Gain of function mutation

When the protein product produced by a mutant gene acquires
a completely novel function, the mutation is referred to as
having a gain of function effect. These mutations usually result
in dominant phenotypes because of the independent action of
the gene product. The CAG repeat expansions in Huntington
disease and the spinocerebellar ataxias exert a gain of function
effect, by resulting in the incorporation of elongated
polyglutamine tracts in the protein products. This causes
formation of intracellular aggregates that result in neuronal
cell death. Mutations producing a gain of function effect are
likely to be very specific and other mutations in the same gene
are unlikely to produce the same phenotype. In the androgen
receptor gene, for example, a trinucleotide repeat expansion
mutation results in the phenotype of spinobulbar muscular
atrophy (Kennedy syndrome), whereas a point mutation
leading to loss of function results in the completely different
phenotype of testicular feminisation syndrome.