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serpin family A member 1

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. The first identified role for alpha-1 antitrypsin was to control the activity of the digestive enzyme trypsin. 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 is produced in the liver and then transported throughout the body via the blood. Alpha-1 antitrypsin protects the lungs from neutrophil elastase, which can damage lung tissue if not properly controlled. 

Health Conditions Related to Genetic Changes

Alpha-1 antitrypsin deficiency

More than 100 variants (also known as mutations) in the SERPINA1 gene have been associated with a condition called alpha-1 antitrypsin deficiency. This condition is characterized by a shortage (deficiency) of the alpha-1 antitrypsin protein, which increases a person's risk of developing lung disease, liver disease, and other abnormalities.

Many SERPINA1 gene variants change single protein building blocks (amino acids) in alpha-1 antitrypsin, which can alter the protein's structure. The most common variant 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 genetic change creates  a version of the SERPINA1 gene called the Z allele. Another common variant creates a version of the gene called the S allele. This variant replaces the amino acid glutamic acid with the amino acid valine at protein position 264 (written as Glu264Val or E264V). (The unaltered version of the SERPINA1 gene is known as the M allele.) 

Abnormal alpha-1 antitrypsin proteins, including those produced from the Z allele, 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 there is not enough alpha-1 antitrypsin 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.

The S allele and some other SERPINA1 gene variants lead to the production of an abnormal form of alpha-1 antitrypsin that is quickly broken down in the liver. Still other gene variants prevent the production of any alpha-1 antitrypsin protein. As a result, little or no alpha-1 antitrypsin is available in the lungs. While the liver remains healthy in individuals with these variants, the lungs are left unprotected from neutrophil elastase.

More About This Health Condition

Other Names for This Gene

  • A1A
  • A1AT
  • AAT
  • alpha-1 antiproteinase
  • alpha-1 antitrypsin
  • alpha-1 proteinase inhibitor
  • alpha1AT
  • PI
  • PI1
  • protease inhibitor 1 (anti-elastase)
  • serine protease 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

Gene and Variant Databases


  • 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. doi: 10.1016/s0022-2836(02)01221-4. 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. 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. doi: 10.1136/thx.2003.006528. 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. doi: 10.1016/s1357-2725(02)00250-9. 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. doi: 10.1002/hep.21628. 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. doi: 10.1055/s-2005-869536. Citation on PubMed
  • Seixas S, Marques PI. Known Mutations at the Cause of Alpha-1 Antitrypsin Deficiency an Updated Overview of SERPINA1 Variation Spectrum. Appl Clin Genet. 2021 Mar 22;14:173-194. doi: 10.2147/TACG.S257511. eCollection 2021. Citation on PubMed

The information on this site should not be used as a substitute for professional medical care or advice. Contact a health care provider if you have questions about your health.