MTR A2756G: Vitamin B12, Folate, and Homocysteine

6 days ago

3 min read

Vitamin B12 and folate work together at an important junction in your metabolism: recycling homocysteine into methionine. The enzyme responsible for this reaction is methionine synthase, produced by the MTR gene. It connects these nutrients with processes involved in protein production and methylation [R].

One commonly studied variant is MTR A2756G, also called rs1805087.

You can explore your result in the free GenesUnveiled Methylation Panel.

Folate 400 mcg supplement bottle with spinach, broccoli, chickpeas, lentils and avocado on a wooden surface.

What Does the MTR Gene Do?

MTR provides instructions for making methionine synthase, an enzyme that converts homocysteine into methionine using a methyl group supplied by 5-methyltetrahydrofolate, a form of folate. Vitamin B12 acts as an essential cofactor in this reaction [R].

This reaction helps:

Recycle homocysteine into an amino acid the body can reuse.
Regenerate tetrahydrofolate, allowing folate to participate in other reactions.
Supply methionine, which is used to produce S-adenosylmethionine, or SAM.

SAM supplies methyl groups for reactions involving DNA, proteins, and other molecules. This explains why MTR appears in methylation panels: its enzyme helps maintain the supply chain supporting these reactions [R, R].

What Is MTR A2756G?

The A2756G name describes an A-to-G change in the gene’s coding sequence. At the protein level, it replaces aspartate with glycine at position 919, explaining the alternative names Asp919Gly and D919G [R].

Your result may appear as:

Genotype	Protein versions at position 919
AA	Aspartate on both copies
AG	One aspartate copy and one glycine copy
GG	Glycine on both copies

These letters identify the versions you carry. They do not directly measure enzyme speed, B12 availability, or your current methylation activity.

Does the G Allele Raise or Lower Homocysteine?

Some research points toward lower homocysteine among G-allele carriers.

A 2013 study involving 570 healthy Canadian adults reported the following adjusted average homocysteine concentrations:

AA: 9.2 μmol/L.
AG and GG combined: 8.7 μmol/L.

The difference was statistically significant, but modest: approximately 0.5 μmol/L. Only 15 participants had GG, so the researchers combined AG and GG for the main analysis. The study therefore does not establish a separate, stronger effect for GG [R].

Other findings have been less clear. In the NHLBI Family Heart Study, researchers had MTR genotype data for 677 participants and found no association between AA, AG, or GG and fasting homocysteine [R].

Does MTR A2756G Mean Faster Methylation?

Lower homocysteine has led researchers to propose that A2756G might increase methionine synthase activity. However, a blood-marker association does not establish a fixed percentage change in enzyme function.

The Canadian study also found no significant association between MTR genotype and circulating SAM, despite the difference in homocysteine [R].

How MTR Differs From MTHFR and MTRR

These genes support connected steps:

MTHFR helps produce the folate form that supplies the methyl group.
MTR carries out the conversion of homocysteine into methionine.
MTRR helps reactivate methionine synthase so it can continue functioning.

Vitamin B12 is essential to the MTR reaction, linking folate metabolism with B12-dependent homocysteine recycling [R].

For another part of this pathway, read our guide to MTHFR rs1801133.

What Does Your Result Mean for Vitamin B12?

Because methionine synthase requires B12, the connection is biologically important. However, rs1805087 does not reveal whether you are B12 deficient or determine your supplement dose.

When B12 status needs investigation, clinicians generally assess blood B12 and may use methylmalonic acid (MMA) to clarify an uncertain result. Homocysteine can provide additional information, but it is also influenced by folate status and kidney function [R].

Explore Your MTR Result for Free

MTR A2756G offers a window into the reaction where folate and vitamin B12 work together to recycle homocysteine.

The free GenesUnveiled Methylation Panel checks rs1805087 alongside six other markers across MTHFR, MTRR, TCN2, COMT, and MTHFD1.

Your raw DNA file is processed in your browser, and your raw file and individual genetic results are not uploaded to our servers during analysis. If a marker is missing from your file, the panel cannot determine its genotype.