Identification of a new genetic mutation associated with intellectual disability

Study contributes to the understanding of mechanisms involved in neurodevelopmental disorders

Once a disease-related protein or enzyme is identified as a therapeutic target, the study of its three-dimensional structure – the positions of each of its atoms and their interactions – allows a deeper understanding of its mechanisms of action.

This is possible not only for these substances produced by microorganisms, such as viruses or bacteria, capable of attacking our body. It is also possible, for example, to understand molecules normally produced by the human body itself, but which had their structure and function altered due to some genetic mutation.

Thus, in an article recently published in Nature Chemical Biology, Juliana F. de Oliveira, of the Brazilian Biosciences National Laboratory (LNBio), and collaborators elucidates the mechanism of action of a new genetic mutation in the UBE2A gene identified in patients with intellectual disability.

The UBE2A gene is located on the X chromosome and encodes the protein of the same name that participates in the process of “labeling” defective proteins inside the cell. This labeling is done by adding and protein called ubiquitin to the defective proteins as if it were a label. Next, under normal conditions, the defective proteins are sent for degradation.

>Read more on the Brazilian Synchrotron Light Laboratory (LNLS) website

Image: Overlap of the patient’s UBE2A protein structure (blue) with the normal protein (gray) evidences similarity between them. On the right, it is shown in detail the only altered amino acid in the patient’s protein due to the genetic mutation.