TP53 and sickle cell disease: The extent of compensatory expression of the mutated gene and of other genes (epistasis) are important to understand the full proteostatic effects of mutations in a given protein, and such compensation will be protein-specific: For highly systemic proteins, compensation may be large, as seen e.g. in sickle cell disease where hemoglobin mutations reduce the oxygen-carrying ability of the protein and substantially increase the protein's expression [62], [63], or in cancers where mutant p53 are subject to higher expression levels [64].