{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,28]],"date-time":"2026-10-28T02:49:58Z","timestamp":1793155798205,"version":"4.5.0"},"reference-count":134,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,3,1]],"date-time":"2022-03-01T00:00:00Z","timestamp":1646092800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Endocrinol."],"abstract":"<jats:p>Diabetes, a disease characterized by hyperglycemia, has a serious impact on the lives and families of patients as well as on society. Diabetes is a group of highly heterogeneous metabolic diseases that can be classified as type 1 diabetes (T1D), type 2 diabetes (T2D), gestational diabetes mellitus (GDM), or other according to the etiology. The clinical manifestations are more or less similar among the different types of diabetes, and each type is highly heterogeneous due to different pathogenic factors. Therefore, distinguishing between various types of diabetes and defining their subtypes are major challenges hindering the precise treatment of the disease. T2D is the main type of diabetes in humans as well as the most heterogeneous. Fortunately, some studies have shown that variants of certain genes involved in monogenic diabetes also increase the risk of T2D. We hope this finding will enable breakthroughs regarding the pathogenesis of T2D and facilitate personalized treatment of the disease by exploring the function of the signal genes involved. Hepatocyte nuclear factor 1 homeobox A (HNF1\u03b1) is widely expressed in pancreatic \u03b2 cells, the liver, the intestines, and other organs. HNF1\u03b1 is highly polymorphic, but lacks a mutation hot spot. Mutations can be found at any site of the gene. Some single nucleotide polymorphisms (SNPs) cause maturity-onset diabetes of the young type 3 (MODY3) while some others do not cause MODY3 but increase the susceptibility to T2D or GDM. The phenotypes of MODY3 caused by different SNPs also differ. MODY3 is among the most common types of MODY, which is a form of monogenic diabetes mellitus caused by a single gene mutation. Both T2D and GDM are multifactorial diseases caused by both genetic and environmental factors. Different types of diabetes mellitus have different clinical phenotypes and treatments. This review focuses on HNF1\u03b1 gene polymorphisms, HNF1A-MODY3, HNF1A-associated T2D and GDM, and the related pathogenesis and treatment methods. We hope this review will provide a valuable reference for the precise and individualized treatment of diabetes caused by abnormal HNF1\u03b1 by summarizing the clinical heterogeneity of blood glucose abnormalities caused by HNF1\u03b1 mutation.<\/jats:p>","DOI":"10.3389\/fendo.2022.829565","type":"journal-article","created":{"date-parts":[[2022,3,1]],"date-time":"2022-03-01T05:36:10Z","timestamp":1646112970000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":63,"title":["HNF1A\uff1aFrom Monogenic Diabetes to Type 2 Diabetes and Gestational Diabetes Mellitus"],"prefix":"10.3389","volume":"13","author":[{"given":"Li-Mei","family":"Li","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bei-Ge","family":"Jiang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liang-Liang","family":"Sun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2022,3,1]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1016\/j.diabres.2019.107843","article-title":"Global and Regional Diabetes Prevalence Estimates for 2019 and Projections for 2030 and 2045: Results From the International Diabetes Federation Diabetes Atlas, 9(Th) Edition","volume":"157","author":"Saeedi","year":"2019","journal-title":"Diabetes Res Clin Pract"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1016\/S2213-8587(17)30097-9","article-title":"The Global Economic Burden of Diabetes in Adults Aged 20-79 Years: A Cost-of-Illness Study","volume":"5","author":"Bommer","year":"2017","journal-title":"Lancet Diabetes Endocrinol"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.2337\/dc14-S081","article-title":"Diagnosis and Classification of Diabetes Mellitus","year":"2014","journal-title":"Diabetes Care"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1007\/s00125-020-05211-7","article-title":"The Clinical Consequences of Heterogeneity Within and Between Different Diabetes Types","volume":"63","author":"Redondo","year":"2020","journal-title":"Diabetologia"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1210\/er.2019-00088","article-title":"Genetic Risk Scores for Diabetes Diagnosis and Precision Medicine","volume":"40","author":"Udler","year":"2019","journal-title":"Endocr Rev"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1007\/s00125-017-4226-2","article-title":"Precision Diabetes: Learning From Monogenic Diabetes","volume":"60","author":"Hattersley","year":"2017","journal-title":"Diabetologia"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1007\/s00125-013-3119-2","article-title":"De Novo Mutations of GCK, HNF1A and HNF4A may be More Frequent in MODY Than Previously Assumed","volume":"57","author":"Stanik","year":"2014","journal-title":"Diabetologia"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1210\/clinem\/dgab545","article-title":"Toward an Improved Classification of Type 2 Diabetes: Lessons From Research Into the Heterogeneity of a Complex