nonsense mutation

A nonsense mutation is a substitution that turns a codon for an amino acid into a stop codon — a signal that tells the ribosome to halt. It is like inserting a period in the middle of a sentence: everything after it is simply not read.

Three codons (UAA, UAG, UGA) mean stop. When a point mutation creates one of these prematurely, translation ends early and the protein is cut short. A truncated protein is usually missing whole functional regions and so is typically non-functional, making nonsense mutations a common cause of loss of function.

Cells have a quality-control system called nonsense-mediated decay that recognises many of these prematurely stopped messenger RNAs and destroys them before a faulty protein is even made. Because of this, a nonsense mutation often results in little or no protein rather than a shortened one — an important detail when designing therapies that try to read through premature stops.