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Cytochrome P450, family 24, subfamily A, polypeptide 1

CYP24, CYP24A1, 24-OHase, 25-hydroxyvitamin D3 24-hydroxylase
This gene encodes a member of the cytochrome P450 superfamily of enzymes. The cytochrome P450 proteins are monooxygenases which catalyze many reactions involved in drug metabolism and synthesis of cholesterol, steroids and other lipids. This mitochondrial protein initiates the degradation of 1,25-dihydroxyvitamin D3, the physiologically active form of vitamin D3, by hydroxylation of the side chain. In regulating the level of vitamin D3, this enzyme plays a role in calcium homeostasis and the vitamin D endocrine system. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008] (from NCBI)
Top mentioned proteins: xVDR, CAN, HAD, V1a, CYP2R1
Papers on CYP24
CYP24 inhibition as a therapeutic target in FGF23-mediated renal phosphate wasting disorders.
New
Karaplis et al., In J Clin Invest, Feb 2016
UNASSIGNED: CYP24A1 (hereafter referred to as CYP24) enzymatic activity is pivotal in the inactivation of vitamin D metabolites.
Pruning the ricket thicket.
New
Wolf et al., In J Clin Invest, Feb 2016
In this issue of the JCI, Bai and colleagues demonstrate that deletion or inhibition of CYP24A1, which initiates degradation of the active form of vitamin D, ameliorates skeletal abnormalities in two mouse models of hypophosphatemic rickets.
CYP24A1 variant modifies the association between use of oestrogen plus progestogen therapy and colorectal cancer risk.
New
Chang-Claude et al., Boston, United States. In Br J Cancer, Feb 2016
RESULTS: The EB test identified a significant interaction between rs964293 at 20q13.2/CYP24A1 and E+P (interaction OR (95% CIs)=0.61
Environmental and genetic determinants of vitamin D status among older adults in London, UK.
Review
New
Martineau et al., Adelaide, Australia. In J Steroid Biochem Mol Biol, Feb 2016
Fifteen single nucleotide polymorphisms (SNP) in 6 genes (DBP, DHCR7, CYP2R1, CYP27B1, CYP24A1, VDR) previously reported to associate with circulating 25(OH)D concentration were typed using Taqman allelic discrimination assays.
Synthesis and evaluation of vitamin D receptor-mediated activities of cholesterol and vitamin D metabolites.
New
Arnold et al., Milwaukee, United States. In Eur J Med Chem, Feb 2016
LCA Gluc II increased the expression of CYP24A1 in DU145 cancer cells especially in the presence of the endogenous VDR ligand 1,25(OH)2D3.
Loss of miR-125b contributes to up-regulation of CYP24 in uremic rats.
New
Gao et al., Shijiazhuang, China. In Nephrology (carlton), Feb 2016
AIM: Abnormal up-regulation of CYP24 contributes to vitamin D insufficiency and resistance to vitamin D therapy in chronic kidney disease (CKD), because human CYP24 is a key enzyme involved in the inactivation of 1a,25-dihydroxyvitamin D3 (1a,25(OH)2D3; calcitriol) and 1,25(OH)2D3.
Vitamin D: Metabolism, Molecular Mechanism of Action, and Pleiotropic Effects.
Review
New
Impact
Carmeliet et al., Newark, United States. In Physiol Rev, Jan 2016
Although the identification of mechanisms mediating VDR-regulated transcription has been one focus of recent research in the field, other topics of fundamental importance include the identification and functional significance of proteins involved in the metabolism of vitamin D. CYP2R1 has been identified as the most important 25-hydroxylase, and a critical role for CYP24A1 in humans was noted in studies showing that inactivating mutations in CYP24A1 are a probable cause of idiopathic infantile hypercalcemia.
Motor neuron-like NSC-34 cells as a new model for the study of vitamin D metabolism in the brain.
New
Norlin et al., Uppsala, Sweden. In J Steroid Biochem Mol Biol, Jan 2016
The 25-hydroxylation involves mainly CYP2R1 and CYP27A1, whereas 1α-hydroxylation and 24-hydroxylation are catalyzed by CYP27B1 and CYP24A1, respectively, and are tightly regulated to maintain adequate levels of the active vitamin D hormone, 1α,25(OH)2D3.
Single nucleotide polymorphisms in the vitamin D pathway associating with circulating concentrations of vitamin D metabolites and non-skeletal health outcomes: Review of genetic association studies.
Review
New
Martineau et al., London, United Kingdom. In J Steroid Biochem Mol Biol, Jan 2016
We therefore conducted a literature review to identify reports of statistically significant associations between single nucleotide polymorphisms (SNP) in 11 vitamin D pathway genes (DHCR7, CYP2R1, CYP3A4, CYP27A1, DBP, LRP2, CUB, CYP27B1, CYP24A1, VDR and RXRA) and non-bone health outcomes and circulating levels of 25-hydroxyvitamin D (25[OH]D and 1,25-dihydroxyvitamin D (1,25[OH]2D).
