Gene SERPINA1
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Also known as
Alpha-1 Antitrypsin, AAT, A1AT, PI, alpha1ATOverview
SERPINA1 (Serpin Family A Member 1) encodes alpha-1 antitrypsin (AAT), a protease inhibitor primarily produced by the liver and secreted into the bloodstream. This protein belongs to the serpin superfamily and functions as the main inhibitor of neutrophil elastase, a powerful protease enzyme released by white blood cells during inflammation. AAT protects tissues, particularly the lungs, from degradation by elastase and other proteases. The protein also has anti-inflammatory and immunomodulatory properties that extend beyond its protease inhibitor function.Mutations in SERPINA1 cause alpha-1 antitrypsin deficiency (AATD), one of the most common genetic disorders, particularly among individuals of European descent. The most clinically significant variants are the PiZ and PiS alleles. Severe deficiency (most commonly the PiZZ genotype) leads to reduced AAT levels in the blood, resulting in two major clinical manifestations: early-onset chronic obstructive pulmonary disease (COPD) and emphysema due to uncontrolled elastase activity in the lungs, and liver disease from accumulation of misfolded AAT protein in hepatocytes. Smoking dramatically accelerates lung disease in affected individuals. Genetic testing for SERPINA1 variants is crucial for early diagnosis, risk assessment, and implementation of preventive strategies including smoking avoidance, augmentation therapy with intravenous AAT, and monitoring for liver disease.