Gene Symbol: HNF1A
Description: HNF1 homeobox A
Alias: HNF-1A, HNF1, HNF4A, IDDM20, LFB1, MODY3, TCF-1, TCF1, hepatocyte nuclear factor 1-alpha, HNF-1-alpha, albumin proximal factor, hepatic nuclear factor 1, interferon production regulator factor, liver-specific transcription factor LF-B1, transcription factor 1, hepatic, truncated hepatocyte nuclear factor 1 alpha
Species: human
Products:     HNF1A

Top Publications

  1. Navalón García K, Mendoza Alcantar L, Díaz Vargas M, Martinez Godinez M, Reyna Garfias H, Aguilar Salinas C, et al. HNF-1alpha G574S is a functional variant with decreased transactivation activity. Diabet Med. 2006;23:1295-300 pubmed
    ..Although it has been difficult to prove its role in the development of diabetes in case-control association studies, this variant exhibits functional effects consistent with it being a potential diabetes susceptibility allele. ..
  2. Edghill E, Bingham C, Ellard S, Hattersley A. Mutations in hepatocyte nuclear factor-1beta and their related phenotypes. J Med Genet. 2006;43:84-90 pubmed
    ..Molecular genetic testing for HNF-1beta mutations should be considered in patients with unexplained renal cysts (including GCKD), especially when associated with diabetes, early-onset gout, or uterine abnormalities. ..
  3. Armendariz A, Krauss R. Hepatic nuclear factor 1-alpha: inflammation, genetics, and atherosclerosis. Curr Opin Lipidol. 2009;20:106-11 pubmed
    ..genes that are strongly related to plasma CRP levels, including several on chromosome 12 in the vicinity of the HNF1A gene. The CRP gene promoter has two HNF1-alpha-binding sites...
  4. Glucksmann M, Lehto M, Tayber O, Scotti S, Berkemeier L, Pulido J, et al. Novel mutations and a mutational hotspot in the MODY3 gene. Diabetes. 1997;46:1081-6 pubmed
    Maturity-onset diabetes of the young 3 (MODY3) is a type of NIDDM caused by mutations in the transcription factor hepatocyte nuclear factor-1alpha (HNF-1alpha) located on chromosome 12q...
  5. Okada Y, Takahashi A, Ohmiya H, Kumasaka N, Kamatani Y, Hosono N, et al. Genome-wide association study for C-reactive protein levels identified pleiotropic associations in the IL6 locus. Hum Mol Genet. 2011;20:1224-31 pubmed publisher
    ..Our study also replicated the associations in the CRP (rs3093059, P = 3.5 × 10(-21)) and HNF1A loci (rs7310409, P = 2.7 × 10(-8))...
  6. Elliott P, Chambers J, Zhang W, Clarke R, Hopewell J, Peden J, et al. Genetic Loci associated with C-reactive protein levels and risk of coronary heart disease. JAMA. 2009;302:37-48 pubmed publisher
    ..3 x 10(-12)), rs7553007 in the CRP locus (-20.7%; 95% CI, -23.4% to -17.9%; P = 1.3 x 10(-38)), rs1183910 in HNF1A (-13.8%; 95% CI, -16.6% to -10.9%; P = 1.9 x 10(-18)), and rs4420638 in APOE-CI-CII (-21.8%; 95% CI, -25.3% to -18...
  7. Nishigori H, Yamada S, Kohama T, Utsugi T, Shimizu H, Takeuchi T, et al. Mutations in the hepatocyte nuclear factor-1 alpha gene (MODY3) are not a major cause of early-onset non-insulin-dependent (type 2) diabetes mellitus in Japanese. J Hum Genet. 1998;43:107-10 pubmed
    Maturity-onset diabetes of the young (MODY3), a monogenic subtype of non-insulin-dependent diabetes mellitus (NIDDM) with an early age of onset, is characterized by a primary defect in insulin secretion...
  8. Chiu K, Chuang L, Chu A, Yoon C, Wang M. Comparison of the impact of the I27L polymorphism of the hepatocyte nuclear factor-1alpha on estimated and measured beta cell indices. Eur J Endocrinol. 2003;148:641-7 pubmed
    ..The conservation among species suggests a possible biological importance of this amino acid. Analysis of the published data confirms a modest role of this polymorphism in type 2 diabetes. ..
  9. Leu J, Crissey M, Leu J, Ciliberto G, Taub R. Interleukin-6-induced STAT3 and AP-1 amplify hepatocyte nuclear factor 1-mediated transactivation of hepatic genes, an adaptive response to liver injury. Mol Cell Biol. 2001;21:414-24 pubmed

More Information

Publications104 found, 100 shown here

  1. Bingham C, Ellard S, Nicholls A, Pennock C, Allen J, James A, et al. 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. Diabetes. 2001;50:2047-52 pubmed
    ..Glucose may depolarize and dissipate the electrical gradient of the sodium-dependent amino acid transporters in the proximal renal tubule, causing a reduction in amino acid resorption. ..
  2. Yokoi N, Kanamori M, Horikawa Y, Takeda J, Sanke T, Furuta H, et al. Association studies of variants in the genes involved in pancreatic beta-cell function in type 2 diabetes in Japanese subjects. Diabetes. 2006;55:2379-86 pubmed
    ..We examined the association of variants in genes encoding several transcription factors (TCF1, TCF2, HNF4A, ISL1, IPF1, NEUROG3, PAX6, NKX2-2, NKX6-1, and NEUROD1) and genes encoding the ATP-sensitive K(+) channel ..
