Human ‘Domainome’ reveals root cause of inherited conditions.
 
The largest catalogue of human protein variants to date has revealed that protein destabilisation is the main driver of inherited genetic conditions and paves the way for precision medicine and A.I. driven treatments.
 
Most genetic changes that swap one amino acid for another cause disease by making the protein less stable, according to the largest study of human protein variants to date. Unstable proteins are more likely to misfold and degrade, causing them to stop working or accumulate in harmful amounts inside cells.
 
The study, published today (8 January 2025) in the research journal Nature, helps explain why minimal changes in the human genome, also known as missense variants, can cause disease at the molecular level.