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GAMT

guanidinoacetate N-methyltransferase

The GAMT gene provides instructions for an enzyme essential for the body's synthesis of creatine, a compound vital for energy storage and utilisation in muscles and the nervous system. The GAMT gene encodes guanidinoacetate N-methyltransferase, an enzyme primarily active in the liver that plays a critical role in the second step of creatine production.

Chromosome 19p13.3 HGNC:4136 Tier C
GAMT 19p13.3 p arm q arm 19

GAMT is located on the short (p) arm of chromosome 19, at band 19p13.3. Arm ratio per GRCh38 - banding schematic.

Explore chromosome 19 in the library →

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Clinical tests that include this

Carrier Screening panel
GAMT is 1 of 1,008 genes on this panel
Expanded carrier screening for recessive and X-linked conditions
Newborn Genetic Screening panel
GAMT is 1 of 258 genes on this panel
Genomic newborn screening for actionable paediatric conditions

Overview

The GAMT gene, which stands for guanidinoacetate N-methyltransferase, directs the production of an enzyme crucial for the body's creatine synthesis pathway. Creatine is an essential compound for energy storage and its efficient use within cells, especially in muscle and nervous system tissues. The GAMT enzyme completes the final stage of creatine production, ensuring sufficient levels for various physiological processes.

Pathogenic variants within the GAMT gene can impair the enzyme's function, potentially leading to a creatine deficiency. This can be associated with conditions such as cerebral creatine deficiency, which may significantly impact neurological function due to the high energy demands of the brain.

What the gene does

The GAMT gene contains the genetic blueprint for the enzyme guanidinoacetate methyltransferase. This enzyme is predominantly active in the liver and plays a key role in the two-step biochemical pathway that creates creatine. Specifically, the GAMT enzyme catalyses the second stage of this process, converting guanidinoacetate into creatine.

Creatine itself is vital for the efficient storage and distribution of energy throughout the body. It is important in facilitating muscle contraction and is also essential for the healthy functioning of the nervous system. Beyond its primary role in creatine synthesis, the guanidinoacetate methyltransferase enzyme is also thought to support fatty acid oxidation, a metabolic process that provides an alternative energy source for cells, especially when glucose levels are low.

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Chromosome location

The GAMT gene is located on the short arm of chromosome 19 at position 19p13.3. This specific chromosomal address defines its place within the human genome.

Protein structure

The GAMT protein, known as guanidinoacetate N-methyltransferase, comprises 236 amino acids. A crucial functional region of this protein is the RMT2 domain, which spans from amino acid positions 13 to 236. This domain is essential for the enzyme's catalytic activity in creatine synthesis.

Domain map · 236 amino acids
RMT2 (13–236)RMT213–2361~118236
Domain - independent functional unit
🧬 Explore 3D structure on AlphaFold
UniProt:Q14353Length:236 aaStructure:AlphaFold

Key variants

Variations within the GAMT gene can range from benign changes with no health impact to pathogenic variants that impair the gene's function. These pathogenic variants can disrupt the production or activity of the GAMT enzyme, affecting creatine synthesis. The specific clinical consequences depend on the type and location of the genetic alteration.

The table below shows the top 10 pathogenic or likely-pathogenic variants currently classified in ClinVar for GAMT.
View all on ClinVar →

Sample of pathogenic variants

10 pathogenic / likely-pathogenic variants from ClinVar, ranked by review status (expert-panel-reviewed first). This is a sample; recurrent founder variants in a specific population may not appear here - see the full ClinVar listing via the link above.

Variant (HGVS) Protein change Classification Evidence Associated condition
c.194T>C
single nucleotide variant
 p.Leu65Pro Pathogenic ★★★☆ Deficiency of guanidinoacetate methyltransferase
c.235C>T
single nucleotide variant
 p.Gln79Ter Pathogenic ★★★☆ Deficiency of guanidinoacetate methyltransferase
c.352G>T
single nucleotide variant
 p.Glu118Ter Pathogenic ★★★☆ Deficiency of guanidinoacetate methyltransferase
c.391G>C
single nucleotide variant
 p.Gly131Arg Pathogenic ★★★☆ Deficiency of guanidinoacetate methyltransferase
c.403G>T
single nucleotide variant
 p.Asp135Tyr Pathogenic ★★★☆ Deficiency of guanidinoacetate methyltransferase
c.418_419del
Microsatellite
 p.Ser140fs Pathogenic ★★★☆ Deficiency of guanidinoacetate methyltransferase
c.432G>A
single nucleotide variant
 p.Trp144Ter Pathogenic ★★★☆ Deficiency of guanidinoacetate methyltransferase
c.497T>C
single nucleotide variant
 p.Leu166Pro Pathogenic ★★★☆ Deficiency of guanidinoacetate methyltransferase
c.526dup
Duplication
 p.Glu176fs Pathogenic ★★★☆ Deficiency of guanidinoacetate methyltransferase
c.590T>C
single nucleotide variant
 p.Leu197Pro Pathogenic ★★★☆ Deficiency of guanidinoacetate methyltransferase

Evidence stars indicate ClinVar review status. Individual variant interpretation should always be performed by a qualified clinical laboratory - many variants remain classified as Variants of Uncertain Significance (VUS) pending more research.

