WT1 Gene (Wilms Tumor 1): Structure, Function, and Clinical Significance
A comprehensive overview of the WT1 gene, its protein product, associated diseases, expression patterns, and mutation landscape.
Gene Information Card
| Symbol | WT1 |
|---|---|
| Full Name | Wilms tumor 1 |
| Gene Type | Protein coding |
| Chromosomal Location | 11p13 |
| NCBI Gene ID | 7490 ncbi.nlm.nih.gov/gene/7490 |
| Ensembl ID | ENSG00000184937 |
| UniProt ID | P19544 |
| OMIM ID | 607102 |
| HGNC ID | 12796 |
| Aliases | GUD, WAGR, WT33, NPHS4, EWS-WT1 |
Description
The WT1 gene encodes a transcription factor that is essential for normal development of the urogenital system. It contains four zinc finger motifs at the C-terminus and a proline/glutamine-rich DNA-binding domain at the N-terminus. WT1 is involved in cell growth, differentiation, and apoptosis. Mutations in WT1 are associated with Wilms tumor, Denys-Drash syndrome, Frasier syndrome, and other genitourinary anomalies. The gene is also implicated in acute myeloid leukemia and other cancers.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Wilms tumor | Loss-of-function mutations or deletions in WT1 lead to aberrant kidney development and tumorigenesis. | ClinVar, COSMIC |
| Denys-Drash syndrome | Dominant negative mutations in the zinc finger domains disrupt DNA binding, causing severe urogenital anomalies and renal failure. | OMIM, ClinVar |
| Frasier syndrome | Mutations in the donor splice site of intron 9 lead to altered WT1 isoforms, resulting in focal segmental glomerulosclerosis and male pseudohermaphroditism. | OMIM, ClinVar |
| Acute myeloid leukemia | WT1 is overexpressed in many AML cases; mutations can contribute to leukemogenesis. | COSMIC, PubMed |
| Mesothelioma | WT1 is expressed in mesothelial cells and may play a role in tumor progression. | UniProt, PubMed |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Kidney | High | High |
| Testis | Medium | Medium |
| Ovary | Medium | Medium |
| Spleen | Low | Low |
| Bone Marrow | Low | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK293 | High | Embryonic kidney cells |
| K562 | Medium | Leukemia cell line |
| A549 | Low | Lung carcinoma |
| MCF7 | Low | Breast cancer |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1387C>T (p.Arg463Ter) | Nonsense | Rare | Loss of function |
| c.1432G>A (p.Asp478Asn) | Missense | Rare | Dominant negative |
| c.1447+5G>A | Splice site | Rare | Isoform imbalance |
| c.440C>T (p.Pro147Leu) | Missense | Rare | Loss of function |
Mutation functional classification
Loss of Function (LOF)
Mutations that result in truncated or absent protein, leading to haploinsufficiency or complete loss of WT1 activity, often seen in Wilms tumor.
Gain of Function (GOF)
Some mutations may confer oncogenic properties, though less common; overexpression of WT1 in leukemia suggests a potential gain-of-function role.
Dominant Negative (DN)
Mutations in the zinc finger region produce a protein that can bind to DNA but not activate transcription, interfering with the normal allele's function, as seen in Denys-Drash syndrome.
View complete mutation data：
Gene Ontology (GO)
| • DNA binding | • RNA polymerase II transcription factor activity |
| • zinc ion binding | • regulation of transcription by RNA polymerase II |
| • cell differentiation | • apoptosis |
| • kidney development | • urogenital system development |
Pathways
• p53 signaling pathway
• Apoptosis
• Cell cycle
• TGF-beta signaling pathway
• Wnt signaling pathway
Protein Summary
The WT1 protein is a 449-amino acid transcription factor with four C-terminal zinc finger domains and an N-terminal proline/glutamine-rich region. It binds to DNA at the consensus sequence 5'-GCGGGGGCG-3' and regulates the expression of genes involved in cell growth and differentiation. WT1 can also interact with RNA and is involved in mRNA splicing. Alternative splicing generates multiple isoforms with distinct functions. The protein is predominantly nuclear and is critical for kidney and gonad development.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| SWT1 Knockout HEK293 Cell Line | EDJ-KQ1675 | Human | 54823 | Details Get a Quote |
| WT1 Knockout HEK293 Cell Line | EDJ-KQ2401 | Human | 7490 | Details Get a Quote |
| WT1 Knockout A-549 Cell Line | EDJ-KQ21567 | Human | 7490 | Details Get a Quote |
| SWT1 Knockout A-549 Cell Line | EDJ-KQ22773 | Human | 54823 | Details Get a Quote |
| SWT1 Knockout HCT 116 Cell Line | EDJ-KQ22775 | Human | 54823 | Details Get a Quote |
| SWT1 Knockout HeLa Cell Line | EDJ-KQ22776 | Human | 54823 | Details Get a Quote |
| WT1 Knockout HeLa Cell Line | EDJ-KQ54758 | Human | 7490 | Details Get a Quote |
| WT1 Knockout HCT 116 Cell Line | EDJ-KQ71716 | Human | 7490 | Details Get a Quote |
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