MTHFD1 rs2236225: What Your Genotype Means
The rs2236225 variant in the MTHFD1 gene is a common genetic change that alters the structure of an enzyme involved in folate metabolism. Research has investigated its potential role in various health outcomes, including congenital heart defects and nutrient-environment interactions.
What each genotype means
Typical enzyme stability
You carry two copies of the common G allele, corresponding to the typical arginine (R) amino acid at position 653 (c.1958G/G). Research indicates this genotype confers standard MTHFD1 enzyme stability and baseline one-carbon metabolic flux without the increased maternal risk for neural tube defects or heightened sensitivity to low dietary choline seen with the variant allele.
Carried by approximately 35% to 40% of individuals of European ancestry, and generally more common across African and East Asian populations.
Moderately reduced enzyme stability
You carry one copy of the A variant allele (c.1958G>A, p.Arg653Gln). Clinical studies suggest this causes a moderate reduction in MTHFD1 synthetase stability and can moderately increase metabolic reliance on dietary choline for methyl donation, especially under low-folate conditions. Evidence regarding clinical risk for maternal neural tube defects remains mixed and limited for heterozygous carriers.
Carried by roughly 45% to 50% of people of European descent; less common in East Asian populations.
Reduced enzyme stability
You carry two copies of the A variant allele, historically designated as 1958AA or the 653QQ genotype. Published nutritional research links this genotype with reduced stability of the trifunctional MTHFD1 enzyme, resulting in a higher sensitivity to low dietary choline and an elevated maternal risk for neural tube defects when folate intake is marginal. These findings represent population associations and evidence remains limited, so dietary requirements should be discussed with a qualified healthcare professional.
Carried by roughly 15% to 20% of individuals of European ancestry, but is significantly rarer in East Asian and African populations.
Understanding the rs2236225 Variant
The rs2236225 variant, often referred to as R653Q, is a single nucleotide polymorphism (SNP) located within the MTHFD1 gene. This specific change involves a substitution of the amino acid arginine with glutamine at position 653 of the protein. Because this change occurs in the coding region of the gene, it is classified as a nonsynonymous variant, meaning it has the potential to alter the function or stability of the resulting enzyme. Scientists study this variant because it sits in a critical domain of the MTHFD1 protein, which is responsible for essential chemical reactions in the body. By analyzing how this specific change affects enzyme activity, researchers aim to understand how genetic diversity influences metabolic processes at a molecular level.
The Role of the MTHFD1 Gene
The MTHFD1 gene provides instructions for making an enzyme that performs three distinct functions in the one-carbon metabolism pathway. This pathway is vital for the synthesis of nucleotides, which are the building blocks of DNA, and for the methylation of various molecules, including proteins and DNA itself. The enzyme acts as a bridge in folate metabolism, helping to convert different forms of folate into the active versions needed for cellular health. Because this pathway is so fundamental to cell division and gene regulation, variations in the MTHFD1 gene are of significant interest to scientists studying developmental biology and nutrition. When the enzyme's efficiency is altered, it may change how the body processes dietary folate and choline, potentially impacting metabolic balance under certain environmental conditions.
Research and Health Associations
Research into rs2236225 has produced mixed and sometimes limited evidence regarding its health impact. Some studies have suggested that the variant may be a modulator of risk for congenital heart defects, particularly when maternal folate intake is low during early pregnancy. Other investigations have explored its potential influence on homocysteine levels and its interaction with environmental factors like ultraviolet radiation. Additionally, some preliminary studies have looked at its association with conditions such as schizophrenia or neural tube defects, though results have not always been consistent across different populations. It is important to note that many of these associations are statistical in nature and do not imply a direct cause-and-effect relationship. Because the evidence is often context-dependent, scientists emphasize the need for further large-scale studies to clarify the clinical significance of this variant.
Population Frequency
The rs2236225 variant is relatively common, though its frequency varies significantly across different ancestral groups. It is generally more prevalent in European and South Asian populations compared to those of East Asian or African descent. Understanding these frequency differences is a key part of genetic research, as it helps scientists account for population-specific genetic backgrounds when studying disease risk. Because the minor allele frequency is approximately 0.30 in European populations, a significant portion of the population carries at least one copy of the variant, making it a standard subject for studies on genetic diversity and metabolic health.
Interpreting Your Genetic Information
If you have information about your MTHFD1 genotype, it is important to view it as one small piece of a much larger biological puzzle. Genetic variants like rs2236225 do not act in isolation; they interact with your diet, lifestyle, and other genes. Having a particular genotype does not mean you will develop a specific condition, nor does it guarantee protection against one. This information is intended for educational purposes and should not be used to make medical decisions or self-diagnose. If you are concerned about your nutritional status, folate intake, or any health-related outcomes, the best course of action is to consult with a qualified healthcare provider or a registered dietitian. They can provide personalized guidance based on your overall health history rather than a single genetic marker.
How common is this variant?
The minor allele frequency for rs2236225 is approximately 0.30 in European populations, with notable variations observed across different global ancestries.
Frequently asked questions
Is the MTHFD1 rs2236225 variant a cause of disease?
No, this variant is not a direct cause of disease. It is a genetic polymorphism that may statistically influence metabolic processes, but it does not determine health outcomes on its own.
Should I change my diet based on my MTHFD1 genotype?
You should not make significant dietary changes based solely on a genetic test. Always consult with a healthcare professional or a registered dietitian to discuss your nutritional needs.
Does this variant affect how I process folate?
Research suggests that the rs2236225 variant may alter the function of the MTHFD1 enzyme, which is involved in folate metabolism. However, the clinical impact of this change is still a subject of ongoing scientific study.
Where can I find more information about MTHFD1?
You can find reliable information through resources like the National Library of Medicine's MedlinePlus Genetics or by searching for the gene on the NCBI database.
Sources & further reading
Educational information only, last refreshed 10/27/2026. Not medical advice — these associations describe population statistics, not individual predictions.
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