CYP2R1 rs1074416: Vitamin D Hydroxylation and Status
The single-nucleotide polymorphism rs1074416 is located in the CYP2R1 gene on chromosome 11, which encodes the primary liver enzyme responsible for turning vitamin D into its circulating form. Research links this variant to modest differences in hepatic 25-hydroxylation efficiency and circulating 25-hydroxyvitamin D concentrations across diverse populations. However, evidence connecting it directly to clinical disease outcomes remains limited, and lifestyle factors like sun exposure and diet exert far larger influences on vitamin D status.
What each genotype means
Typical vitamin D metabolism
This genotype is considered the major allele configuration in many populations. Research suggests individuals with this profile typically maintain standard efficiency in the hepatic 25-hydroxylation of vitamin D. As associations with circulating 25(OH)D levels can be influenced by environmental factors and other genetic markers, this result should be viewed as one component of your overall nutritional profile.
This genotype is common in many global populations, though exact frequencies vary significantly by ancestry.
Intermediate vitamin D metabolism
Carrying one copy of the minor allele may be associated with slight variations in the efficiency of converting vitamin D into its circulating 25-hydroxy form. Studies on this variant indicate that while it may influence vitamin D status, the effect is often modest and can be modulated by dietary intake and sun exposure. You should discuss your vitamin D levels and any supplementation needs with your healthcare provider.
This heterozygous genotype is frequently observed, with the minor allele appearing in approximately 35% to 45% of individuals in many European and Asian populations.
Potential reduced metabolic efficiency
This genotype is associated with the minor allele, which some research links to lower circulating concentrations of 25-hydroxyvitamin D due to differences in hepatic hydroxylation efficiency. While this variant is a known factor in vitamin D metabolism, it is not a diagnostic indicator of deficiency. Please consult with a clinician or pharmacist to determine if your vitamin D levels are optimal and if supplementation is appropriate for your health needs.
This genotype is less common than the homozygous major or heterozygous states, reflecting the distribution of the minor allele across various ancestral groups.
What Is rs1074416 and Where Is It Located?
The single-nucleotide polymorphism rs1074416 represents a common single base-pair change situated within or near the CYP2R1 gene on human chromosome 11. Chromosome 11 harbors several key metabolic regulators, and variations in this specific genomic locus are frequently evaluated in population-scale association studies. Polymorphisms in non-coding and regulatory segments of CYP2R1 can subtly modify transcript levels or splicing patterns rather than abolishing protein function altogether. Unlike severe, rare loss-of-function mutations that cause rare monogenic disorders, rs1074416 is a common polymorphism that occurs frequently in healthy individuals worldwide. In scientific literature and reference databases such as dbSNP, it is tracked as a diallelic marker that segregates through normal Mendelian inheritance. Its presence reflects natural genetic diversity in human metabolic pathways, serving as a subtle modifier of biochemical processing rather than a direct trigger for illness.
The Biological Function of the CYP2R1 Gene
The CYP2R1 gene provides instructions for producing the cytochrome P450 family 2 subfamily R member 1 enzyme, also referred to as microsomal vitamin D 25-hydroxylase. This enzyme functions primarily in the liver, where it performs the initial and rate-limiting step in bioactivating vitamin D obtained through cutaneous synthesis or dietary sources. Specifically, CYP2R1 adds a hydroxyl group at carbon 25 of cholecalciferol (vitamin D3) or ergocalciferol (vitamin D2) to create 25-hydroxyvitamin D, commonly written as 25(OH)D. Circulating 25(OH)D is the principal storage metabolite measured during routine clinical blood tests to gauge a person's total vitamin D reserves. While downstream conversion to the fully active hormonal form, 1,25-dihydroxyvitamin D, takes place primarily in the kidneys via CYP27B1, efficient hepatic conversion by CYP2R1 is critical for maintaining an adequate systemic pool of the precursor.
