Antimorphic

Antimorphic, in genetics, refers to a class of mutations whose gene product antagonizes the normal, wild-type product. A mutation is antimorphic when the product interferes with the function of the wild-type protein, often by forming nonfunctional complexes or by titrating substrates or cofactors. This contrasts with loss-of-function, which reduces or eliminates activity, and with gain-of-function (neomorphic) mutations, which confer a new or altered activity.

Mechanism: In many antimorphic mutations, the affected gene encodes a protein that operates as part of a multimeric complex. A mutant subunit can be incorporated into a complex but disrupt its activity, decreasing overall function even when a normal allele is present. Antimorphic effects are typically dominant because a single copy of the mutant allele can interfere with the wild-type protein.

Examples: The best-known antimorphic mutations are dominant-negative variants in the tumor suppressor p53, where mutant p53 subunits form inactive tetramers with the wild-type protein and impair transcriptional activation. Similar effects occur in other multimeric transcription factors and in structural protein systems where subunit stoichiometry governs function.

Clinical and research relevance: Antimorphic mutations contribute to diseases with dominant inheritance and can complicate genotype–phenotype relationships. They are a consideration in genetic counseling and in studies of protein complex assembly, signaling pathways, and drug design aimed at mitigating dominant-negative effects.

Terminology: Antimorphic is sometimes used interchangeably with dominant-negative; however, some authors distinguish the terms by context or mechanism. It is also contrasted with neomorphic (new function) and haploinsufficiency (loss of one copy causing reduced activity).