Wilms Tumor Protein (WT1)

WAGR; GUD; WIT-2; WT33

SPN	R686
HGNC	12796
MGI	98968
PubMed	22215675
RGD	3974
UniProt	P19544
Wiki	WT1

Wilms tumor protein is 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 subset of patients with Wilms' tumor, the gene's namesake. Multiple transcript variants, resulting from alternative splicing at two coding exons, have been well characterized. There is also evidence for the use of non-AUG (CUG) translation initiation site upstream of, and in-frame with the first AUG, leading to additional isoforms.WT1 mRNA undergoes RNA editing in human and rat, and that this process is tissue-restricted and developmentally regulated.The WT1 protein has been found to bind a host of cellular factors, e.g. p53, a known tumor suppressor.

Reference

"Homozygous deletion in Wilms tumours of a zinc-finger gene identified by chromosome jumping."
Nature 343:774-778(1990) [PubMed] [Europe PMC] [Abstract]

"Alternative splicing and genomic structure of the Wilms tumor gene WT1."
Proc. Natl. Acad. Sci. U.S.A. 88:9618-9622(1991) [PubMed] [Europe PMC] [Abstract]

"The genomic organization and expression of the WT1 gene."
Genomics 12:807-813(1992) [PubMed] [Europe PMC] [Abstract]

"Complete sequencing and characterization of 21,243 full-length human cDNAs."
Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]

"Human chromosome 11 DNA sequence and analysis including novel gene identification."
Nature 440:497-500(2006) [PubMed] [Europe PMC] [Abstract]

"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]

"Isolation and characterization of a zinc finger polypeptide gene at the human chromosome 11 Wilms' tumor locus."
Cell 60:509-520(1990) [PubMed] [Europe PMC] [Abstract]

"High affinity binding sites for the Wilms' tumour suppressor protein WT1."
Nucleic Acids Res. 23:277-284(1995) [PubMed] [Europe PMC] [Abstract]

"Germline mutations in the Wilms' tumor suppressor gene are associated with abnormal urogenital development in Denys-Drash syndrome."
Cell 67:437-447(1991) [PubMed] [Europe PMC] [Abstract]

"Germline intronic and exonic mutations in the Wilms' tumour gene (WT1) affecting urogenital development."
Nat. Genet. 1:144-148(1992) [PubMed] [Europe PMC] [Abstract]

"Isolation, characterization, and expression of the murine Wilms' tumor gene (WT1) during kidney development."
Mol. Cell. Biol. 11:1707-1712(1991) [PubMed] [Europe PMC] [Abstract]

"RNA editing in the Wilms' tumor susceptibility gene, WT1."
Genes Dev. 8:720-731(1994) [PubMed] [Europe PMC] [Abstract]

"A non-AUG translational initiation event generates novel WT1 isoforms."
J. Biol. Chem. 271:8646-8654(1996) [PubMed] [Europe PMC] [Abstract]

"Identification of WTAP, a novel Wilms' tumour 1-associating protein."
Hum. Mol. Genet. 9:2231-2239(2000) [PubMed] [Europe PMC] [Abstract]

"Inhibition of Wilms tumor 1 transactivation by bone marrow zinc finger 2, a novel transcriptional repressor."
J. Biol. Chem. 277:44826-44837(2002) [PubMed] [Europe PMC] [Abstract]

"Transcriptional activity of testis-determining factor SRY is modulated by the Wilms' tumor 1 gene product, WT1."
Oncogene 22:7900-7904(2003) [PubMed] [Europe PMC] [Abstract]

"WT1: a novel tumor suppressor gene inactivated in Wilms' tumor."
New Biol. 4:97-106(1992) [PubMed] [Europe PMC] [Abstract]

"The WT1 Wilms tumor gene product: a developmentally regulated transcription factor in the kidney that functions as a tumor suppressor."
FASEB J. 7:896-903(1993) [PubMed] [Europe PMC] [Abstract]

"WT1 mutations contribute to abnormal genital system development and hereditary Wilms' tumour."
Nature 353:431-434(1991) [PubMed] [Europe PMC] [Abstract]

"A tumor suppressor and oncogene: the WT1 story."
Leukemia 21:868-876(2007) [PubMed] [Europe PMC] [Abstract]

"SUMO-1 modification of the Wilms' tumor suppressor WT1."
Cancer Res. 64:7846-7851(2004) [PubMed] [Europe PMC] [Abstract]

"WT1 interacts with the splicing protein RBM4 and regulates its ability to modulate alternative splicing in vivo."
Exp. Cell Res. 312:3379-3388(2006) [PubMed] [Europe PMC] [Abstract]

"Contribution of individual amino acids to the RNA binding activity of the Wilms' tumor suppressor protein WT1."
Biochemistry 48:148-155(2009) [PubMed] [Europe PMC] [Abstract]

"The tumor suppressor WTX shuttles to the nucleus and modulates WT1 activity."
Proc. Natl. Acad. Sci. U.S.A. 106:8338-8343(2009) [PubMed] [Europe PMC] [Abstract]

"Why zinc fingers prefer zinc: ligand-field symmetry and the hidden thermodynamics of metal ion selectivity."
Biochemistry 43:13910-13925(2004) [PubMed] [Europe PMC] [Abstract]