Disease","volume":"106","author":"Redondo","year":"2021","journal-title":"J Clin Endocrinol Metab"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1038\/384455a0","article-title":"Mutations in the Hepatocyte Nuclear Factor-1alpha Gene in Maturity-Onset Diabetes of the Young (MODY3)","volume":"384","author":"Yamagata","year":"1996","journal-title":"Nature"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0007855","article-title":"Species-Specific Differences in the Expression of the HNF1A, HNF1B and HNF4A Genes","volume":"4","author":"Harries","year":"2009","journal-title":"PloS One"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1126\/science.277.5322.109","article-title":"Modulation of Hepatic Gene Expression by Hepatocyte Nuclear Factor 1","volume":"277","author":"Ktistaki","year":"1997","journal-title":"Science"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1038\/86871","article-title":"Hepatocyte Nuclear Factor-1alpha is an Essential Regulator of Bile Acid and Plasma Cholesterol Metabolism","volume":"27","author":"Shih","year":"2001","journal-title":"Nat Genet"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1194\/jlr.M600082-JLR200","article-title":"Transcriptional Regulation of the Human Hepatic Lipase (LIPC) Gene Promoter","volume":"47","author":"Rufibach","year":"2006","journal-title":"J Lipid Res"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.241349398","article-title":"A Transcription Factor Regulatory Circuit in Differentiated Pancreatic Cells","volume":"98","author":"Boj","year":"2001","journal-title":"Proc Natl Acad Sci USA"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1093\/emboj\/19.16.4257","article-title":"Molecular Targets of a Human HNF1 Alpha Mutation Responsible for Pancreatic Beta-Cell Dysfunction","volume":"19","author":"Wang","year":"2000","journal-title":"EMBO J"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1210\/me.2008-0274","article-title":"Increased Insulin Sensitivity in Mice Lacking Collectrin, a Downstream Target of HNF-1alpha","volume":"23","author":"Malakauskas","year":"2009","journal-title":"Mol Endocrinol"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1038\/nature19057","article-title":"Analysis of Protein-Coding Genetic Variation in 60,706 Humans","volume":"536","author":"Lek","year":"2016","journal-title":"Nature"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1002\/humu.20357","article-title":"Mutations in the Genes Encoding the Transcription Factors Hepatocyte Nuclear Factor 1 Alpha (HNF1A) and 4 Alpha (HNF4A) in Maturity-Onset Diabetes of the Young","volume":"27","author":"Ellard","year":"2006","journal-title":"Hum Mutat"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1002\/humu.22279","article-title":"Mutations in the Genes Encoding the Transcription Factors Hepatocyte Nuclear Factor 1 Alpha and 4 Alpha in Maturity-Onset Diabetes of the Young and Hyperinsulinemic Hypoglycemia","volume":"34","author":"Colclough","year":"2013","journal-title":"Hum Mutat"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1016\/s0378-1119(03)00670-x","article-title":"Investigating Single Nucleotide Polymorphism (SNP) Density in the Human Genome and its Implications for Molecular Evolution","volume":"312","author":"Zhao","year":"2003","journal-title":"Gene"},{"key":"B21","doi-asserted-by":"publisher","first-page":"288","DOI":"10.3390\/jcm9010288","article-title":"Maturity-Onset Diabetes of the Young (MODY) in Portugal: Novel GCK, HNFA1 and HNFA4 Mutations","volume":"9","author":"Alvelos","year":"2020","journal-title":"J Clin Med"},{"key":"B22","doi-asserted-by":"publisher","first-page":"996","DOI":"10.1038\/nsmb.1658","article-title":"Nucleosome Positioning as a Determinant of Exon Recognition","volume":"16","author":"Tilgner","year":"2009","journal-title":"Nat Struct Mol Biol"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1111\/j.1742-4658.2009.07520.x","article-title":"Alternative Splicing: Role of Pseudoexons in Human Disease and Potential Therapeutic Strategies","volume":"277","author":"Dhir","year":"2010","journal-title":"FEBS J"},{"key":"B24","doi-asserted-by":"publisher","first-page":"50","DOI":"10.1186\/s13098-020-00557-9","article-title":"Update on Clinical Screening of Maturity-Onset Diabetes of the Young (MODY)","volume":"12","author":"Peixoto-Barbosa","year":"2020","journal-title":"Diabetol Metab Syndr"},{"key":"B25","doi-asserted-by":"publisher","first-page":"47","DOI":"10.1111\/pedi.12772","article-title":"ISPAD Clinical Practice Consensus Guidelines 2018: The Diagnosis and Management of Monogenic Diabetes in Children and Adolescents","volume":"19","author":"Hattersley","year":"2018","journal-title":"Pediatr Diabetes"},{"key":"B26","doi-asserted-by":"publisher","first-page":"S94","DOI":"10.2337\/diabetes.50.2007.s94","article-title":"Beta-Cell Genes and Diabetes: Molecular and Clinical Characterization of Mutations in Transcription Factors","volume":"50","author":"Frayling","year":"2001","journal-title":"Diabetes"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.2337\/diab.46.4.726","article-title":"Novel MODY3 Mutations in the Hepatocyte Nuclear Factor-1alpha Gene: Evidence for a Hyperexcitability of Pancreatic Beta-Cells to Intravenous Secretagogues in a Glucose-Tolerant Carrier of a P447L