CYP24A1

gene
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Also known as CP24P450-CC24lncBCAS1-4_1

Summary

CYP24A1 (cytochrome P450 family 24 subfamily A member 1, HGNC:2602) is a protein-coding gene on chromosome 20q13.2, encoding 1,25-dihydroxyvitamin D(3) 24-hydroxylase, mitochondrial (Q07973). A cytochrome P450 monooxygenase with a key role in vitamin D catabolism and calcium homeostasis.

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.

Source: NCBI Gene 1591 — RefSeq curated summary.

At a glance

  • Gene–disease (curated): hypercalcemia, infantile, 1 (Strong, GenCC) — +1 more curated relationship
  • GWAS associations: 27
  • Clinical variants (ClinVar): 460 total — 31 pathogenic, 23 likely-pathogenic
  • Phenotypes (HPO): 15
  • Druggable target: yes — 4 molecules with ChEMBL bioactivity
  • Dosage sensitivity (ClinGen): haploinsufficiency autosomal recessive, triplosensitivity unscored
  • MANE Select transcript: NM_000782

Identifiers

Gene identifiers

FieldValue
HGNC IDHGNC:2602
Approved symbolCYP24A1
Namecytochrome P450 family 24 subfamily A member 1
Location20q13.2
Locus typegene with protein product
StatusApproved
AliasesCP24, P450-CC24, lncBCAS1-4_1
Ensembl geneENSG00000019186
Ensembl biotypeprotein_coding
OMIM126065
Entrez1591

Gene structure

Transcript identifiers

Ensembl transcripts: 9 — 6 protein_coding, 3 protein_coding_CDS_not_defined

ENST00000216862, ENST00000395954, ENST00000395955, ENST00000460643, ENST00000472970, ENST00000487593, ENST00000869535, ENST00000869536, ENST00000869537

RefSeq mRNA: 6 — MANE Select: NM_000782 NM_000782, NM_001128915, NM_001424340, NM_001424341, NM_001424342, NM_001424343

CCDS: CCDS33491, CCDS46616

Canonical transcript exons

ENST00000216862 — 12 exons

ExonStartEnd
ENSE000006628465415738854157585
ENSE000006628475415808654158164
ENSE000006628485415895754159123
ENSE000006628495416271754162862
ENSE000006628505416445254164563
ENSE000006628515416574254165833
ENSE000006628525416959254169688
ENSE000006628535417157754171670
ENSE000006628545417290954173099
ENSE000008456695415344654154761
ENSE000008456705415716954157289
ENSE000008456715417332254173986

Expression profiles

Bgee: expression breadth ubiquitous, 163 present calls, max score 91.53.

FANTOM5 (CAGE): breadth broad, TPM avg 4.6652 / max 635.0835, expressed in 331 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter IDTPM avgSamples expressed
1880724.5316321
1880710.055423
1880690.041515
1880730.036714

Top tissues by expression

273 total, by Bgee expression score (0-100, higher = more expressed):

TissueAnatomy IDExpression scoreQuality
olfactory segment of nasal mucosaUBERON:000538691.53gold quality
secondary oocyteCL:000065587.96gold quality
male germ line stem cell (sensu Vertebrata) in testisCL:0000089 ∩ UBERON:000047383.34gold quality
mucosa of urinary bladderUBERON:000125980.24gold quality
oocyteCL:000002379.31gold quality
adult mammalian kidneyUBERON:000008278.91gold quality
epithelium of nasopharynxUBERON:000195177.44silver quality
primordial germ cell in gonadCL:0000670 ∩ UBERON:000099175.36gold quality
urinary bladderUBERON:000125574.68gold quality
metanephros cortexUBERON:001053374.23gold quality
lower esophagus mucosaUBERON:003583473.85gold quality
gingival epitheliumUBERON:000194971.96silver quality
kidneyUBERON:000211371.88gold quality
nasal cavity mucosaUBERON:000182671.74gold quality
esophagus mucosaUBERON:000246969.83gold quality
gingivaUBERON:000182868.56silver quality
palpebral conjunctivaUBERON:000181266.99silver quality
cortex of kidneyUBERON:000122566.78gold quality
tonsilUBERON:000237265.96gold quality
nephron tubuleUBERON:000123165.85silver quality
endocervixUBERON:000045864.80gold quality
metanephrosUBERON:000008164.38gold quality
seminal vesicleUBERON:000099864.09gold quality
bronchial epithelial cellCL:000232863.22silver quality
metanephric glomerulusUBERON:000473662.81silver quality
epithelium of bronchusUBERON:000203161.52silver quality
bronchusUBERON:000218561.24silver quality
mucosa of paranasal sinusUBERON:000503061.12silver quality
placentaUBERON:000198760.97gold quality
prefrontal cortexUBERON:000045160.54gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 1.