"Structure of the Wilms tumor suppressor protein zinc finger domain bound to DNA."
J. Mol. Biol. 372:1227-1245(2007) [PubMed] [Europe PMC] [Abstract]

"Zinc finger point mutations within the WT1 gene in Wilms tumor patients."
Proc. Natl. Acad. Sci. U.S.A. 89:4791-4795(1992) [PubMed] [Europe PMC] [Abstract]

"Constitutional mutations in the WT1 gene in patients with Denys-Drash syndrome."
Hum. Mol. Genet. 1:301-305(1992) [PubMed] [Europe PMC] [Abstract]

"Evidence that WT1 mutations in Denys-Drash syndrome patients may act in a dominant-negative fashion."
Hum. Mol. Genet. 2:259-264(1993) [PubMed] [Europe PMC] [Abstract]

"A novel zinc finger mutation in a patient with Denys-Drash syndrome."
Hum. Mol. Genet. 2:2193-2194(1993) [PubMed] [Europe PMC] [Abstract]

"Molecular analysis of two Japanese cases of Denys-Drash syndrome."
J. Inherit. Metab. Dis. 16:876-880(1993) [PubMed] [Europe PMC] [Abstract]

"Mutational screening of the Wilms's tumour gene, WT1, in males with genital abnormalities."
J. Med. Genet. 30:767-772(1993) [PubMed] [Europe PMC] [Abstract]

"The Wilms tumour gene WT1 is expressed in murine mesoderm-derived tissues and mutated in a human mesothelioma."
Nat. Genet. 4:415-420(1993) [PubMed] [Europe PMC] [Abstract]

"WT1 mutations in patients with Denys-Drash syndrome: a novel mutation in exon 8 and paternal allele origin."
Hum. Genet. 93:115-120(1994) [PubMed] [Europe PMC] [Abstract]

"A newly identified exonic mutation of the WT1 gene in a patient with Denys-Drash syndrome."
Acta Paediatr. Jpn. Overseas Ed. 38:265-266(1996) [PubMed] [Europe PMC] [Abstract]

"A novel mutation H373Y in the Wilms' tumor suppressor gene, WT1, associated with Denys-Drash syndrome."
Hum. Hered. 46:336-338(1996) [PubMed] [Europe PMC] [Abstract]

"Correlation of germ-line mutations and two-hit inactivation of the WT1 gene with Wilms tumors of stromal-predominant histology."
Proc. Natl. Acad. Sci. U.S.A. 94:3972-3977(1997) [PubMed] [Europe PMC] [Abstract]

"Identification of constitutional WT1 mutations, in patients with isolated diffuse mesangial sclerosis, and analysis of genotype/phenotype correlations by use of a computerized mutation database."
Am. J. Hum. Genet. 62:824-833(1998) [PubMed] [Europe PMC] [Abstract]

"Do intronic mutations affecting splicing of WT1 exon 9 cause Frasier syndrome?"
J. Med. Genet. 35:45-48(1998) [PubMed] [Europe PMC] [Abstract]

"Spectrum of early onset nephrotic syndrome associated with WT1 missense mutations."
Kidney Int. 53:1594-1600(1998) [PubMed] [Europe PMC] [Abstract]

"Exon 9 mutations in the WT1 gene, without influencing KTS splice isoforms, are also responsible for Frasier syndrome."
Hum. Mutat. 14:466-470(1999) [PubMed] [Europe PMC] [Abstract]

"Novel WT1 exon 9 mutation (D396Y) in a patient with early onset Denys Drash syndrome."
Hum. Mutat. 15:389-389(2000) [PubMed] [Europe PMC] [Abstract]

"Constitutional WT1 correlate with clinical features in children with progressive nephropathy."
J. Med. Genet. 37:698-701(2000) [PubMed] [Europe PMC] [Abstract]

"A novel missense mutation of the WT1 gene causing Denys-Drash syndrome with exceptionally mild renal manifestations."
J. Urol. 163:1857-1858(2000) [PubMed] [Europe PMC] [Abstract]

"Novel WT1 mutation (C388Y) in a female child with Denys-Drash syndrome."
Pediatr. Nephrol. 16:627-630(2001) [PubMed] [Europe PMC] [Abstract]

"Twenty-four new cases of WT1 germline mutations and review of the literature: genotype/phenotype correlations for Wilms tumor development."
Am. J. Med. Genet. A 127:249-257(2004) [PubMed] [Europe PMC] [Abstract]

"Mutation analysis of five candidate genes in Chinese patients with hypospadias."
Eur. J. Hum. Genet. 12:706-712(2004) [PubMed] [Europe PMC] [Abstract]

"Prevalence of WT1 mutations in a large cohort of patients with steroid-resistant and steroid-sensitive nephrotic syndrome."
Kidney Int. 66:564-570(2004) [PubMed] [Europe PMC] [Abstract]

"A novel mutation of WT1 exon 9 in a patient with Denys-Drash syndrome and pyloric stenosis."
Pediatr. Nephrol. 19:1160-1163(2004) [PubMed] [Europe PMC] [Abstract]

"WT1 mutations in Meacham syndrome suggest a coelomic mesothelial origin of the cardiac and diaphragmatic malformations."
Am. J. Med. Genet. A 143:2312-2320(2007) [PubMed] [Europe PMC] [Abstract]