Reviewed June 2015
What is the official name of the GAMT gene?
The official name of this gene is “guanidinoacetate N-methyltransferase.”
GAMT is the gene's official symbol. The GAMT gene is also known by other names, listed below.
What is the normal function of the GAMT gene?
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.
How are changes in the GAMT gene related to health conditions?
- guanidinoacetate methyltransferase deficiency - caused by mutations in the GAMT gene
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.
Where is the GAMT gene located?
Cytogenetic Location: 19p13.3
Molecular Location on chromosome 19: base pairs 1,397,026 to 1,401,570
(Homo sapiens Annotation Release 107, GRCh38.p2) (NCBI (http://www.ncbi.nlm.nih.gov/gene/2593))
The GAMT gene is located on the short (p) arm of chromosome 19 at position 13.3.
More precisely, the GAMT gene is located from base pair 1,397,026 to base pair 1,401,570 on chromosome 19.
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 GAMT?
You and your healthcare professional may find the following resources about GAMT helpful.
- Gene Reviews - Clinical summary (http://www.ncbi.nlm.nih.gov/books/NBK3794)
Genetic Testing Registry - Repository of genetic test information
- GTR: Genetic tests for GAMT (http://www.ncbi.nlm.nih.gov/gtr/tests/?term=2593%5Bgeneid%5D)
You may also be interested in these resources, which are designed for genetics professionals and researchers.
- PubMed - Recent literature (http://www.ncbi.nlm.nih.gov/pubmed?term=%28%28GAMT%5BTIAB%5D%29%20OR%20%28guanidinoacetate%20N-methyltransferase%5BTIAB%5D%29%29%20OR%20%28PIG2%5BTIAB%5D%29%20AND%20%28%28Genes%5BMH%5D%29%20OR%20%28Genetic%20Phenomena%5BMH%5D%29%29%20AND%20english%5Bla%5D%20AND%20human%5Bmh%5D%20AND%20%22last%203600%20days%22%5Bdp%5D)
- OMIM - Genetic disorder catalog (http://omim.org/entry/601240)
Research Resources - Tools for researchers
- HGNC Gene Symbol Report (http://www.genenames.org/cgi-bin/gene_symbol_report?q=data/hgnc_data.php&hgnc_id=4136)
- NCBI Gene (http://www.ncbi.nlm.nih.gov/gene/2593)
What other names do people use for the GAMT gene or gene products?
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 GAMT?
amino acid ;
nervous system ;
simple sugar ;
You may find definitions for these and many other terms in the Genetics Home Reference
- Almeida LS, Vilarinho L, Darmin PS, Rosenberg EH, Martinez-Muñoz C, Jakobs C, Salomons GS. A prevalent pathogenic GAMT mutation (c.59G>C) in Portugal. Mol Genet Metab. 2007 May;91(1):1-6. Epub 2007 Mar 1. (http://www.ncbi.nlm.nih.gov/pubmed/17336114?dopt=Abstract)
- Béard 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. Review. (http://www.ncbi.nlm.nih.gov/pubmed/20796169?dopt=Abstract)
- Braissant O, Henry H, Béard 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. Review. (http://www.ncbi.nlm.nih.gov/pubmed/21390529?dopt=Abstract)
- 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. (http://www.ncbi.nlm.nih.gov/pubmed/19027335?dopt=Abstract)
- 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. Review. (http://www.ncbi.nlm.nih.gov/pubmed/19289269?dopt=Abstract)
- OMIM: GUANIDINOACETATE METHYLTRANSFERASE (http://omim.org/entry/601240)
- 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. Retraction in: Mol Cell. 2013 Aug 22;51(4):552. (http://www.ncbi.nlm.nih.gov/pubmed/19917247?dopt=Abstract)
- 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. Epub 2005 Nov 15. (http://www.ncbi.nlm.nih.gov/pubmed/16293431?dopt=Abstract)
- 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. (http://www.ncbi.nlm.nih.gov/pubmed/24415674?dopt=Abstract)
- 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. Review. (http://www.ncbi.nlm.nih.gov/pubmed/20159424?dopt=Abstract)
- NCBI Gene (http://www.ncbi.nlm.nih.gov/gene/2593)
- Schulze A. Creatine deficiency syndromes. Mol Cell Biochem. 2003 Feb;244(1-2):143-50. Review. (http://www.ncbi.nlm.nih.gov/pubmed/12701824?dopt=Abstract)
- Stöckler S, Holzbach U, Hanefeld F, Marquardt I, Helms G, Requart M, Hänicke W, Frahm J. Creatine deficiency in the brain: a new, treatable inborn error of metabolism. Pediatr Res. 1994 Sep;36(3):409-13. (http://www.ncbi.nlm.nih.gov/pubmed/7808840?dopt=Abstract)
- Sykut-Cegielska J, Gradowska W, Mercimek-Mahmutoglu S, Stöckler-Ipsiroglu S. Biochemical and clinical characteristics of creatine deficiency syndromes. Acta Biochim Pol. 2004;51(4):875-82. Review. (http://www.ncbi.nlm.nih.gov/pubmed/15625559?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
See How can I find a genetics professional in my area? (http://ghr.nlm.nih.gov/handbook/consult/findingprofessional) in the Handbook.