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Primary topic: MTR methionine synthase gene

MTR Gene and Metabolism: What It Means for Your Body

MTR matters when the final B12-dependent remethylation step looks less reliable than expected.

What is the MTR gene?

MTR encodes methionine synthase, the enzyme that uses methyl-B12 to move homocysteine back toward methionine. That makes it central to methylation flow rather than a peripheral nutrient detail.

How MTR affects metabolism

If MTR-related throughput is lower, methylation support can stall even when folate intake looks reasonable. In practice this overlaps with homocysteine, B12 handling, and one-carbon resilience.

What happens when MTR is altered

Altered MTR function does not prove deficiency, but it raises the value of checking functional B12 and methylation markers before assuming the pathway is fine.

Curated SNP evidence for MTR

These SNPs come from the approved study-level evidence model. Each claim is scored from curated study rows, then gated before it can influence pathway scoring.

B12 transport Methylation

Evidence-backed report connection

MTR currently has 4 curated SNPs, 11 claim-level scores, and 2 claims eligible for pathway scoring.

Open the sample report
rs10925235MTR supporting signal6 claims · 18 study rows

unknown · AA

MTR unscored target

Not used for pathway scoring

rs10925235 AA has no scored directional claim for MTR unscored target.

MTR rs10925235 is currently not scored for a clear metabolic effect because available evidence is indirect and not strong enough for a user-facing direction.

Likely effectNo clear DNA signal
Signal sizeMinimal signal
Evidence supportVery limited support
Report useEvidence only, not scored
Show study evidence
NCBI RefSNP recordidentity only · unknownNCBI RefSNP data identify rs10925235 as an MTR variant with A, C, and T alleles and intronic transcript annotations. This supports curation as an MTR locus marker, but not as a direct enzyme-changing variant.PubMed 21743092other · loose proxyHo et al. studied candidate genes in frailty and reported that several MTR-region SNPs, including rs10925235, ranked among the stronger frailty associations in their exploratory analysis. The study also stated that no SNP reached study-wide significance after controlling the family-wise false-discovery rate, so this is not strong enough for a directional genotype effect.PubMed 17035141other · loose proxyBoyles et al. included rs10925235 while studying folate-pathway genes and neural tube defects. Their overall significant findings centered on BHMT rather than MTR, supporting a conservative no-direction score for rs10925235.

unknown · AC

MTR unscored target

Not used for pathway scoring

rs10925235 AC has no scored directional claim for MTR unscored target.

MTR rs10925235 is currently not scored for a clear metabolic effect because available evidence is indirect and not strong enough for a user-facing direction.

Likely effectNo clear DNA signal
Signal sizeMinimal signal
Evidence supportVery limited support
Report useEvidence only, not scored
Show study evidence
NCBI RefSNP recordidentity only · unknownNCBI RefSNP data identify rs10925235 as an MTR variant with A, C, and T alleles and intronic transcript annotations. This supports curation as an MTR locus marker, but not as a direct enzyme-changing variant.PubMed 21743092other · loose proxyHo et al. studied candidate genes in frailty and reported that several MTR-region SNPs, including rs10925235, ranked among the stronger frailty associations in their exploratory analysis. The study also stated that no SNP reached study-wide significance after controlling the family-wise false-discovery rate, so this is not strong enough for a directional genotype effect.PubMed 17035141other · loose proxyBoyles et al. included rs10925235 while studying folate-pathway genes and neural tube defects. Their overall significant findings centered on BHMT rather than MTR, supporting a conservative no-direction score for rs10925235.

unknown · AT

MTR unscored target

Not used for pathway scoring

rs10925235 AT has no scored directional claim for MTR unscored target.

MTR rs10925235 is currently not scored for a clear metabolic effect because available evidence is indirect and not strong enough for a user-facing direction.

