Endocrine Abstracts

Investigating the protein structural context of human genetic variants offers a powerful framework for understanding their effects. Recent years have witnessed an exponential growth in our ability to access structural information about the human proteome, driven by advancements in cryo-electron microscopy and computational protein structure prediction, exemplified by AlphaFold. In this talk, I will first briefly cover approaches obtaining a 3D structural model of your protein of interest, including through computational structure prediction of individual proteins and protein complexes. Next, I will review computational tools for prediction of variant effects, focusing on tools that can be used to score variants in terms of their likely pathogenicity, and the increasing importance of protein structural information in this. Finally, I will discuss how protein structural models can be used provide insight into the likely molecular mechanisms underlying disease mutations, and how these mechanisms can have implications for genetic diagnosis and treatment.