ExperimentMarker?Max mean expression
E-ANND-3yes7.27

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): CTNNB1, ETS1, ETV7, HR, KAT7, NCOR2, NR1I2, NR1I3, NR2C2, RXRA, SNAI2, TBP, TP53, VDR

miRNA regulators (miRDB)

81 targeting CYP24A1, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNAMax scoreAvg scoremiRNA target_count
HSA-MIR-30A-5P100.0076.313233
HSA-MIR-30B-5P100.0076.293248
HSA-MIR-30C-5P100.0076.293248
HSA-MIR-30D-5P100.0076.323233
HSA-MIR-30E-5P100.0076.323242
HSA-MIR-8485100.0077.574731
HSA-MIR-5692A100.0074.406850
HSA-MIR-5692B100.0071.322622
HSA-MIR-5692C100.0071.322622
HSA-MIR-340-5P100.0072.504437
HSA-MIR-548C-3P99.9974.017587
HSA-MIR-548AJ-3P99.9673.385345
HSA-MIR-548X-3P99.9673.385345
HSA-MIR-493-5P99.9672.472382
HSA-MIR-551B-5P99.9671.283493
HSA-MIR-23A-3P99.9574.243163
HSA-MIR-23B-3P99.9574.243163
HSA-MIR-23C99.9573.923192
HSA-MIR-548J-3P99.9472.614881
HSA-MIR-144-3P99.9473.982698
HSA-MIR-548AE-3P99.9372.664867
HSA-MIR-548AH-3P99.9372.544872
HSA-MIR-548AM-3P99.9372.544872
HSA-MIR-548AQ-3P99.9372.664867
HSA-MIR-338-5P99.9272.342951
HSA-MIR-6768-5P99.9267.361942
HSA-MIR-498-3P99.9171.271114
HSA-MIR-374A-5P99.9071.342923
HSA-MIR-374B-5P99.9069.982734
HSA-MIR-345-3P99.8970.231421

Functional genomics

ClinGen dosage: haploinsufficiency 30 (autosomal recessive), triplosensitivity Not yet evaluated (unscored). ClinGen Gene Dosage Map

Literature-anchored findings (GeneRIF, showing 40)