Likely effectNo clear DNA signal
Signal sizeMinimal signal
Evidence supportVery limited support
Report useEvidence only, not scored
Show study evidence
NCBI RefSNP recordidentity only · unknownNCBI RefSNP data identify rs10925235 as an MTR variant with A, C, and T alleles and intronic transcript annotations. This supports curation as an MTR locus marker, but not as a direct enzyme-changing variant.PubMed 21743092other · loose proxyHo et al. studied candidate genes in frailty and reported that several MTR-region SNPs, including rs10925235, ranked among the stronger frailty associations in their exploratory analysis. The study also stated that no SNP reached study-wide significance after controlling the family-wise false-discovery rate, so this is not strong enough for a directional genotype effect.PubMed 17035141other · loose proxyBoyles et al. included rs10925235 while studying folate-pathway genes and neural tube defects. Their overall significant findings centered on BHMT rather than MTR, supporting a conservative no-direction score for rs10925235.

unknown · CC

MTR unscored target

Not used for pathway scoring

rs10925235 CC has no scored directional claim for MTR unscored target.

MTR rs10925235 is currently not scored for a clear metabolic effect because available evidence is indirect and not strong enough for a user-facing direction.

Likely effectNo clear DNA signal
Signal sizeMinimal signal
Evidence supportVery limited support
Report useEvidence only, not scored
Show study evidence
NCBI RefSNP recordidentity only · unknownNCBI RefSNP data identify rs10925235 as an MTR variant with A, C, and T alleles and intronic transcript annotations. This supports curation as an MTR locus marker, but not as a direct enzyme-changing variant.PubMed 21743092other · loose proxyHo et al. studied candidate genes in frailty and reported that several MTR-region SNPs, including rs10925235, ranked among the stronger frailty associations in their exploratory analysis. The study also stated that no SNP reached study-wide significance after controlling the family-wise false-discovery rate, so this is not strong enough for a directional genotype effect.PubMed 17035141other · loose proxyBoyles et al. included rs10925235 while studying folate-pathway genes and neural tube defects. Their overall significant findings centered on BHMT rather than MTR, supporting a conservative no-direction score for rs10925235.

unknown · CT

MTR unscored target

Not used for pathway scoring

rs10925235 CT has no scored directional claim for MTR unscored target.

MTR rs10925235 is currently not scored for a clear metabolic effect because available evidence is indirect and not strong enough for a user-facing direction.

Likely effectNo clear DNA signal
Signal sizeMinimal signal
Evidence supportVery limited support
Report useEvidence only, not scored
Show study evidence
NCBI RefSNP recordidentity only · unknownNCBI RefSNP data identify rs10925235 as an MTR variant with A, C, and T alleles and intronic transcript annotations. This supports curation as an MTR locus marker, but not as a direct enzyme-changing variant.PubMed 21743092other · loose proxyHo et al. studied candidate genes in frailty and reported that several MTR-region SNPs, including rs10925235, ranked among the stronger frailty associations in their exploratory analysis. The study also stated that no SNP reached study-wide significance after controlling the family-wise false-discovery rate, so this is not strong enough for a directional genotype effect.PubMed 17035141other · loose proxyBoyles et al. included rs10925235 while studying folate-pathway genes and neural tube defects. Their overall significant findings centered on BHMT rather than MTR, supporting a conservative no-direction score for rs10925235.

unknown · TT

MTR unscored target

Not used for pathway scoring

rs10925235 TT has no scored directional claim for MTR unscored target.

MTR rs10925235 is currently not scored for a clear metabolic effect because available evidence is indirect and not strong enough for a user-facing direction.

Likely effectNo clear DNA signal
Signal sizeMinimal signal
Evidence supportVery limited support
Report useEvidence only, not scored
Show study evidence
NCBI RefSNP recordidentity only · unknownNCBI RefSNP data identify rs10925235 as an MTR variant with A, C, and T alleles and intronic transcript annotations. This supports curation as an MTR locus marker, but not as a direct enzyme-changing variant.PubMed 21743092other · loose proxyHo et al. studied candidate genes in frailty and reported that several MTR-region SNPs, including rs10925235, ranked among the stronger frailty associations in their exploratory analysis. The study also stated that no SNP reached study-wide significance after controlling the family-wise false-discovery rate, so this is not strong enough for a directional genotype effect.PubMed 17035141other · loose proxyBoyles et al. included rs10925235 while studying folate-pathway genes and neural tube defects. Their overall significant findings centered on BHMT rather than MTR, supporting a conservative no-direction score for rs10925235.
rs1131450MTR 3' UTR remethylation-capacity signal1 claims · 3 study rows

biomarker tendency · AA

MTR-mediated homocysteine remethylation

Moderate

rs1131450 AA is associated with lower MTR-mediated homocysteine remethylation capacity.

