WT1

Chr 11ADSomatic

WT1 transcription factor

ENSG00000184937 UniProt: P19544

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)

Primary Disease Associations & Inheritance

Wilms tumor, type 1MIM #194070

ADSomatic

Wilms tumorMIM #194070

ADSomatic

Wilms tumor, somaticMIM #194070

Denys-Drash syndromeMIM #194080

ADSomatic

Frasier syndromeMIM #136680

ADSomatic

Meacham syndromeMIM #608978

Mesothelioma, somaticMIM #156240

Nephrotic syndrome, type 4MIM #256370

Wilms tumor, type 1MIM #194070

ADSomatic

UniProtWilms tumor 1

UniProtMesothelioma, malignant

ClinVar variants

Pathogenic / LP

1.00

pLI score· haploinsufficient

Active trials

Clinical Summary— WT1

⚡

Population Constraint (gnomAD)

Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 1.00). One damaged copy is likely sufficient to cause disease.

💊

Clinical Trials

12 active or recruiting trials — potential therapeutic options may be available

Some data sources returned errors (2)

ncbi: Error: NCBI fetch failed: 429 https://eutils.ncbi.nlm.nih.gov/entrez/eutils/esearch.fcgi

clinvarCount: Error: NCBI fetch failed: 429 https://eutils.ncbi.nlm.nih.gov/entrez/eutils/esearch.fcgi

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

LoF intolerant — likely haploinsufficient

LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.

0.25LOEUF

pLI 0.996

Z-score 4.31

OE 0.08 (0.03–0.25)

Highly constrained

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

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.

1.78Z-score

OE missense 0.70 (0.63–0.79)

201 obs / 285.7 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.

LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.08 (0.03–0.25)

0≤0.351.4

Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.70 (0.63–0.79)

0≤0.61.4

Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.00

0≤1.21.6

LoF obs/exp: 2 / 25.5Missense obs/exp: 201 / 285.7Syn Z: -0.03

ClinVar Variant Classifications

0 submitted variants in ClinVar

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.

Gene2Phenotype Curations

WT1-related Wilms tumour

definitive

ADLoss Of FunctionAbsent Gene Product

Cancer

G2P ↗

WT1-related Denys-Drash syndrome

definitive

ADDominant NegativeAltered Gene Product Structure

Dev. Disorders

G2P ↗

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype Relationships

2 OMIM entries

OMIM

WILMS TUMOR 1; WT1

MIM #194070 · #

Wilms tumor, type 1

MIM #194070