  • Transcription is inhibited by genistein. (PMID:12485911)
  • results suggest that 1,25-dihydroxyvitamin D3 rapid effects require the presence of vitamin D receptor and control, in part, the vitamin D catabolism via increased expression of the 24-hydroxylase and ferredoxin genes (PMID:14665637)
  • Overexpression of the candidate oncogene CYP24 is inversely correlated to vitamin D receptor expression, and may play an important role in determination of the malignant potential of esophageal cancer (PMID:14760115)
  • In this paper, novel metabolites of 1 alpha,25-dihydroxyvitamin D3 and 25(OH)D3 catalyzed by human enzyme CYP24A1 are presented. These metabolites appear to be closely related to the C-23 hydroxylation pathway. (PMID:15078099)
  • Metabolism of A-ring diastereomers of calcitriol was examined to compare the substrate specificity and reaction specificity of CYP24A1 between humans and rats. (PMID:15358094)
  • xenobiotics and drugs can modulate CYP24 gene expression and alter vitamin D(3) hormonal activity and calcium homeostasis through the activation of pregnane X receptor (PMID:15630458)
  • data suggest that alternative splicing of vitamin D-24-hydroxylase (CYP24) leads to the generation of a dominant negative-acting protein that is catalytically dysfunctional and may contribute to the extracellular accumulation of 1,25-dihydroxyvitamin D (PMID:15788398)
  • information concerning the regulation of the CYP24 gene by 1alpha,25OH2D3, and is a demonstration of the simultaneous participation of multiple, structurally diverse response elements in promoter activation in a living cell (PMID:15919092)
  • Real-time RT-PCR showed that exposure of HL-60 cells to 1,25(OH)(2)D(3) induced expression of CYP24. (PMID:16457885)
  • CYP24A1 can activate and inactivate vitamin D prodrugs in skin and other target cells in vitro (PMID:16516540)
  • Haplotype association were found only for CYP24A1, the main calcidiol degrading enzyme in the vitamin D turnover or signalling pathway. (PMID:16600026)
  • CYP24A1 mutant I500F showed quite a different metabolism of 1alpha,25-dihydroxyvitamin D3. (PMID:16617161)
  • Data show that activation of steroid and xenobiotic receptor does not induce cytochrome P450, family 24 (CYP24)-mediated expression, but inhibits vitamin D receptor-mediated CYP24 promoter activity. (PMID:16691293)
  • increased CYP24 expression in lung tumors restricts 1,25D3 activity and support the preclinical evaluation of CYP24 inhibitors for lung cancer treatment (PMID:16708384)
  • The overall data suggest that calcitriol downregulates CYP27B1 expression via a cAMP-dependent signaling pathway, whereas upregulates 24-hydroxylase gene expression through a VDR-dependent mechanism. (PMID:17079137)
  • CYP27B1 gene could play a functional role in the pathogenesis of type 1 diabetes through modulation of its mRNA expression and influence serum levels of 1,25(OH)(2)D(3) via the -1260 C/A polymorphism (PMID:17223345)
  • local 1,25D synthesis has paracrine effects in the bone microenvironment implying that vitamin D metabolism in human osteoblasts represents a physiologically important pathway (PMID:17254772)
  • differences in CYP24 splicing are associated with different patterns of CYP24 activity (PMID:17368180)
  • Upstream sequence and the 5’-untranslated region of CYP24 did not appear to play a major role in the vitamin D response. (PMID:17475215)
  • In conclusion, CAR/PXR and VDR bind to and transactivate the same response elements in CYP24 promoter. (PMID:17585873)
  • Ala-326 is located in the I-helix, close to the terminus of the docked 25-hydroxylated side chain in a CYP24A1 homology model (PMID:17646648)
  • CYP27A1 and CYP24 expression is a function of malignant transformation in the colon (PMID:17875655)
  • Genotypes of CYP27B1 and CYP24A1 were not associated with prostate cancer risk. (PMID:17932346)
  • It inactivate vitamin D and its expression is controlled by mechanical stress and mitogen activated protein kinase. (PMID:18467787)
  • VDRE2 variant results in decreased protein binding and transactivation in vitro, and reduced expression of CYP24A1 in cultured primary human lymphocytes (PMID:18824104)
  • Data show that there are both promoter-specific and cell stage-specific roles for the ERK1/2 signaling pathway on 1,25(OH)(2)D(3)-mediated CYP24 gene induction in enterocyte-like Caco-2 cells. (PMID:19097033)
  • CYP24A1 gene is methylated in human placenta, purified cytotrophoblasts, and primary and cultured chorionic villus sampling tissue. (PMID:19237542)
  • Single nucleotide polymorphisms may be associated with risk of prostate cancer in men with low vitamin D status. (PMID:19255064)
  • These results indicate that human CYP24A1 catalyzes the C24-C25 bond cleavage of 1alpha,24,25(OH)2D2, which is quite effective in the inactivation of the active form of vitamin D2. (PMID:19393625)
  • common genotypic variation found in VDR, CYP27B1, and CYP24A1 has little or no effect on overall prostate cancer risk (PMID:19454612)
  • Alternative splicing of 24-OHase may lead to a catalytically dysfunctional enzyme and may lead to less reduction of the target protein (PMID:19667160)
  • The CYP24A1 polymorphism IVS4-66T > G showed a statistically significant association with risk of colon cancer overall, particularly for proximal colon cancer. (PMID:19706847)
  • This is the first study to correlate CYP24A1 protein levels with proliferation, suggesting that CYP24A1 overexpression counteracts the antiproliferative effect of 1,25-D3 during tumor progression. (PMID:19901270)
  • 1,25-dihydroxyvitamin D3 can activate PKC zeta and that the PI3-kinase-PKC zeta cascade regulates the CYP24 promoter. (PMID:19922790)
  • analysis of expression of serum vitamin D receptor, cyclooxygenase-2, and 15-hydroxyprostaglandin dehydrogenase in benign and malignant ovarian tissue and 25-hydroxycholecalciferol and prostaglandin E2 in ovarian cancer patients (PMID:20304053)
  • human PBLs show only weak methylation in the upstream region of CYP27B1 and none in CYP24A1 (PMID:20304056)
  • epigenetic silencing of CYP24 modulates cellular responses to calcitriol (PMID:20304059)
  • analysis of CYP24A1 splicing variants in human colon cancer cell lines and tissue samples (PMID:20398751)
  • 1,25D-mediated induction of human CYP24A1 is dependant upon a promoter region spanning nucleotides -470 to -392 of the human CYP24A1 promoter. (PMID:20450955)
  • the number of vitamin D receptor binding sites defines the different vitamin D responsiveness of the CYP24 gene in malignant and normal mammary cells (PMID:20460683)

