biostudies-literatureFitzHugh ZTNational Institutes of Health355https://www.ebi.ac.uk/biostudies/studies/S-EPMC9953674biostudies-literatureUnknown13(2)All proteins have a carboxyl terminus, and we previously summarized eight mutations in binding and trafficking sequence determinants in the C-terminus that, when disrupted, cause human diseases. These sequence elements for binding and trafficking sites, as well as post-translational modifications (PTMs), are called minimotifs or short linear motifs. We wanted to determine how frequently mutations in minimotifs in the C-terminus cause disease. We searched specifically for PTMs because mutation of a modified amino acid almost always changes the chemistry of the side chain and can be interpreted as loss-of-function. We analyzed data from ClinVar for disease variants, Minimotif Miner and the C-terminome for PTMs, and RefSeq for protein sequences, yielding 20 such potential disease-causing variBiomoleculesSystematic Assessment of Protein C-Termini Mutated in Human Disorders.PMC9953674R15GM107983R01GM079689P20GM121325LM010101GM103440Schiller MRFitzHugh ZTfalseSystematic Assessment of Protein C-Termini Mutated in Human Disorders.All proteins have a carboxyl terminus, and we previously summarized eight mutations in binding and trafficking sequence determinants in the C-terminus that, when disrupted, cause human diseases. These sequence elements for binding and trafficking sites, as well as post-translational modifications (PTMs), are called minimotifs or short linear motifs. We wanted to determine how frequently mutations in minimotifs in the C-terminus cause disease. We searched specifically for PTMs because mutation of a modified amino acid almost always changes the chemistry of the side chain and can be interpreted as loss-of-function. We analyzed data from ClinVar for disease variants, Minimotif Miner and the C-terminome for PTMs, and RefSeq for protein sequences, yielding 20 such potential disease-causing vari2023-01-01T00:00:00Z2023 Feb2025-04-05T13:21:01.528Z2024-10-15T13:18:12.26ZS-EPMC99536743683072410.3390/biom13020355