Idiopathic Infantile Hypercalcemia, Presenting in Adulthood--No Longer Idiopathic Nor Infantile: Two Case Reports and Review.
Review
New
Saidi et al., In Conn Med, Nov 2015
Both were found to have a loss-of-function mutation in the CYP24A1 gene, which encodes the vitamin D-metabolizing enzyme 25-hydroxyvitamin D 24-hydroxylase.
Eldecalcitol (ED-71), an analog of 1α,25-dihydroxyvitamin D3 as a potential anti-cancer agent for oral squamous cell carcinomas.
Review
New
Okamoto et al., Hiroshima, Japan. In J Steroid Biochem Mol Biol, Nov 2015
As Cyp24A1 was reportedly induced in cancer cells, we measured the expression of CYP24A1 in OSCC cell lines (NA and UE), A431 epidermoid carcinoma and normal fibroblast cell (gfi) in serum-free culture.
Genetic variants and associations of 25-hydroxyvitamin D concentrations with major clinical outcomes.
Impact
Kestenbaum et al., Seattle, United States. In Jama, 2012
Substrate 25-hydroxyvitamin D must be converted to 1,25-dihydroxyvitamin D for full biological activity, and complex metabolic pathways suggest that interindividual variability in vitamin D metabolism may alter the clinical consequences of measured serum 25-hydroxyvitamin D. OBJECTIVE: To investigate whether common variation within genes encoding the vitamin D-binding protein, megalin, cubilin, CYP27B1, CYP24A1, and the vitamin D receptor (VDR) modify associations of low 25-hydroxyvitamin D with major clinical outcomes.
Genome-wide association study identifies eight new susceptibility loci for atopic dermatitis in the Japanese population.
Impact
Tamari et al., Yokohama, Japan. In Nat Genet, 2012
On the basis of data from a genome-wide association study (GWAS) and a validation study comprising a total of 3,328 subjects with atopic dermatitis and 14,992 controls in the Japanese population, we report here 8 new susceptibility loci: IL1RL1-IL18R1-IL18RAP (P(combined) = 8.36 × 10(-18)), the major histocompatibility complex (MHC) region (P = 8.38 × 10(-20)), OR10A3-NLRP10 (P = 1.54 × 10(-22)), GLB1 (P = 2.77 × 10(-16)), CCDC80 (P = 1.56 × 10(-19)), CARD11 (P = 7.83 × 10(-9)), ZNF365 (P = 5.85 × 10(-20)) and CYP24A1-PFDN4 (P = 1.65 × 10(-8)).
Association analyses identify multiple new lung cancer susceptibility loci and their interactions with smoking in the Chinese population.
Impact
Shen et al., Nanjing, China. In Nat Genet, 2012
(rs4809957 in CYP24A1, P = 1.20 × 10(-8)).
Altered expression of key players in vitamin D metabolism and signaling in malignant and benign thyroid tumors.
GeneRIF
Decallonne et al., Leuven, Belgium. In J Histochem Cytochem, 2012
The CYP24A1 expression was increased in follicular adenoma and differentiated thyroid cancer compared with normal thyroid.
Maternal vitamin D predominates over genetic factors in determining neonatal circulating vitamin D concentrations.
GeneRIF
Saffery et al., Australia. In Am J Clin Nutr, 2012
The placental methylation of the CYP24A1 gene promoter appears subject to genetic influence, although no evidence of a relation between the methylation level of this gene and circulating maternal or neonatal 25-hydroxyvitamin D is apparent.
A local effect of CYP24 inhibition on lung tumor xenograft exposure to 1,25-dihydroxyvitamin D(3) is revealed using a novel LC-MS/MS assay.
GeneRIF
Hershberger et al., Pittsburgh, United States. In Steroids, 2012
Results provide evidence that CYP24-expressing lung tumors eliminate 1,25(OH)(2)D(3) by a CYP24-dependent process in vivo.
Expression of prostaglandin- and vitamin D-metabolising enzymes in benign and malignant breast cells.
GeneRIF
Cordes et al., Lübeck, Germany. In Anticancer Res, 2012
Low CYP24 is associated with breast cancer.
Polymorphisms related to the serum 25-hydroxyvitamin D level and risk of myocardial infarction, diabetes, cancer and mortality. The Tromsø Study.
GeneRIF
Grimnes et al., Tromsø, Norway. In Plos One, 2011
A significant association with breast cancer found with the rs6013897 genotypes in CYP24A1 protein.
Mutations in CYP24A1 and idiopathic infantile hypercalcemia.
Impact
GeneRIF
Konrad et al., Münster, Germany. In N Engl J Med, 2011
The presence of CYP24A1 mutations explains the increased sensitivity to vitamin D in patients with idiopathic infantile hypercalcemia and is a genetic risk factor for the development of symptomatic hypercalcemia.
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