Multifaceted disruption of AMPA receptor signaling by <i>CACNG8</i> variants: Integrated evidence from human genetics and molecular simulation.

ABSTRACT: The Transmembrane AMPA Receptor Regulatory Protein Gamma-8 (TARP γ-8), encoded by CACNG8, regulates AMPA receptor (AMPAR) trafficking, gating, and synaptic localization. Although well-characterized in central synapses, its role in retinal development and disease remains underexplored. This study investigates CACNG8 within the context of inherited retinal dystrophies (IRDs) by integrating human genetics within silico structural analysis. Whole Exome Sequencing (WES) was performed on IRD-affected families with atypical phenotypes-such as residual photoreceptor activity alongside severe optic atrophy or abnormal electroretinogram (ERG) profiles-yet no biallelic mutations in known IRD genes. In all families, rare heterozygous or compound heterozygous CACNG8 variants were i

SUBMITTER: Alibrandi S 

PROVIDER: S-EPMC12538086 | biostudies-literature | 2025

REPOSITORIES: biostudies-literature