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Primary topic: SLC46A1 gene methylation and B-vitamin use

SLC46A1 Gene and Metabolism: What It Can Mean in a Pathway Report

SLC46A1 is tracked because it connects to homocysteine handling, folate use, and one-carbon metabolism. The current evidence index links this gene to Methylation with 4 SNPs and 4 curated claims.

What is the SLC46A1 gene?

Proton-coupled folate transporter supporting intestinal folate absorption and folate delivery into one-carbon metabolism.

How SLC46A1 affects metabolism

When SLC46A1-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 SLC46A1 is altered

Altered SLC46A1 signal should be treated as a DNA-based tendency, not a diagnosis. 4 claims currently pass the report-use gate. The useful question is whether symptoms, labs, and lifestyle context line up with the pathway signal.

Curated SNP evidence for SLC46A1

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

SLC46A1 currently has 4 curated SNPs, 4 claim-level scores, and 4 claims eligible for pathway scoring.

Open the sample report
rs281875209SLC46A1 c.1012G>C / Gly338Arg1 claims · 3 study rows

transport activity · GG or compound-heterozygous SLC46A1 deficiency context

Proton-coupled folate transporter activity tendency

Strong

rs281875209 G (forward-genomic; SLC46A1 c.1012G>C / p.Gly338Arg transcript context) is associated with lower proton-coupled folate transporter activity tendency and impaired folate absorption in recessive or compound-heterozygous hereditary folate-malabsorption contexts.

SLC46A1 rs281875209 G is staged as the forward-genomic recessive hereditary folate-malabsorption allele affecting PCFT folate transport and methylation folate supply.

Likely effectLower transport signal
Signal sizeModerate signal
Evidence supportStrong support
Report useIncluded in pathway scoring
Show study evidence
ClinVar Variation 30925clinical curation · directClinVar maps rs281875209 to SLC46A1 c.1012G>C / p.Gly338Arg and hereditary folate malabsorption, supporting exact-allele pathogenic PCFT deficiency curation.PMCID PMC3081934functional assay · directThe checked PCFT functional study reports complete loss of transport activity for the G338R mutant in folate transporter-deficient cells, matching the rs281875209 p.Gly338Arg allele biology.GeneReviews Hereditary Folate Malabsorptionclinical curation · directGeneReviews supports SLC46A1/PCFT loss of function as the molecular basis for hereditary folate malabsorption with impaired intestinal and CSF folate transport.
rs80338769SLC46A1 c.194del / Gly65fs1 claims · 2 study rows

transport activity · biallelic or compound-heterozygous SLC46A1 c.194del context

PCFT folate transport activity tendency

Strong

rs80338769 / SLC46A1 c.194del frameshift is associated with lower PCFT folate transport activity tendency in recessive or compound-heterozygous deficiency contexts.

SLC46A1 rs80338769 is staged as a recessive hereditary folate-malabsorption frameshift allele affecting proton-coupled folate transport.

Likely effectLower transport signal
Signal sizeModerate signal
Evidence supportStrong support
Report useIncluded in pathway scoring
Show study evidence
ClinVar Variation 851clinical curation · directClinVar maps rs80338769 to SLC46A1 c.194del / p.Gly65fs, identifies it as a 1 bp deletion, and classifies it as pathogenic for congenital defect of folate absorption.MedlinePlus SLC46A1clinical curation · directThe checked MedlinePlus SLC46A1 source states that PCFT transports folates from the small intestine and into brain/CSF context, and that SLC46A1 variants can produce shortened PCFT with little or no activity.
rs80338770SLC46A1 c.337C>T / Arg113Cys1 claims · 2 study rows

transport activity · AA or compound-heterozygous SLC46A1 deficiency context

PCFT folate transport activity tendency

Strong

rs80338770 A on the genomic plus strand / SLC46A1 c.337C>T / p.Arg113Cys is associated with lower proton-coupled folate transporter activity in recessive or compound-heterozygous hereditary folate malabsorption contexts.

SLC46A1 rs80338770 A is staged as a pathogenic PCFT folate transport allele relevant to methylation support.

Likely effectLower transport signal
Signal sizeModerate signal
Evidence supportStrong support
Report useIncluded in pathway scoring
Show study evidence
ClinVar Variation 855clinical curation · directClinVar maps rs80338770 to SLC46A1 c.337C>T / p.Arg113Cys and classifies it pathogenic for hereditary folate malabsorption.MedlinePlus SLC46A1clinical curation · directMedlinePlus describes SLC46A1 as the proton-coupled folate transporter needed for intestinal folate absorption and folate transport into the brain; pathogenic variants cause hereditary folate malabsorption.
rs80338775SLC46A1 c.1082-1G>A1 claims · 2 study rows

transport activity · TT or compound-heterozygous SLC46A1 deficiency context

PCFT folate transport activity tendency

Strong

rs80338775 T on the genomic plus strand / SLC46A1 c.1082-1G>A is associated with lower PCFT folate transport activity tendency in recessive or compound-heterozygous deficiency contexts.

SLC46A1 rs80338775 T is staged as a recessive hereditary folate-malabsorption allele affecting proton-coupled folate transport.

Likely effectLower transport signal
Signal sizeModerate signal
Evidence supportStrong support
Report useIncluded in pathway scoring
Show study evidence
ClinVar Variation 850clinical curation · directClinVar maps rs80338775 to SLC46A1 c.1082-1G>A and classifies it as pathogenic for hereditary folate malabsorption.PMCID PMC3012536functional assay · directThe checked functional source supports SLC46A1 splice-disrupting hereditary folate-malabsorption alleles as reducing PCFT expression, localization, or folate transport function.

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 SLC46A1 deserves attention inside the broader Methylation pathway. It is most useful when combined with biomarkers instead of used as a standalone answer.

Example interpretation

SLC46A1 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 SLC46A1 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.

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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

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