← Back to Knowledge Base

Primary topic: MTHFD1 gene methylation and B-vitamin use

MTHFD1 Gene and Metabolism: What It Can Mean in a Pathway Report

MTHFD1 is tracked because it connects to homocysteine handling, folate use, and one-carbon metabolism. The current evidence index links this gene to Methylation with 1 SNP and 1 curated claim.

What is the MTHFD1 gene?

Trifunctional folate-cycle enzyme supplying one-carbon units for purine synthesis and methylation support.

How MTHFD1 affects metabolism

When MTHFD1-related function is shifted, the practical effect is interpreted through homocysteine handling, folate use, and one-carbon metabolism. This does not mean the pathway is active or impaired right now; it means the gene can help prioritize what to check next.

What happens when MTHFD1 is altered

Altered MTHFD1 signal should be treated as a DNA-based tendency, not a diagnosis. 1 claim currently passes the report-use gate. The useful question is whether symptoms, labs, and lifestyle context line up with the pathway signal.

Curated SNP evidence for MTHFD1

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.

Methylation

Evidence-backed report connection

MTHFD1 currently has 2 curated SNPs, 2 claim-level scores, and 2 claims eligible for pathway scoring.

Open the sample report
rs1076991MTHFD1 promoter activity signal1 claims · 2 study rows

expression · T

MTHFD1 promoter activity

Moderate

rs1076991 T is associated with reduced MTHFD1 promoter activity in vitro compared with C.

MTHFD1 rs1076991 is scored only as a promoter-activity tendency for the T allele compared with the C allele.

Likely effectLower gene expression signal
Signal sizeModerate signal
Evidence supportModerate support
Report useIncluded in pathway scoring
Show study evidence
NCBI RefSNP recordidentity only · unknownNCBI RefSNP identifies rs1076991 on chromosome 14 in the MTHFD1 region and lists T, C, and G alleles on the current preferred genomic placement. This supports the variant identity only; the rare G allele is not scored because the functional source compared only T and C promoter constructs.Carroll et al. MTHFD1 promoter analysisfunctional assay · directCarroll et al. reported that rs1076991 is located in the MTHFD1 transcription initiation window and that the T 0.59 kb promoter construct had significantly lower luciferase reporter activity than the C construct. The paper reports T construct activity at about 38% of the C construct, supporting a lower promoter-activity direction for T versus C in vitro.
rs2236225G1958A / Arg653Gln1 claims · 2 study rows

enzyme activity · A

MTHFD1 one-carbon enzyme activity

Moderate

rs2236225 A, encoding MTHFD1 Arg653Gln, is associated with reduced MTHFD1 enzyme stability and one-carbon metabolic activity.

MTHFD1 rs2236225 A is staged as a reduced folate-cycle enzyme function allele with one-carbon metabolism relevance.

Likely effectLower enzyme activity signal
Signal sizeSmall signal
Evidence supportModerate support
Report useIncluded in pathway scoring
Show study evidence
PubMed 18767138functional assay · directThe checked PubMed abstract for the MTHFD1 p.Arg653Gln study reports that the purified Arg653Gln enzyme has reduced thermal half-life and that cells transfected with Arg653Gln show reduced formate incorporation into DNA compared with wild-type protein. This directly supports lower enzyme stability/metabolic activity for the A allele encoding Gln653.PMCID PMC9224796clinical curation · directThe checked folate-pathway article describes rs2236225 as a well-studied MTHFD1 polymorphism leading to enzyme thermolability and decreased enzyme activity. The article itself is disease-context, so it is used only as supporting functional curation, not disease-risk evidence.

Common symptoms people report

  • fatigue or brain fog under workload
  • higher concern around homocysteine balance
  • unpredictable response to B-vitamin intake

Biomarkers to validate

Homocysteine

Checks whether methylation support is actually under strain.

Folate and B12

Helps separate folate-cycle pressure from broader B-vitamin status.

CBC and MCV

Adds context for red-blood-cell and B-vitamin patterns.

Where DNA analysis helps

DNA helps decide whether MTHFD1 deserves attention inside the broader Methylation pathway. It is most useful when combined with biomarkers instead of used as a standalone answer.

Example interpretation

MTHFD1 may add context to homocysteine handling, folate use, and one-carbon metabolism, especially when its SNP evidence lines up with other genes in the same pathway.

Suggested validation: Homocysteine.

What to do next

  • Review the Methylation pathway result before interpreting MTHFD1 on its own.
  • Use relevant biomarkers to confirm whether this DNA tendency is visible in current biology.
  • Treat supplement or nutrition decisions as follow-up steps only after the pattern fits symptoms or labs.

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

Get My DNA Report

Related pages

MTHFR

MTHFR gene metabolism

BHMT

BHMT gene function

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

Browse the knowledge base

See the full index of gene guides, biomarker guides, pathway guides, symptoms, buyer pages, and common questions.