Hepatocyte nuclear factor 1 alpha (HNF-1 alpha) mutations in maturity-onset diabetes of the young

Hum Mutat. 2000 Nov;16(5):377-85. doi: 10.1002/1098-1004(200011)16:5<377::AID-HUMU1>3.0.CO;2-2.


Maturity-onset diabetes of the young (MODY) is a monogenic form of diabetes mellitus characterized by autosomal dominant inheritance, early age of onset (<25 years) and pancreatic beta-cell dysfunction. MODY is genetically heterogeneous with five different genes identified to date: hepatocyte nuclear factor-4 alpha (HNF-4 alpha) [MODY1]; glucokinase [MODY2]; hepatocyte nuclear factor-1 alpha (HNF-1 alpha) [MODY3]; insulin promoter factor-1 (IPF-1) [MODY4]; and hepatocyte nuclear factor-1 beta (HNF-1 beta) [MODY5]. Mutations in the HNF-1 alpha gene represent a common cause of MODY in the majority of populations studied. Sixty-five different mutations have been described in a total of 116 families. The most common mutation is a C-insertion (P291fsinsC) in the polyC tract of exon 4, which has been reported in 22 families. The identification of an HNF-1 alpha gene mutation in a patient with type 2 diabetes confirms the diagnosis of MODY and has important implications for clinical management.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Adult
  • Animals
  • DNA-Binding Proteins*
  • Diabetes Mellitus, Type 2 / genetics*
  • Hepatocyte Nuclear Factor 1
  • Hepatocyte Nuclear Factor 1-alpha
  • Hepatocyte Nuclear Factor 1-beta
  • Humans
  • Mutation / genetics*
  • Nuclear Proteins / genetics*
  • Polymorphism, Genetic / genetics
  • Transcription Factors / genetics*


  • DNA-Binding Proteins
  • HNF1A protein, human
  • HNF1B protein, human
  • Hepatocyte Nuclear Factor 1-alpha
  • Nuclear Proteins
  • Transcription Factors
  • Hepatocyte Nuclear Factor 1
  • Hepatocyte Nuclear Factor 1-beta