gain-of-function

A gain-of-function mutation gives a gene product a new ability or makes it more active, louder, or always on, rather than simply breaking it. If a loss-of-function mutation is a broken tool, a gain-of-function mutation is a tool that now does something extra or refuses to switch off.

This can happen in several ways: a protein may become overactive, lose the off-switch that normally regulates it, be made in too much or in the wrong place, or acquire an entirely new harmful property. In cancer, gain-of-function mutations turn ordinary growth-promoting genes called proto-oncogenes into hyperactive oncogenes that drive uncontrolled division.

Gain-of-function mutations tend to be dominant, because the altered gene product imposes its new behaviour even when a normal copy of the gene is still present. This makes them distinct from most loss-of-function mutations and important to recognise, since a single altered allele can produce a phenotype on its own.