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Genetics Home Reference: your guide to understanding genetic conditions
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GSS

Reviewed March 2015

What is the official name of the GSS gene?

The official name of this gene is “glutathione synthetase.”

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

What is the normal function of the GSS gene?

The GSS gene provides instructions for making an enzyme called glutathione synthetase. Glutathione synthetase participates in a process called the gamma-glutamyl cycle. The gamma-glutamyl cycle is a sequence of chemical reactions that takes place in most of the body's cells. These reactions are necessary for the production of glutathione, a small molecule made of three protein building blocks (amino acids). Glutathione protects cells from damage caused by unstable oxygen-containing molecules, which are byproducts of energy production. Glutathione is called an antioxidant because of its role in protecting cells from the damaging effects of these unstable molecules. Glutathione also helps process medications and cancer-causing compounds (carcinogens), and helps build DNA, proteins, and other important cellular components.

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

glutathione synthetase deficiency - caused by mutations in the GSS gene

More than 30 mutations in the GSS gene have been identified in people with glutathione synthetase deficiency. Characteristic features of this condition include the abnormal destruction of red blood cells (hemolytic anemia), the release of large amounts of a compound called 5-oxoproline in the urine (5-oxoprolinuria), and elevated acidity in the blood and tissues (metabolic acidosis). Severely affected individuals may also have neurological problems.

Most of the GSS mutations involved in glutathione synthetase deficiency change single amino acids in glutathione synthetase. Other mutations disrupt how genetic information from the GSS gene is pieced together to make a blueprint for producing the enzyme. The altered glutathione synthetase enzyme may be unstable, shorter than usual, or the wrong shape. All of these changes reduce the activity of the enzyme and disrupt the gamma-glutamyl cycle, preventing adequate production of glutathione. Low levels of glutathione affect other chemical reactions in the body, leading to the overproduction of 5-oxoproline. Accumulation of this compound in red blood cells and other tissues causes hemolytic anemia and metabolic acidosis, and its release leads to 5-oxoprolinuria.

Where is the GSS gene located?

Cytogenetic Location: 20q11.2

Molecular Location on chromosome 20: base pairs 34,928,432 to 34,955,991

The GSS gene is located on the long (q) arm of chromosome 20 at position 11.2.

The GSS gene is located on the long (q) arm of chromosome 20 at position 11.2.

More precisely, the GSS gene is located from base pair 34,928,432 to base pair 34,955,991 on chromosome 20.

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 GSS?

You and your healthcare professional may find the following resources about GSS 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 GSS gene or gene products?

  • gamma-L-Glutamyl-L-cysteine:glycine ligase (ADP-forming)
  • glutathione synthase
  • GSHB_HUMAN
  • GSHS
  • GSH synthetase
  • MGC14098

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 GSS?

acidity ; acidosis ; acids ; ADP ; anemia ; cancer ; compound ; cysteine ; deficiency ; DNA ; enzyme ; gene ; glutathione ; glycine ; hemolytic anemia ; L-cysteine ; ligase ; molecule ; neurological ; oxygen ; protein

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

References

  • De Jesus MC, Ingle BL, Barakat KA, Shrestha B, Slavens KD, Cundari TR, Anderson ME. The role of strong electrostatic interactions at the dimer interface of human glutathione synthetase. Protein J. 2014 Oct;33(5):403-9. doi: 10.1007/s10930-014-9573-y. (http://www.ncbi.nlm.nih.gov/pubmed/25070563?dopt=Abstract)
  • Dinescu A, Brown TR, Barelier S, Cundari TR, Anderson ME. The role of the glycine triad in human glutathione synthetase. Biochem Biophys Res Commun. 2010 Oct 1;400(4):511-6. doi: 10.1016/j.bbrc.2010.08.081. Epub 2010 Aug 26. (http://www.ncbi.nlm.nih.gov/pubmed/20800579?dopt=Abstract)
  • Dinescu A, Cundari TR, Bhansali VS, Luo JL, Anderson ME. Function of conserved residues of human glutathione synthetase: implications for the ATP-grasp enzymes. J Biol Chem. 2004 May 21;279(21):22412-21. Epub 2004 Feb 27. (http://www.ncbi.nlm.nih.gov/pubmed/14990577?dopt=Abstract)
  • OMIM: GLUTATHIONE SYNTHETASE (http://omim.org/entry/601002)
  • Janáky R, Ogita K, Pasqualotto BA, Bains JS, Oja SS, Yoneda Y, Shaw CA. Glutathione and signal transduction in the mammalian CNS. J Neurochem. 1999 Sep;73(3):889-902. Review. (http://www.ncbi.nlm.nih.gov/pubmed/10461878?dopt=Abstract)
  • NCBI Gene (http://www.ncbi.nlm.nih.gov/gene/2937)
  • Njålsson R, Carlsson K, Bhansali V, Luo JL, Nilsson L, Ladenstein R, Anderson M, Larsson A, Norgren S. Human hereditary glutathione synthetase deficiency: kinetic properties of mutant enzymes. Biochem J. 2004 Jul 15;381(Pt 2):489-94. (http://www.ncbi.nlm.nih.gov/pubmed/15056072?dopt=Abstract)
  • Njålsson R, Carlsson K, Olin B, Carlsson B, Whitbread L, Polekhina G, Parker MW, Norgren S, Mannervik B, Board PG, Larsson A. Kinetic properties of missense mutations in patients with glutathione synthetase deficiency. Biochem J. 2000 Jul 1;349(Pt 1):275-9. (http://www.ncbi.nlm.nih.gov/pubmed/10861239?dopt=Abstract)
  • Ristoff E, Larsson A. Inborn errors in the metabolism of glutathione. Orphanet J Rare Dis. 2007 Mar 30;2:16. Review. (http://www.ncbi.nlm.nih.gov/pubmed/17397529?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: March 2015
Published: March 23, 2015