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Primary topic: SHMT1 gene metabolism

SHMT1 Gene and Metabolism: What It Means for Your Body

SHMT1 participates in one-carbon metabolism and helps move folate-related chemistry toward processes that support methylation and nucleotide balance.

What is the SHMT1 gene?

SHMT1 helps interconvert serine and glycine while moving one-carbon units within folate metabolism. It contributes to the balance between methylation support and related cellular demands.

How SHMT1 affects metabolism

If SHMT1-related handling is less efficient, folate-cycle flexibility may drop. That can make the broader one-carbon network more sensitive when folate availability, methylation demand, or cell-repair needs increase.

What happens when SHMT1 is altered

Altered SHMT1 function rarely makes sense as a standalone interpretation. It is most useful as part of a network view alongside MTHFR, BHMT, and biomarkers.

Curated SNP evidence for SHMT1

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

SHMT1 currently has 2 curated SNPs, 6 claim-level scores, and 0 claims eligible for pathway scoring.

Open the sample report
rs1979277SHMT1 C1420T3 claims · 9 study rows

transport activity · AA

SHMT1 transport activity

Not used for pathway scoring

rs1979277 AA is associated with reduced SHMT1 transport activity.

SHMT1 rs1979277 is scored as a modest tendency toward reduced SHMT1 nuclear transport or localization when the A allele is present.

Likely effectLower transport signal
Signal sizeSmall signal
Evidence supportLimited support
Report useEvidence only, not scored
Show study evidence
NCBI RefSNP recordidentity only · unknownNCBI RefSNP data for rs1979277 list SHMT1, serine hydroxymethyltransferase 1, as the annotated gene and A/G as the common alleles. The A allele is annotated as a missense change in SHMT1.PubMed 17446168functional assay · directWoeller et al. studied the common SHMT1 L474F form and reported impaired interaction with UBC9 and reduced SUMOylation in vitro. The authors concluded that this polymorphism is likely to modify the efficiency of nuclear folate metabolism. This supports a conservative lower nuclear transport or localization tendency for A-containing genotypes.PubMed 31713293other · loose proxySalamanca et al. describe rs1979277 and cite prior functional evidence, but the reported study is a clinical association sample rather than a direct SHMT1 transport/localization assay. It is retained as context and not scored for this transport-activity claim.

transport activity · AG

SHMT1 transport activity

Not used for pathway scoring

rs1979277 AG is associated with reduced SHMT1 transport activity.

SHMT1 rs1979277 is scored as a modest tendency toward reduced SHMT1 nuclear transport or localization when the A allele is present.

Likely effectLower transport signal
Signal sizeSmall signal
Evidence supportLimited support
Report useEvidence only, not scored
Show study evidence
NCBI RefSNP recordidentity only · unknownNCBI RefSNP data for rs1979277 list SHMT1, serine hydroxymethyltransferase 1, as the annotated gene and A/G as the common alleles. The A allele is annotated as a missense change in SHMT1.PubMed 17446168functional assay · directWoeller et al. studied the common SHMT1 L474F form and reported impaired interaction with UBC9 and reduced SUMOylation in vitro. The authors concluded that this polymorphism is likely to modify the efficiency of nuclear folate metabolism. This supports a conservative lower nuclear transport or localization tendency for A-containing genotypes.PubMed 31713293other · loose proxySalamanca et al. describe rs1979277 and cite prior functional evidence, but the reported study is a clinical association sample rather than a direct SHMT1 transport/localization assay. It is retained as context and not scored for this transport-activity claim.

transport activity · GG

SHMT1 transport activity

Not used for pathway scoring

rs1979277 GG has no scored directional claim for SHMT1 transport activity.

SHMT1 rs1979277 is scored as a modest tendency toward reduced SHMT1 nuclear transport or localization when the A allele is present.

Likely effectNo clear transport signal
Signal sizeMinimal signal
Evidence supportVery limited support
Report useEvidence only, not scored
Show study evidence
NCBI RefSNP recordidentity only · unknownNCBI RefSNP data for rs1979277 list SHMT1, serine hydroxymethyltransferase 1, as the annotated gene and A/G as the common alleles. The A allele is annotated as a missense change in SHMT1.PubMed 17446168functional assay · directWoeller et al. studied the common SHMT1 L474F form and reported impaired interaction with UBC9 and reduced SUMOylation in vitro. The authors concluded that this polymorphism is likely to modify the efficiency of nuclear folate metabolism. This supports a conservative lower nuclear transport or localization tendency for A-containing genotypes.PubMed 31713293other · loose proxySalamanca et al. described rs1979277 as SHMT1 G>A, p.Leu474Phe. Their abstract notes previous functional evidence and bioinformatic prediction suggesting lower SHMT activity for the A allele, but the clinical association was studied in one Chilean case-control sample. This supports modest certainty and avoids treating the genotype as a broad health prediction.
rs9909104SHMT1 supporting signal3 claims · 9 study rows

unknown · CC

SHMT1 unscored target

Not used for pathway scoring

rs9909104 CC has no scored directional claim for SHMT1 unscored target.

