CYP2R1 rs1074145: Vitamin D Metabolism and Population Traits
The rs1074145 single nucleotide polymorphism is a widely studied genetic variant located in the CYP2R1 gene on chromosome 11. CYP2R1 encodes microsomal vitamin D 25-hydroxylase, the key hepatic enzyme responsible for carrying out the initial activation step of dietary and sun-synthesized vitamin D into 25-hydroxyvitamin D. Genome-wide association studies link this variant to modest variations in circulating vitamin D levels across diverse human populations.
What each genotype means
Typical 25-hydroxylase activity
You carry two copies of the G allele, which is the ancestral and major allele in most human populations. Research has associated this genotype with typical enzymatic conversion of vitamin D into 25-hydroxyvitamin D [25(OH)D]. However, individual circulating vitamin D levels depend heavily on sun exposure, dietary intake, and overall health.
Carried by approximately 35% to 40% of people of European ancestry and over 70% of people of East Asian ancestry.
Slightly lower vitamin D conversion
You carry one copy of the A variant allele and one copy of the G allele. Genome-wide association studies have linked this genotype to modestly lower circulating 25-hydroxyvitamin D concentrations compared to the GG genotype. The clinical impact of this single variant is modest, and overall vitamin D status is influenced by lifestyle, geography, and dietary habits.
Carried by roughly 45% to 50% of people of European ancestry and about 25% of individuals of East Asian descent.
Reduced circulating vitamin D baseline
You carry two copies of the A variant allele. Observational and genome-wide association studies have consistently correlated this genotype with lower baseline serum 25-hydroxyvitamin D levels compared to AG or GG carriers. Evidence suggests this allele increased in frequency in higher-latitude populations, but maintaining healthy vitamin D levels through nutrition and sunlight remains readily achievable.
Found in roughly 15% to 18% of individuals of European ancestry, but in fewer than 3% of individuals of East Asian descent.
Genetic Location and Molecular Function
The rs1074145 variant resides within the CYP2R1 gene on chromosome 11. This gene provides instructions for producing cytochrome P450 family 2 subfamily R member 1, an essential hepatic monooxygenase enzyme also known as vitamin D 25-hydroxylase. When your skin absorbs ultraviolet B radiation or when you consume vitamin D through diet, the unactivated precursor travels through the bloodstream to the liver. There, CYP2R1 catalyzes the addition of a hydroxyl group to position 25, creating 25-hydroxyvitamin D [25(OH)D], which is the principal circulating storage form of vitamin D measured during standard laboratory blood tests.
Genome-Wide Associations and Evidence Strength
Large-scale genome-wide association studies (GWAS) have repeatedly identified the CYP2R1 locus, including rs1074145 and nearby linked markers, as a major common determinant of baseline circulating 25(OH)D concentrations. Individuals carrying the alternative A allele generally present with slightly lower average circulating 25(OH)D levels compared to homozygous reference carriers. However, the evidence strength for rs1074145 as a high-penetrance risk factor is considered limited. The variant exerts only an incremental statistical effect on circulating hormone concentrations, explaining a small fraction of overall variance rather than directly causing deficiency.
Population Divergence and Evolutionary Selection
Allele frequencies for rs1074145 demonstrate notable population divergence that reflects historical human migrations and latitude-dependent environmental selection pressures. The alternative allele occurs at an estimated frequency of approximately 0.40 in populations of European descent, around 0.28 in individuals of African ancestry, and near 0.15 in East Asian cohorts. Evolutionary geneticists suggest that selective sweeps across key vitamin D pathway genes, such as CYP2R1, may have arisen as ancestral human groups moved away from the equator into higher latitudes with reduced seasonal ultraviolet radiation exposure.
Clinical Distinctions and Pathogenic Alleles
It is critical to distinguish common regulatory and non-coding polymorphisms like rs1074145 from rare pathogenic mutations in the CYP2R1 gene. Severe loss-of-function coding mutations in CYP2R1 are known causes of vitamin D-dependent rickets type 1B (VDDR1B), an autosomal recessive disorder that impairs bone mineralization, causes bowed limbs, and leads to profound hypocalcemia. In contrast, rs1074145 is a benign trait-associated polymorphism commonly carried by millions of healthy individuals and does not cause congenital rickets or monogenic enzyme inactivation.
What You Can and Cannot Do with This Result
Your rs1074145 genotype is an educational snapshot of background genetic variation rather than a diagnostic tool. Having one or two copies of an allele correlated with lower statistical vitamin D levels does not confirm deficiency, nor does a protective genotype guarantee optimal bone health. Serum 25(OH)D levels are overwhelmingly driven by dynamic environmental factors, including sunlight exposure, latitude, dietary intake, age, and body mass index. Always consult a qualified healthcare provider or registered dietitian before initiating high-dose vitamin D supplementation or modifying medication regimens.
How common is this variant?
The alternative allele frequency for rs1074145 varies considerably by ancestry, occurring at approximately 0.40 in European populations, 0.28 in African populations, and 0.15 in East Asian populations.
Frequently asked questions
Does having the rs1074145 variant mean I have a vitamin D deficiency?
No. The rs1074145 variant is associated with slight statistical shifts in average circulating 25(OH)D concentrations across populations, but it does not diagnose clinical deficiency. Your actual vitamin D status is predominantly influenced by sun exposure, geography, and dietary intake, and can only be evaluated through a serum blood test.
What is the function of the CYP2R1 gene?
The CYP2R1 gene encodes the vitamin D 25-hydroxylase enzyme in the liver. This enzyme catalyzes the first chemical step in activating vitamin D by converting cholecalciferol into 25-hydroxyvitamin D, the circulating form measured in routine clinical labs.
Can rs1074145 cause vitamin D-dependent rickets?
No. Vitamin D-dependent rickets type 1B is caused by rare, severe loss-of-function pathogenic mutations in CYP2R1 that prevent the enzyme from functioning. Common variants like rs1074145 merely introduce subtle variations in enzyme expression or activity and do not cause monogenic rickets.
Should I start taking high-dose vitamin D supplements based on my genotype?
You should not begin high-dose vitamin D supplementation based solely on genetic test results. Excessive vitamin D intake can lead to toxicity, hypercalcemia, and renal complications. Speak with your physician, who can measure your circulating 25(OH)D levels and recommend an appropriate, safe dosage if needed.
Sources & further reading
Educational information only, last refreshed 9/10/2026. Not medical advice — these associations describe population statistics, not individual predictions.
Curious what your genotype is for rs1074145?
Upload a raw DNA file from 23andMe, AncestryDNA, MyHeritage, or FamilyTreeDNA and see this variant — plus thousands more — interpreted in your full report.
Get my report — $29