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Wilms Tumor Protein

Domain

Binds to DNA motifs with the sequence 5'-GCG(T/G)GGGCG-3' via its C2H2-type zinc fingers. Starting from the N-terminus, the second zinc finger binds to the 3'-GCG motif, the middle zinc finger interacts with the central TGG motif, and the C-terminal zinc finger binds to the 5'-GCG motif. Binds double-stranded target DNA, irrespective of the cytosine methylation status. Has reduced affinity for target DNA where the cytosines have been oxidized to 5-hydroxymethylcytosine, 5-formylcytosine or 5-carboxylcytosine.

The 9aaTAD motif is a transactivation domain present in a large number of yeast and animal transcription factors.

Function

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:17716689, PubMed:25258363, PubMed:7862533). 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).

Involvement in disease

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.

None

The disease is caused by variants affecting the gene represented in this entry.

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.

None

The disease is caused by variants affecting the gene represented in this entry.

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.

None

The disease is caused by variants affecting the gene represented in this entry.

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.

None

The disease is caused by variants affecting the gene represented in this entry.

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.

None

The disease is caused by variants affecting the gene represented in this entry.

A chromosomal aberration involving WT1 may be a cause of desmoplastic small round cell tumor (DSRCT). Translocation t(11;22)(p13;q12) with EWSR1.

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.

None

The disease may be caused by variants affecting the gene represented in this entry.

Sequence similarities

Belongs to the EGR C2H2-type zinc-finger protein family.

Tissue specificity

Expressed in the kidney and a subset of hematopoietic cells.

Cellular localization

  • 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

Alternative names

Wilms tumor protein, WT33, WT1

Target type

Proteins

Primary research area

Immuno-oncology

Molecular weight

49188Da

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