SHMT1 rs9909104 is kept neutral because available sources do not establish a clear end-user metabolomics effect for any genotype.

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 rs9909104 as a SHMT1 variant with a GRCh38 top-level placement on chromosome 17 and T/C alleles. SHMT1 encodes serine hydroxymethyltransferase 1, but this variant is annotated within an intronic region rather than as a protein-changing variant.PubMed 10other · loose proxyA childhood acute lymphoblastic leukemia association study evaluated rs9909104 among folate-pathway SNPs and reported an association with survival in that treated disease cohort. The discussion states that no function had been associated with rs9909104, so this file does not assign an enzyme, expression, transport, or biomarker direction.PubMed 26950450other · loose proxyA smaller Iranian childhood acute lymphoblastic leukemia case-control study reported that rs9909104 was associated with lower disease risk, while also stating that larger studies in different ethnicities were needed. This supports treating the variant as an uncertain association signal rather than a direct metabolomics effect.

unknown · CT

SHMT1 unscored target

Not used for pathway scoring

rs9909104 CT has no scored directional claim for SHMT1 unscored target.

SHMT1 rs9909104 is kept neutral because available sources do not establish a clear end-user metabolomics effect for any genotype.

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 rs9909104 as a SHMT1 variant with a GRCh38 top-level placement on chromosome 17 and T/C alleles. SHMT1 encodes serine hydroxymethyltransferase 1, but this variant is annotated within an intronic region rather than as a protein-changing variant.PubMed 10other · loose proxyA childhood acute lymphoblastic leukemia association study evaluated rs9909104 among folate-pathway SNPs and reported an association with survival in that treated disease cohort. The discussion states that no function had been associated with rs9909104, so this file does not assign an enzyme, expression, transport, or biomarker direction.PubMed 26950450other · loose proxyA smaller Iranian childhood acute lymphoblastic leukemia case-control study reported that rs9909104 was associated with lower disease risk, while also stating that larger studies in different ethnicities were needed. This supports treating the variant as an uncertain association signal rather than a direct metabolomics effect.

unknown · TT

SHMT1 unscored target

Not used for pathway scoring

rs9909104 TT has no scored directional claim for SHMT1 unscored target.

SHMT1 rs9909104 is kept neutral because available sources do not establish a clear end-user metabolomics effect for any genotype.

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 rs9909104 as a SHMT1 variant with a GRCh38 top-level placement on chromosome 17 and T/C alleles. SHMT1 encodes serine hydroxymethyltransferase 1, but this variant is annotated within an intronic region rather than as a protein-changing variant.PubMed 10other · loose proxyA childhood acute lymphoblastic leukemia association study evaluated rs9909104 among folate-pathway SNPs and reported an association with survival in that treated disease cohort. The discussion states that no function had been associated with rs9909104, so this file does not assign an enzyme, expression, transport, or biomarker direction.PubMed 26950450other · loose proxyA smaller Iranian childhood acute lymphoblastic leukemia case-control study reported that rs9909104 was associated with lower disease risk, while also stating that larger studies in different ethnicities were needed. This supports treating the variant as an uncertain association signal rather than a direct metabolomics effect.

Common symptoms people report

  • fatigue with a methylation-related pattern
  • brain fog when under sustained cognitive load
  • unclear response to folate support
  • interest in deeper folate-cycle interpretation

Biomarkers to validate

Homocysteine

Helpful downstream marker for one-carbon and methylation balance.

Folate markers

Useful for understanding substrate context.

Vitamin B12

Adds necessary context for interpreting folate-cycle pressure.

Where DNA analysis helps

DNA analysis helps identify whether SHMT1 belongs in the first-wave methylation questions worth validating. The value is in network-level prioritization, not isolated gene interpretation.

Example Insight

Your one-carbon metabolism network may be a little less flexible when folate demand rises.

Suggested validation: homocysteine plus folate and B12 markers.

What to do next

  • Use SHMT1 as part of a folate-network interpretation rather than a solo explanation.
  • Validate homocysteine, folate, and B12 before changing strategy.
  • Compare SHMT1 with MTHFR and BHMT to understand one-carbon balance.

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

Fatigue after eating carbs

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