WT1
Chr 11ADSomaticWT1 transcription factor
Also known as: AWT1, GUD, NPHS4, WAGR, WIT-2, WT-1, WT33
The WT1 protein is a transcription factor with four zinc-finger motifs that is essential for normal urogenital system development. Mutations cause Denys-Drash syndrome, Frasier syndrome, Meacham syndrome, and nephrotic syndrome type 4 through an autosomal dominant inheritance pattern, while somatic mutations can lead to Wilms tumor. The pathogenic mechanism involves loss of function of this critical developmental transcription factor.
Definitive — sufficient evidence for diagnostic panels
2 total gene-disease associations curated
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Highly LoF-intolerant (top ~10% of genes)
Mild missense constraint
This gene has evidence for multiple mechanisms of pathogenicity (loss-of-function, dominant-negative and gain-of-function). Both the Badonyi & Marsh prediction and the broader genomic evidence point to loss-of-function as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.
Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.
Literature Evidence
Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.
ClinVar Variant Classifications
0 submitted variants in ClinVar
Protein Context — Lollipop Plot
WT1 · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
3D Protein StructureAlphaFold
External Resources
Links to major genomics databases and tools
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
Selpercatinib for the Treatment of Advanced Solid Tumors, Lymphomas, or Histiocytic Disorders With Activating RET Gene Alterations, a Pediatric MATCH Treatment Trial
ACTIVE NOT RECRUITINGINO-5401 and INO-9012 Delivered by Electroporation (EP) in Combination With Cemiplimab (REGN2810) in Newly-Diagnosed Glioblastoma (GBM)
ACTIVE NOT RECRUITINGFamilial Investigations of Childhood Cancer Predisposition
RECRUITINGInternational PPB/DICER1 Registry
RECRUITINGLurbinectedin in FET-Fused Tumors
RECRUITINGTipifarnib for the Treatment of Advanced Solid Tumors, Lymphoma, or Histiocytic Disorders With HRAS Gene Alterations, a Pediatric MATCH Treatment Trial
ACTIVE NOT RECRUITINGRole of Finerenone in African American Veterans With Diabetic Kidney Disease
NOT YET RECRUITINGInterleukin-15 Armored Glypican 3-specific Chimeric Antigen Receptor Expressed in Autologous T Cells for Solid Tumors
ACTIVE NOT RECRUITINGRare Disease Patient Registry & Natural History Study - Coordination of Rare Diseases at Sanford
RECRUITINGAdministration of Donor Multi TAA-Specific T Cells for AML or MDS (ADSPAM)
ACTIVE NOT RECRUITINGInterleukin-15 Armored Glypican 3-specific Chimeric Antigen Receptor Expressed in T Cells for Pediatric Solid Tumors
ACTIVE NOT RECRUITINGTargeted Therapy Directed by Genetic Testing in Treating Pediatric Patients With Relapsed or Refractory Advanced Solid Tumors, Non-Hodgkin Lymphomas, or Histiocytic Disorders (The Pediatric MATCH Screening Trial)
ACTIVE NOT RECRUITINGExternal Resources
Links to major genomics databases and tools