Loss-of-function mutation


A loss-of-function mutation is any mutation that causes a gene to lose its function, either partially or completely. An organism with such a mutation is called a loss-of-function mutant. Subcategories of loss-of-function mutation include amorphic and hypomorphic mutations.

An amorphic mutation is a type of loss-of-function mutation that causes a complete loss of gene function, either by preventing transcription (creating an RNA null), or preventing translation (creating a protein null). An amorphic allele elicits the same phenotype whether homozygous or heterozygous to a chromosome deletion that disrupts the same gene. An amorphic allele is commonly recessive to its wild-type counterpart, though it is possible for an amorphic allele to be dominant where two copies of the gene are required to elicit a normal phenotype (i.e. in cases of haploinsufficiency)

A hypomorphic mutation is a type of loss-of-function mutation that causes only a partial loss of gene function. There is a reduction in RNA and protein expression, but not a complete elimination. The phenotype of a hypomorph is more severe in trans to a deletion allele than when homozygous. Hypomorphs are usually recessive, but may occasionally be dominant due to haploinsufficiency.