ArticleProceedings of the National Academy of Sciences of the United States of America2013
CYP2R1 is a major, but not exclusive, contributor to 25-hydroxyvitamin D production in vivo.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 148 papers, 3 of them syntheses that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
148 citing papers in PubMed, 3 syntheses or guidelines pooled it, 316 citations in OpenAlex.
- Vitamin D Metabolic Pathway Components in Orthopedic Patientes-Systematic Review.International journal of molecular sciences · 2022Pooled it
- Vitamin D-Related Genetic Variations and Nonalcoholic Fatty Liver Disease: A Systematic Review.International journal of molecular sciences · 2022Pooled it
- A Bidirectional Mendelian Randomization Study to evaluate the causal role of reduced blood vitamin D levels with type 2 diabetes risk in South Asians and Europeans.Nutrition journal · 2021Pooled it
- UVB-exposed wheat germ oil increases serum 25-hydroxyvitamin DEuropean journal of nutrition · 2022Trial
- Changes in hepatic fibrosis and vitamin D levels after viral hepatitis C eradication using direct-acting antiviral therapy.BMC gastroenterology · 2020Trial
- Randomized phase 2 trial of monthly vitamin D to prevent respiratory complications in children with sickle cell disease.Blood advances · 2018Trial
- CYP2R1 polymorphisms are important modulators of circulating 25-hydroxyvitamin D levels in elderly females with vitamin insufficiency, but not of the response to vitamin D supplementation.Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA · 2017Trial
- Free Fatty acid-induced disruption of hepatic vitamin D metabolism impairs bone homeostasis in an in vitro 3D human liver-bone model.Archives of toxicology · 2026Article
- Phosphate: An Anion Controlling Metabolic Functions.Nutrients · 2026Review
- Germ cells are hidden contributors to sex differences in vertebrate lifespan.The Journal of reproduction and development · 2026Review
- Investigation of the causal effect and molecular signatures of serum hydroxyvitamin D on atherosclerosis: a Mendelian randomization and transcriptomic approach.The Korean journal of physiology & pharmacology : official journal of the Korean Physiological Society and the Korean Society of Pharmacology · 2026Article
- The Role of Vitamin DNutrients · 2026Review
- Disrupted Vitamin D Signaling and Metabolism in Neurodevelopmental and Neurodegenerative Disorders.ASN neuro · 2026Review
- Article
- Manganese Deficiency and MnInternational journal of molecular sciences · 2025Article
- Association of stress urinary incontinence with serum 25-hydroxyvitamin D level in adult women: A cross-sectional analysis of the National Health and Nutrition Examination Survey (2005-2018) data.The Journal of international medical research · 2025Article
- Diversity of ThDP-Dependent Enzymes Forming Chiral Tertiary Alcohols.Chembiochem : a European journal of chemical biology · 2025Review
- Vitamin D: an important treatment for secondary hyperparathyroidism in chronic kidney disease?International urology and nephrology · 2025Review
- Differences in the absorption and metabolism of vitamin DThe Journal of steroid biochemistry and molecular biology · 2025Review
- Obesity may extend the time required to reach a steady-state 25(OH)D level after initiating vitamin D supplementation.JBMR plus · 2025Article
88 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Bioactivation of vitamin D consists of two sequential hydroxylation steps to produce 1α,25-dihydroxyvitamin D3. It is clear that the second or 1α-hydroxylation step is carried out by a single enzyme, 25-hydroxyvitamin D 1α-hydroxylase CYP27B1. However, it is not certain what enzyme or enzymes are responsible for the initial 25-hydroxylation. An excellent case has been made for vitamin D 25-hydroxylase CYP2R1, but this hypothesis has not yet been tested. We have now produced Cyp2r1 (-/-) mice. These mice had greater than 50% reduction in serum 25-hydroxyvitamin D3. Curiously, the 1α,25-dihydroxyvitamin D3 level in the serum remained unchanged. These mice presented no health issues. A double knockout of Cyp2r1 and Cyp27a1 maintained a similar circulating level of 25-hydroxyvitamin D3 and 1α,25-dihydroxyvitamin D3. Our results support the idea that the CYP2R1 is the major enzyme responsible for 25-hydroxylation of vitamin D, but clearly a second, as-yet unknown, enzyme is another contributor to this important step in vitamin D activation.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.