MTR rs1805087: What Your Genotype Means
The rs1805087 variant is a widely studied single-nucleotide polymorphism in the MTR gene, which provides instructions for methionine synthase. It leads to an amino acid substitution (often noted as A2756G or Asp919Gly) involved in folate- and vitamin B12-dependent homocysteine remethylation. Research associates this variant with subtle variations in circulating homocysteine and methylation biomarkers, though overall clinical effect sizes are limited.
What each genotype means
| Genotype | What the research suggests | Reading |
|---|---|---|
| AA | This genotype represents two copies of the common ancestral allele. Individuals with this genotype typically exhibit standard methionine synthase baseline activity. Circulating homocysteine levels generally reflect typical metabolic handling assuming normal dietary intake of vitamin B12 and folate. | Informational |
| AG | This genotype indicates one copy of the common allele and one copy of the minor G allele. Methionine synthase activity is generally considered typical or slightly modified, with no substantial independent elevation in homocysteine demonstrated in healthy populations. Nutritional adequacy of folate and cobalamin remains the primary determinant of metabolic balance. | Informational |
| GG | This genotype indicates two copies of the minor G variant allele. In some observational research, this status is associated with subtle alterations in homocysteine remethylation efficiency, particularly in contexts of low dietary vitamin B12 or folate. It does not cause medical disorders on its own and is common among healthy individuals. | Higher attention |
Genomic Location and the Nature of rs1805087
The single-nucleotide polymorphism rs1805087 is located on chromosome 1 within the coding sequence of the MTR (5-methyltetrahydrofolate-homocysteine methyltransferase) gene. In literature and consumer panels, it is frequently designated as A2756G or Asp919Gly (D919G). At the molecular level, an adenine (A) is substituted by a guanine (G) at nucleotide position 2756 of the coding transcript, changing codon 919 from aspartate (Asp) to glycine (Gly). This missense alteration occurs in a region close to the enzyme's binding domains, prompting investigators to explore whether it alters structural stability or enzymatic catalytic rates. Unlike pathogenic loss-of-function variants that cause severe inborn errors of metabolism such as homocystinuria, rs1805087 is a common benign polymorphism present in healthy global populations. Genetic databases like dbSNP catalog it as a standard missense variant that modestly modulates physiological activity rather than completely disrupting gene translation.
The Biological Role of the MTR Gene in Methylation
The MTR gene encodes methionine synthase, an essential enzyme positioned at the junction between the folate cycle and the methionine cycle. Methionine synthase carries out the remethylation of homocysteine into the essential amino acid methionine. To execute this conversion, the enzyme requires cobalamin (vitamin B12) as an intermediate cofactor and accepts a methyl group from 5-methyltetrahydrofolate, the active folate form generated by MTHFR. The newly formed methionine is the direct precursor to S-adenosylmethionine (SAMe), the primary methyl donor utilized across hundreds of cellular processes, including DNA methylation, neurotransmitter synthesis, and phospholipid production. If methionine synthase function is impaired or lacks cofactors, homocysteine can accumulate in the bloodstream, and folate can become functionally trapped. Methionine synthase also closely collaborates with methionine synthase reductase (encoded by MTRR), which maintains cobalamin in its catalytically active state.
Evaluating Research Associations and Strength of Evidence
The clinical evidence linking rs1805087 to significant health endpoints remains classified as limited and mixed. Numerous observational studies and meta-analyses have investigated whether the G allele influences plasma total homocysteine concentrations, vascular disease risk, cognitive traits, and pregnancy outcomes like neural tube defects. While some studies report slight elevations in homocysteine among GG homozygotes, others identify minimal to no detectable differences, particularly in populations with adequate dietary intake of vitamin B12 and folate. The biological impact of rs1805087 appears largely dependent on nutritional status: any subtle functional decrease in enzyme kinetics is often buffered when cellular levels of cobalamin and active folate are sufficient. Because modern genome-wide association studies (GWAS) show very small effect sizes, rs1805087 is viewed in nutrigenomics as a minor modifier rather than an independent causal driver of clinical disease.
How to Interpret rs1805087 Responsibly
Finding your rs1805087 genotype provides educational context regarding one component of your one-carbon metabolism, but it is never a diagnosis or an indicator of illness. You cannot alter your inherited genotype, nor should you make drastic changes to your diet or supplement regimen based solely on a DNA report. Genotypes cannot reliably predict actual homocysteine levels, which are shaped far more by dietary vitamin B12, folate, kidney health, smoking, and age. If you are curious about your methylation pathway or metabolic status, speak to a primary care clinician or registered dietitian to assess objective blood biomarkers, such as serum homocysteine, methylmalonic acid (MMA), and serum cobalamin. Individuals taking medications that interfere with folate or B12 absorption should consult their pharmacist or physician before introducing high-dose vitamins.
How common is this variant?
The minor G allele is relatively common across global populations, with an estimated minor allele frequency of approximately 0.15 to 0.20 in European populations, while varying moderately across other ancestral groups.
Frequently asked questions
Does having the rs1805087 G allele mean I have a methylation deficiency?
No, having the G allele does not mean you have a medical disorder or a broken methylation pathway. rs1805087 is a common, natural variation that slightly alters the structure of methionine synthase. In individuals with adequate B-vitamin intake, the enzyme generally functions normally.
How does MTR rs1805087 interact with the MTHFR gene?
MTR and MTHFR operate consecutively in the folate-methionine pathway. MTHFR produces 5-methyltetrahydrofolate, which is then passed to MTR to convert homocysteine into methionine. While variations in both genes are frequently tested together, having variants in both is common and best evaluated by checking actual nutrient and homocysteine levels in the blood.
Should I take high-dose methylated vitamins if I have the GG genotype?
You should not start high-dose supplements solely because of your genetic test result. While methionine synthase requires vitamin B12 and folate to function, excess supplementation is not always necessary and may cause side effects. It is best to have standard blood tests evaluated by your clinician before beginning new supplements.
Can rs1805087 diagnose cardiovascular disease or birth defects?
No, rs1805087 cannot be used as a standalone diagnostic or risk test for cardiovascular disease, neural tube defects, or any other clinical condition. The scientific evidence showing an association is limited, and overall health outcomes depend primarily on complex lifestyle, nutritional, and multifactorial elements.
Sources & further reading
Educational information only, last refreshed 9/5/2026. Not medical advice — these associations describe population statistics, not individual predictions.
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