HNF1B Transcription Factor: Key Regulator in Renal Physiology and Pathogenesis

• Published in: International journal of molecular sciences Vol. 25; no. 19; p. 10609
• Main Authors: Sánchez-Cazorla, Eloísa, Carrera, Noa, García-González, Miguel Ángel
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 01.10.2024; MDPI
• Subjects: 17q12 region; Animals; apico-basal polarity; Cysts; Development and progression; Diabetes; Electrolytes; Gene expression; gene expression regulation; Genetic aspects; Genotype & phenotype; Health aspects; Hepatocyte Nuclear Factor 1-beta - genetics; Hepatocyte Nuclear Factor 1-beta - metabolism; HNF1B; Humans; Kidney - metabolism; Kidney - pathology; Kidney diseases; Kidney Diseases - etiology; Kidney Diseases - genetics; Kidney Diseases - metabolism; Kidney Diseases - pathology; Kidneys; Liver; Mutation; nephrogenesis; Patients; Physiological aspects; Physiology; Postpartum period; Proteins; renal physiology; Review; Transcription factors; Spain; gene expression regulation; nephrogenesis; cyst formation; renal physiology; intrarenal metabolism; renal ion transport; apico-basal polarity; cilia development; 17q12 region; HNF1B
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms251910609

The gene, located on chromosome 17q12, encodes a transcription factor essential for the development of several organs. It regulates the expression of multiple genes in renal, pancreatic, hepatic, neurological, and genitourinary tissues during prenatal and postnatal development, influencing processes such as nephrogenesis, cellular polarity, tight junction formation, cilia development, ion transport in the renal tubule, and renal metabolism. Mutations that alter the function of Hnf1b deregulate those processes, leading to various pathologies characterized by both renal and extrarenal manifestations. The main renal diseases that develop are polycystic kidney disease, hypoplastic or dysplastic kidneys, structural abnormalities, Congenital Anomalies of the Kidney and Urinary Tract (CAKUT), and electrolyte imbalances such as hyperuricemia and hypomagnesemia. Extrarenal manifestations include Maturity-Onset Diabetes of the Young (MODY), hypertransaminasemia, genital and urinary tract malformations, Autism Spectrum Disorder (ASD), and other neurodevelopmental disorders. Patients with alterations typically carry either punctual mutations or a monoallelic microdeletion in the 17q12 region. Future research on the molecular mechanisms and genotype-phenotype correlations in -related conditions will enhance our understanding, leading to improved clinical management, genetic counseling, monitoring, and patient care.