이 유전자가 하는 일
White blood cells release enzymes that break down tissue as part of fighting infection. Alpha-1 antitrypsin is the brake that stops those enzymes damaging healthy lung. In alpha-1 antitrypsin deficiency, one wrong letter makes the protein misfold: the lungs go unprotected and the misfolded protein piles up in the liver and damages it too.
SERPINA1, at 14q32.13, encodes alpha-1 antitrypsin, a serine protease inhibitor whose principal target is neutrophil elastase. The PiZ allele (E342K) causes misfolding and hepatocyte polymer accumulation, producing both loss-of-function lung disease and gain-of-function liver disease. Correcting the point mutation addresses both mechanisms simultaneously, which is why it was chosen for the first in vivo correction demonstrated in humans.
Sources
- MedlinePlus Genetics, U.S. National Library of Medicine
SERPINA1 gene ↗