  3. Gardner Stephen D, Mackenzie P. Hepatocyte nuclear factor1 transcription factors are essential for the UDP-glucuronosyltransferase 1A9 promoter response to hepatocyte nuclear factor 4alpha. Pharmacogenet Genomics. 2007;17:25-36 pubmed
    ..The discovery of two unique and cooperative liver-enriched transcription factor binding sites in the UGT1A9 promoter is a significant step towards understanding the unique hepatic expression of UGT1A9 amongst the UGT1A7-10 gene cluster. ..
  4. Mitchelmore C, Troelsen J, Spodsberg N, Sjostrom H, Noren O. Interaction between the homeodomain proteins Cdx2 and HNF1alpha mediates expression of the lactase-phlorizin hydrolase gene. Biochem J. 2000;346 Pt 2:529-35 pubmed
    ..Synergistic interaction between tissue-restricted factors is likely to be an important mechanism for reinforcing developmental and tissue-specific gene expression within the intestine. ..
  5. Thomas H, Badenberg B, Bulman M, Lemm I, Lausen J, Kind L, et al. Evidence for haploinsufficiency of the human HNF1alpha gene revealed by functional characterization of MODY3-associated mutations. Biol Chem. 2002;383:1691-700 pubmed
    ..In humans mutations in the HNF1 gene are responsible for one form of maturity onset diabetes of the young (MODY3)...
  6. Kleber M, Grammer T, Renner W, März W. Effect of the rs2259816 polymorphism in the HNF1A gene on circulating levels of c-reactive protein and coronary artery disease (the ludwigshafen risk and cardiovascular health study). BMC Med Genet. 2010;11:157 pubmed publisher
    ..We investigated the association of the rs2259816 polymorphism in the HNF1A gene with the circulating level of C-reactive protein and the hazard of coronary artery disease in the LURIC Study ..
  7. Kyithar M, Bacon S, Pannu K, Rizvi S, Colclough K, Ellard S, et al. Identification of HNF1A-MODY and HNF4A-MODY in Irish families: phenotypic characteristics and therapeutic implications. Diabetes Metab. 2011;37:512-9 pubmed publisher
    The prevalence of hepatocyte nuclear factor (HNF)-1A and HNF4A mutations, and the clinical implications following the genetic diagnosis of maturity-onset diabetes of the young (MODY) in the Irish population, remain unknown...
  8. Colclough K, Bellanne Chantelot C, Saint Martin C, Flanagan S, Ellard S. 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. Hum Mutat. 2013;34:669-85 pubmed publisher
    ..MODY is both clinically and genetically heterogeneous with mutations in at least 10 genes. Mutations in the HNF1A gene encoding hepatocyte nuclear factor-1 alpha are the most common cause of MODY in most adult populations ..
  9. Yuan X, Waterworth D, Perry J, Lim N, Song K, Chambers J, et al. Population-based genome-wide association studies reveal six loci influencing plasma levels of liver enzymes. Am J Hum Genet. 2008;83:520-8 pubmed publisher
    ..chromosome 10 and PNPLA3-SAMM50 on chromosome 22), one locus influencing gamma-glutamyl transferase (GGT) levels (HNF1A on chromosome 12), and three loci for alkaline phosphatase (ALP) levels (ALPL on chromosome 1, GPLD1 on chromosome ..
  10. Vaxillaire M, Rouard M, Yamagata K, Oda N, Kaisaki P, Boriraj V, et al. Identification of nine novel mutations in the hepatocyte nuclear factor 1 alpha gene associated with maturity-onset diabetes of the young (MODY3). Hum Mol Genet. 1997;6:583-6 pubmed
    ..two functionally related transcription factors, hepatocyte nuclear factor 4 alpha (HNF-4alpha) and hepatocyte nuclear factor 1 alpha (HNF-1alpha) are associated with the MODY1 and MODY3 forms of diabetes respectively, whereas ..
  11. Lambert A, Ellard S, Allen L, Gallen I, Gillespie K, Bingley P, et al. Identifying hepatic nuclear factor 1alpha mutations in children and young adults with a clinical diagnosis of type 1 diabetes. Diabetes Care. 2003;26:333-7 pubmed
    HNF-1alpha gene mutations (MODY3) present with marked hyperglycemia in lean young adults and may, therefore, be mistaken for type 1 diabetes, with implications for individual treatment and risk of diabetes in other family members...
  12. Bjørkhaug L, Sagen J, Thorsby P, Søvik O, Molven A, Njølstad P. Hepatocyte nuclear factor-1 alpha gene mutations and diabetes in Norway. J Clin Endocrinol Metab. 2003;88:920-31 pubmed
    ..To estimate the prevalence of MODY3 in Norwegian diabetic pedigrees, we screened a total of 130 families for HNF-1 alpha mutations; 42 families with ..
  13. Stride A, Shepherd M, Frayling T, Bulman M, Ellard S, Hattersley A. Intrauterine hyperglycemia is associated with an earlier diagnosis of diabetes in HNF-1alpha gene mutation carriers. Diabetes Care. 2002;25:2287-91 pubmed
    ..We conclude that maternal hyperglycemia during pregnancy probably increases the penetrance of HNF-1alpha mutations. The potential role of exposure to hyperglycemia in utero in a monogenic diabetic subgroup warrants prospective study. ..
  14. Babaya N, Ikegami H, Fujisawa T, Nojima K, Itoi Babaya M, Inoue K, et al. Association of I27L polymorphism of hepatocyte nuclear factor-1 alpha gene with high-density lipoprotein cholesterol level. J Clin Endocrinol Metab. 2003;88:2548-51 pubmed
    ..These results demonstrate that the HNF-1 alpha gene locus is associated with serum HDL-c level and suggest that the Ile27 allele is a risk marker for atherosclerosis. ..
