HNF1 (Hepatocyte Nuclear Factor-1) is a protein involved in liver development, metabolism and glucose homeostasis. HNF1α and 1β (vHNF1) are two related transcription factors of the homeodomain family. Unlike other family members, HNF1α and 1β have an extra 21 amino acid DNA binding segment in their homeobox, and a POU A-related domain that is involved in DNA binding. The N-terminus contains a dimerization domain allowing for homo- or heterodimerization. There are also three C-terminus activation domains that are rich in proline and glycine, proline and glutamine, and serine, respectively. HNF1α is located on chromosome 12 and HNF1β is found on chromosome 17.

HNF1 was originally discovered in the liver, where it was thought to be restricted. Later, it was also found to play important roles in the kidney, small intestine, thymus and pancreas. The HNF1 consensus-binding site is the inverted palindrome GTTAATNATTAAC. HNF1 can bind to this sequence as a homodimer, but other factors, such as NF-1 or C/EBP, are required for efficient transcriptional activity. HNF1 plays a crucial role in liver development during embryogenesis and metabolism homeostasis in the adult. It helps regulate such genes as glucose-cotransporter-2 in the kidney, phenylalanine hydroxylase (PAH) in the liver, and insulin, L-pyruvate kinase and aldolase B in pancreatic B cells.

Mutations in HNF1 have been implicated in the early onset of type II diabetes referred to as MODY (maturity onset diabetes of the young). MODY is an inherited disease characterized by early onset of diabetes mellitus. MODY3 and 5 represent mutations in genes encoding HNF1α and 1β, respectively. The most common form is MODY3, which accounts for about 60% of cases, while MODY5 is relatively rare. In all forms of MODY, insulin levels are affected by defective secretions of pancreatic B-cells.