Mutation","volume":"46","author":"Hansen","year":"1997","journal-title":"Diabetes"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/6.4.583","article-title":"Identification of Nine Novel Mutations in the Hepatocyte Nuclear Factor 1 Alpha Gene Associated With Maturity-Onset Diabetes of the Young (MODY3)","volume":"6","author":"Vaxillaire","year":"1997","journal-title":"Hum Mol Genet"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1007\/s13300-019-0633-3","article-title":"Maturity Onset Diabetes of the Young is Not Necessarily Associated With Autosomal Inheritance: Case Description of a De Novo HFN1A Mutation","volume":"10","author":"Salzano","year":"2019","journal-title":"Diabetes Ther"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1016\/j.tig.2021.10.001","article-title":"Why All MODY Variants are Dominantly Inherited: A Hypothesis","author":"Li","year":"2021","journal-title":"Trends Genet"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.2337\/diacare.46.10.1648","article-title":"Maturity-Onset Diabetes of the Young Due to a Mutation in the Hepatocyte Nuclear Factor-4 Alpha Binding Site in the Promoter of the Hepatocyte Nuclear Factor-1 Alpha Gene","volume":"46","author":"Gragnoli","year":"1997","journal-title":"Diabetes"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2002-020945","article-title":"Hepatocyte Nuclear Factor-1 Alpha Gene Mutations and Diabetes in Norway","volume":"88","author":"Bj\u00f8rkhaug","year":"2003","journal-title":"J Clin Endocrinol Metab"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1007\/s001250051101","article-title":"Mutations in the Hepatocyte Nuclear Factor-1alpha Gene in Caucasian Families Originally Classified as Having Type I Diabetes","volume":"41","author":"M\u00f8ller","year":"1998","journal-title":"Diabetologia"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.2337\/diacare.26.2.333","article-title":"Identifying Hepatic Nuclear Factor 1alpha Mutations in Children and Young Adults With a Clinical Diagnosis of Type 1 Diabetes","volume":"26","author":"Lambert","year":"2003","journal-title":"Diabetes Care"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1016\/j.diabres.2015.05.026","article-title":"A Novel Nonsense Mutation of the HNF1alpha in Maturity-Onset Diabetes of the Young Type 3 in Asian Population","volume":"109","author":"Fang","year":"2015","journal-title":"Diabetes Res Clin Pract"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1111\/cge.12757","article-title":"Structure-Function Studies of HNF1A (MODY3) Gene Mutations in South Indian Patients With Monogenic Diabetes","volume":"90","author":"Balamurugan","year":"2016","journal-title":"Clin Genet"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.1007\/s00125-002-0977-4","article-title":"Characterization of a Naturally Occurring Mutation (L107I) in the HNF1 Alpha (MODY3) Gene","volume":"45","author":"Cervin","year":"2002","journal-title":"Diabetologia"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.1111\/j.1399-5448.2010.00681.x","article-title":"Persistently Autoantibody Negative (PAN) Type 1 Diabetes Mellitus in Children","volume":"12","author":"Hameed","year":"2011","journal-title":"Pediatr Diabetes"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddl147","article-title":"Isomers of the TCF1 Gene Encoding Hepatocyte Nuclear Factor-1 Alpha Show Differential Expression in the Pancreas and Define the Relationship Between Mutation Position and Clinical Phenotype in Monogenic Diabetes","volume":"15","author":"Harries","year":"2006","journal-title":"Hum Mol Genet"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.2337\/diacare.28.7.1751","article-title":"Beta-Cell Dysfunction, Insulin Sensitivity, and Glycosuria Precede Diabetes in Hepatocyte Nuclear Factor-1alpha Mutation Carriers","volume":"28","author":"Stride","year":"2005","journal-title":"Diabetes Care"},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.2337\/db07-0859","article-title":"The Type and the Position of HNF1A Mutation Modulate Age at Diagnosis of Diabetes in Patients With Maturity-Onset Diabetes of the Young (MODY)-3","volume":"57","author":"Bellanne-Chantelot","year":"2008","journal-title":"Diabetes"},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.2337\/diab.45.11.1503","article-title":"Altered Insulin Secretory Responses to Glucose in Diabetic and Nondiabetic Subjects With Mutations in the Diabetes Susceptibility Gene MODY3 on Chromosome 12","volume":"45","author":"Byrne","year":"1996","journal-title":"Diabetes"},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.2337\/diacare.21.12.2144","article-title":"Liver and Kidney Function in Japanese Patients With Maturity-Onset Diabetes of the Young","volume":"21","author":"Iwasaki","year":"1998","journal-title":"Diabetes Care"},{"key":"B44","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1096-9136(199810)15:10<816::AID-DIA714>3.0.CO;2-P","article-title":"A Low Renal Threshold for Glucose in Diabetic Patients With a Mutation in the Hepatocyte Nuclear Factor-1alpha (HNF-1alpha) Gene","volume":"15","author":"Menzel","year":"1998","journal-title":"Diabetes Med"},{"key":"B45","doi-asserted-by":"publisher","DOI":"10.2337\/diabetes.50.9.2047","article-title":"The Generalized Aminoaciduria Seen in Patients With Hepatocyte Nuclear Factor-1alpha Mutations is a Feature