  15. Reiner A, Gross M, Carlson C, Bielinski S, Lange L, Fornage M, et al. Common coding variants of the HNF1A gene are associated with multiple cardiovascular risk phenotypes in community-based samples of younger and older European-American adults: the Coronary Artery Risk Development in Young Adults Study and The Cardiova. Circ Cardiovasc Genet. 2009;2:244-54 pubmed publisher
    ..Common polymorphisms of the HNF-1 alpha gene (HNF1A) were recently associated with plasma C-reactive protein and gamma-glutamyl transferase concentration in middle-..
  16. Soutoglou E, Papafotiou G, Katrakili N, Talianidis I. Transcriptional activation by hepatocyte nuclear factor-1 requires synergism between multiple coactivator proteins. J Biol Chem. 2000;275:12515-20 pubmed
    ..The results support a model that involves the combined action of multiple coactivators recruited by HNF-1, which activate transcription by coupling nucleosome modification and recruitment of the general transcription machinery. ..
  17. Sourdive D, Transy C, Garbay S, Yaniv M. The bifunctional DCOH protein binds to HNF1 independently of its 4-alpha-carbinolamine dehydratase activity. Nucleic Acids Res. 1997;25:1476-84 pubmed
    b>HNF1 is a liver enriched atypical homeoprotein isolated from vertebrates which is involved in the transcriptional activation of liver, kidney, intestine and pancreas specific genes...
  18. Rebouissou S, Rosty C, Lecuru F, Boisselier S, Bui H, Le Frere Belfa M, et al. Mutation of TCF1 encoding hepatocyte nuclear factor 1alpha in gynecological cancer. Oncogene. 2004;23:7588-92 pubmed
    b>TCF1: (transcription factor 1) encoding hepatocyte nuclear factor 1alpha (HNF1alpha) is mutated in 50% of liver cell adenomas, a benign tumor closely associated with oral contraceptive use...
  19. Ellard S, Thomas K, Edghill E, Owens M, Ambye L, Cropper J, et al. Partial and whole gene deletion mutations of the GCK and HNF1A genes in maturity-onset diabetes of the young. Diabetologia. 2007;50:2313-7 pubmed
    Heterozygous mutations of glucokinase (GCK) and hepatocyte nuclear factor-1 alpha (HNF1A; also known as hepatic transcription factor 1 [TCF1]) genes are the most common cause of MODY...
  20. Pal A, Farmer A, Dudley C, Selwood M, Barrow B, Klyne R, et al. Evaluation of serum 1,5 anhydroglucitol levels as a clinical test to differentiate subtypes of diabetes. Diabetes Care. 2010;33:252-7 pubmed publisher
    ..1,5 anhydroglucitol (1,5AG) levels were reported to differentiate maturity-onset diabetes of the young due to HNF1A mutations (HNF1A-MODY) from type 2 diabetes, but this requires further validation...
  21. Bellanne Chantelot C, Carette C, Riveline J, Valéro R, Gautier J, Larger E, et al. 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. Diabetes. 2008;57:503-8 pubmed
    ..We analyzed the mutations identified in 356 unrelated MODY3 patients, including 118 novel mutations, and searched for correlations between the genotype and age at diagnosis ..
  22. Gragnoli C, Lindner T, Cockburn B, Kaisaki P, Gragnoli F, Marozzi G, et al. 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. Diabetes. 1997;46:1648-51 pubmed
    ..factor hepatocyte nuclear factor (HNF)-1 alpha are the cause of one form of maturity-onset diabetes of the young (MODY3)...
  23. Frayling T, Bulman M, Appleton M, Hattersley A, Ellard S. A rapid screening method for hepatocyte nuclear factor 1 alpha frameshift mutations; prevalence in maturity-onset diabetes of the young and late-onset non-insulin dependent diabetes. Hum Genet. 1997;101:351-4 pubmed
    ..Mutations in the hepatocyte nuclear factor 1 alpha (HNF-1 alpha) gene have recently been shown to cause MODY...
  24. Dohda T, Kaneoka H, Inayoshi Y, Kamihira M, Miyake K, Iijima S. Transcriptional coactivators CBP and p300 cooperatively enhance HNF-1alpha-mediated expression of the albumin gene in hepatocytes. J Biochem. 2004;136:313-9 pubmed
    ..In addition, inhibition of CBP or p300 using small interfering RNAs (siRNAs) resulted in a reduction in albumin expression. These results suggest that both CBP and p300 are required for enhanced expression of albumin. ..
  25. Lee H, Ahn C, Kim S, Song Y, Lim S, Kim K, et al. Mutation in hepatocyte nuclear factor-1alpha is not a common cause of MODY and early-onset type 2 diabetes in Korea. Acta Diabetol. 2001;38:123-7 pubmed
    ..We concluded that this genetic mutation in HNF-1alpha gene may not be a common contributor to MODY and early-onset type 2 diabetes susceptibility in Korea. ..
  26. Kaisaki P, Menzel S, Lindner T, Oda N, Rjasanowski I, Sahm J, et al. Mutations in the hepatocyte nuclear factor-1alpha gene in MODY and early-onset NIDDM: evidence for a mutational hotspot in exon 4. Diabetes. 1997;46:528-35 pubmed
    ..factor hepatocyte nuclear factor (HNF)-1alpha are the cause of one form of maturity-onset diabetes of the young (MODY3). Here, we report the exon-intron organization and partial sequence of the human HNF-1alpha gene...