Cross-species orthologs

4 orthologs

OrganismSymbolGene ID
danio_reriocyp24a1ENSDARG00000103277
mus_musculusCyp24a1ENSMUSG00000038567
rattus_norvegicusCyp24a1ENSRNOG00000013062
drosophila_melanogastersadFBGN0003312

Paralogs (3): CYP27B1 (ENSG00000111012), CYP27A1 (ENSG00000135929), CYP27C1 (ENSG00000186684)

Protein

Protein identifiers

1,25-dihydroxyvitamin D(3) 24-hydroxylase, mitochondrialQ07973 (reviewed: Q07973)

Alternative names: Cytochrome P450 24A1, Cytochrome P450-CC24

All UniProt accessions (1): Q07973

UniProt curated annotations — full annotation on UniProt →

Function. A cytochrome P450 monooxygenase with a key role in vitamin D catabolism and calcium homeostasis. Via C24- and C23-oxidation pathways, catalyzes the inactivation of both the vitamin D precursor calcidiol (25-hydroxyvitamin D(3)) and the active hormone calcitriol (1-alpha,25-dihydroxyvitamin D(3)). With initial hydroxylation at C-24 (via C24-oxidation pathway), performs a sequential 6-step oxidation of calcitriol leading to the formation of the biliary metabolite calcitroic acid. With initial hydroxylation at C-23 (via C23-oxidation pathway), catalyzes sequential oxidation of calcidiol leading to the formation of 25(OH)D3-26,23-lactone as end product. Preferentially hydroxylates at C-25 other vitamin D active metabolites, such as CYP11A1-derived secosteroids 20S-hydroxycholecalciferol and 20S,23-dihydroxycholecalciferol. Mechanistically, uses molecular oxygen inserting one oxygen atom into a substrate, and reducing the second into a water molecule, with two electrons provided by NADPH via FDXR/adrenodoxin reductase and FDX1/adrenodoxin.

Subcellular location. Mitochondrion.

Disease relevance. Hypercalcemia, infantile, 1 (HCINF1) [MIM:143880] A disorder characterized by abnormally high level of calcium in the blood, failure to thrive, vomiting, dehydration, and nephrocalcinosis. The disease is caused by variants affecting the gene represented in this entry.

Miscellaneous. Specifically expressed in macrophages. Lacks the transit peptide. May be a dominant negative-acting isoform possibly by sequestering vitamin D metabolites.

Similarity. Belongs to the cytochrome P450 family.

Isoforms (3)

UniProt IDNamesCanonical?
Q07973-11yes
Q07973-22
Q07973-33, CYP24-SV

RefSeq proteins (6): NP_000773, NP_001122387, NP_001411269, NP_001411270, NP_001411271, NP_001411272 (=MANE)

Domains & families (InterPro)

IDNameType
IPR001128Cyt_P450Family
IPR002401Cyt_P450_E_grp-IFamily
IPR017972Cyt_P450_CSConserved_site
IPR036396Cyt_P450_sfHomologous_superfamily
IPR050479CYP11_CYP27_familiesFamily

Pfam: PF00067

Enzyme classification (BRENDA):

  • EC 1.14.14.24 — vitamin D 25-hydroxylase (BRENDA: 7 organisms, 34 substrates, 4 inhibitors, 22 Km, 14 kcat entries)
  • EC 1.14.15.16 — vitamin D3 24-hydroxylase (BRENDA: 3 organisms, 62 substrates, 46 inhibitors, 21 Km, 13 kcat entries)

Substrate kinetics (BRENDA)

15 substrates with measured Km, best-characterized 15. Km ranges are aggregated across organisms/conditions.

