Gain-of-function mutation


A gain-of-function mutation is any mutation that creates a gene with a new and abnormal function. An organism with such a mutation is called a gain-of-function mutant. Subcategories of gain-of-function mutation include antimorphic, hypermorphic and neomorphic mutations.

Antimorphic mutations (sometimes called dominant negative mutations) create dominant alleles that act antagonistically to normal gene activity. Thus increasing wild-type gene function serves to lessen the phenotypic severity of an antimorphic mutation. Antimorphic mutations may be detriment to an organism if, for example, the antimorphic allele codes for one monomer in a dimeric protein (the whole protein will become defunct).

Hypermorphic mutations create dominant alleles that act in coordination with gene activity; thus they increase it. A hypermorph might result from gene amplification or constitutive protein expression. The phenotype of a hypermorph is worsened by increasing wild-type gene activity; it is lessened by reducing wild-type gene activity.

Neomorphic mutations creates dominant alleles with a completely novel function. A neomorph may result in ectopic mRNA or protein expression, or the synthesis of a novel protein with a new function. Unlike antimorphic and hypermorphic mutations, neomorphic mutations are unaffected by changes in the gene dose of the wild-type allele.