Research Findings and Scientific Evidence
Genome-wide association studies (GWAS) and candidate gene analyses cataloged in repositories like the GWAS Catalog have repeatedly identified the CYP2R1 locus as a determinant of circulating 25(OH)D concentrations. Specifically, rs1074416 has been evaluated alongside other well-known CYP2R1 variants for its statistical relationship with 25-hydroxylation efficiency and baseline blood levels. The current evidence strength for rs1074416 is classified as limited to modest because the variant explains only a minor fraction of the overall variation in blood vitamin D levels. Studies consistently find that environmental factors, including ultraviolet-B radiation exposure, geographic latitude, skin pigmentation, age, and dietary intake, contribute much more heavily to measured serum levels than any individual common single-nucleotide polymorphism. Furthermore, association studies assessing downstream health risks, such as bone mineral density or immune function, have yielded mixed findings that often fail to demonstrate direct clinical causation.
Genomic Context and Population Distribution
Populations across the globe exhibit a high prevalence of the minor allele for rs1074416, demonstrating that it is an established component of human genetic variation rather than a recent or deleterious mutation. According to reference genomic datasets such as dbSNP and catalog records, the minor allele frequency typically ranges between 0.35 and 0.45 across European and Asian ancestral cohorts. Because both alleles are widespread, heterozygous and homozygous genotypes are commonly seen in everyday populations without signaling underlying metabolic pathology. Frequency distributions can fluctuate moderately between distinct continental groups, highlighting the importance of evaluating genetic background when interpreting epidemiological findings. This broad geographic spread indicates that the variant has persisted across millennia without subjecting carriers to negative evolutionary selection pressures.
Interpreting Your Results and Practical Next Steps
Learning your rs1074416 genotype provides an interesting glimpse into your unique biochemical makeup, but it cannot diagnose vitamin D deficiency, insufficiency, or any bone disorder. Because genetic variants account for only a small percentage of circulating 25(OH)D levels, relying solely on DNA data can be misleading. If you have concerns about your vitamin D levels, a standard serum 25(OH)D blood test ordered by a healthcare provider is the only accurate way to assess your actual status. Never start high-dose vitamin D supplements or discontinue prescribed therapies based solely on genetic test results. Nutritional needs, supplement safety, and optimal target ranges should always be evaluated with a qualified physician, registered dietitian, or pharmacist who can consider your overall medical history, diet, and lifestyle.
How common is this variant?
The minor allele frequency for rs1074416 is approximately 0.35 to 0.45 across European and Asian populations, making both homozygous and heterozygous genotypes common worldwide.
Frequently asked questions
Can rs1074416 tell me if I am deficient in vitamin D?
No, a genetic test cannot diagnose vitamin D deficiency. Genetic variations like rs1074416 exert only subtle statistical effects on how your liver processes vitamin D, whereas your actual blood level is governed primarily by sun exposure, diet, and supplements. The only way to know if you are deficient is to have your doctor order a 25(OH)D blood test.
Does having a higher-attention genotype mean I should take high-dose supplements?
No, you should never begin high-dose vitamin D supplementation based purely on genetic information. Excess vitamin D can cause toxicity, hypercalcemia, and kidney issues if taken improperly. Always consult a healthcare provider or pharmacist, who can interpret your actual blood levels before recommending supplementation.
What is the primary role of the CYP2R1 gene?
CYP2R1 provides instructions for the enzyme vitamin D 25-hydroxylase, which operates mainly in the liver. This enzyme adds a hydroxyl group to dietary or sun-derived vitamin D to convert it into 25-hydroxyvitamin D, the circulating form measured on lab tests.
How strong is the scientific evidence linking rs1074416 to vitamin D levels?
The evidence is considered limited to modest. While genome-wide association studies show statistically significant connections between the CYP2R1 region and circulating 25(OH)D concentrations, the individual effect size of rs1074416 is small and easily overshadowed by lifestyle and seasonal factors.
Sources & further reading
Educational information only, last refreshed 9/7/2026. Not medical advice — these associations describe population statistics, not individual predictions.
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This variant is associated with variations in Vitamin D metabolism and circulating levels of 25(OH)D.
This variant in the CYP2R1 gene, which encodes a key vitamin D 25-hydroxylase, is associated with altered serum 25-hydroxyvitamin D concentrations.
Associated with altered hepatic 25-hydroxylase enzyme levels and baseline circulating serum 25-hydroxyvitamin D concentrations.
This variant in the CYP2R1 gene is associated with circulating 25-hydroxyvitamin D levels and, in rare cases, pathogenic variants in this gene can cause vitamin D-dependent rickets type 1B.
Affects the body's ability to convert sunlight into active Vitamin D.