	2G7X [ SRS ]    2G7X [ PdbSum ],   2G7X [ IMB ]   2G7X [ RSDB ]
HPRD	06163
	Protein Interaction databases
DIP	P19544
IntAct	P19544
	Polymorphism : SNP, mutations, diseases
OMIM	136680    [ map ]
OMIM	194070    [ map ]
OMIM	194072    [ map ]
OMIM	194080    [ map ]
OMIM	256370    [ map ]
OMIM	607102    [ map ]
GENETests	136680
GENETests	194070
GENETests	194072
GENETests	194080
GENETests	256370
GENETests	607102
SNP	WT1 [dbSNP-NCBI]
SNP	NM_000378 [SNP-NCI]
SNP	NM_024424 [SNP-NCI]
SNP	NM_024425 [SNP-NCI]
SNP	NM_024426 [SNP-NCI]
SNP	WT1 [GeneSNPs - Utah]  WT1] [HGBASE - SRS]
HAPMAP	WT1 [HAPMAP]
COSMIC	WT1 [Somatic mutation (COSMIC-CGP-Sanger)]
TICdb	WT1 [Translocation breakpoints In Cancer]
HGMD	WT1
Genetic Association	WT1
CDC HuGE	WT1
	General knowledge
Family Browser	WT1 [UCSC Family Browser]
SOURCE	NM_000378
SOURCE	NM_024424
SOURCE	NM_024425
SOURCE	NM_024426
SMD	Hs.591980
SAGE	Hs.591980
GO	negative regulation of transcription from RNA polymerase II promoter [Amigo]  negative regulation of transcription from RNA polymerase II promoter
GO	transcription factor activity [Amigo]  transcription factor activity
GO	intracellular [Amigo]  intracellular
GO	nucleus [Amigo]  nucleus
GO	transcription [Amigo]  transcription
GO	regulation of transcription, DNA-dependent [Amigo]  regulation of transcription, DNA-dependent
GO	zinc ion binding [Amigo]  zinc ion binding
GO	negative regulation of cell cycle [Amigo]  negative regulation of cell cycle
GO	metal ion binding [Amigo]  metal ion binding
BIOCARTA	Overview of telomerase protein component gene hTert Transcriptional Regulation    [Genes]
BIOCARTA	Chaperones modulate interferon Signaling Pathway    [Genes]
PubGene	WT1
TreeFam	WT1
CTD	7490 [Comparative ToxicoGenomics Database]
	Other databases
Other database	WT1 mutation database
	Probes
Probe	WT1 Related clones (RZPD - Berlin)
	PubMed
PubMed	184 Pubmed reference(s) in Entrez

Bibliography

Isolation and characterization of a zinc finger polypeptide gene at the human chromosome 11 Wilms' tumor locus.

Call KM, Glaser T, Ito CY, Buckler AJ, Pelletier J, Haber DA, Rose EA, Kral A, Yeger H, Lewis WH

Cell. 1990 ; 60 (3) : 509-520.

PMID 2154335

Homozygous deletion in Wilms tumours of a zinc-finger gene identified by chromosome jumping.

Gessler M, Poustka A, Cavenee W, Neve RL, Orkin SH, Bruns GA

Nature. 1990 ; 343 (6260) : 774-778.

PMID 2154702

Binding of the Wilms' tumor locus zinc finger protein to the EGR-1 consensus sequence.

Rauscher FJ 3rd, Morris JF, Tournay OE, Cook DM, Curran T

Science (New York, N.Y.). 1990 ; 250 (4985) : 1259-1262.

PMID 2244209

Alternative splicing and genomic structure of the Wilms tumor gene WT1.

Haber DA, Sohn RL, Buckler AJ, Pelletier J, Call KM, Housman DE

Proceedings of the National Academy of Sciences of the United States of America. 1991 ; 88 (21) : 9618-9622.

PMID 1658787

Germline mutations in the Wilms' tumor suppressor gene are associated with abnormal urogenital development in Denys-Drash syndrome.

