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Genetics Home Reference: your guide to understanding genetic conditions
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SERPINA1

Reviewed August 2009

What is the official name of the SERPINA1 gene?

The official name of this gene is “serpin peptidase inhibitor, clade A (alpha-1 antiproteinase, antitrypsin), member 1.”

SERPINA1 is the gene's official symbol. The SERPINA1 gene is also known by other names, listed below.

What is the normal function of the SERPINA1 gene?

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.

Does the SERPINA1 gene share characteristics with other genes?

The SERPINA1 gene belongs to a family of genes called SERPIN (serine (or cysteine) peptidase inhibitors).

A gene family is a group of genes that share important characteristics. Classifying individual genes into families helps researchers describe how genes are related to each other. For more information, see What are gene families? (http://ghr.nlm.nih.gov/handbook/howgeneswork/genefamilies) in the Handbook.

How are changes in the SERPINA1 gene related to health conditions?

alpha-1 antitrypsin deficiency - caused by mutations in the SERPINA1 gene

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.

Where is the SERPINA1 gene located?

Cytogenetic Location: 14q32.1

Molecular Location on chromosome 14: base pairs 94,376,746 to 94,390,691

The SERPINA1 gene is located on the long (q) arm of chromosome 14 at position 32.1.

The SERPINA1 gene is located on the long (q) arm of chromosome 14 at position 32.1.

More precisely, the SERPINA1 gene is located from base pair 94,376,746 to base pair 94,390,691 on chromosome 14.

See How do geneticists indicate the location of a gene? (http://ghr.nlm.nih.gov/handbook/howgeneswork/genelocation) in the Handbook.

Where can I find additional information about SERPINA1?

You and your healthcare professional may find the following resources about SERPINA1 helpful.

You may also be interested in these resources, which are designed for genetics professionals and researchers.

What other names do people use for the SERPINA1 gene or gene products?

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

See How are genetic conditions and genes named? (http://ghr.nlm.nih.gov/handbook/mutationsanddisorders/naming) in the Handbook.

What glossary definitions help with understanding SERPINA1?

acids ; allele ; alveoli ; amino acid ; cysteine ; deficiency ; digestive ; emphysema ; enzyme ; gene ; glutamic acid ; infection ; inflammation ; lysine ; molecule ; mutation ; panniculitis ; protease ; protein ; proteinase ; serine ; tissue ; trypsin ; white blood cells

You may find definitions for these and many other terms in the Genetics Home Reference Glossary (http://www.ghr.nlm.nih.gov/glossary).

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. (http://www.ncbi.nlm.nih.gov/pubmed/12498804?dopt=Abstract)
  • 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. (http://www.ncbi.nlm.nih.gov/pubmed/18591408?dopt=Abstract)
  • Lomas DA, Parfrey H. Alpha1-antitrypsin deficiency. 4: Molecular pathophysiology. Thorax. 2004 Jun;59(6):529-35. Review. (http://www.ncbi.nlm.nih.gov/pubmed/15170041?dopt=Abstract)
  • NCBI Gene (http://www.ncbi.nlm.nih.gov/gene/5265)
  • 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. (http://www.ncbi.nlm.nih.gov/pubmed/12672469?dopt=Abstract)
  • 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. (http://www.ncbi.nlm.nih.gov/pubmed/17464974?dopt=Abstract)
  • Ranes J, Stoller JK. A review of alpha-1 antitrypsin deficiency. Semin Respir Crit Care Med. 2005 Apr;26(2):154-66. Review. (http://www.ncbi.nlm.nih.gov/pubmed/16088434?dopt=Abstract)

 

The resources on this site should not be used as a substitute for professional medical care or advice. Users seeking information about a personal genetic disease, syndrome, or condition should consult with a qualified healthcare professional. See How can I find a genetics professional in my area? (http://ghr.nlm.nih.gov/handbook/consult/findingprofessional) in the Handbook.

 
Reviewed: August 2009
Published: December 16, 2014