gain-of-function mutation
A genetic alteration that enhances or creates new protein activity, often causing immune dysregulation in pediatric patients.
Full Definition
A gain-of-function mutation is a genetic alteration that increases the normal activity of a protein or confers new functionality. In pediatric immunology, these mutations often lead to immune dysregulation syndromes rather than classic immunodeficiencies. For example, gain-of-function mutations in STAT1 can cause chronic mucocutaneous candidiasis, while mutations in PIK3CD can lead to activated PI3K-delta syndrome with immunodeficiency and autoimmunity. These mutations typically result in dominant inheritance patterns and may cause constitutive activation of immune pathways, leading to autoinflammation, autoimmunity, or paradoxical immunodeficiency despite enhanced protein function.
Usage
Usage note: Always hyphenate when used as a compound adjective before a noun.
In Context
- "The gain-of-function mutation in STAT1 explained the patient's chronic candidiasis and autoimmune features." — Genetic testing interpretation
- "Gain-of-function mutations often present with immune dysregulation rather than classic immunodeficiency." — Molecular immunology review