Hepatocyte nuclear factor 1 alpha (HNF1A)

Hepatocyte nuclear factor 1 alpha (HNF1A) is a DNA-binding transcription factor from the HNF1 homeobox protein family, encoded by the HNF1A gene on chromosome 12q24.2. It contains a dimerization domain, an atypical POU-homeodomain for DNA binding, and a C-terminal transactivation domain. HNF1A regulates the expression of liver-specific and pancreatic genes involved in glucose transport, metabolism, and insulin secretion, playing a central role in glucose and lipid homeostasis as well as cell differentiation in liver, kidney, and pancreas. Mutations in HNF1A cause monogenic diabetes (MODY3) and are implicated in hepatic tumors and increased cardiovascular risk. Although no approved therapeutics directly target HNF1A, knowledge of its mutation status guides clinical management, especially in diabetes subtypes where sulfonylurea treatment is effective.

Other names

Hepatocyte nuclear factor 1αHNF-1αHNF1A homeobox ATCF1transcription factor 1MODY3 gene

In MODY3, sulfonylureas increase insulin release from pancreatic β-cells with defective HNF1A-mediated transcription; therapy leverages the remaining β-cell function.