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SERPINA1 gene

serpin family A member 1
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Normal Function

The SERPINA1 gene provides instructions for making a protein called alpha-1 antitrypsin, which is a type of serine protease inhibitor (serpin). Serpins help control several types of chemical reactions by blocking (inhibiting) the activity of certain enzymes. Alpha-1 antitrypsin prevents the digestive enzyme trypsin from breaking down proteins until trypsin reaches the intestines. Alpha-1 antitrypsin also inhibits other enzymes, including a powerful enzyme called neutrophil elastase that is released from white blood cells to fight infection.

Alpha-1 antitrypsin protects the lungs from neutrophil elastase, which can damage lung tissue if not properly controlled. Alpha-1 antitrypsin is produced in the liver and then transported to the lungs via the blood.

Health Conditions Related to Genetic Changes

Alpha-1 antitrypsin deficiency

More than 120 mutations in the SERPINA1 gene have been identified. Some of these mutations do not affect the production of alpha-1 antitrypsin, while others cause a shortage (deficiency) of the protein. Without enough functional alpha-1 antitrypsin, neutrophil elastase destroys the small air sacs in the lungs (alveoli) and causes lung disease. Excessive damage to the alveoli leads to emphysema, an irreversible lung disease that causes extreme shortness of breath.

Many SERPINA1 gene mutations change single protein building blocks (amino acids) in alpha-1 antitrypsin, which alters the protein's structure. The most common mutation that causes alpha-1 antitrypsin deficiency replaces the amino acid glutamic acid with the amino acid lysine at protein position 342 (written as Glu342Lys or E342K). This mutation results in a version of the SERPINA1 gene called the Z allele that produces very little alpha-1 antitrypsin.

Abnormal alpha-1 antitrypsin proteins may bind together to form a large molecule, or polymer, that cannot leave the liver. The accumulation of these polymers results in liver damage. In addition, lung tissue is destroyed because not enough alpha-1 antitrypsin is available to protect against neutrophil elastase. Polymers of alpha-1 antitrypsin may also contribute to excessive inflammation, which may explain some of the other features of alpha-1 antitrypsin deficiency, such as a skin condition called panniculitis.

Other SERPINA1 gene mutations lead to the production of an abnormally small form of alpha-1 antitrypsin that is quickly broken down in the liver. As a result, little or no alpha-1 antitrypsin is available in the lungs. While the liver remains healthy in individuals with these mutations, the lungs are left unprotected from neutrophil elastase.

More About This Health Condition

Other Names for This Gene

  • A1A
  • A1AT
  • A1AT_HUMAN
  • AAT
  • alpha-1 antiproteinase
  • alpha-1 antitrypsin
  • alpha-1 proteinase inhibitor
  • alpha1AT
  • PI
  • PI1
  • protease inhibitor 1 (anti-elastase)
  • serine (or cysteine) proteinase inhibitor, clade A (alpha-1 antiproteinase, antitrypsin), member 1
  • serpin peptidase inhibitor, clade A (alpha-1 antiproteinase, antitrypsin), member 1

Additional Information & Resources

Tests Listed in the Genetic Testing Registry

Scientific Articles on PubMed

Catalog of Genes and Diseases from OMIM

Research Resources

References

  • Gilis D, McLennan HR, Dehouck Y, Cabrita LD, Rooman M, Bottomley SP. In vitro and in silico design of alpha1-antitrypsin mutants with different conformational stabilities. J Mol Biol. 2003 Jan 17;325(3):581-9. Citation on PubMed
  • Gooptu B, Lomas DA. Polymers and inflammation: disease mechanisms of the serpinopathies. J Exp Med. 2008 Jul 7;205(7):1529-34. doi: 10.1084/jem.20072080. Review. Citation on PubMed or Free article on PubMed Central
  • Lomas DA, Parfrey H. Alpha1-antitrypsin deficiency. 4: Molecular pathophysiology. Thorax. 2004 Jun;59(6):529-35. Review. Citation on PubMed or Free article on PubMed Central
  • Parfrey H, Mahadeva R, Lomas DA. Alpha(1)-antitrypsin deficiency, liver disease and emphysema. Int J Biochem Cell Biol. 2003 Jul;35(7):1009-14. Review. Citation on PubMed
  • Perlmutter DH, Brodsky JL, Balistreri WF, Trapnell BC. Molecular pathogenesis of alpha-1-antitrypsin deficiency-associated liver disease: a meeting review. Hepatology. 2007 May;45(5):1313-23. Review. Citation on PubMed
  • Ranes J, Stoller JK. A review of alpha-1 antitrypsin deficiency. Semin Respir Crit Care Med. 2005 Apr;26(2):154-66. Review. Citation on PubMed
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