Gene WT1
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Also known as
Wilms tumor 1, WAGR, WIT-2, WT33Overview
WT1 (Wilms Tumor 1) encodes a zinc finger transcription factor that plays critical roles in urogenital development, cell proliferation, differentiation, and apoptosis. The protein functions as both a transcriptional activator and repressor, regulating the expression of numerous genes involved in kidney development, sex determination, and cellular growth control. WT1 is essential for the normal development of the kidneys, gonads, spleen, and mesothelium.Germline mutations in WT1 are associated with several distinct syndromes, most notably WAGR syndrome (Wilms tumor, Aniridia, Genitourinary abnormalities, and mental Retardation), Denys-Drash syndrome (characterized by kidney disease and ambiguous genitalia), and Frasier syndrome (focal segmental glomerulosclerosis and gonadal dysgenesis). These conditions carry significant risk for Wilms tumor, a pediatric kidney cancer, as well as progressive kidney failure and gonadoblastoma in dysgenetic gonads.
Beyond inherited mutations, somatic WT1 alterations are found in various cancers including leukemias and solid tumors. The gene's role as a tumor suppressor makes genetic testing important for families with a history of Wilms tumor or related syndromes. Early surveillance and intervention can significantly improve outcomes for at-risk individuals.