  27. Yamada M, Ohnishi J, Ohkawara B, Iemura S, Satoh K, Hyodo Miura J, et al. NARF, an nemo-like kinase (NLK)-associated ring finger protein regulates the ubiquitylation and degradation of T cell factor/lymphoid enhancer factor (TCF/LEF). J Biol Chem. 2006;281:20749-60 pubmed
    ..Collectively, our findings raise the possibility that NARF functions as a novel ubiquitin-ligase to suppress the Wnt-beta-catenin signaling. ..
  28. Bulman M, Harries L, Hansen T, Shepherd M, Kelly W, Hattersley A, et al. Abnormal splicing of hepatocyte nuclear factor 1 alpha in maturity-onset diabetes of the young. Diabetologia. 2002;45:1463-7 pubmed
    ..This analysis of the mRNA is required to define mutational mechanisms and confirm pathogenic status. ..
  29. van de Wetering M, Oosterwegel M, Dooijes D, Clevers H. Identification and cloning of TCF-1, a T lymphocyte-specific transcription factor containing a sequence-specific HMG box. EMBO J. 1991;10:123-32 pubmed
    ..These results identify TCF-1 as a T cell-specific transcription factor, which might play a role in the establishment of the mature T cell phenotype. ..
  30. Hansen S, Parrizas M, Jensen M, Pruhova S, Ek J, Boj S, et al. Genetic evidence that HNF-1alpha-dependent transcriptional control of HNF-4alpha is essential for human pancreatic beta cell function. J Clin Invest. 2002;110:827-33 pubmed
    ..Furthermore, they indicate that this regulation is essential to maintain normal pancreatic function. ..
  31. Winckler W, Burtt N, Holmkvist J, Cervin C, de Bakker P, Sun M, et al. Association of common variation in the HNF1alpha gene region with risk of type 2 diabetes. Diabetes. 2005;54:2336-42 pubmed
    ..The gene for MODY3 diabetes, HNF1alpha, lies in a region that has shown linkage to late-onset type 2 diabetes (12q24, NIDDM2), and ..
  32. Behn P, Wasson J, Chayen S, Smolovitch I, Thomas J, Glaser B, et al. Hepatocyte nuclear factor 1alpha coding mutations are an uncommon contributor to early-onset type 2 diabetes in Ashkenazi Jews. Diabetes. 1998;47:967-9 pubmed
  33. Odom D, Zizlsperger N, Gordon D, Bell G, Rinaldi N, Murray H, et al. Control of pancreas and liver gene expression by HNF transcription factors. Science. 2004;303:1378-81 pubmed
    ..Our results suggest how misregulation of HNF4alpha can contribute to type 2 diabetes. ..
  34. Thanabalasingham G, Huffman J, Kattla J, Novokmet M, Rudan I, Gloyn A, et al. Mutations in HNF1A result in marked alterations of plasma glycan profile. Diabetes. 2013;62:1329-37 pubmed publisher
    A recent genome-wide association study identified hepatocyte nuclear factor 1-α (HNF1A) as a key regulator of fucosylation...
  35. Klupa T, Warram J, Antonellis A, Pezzolesi M, Nam M, Malecki M, et al. Determinants of the development of diabetes (maturity-onset diabetes of the young-3) in carriers of HNF-1alpha mutations: evidence for parent-of-origin effect. Diabetes Care. 2002;25:2292-301 pubmed
    To determine the distribution of the age at onset of diabetes (maturity-onset diabetes of the young-3 [MODY3]) and to identify determinants of the onset of diabetes in carriers of HNF-1alpha mutations...
  36. Hegele R, Zinman B, Hanley A, Harris S, Barrett P, Cao H. Genes, environment and Oji-Cree type 2 diabetes. Clin Biochem. 2003;36:163-70 pubmed
    ..genetic discovery by far was the private G319S mutation in transcription factor HNF-1alpha, encoded by the HNF1A gene...
  37. Reiner A, Barber M, Guan Y, Ridker P, Lange L, Chasman D, et al. Polymorphisms of the HNF1A gene encoding hepatocyte nuclear factor-1 alpha are associated with C-reactive protein. Am J Hum Genet. 2008;82:1193-201 pubmed publisher
    ..Study (CHS) provide independent and confirmatory evidence for association between common polymorphisms of the HNF1A gene encoding hepatocyte nuclear factor-1 alpha and plasma C-reactive protein (CRP) concentration...
  38. Harries L, Brown J, Gloyn A. Species-specific differences in the expression of the HNF1A, HNF1B and HNF4A genes. PLoS ONE. 2009;4:e7855 pubmed publisher
    The HNF1A, HNF1B and HNF4A genes are part of an autoregulatory network in mammalian pancreas, liver, kidney and gut...
  39. Mendel D, Hansen L, Graves M, Conley P, Crabtree G. HNF-1 alpha and HNF-1 beta (vHNF-1) share dimerization and homeo domains, but not activation domains, and form heterodimers in vitro. Genes Dev. 1991;5:1042-56 pubmed
    ..These studies define a pair of homeo domain proteins that have the potential to interact to produce an embryologically complex pattern of gene expression. ..
  40. Wu K, Wilson D, Shih C, Darlington G. The transcription factor HNF1 acts with C/EBP alpha to synergistically activate the human albumin promoter through a novel domain. J Biol Chem. 1994;269:1177-82 pubmed
    b>HNF1 and C/EBP alpha are transcription factors that bind to and trans-activate the human albumin gene proximal promoter...
