Loss of Function

Too little of a protein’s normal activity

A loss-of-function variant reduces or abolishes a gene product’s normal activity. Loss of function ranges from haploinsufficiency, where one working copy is not enough, through hypomorphic alleles that retain partial activity, to biallelic null variants that remove function from both copies. Because the problem is too little normal activity, restoring the wild-type protein is generally expected to rescue. In CMT, many recessive subtypes act through biallelic loss of function.

See how loss of function is called across subtypes in the CMT Variant Mechanisms Browser.

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