G
Genetic Archaeology
GENETIC ARCHAEOLOGY // PROFILE

MTR

Methionine Synthase

CHR 1
1q43

Overview

MTR encodes the enzyme methionine synthase, which requires Vitamin B12 (cobalamin) to convert homocysteine into methionine. This process is essential for DNA methylation and one-carbon metabolism.

📍 Chromosomal Position

1q43 (Chromosome 1)

🧬 Gene Category

Vitamins

🔬 Inheritance

Complex

📊 Prevalence

G allele ~15-20%

Function & Significance

Methionine synthase is a key enzyme in one-carbon metabolism:

  • Homocysteine Remethylation: Converts homocysteine → methionine
  • Vitamin B12 Dependent: Requires cobalamin as a cofactor
  • Folate Cycle: Uses 5-methyltetrahydrofolate as a methyl group donor
  • DNA Methylation: Provides methionine for S-adenosylmethionine (SAM)

🔄 The Methionine Cycle

MTR works together with:

  • MTHFR: Provides 5-methyltetrahydrofolate
  • MTRR: Reactivates MTR when B12 is oxidized
  • Vitamin B12: Essential cofactor
  • Folic Acid: Methyl group donor

Important: All three genes (MTHFR, MTR, MTRR) operate in the same metabolic pathway!

🧬 Relevant SNPs

The A2756G variant (D919G):

rs1805087
1:236885200
Allele 1

A

/

Allele 2

G

Significance: A2756G (D919G) – Aspartate → Glycine at position 919

• AA (Wild type): Normal MTR activity

• GG: Slightly reduced enzyme activity (~10-20%)

• AG: Intermediate

⚠️ Impact of the G Variant

G carriers (AG or GG) may have:

  • Slightly elevated homocysteine: Especially with low B12 levels
  • Increased B12 requirement: For optimal MTR function
  • Neural tube defect risk: In combination with MTHFR C677T
  • Cardiovascular risk: If homocysteine levels are high

Important: The effect is usually mild and primarily relevant during B12 deficiency!

💊 Recommendations for G Carriers

Optimizing B12 metabolism:

  • Vitamin B12: Ensure adequate intake (2.5-10 µg/day)
    • Meat, fish, eggs, dairy products
    • Vegans: Supplementation required!
    • Prefer methylcobalamin or hydroxocobalamin
  • Folic Acid: 400-800 µg/day
    • Green leafy vegetables, legumes
    • With MTHFR variant: use methylated form (5-MTHF)
  • Vitamin B6: Supports homocysteine breakdown (alternative pathway)
  • Homocysteine Test: Regular monitoring recommended

🧬 Gene Combinations

MTR works in synergy with other genes:

  • MTR GG + MTHFR 677TT: Higher risk of elevated homocysteine
  • MTR GG + MTRR AA: Both are B12-dependent, increased demand
  • MTR AA + MTHFR TT: MTR can partially compensate for the MTHFR effect

Conclusion: The combination of several variants is more important than a single one!

📚 Data Sources

The information on this page is based on the following scientific sources:

  • OMIM: #156570 – Online Mendelian Inheritance in Man
  • dbSNP: rs1805087 – SNP Database (NCBI)
  • ClinVar: Clinical variant database (NCBI)
  • PubMed: MTR and Homocysteine Research
  • Molecular Genetics and Metabolism: B12 metabolism studies

Last Update: February 2026

Biological Function

Methionine synthase is an essential enzyme in one-carbon metabolism. It catalyzes the remethylation of homocysteine to methionine using 5-methyltetrahydrofolate as a methyl donor and Vitamin B12 (cobalamin) as a cofactor. This process is crucial for DNA methylation, protein synthesis, and homocysteine metabolism.

Associated Conditions

Hyperhomocysteinemia Neural Tube Defects Cardiovascular Diseases Megaloblastic Anemia
Molecular Analysis

Analyzed Markers

rs1805087 Risk Factor
Pos: 1:236885200 | Alleles: A/G

A2756G (D919G) - G-allele: slightly reduced enzyme activity, influences B12 metabolism and homocysteine levels