  41. Frayling T, Bulamn M, Ellard S, Appleton M, Dronsfield M, Mackie A, et al. Mutations in the hepatocyte nuclear factor-1alpha gene are a common cause of maturity-onset diabetes of the young in the U.K. Diabetes. 1997;46:720-5 pubmed
    ..K. families and result in early onset NIDDM with a progressive clinical course. Mutation-based genetic counseling can now be considered for the majority of patients with MODY. ..
  42. Ban N, Yamada Y, Someya Y, Miyawaki K, Ihara Y, Hosokawa M, et al. Hepatocyte nuclear factor-1alpha recruits the transcriptional co-activator p300 on the GLUT2 gene promoter. Diabetes. 2002;51:1409-18 pubmed
    ..In addition, these results provided new insight into the regulatory function of HNF-1alpha by suggesting a molecular basis for human GLUT2 gene expression. ..
  43. Chi Y, Frantz J, Oh B, Hansen L, Dhe Paganon S, Shoelson S. Diabetes mutations delineate an atypical POU domain in HNF-1alpha. Mol Cell. 2002;10:1129-37 pubmed
    ..The numerous diabetes-causing mutations in HNF-1alpha thus identified a previously unrecognized POU domain which was used as a search model to identify additional POU domain proteins in sequence databases. ..
  44. Sellers E, Triggs Raine B, Rockman Greenberg C, Dean H. The prevalence of the HNF-1alpha G319S mutation in Canadian aboriginal youth with type 2 diabetes. Diabetes Care. 2002;25:2202-6 pubmed
    ..Further investigation of the pathophysiology of the S319 homo- and heterozygote is needed because it may impact treatment and/or prevention of this disease. ..
  45. Anuradha S, Radha V, Deepa R, Hansen T, Carstensen B, Pedersen O, et al. A prevalent amino acid polymorphism at codon 98 (Ala98Val) of the hepatocyte nuclear factor-1alpha is associated with maturity-onset diabetes of the young and younger age at onset of type 2 diabetes in Asian Indians. Diabetes Care. 2005;28:2430-5 pubmed
    ..0002). Among Asian Indians, the Ala98Val polymorphism of HNF1alpha gene is associated with MODY and with earlier age at onset of type 2 diabetes. ..
  46. Thanabalasingham G, Pal A, Selwood M, Dudley C, Fisher K, Bingley P, et al. Systematic assessment of etiology in adults with a clinical diagnosis of young-onset type 2 diabetes is a successful strategy for identifying maturity-onset diabetes of the young. Diabetes Care. 2012;35:1206-12 pubmed publisher
    ..type 1 diabetes, we sequenced hepatocyte nuclear factor 1 α (HNF1A) and hepatocyte nuclear factor 4 α (HNF4A) in 20 with residual β-cell function ≥ 3 years from diagnosis (random or glucagon-stimulated C-peptide â..
  47. Bach I, Yaniv M. More potent transcriptional activators or a transdominant inhibitor of the HNF1 homeoprotein family are generated by alternative RNA processing. EMBO J. 1993;12:4229-42 pubmed
    ..the isolation of cDNAs from human liver encoding several isoforms of the hepatocyte nuclear factor homeoproteins HNF1 and vHNF1 generated by the differential use of polyadenylation sites and by alternative splicing...
  48. Mauvais Jarvis F, Boudou P, Sobngwi E, Riveline J, Kevorkian J, Villette J, et al. The polymorphism Gly574Ser in the transcription factor HNF-1alpha is not a marker of adult-onset ketosis-prone atypical diabetes in Afro-Caribbean patients. Diabetologia. 2003;46:728-9 pubmed
  49. Stride A, Pearson E, Brown A, Gooding K, Castleden H, Hattersley A. Serum amino acids in patients with mutations in the hepatocyte nuclear factor-1 alpha gene. Diabet Med. 2004;21:928-30 pubmed
    Knockout mice lacking both copies of the hepatocyte nuclear factor 1 (HNF1) gene have altered serum levels of amino acids and generalized aminoaciduria...
  50. Aguilera E, Casamitjana R, Ercilla G, Oriola J, Nicoletti F, Gomis R, et al. Clinical characteristics, beta-cell function, HLA class II and mutations in MODY genes in non-paediatric subjects with Type 1 diabetes without pancreatic autoantibodies. Diabet Med. 2005;22:137-43 pubmed
    ..Variants in HNF-1alpha and HNF-4alpha are unlikely to be major contributors to the pathogenesis of diabetes in antibody-negative T1D. ..
  51. Umeyama K, Watanabe M, Saito H, Kurome M, Tohi S, Matsunari H, et al. Dominant-negative mutant hepatocyte nuclear factor 1alpha induces diabetes in transgenic-cloned pigs. Transgenic Res. 2009;18:697-706 pubmed publisher
    ..Histochemical analysis of pancreas tissue from the cloned pigs showed small and irregularly formed Langerhans Islets, in which poor insulin secretion was detected. ..
  52. Ley S, Hegele R, Connelly P, Harris S, Mamakeesick M, Cao H, et al. Assessing the association of the HNF1A G319S variant with C-reactive protein in Aboriginal Canadians: a population-based epidemiological study. Cardiovasc Diabetol. 2010;9:39 pubmed publisher
    ..Common variants of the hepatocyte nuclear factor 1A (HNF1A) gene encoding HNF-1alpha have been associated with plasma CRP in predominantly European Caucasian samples...
