MODY mutations in transcription factors HNF1A and HNF1B affect the production of interferon signaling proteins: evidence at the proteome level

Abstract

We investigated the proteomic consequences of MODY-associated mutations in the transcription factors HNF1A and HNF1B using two cell line models. Quantitative label-free mass spectrometry, employing both data-dependent and data-independent acquisition methods, revealed consistent suppression of energy metabolism and interferon signaling pathways. Pathway and protein interaction analyses confirmed these findings. In cells with the HNF1A frameshift mutation, several predicted transcriptional targets, including A1CF, were significantly downregulated. These results reinforce the link between HNF1A/HNF1B function and mitochondrial activity as well as innate immune signaling, providing a foundation for further mechanistic studies and causal inference research.