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Updated: Aug 21, 2026

Determining the Likelihood of Variant Pathogenicity Using Amino Acid-level Signal-to-Noise Analysis of Genetic Variation
Published on: January 16, 2019
Beyond the signal sequence: protein routing in health and disease
Cecilia Castro-Fernández1, Guadalupe Maya-Núñez, P Michael Conn
1Oregon National Primate Research Center/Oregon Health and Science University, 505 NW 185th Avenue, Beaverton, Oregon 97006, USA.
Abstract:
Receptors, hormones, enzymes, ion channels, and structural components of the cell are created by the act of protein synthesis. Synthesis alone is insufficient for proper function, of course; for a cell to operate effectively, its components must be correctly compartmentalized. The mechanism by which proteins maintain the fidelity of localization warrants attention in light of the large number of different molecules that must be routed to distinct subcellular loci, the potential for error, and resultant disease. This review summarizes diseases known to have etiologies based on defective protein folding or failure of the cell's quality control apparatus and presents approaches for therapeutic intervention.
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