MODY3 is located on chromosome 12q24.2 and encodes hepatocyte nuclear factor 1-alpha (HNF1A; OMIM 142410).  It is also known as TCF1 (transcription factor 1).  HNF1A is a transcription factor that regulates expression of the insulin gene and other genes encoding proteins involved in glucose transport and metabolism. MODY3 mutations may contribute to abnormal pancreatic islet cell development during fetal life, as well as impaired transcriptional regulation of genes involved in normal islet cell function. MODY3 mutations also influence expression of HNF4A (MODY1).  This suggests that the MODY transcription factors form a regulator network that is necessary to maintain glucose homostasis.

 

MODY3 mutations may also contribute to the development of T1D and T2D. Approximately 100 genetic variants of MODY3 have been identified.  These include frameshift, and missense mutations.  MODY3 accounts for the majority (~65%) of MODY cases.