{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,17]],"date-time":"2026-07-17T16:27:03Z","timestamp":1784305623405,"version":"3.55.0"},"reference-count":61,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2021,12,12]],"date-time":"2021-12-12T00:00:00Z","timestamp":1639267200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100007771","name":"Medical University of Silesia","doi-asserted-by":"publisher","award":["KNW-2-045\/D\/8\/N"],"award-info":[{"award-number":["KNW-2-045\/D\/8\/N"]}],"id":[{"id":"10.13039\/100007771","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>Background: Vitamin D is a fat-soluble cholesterol derivative found in two forms, vitamin D2, and vitamin D3. Cytochrome P450 2R1 (CYP2R1) encoded by the CYP2R1 gene is the major hydroxylase that activates vitamin D by catalyzing the formation of 25-hydroxyvitamin D (25(OH)D). Methods: We collected 89 (100%) subjects, 46 of which (51.69%) had a documented severe deficiency of 25(OH)D (&lt;10 ng\/mL) and 43 (48.31%) in the control group with documented optimum levels of 25(OH)D (&gt;30 ng\/mL). We performed Sanger sequencing of three selected fragments of the CYP2R1 gene (Ch11: 14878000\u201314878499; Ch11: 14880058\u201314880883 and Ch11: 14885321\u201314886113) that affect the binding of substrates to this enzyme and analyzed the possible involvement of genetic variation in these regions with an increased risk of vitamin D deficiency in healthy Polish individuals. Results: Two substitutions were found within the three fragments. Bioinformatic analysis suggested that one of these (NC_000011.10: g.14878291G&gt;A) may influence the structure and function of CYP2R1. Conclusions: Variant NC_000011.10: g.14878291G&gt;A may have a perturbing effect on heme binding in the active site of CYP2R1 and on the function of 25-hydroxylase and probably affects the concentration of 25(OH)D in vivo. We intend to perform functional verification in a larger patient population to confirm and extend these results.<\/jats:p>","DOI":"10.3390\/biom11121867","type":"journal-article","created":{"date-parts":[[2021,12,13]],"date-time":"2021-12-13T01:28:11Z","timestamp":1639358891000},"page":"1867","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["New Variants of the Cytochrome P450 2R1 (CYP2R1) Gene in Individuals with Severe Vitamin D-Activating Enzyme 25(OH)D Deficiency"],"prefix":"10.3390","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3669-1416","authenticated-orcid":false,"given":"Martyna","family":"Fronczek","sequence":"first","affiliation":[{"name":"Department of Medical and Molecular Biology, Faculty of Medical Sciences in Zabrze, Medical University of Silesia, 40-055 Katowice, Poland"},{"name":"Department of Pharmacology, Faculty of Medical Sciences in Zabrze, Medical University of Silesia, 40-055 Katowice, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3686-5685","authenticated-orcid":false,"given":"Joanna Katarzyna","family":"Strzelczyk","sequence":"additional","affiliation":[{"name":"Department of Medical and Molecular Biology, Faculty of Medical Sciences in Zabrze, Medical University of Silesia, 40-055 Katowice, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2620-3880","authenticated-orcid":false,"given":"Krzysztof","family":"Biernacki","sequence":"additional","affiliation":[{"name":"Department of Medical and Molecular Biology, Faculty of Medical Sciences in Zabrze, Medical University of Silesia, 40-055 Katowice, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1286-3076","authenticated-orcid":false,"given":"Silvia","family":"Salatino","sequence":"additional","affiliation":[{"name":"Molecular Biology, Core Research Laboratories, Natural History Museum, London SW7 5BD, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3202-6972","authenticated-orcid":false,"given":"Tadeusz","family":"Osadnik","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Faculty of Medical Sciences in Zabrze, Medical University of Silesia, 40-055 Katowice, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4301-2429","authenticated-orcid":false,"given":"Zofia","family":"Ostrowska","sequence":"additional","affiliation":[{"name":"Department of Medical and Molecular Biology, Faculty of Medical Sciences in Zabrze, Medical University of Silesia, 40-055 Katowice, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,12,12]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Sirajudeen, S., Shah, I., and Al Menhali, A. 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