SubstrateKm (mM)Measurements
1ALPHA,25-DIHYDROXYVITAMIN D30.0001–0.001111
1ALPHA-HYDROXYVITAMIN D30.0006–0.01136
VITAMIN D30.0008–0.0326
1ALPHA-HYDROXYVITAMIN D20.0042–0.0184
BUFURALOL0.001–0.00142
VITAMIN D20.0004–0.0022
25-HYDROXYVITAMIN D30.0002–0.00032
CALCITRIOL0.0086–0.0092
1ALPHA-HYDROXYCHOLECALCIFEROL0.0541
25-HYDROXY-VITAMIN D30.00711
1ALPHA,25-DIHYDROXY-3-EPI-VITAMIN D30.00011
1BETA,25-DIHYDROXY-3-EPI-VITAMIN D30.00121
1BETA,25-DIHYDROXYVITAMIN D30.00011
2-METHYLENE-19-NOR-(20R)-1,25-DIHYDROXYVITAMIN D0.00031
2-METHYLENE-19-NOR-(20S)-1,25-DIHYDROXYVITAMIN D0.00011

Catalyzed reactions (Rhea), 12 shown:

  • calcitriol + 2 reduced [adrenodoxin] + O2 + 2 H(+) = calcitetrol + 2 oxidized [adrenodoxin] + H2O (RHEA:24964)
  • calcidiol + 2 reduced [adrenodoxin] + O2 + 2 H(+) = secalciferol + 2 oxidized [adrenodoxin] + H2O (RHEA:24968)
  • calcitetrol + 2 reduced [adrenodoxin] + O2 + 2 H(+) = (1S)-1,25-dihydroxy-24-oxocalciol + 2 oxidized [adrenodoxin] + 2 H2O (RHEA:24972)
  • (1S)-1,25-dihydroxy-24-oxocalciol + 2 reduced [adrenodoxin] + O2 + 2 H(+) = (1S)-1,23,25-trihydroxy-24-oxocalciol + 2 oxidized [adrenodoxin] + H2O (RHEA:24976)
  • (1S)-1,23-dihydroxy-24,25,26,27-tetranorcalciol + 2 reduced [adrenodoxin] + O2 + 2 H(+) = (1S)-1-hydroxy-23-oxo-24,25,26,27-tetranorcalciol + 2 oxidized [adrenodoxin] + 2 H2O (RHEA:24984)
  • (1S)-1-hydroxy-23-oxo-24,25,26,27-tetranorcalciol + 2 reduced [adrenodoxin] + O2 + H(+) = calcitroate + 2 oxidized [adrenodoxin] + H2O (RHEA:24988)
  • calcidiol + 2 reduced [adrenodoxin] + O2 + 2 H(+) = (23S)-23,25-dihydroxycalciol + 2 oxidized [adrenodoxin] + H2O (RHEA:46616)
  • calcitriol + 2 reduced [adrenodoxin] + O2 + 2 H(+) = 1alpha,23S,25-trihydroxycholecalciferol + 2 oxidized [adrenodoxin] + H2O (RHEA:49192)
  • secalciferol + 2 reduced [adrenodoxin] + O2 + 2 H(+) = 25-hydroxy-24-oxocalciol + 2 oxidized [adrenodoxin] + 2 H2O (RHEA:49196)
  • 20S-hydroxycholecalciferol + 2 reduced [adrenodoxin] + O2 + 2 H(+) = 20S,24R-dihydroxycholecalciferol + 2 oxidized [adrenodoxin] + H2O (RHEA:49204)
  • 20S-hydroxycholecalciferol + 2 reduced [adrenodoxin] + O2 + 2 H(+) = 20S,25-dihydroxycholecalciferol + 2 oxidized [adrenodoxin] + H2O (RHEA:49212)
  • 25-hydroxy-24-oxocalciol + 2 reduced [adrenodoxin] + O2 + 2 H(+) = 23S,25-dihydroxy-24-oxocholecalciferol + 2 oxidized [adrenodoxin] + H2O (RHEA:49268)

UniProt features (20 total): sequence variant 7, sequence conflict 7, splice variant 3, transit peptide 1, chain 1, binding site 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

ModelpLDDTFraction very-high
AF-Q07973-F189.030.78

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Ligand- & substrate-binding residues (1): 462 (axial binding residue)

Function

Pathways and Gene Ontology

Reactome pathways

3 pathways

IDPathway
R-HSA-196791Vitamin D (calciferol) metabolism
R-HSA-211916Vitamins
R-HSA-5579010Defective CYP24A1 causes HCAI