of All Patients With Diabetes and is Associated With Glucosuria","volume":"50","author":"Bingham","year":"2001","journal-title":"Diabetes"},{"key":"B46","doi-asserted-by":"publisher","DOI":"10.1093\/embo-reports\/kvd071","article-title":"HNF1alpha Controls Renal Glucose Reabsorption in Mouse and Man","volume":"1","author":"Pontoglio","year":"2000","journal-title":"EMBO Rep"},{"key":"B47","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.275.17.12515","article-title":"Transcriptional Activation by Hepatocyte Nuclear Factor-1 Requires Synergism Between Multiple Coactivator Proteins","volume":"275","author":"Soutoglou","year":"2000","journal-title":"J Biol Chem"},{"key":"B48","doi-asserted-by":"publisher","DOI":"10.1002\/bies.950140902","article-title":"HNF1, a Homeoprotein Member of the Hepatic Transcription Regulatory Network","volume":"14","author":"Tronche","year":"1992","journal-title":"Bioessays"},{"key":"B49","doi-asserted-by":"publisher","DOI":"10.1038\/ng1297-384","article-title":"Mutation in Hepatocyte Nuclear Factor-1 Beta Gene (TCF2) Associated With MODY","volume":"17","author":"Horikawa","year":"1997","journal-title":"Nat Genet"},{"key":"B50","doi-asserted-by":"publisher","DOI":"10.2337\/diab.47.8.1354","article-title":"Frameshift Mutation, A263fsinsGG, in the Hepatocyte Nuclear Factor-1beta Gene Associated With Diabetes and Renal Dysfunction","volume":"47","author":"Nishigori","year":"1998","journal-title":"Diabetes"},{"key":"B51","doi-asserted-by":"publisher","DOI":"10.1111\/j.1399-5448.2011.00788.x","article-title":"Onset of Type 1 Diabetes Mellitus in Two Patients With Maturity Onset Diabetes of the Young","volume":"13","author":"Maltoni","year":"2012","journal-title":"Pediatr Diabetes"},{"key":"B52","doi-asserted-by":"publisher","DOI":"10.1111\/1753-0407.13097","article-title":"Clinical and Laboratory Clues of Maturity-Onset Diabetes of the Young and Determination of Association With Molecular Diagnosis","volume":"13","author":"Karaoglan","year":"2021","journal-title":"J Diabetes"},{"key":"B53","doi-asserted-by":"publisher","DOI":"10.1136\/bcr-2019-231837","article-title":"Monogenic Diabetes: A New Pathogenic Variant of HNF1A Gene","volume":"14","author":"Oliveira","year":"2021","journal-title":"BMJ Case Rep"},{"key":"B54","doi-asserted-by":"publisher","first-page":"16294","DOI":"10.1038\/s41598-020-73048-6","article-title":"A Study of Associations Between CUBN, HNF1A, and LIPC Gene Polymorphisms and Coronary Artery Disease","volume":"10","author":"Park","year":"2020","journal-title":"Sci Rep"},{"key":"B55","doi-asserted-by":"publisher","DOI":"10.2337\/diacare.28.11.2774","article-title":"Renal Malformations may be Linked to Mutations in the Hepatocyte Nuclear Factor-1\u03b1 (MODY3) Gene","volume":"28","author":"Malecki","year":"2005","journal-title":"Diabetes Care"},{"key":"B56","doi-asserted-by":"publisher","DOI":"10.1111\/j.1464-5491.2009.02913.x","article-title":"Increased All-Cause and Cardiovascular Mortality in Monogenic Diabetes as a Result of Mutations in the HNF1A Gene","volume":"27","author":"Steele","year":"2010","journal-title":"Diabetes Med"},{"key":"B57","doi-asserted-by":"publisher","first-page":"28","DOI":"10.1186\/1475-2840-8-28","article-title":"HNF1A Gene Polymorphisms and Cardiovascular Risk Factors in Individuals With Late-Onset Autosomal Dominant Diabetes: A Cross-Sectional Study","volume":"8","author":"Giuffrida","year":"2009","journal-title":"Cardiovasc Diabetol"},{"key":"B58","doi-asserted-by":"publisher","DOI":"10.1038\/nature09270","article-title":"Biological, Clinical and Population Relevance of 95 Loci for Blood Lipids","volume":"466","author":"Teslovich","year":"2010","journal-title":"Nature"},{"key":"B59","doi-asserted-by":"publisher","DOI":"10.1007\/s001250050931","article-title":"Chronic Diabetic Complications in Patients With MODY3 Diabetes","volume":"41","author":"Isomaa","year":"1998","journal-title":"Diabetologia"},{"key":"B60","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2002-021891","article-title":"Association of I27L Polymorphism of Hepatocyte Nuclear Factor-1 Alpha Gene With High-Density Lipoprotein Cholesterol Level","volume":"88","author":"Babaya","year":"2003","journal-title":"J Clin Endocrinol Metab"},{"key":"B61","doi-asserted-by":"publisher","DOI":"10.1093\/carcin\/bgu193","article-title":"Transcriptome Analysis of Pancreatic Cancer Reveals a Tumor Suppressor Function for HNF1A","volume":"35","author":"Hoskins","year":"2014","journal-title":"Carcinogenesis"},{"key":"B62","doi-asserted-by":"publisher","DOI":"10.1016\/j.ebiom.2019.05.013","article-title":"HNF1A Inhibition Induces the Resistance of Pancreatic Cancer Cells to Gemcitabine by Targeting ABCB1","volume":"44","author":"Lu","year":"2019","journal-title":"EBioMedicine"},{"key":"B63","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2013.05.024","article-title":"Primary Hepatocellular Neoplasms in a MODY3 Family With a Novel HNF1A Germline Mutation","volume":"59","author":"Willson","year":"2013","journal-title":"J Hepatol"},{"key":"B64","doi-asserted-by":"publisher","DOI":"10.1007\/s12020-019-02138-x","article-title":"Primary Hepatocellular Adenoma Due to Biallelic HNF1A Mutations and its Co-Occurrence With MODY 3: Case-Report and Review of the