Associated conditions

Pathogenic variants in the GAMT gene are associated with an inherited metabolic disorder known as Cerebral creatine deficiency (GAMT). This condition results from insufficient creatine, which can lead to significant neurological issues given the brain's high energy demands. For Cerebral creatine deficiency (GAMT), inheritance is typically autosomal recessive, meaning an individual generally inherits two copies of the altered gene (one from each parent) to develop the condition.

UK clinical status

The GAMT gene is included in several UK NHS national genomic testing panels, indicating its recognised clinical significance within the UK healthcare system. It is listed as green on the DDG2P panel, as well as panels for Early onset or syndromic epilepsy, Intellectual disability, Likely inborn error of metabolism (R98), and Undiagnosed metabolic disorders.

Green-listed
High evidence · clinically actionable in NHS testing
Included in NHS GMS signed-off panels
Likely inborn error of metabolism · R98 NHS GMS → DDG2P NHS GMS → Early onset or syndromic epilepsy NHS GMS → Intellectual disability NHS GMS →
NHS Genomic Medicine Service Jeen carrier screening

Sources: NHS GMS PanelApp · Genomics England PanelApp · NHS National Genomic Test Directory

Frequently asked questions

What is the main function of the GAMT gene?

The GAMT gene provides instructions for an enzyme called guanidinoacetate N-methyltransferase, which is crucial for the second step in the body's synthesis of creatine. Creatine is vital for energy storage and utilisation in muscles and the nervous system.

What condition is associated with GAMT gene variants?

Pathogenic variants in the GAMT gene are associated with Cerebral creatine deficiency (GAMT), a metabolic disorder that results from insufficient creatine production in the body.

How is Cerebral creatine deficiency (GAMT) inherited?

Research suggests that Cerebral creatine deficiency (GAMT) may typically be inherited in an autosomal recessive pattern. This means an individual usually inherits two altered copies of the GAMT gene, one from each parent, to develop the condition, though inheritance patterns can vary.

References

  1. Mercimek-Mahmutoglu S, Ndika J, Kanhai W. Thirteen new patients with guanidinoacetate methyltransferase deficiency and functional characterization of nineteen novel missense variants in the GAMT gene. Human mutation. 2014. PMID: 24415674
  2. Braissant O, Henry H, Béard E. Creatine deficiency syndromes and the importance of creatine synthesis in the brain. Amino acids. 2011. PMID: 21390529
  3. Gordon N. Guanidinoacetate methyltransferase deficiency (GAMT). Brain & development. 2010. PMID: 19289269
  4. Nasrallah F, Feki M, Kaabachi N. Creatine and creatine deficiency syndromes: biochemical and clinical aspects. Pediatric neurology. 2010. PMID: 20159424
  5. Béard E, Braissant O. Synthesis and transport of creatine in the CNS: importance for cerebral functions. Journal of neurochemistry. 2010. PMID: 20796169
  6. Dhar SU, Scaglia F, Li FY. Expanded clinical and molecular spectrum of guanidinoacetate methyltransferase (GAMT) deficiency. Molecular genetics and metabolism. 2009. PMID: 19027335
  7. Ide T, Brown-Endres L, Chu K. GAMT, a p53-inducible modulator of apoptosis, is critical for the adaptive response to nutrient stress. Molecular cell. 2009. PMID: 19917247
  8. Almeida LS, Vilarinho L, Darmin PS. A prevalent pathogenic GAMT mutation (c.59G>C) in Portugal. Molecular genetics and metabolism. 2007. PMID: 17336114
  9. Leuzzi V, Carducci C, Carducci C. A mutation on exon 6 of guanidinoacetate methyltransferase (GAMT) gene supports a different function for isoform a and b of GAMT enzyme. Molecular genetics and metabolism. 2006. PMID: 16293431
  10. Sykut-Cegielska J, Gradowska W, Mercimek-Mahmutoglu S. Biochemical and clinical characteristics of creatine deficiency syndromes. Acta biochimica Polonica. 2004. PMID: 15625559
  11. Schulze A. Creatine deficiency syndromes. Molecular and cellular biochemistry. 2003. PMID: 12701824
  12. Stöckler S, Holzbach U, Hanefeld F. Creatine deficiency in the brain: a new, treatable inborn error of metabolism. Pediatric research. 1994. PMID: 7808840
Educational content. This page is not medical or genetic advice, is not individually reviewed by a clinician for each reader, and should not replace a consultation with a qualified healthcare professional or genetic counsellor. If you are considering genetic testing or acting on a test result, book a consultation.
Data sources Last updated 20 September 2026. Content compiled from HGNC · MedlinePlus Genetics · ClinGen · Genomics England PanelApp · NHS National Genomic Test Directory · ClinVar · UniProt · AlphaFold .