MSigDB gene sets: 242 (showing top): REACTOME_BIOLOGICAL_OXIDATIONS, BUYTAERT_PHOTODYNAMIC_THERAPY_STRESS_DN, BENPORATH_ES_WITH_H3K27ME3, GOMF_OXIDOREDUCTASE_ACTIVITY_ACTING_ON_PAIRED_DONORS_WITH_INCORPORATION_OR_REDUCTION_OF_MOLECULAR_OXYGEN, GOBP_CELLULAR_RESPONSE_TO_LIPID, SHEPARD_CRASH_AND_BURN_MUTANT_UP, GRAESSMANN_APOPTOSIS_BY_SERUM_DEPRIVATION_DN, GOBP_POLYOL_METABOLIC_PROCESS, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, GOBP_OSTEOBLAST_DIFFERENTIATION, LINDGREN_BLADDER_CANCER_CLUSTER_3_DN, NAGASHIMA_NRG1_SIGNALING_UP, GOBP_CELLULAR_RESPONSE_TO_OXYGEN_CONTAINING_COMPOUND, TTGCWCAAY_CEBPB_02, GOBP_SMALL_MOLECULE_BIOSYNTHETIC_PROCESS

GO Biological Process (12): osteoblast differentiation (GO:0001649), vitamin metabolic process (GO:0006766), response to vitamin D (GO:0033280), vitamin D metabolic process (GO:0042359), vitamin D catabolic process (GO:0042369), vitamin D receptor signaling pathway (GO:0070561), alcohol metabolic process (GO:0006066), lipid metabolic process (GO:0006629), lipid biosynthetic process (GO:0008610), calcitriol biosynthetic process from calciol (GO:0036378), small molecule biosynthetic process (GO:0044283), cellular response to vitamin D (GO:0071305)

GO Molecular Function (12): iron ion binding (GO:0005506), 25-hydroxycholecalciferol-24-hydroxylase activity (GO:0008403), heme binding (GO:0020037), 1-alpha,25-dihydroxyvitamin D3 24-hydroxylase activity (GO:0030342), vitamin D 25-hydroxylase activity (GO:0030343), 25-hydroxycholecalciferol-23-hydroxylase activity (GO:0062180), 1-alpha,25-dihydroxyvitamin D3 23-hydroxylase activity (GO:0062181), monooxygenase activity (GO:0004497), oxidoreductase activity (GO:0016491), oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen (GO:0016705), metal ion binding (GO:0046872), vitamin D 24-hydroxylase activity (GO:0070576)

GO Cellular Component (2): mitochondrion (GO:0005739), mitochondrial inner membrane (GO:0005743)

Reactome top-level categories

Rollup of top-3 pathways:

CategoryPathways
Metabolism of steroids1
Cytochrome P450 - arranged by substrate type1
Metabolic disorders of biological oxidation enzymes1

GO top-level categories

Rollup of top GO terms by namespace:

CategoryTerms
small molecule metabolic process3
biosynthetic process2
vitamin D 24-hydroxylase activity2
steroid hydroxylase activity2
vitamin D 23-hydroxylase activity2
oxidoreductase activity2
ossification1
cell differentiation1
response to vitamin1
response to lipid1
response to oxygen-containing compound1
steroid metabolic process1
steroid catabolic process1
vitamin D metabolic process1
fat-soluble vitamin catabolic process1
hormone-mediated signaling pathway1
cellular response to vitamin D1
nuclear receptor-mediated signaling pathway1
primary metabolic process1
lipid metabolic process1
vitamin D biosynthetic process1
polyol biosynthetic process1
vitamin D3 metabolic process1
response to vitamin D1
cellular response to vitamin1
cellular response to lipid1
cellular response to oxygen-containing compound1
transition metal ion binding1
oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen1
tetrapyrrole binding1
calcitriol biosynthetic process from calciol1
catalytic activity1
cation binding1
cytoplasm1
intracellular membrane-bounded organelle1
organelle inner membrane1
mitochondrial membrane1

Protein interactions and networks

STRING

2026 interactions, top by confidence (×1000):

