WT1

Chr 11

WT1 transcription factor

Also known as: AWT1, GUD, NPHS4, WAGR, WIT-2, WT-1, WT33

This gene encodes 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. Multiple transcript variants have been described. In several variants, there is evidence for the use of a non-AUG (CUG) translation initiation codon upstream of, and in-frame with the first AUG. Authors of PMID:7926762 also provide evidence that WT1 mRNA undergoes RNA editing in human and rat, and that this process is tissue-restricted and developmentally regulated. [provided by RefSeq, Mar 2015]

GeneReviewsResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

UniProtFrasier syndrome
UniProtWilms tumor 1
UniProtDenys-Drash syndrome
UniProtNephrotic syndrome 4

Clinical highlights

Gene-disease validity (ClinGen)
Wilms tumor 1 · ADDefinitivesufficient evidence for diagnostic panels2 gene-disease associations curated in total
Interpreting a novel variant
Loss of function is the curated mechanism (Gene2Phenotype) and the gene is intolerant of it in the population — truncating, frameshift and canonical splice variants carry more prior weight here than missense.Curated gene-level mechanism — a prior for triage, not a per-variant call.
12
Active trials
516
Pubs (1 yr)
P/LP submissions
P/LP missense
0.25
LOEUF· LoF intol.
Multiple*
Mechanism· G2P
📖
GeneReview available — WT1
Authoritative clinical overview · Recommended first read
Open GeneReview ↗
Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

LoF intolerant — likely haploinsufficient
LoF Constraint?
0.25LOEUF
pLI 0.996
Z-score 4.31
OE 0.08 (0.030.25)
Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint?
1.78Z-score
OE missense 0.70 (0.630.79)
201 obs / 285.7 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?
LoF OE?0.08 (0.030.25)
00.351.4
Missense OE?0.70 (0.630.79)
00.61.4
Synonymous OE?1.00
01.21.6
LoF obs/exp: 2 / 25.5Missense obs/exp: 201 / 285.7Syn Z: -0.03

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.

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

Pleuropulmonary BlastomaCystic NephromaOvarian Sertoli-Leydig Cell Tumors

DICER1-related Pleuropulmonary Blastoma Cancer Predisposition Syndrome: A Natural History Study

RECRUITING
NCT01247597National Cancer Institute (NCI)Started 2011-02-13
Advanced Malignant Solid NeoplasmRecurrent Ependymal TumorRecurrent Ewing Sarcoma

Ulixertinib in Treating Patients With Advanced Solid Tumors, Non-Hodgkin Lymphoma, or Histiocytic Disorders With MAPK Pathway Mutations (A Pediatric MATCH Treatment Trial)

ACTIVE NOT RECRUITING
NCT03698994Phase PHASE2National Cancer Institute (NCI)Started 2018-11-14
Pharmacokinetic StudyUlixertinib
Acute LeukemiaAdenomatous PolyposisAdrenocortical Carcinoma

Familial Investigations of Childhood Cancer Predisposition

RECRUITING
NCT03050268St. Jude Children's Research HospitalStarted 2017-04-06
Liver CancerRhabdomyosarcomaMalignant Rhabdoid Tumor

Interleukin-15 and -21 Armored Glypican-3-specific Chimeric Antigen Receptor Expressed in T Cells for Pediatric Solid Tumors

RECRUITING
NCT04715191Phase PHASE1Baylor College of MedicineStarted 2024-05-24
CARE T cells
Ewing SarcomaDesmoplastic Small Round Cell TumorPediatric Cancer

Lurbinectedin in FET-Fused Tumors

RECRUITING
NCT05918640Phase PHASE1, PHASE2Children's Hospital of PhiladelphiaStarted 2023-07-27
Lurbinectedin
Advanced Malignant Solid NeoplasmAnn Arbor Stage III Non-Hodgkin LymphomaAnn Arbor Stage IV Non-Hodgkin Lymphoma

Targeted 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 RECRUITING
NCT03155620Phase PHASE2National Cancer Institute (NCI)Started 2017-07-31
Biopsy ProcedureBiospecimen CollectionBone Marrow Aspiration and Biopsy
Pleuropulmonary BlastomaSertoli-Leydig Cell TumorDICER1 Syndrome

International PPB/DICER1 Registry

RECRUITING
NCT03382158Children's Hospitals and Clinics of MinnesotaStarted 2016-12-06
Glioblastoma

INO-5401 and INO-9012 Delivered by Electroporation (EP) in Combination With Cemiplimab (REGN2810) in Newly-Diagnosed Glioblastoma (GBM)

ACTIVE NOT RECRUITING
NCT03491683Phase PHASE1, PHASE2Inovio PharmaceuticalsStarted 2018-05-31
INO-5401INO-9012Cemiplimab
Rare DisordersUndiagnosed DisordersDisorders of Unknown Prevalence

Rare Disease Patient Registry & Natural History Study - Coordination of Rare Diseases at Sanford

RECRUITING
NCT01793168Sanford HealthStarted 2010-07
Solid TumorsCNS Tumors

Study Of Entrectinib (Rxdx-101) in Children and Adolescents With Locally Advanced Or Metastatic Solid Or Primary CNS Tumors And/Or Who Have No Satisfactory Treatment Options

ACTIVE NOT RECRUITING
NCT02650401Phase PHASE1, PHASE2Hoffmann-La RocheStarted 2016-05-03
Entrectinib
Desmoplastic Small Round Cell TumorSynovial Sarcoma

Pasireotide as Maintenance Treatment in Synovial Sarcoma and Desmoplastic Small Round Cell Tumor

RECRUITING
NCT06456359Phase PHASE2University Hospital HeidelbergStarted 2024-12-19
Signifor
Indirect Inguinal HerniaUndescended Testis

INVESTIGATION OF THE GENETIC ETIOLOGY OF HERNIA SAC DEVELOPMENT IN MALE CHILDREN WITH UNDESCENDED TESTIS AND INGUINAL HERNIA

ACTIVE NOT RECRUITING
NCT07586332Trakya UniversityStarted 2025-09-09