Ask about this productRelated genes to: CYP2R1 Blocking Peptide
- Gene:
- CYP2R1 NIH gene
- Name:
- cytochrome P450 family 2 subfamily R member 1
- Previous symbol:
- -
- Synonyms:
- -
- Chromosome:
- 11p15.2
- Locus Type:
- gene with protein product
- Date approved:
- 2004-03-11
- Date modifiied:
- 2018-02-28
Related products to: CYP2R1 Blocking Peptide
Related articles to: CYP2R1 Blocking Peptide
- Metabolic dysfunction-associated steatohepatitis (MASH) is a progressive liver disease frequently linked to vitamin D deficiency, which correlates with the severity of the disease and fibrosis. Although reduced dietary intake and sunlight exposure are known contributors, the effect of impaired hepatic vitamin D bioactivation remains unclear. CYP2R1, an enzyme in the liver, converts vitamin D into 25-hydroxyvitamin D (calcifediol), a crucial step in its activation. This study explored the impact of MASH-associated lipotoxicity on CYP2R1 expression and vitamin D metabolism. Analysis of human liver transcriptomic data revealed a significant reduction in CYP2R1 expression in MASH, particularly in advanced fibrosis stages. Similarly, murine models of MASH show decreased hepatic Cyp2r1 expression, elevated liver injury markers, and reduced circulating 25-hydroxyvitamin D levels. Furthermore, in vitro studies demonstrated that palmitic acid caused a dose-dependent decrease in CYP2R1 expression in human hepatocytes, indicating a cell-autonomous effect. Calcifediol significantly induced vitamin D receptor (VDR) expression in human hepatocytes and hepatic stellate cell lines, suggesting the role of intra-hepatic calcifediol in maintaining VDR signalling. These findings uncover lipotoxic repression of CYP2R1 as a previously unrecognized mechanism contributing to vitamin D deficiency and impaired hepatic VDR signalling in MASH, highlighting hepatic vitamin D bioactivation as a potential therapeutic target. - Source: PubMed
Publication date: 2026/04/28
Yadav AbhishekShahi AmbujSinha Rohit ASingh SushmitaMedhe PratikSingh Mable MGoel Amit - Hepatocellular carcinoma (HCC) remains a major cause of cancer mortality worldwide, yet reliable molecular biomarkers for early diagnosis and prognosis are limited. The cytochrome P450 (CYP) enzyme superfamily plays central roles in hepatic metabolism and tumor biology, but its global dysregulation in HCC has not been comprehensively defined. Here, we systematically analyzed 57 CYP genes across multi-cohort transcriptomic datasets (GepLiver, TCGA-LIHC, HCCDB2.0) to delineate their diagnostic, prognostic, and functional significance. emerged as a consistently upregulated and clinically relevant member, showing excellent diagnostic accuracy (AUC = 0.95, 95% CI: 0.94-0.98, < 0.001) and strong overexpression validated across independent cohorts and spatial transcriptomics. Prognostic modeling identified (favorable) and (unfavorable) as independent survival markers. Functional enrichment analyses revealed that high expression was associated with activation of DNA repair and replication pathways (NES = 1.31, adjusted = 1.05 × 10) and with co-expression of core repair genes such as , , and . Moreover, correlated with myeloid-derived suppressor cell infiltration, suggesting an immunosuppressive phenotype. These findings establish as a novel metabolic and immunogenomic biomarker in HCC, linking hepatic metabolism, genomic maintenance, and tumor immune modulation. - Source: PubMed
Publication date: 2026/04/01
Jung Hyun SunBaek Geum OkYoon Moon GyeongJang Se HaCheong Jae YounKim Soon SunEun Jung Woo - Vitamin D plays a pivotal role in immune regulation, metabolic balance, skeletal health, and gene expression. Growing evidence indicates that genetic and epigenetic factors contribute to interindividual differences in vitamin D status and physiological responses. This review summarizes current findings on the nutrigenomic determinants of vitamin D metabolism, with emphasis on genetic polymorphisms in vitamin D receptor (VDR), GC, CYP2R1, CYP27B1, and CYP24A1, as well as epigenetic mechanisms that modulate vitamin D related gene expression. Peer-reviewed original studies and review articles published between 2010 and 2025 were examined to highlight associations between genetic variation in the vitamin D pathway and