Protein AProtein BPartner UniProtScore
CYP24A1GCP02774897
CYP24A1CA1P00915879
CYP24A1CA8P35219870
CYP24A1CA5BQ9Y2D0870
CYP24A1CA13Q8N1Q1848
CYP24A1PTHP01270842
CYP24A1CA5AP35218841
CYP24A1CA14Q9ULX7841
CYP24A1CA7P43166819
CYP24A1CA6P23280806
CYP24A1CA12O43570799
CYP24A1FGF23Q9GZV9793
CYP24A1CA2P00918792
CYP24A1DHCR7Q9UBM7783
CYP24A1CA3P07451779

IntAct

57 interactions, top by confidence:

ABTypeScore
NDUFS6NDUFS8psi-mi:“MI:0914”(association)0.640
PTGR3DBTpsi-mi:“MI:0914”(association)0.640
ZNF764SH3PXD2Bpsi-mi:“MI:0914”(association)0.530
UQCRFS1NDUFAB1psi-mi:“MI:0914”(association)0.530
AGMATDCXpsi-mi:“MI:0914”(association)0.500
Dlg4CYP24A1psi-mi:“MI:0407”(direct interaction)0.440
ECSITNDUFS2psi-mi:“MI:0914”(association)0.350
ZNF254TRIM24psi-mi:“MI:0914”(association)0.350
ZNF785CASKpsi-mi:“MI:0914”(association)0.350
PAESYT2psi-mi:“MI:0914”(association)0.350
THEM5PRORPpsi-mi:“MI:0914”(association)0.350
RBAKCYP24A1psi-mi:“MI:0914”(association)0.350
MRPS7RPSA2psi-mi:“MI:0914”(association)0.350
FFAR1SLC12A8psi-mi:“MI:0914”(association)0.350
GPR182SLC12A8psi-mi:“MI:0914”(association)0.350
TRIM43VWA8psi-mi:“MI:0914”(association)0.350
QRSL1VWA8psi-mi:“MI:0914”(association)0.350
SHC2VWA8psi-mi:“MI:0914”(association)0.350
YARS2VWA8psi-mi:“MI:0914”(association)0.350
MRPS24VWA8psi-mi:“MI:0914”(association)0.350
AMACRVWA8psi-mi:“MI:0914”(association)0.350
ACSM5VWA8psi-mi:“MI:0914”(association)0.350
RASL10BVWA8psi-mi:“MI:0914”(association)0.350
AK4VWA8psi-mi:“MI:0914”(association)0.350
FAHD1VWA8psi-mi:“MI:0914”(association)0.350
GPR45VWA8psi-mi:“MI:0914”(association)0.350
THEM5GTPBP10psi-mi:“MI:0914”(association)0.350
MALSU1GTPBP10psi-mi:“MI:0914”(association)0.350

BioGRID (60): CYP24A1 (Affinity Capture-MS), CYP24A1 (Affinity Capture-MS), CYP24A1 (Affinity Capture-MS), CYP24A1 (Affinity Capture-MS), CYP24A1 (Synthetic Lethality), CYP24A1 (Proximity Label-MS), FZR1 (Affinity Capture-Western), CDC20 (Affinity Capture-Western), CYP24A1 (Affinity Capture-MS), CYP24A1 (Affinity Capture-MS), CYP24A1 (Affinity Capture-MS), CYP24A1 (Affinity Capture-MS), CYP24A1 (Affinity Capture-MS), CYP24A1 (Affinity Capture-MS), CYP24A1 (Affinity Capture-MS)

ESM2 similar proteins: A0A1I9Q5Z0, A0A481NR20, A8WGA0, E1BHJ4, G3V7X8, O18635, O23051, O44220, O73853, P05093, P0DOX0, P11715, P48416, P82712, Q07973, Q09128, Q09660, Q2XVA1, Q4G0S4, Q64441, Q6JD68, Q6WG30, Q7KR10, Q811W2, Q8HYM9, Q8HYN0, Q8HYN1, Q8W4T9, Q91Z85, Q92045, Q92113, Q940V4, Q95328, Q9EPT4, Q9GLD2, Q9GMC8, Q9LUC5, Q9NGX9, Q9NR63, Q9SHG5

Diamond homologs: A0A017SFB8, A0A017SR40, A0A0C3HJL3, A0A0S2II38, A0A0U5GRB4, A0A100IM63, A0A1E3B0R7, A0A1L9WN72, A0A1L9WQP6, A0A1L9WUS5, A0A1U9YHZ8, A0A1V0QSE7, A0A2H3CNY6, A0A2H3CSA7, A0A2H3CZX2, A0A2P1DP94, A0A2Z5U6I9, A0A3Q7HBJ5, A0A516F411, A0A6J4BC30, A0A6S6QI82, A0A7T8F1L2, A1DA63, A7VMU4, A8NCK4, A8NCK6, A9QNE7, B9WZX4, C8VJR0, F1SY52, F1SY62, F1SY66, F1SY68, F1SY70, F1SY73, F1SY75, F1SY82, F1SY91, F1SY96, F1SYA2

SIGNOR signaling

5 interactions.

