WT1

WT1 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 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.

Wilms Tumor 1

Transcription factor that plays an important role in cellular development and cell survival (PubMed:7862533).
Recognizes and binds to the DNA sequence 5'-GCG(T/G)GGGCG-3' (PubMed:7862533, PubMed:17716689, PubMed:25258363).
Regulates the expression of numerous target genes, including EPO. Plays an essential role for development of the urogenital system. It has a tumor suppressor as well as an oncogenic role in tumor formation. Function may be isoform-specific: isoforms lacking the KTS motif may act as transcription factors (PubMed:15520190).
Isoforms containing the KTS motif may bind mRNA and play a role in mRNA metabolism or splicing (PubMed:16934801).
Isoform 1 has lower affinity for DNA, and can bind RNA (PubMed:19123921).

Biological Process adrenal cortex formation Source:UniProtKB
Biological Process adrenal gland development Source:UniProtKB1 Publication
Biological Process branching involved in ureteric bud morphogenesis Source:UniProtKB1 Publication
Biological Process camera-type eye development Source:UniProtKB
Biological Process cardiac muscle cell fate commitment Source:BHF-UCL
Biological Process cellular response to cAMP Source:UniProtKB1 Publication
Biological Process cellular response to gonadotropin stimulus Source:UniProtKB1 Publication
Biological Process diaphragm development Source:UniProtKB
Biological Process epithelial cell differentiation Source:UniProtKB
Biological Process germ cell development Source:UniProtKB
Biological Process glomerular basement membrane development Source:UniProtKB1 Publication
Biological Process glomerulus development Source:UniProtKB1 Publication
Biological Process gonad development Source:UniProtKB
Biological Process heart development Source:UniProtKB1 Publication
Biological Process kidney development Source:UniProtKB1 Publication
Biological Process male genitalia development Source:UniProtKB
Biological Process male gonad development Source:UniProtKB1 Publication
Biological Process mesenchymal to epithelial transition Source:UniProtKB
Biological Process metanephric epithelium development Source:UniProtKB1 Publication
Biological Process metanephric mesenchyme development Source:UniProtKB
Biological Process metanephric S-shaped body morphogenesis Source:UniProtKB1 Publication
Biological Process negative regulation of apoptotic process Source:UniProtKB1 Publication
Biological Process negative regulation of cell growth Source:UniProtKB2 Publications
Biological Process negative regulation of cell population proliferation Source:UniProtKB2 Publications
Biological Process negative regulation of DNA-templated transcription Source:UniProtKB7 Publications
Biological Process negative regulation of female gonad development Source:UniProtKB
Biological Process negative regulation of metanephric glomerular mesangial cell proliferation Source:UniProtKB
Biological Process negative regulation of transcription by RNA polymerase II Source:MGI1 Publication
Biological Process negative regulation of translation Source:UniProtKB
Biological Process podocyte differentiation Source:UniProtKB
Biological Process positive regulation of apoptotic process Source:UniProtKB
Biological Process positive regulation of DNA methylation Source:ARUK-UCL1 Publication
Biological Process positive regulation of DNA-templated transcription Source:UniProtKB8 Publications
Biological Process positive regulation of gene expression Source:ARUK-UCL1 Publication
Biological Process positive regulation of heart growth Source:UniProtKB
Biological Process positive regulation of male gonad development Source:UniProtKB
Biological Process positive regulation of metanephric ureteric bud development Source:UniProtKB
Biological Process positive regulation of miRNA transcription Source:ARUK-UCL1 Publication
Biological Process positive regulation of transcription by RNA polymerase II Source:ARUK-UCL1 Publication
Biological Process posterior mesonephric tubule development Source:UniProtKB
Biological Process regulation of animal organ formation Source:UniProtKB
Biological Process regulation of DNA-templated transcription Source:UniProtKB
Biological Process regulation of transcription by RNA polymerase II Source:UniProtKB
Biological Process RNA splicing Source:UniProtKB
Biological Process sex determination Source:UniProtKB1 Publication
Biological Process thorax and anterior abdomen determination Source:UniProtKB
Biological Process tissue development Source:UniProtKB
Biological Process ureteric bud development Source:UniProtKB
Biological Process vasculogenesis Source:UniProtKB
Biological Process visceral serous pericardium development Source:UniProtKB1 Publication

Nucleus
Nucleus, nucleolus
Cytoplasm
Isoforms lacking the KTS motif have a diffuse nuclear location (PubMed:15520190).
Shuttles between nucleus and cytoplasm
Isoform 1
Nucleus speckle
Isoform 4
Nucleus, nucleoplasm

Frasier syndrome (FS):
Characterized by a slowly progressing nephropathy leading to renal failure in adolescence or early adulthood, male pseudohermaphroditism, and no Wilms tumor. As for histological findings of the kidneys, focal glomerular sclerosis is often observed. There is phenotypic overlap with Denys-Drash syndrome. Inheritance is autosomal dominant.
Wilms tumor 1 (WT1):
Embryonal malignancy of the kidney that affects approximately 1 in 10'000 infants and young children. It occurs both in sporadic and hereditary forms.
Denys-Drash syndrome (DDS):
Typical nephropathy characterized by diffuse mesangial sclerosis, genital abnormalities, and/or Wilms tumor. There is phenotypic overlap with WAGR syndrome and Frasier syndrome. Inheritance is autosomal dominant, but most cases are sporadic.
Nephrotic syndrome 4 (NPHS4):
A form of nephrotic syndrome, a renal disease clinically characterized by severe proteinuria, resulting in complications such as hypoalbuminemia, hyperlipidemia and edema. Kidney biopsies show non-specific histologic changes such as focal segmental glomerulosclerosis and diffuse mesangial proliferation. Some affected individuals have an inherited steroid-resistant form and progress to end-stage renal failure. Most patients with NPHS4 show diffuse mesangial sclerosis on renal biopsy, which is a pathologic entity characterized by mesangial matrix expansion with no mesangial hypercellularity, hypertrophy of the podocytes, vacuolized podocytes, thickened basement membranes, and diminished patency of the capillary lumen.
Meacham syndrome (MEACHS):
Rare sporadically occurring multiple malformation syndrome characterized by male pseudohermaphroditism with abnormal internal female genitalia comprising a uterus and double or septate vagina, complex congenital heart defect and diaphragmatic abnormalities.
Mesothelioma, malignant (MESOM):
An aggressive neoplasm of the serosal lining of the chest. It appears as broad sheets of cells, with some regions containing spindle-shaped, sarcoma-like cells and other regions showing adenomatous patterns. Pleural mesotheliomas have been linked to exposure to asbestos.