Functional Analysis of the Yeast Counterpart to the Human GCN2 p.Glu738_Asp739insArgArg Variant

GCN2, a cytoplasmic protein kinase, helps cells adapt to nutrient deprivation and is implicated in various cancers. The GCN2 p.Glu738_Asp739insArgArg variant was found to be significantly enriched in a cohort of early-onset colorectal cancer cases, indicating possible lineage-associated predisposition. Introducing an equivalent variant into the yeast model Saccharomyces cerevisiae showed no direct impact on Gcn2 function, suggesting that the variant's pathogenicity likely does not simply stem from altered GCN2 enzyme activity. Our yeast-based study helped narrow potential mechanisms, accelerating efforts to understand the variant's role in colorectal cancer.