James P Allen, Kathryn B Garber, Riley Perszyk, Cara T Khayat, Steven A Kell, Maki Kaneko, Catherine Quindipan, Sulagna Saitta, Roger L Ladda, Stacy Hewson, Michal Inbar-Feigenberg, Chitra Prasad, Asuri N Prasad, Leah Olewiler, Weiyi Mu, Liana S Rosenthal, Marcello Scala, Pasquale Striano, Federico Zara, Tyler W McCullock, Robin-Tobias Jauss, Johannes R Lemke, David M MacLean, Cheng Zhu, Hongjie Yuan, Scott J Myers, Stephen F Traynelis
GRID1 and GRID2 encode the enigmatic GluD1 and GluD2 proteins, which form tetrameric receptors that play important roles in synapse organization and development of the central nervous system. Variation in these genes has been implicated in neurodevelopmental phenotypes. We evaluated GRID1 and GRID2 human variants from the literature, ClinVar, and clinical laboratories and found that many of these variants reside in intolerant domains, including the amino terminal domain of both GRID1 and GRID2. Other conserved regions, such as the M3 transmembrane domain, show different intolerance between GRID1 and GRID2...
November 7, 2023: Human Molecular Genetics