%0 Journal Article
%T From Genetic Variants to Cellular Function: Integrating Functional Genomics and Quantitative Proteomics to Resolve Mutation Effects
%A Sarah Thompson
%A Mariana Silva
%A Rafael Duarte
%A Emily Carter
%J Journal of Biochemical Technology
%@ 0974-2328
%D 2026
%V 17
%N 4
%R 10.51847/rzu9JnoYIJ
%P 84-91
%X A sequence variant can alter RNA processing, the amount of protein produced, its molecular properties, or a downstream cellular phenotype. These effects may coexist, yet measurements at different levels need not agree. Functional-genomic screens measure such endpoints as transcript inclusion, growth, or reporter activity, whereas quantitative proteomics measures sampled peptides and proteins under particular analytical conditions. This integrative methodological review examines how complementary assays can be interpreted together without equating a change in signal with a single disease mechanism. Targeted literature selection prioritizes experimental variant-effect maps, RNA analyses, quantitative protein measurements, and methodological guidance on assay calibration and missing observations. The proposed interpretation approach distinguishes directly observed molecular layers from inferred intermediates, accounts for endogenous versus engineered expression, and uses discordance to select discriminating experiments. Reduced protein abundance may explain impaired activity in some variants; other variants preserve abundance while changing catalysis, interactions, localization, or pathway output. Missing peptides, tissue-restricted transcripts, saturation of cellular readouts, and background-dependent effects further limit apparent agreement. Integration is most defensible when samples, isoforms, controls, normalization, biological context, and uncertainty are explicitly aligned. The resulting evidence can prioritize mechanistic hypotheses and validation experiments, but does not independently establish clinical pathogenicity.
%U https://jbiochemtech.com/article/from-genetic-variants-to-cellular-function-integrating-functional-genomics-and-quantitative-proteom-ueafqlyk7l5qtmo