HNF1A encodes a transcriptional activator that regulates the tissue specific expression of multiple genes, especially in pancreatic islet cells and in liver. The encoded protein functions as a homodimer and binds to the inverted palindrome 5'-GTTAATNATTAAC-3'.
Defects in HNF1A are a cause of hepatic adenomas familial (HEPAF). Hepatic adenomas are rare benign liver tumors of presumable epithelial origin that develop in an otherwise normal liver. Hepatic adenomas may be single or multiple. They consist of sheets of well-differentiated hepatocytes that contain fat and glycogen and can produce bile. Bile ducts or portal areas are absent. Kupffer cells, if present, are reduced in number and are non-functional. Conditions associated with adenomas are insulin-dependent diabetes mellitus and glycogen storage diseases (types 1 and 3).
Somatic HNF1A mutations (deletions, insertions, substitutions…) have been observed in liver (about 20% of cases), large intestine, endometrium and breast tumors. Mutation distribution is variable, with, however, amino acids 291 and 292 as hot spots for deletions and insertions, respectively.
References (open access):
Genotype phenotype classification of hepatocellular adenoma. Bioulac-Sage P, Blanc JF, Rebouissou S, Balabaud C, Zucman-Rossi J. World J Gastroenterol. 2007 May 21;13(19):2649-54.
Spectrum of HNF1A somatic mutations in hepatocellular adenoma differs from that in patients with MODY3 and suggests genotoxic damage. Jeannot E, Mellottee L, Bioulac-Sage P, Balabaud C, Scoazec JY, Tran Van Nhieu J, Bacq Y, Michalak S, Buob D; Groupe d'étude Génétique des Tumeurs Hépatiques (INSERM Network), Laurent-Puig P, Rusyn I, Zucman-Rossi J. Diabetes. 2010 Jul;59(7):1836-44.