  53. Lauc G, Essafi A, Huffman J, Hayward C, Knezevic A, Kattla J, et al. Genomics meets glycomics-the first GWAS study of human N-Glycome identifies HNF1? as a master regulator of plasma protein fucosylation. PLoS Genet. 2010;6:e1001256 pubmed publisher
    ..of 2,705 individuals in three population cohorts showed that common variants in the Hepatocyte Nuclear Factor 1? (HNF1?) and fucosyltransferase genes FUT6 and FUT8 influence N-glycan levels in human plasma...
  54. Bach I, Mattei M, Cereghini S, Yaniv M. Two members of an HNF1 homeoprotein family are expressed in human liver. Nucleic Acids Res. 1991;19:3553-9 pubmed
    b>HNF1 is a transcriptional activator, required for the liver-specific expression of a variety of genes, that binds to DNA as a dimer via the most diverged homeodomain known so far...
  55. Urhammer S, Rasmussen S, Kaisaki P, Oda N, Yamagata K, Møller A, et al. Genetic variation in the hepatocyte nuclear factor-1 alpha gene in Danish Caucasians with late-onset NIDDM. Diabetologia. 1997;40:473-5 pubmed
    ..genome mapping study has localized a locus termed NIDDM2 that maps to the region of chromosome 12 that includes MODY3, one of the three genes responsible for maturity-onset diabetes of the young, a monogenic form of NIDDM ..
  56. Pontoglio M, Prie D, Cheret C, Doyen A, Leroy C, Froguel P, et al. HNF1alpha controls renal glucose reabsorption in mouse and man. EMBO Rep. 2000;1:359-65 pubmed
    ..that is expressed in liver, kidney, pancreas and intestine, result in maturity onset diabetes of the young type 3 (MODY3)...
  57. Collet C, Ducorps M, Mayaudon H, Dupuy O, Ceppa F, Boutin P, et al. Prevalence of the missense mutation Gly574Ser in the hepatocyte nuclear factor-1alpha in Africans with diabetes. Diabetes Metab. 2002;28:39-44 pubmed
    ..Diabetes was as severe as in non carriers of mutation. This mutation has been implicated in atypical diabetes of Afro-American children. The study confirms its prevalence in Africans with diabetes. ..
  58. Johansen A, Ek J, Mortensen H, Pedersen O, Hansen T. Half of clinically defined maturity-onset diabetes of the young patients in Denmark do not have mutations in HNF4A, GCK, and TCF1. J Clin Endocrinol Metab. 2005;90:4607-14 pubmed
    ..aims of the present study were to examine the prevalence and nature of mutations in the three common MODY genes, HNF4A, GCK, and TCF1, in Danish patients with a clinical diagnosis of MODY and to describe metabolic differences in ..
  59. Reiner A, Beleza S, Franceschini N, Auer P, Robinson J, Kooperberg C, et al. Genome-wide association and population genetic analysis of C-reactive protein in African American and Hispanic American women. Am J Hum Genet. 2012;91:502-12 pubmed publisher
    ..associated with CRP through GWASs of European populations, most loci (LEPR, IL1RN, IL6R, GCKR, NLRP3, HNF1A, HNF4A, and APOC1) showed consistent patterns of association with CRP in AA and HA women...
  60. Courtois G, Baumhueter S, Crabtree G. Purified hepatocyte nuclear factor 1 interacts with a family of hepatocyte-specific promoters. Proc Natl Acad Sci U S A. 1988;85:7937-41 pubmed
    ..We also show that this protein binds to the promoter of the surface-antigen gene of the hepatitis B virus, a virus characterized by a high degree of hepatotropism. ..
  61. Iwasaki N, Oda N, Ogata M, Hara M, Hinokio Y, Oda Y, et al. Mutations in the hepatocyte nuclear factor-1alpha/MODY3 gene in Japanese subjects with early- and late-onset NIDDM. Diabetes. 1997;46:1504-8 pubmed the hepatocyte nuclear factor (HNF)-1alpha gene are the cause of maturity-onset diabetes of the young type 3 (MODY3)...
  62. van Wering H, Huibregtse I, van der Zwan S, de Bie M, Dowling L, Boudreau F, et al. Physical interaction between GATA-5 and hepatocyte nuclear factor-1alpha results in synergistic activation of the human lactase-phlorizin hydrolase promoter. J Biol Chem. 2002;277:27659-67 pubmed
    ..Parallel mechanisms in other tissues as well as in Drosophila suggest that zinc finger/homeodomain interactions are an efficient pathway of cooperative activation of gene transcription that has been conserved throughout evolution. ..
  63. Pearson E, Badman M, Lockwood C, Clark P, Ellard S, Bingham C, et al. Contrasting diabetes phenotypes associated with hepatocyte nuclear factor-1alpha and -1beta mutations. Diabetes Care. 2004;27:1102-7 pubmed
    ..This result suggests a new etiological pathway for insulin resistance involving HNF-1beta. ..
  64. Harries L, Ellard S, Stride A, Morgan N, Hattersley A. 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. Hum Mol Genet. 2006;15:2216-24 pubmed
    ..Heterozygous mutations in the transcription factor hepatocyte nuclear factor-1 alpha (HNF1A or TCF1 gene) result in early-onset diabetes as a result of pancreatic beta-cell dysfunction...
  65. Winckler W, Weedon M, Graham R, McCarroll S, Purcell S, Almgren P, et al. Evaluation of common variants in the six known maturity-onset diabetes of the young (MODY) genes for association with type 2 diabetes. Diabetes. 2007;56:685-93 pubmed
    ..We combined these results with our previous studies on HNF4alpha and TCF1 and explicitly tested for gene-gene interactions among these variants and with several known type 2 diabetes ..