MTR rs1131450 AA is scored as a lower MTR/remethylation tendency based on functional reporter data and homocysteine-related biomarkers.

Likely effectLower biomarker tendency
Signal sizeSmall signal
Evidence supportModerate support
Report useIncluded in pathway scoring
Show study evidence
NCBI RefSNP recordidentity only · unknownNCBI RefSNP places rs1131450 on chromosome 1 and lists G and A alleles on the current preferred genomic placement. This supports using A-containing genotype labels for the MTR G>A source claim, but does not itself assign effect direction.Scientific Reports 2016 MTR functional variant studyfunctional assay · directQu et al. reported rs1131450 G>A in the MTR 3 prime UTR. In luciferase assays, the A-allele construct showed lower reporter activity than the G construct in LNCaP and PC3 cells. The same paper notes that prostate tissue qPCR did not show a direct mRNA-expression association for rs1131450, so this evidence supports a conservative lower MTR pathway-function tendency rather than a high-certainty expression claim.Scientific Reports 2016 plasma homocysteine analysisbiomarker association · close proxyThe same study measured plasma homocysteine in 201 prostate cancer patients and 210 matched controls. For rs1131450 G>A, AA carriers had the highest plasma homocysteine concentration, approximately 1.5-fold higher than GG carriers in the case cohort, control cohort, and combined analysis. Because MTR remethylates homocysteine to methionine, this is close metabolic biomarker support for lower MTR-mediated remethylation capacity in AA.
rs1805087A2756G3 claims · 9 study rows

unknown · AA

MTR unscored target

Not used for pathway scoring

rs1805087 AA has no scored directional claim for MTR unscored target.

MTR rs1805087 is not assigned a clear user-facing genotype effect in this file because published evidence does not support a stable direction for enzyme activity or biomarkers.

Likely effectNo clear DNA signal
Signal sizeMinimal signal
Evidence supportVery limited support
Report useEvidence only, not scored
Show study evidence
NCBI RefSNP recordidentity only · unknownNCBI RefSNP data identify rs1805087 in MTR with A and G alleles. Transcript annotations include NM_000254.3:c.2756A>G and a predicted Asp-to-Gly protein substitution, so the variant is biologically plausible but not automatically interpretable as a user-facing activity score.ClinVar recordclinical curation · close proxyClinVar Variation ID 138289 lists rs1805087 as NM_000254.3(MTR):c.2756A>G, p.Asp919Gly, and describes it as a common MTR polymorphism. ClinVar does not provide a simple benign-or-pathogenic user interpretation for metabolism scoring.PubMed 19826453review · loose proxyA meta-analysis of MTR A2756G noted that earlier work proposed lower enzyme activity and higher homocysteine for the G allele, while later studies suggested the opposite for homocysteine in some settings. Because the biomarker and disease-association literature is mixed, this file does not assign a directional genotype effect.

unknown · AG

MTR unscored target

Not used for pathway scoring

rs1805087 AG has no scored directional claim for MTR unscored target.

MTR rs1805087 is not assigned a clear user-facing genotype effect in this file because published evidence does not support a stable direction for enzyme activity or biomarkers.

Likely effectNo clear DNA signal
Signal sizeMinimal signal
Evidence supportVery limited support
Report useEvidence only, not scored
Show study evidence
NCBI RefSNP recordidentity only · unknownNCBI RefSNP data identify rs1805087 in MTR with A and G alleles. Transcript annotations include NM_000254.3:c.2756A>G and a predicted Asp-to-Gly protein substitution, so the variant is biologically plausible but not automatically interpretable as a user-facing activity score.ClinVar recordclinical curation · close proxyClinVar Variation ID 138289 lists rs1805087 as NM_000254.3(MTR):c.2756A>G, p.Asp919Gly, and describes it as a common MTR polymorphism. ClinVar does not provide a simple benign-or-pathogenic user interpretation for metabolism scoring.PubMed 19826453review · loose proxyA meta-analysis of MTR A2756G noted that earlier work proposed lower enzyme activity and higher homocysteine for the G allele, while later studies suggested the opposite for homocysteine in some settings. Because the biomarker and disease-association literature is mixed, this file does not assign a directional genotype effect.

unknown · GG

MTR unscored target

Not used for pathway scoring

rs1805087 GG has no scored directional claim for MTR unscored target.