Literature","volume":"67","author":"Fu","year":"2020","journal-title":"Endocrine"},{"key":"B65","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddi057","article-title":"Germline Hepatocyte Nuclear Factor 1alpha and 1beta Mutations in Renal Cell Carcinomas","volume":"14","author":"Rebouissou","year":"2005","journal-title":"Hum Mol Genet"},{"key":"B66","doi-asserted-by":"publisher","first-page":"16","DOI":"10.3892\/mco.2020.2178","article-title":"Circulating Tumor DNA Analysis of Metastatic Renal Cell Carcinoma","volume":"14","author":"Zhang","year":"2021","journal-title":"Mol Clin Oncol"},{"key":"B67","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.humpath.2018.08.004","article-title":"Somatic HNF1A Mutations in the Malignant Transformation of Hepatocellular Adenomas: A Retrospective Analysis of Data From MSK-IMPACT and TCGA","volume":"83","author":"Hechtman","year":"2019","journal-title":"Hum Pathol"},{"key":"B68","doi-asserted-by":"publisher","first-page":"5","DOI":"10.1186\/s13098-016-0198-5","article-title":"Genetic Diagnosis and Treatment of a Chinese Ketosis-Prone MODY 3 Family With Depression","volume":"9","author":"Tang","year":"2017","journal-title":"Diabetol Metab Syndr"},{"key":"B69","doi-asserted-by":"publisher","DOI":"10.1007\/s13300-020-00864-4","article-title":"Treatment Options for MODY Patients: A Systematic Review of Literature","volume":"11","author":"Delvecchio","year":"2020","journal-title":"Diabetes Ther"},{"key":"B70","doi-asserted-by":"publisher","DOI":"10.1046\/j.1464-5491.2000.00305.x","article-title":"Sensitivity to Sulphonylureas in Patients With Hepatocyte Nuclear Factor-1alpha Gene Mutations: Evidence for Pharmacogenetics in Diabetes","volume":"17","author":"Pearson","year":"2000","journal-title":"Diabetes Med"},{"key":"B71","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(03)14571-0","article-title":"Genetic Cause of Hyperglycaemia and Response to Treatment in Diabetes","volume":"362","author":"Pearson","year":"2003","journal-title":"Lancet"},{"key":"B72","doi-asserted-by":"publisher","DOI":"10.2337\/diabetes.51.2007.s343","article-title":"Decreased Glibenclamide Uptake in Hepatocytes of Hepatocyte Nuclear Factor-1alpha-Deficient Mice: A Mechanism for Hypersensitivity to Sulfonylurea Therapy in Patients With Maturity-Onset Diabetes of the Young, Type 3 (MODY3)","volume":"51","author":"Boileau","year":"2002","journal-title":"Diabetes"},{"key":"B73","doi-asserted-by":"publisher","DOI":"10.1177\/0004563213483458","article-title":"Ellard. Maturity Onset Diabetes of the Young: Identification and Diagnosis","volume":"50","author":"McDonald","year":"2013","journal-title":"Ann Clin Biochem"},{"key":"B74","doi-asserted-by":"publisher","DOI":"10.1159\/000356925","article-title":"A Family With a Novel Termination Mutation in Hepatic Nuclear Factor 1alpha in Maturity-Onset Diabetes of the Young Type 3 Which is Unresponsive to Sulphonylurea Therapy","volume":"81","author":"Demol","year":"2014","journal-title":"Horm Res Paediatr"},{"key":"B75","doi-asserted-by":"publisher","DOI":"10.1038\/s41431-019-0561-8","article-title":"Response to Multiple Glucose-Lowering Agents in a Sib-Pair With a Novel HNF1alpha (MODY3) Variant","volume":"28","author":"Tan","year":"2020","journal-title":"Eur J Hum Genet"},{"key":"B76","doi-asserted-by":"publisher","DOI":"10.2337\/dc18-0384","article-title":"Mexican Carriers of the HNF1A P.E508K Variant Do Not Experience an Enhanced Response to Sulfonylureas","volume":"41","author":"Martagon","year":"2018","journal-title":"Diabetes Care"},{"key":"B77","doi-asserted-by":"publisher","DOI":"10.1038\/s41588-019-0504-x","article-title":"Polymorphisms of the HNF1A Gene Encoding Hepatocyte Nuclear Factor-1 Alpha are Associated With C-Reactive Protein","volume":"82","author":"Tin","year":"2008","journal-title":"Am J Hum Genet"},{"key":"B78","doi-asserted-by":"publisher","DOI":"10.1038\/jhg.2011.106","article-title":"Single-Nucleotide Polymorphisms at Five Loci are Associated With C-Reactive Protein Levels in a Cohort of Filipino Young Adults","volume":"56","author":"Curocichin","year":"2011","journal-title":"J Hum Genet"},{"key":"B79","doi-asserted-by":"publisher","first-page":"e126","DOI":"10.5001\/omj.2020.44","article-title":"Genetics and Pathophysiology of Maturity-Onset Diabetes of the Young (MODY): A Review of Current Trends","volume":"35","author":"Yahaya","year":"2020","journal-title":"Oman Med J"},{"key":"B80","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2011-0268","article-title":"French Monogenic Diabetes Study, Clinical Characteristics and Diagnostic Criteria of Maturity-Onset Diabetes of the Young (MODY) Due to Molecular Anomalies of the HNF1A Gene","volume":"96","author":"Bellanne-Chantelot","year":"2011","journal-title":"J Clin Endocrinol Metab"},{"key":"B81","doi-asserted-by":"publisher","DOI":"10.2337\/diabetes.53.3.855","article-title":"Evidence From a Large U.K. Family Collection That Genes Influencing Age of Onset of Type 2 Diabetes Map to Chromosome 12p and to the MODY3\/NIDDM2 Locus on 12q24","volume":"53","author":"BellanneWiltshire","year":"2004","journal-title":"Diabetes"},{"key":"B82","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2014.6511","article-title":"Association of a Low-Frequency Variant in HNF1A With Type 2 Diabetes in a Latino