The MTR gene provides instructions for making an enzyme called methionine synthase. This enzyme plays a role in processing amino acids, the building blocks of proteins. Specifically, methionine synthase carries out a chemical reaction that converts the amino acid homocysteine to another amino acid called methionine. The body uses methionine to make proteins and other important compounds. To function properly, methionine synthase requires methylcobalamin (a form of vitamin B12) and another enzyme called methionine synthase reductase, which is produced from the MTRR gene.
More than 20 mutations in the MTR gene have been identified in people with homocystinuria. Many of these mutations lead to the production of an abnormally small, nonfunctional version of methionine synthase. Other mutations change single amino acids in the enzyme. One of the most common mutations replaces the amino acid proline with the amino acid leucine at position 1173 (written as Pro1173Leu or P1173L), resulting in an enzyme with reduced function. Without functional methionine synthase, homocysteine cannot be converted to methionine. As a result, homocysteine builds up in the bloodstream, and the amount of methionine is reduced. Some of the excess homocysteine is excreted in urine. Researchers have not determined how altered levels of homocysteine and methionine lead to the health problems associated with homocystinuria.
A specific version (variant) of the MTR gene has been associated with various health problems before birth. The variant replaces one building block of DNA (nucleotide) called adenine with the nucleotide guanine at position 2756 in the MTR gene (written as A2756G). This variant has been associated with an increased risk of birth defects that occur during the development of the brain and spinal cord (neural tube defects). Some studies have suggested that the variant also increases the risk of having a child with Down syndrome, which is a condition characterized by intellectual disability and associated health problems, but other studies found no increased risk. Researchers do not know why there may be a connection between the A2756G variant of the MTR gene and the risk of neural tube defects or Down syndrome. Many factors play a part in determining the risk of these complex disorders.
- 5-methyltetrahydrofolate-homocysteine methyltransferase 1
- 5-Methyltetrahydrofolate-Homocysteine S-Methyltransferase
- cobalamin-dependent methionine synthase
- Homocysteine-methyl tetrahydrofolate methyltransferase
- Methionine Synthase
- Tetrahydropteroylglutamate Methyltransferase