  66. Yoshiuchi I, Yamagata K, Yang Q, Iwahashi H, Okita K, Yamamoto K, et al. Three new mutations in the hepatocyte nuclear factor-1alpha gene in Japanese subjects with diabetes mellitus: clinical features and functional characterization. Diabetologia. 1999;42:621-6 pubmed
    ..Mutations in the HNF-1alpha gene may affect the normal islet function by different molecular mechanisms. ..
  67. Wang H, Antinozzi P, Hagenfeldt K, Maechler P, Wollheim C. Molecular targets of a human HNF1 alpha mutation responsible for pancreatic beta-cell dysfunction. EMBO J. 2000;19:4257-64 pubmed
    ..alpha)-P291fsinsC, the most common mutation associated with subtype 3 of maturity-onset diabetes of the young (MODY3)...
  68. Bluteau O, Jeannot E, Bioulac Sage P, Marqués J, Blanc J, Bui H, et al. Bi-allelic inactivation of TCF1 in hepatic adenomas. Nat Genet. 2002;32:312-5 pubmed
    ..mutations of TCF1 have been identified in individuals affected with maturity-onset diabetes of the young type 3 (MODY3; ref. 3)...
  69. Harries L, Hattersley A, Ellard S. Messenger RNA transcripts of the hepatocyte nuclear factor-1alpha gene containing premature termination codons are subject to nonsense-mediated decay. Diabetes. 2004;53:500-4 pubmed
    ..Haploinsufficiency is therefore likely to be the most important mutational mechanism of HNF-1alpha mutations causing MODY. ..
  70. Holmkvist J, Cervin C, Lyssenko V, Winckler W, Anevski D, Cilio C, et al. Common variants in HNF-1 alpha and risk of type 2 diabetes. Diabetologia. 2006;49:2882-91 pubmed known as the transcription factor 1 gene [TCF1]) cause the most common monogenic form of diabetes, MODY3, but it is not known if common variants in HNF-1a are associated with decreased transcriptional activity or ..
  71. Holmkvist J, Almgren P, Lyssenko V, Lindgren C, Eriksson K, Isomaa B, et al. Common variants in maturity-onset diabetes of the young genes and future risk of type 2 diabetes. Diabetes. 2008;57:1738-44 pubmed publisher
  72. Erdmann J, Grosshennig A, Braund P, König I, Hengstenberg C, Hall A, et al. New susceptibility locus for coronary artery disease on chromosome 3q22.3. Nat Genet. 2009;41:280-2 pubmed publisher
    ..We identified one new CAD risk locus on 3q22.3 in MRAS (P = 7.44 x 10(-13); OR = 1.15, 95% CI = 1.11-1.19), and suggestive association with a locus on 12q24.31 near HNF1A-C12orf43 (P = 4.81 x 10(-7); OR = 1.08, 95% CI = 1.05-1.11).
  73. Servitja J, Pignatelli M, Maestro M, Cardalda C, Boj S, Lozano J, et al. Hnf1alpha (MODY3) controls tissue-specific transcriptional programs and exerts opposed effects on cell growth in pancreatic islets and liver. Mol Cell Biol. 2009;29:2945-59 pubmed publisher
    Heterozygous HNF1A mutations cause pancreatic-islet beta-cell dysfunction and monogenic diabetes (MODY3). Hnf1alpha is known to regulate numerous hepatic genes, yet knowledge of its function in pancreatic islets is more limited...
  74. Najdi R, Syed A, Arce L, Theisen H, Ting J, Atcha F, et al. A Wnt kinase network alters nuclear localization of TCF-1 in colon cancer. Oncogene. 2009;28:4133-46 pubmed publisher
    ..We propose that dnTCF-1 provides homeostatic regulation of Wnt signaling and growth in normal colon, and the alterations in nuclear export and promoter usage contribute to aberrant Wnt activity in colon cancer. ..
  75. Pierce B, Ahsan H. Genome-wide "pleiotropy scan" identifies HNF1A region as a novel pancreatic cancer susceptibility locus. Cancer Res. 2011;71:4352-8 pubmed publisher
    ..Of the 1,087 SNPs tested, the strongest association observed was for HNF1A SNP rs7310409 (P = 3 × 10(-5); P(Bonferroni) = 0...
  76. Yamagata K, Oda N, Kaisaki P, Menzel S, Furuta H, Vaxillaire M, et al. Mutations in the hepatocyte nuclear factor-1alpha gene in maturity-onset diabetes of the young (MODY3). Nature. 1996;384:455-8 pubmed
    ..Here we show that subjects with the MODY3-form of NIDDM have mutations in the gene encoding hepatocyte nuclear factor-1alpha (HNF-1alpha, which is encoded ..
  77. Hegele R, Cao H, Harris S, Hanley A, Zinman B. The hepatic nuclear factor-1alpha G319S variant is associated with early-onset type 2 diabetes in Canadian Oji-Cree. J Clin Endocrinol Metab. 1999;84:1077-82 pubmed
    ..Also, G319S is associated with a distinct form of type 2 diabetes, characterized by onset at an earlier age, lower body mass, and a higher postchallenge plasma glucose. ..
  78. Weedon M, Owen K, Shields B, Hitman G, Walker M, McCarthy M, et al. A large-scale association analysis of common variation of the HNF1alpha gene with type 2 diabetes in the U.K. Caucasian population. Diabetes. 2005;54:2487-91 pubmed
    HNF1alpha (TCF1) is a key transcription factor that is essential for pancreatic beta-cell development and function. Rare mutations of HNF1alpha cause maturity-onset diabetes of the young...