Population","volume":"311","author":"Estrada","year":"2014","journal-title":"JAMA"},{"key":"B83","doi-asserted-by":"publisher","DOI":"10.2337\/diabetes.54.8.2487","article-title":"A Large-Scale Association Analysis of Common Variation of the HNF1alpha Gene With Type 2 Diabetes in the U.K. Caucasian Population","volume":"54","author":"Weedon","year":"2005","journal-title":"Diabetes"},{"key":"B84","doi-asserted-by":"publisher","DOI":"10.1007\/s005920170008","article-title":"Mutation in Hepatocyte Nuclear Factor-1alpha is Not a Common Cause of MODY and Early-Onset Type 2 Diabetes in Korea","volume":"38","author":"Lee","year":"2001","journal-title":"Acta Diabetol"},{"key":"B85","doi-asserted-by":"publisher","DOI":"10.1210\/jcem.84.3.5528","article-title":"The Hepatic Nuclear Factor-1alpha G319S Variant is Associated With Early-Onset Type 2 Diabetes in Canadian Oji-Cree","volume":"84","author":"Hegele","year":"1999","journal-title":"J Clin Endocrinol Metab"},{"key":"B86","doi-asserted-by":"publisher","DOI":"10.1007\/s100380050208","article-title":"Disparity Between Association and Linkage Analysis for HNF1A G319S in Type 2 Diabetes in Canadian Oji-Cree","volume":"45","author":"Hegele","year":"2000","journal-title":"J Hum Genet"},{"key":"B87","doi-asserted-by":"publisher","DOI":"10.1016\/s0009-9120(03)00004-3","article-title":"Genes, Environment and Oji-Cree Type 2 Diabetes","volume":"36","author":"Hegele","year":"2003","journal-title":"Clin Biochem"},{"key":"B88","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.062059799","article-title":"HNF-1alpha G319S, a Transactivation-Deficient Mutant, is Associated With Altered Dynamics of Diabetes Onset in an Oji-Cree Community","volume":"99","author":"Triggs-Raine","year":"2002","journal-title":"Proc Natl Acad Sci USA"},{"key":"B89","doi-asserted-by":"publisher","DOI":"10.2337\/db07-1663","article-title":"Diabetes Susceptibility in the Canadian Oji-Cree Population is Moderated by Abnormal mRNA Processing of HNF1A G319S Transcripts","volume":"57","author":"Harries","year":"2008","journal-title":"Diabetes"},{"key":"B90","doi-asserted-by":"publisher","DOI":"10.1016\/j.diabres.2017.08.001","article-title":"The HNF1A Mutant Ala180Val: Clinical Challenges in Determining Causality of a Rare HNF1A Variant in Familial Diabetes","volume":"133","author":"Sagen","year":"2017","journal-title":"Diabetes Res Clin Pract"},{"key":"B91","doi-asserted-by":"publisher","first-page":"2792","DOI":"10.3390\/nu12092792","article-title":"Gestational Diabetes Mellitus Affects Offspring\u2019s Epigenome. Is There a Way to Reduce the Negative Consequences","volume":"12","author":"S\u0142upecka-Ziemilska","year":"2020","journal-title":"Nutrients"},{"key":"B92","doi-asserted-by":"publisher","DOI":"10.1111\/ahg.12356","article-title":"The Role of Genetics and Epigenetics in the Pathogenesis of Gestational Diabetes Mellitus","volume":"84","author":"Rosik","year":"2020","journal-title":"Ann Hum Genet"},{"key":"B93","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2020.602477","article-title":"Genetics and Epigenetics: New Insight on Gestational Diabetes Mellitus","volume":"11","author":"Dalfr\u00e0","year":"2020","journal-title":"Front Endocrinol (Lausanne)"},{"key":"B94","doi-asserted-by":"publisher","DOI":"10.1210\/js.2017-00040","article-title":"High Prevalence of Diabetes-Predisposing Variants in MODY Genes Among Danish Women With Gestational Diabetes Mellitus","volume":"1","author":"Gjesing","year":"2017","journal-title":"J Endocr Soc"},{"key":"B95","doi-asserted-by":"publisher","DOI":"10.1055\/s-2008-1081492","article-title":"The A98V Single Nucleotide Polymorphism (SNP) in Hepatic Nuclear Factor 1 Alpha (HNF-1alpha) is Associated With Insulin Sensitivity and Beta-Cell Function","volume":"116","author":"Bergmann","year":"2008","journal-title":"Exp Clin Endocrinol Diabetes"},{"key":"B96","doi-asserted-by":"publisher","DOI":"10.1007\/s00125-006-0258-8","article-title":"Common Variants in MODY Genes Increase the Risk of Gestational Diabetes Mellitus","volume":"49","author":"Shaat","year":"2006","journal-title":"Diabetologia"},{"key":"B97","doi-asserted-by":"publisher","DOI":"10.1080\/09513590.2019.1698023","article-title":"HNF1A Gene P.I27L is Associated With Co-Existing Preeclampsia in Gestational Diabetes Mellitus","volume":"36","author":"Beysel","year":"2020","journal-title":"Gynecol Endocrinol"},{"key":"B98","doi-asserted-by":"publisher","first-page":"6","DOI":"10.1002\/jgm.2962","article-title":"Variants in MODY Genes Associated With Maternal Lipids Profiles in Second Trimester of Pregnancy","volume":"19","author":"Wang","year":"2017","journal-title":"J Gene Med"},{"key":"B99","doi-asserted-by":"publisher","DOI":"10.1007\/s10753-011-9348-y","article-title":"Genome-Wide Association With C-Reactive Protein Levels in CLHNS: Evidence for the CRP and HNF1A Loci and Their Interaction With Exposure to a Pathogenic Environment","volume":"35","author":"Wu","year":"2012","journal-title":"Inflammation"},{"key":"B100","doi-asserted-by":"publisher","DOI":"10.2337\/dc11-0323","article-title":"High-Sensitivity CRP Discriminates HNF1A-MODY From Other Subtypes of Diabetes","volume":"34","author":"McDonald","year":"2011","journal-title":"Diabetes