Uncovering Glycoprotein and Deregulated Gene Targets in OGT-Linked Intellectual Disability

X-linked intellectual disability (XLID) is a rare genetic condition that primarily affects boys and leads to significant challenges in learning, development, and communication. In some patients, XLID is caused by mutations in the OGT gene that is located on the X chromosome and plays a crucial role in cellular function by adding a specific sugar molecule, called O-GlcNAc, to proteins inside our cells. This sugar modification is essential for the normal operation of many cellular processes, including gene expression and protein stability. Our research aims to understand how mutations in the OGT gene lead to XLID. To achieve this, we have developed a specialized cell line that mimics the reduced levels of OGT found in patients with XLID. This cell line allows us to control and study the effects of OGT reduction at the level of the molecules inside the cell. Using advanced techniques created by our collaborator, we will make a comprehensive catalog of all the proteins that are modified by O-GlcNAc in these cells. By identifying which proteins lose their sugar tags when OGT is reduced, we hope to uncover the molecular mechanisms underlying XLID. This information will provide critical insights into how the disease develops and progresses, potentially revealing new targets for therapeutic intervention.