Pathogenic variants that enhance the activity of a particular protein are known as gain-of-function; these types of protein alterations are generally associated with de novo/dominant disorders, though there are rare examples of putative recessive gain-of-function alleles in the epilepsies [15]. These gain-of-function alleles are almost always missense variants, for example, SCN8A variants in the voltage-gated sodium channel can lead to alterations in this sodium channel electrophysiological properties that shift the neuron to a more hyperexcitable state [16].
« Back to Glossary IndexGain of function or GOF
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