susceptibility to cancer, autoimmune disorders, metabolic diseases, cardiovascular conditions, and neurodegenerative outcomes. Advances in omics technologies and epigenetic biomarker research have improved understanding the molecular pathways through which vitamin D acts across multiple body systems. Evidence from gene-environment interactions and genotype-specific supplementation responses highlights the conceptual relevance of precision nutrition, while underscoring substantial gaps in clinical validation. Collectively, current research suggests that genetic information may inform future personalized vitamin D strategies, although translation into clinical practice remains limited by inconsistent evidence and methodological heterogeneity. - Source: PubMed
Publication date: 2026/03/06
Qahtan FatimaAbu-Qiyas SalmaPapandreou Dimitrios - Obesity and metabolic dysfunction-associated fatty liver disease (MAFLD) are increasingly recognized as risk factors for skeletal fragility, yet the mechanisms linking these conditions to impaired bone health remain poorly defined. The liver is central to vitamin D homeostasis through 25-hydroxylation, while skeletal responsiveness relies on vitamin D receptor (VDR) signaling. Disruption of either process may compromise bone remodeling. In this study, we investigated the long-term effects of Western diet (WD) feeding on hepatic vitamin D metabolism and bone integrity in a mouse model. Male C57BL/6N mice were fed a standard diet (SD) or WD for 48 weeks. WD-fed mice developed obesity, hepatic injury, and trabecular bone deterioration characterized by reduced bone mineral density and increased trabecular separation. Although trabecular architecture was compromised, three-point bending revealed no significant impairment in cortical bone mechanical properties. Histological analyses showed increased bone marrow adiposity and macrophage/monocyte lineage cells. Bone gene expression profiling indicated enhanced osteoclastogenic signaling. Hepatic transcriptomics demonstrated marked downregulation of key 25-hydroxylases (, ) and vitamin D-binding protein, accompanied by reduced circulating 25‑hydroxyvitamin D. Bone tissue also exhibited decreased VDR protein abundance. Together, these findings suggest that long-term WD-induced obesity and hepatic dysfunction impair hepatic vitamin D metabolism and diminish skeletal vitamin D responsiveness, contributing to bone fragility. Targeting the liver-bone axis and restoring vitamin D homeostasis may provide therapeutic potential for obesity-related bone loss. See also the graphical abstract(Fig. 1). - Source: PubMed
Publication date: 2026/01/23
Zhou PengchengHammour Mohammad MajdAspera-Werz Romina HEhnert SabrinaMyllys MaijuHobloss ZaynabHassan RehamGonzalez DanielaHendawi RamaEdlund KarolinaHans SandraLaschke Matthias WGhallab AhmedHengstler Jan GNüssler Andreas KMaisenbacher Tanja C - Hepatocellular carcinoma (HCC) remains a leading cause of cancer-related death worldwide. While age-standardized incidence and mortality have declined in some regions, the overall global burden continues to increase because of population aging and persistent etiologic factors. Curative options are limited to selected patients, and systemic therapies provide modest long-term benefit. Beyond its canonical role in calcium-phosphate homeostasis, vitamin D signals through the nuclear vitamin D receptor (VDR) to modulate immunity, oxidative stress, fibrosis, and cellular metabolism. In HCC, this axis is frequently dysregulated, including downregulation of CYP2R1, reduced CYP27B1 activity, upregulation of CYP24A1, and VDR dysfunction, which together blunt the antitumor actions of vitamin D and are linked to inflammation, aberrant lipogenesis, and immune evasion. Here, we summarize mechanisms by which vitamin D impacts key oncogenic pathways in HCC, including PI3K/AKT/mTOR, IL-6/STAT3, NF-κB, and TGF-β/SMAD, and highlight downstream nodes such as SREBP-1 and TXNIP as potential therapeutic targets. We also discuss emerging strategies to restore vitamin D signaling, such as CYP24A1 inhibition, next-generation vitamin D analogs, and VDR-biased agonists, to facilitate clinical translation and drug development. - Source: PubMed
Publication date: 2026/03/11
Gao HanlinHe LiChen ZhiWang Gang