ArticleNucleic acids research2000
Naturally occurring mutations in the human HNF4alpha gene impair the function of the transcription factor to a varying degree.
Article in Nucleic acids research, 2000. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed, 76 citations in OpenAlex.
- PXR, CAR and HNF4alpha genotypes and their association with pharmacokinetics and pharmacodynamics of docetaxel and doxorubicin in Asian patients.The pharmacogenomics journal · 2008Trial
- SAMHD1 depletion restricts SARS-CoV-2 infection by suppressing HNF1-dependent ACE2 expression in lung epithelial cells.PLoS pathogens · 2026Article
- SAMHD1 promotes SARS-CoV-2 infection by enhancing HNF1-dependent ACE2 expression in lung epithelial cells.bioRxiv : the preprint server for biology · 2025Article
- Mitogen-Activated Protein Kinase and Exploratory Nuclear Receptor Crosstalk in Cancer Immunotherapy.International journal of molecular sciences · 2023Review
- Expanding the p.(Arg85Trp) Variant-Specific Phenotype of HNF4A: Features of Glycogen Storage Disease, Liver Cirrhosis, Impaired Mitochondrial Function, and Glomerular Changes.Molecular syndromology · 2023Article
- Insights into the Genetics and Signaling Pathways in Maturity-Onset Diabetes of the Young.International journal of molecular sciences · 2022Review
- Therapeutic Potential of HNF4α in End-stage Liver Disease.Organogenesis · 2021Review
- Modeling different types of diabetes using human pluripotent stem cells.Cellular and molecular life sciences : CMLS · 2021Review
- HNF4A Haploinsufficiency in MODY1 Abrogates Liver and Pancreas Differentiation from Patient-Derived Induced Pluripotent Stem Cells.iScience · 2019Article
- Novel mechanisms of regulation of the expression and transcriptional activity of hepatocyte nuclear factor 4α.Journal of cellular biochemistry · 2019Article
- Expression of mutant mRNA and protein in pancreatic cells derived from MODY3- iPS cells.PloS one · 2019Article
- The Common p.R114W HNF4A Mutation Causes a Distinct Clinical Subtype of Monogenic Diabetes.Diabetes · 2016Article
- Digenic heterozygous HNF1A and HNF4A mutations in two siblings with childhood-onset diabetes.Pediatric diabetes · 2013Article
- A systematic analysis of the 3'UTR of HNF4A mRNA reveals an interplay of regulatory elements including miRNA target sites.PloS one · 2011Article
- Pathway-Targeted Pharmacogenomics of CYP1A2 in Human Liver.Frontiers in pharmacology · 2010Article
- DAX-1 acts as a novel corepressor of orphan nuclear receptor HNF4alpha and negatively regulates gluconeogenic enzyme gene expression.The Journal of biological chemistry · 2009Article
- Hepatocyte nuclear factor 4alpha regulation of bile acid and drug metabolism.Expert opinion on drug metabolism & toxicology · 2009Review
- Molecular cloning and characterization of the human PED/PEA-15 gene promoter reveal antagonistic regulation by hepatocyte nuclear factor 4alpha and chicken ovalbumin upstream promoter transcription factor II.The Journal of biological chemistry · 2008Article
- Crystallization of hepatocyte nuclear factor 4 alpha (HNF4 alpha) in complex with the HNF1 alpha promoter element.Acta crystallographica. Section F, Structural biology and crystallization communications · 2008Article
- HNF4alpha reduces proliferation of kidney cells and affects genes deregulated in renal cell carcinoma.Oncogene · 2005Article
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The hepatocyte nuclear factor (HNF)4alpha, a member of the nuclear receptor superfamily, regulates genes that play a critical role in embryogenesis and metabolism. Recent studies have shown that mutations in the human HNF4alpha gene cause a rare form of type 2 diabetes, maturity onset diabetes of the young (MODY1). To investigate the properties of these naturally occurring HNF4alpha mutations we analysed five MODY1 mutations (R154X, R127W, V255M, Q268X and E276Q) and one other mutation (D69A), which we found in HepG2 hepatoma cells. Activation of reporter genes in transfection assays and DNA binding studies showed that the MODY1-associated mutations result in a variable reduction in function, whereas the D69A mutation showed an increased activity on some promoters. None of the MODY mutants acted in a dominant negative manner, thus excluding inactivation of the wild-type factor as a critical event in MODY development. A MODY3-associated mutation in the HNF1alpha gene, a well-known target gene of HNF4alpha, results in a dramatic loss of the HNF4 binding site in the promoter, indicating that mutations in the HNF4alpha gene might cause MODY through impaired HNF1alpha gene function. Based on these data we propose a two-hit model for MODY development.
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