Care"},{"key":"B101","doi-asserted-by":"publisher","DOI":"10.1080\/09674845.2014.11978288","article-title":"Comparability of High-Sensitivity CRP Methods to Detect Maturity-Onset Diabetes of the Young Due to HNF1A Mutations","volume":"71","author":"Shah","year":"2014","journal-title":"Br J BioMed Sci"},{"key":"B102","doi-asserted-by":"publisher","first-page":"397","DOI":"10.1074\/mcp.M113.035600","article-title":"Analysis of the Human Tissue-Specific Expression by Genome-Wide Integration of Transcriptomics and Antibody-Based Proteomics","volume":"13","author":"Fagerberg","year":"2014","journal-title":"Mol Cell Proteomics"},{"key":"B103","doi-asserted-by":"publisher","DOI":"10.1126\/science.1089769","article-title":"Control of Pancreas and Liver Gene Expression by HNF Transcription Factors","volume":"303","author":"Odom","year":"2004","journal-title":"Science"},{"key":"B104","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.274.50.35639","article-title":"Anatomy of a Homeoprotein Revealed by the Analysis of Human MODY3 Mutations","volume":"274","author":"Vaxillaire","year":"1999","journal-title":"J Biol Chem"},{"key":"B105","doi-asserted-by":"publisher","DOI":"10.2337\/diabetes.50.2007.s101","article-title":"Beta-Cell Genes and Diabetes: Quantitative and Qualitative Differences in the Pathophysiology of Hepatic Nuclear Factor-1alpha and Glucokinase Mutations","volume":"50","author":"Pearson","year":"2001","journal-title":"Diabetes"},{"key":"B106","doi-asserted-by":"publisher","DOI":"10.1172\/JCI121994","article-title":"Human Islets Expressing HNF1A Variant Have Defective \u03b2 Cell Transcriptional Regulatory Networks","volume":"129","author":"Haliyur","year":"2019","journal-title":"J Clin Invest"},{"key":"B107","doi-asserted-by":"publisher","first-page":"50","DOI":"10.1002\/mgg3.261","article-title":"Identification and Functional Analysis of C.422_423inst, a Novel Mutation of the HNF1A Gene in a Patient With Diabetes","volume":"5","author":"Maga\u00f1a-Cerino","year":"2017","journal-title":"Mol Genet Genomic Med"},{"key":"B108","doi-asserted-by":"publisher","DOI":"10.1007\/s00125-002-0892-8","article-title":"Expression Profile of MODY3\/HNF-1alpha Protein in the Developing Mouse Pancreas","volume":"45","author":"Nammo","year":"2002","journal-title":"Diabetologia"},{"key":"B109","doi-asserted-by":"publisher","DOI":"10.1210\/endo.142.12.8592","article-title":"Beta-Cell-Targeted Expression of a Dominantnegative Hepatocyte Nuclear Factor-1 Alpha Induces a Maturity-Onset Diabetes of the Young (MODY)3-Like Phenotype in Transgenic Mice","volume":"142","author":"Hagenfeldt-Johansson","year":"2001","journal-title":"Endocrinology"},{"key":"B110","doi-asserted-by":"publisher","DOI":"10.2337\/diabetes.51.1.114","article-title":"Overexpression of Dominant-Negative Mutant Hepatocyte Nuclear Fctor-1alpha in Pancreatic Beta-Cells Causes Abnormal Islet Architecture With Decreased Expression of E-Cadherin, Reduced Beta-Cell Proliferation, and Diabetes","volume":"51","author":"Yamagata","year":"2002","journal-title":"Diabetes"},{"key":"B111","doi-asserted-by":"publisher","DOI":"10.1007\/s00125-008-1006-z","article-title":"Transcription Factor Expression in the Developing Human Fetal Endocrine Pancreas","volume":"51","author":"Lyttle","year":"2008","journal-title":"Diabetologia"},{"key":"B112","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M109.064238","article-title":"Distinct Regulation of Hepatic Nuclear Factor 1alpha by NKX6.1 in Pancreatic Beta Cells","volume":"285","author":"Donelan","year":"2010","journal-title":"J Biol Chem"},{"key":"B113","doi-asserted-by":"publisher","DOI":"10.1210\/me.2010-0362","article-title":"Hnf1\u03b1 (MODY3) Regulates \u03b2-Cell-Enriched MafA Transcription Factor Expression","volume":"25","author":"Hunter","year":"2011","journal-title":"Mol Endocrinol"},{"key":"B114","doi-asserted-by":"publisher","DOI":"10.1172\/JCI2548","article-title":"Defective Insulin Secretion in Hepatocyte Nuclear Factor 1alpha-Deficient Mice","volume":"101","author":"Pontoglio","year":"1998","journal-title":"J Clin Invest"},{"key":"B115","doi-asserted-by":"publisher","DOI":"10.2337\/db13-1878","article-title":"Incretin Effect and Glucagon Responses to Oral and Intravenous Glucose in Patients With Maturity-Onset Diabetes of the Young\u2013Type 2 and Type 3","volume":"63","author":"\u00d8stoft","year":"2014","journal-title":"Diabetes"},{"key":"B116","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbadis.2020.165898","article-title":"Hnf1\u03b1 Controls Glucagon Secretion in Pancreatic \u03b1-Cells Through Modulation of SGLT1","volume":"1866","author":"Sato","year":"2020","journal-title":"Biochim Biophys Acta Mol Basis Dis"},{"key":"B117","doi-asserted-by":"publisher","DOI":"10.1016\/j.stem.2019.07.007","article-title":"Modeling Monogenic Diabetes using Human ESCs Reveals Developmental and Metabolic Deficiencies Caused by Mutations in HNF1A","volume":"25","author":"Cardenas-Diaz","year":"2019","journal-title":"Cell Stem Cell"},{"key":"B118","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M010523200","article-title":"A Molecular Link Between the Common Phenotypes of Type 1 Glycogen Storage Disease and HNF1alpha-Null Mice","volume":"276","author":"Hiraiwa","year":"2001","journal-title":"J Biol Chem"},{"key":"B119","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M004388200","article-title":"Regulation