loss-of-function

A loss-of-function mutation reduces or abolishes what a gene's product can do. If the gene is a tool, this kind of mutation chips, blunts, or breaks the tool so it works poorly or not at all. It is the most common way that mutations cause disease.

The damage can act through several routes: a nonsense or frameshift change that truncates the protein, a missense change that cripples its active site, a deletion that removes the gene, or a mutation in a regulatory region that switches the gene off. When function drops only partly the allele is called hypomorphic; when it is wiped out completely it is called null, or amorphic.

Loss-of-function mutations are usually recessive, because one working copy of the gene is often enough to supply normal function — so an affected individual typically needs both copies altered. The exception is haploinsufficiency, where a single working copy cannot keep up and losing the other copy alone already causes a phenotype, making the loss behave as dominant.