MTR rs1805087 is not assigned a clear user-facing genotype effect in this file because published evidence does not support a stable direction for enzyme activity or biomarkers.

Likely effectNo clear DNA signal
Signal sizeMinimal signal
Evidence supportVery limited support
Report useEvidence only, not scored
Show study evidence
NCBI RefSNP recordidentity only · unknownNCBI RefSNP data identify rs1805087 in MTR with A and G alleles. Transcript annotations include NM_000254.3:c.2756A>G and a predicted Asp-to-Gly protein substitution, so the variant is biologically plausible but not automatically interpretable as a user-facing activity score.ClinVar recordclinical curation · close proxyClinVar Variation ID 138289 lists rs1805087 as NM_000254.3(MTR):c.2756A>G, p.Asp919Gly, and describes it as a common MTR polymorphism. ClinVar does not provide a simple benign-or-pathogenic user interpretation for metabolism scoring.PubMed 19826453review · loose proxyA meta-analysis of MTR A2756G noted that earlier work proposed lower enzyme activity and higher homocysteine for the G allele, while later studies suggested the opposite for homocysteine in some settings. Because the biomarker and disease-association literature is mixed, this file does not assign a directional genotype effect.
rs2275565MTR homocysteine supporting signal1 claims · 3 study rows

biomarker tendency · GT

Plasma total homocysteine tendency

Moderate

rs2275565 GT carries one T allele in MTR and is associated with lower plasma total homocysteine tendency.

MTR rs2275565 GT is staged as a modest lower-homocysteine biomarker genotype within the B12-dependent remethylation route.

Likely effectLower biomarker tendency
Signal sizeSmall signal
Evidence supportStrong support
Report useIncluded in pathway scoring
Show study evidence
NCBI RefSNP recordidentity only · unknownNCBI RefSNP identifies rs2275565 as a chromosome 1 MTR-region variant. This row supports variant identity only and does not assign biomarker direction.PubMed 23824729gwas · directvan Meurs et al. reported rs2275565 near MTR among known loci associated with plasma total homocysteine. The coded T allele frequency was 0.21, with beta -0.0542 SD per allele, SE 0.009, and P = 1.96e-10 for total homocysteine.GWAS Catalog association 34418gwas · directGWAS Catalog records rs2275565-T for homocysteine measurement, mapped to MTR, with beta direction decrease, beta 0.0542, SE 0.009, and P = 2e-10. This independently confirms allele orientation in a curated association record.

Common symptoms people report

  • brain fog with unclear B12 context
  • fatigue despite reasonable nutrient intake
  • homocysteine concerns that do not fit a simple folate-only explanation

Biomarkers to validate

Homocysteine

Useful for checking whether remethylation support looks pressured.

Methylmalonic acid

Adds context for functional B12 sufficiency.

Holotranscobalamin

Helpful when transport and recycling questions overlap.

Where DNA analysis helps

DNA helps show whether methionine synthase deserves attention inside a broader methylation or B12 review. The value is in prioritizing follow-up markers, not diagnosing from genetics alone.

Example Insight

Your methionine synthase step may deserve follow-up because B12-dependent methylation support does not always fail at the same place.

Suggested validation: homocysteine plus methylmalonic acid.

What to do next

  • Check homocysteine and methylmalonic acid before assuming MTR is limiting.
  • Review MTR together with MTRR and TCN2 when B12 support looks uneven.
  • Use functional markers before changing supplement strategy aggressively.

Upload your DNA file and receive a structured metabolic pathway analysis with prioritized insights and suggested validation markers.

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Related pages

MTRR

MTRR B12 recycling gene

TCN2

TCN2 B12 transport gene

Holotranscobalamin

holotranscobalamin and B12 transport

Homocysteine

homocysteine and methylation

B12 transport and recycling pathway

B12 transport and recycling pathway

Methylation pathway

methylation pathway explained

Is DNA metabolism analysis worth it?

is DNA metabolism analysis worth it

DNA nutrition analysis report

DNA nutrition analysis report

Related symptom angle

Brain fog metabolism causes

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