MTHFR
Methylenetetrahydrofolate Reductase
Gene Number: 4524
Location: 1p36.22
Key Functions: Folate metabolism, homocysteine recycling and support for methylation
The MTHFR gene produces an enzyme that converts folate into 5-methyltetrahydrofolate (5-MTHF). This form of folate helps recycle homocysteine into methionine, supporting the supply of methyl groups used in DNA regulation and other essential processes [R].
This report examines C677T (rs1801133) and A1298C (rs1801131), two common MTHFR variants that can reduce enzyme activity. C677T has the clearer relationship with higher homocysteine, particularly when folate levels are low.
Explore your genotypes below, or use our free methylation DNA panel to view MTHFR alongside other genes involved in folate and vitamin B12 metabolism.
SNP ID | Your Genotype | Alt Allele | Interpretation |
|---|---|---|---|
rs1801133 | Analyze your DNA to see your genotype | A | Analyze your DNA to see a personalized result. |
rs1801131 | Analyze your DNA to see your genotype | G | Analyze your DNA to see a personalized result. |
rs1801133 — C677T and Folate Metabolism
GG – Normal enzyme activity (~100%); normal homocysteine and folate processing (R).
AG – ~65% enzyme activity; moderate elevation of homocysteine; increased risk in low-folate states (R).
AA – ~10–30% enzyme activity; high homocysteine, reduced folate/B12, linked to neural tube defects, thrombosis, and cancer in low-folate contexts (R).
Functional effect: The A allele (677T) reduces MTHFR activity, elevates homocysteine, and increases disease risk when folate/B12 intake is insufficient; adequate folate can mitigate risk.
rs1801131 — A1298C and Enzyme Activity
TT – Normal enzyme activity; baseline folate/homocysteine metabolism (R).
TG – Slightly reduced activity; possible impaired folate metabolism and mild homocysteine elevation (R).
GG – Slightly reduced activity; possible impaired folate metabolism and mild homocysteine elevation (R).
Functional effect: The G allele (1298C) reduces enzyme activity (less than rs1801133), but in combination with 677T (rs1801133 A allele), it further increases risk for neural tube defects, brain tumors, and cardiovascular/metabolic disease.
Note: Common MTHFR variants can influence enzyme activity, but their effects vary with nutrition and other biological factors. C677T has a clearer association with reduced activity and elevated homocysteine than A1298C alone. These variants do not, by themselves, diagnose a vitamin deficiency, a methylation disorder, or a particular disease.
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