  79. Ridker P, Pare G, Parker A, Zee R, Danik J, Buring J, et al. Loci related to metabolic-syndrome pathways including LEPR,HNF1A, IL6R, and GCKR associate with plasma C-reactive protein: the Women's Genome Health Study. Am J Hum Genet. 2008;82:1185-92 pubmed publisher
    ..9 x 10(-)(8) to 6.2 x 10(-)(28)). Two of these loci (GCKR and HNF1A) are suspected or known to be associated with maturity-onset diabetes of the young, one is a gene-desert region on ..
  80. Michels A, Hagen T. Hepatocyte nuclear factor 1 is essential for transcription of sodium-dependent vitamin C transporter protein 1. Am J Physiol Cell Physiol. 2009;297:C1220-7 pubmed publisher
    ..within this sequence, reporter constructs showed that basal transcription required the binding of hepatic nuclear factor 1 (HNF-1) to its cognate sequence...
  81. Thanabalasingham G, Shah N, Vaxillaire M, Hansen T, Tuomi T, Gašperíková D, et al. A large multi-centre European study validates high-sensitivity C-reactive protein (hsCRP) as a clinical biomarker for the diagnosis of diabetes subtypes. Diabetologia. 2011;54:2801-10 pubmed publisher
    ..demonstrated that high-sensitivity C-reactive protein (hsCRP) levels are lower in UK patients with hepatocyte nuclear factor 1 alpha (HNF1A)-MODY than in other diabetes subtypes...
  82. Hoskins J, Jia J, Flandez M, Parikh H, Xiao W, Collins I, et al. Transcriptome analysis of pancreatic cancer reveals a tumor suppressor function for HNF1A. Carcinogenesis. 2014;35:2670-8 pubmed publisher
    ..Sub-network enrichment analyses identified HNF1A as the regulator of the most significantly and consistently dysregulated expression sub-network in pancreatic ..
  83. Hansen T, Eiberg H, Rouard M, Vaxillaire M, Møller A, Rasmussen S, et al. 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. Diabetes. 1997;46:726-30 pubmed
    One form of maturity-onset diabetes of the young (MODY3) results from mutations in the hepatocyte nuclear factor (HNF)-1alpha gene, located on chromosome 12q24.2...
  84. Magee T, Cai Y, El Houseini M, Locker J, Wan Y. Retinoic acid mediates down-regulation of the alpha-fetoprotein gene through decreased expression of hepatocyte nuclear factors. J Biol Chem. 1998;273:30024-32 pubmed
    ..In addition, HNF4, which is not known to bind to the AFP promoter but does regulate HNF1, was also diminished. The levels of HNF1 and HNF4 mRNA were also decreased following RA treatment...
  85. Ishii Y, Hansen A, Mackenzie P. Octamer transcription factor-1 enhances hepatic nuclear factor-1alpha-mediated activation of the human UDP glucuronosyltransferase 2B7 promoter. Mol Pharmacol. 2000;57:940-7 pubmed
    ..UGT2B7 promoter activity with the HNF1/AT-rich element was stimulated by cotransfection with HNF1alpha...
  86. Kim K, Kang K, Chi Y, Chang I, Lee M, Kim K, et al. Identification and functional characterization of a novel mutation of hepatocyte nuclear factor-1alpha gene in a Korean family with MODY3. Diabetologia. 2003;46:721-7 pubmed
    ..results suggest that the mutation of HNF-1alpha at codon 263 from arginine to leucine leads to the development of MODY3 through decreased insulin production and defective glucose sensing...
  87. Pearson E, Pruhova S, Tack C, Johansen A, Castleden H, Lumb P, et al. Molecular genetics and phenotypic characteristics of MODY caused by hepatocyte nuclear factor 4alpha mutations in a large European collection. Diabetologia. 2005;48:878-85 pubmed
    ..We suggest that sequencing of HNF-4alpha should be performed in patients with clinical characteristics of HNF-1alpha MODY in whom mutations in HNF-1alpha are not found. ..
  88. Rowley C, Staloch L, Divine J, McCaul S, Simon T. Mechanisms of mutual functional interactions between HNF-4alpha and HNF-1alpha revealed by mutations that cause maturity onset diabetes of the young. Am J Physiol Gastrointest Liver Physiol. 2006;290:G466-75 pubmed
    ..These results suggest HNF-1alpha-HNF-4alpha functional interactions are accomplished by regulating factor promoter occupancy and that defective factor-factor interactions may contribute to the MODY phenotype. ..
  89. Hwang J, Shin C, Yang S, Jung S, Huh N. Genetic and clinical characteristics of Korean maturity-onset diabetes of the young (MODY) patients. Diabetes Res Clin Pract. 2006;74:75-81 pubmed
    ..diabetes of the young (MODY) is mostly caused by mutations of the hepatocyte nuclear factor (HNF)-1alpha (MODY3) and glucokinase (MODY2) genes in Caucasians...
  90. Jain S, Li Y, Patil S, Kumar A. HNF-1alpha plays an important role in IL-6-induced expression of the human angiotensinogen gene. Am J Physiol Cell Physiol. 2007;293:C401-10 pubmed
  91. Harries L, Sloman M, Sellers E, Hattersley A, Ellard S. Diabetes susceptibility in the Canadian Oji-Cree population is moderated by abnormal mRNA processing of HNF1A G319S transcripts. Diabetes. 2008;57:1978-82 pubmed publisher
    The G319S HNF1A variant is associated with an increased risk of type 2 diabetes in the Canadian Oji-Cree population...