Key: In the following sections, alleles are referred to as +=wildtype, m=mutant, Df=gene deletion, Dp=gene duplication. Phenotypes are compared with '>', meaning 'phenotype is more severe than'
Amorphic describes a mutation that causes complete loss of gene function. Amorph is sometimes used interchangeably with "genetic null". An amorphic mutation might cause complete loss of protein function by disrupting translation ("protein null") and/or preventing transcription ("RNA null").
An amorphic allele elicits the same phenotype when homozygous and when heterozygous to a chromosomal deletion or deficiency that disrupts the same gene. This relationship can be represented as follows:
m/m = m/Df
An amorphic allele is commonly recessive to its wildtype counterpart. It is possible for an amorph to be dominant if the gene in question is required in two copies to elicit a normal phenotype (i.e. haploinsufficient).
Hypomorphic describes a mutation that causes a partial loss of gene function. A hypomorph is a reduction in gene (protein, RNA) expression, but not a complete loss.
The phenotype of a hypomorph is more severe in trans to a deletion allele than when homozygous.
m/Df > m/m
Hypomorphs are usually recessive, but occasional alleles are dominant due to haploinsufficiency.
A hypermorphic mutation causes an increase in normal gene function. Hypermorphic alleles are dominant gain of function alleles. A hypermorph can result from an increase in gene dose (a gene duplication), from increased mRNA or protein expression, or constitutive protein activity.
The phenotype of a hypermorph is worsened by increasing the wildtype gene dose, and is reduced by lowering wildtype gene dose.
m/Dp > m/+ > m/Df
Increasing wildtype gene function reduces the phenotypic severity of an antimorph, so the phenotype of an antimorph is worse when heterozygous than when in trans to a gene duplication.
m/+ > m/Dp
An antimorphic mutation might affect the function of a protein that acts as a dimer so that a dimer consisting of one normal and one mutated protein is no longer functional.
A Neomorphic mutation causes a dominant gain of gene function that is different from the normal function. A neomorphic mutation can cause ectopic mRNA or protein expression, or new protein functions from altered protein structure.
Changing wildtype gene dose has no effect on the phenotype of a neomorph.
m/Df = m/+ = m/Dp
Muller, HJ (1932) Further studies on the nature and causes of gene mutations. Proceedings of the 6th International Congress of Genetics, pp 213-255.
Wilkie, AO (1994) The molecular basis of genetic dominance. Journal of Medical Genetics 31: 89-98.