Dominant-Negative

A mutant protein that disrupts its normal counterpart

A dominant-negative variant produces a mutant protein that interferes with the function of its normal counterpart, lowering net activity through active disruption rather than simple absence. It is common where a protein oligomerizes or assembles into a complex, so the mutant subunit poisons the assembly. Because the mutant continues to interfere, adding back wild-type protein does not fully rescue. In CMT, dominant MFN2 alleles cause CMT2A through a dominant-negative effect.

See how the dominant-negative call is applied across subtypes in the CMT Variant Mechanisms Browser.

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