N-methyl-d-aspartate (NMDA) receptor genetics: The power of paralog homology and protein dynamics in defining dominant genetic variants.

ABSTRACT: Predicting genotype-to-phenotype correlations from genomic variants has been challenging, particularly for genes that have a complex balance of dominant and recessive inheritance for phenotypes. Variants in NMDA receptor components GRIN1, GRIN2A, and GRIN2B cause a myriad of dominant disease phenotypes, with the most common being epilepsy and autism spectrum disorder. Starting from the analysis of a variant of uncertain significance (VUS, GRIN2A G760S), we realized the need for tools to map dominant variants for the components of the NMDA receptor. Some variants within GRIN1, GRIN2A, and GRIN2B exert dominant epilepsy and developmental delay, yet other amino acid variants are conserved and predicted to alter protein function but do not have dominant phenotypes. Common variant annotation to

SUBMITTER: Charron JG 

PROVIDER: S-EPMC10472328 | biostudies-literature | 2022 Feb

REPOSITORIES: biostudies-literature