MTHFR
Methylenetetrahydrofolate Reductase
Gene Number: 4524
Location: 1p36.22
Key Functions: Folate metabolism, homocysteine regulation, DNA methylation, cardiovascular and neurological health
MTHFR encodes methylenetetrahydrofolate reductase, a critical enzyme in one-carbon metabolism that converts 5,10-methylenetetrahydrofolate to 5-methyltetrahydrofolate, the primary methyl donor for the remethylation of homocysteine to methionine. This reaction underpins DNA methylation, nucleotide synthesis, and methylation-dependent gene regulation, linking folate metabolism directly to genomic stability and epigenetic control.
MTHFR activity is central to:
Epigenetic regulation and gene expression: By supplying methyl groups for S-adenosylmethionine (SAM), MTHFR ensures proper DNA methylation and transcriptional regulation across tissues.
Neural development: Adequate activity is essential during embryogenesis for neural tube closure and proper brain formation.
Cardiovascular health: Efficient homocysteine clearance prevents endothelial dysfunction, vascular inflammation, and thrombotic risk.
Clinical relevance: Common variants such as C677T (rs1801133) and A1298C (rs1801131) reduce enzymatic activity, potentially leading to hyperhomocysteinemia and impaired methylation. These effects can increase susceptibility to cardiovascular disease, neural tube defects, pregnancy complications, and neuropsychiatric disorders. The phenotypic impact is modulated by zygosity, cofactor availability (folate, riboflavin), and overall methylation capacity, highlighting the gene’s role at the intersection of nutrition, metabolism, and epigenetic regulation.
SNP ID | Your Genotype | Alternative Alleles | Interpretation |
|---|---|---|---|
rs1801133 | No matching variant or no valid DNA data | A | No interpretation available |
rs1801131 | No matching variant or no valid DNA data | G | No interpretation available |
rs1801133 (C677T, Ala222Val)
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, Glu429Ala)
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.
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