PKD1 variants, protein structure and function

Now that we know that variants in PKD1 are associated with a disease we can start to use EMBL-EBI protein-centric resources to understand the potential effects of variants on protein structure and function.

These resources provide detailed information on where in the protein sequence such variants lie, and whether these variants overlap with domains and/or sites, potentially affect post-translational modification residues and/or other protein structural features.

Let’s take a look at UniProt’s Feature Viewer display for the human PKD1 protein (Figure 6).

The human PKD1 protein contains a number of disease reviewed variants. Not all of these variants are known to be pathogenic, however the Uniprot Sequence Viewer shows how the known variants overlap with other protein features. As you can see, there are many disease causing variants in PKD1. You can learn more about these variants and how they relate to the protein structure by clicking on them.

From UniProt you can also link out to PDBe where you can explore available protein structures for PKD1. We will look at this in more detail in the next case study.

As you have seen, starting with a gene of interest can unearth a wide variety of information to help you understand how variants in that gene contribute to health and disease and influence protein structure and function.