Pelletier J, Bruening W, Kashtan CE, Mauer SM, Manivel JC, Striegel JE, Houghton DC, Junien C, Habib R, Fouser L

Cell. 1991 ; 67 (2) : 437-447.

PMID 1655284

The genomic organization and expression of the WT1 gene.

Gessler M, K��nig A, Bruns GA

Genomics. 1992 ; 12 (4) : 807-813.

PMID 1572653

The expression of the Wilms' tumour gene, WT1, in the developing mammalian embryo.

Armstrong JF, Pritchard-Jones K, Bickmore WA, Hastie ND, Bard JB

Mechanisms of development. 1993 ; 40 (1-2) : 85-97.

PMID 8382938

Infrequent mutation of the WT1 gene in 77 Wilms' Tumors.

Gessler M, K��nig A, Arden K, Grundy P, Orkin S, Sallan S, Peters C, Ruyle S, Mandell J, Li F

Human mutation. 1994 ; 3 (3) : 212-222.

PMID 8019557

Fine structure analysis of the WT1 gene in sporadic Wilms tumors.

Varanasi R, Bardeesy N, Ghahremani M, Petruzzi MJ, Nowak N, Adam MA, Grundy P, Shows TB, Pelletier J

Proceedings of the National Academy of Sciences of the United States of America. 1994 ; 91 (9) : 3554-3558.

PMID 8170946

Characterization of the genomic breakpoint and chimeric transcripts in the EWS-WT1 gene fusion of desmoplastic small round cell tumor.

Gerald WL, Rosai J, Ladanyi M

Proceedings of the National Academy of Sciences of the United States of America. 1995 ; 92 (4) : 1028-1032.

PMID 7862627

Subnuclear localization of WT1 in splicing or transcription factor domains is regulated by alternative splicing.

Larsson SH, Charlieu JP, Miyagawa K, Engelkamp D, Rassoulzadegan M, Ross A, Cuzin F, van Heyningen V, Hastie ND

Cell. 1995 ; 81 (3) : 391-401.

PMID 7736591

A non-AUG translational initiation event generates novel WT1 isoforms.

Bruening W, Pelletier J

The Journal of biological chemistry. 1996 ; 271 (15) : 8646-8654.

PMID 8621495

A clinical overview of WT1 gene mutations.

Little M, Wells C

Human mutation. 1997 ; 9 (3) : 209-225.

PMID 9090524

Donor splice-site mutations in WT1 are responsible for Frasier syndrome.

Barbaux S, Niaudet P, Gubler MC, Gr��nfeld JP, Jaubert F, Kuttenn F, F��k��t�� CN, Souleyreau-Therville N, Thibaud E, Fellous M, McElreavey K

Nature genetics. 1997 ; 17 (4) : 467-470.

PMID 9398852

Frasier syndrome is caused by defective alternative splicing of WT1 leading to an altered ratio of WT1 +/-KTS splice isoforms.

Klamt B, Koziell A, Poulat F, Wieacker P, Scambler P, Berta P, Gessler M

Human molecular genetics. 1998 ; 7 (4) : 709-714.

PMID 9499425

Internal translation initiation generates novel WT1 protein isoforms with distinct biological properties.

Scharnhorst V, Dekker P, van der Eb AJ, Jochemsen AG

The Journal of biological chemistry. 1999 ; 274 (33) : 23456-23462.

PMID 10438524

REVIEW articles	automatic search in PubMed
Last year publications	automatic search in PubMed

Search in all EBI   NCBI

Contributor(s)

Written	10-1999	Manfred Gessler

Citation

This paper should be referenced as such :

Gessler M . WT1 (Wilms' tumor suppressor gene). Atlas Genet Cytogenet Oncol Haematol. October 1999 . URL : http://AtlasGeneticsOncology.org/Genes/WT1ID78.html

© Atlas of Genetics and Cytogenetics in Oncology and Haematology

indexed on : Thu Nov 27 13:31:23 2008