of the Liver Fatty Acid-Binding Protein Gene by Hepatocyte Nuclear Factor 1alpha (HNF1alpha). Alterations in Fatty Acid Homeostasis in HNF1alpha-Deficient Mice","volume":"275","author":"Akiyama","year":"2000","journal-title":"J Biol Chem"},{"key":"B120","doi-asserted-by":"publisher","DOI":"10.2337\/diabetes.52.12.2989","article-title":"Regulation of Apolipoprotein M Gene Expression by MODY3 Gene Hepatocyte Nuclear Factor-1alpha: Haploinsufficiency is Associated With Reduced Serum Apolipoprotein M Levels","volume":"52","author":"Richter","year":"2003","journal-title":"Diabetes"},{"key":"B121","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.abb.2013.03.002","article-title":"Anti-Inflammatory Effects of Propofol are Mediated by Apolipoprotein M in a Hepatocyte Nuclear Factor-1alpha-Dependent Manner","volume":"533","author":"Ma","year":"2013","journal-title":"Arch Biochem Biophys"},{"key":"B122","doi-asserted-by":"publisher","DOI":"10.1002\/1873-3468.12689","article-title":"Deletion of HNF1alpha in Hepatocytes Results in Fatty Liver-Related Hepatocellular Carcinoma in Mice","volume":"591","author":"Ni","year":"2017","journal-title":"FEBS Lett"},{"key":"B123","doi-asserted-by":"publisher","DOI":"10.1161\/01.atv.20.1.217","article-title":"The Private Hepatocyte Nuclear Factor-1alpha G319S Variant is Associated With Plasma Lipoprotein Variation in Canadian Oji-Cree","volume":"20","author":"Hegele","year":"2000","journal-title":"Arterioscler Thromb Vasc Biol"},{"key":"B124","doi-asserted-by":"publisher","DOI":"10.1097\/MEG.0b013e328347964d","article-title":"New Monoallelic (Partial Tandem Duplication) Mutation of HNF1a Gene in Steatotic Hepatocellular Adenoma","volume":"23","author":"Sakellariou","year":"2011","journal-title":"Eur J Gastroenterol Hepatol"},{"key":"B125","doi-asserted-by":"publisher","DOI":"10.1007\/s00592-019-01298-6","article-title":"Functional Characterization of P.Pro409His Variant in HNF1A, a Hypomorphic Mutation Involved in Pancreatic Beta-Cell Dysfunction","volume":"56","author":"Nocera","year":"2019","journal-title":"Acta Diabetol"},{"key":"B126","doi-asserted-by":"publisher","DOI":"10.1007\/s00125-003-1079-7","article-title":"Identification and Functional Characterization of a Novel Mutation of Hepatocyte Nuclear Factor-1alpha Gene in a Korean Family With MODY3","volume":"46","author":"Kim","year":"2003","journal-title":"Diabetologia"},{"key":"B127","doi-asserted-by":"publisher","DOI":"10.2119\/molmed.2010.00097","article-title":"Differential Effects of HNF-1alpha Mutations Associated With Familial Young-Onset Diabetes on Target Gene Regulation","volume":"17","author":"Gal\u00e1n","year":"2011","journal-title":"Mol Med"},{"key":"B128","doi-asserted-by":"publisher","DOI":"10.1016\/s1097-2765(02)00704-9","article-title":"Diabetes Mutations Delineate an Atypical POU Domain in HNF-1alpha","volume":"10","author":"Chi","year":"2002","journal-title":"Mol Cell"},{"key":"B129","doi-asserted-by":"publisher","DOI":"10.1006\/jmbi.2001.4780","article-title":"The Dimerization Domain of HNF-1alpha: Structure and Plasticity of an Intertwined Four-Helix Bundle With Application to Diabetes Mellitus","volume":"310","author":"Narayana","year":"2001","journal-title":"J Mol Biol"},{"key":"B130","doi-asserted-by":"publisher","DOI":"10.1021\/bi001996t","article-title":"High-Resolution Structure of the HNF-1alpha Dimerization Domain","volume":"39","author":"Rose","year":"2000","journal-title":"Biochemistry"},{"key":"B131","doi-asserted-by":"publisher","DOI":"10.1038\/78966","article-title":"Structural Basis of Dimerization, Coactivator Recognition and MODY3 Mutations in HNF-1alpha","volume":"7","author":"Rose","year":"2000","journal-title":"Nat Struct Biol"},{"key":"B132","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0174953","article-title":"Determining the Role of Missense Mutations in the POU Domain of HNF1A That Reduce the DNA-Binding Affinity: A Computational Approach","volume":"12","author":"Sneha","year":"2017","journal-title":"PloS One"},{"key":"B133","doi-asserted-by":"publisher","DOI":"10.1210\/clinem\/dgaa051","article-title":"Functional Analyses of HNF1A-MODY Variants Refine the Interpretation of Identified Sequence Variants","volume":"105","author":"Malikova","year":"2020","journal-title":"J Clin Endocrinol Metab"},{"key":"B134","doi-asserted-by":"publisher","DOI":"10.2337\/db16-0460","article-title":"Functional Investigations of HNF1A Identify Rare Variants as Risk Factors for Type 2 Diabetes in the General Population","volume":"66","author":"Najmi","year":"2017","journal-title":"Diabetes"}],"container-title":["Frontiers in Endocrinology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fendo.2022.829565\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,3,1]],"date-time":"2022-03-01T05:36:14Z","timestamp":1646112974000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fendo.2022.829565\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,3,1]]},"references-count":134,"alternative-id":["10.3389\/fendo.2022.829565"],"URL":"https:\/\/doi.org\/10.3389\/fendo.2022.829565","relation":{},"ISSN":["1664-2392"],"issn-type":[{"value":"1664-2392","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,3,1]]},"article-number":"829565"}}