On this page
MAT1A
methionine adenosyltransferase 1A
The MAT1A gene provides instructions for producing methionine adenosyltransferase, an enzyme critical for methionine metabolism and various cellular processes. MAT1A encodes the enzyme methionine adenosyltransferase, which exists in two forms, MATI and MATII, primarily in the liver.
MAT1A is located on the long (q) arm of chromosome 10, at band 10q22.3. Arm ratio per GRCh38 - banding schematic.
Explore chromosome 10 in the library →Available at Jeen Health
Clinical tests that include this
Overview
The MAT1A gene is responsible for encoding methionine adenosyltransferase 1A, an enzyme crucial for the metabolism of the amino acid methionine. This enzyme plays a central role in several fundamental biological processes by facilitating the production of S-adenosylmethionine (AdoMet), a key molecule in biochemical reactions.
Variations within the MAT1A gene can affect the enzyme's activity, potentially leading to altered methionine levels in the body.
What the gene does
The MAT1A gene directs the synthesis of methionine adenosyltransferase, an enzyme expressed in two main forms within the liver: MATI and MATII. MATI is structured as a homotetramer, comprising four identical protein subunits, while MATII is a homodimer, made of two identical subunits. Both forms are integral to the breakdown of methionine.
This enzyme catalyses the initial step in converting methionine into S-adenosylmethionine, also known as AdoMet or SAMe. AdoMet is a critical donor of methyl groups in a process called transmethylation. Transmethylation is essential for numerous cellular activities, including the regulation of gene expression, the modification of proteins and lipids, and the synthesis of neurotransmitters, which are chemical messengers in the nervous system.
Video: Genetics 101
Chromosome location
The MAT1A gene is located on chromosome 10, specifically at position 10q22.3. This region of the human genome contains the genetic instructions for the methionine adenosyltransferase 1A enzyme.
Protein structure
The methionine adenosyltransferase 1A protein is composed of 395 amino acids. A notable structural feature is a flexible loop located between amino acids 113 and 125, which is likely important for the enzyme's function or interaction with other molecules.
Key variants
Genetic variations, often referred to as variants or mutations, within the MAT1A gene can influence the efficiency of the methionine adenosyltransferase enzyme. More than 70 such variants have been identified, with many leading to a reduced ability to process methionine.
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.188G>T | p.Gly63Val | Pathogenic/Likely pathogenic | ★★☆☆ | Hepatic methionine adenosyltransferase deficiency |
c.538_539insTG | p.Ser180fs | Pathogenic | ★★☆☆ | Hepatic methionine adenosyltransferase deficiency |
c.595C>T | p.Arg199Cys | Pathogenic/Likely pathogenic | ★★☆☆ | Hepatic methionine adenosyltransferase deficiency |
c.596G>A | p.Arg199His | Pathogenic | ★★☆☆ | Hepatic methionine adenosyltransferase deficiency |
c.763C>T | p.Pro255Ser | Pathogenic/Likely pathogenic | ★★☆☆ | Hepatic methionine adenosyltransferase deficiency |
c.772G>T | p.Asp258Tyr | Pathogenic/Likely pathogenic | ★★☆☆ | Hepatic methionine adenosyltransferase deficiency |
c.776C>T | p.Ala259Val | Pathogenic | ★★☆☆ | MAT1A-related disorder |
c.874C>T | p.Arg292Cys | Pathogenic/Likely pathogenic | ★★☆☆ | Hepatic methionine adenosyltransferase deficiency |
c.895C>T | p.Arg299Cys | Pathogenic/Likely pathogenic | ★★☆☆ | Hepatic methionine adenosyltransferase deficiency |
c.964A>G | p.Ile322Val | Pathogenic | ★★☆☆ | Hepatic methionine adenosyltransferase deficiency |
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
Variants in the MAT1A gene are primarily associated with hypermethioninaemia, a condition characterised by an excessive accumulation of methionine in the body. These genetic changes can impair the function of the methionine adenosyltransferase enzyme, leading to difficulties in metabolising methionine effectively.
No disease links recorded for this gene in our reference set.
Inheritance pattern
Conditions caused by pathogenic MAT1A variants typically follow autosomal recessive inheritance.
When both parents are carriers, each child has a 25% chance of being affected, 50% of being a carrier, and 25% of being unaffected.
UK clinical status
The MAT1A gene is recognised within the NHS Genomic Medicine Service due to its association with inherited conditions. It is listed as 'green' on PanelApp for conditions such as DDG2P, Intellectual disability, and Likely inborn error of metabolism, as well as Undiagnosed metabolic disorders, indicating strong evidence for its role in these conditions.
Sources: NHS GMS PanelApp · Genomics England PanelApp · NHS National Genomic Test Directory
Frequently asked questions
What is hypermethioninaemia?
Hypermethioninaemia is a condition where there are abnormally high levels of methionine in the blood. It is often linked to variants in the MAT1A gene that reduce the efficiency of the methionine adenosyltransferase enzyme.
How do variants in MAT1A affect the enzyme?
Variants in the MAT1A gene can alter the structure or function of the methionine adenosyltransferase enzyme, making it less effective at processing methionine. This reduced efficiency can lead to the accumulation of methionine in the body.
References
- Chien YH, Chiang SC, Huang A. Spectrum of hypermethioninemia in neonatal screening. Early human development. 2005. PMID: 15935930
- Chou JY. Molecular genetics of hepatic methionine adenosyltransferase deficiency. Pharmacology & therapeutics. 2000. PMID: 10674710
- Chamberlin ME, Ubagai T, Mudd SH. Methionine adenosyltransferase I/III deficiency: novel mutations and clinical variations. American journal of human genetics. 2000. PMID: 10677294
- Smythies JR, Gottfries CG, Regland B. Disturbances of one-carbon metabolism in neuropsychiatric disorders: a review. Biological psychiatry. 1997. PMID: 9018395