MTR

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, 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.

homocystinuria - caused by mutations in the MTR gene

More than 15 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, which disrupts the enzyme's activity. For example, one of the most common mutations replaces the amino acid proline with the amino acid leucine at position 1173 (written as Pro1173Leu or P1173L). Without functional methionine synthase, homocysteine cannot be converted to methionine. As a result, homocysteine builds up in the bloodstream and methionine is depleted. 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.

other disorders - increased risk from variations of the MTR gene

A specific version (variant) of the MTR gene has been associated with an increased risk of having a child with spina bifida, a birth defect that affects the spinal cord. Some studies have suggested that the variant also increases the risk of having a child with Down syndrome (a condition characterized by intellectual disability and associated health problems), but other studies found no increased risk. The variant replaces the nucleotide adenine with the nucleotide guanine at position 2756 in the MTR gene (written as A2756G). (Nucleotides are the building blocks of DNA.) Researchers do not know why there may be a connection between the A2576G variant of the MTR gene and the risk of spina bifida or Down syndrome. Many factors, however, play a part in determining the risk of these complex disorders.