Investigation of ALX4 variants in protein models to explain phenotype diversity

The ALX gene family encodes homeodomain-containing transcription factors that play an important role in embryonic development and whose mutations cause craniofacial malformations in human. While ALX1 and ALX3 mutations lead to loss-of-function mutations in the protein, ALX4 shows different phenotypes resulting in loss and gain of function. The full three-dimensional structure of ALX4 and the reason for this behavior is not yet known. In this thesis, we first tried to model the ALX4 protein. It was determined that the effects of changes in the homeodomain region, which can be reliably modeled, can be predicted to be loss or gain of function by looking at amino acid interactions.