The GAMT gene provides instructions for making the enzyme guanidinoacetate methyltransferase, which is active (expressed) mainly in the liver. This enzyme participates in the two-step production (synthesis) of the compound creatine from the protein building blocks (amino acids) glycine, arginine, and methionine. Specifically, guanidinoacetate methyltransferase controls the second step of this process. In this step, creatine is produced from another compound called guanidinoacetate. Creatine is needed for the body to store and use energy properly. It is involved in providing energy for muscle contraction, and is also important in nervous system functioning.
In addition to its role in creatine synthesis, the guanidinoacetate methyltransferase enzyme is thought to help activate a process called fatty acid oxidation. This process provides an energy source for cells during times of stress when their normal fuel, the simple sugar glucose, is scarce.
Health Conditions Related to Genetic Changes
Guanidinoacetate methyltransferase deficiency
At least 49 mutations in the GAMT gene cause guanidinoacetate methyltransferase deficiency, a disorder that involves intellectual disability and seizures. Most affected individuals of Portuguese ancestry have a particular mutation in which the amino acid tryptophan is replaced by the amino acid serine at position 20 in the enzyme (written as Trp20Ser or W20S).
GAMT gene mutations impair the ability of the guanidinoacetate methyltransferase enzyme to participate in creatine synthesis, resulting in a shortage of creatine. The effects of guanidinoacetate methyltransferase deficiency are most severe in organs and tissues that require large amounts of energy, especially the brain.More About This Health Condition
Other Names for This Gene
Additional Information & Resources
Tests Listed in the Genetic Testing Registry
Scientific Articles on PubMed
Catalog of Genes and Diseases from OMIM
- Almeida LS, Vilarinho L, Darmin PS, Rosenberg EH, Martinez-Munoz C, Jakobs C, Salomons GS. A prevalent pathogenic GAMT mutation (c.59G>C) in Portugal. Mol Genet Metab. 2007 May;91(1):1-6. doi: 10.1016/j.ymgme.2007.01.005. Epub 2007 Mar 1. Citation on PubMed
- Beard E, Braissant O. Synthesis and transport of creatine in the CNS: importance for cerebral functions. J Neurochem. 2010 Oct;115(2):297-313. doi: 10.1111/j.1471-4159.2010.06935.x. Epub 2010 Aug 25. Citation on PubMed
- Braissant O, Henry H, Beard E, Uldry J. Creatine deficiency syndromes and the importance of creatine synthesis in the brain. Amino Acids. 2011 May;40(5):1315-24. doi: 10.1007/s00726-011-0852-z. Epub 2011 Mar 10. Citation on PubMed
- Dhar SU, Scaglia F, Li FY, Smith L, Barshop BA, Eng CM, Haas RH, Hunter JV, Lotze T, Maranda B, Willis M, Abdenur JE, Chen E, O'Brien W, Wong LJ. Expanded clinical and molecular spectrum of guanidinoacetate methyltransferase (GAMT) deficiency. Mol Genet Metab. 2009 Jan;96(1):38-43. doi: 10.1016/j.ymgme.2008.10.008. Epub 2008 Nov 21. Citation on PubMed
- Gordon N. Guanidinoacetate methyltransferase deficiency (GAMT). Brain Dev. 2010 Feb;32(2):79-81. doi: 10.1016/j.braindev.2009.01.008. Epub 2009 Mar 16. Citation on PubMed
- Ide T, Brown-Endres L, Chu K, Ongusaha PP, Ohtsuka T, El-Deiry WS, Aaronson SA, Lee SW. GAMT, a p53-inducible modulator of apoptosis, is critical for the adaptive response to nutrient stress. Mol Cell. 2009 Nov 13;36(3):379-92. doi: 10.1016/j.molcel.2009.09.031. Citation on PubMed or Free article on PubMed Central
- Leuzzi V, Carducci C, Carducci C, Matricardi M, Bianchi MC, Di Sabato ML, Artiola C, Antonozzi I. A mutation on exon 6 of guanidinoacetate methyltransferase (GAMT) gene supports a different function for isoform a and b of GAMT enzyme. Mol Genet Metab. 2006 Jan;87(1):88-90. doi: 10.1016/j.ymgme.2005.09.017. Epub 2005 Nov 15. Citation on PubMed
- Mercimek-Mahmutoglu S, Ndika J, Kanhai W, de Villemeur TB, Cheillan D, Christensen E, Dorison N, Hannig V, Hendriks Y, Hofstede FC, Lion-Francois L, Lund AM, Mundy H, Pitelet G, Raspall-Chaure M, Scott-Schwoerer JA, Szakszon K, Valayannopoulos V, Williams M, Salomons GS. Thirteen new patients with guanidinoacetate methyltransferase deficiency and functional characterization of nineteen novel missense variants in the GAMT gene. Hum Mutat. 2014 Apr;35(4):462-9. doi: 10.1002/humu.22511. Epub 2014 Mar 6. Citation on PubMed
- Nasrallah F, Feki M, Kaabachi N. Creatine and creatine deficiency syndromes: biochemical and clinical aspects. Pediatr Neurol. 2010 Mar;42(3):163-71. doi: 10.1016/j.pediatrneurol.2009.07.015. Citation on PubMed
- Schulze A. Creatine deficiency syndromes. Mol Cell Biochem. 2003 Feb;244(1-2):143-50. Citation on PubMed
- Stockler S, Holzbach U, Hanefeld F, Marquardt I, Helms G, Requart M, Hanicke W, Frahm J. Creatine deficiency in the brain: a new, treatable inborn error of metabolism. Pediatr Res. 1994 Sep;36(3):409-13. doi: 10.1203/00006450-199409000-00023. Citation on PubMed
- Sykut-Cegielska J, Gradowska W, Mercimek-Mahmutoglu S, Stockler-Ipsiroglu S. Biochemical and clinical characteristics of creatine deficiency syndromes. Acta Biochim Pol. 2004;51(4):875-82. Citation on PubMed
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