AEffectBMechanism
VDR“down-regulates quantity by repression”CYP24A1“transcriptional regulation”
PTH1R“up-regulates quantity”CYP24A1
CYP24A1“up-regulates quantity”calcitetrol“chemical modification”
CYP24A1“down-regulates quantity”calcitriol“chemical modification”
CYP24A1“up-regulates quantity”propan-2-ol“chemical modification”

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 83 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

PathwayPartnersFoldFDR
Complex I biogenesis617.4×2e-04
Mitochondrial ribosome-associated quality control612.9×7e-04
Fatty acid metabolism511.5×3e-03
Respiratory electron transport610.0×2e-03

GO biological processes:

GO termPartnersFoldFDR
mitochondrial respiratory chain complex I assembly527.4×3e-04
mitochondrial electron transport, NADH to ubiquinone523.9×3e-04
proton motive force-driven mitochondrial ATP synthesis517.6×1e-03
aerobic respiration516.5×1e-03
mitochondrial translation511.6×4e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

460 variants total. Per-class counts are floors (≥ shown; pagination cap):

ClassificationCount (floor)
Pathogenic31
Likely pathogenic23
Uncertain significance210
Likely benign80
Benign63

Top pathogenic / likely-pathogenic (30)

Variant IDHGVSClassification
1072834NM_000782.5(CYP24A1):c.1396C>T (p.Arg466Ter)Pathogenic
1075791NM_000782.5(CYP24A1):c.278del (p.Tyr93fs)Pathogenic
1179111GRCh37/hg19 20q13.2(chr20:52769985-52790525)Pathogenic
1442407NM_000782.5(CYP24A1):c.312del (p.Phe104fs)Pathogenic
1460149NM_000782.5(CYP24A1):c.999_1006del (p.Ser334fs)Pathogenic
1914788NM_000782.5(CYP24A1):c.1171_1174dup (p.Pro392fs)Pathogenic
1941936NM_000782.5(CYP24A1):c.1384_1385del (p.Cys462fs)Pathogenic
2111621NM_000782.5(CYP24A1):c.224G>A (p.Trp75Ter)Pathogenic
2159550NM_000782.5(CYP24A1):c.449+1G>TPathogenic
2506936NM_000782.5(CYP24A1):c.641-1G>APathogenic
2506945NM_000782.5(CYP24A1):c.364G>T (p.Glu122Ter)Pathogenic
2912919NM_000782.5(CYP24A1):c.1022del (p.Asn341fs)Pathogenic
29675NM_000782.5(CYP24A1):c.1426_1427del (p.Cys477fs)Pathogenic
29677NM_000782.5(CYP24A1):c.425AAG[1] (p.Glu143del)Pathogenic
29678NM_000782.5(CYP24A1):c.451G>T (p.Glu151Ter)Pathogenic
2993674NM_000782.5(CYP24A1):c.449+2T>CPathogenic
3234027NM_000782.5(CYP24A1):c.109C>T (p.Gln37Ter)Pathogenic
3236073NM_000782.5(CYP24A1):c.1320G>A (p.Trp440Ter)Pathogenic
3236225NM_000782.5(CYP24A1):c.670_673dup (p.Gly225fs)Pathogenic
3248320NC_000020.10:g.(?52773718)(52790118_?)delPathogenic
3341138NM_000782.5(CYP24A1):c.1039del (p.Gln347fs)Pathogenic
3587448NM_000782.5(CYP24A1):c.845-2A>GPathogenic
3587450NM_000782.5(CYP24A1):c.804G>A (p.Trp268Ter)Pathogenic
3587457NM_000782.5(CYP24A1):c.667A>T (p.Arg223Ter)Pathogenic
3608266NM_000782.5(CYP24A1):c.1497_1504del (p.Thr500fs)Pathogenic
3623870NM_000782.5(CYP24A1):c.1084G>T (p.Glu362Ter)Pathogenic
3642651NM_000782.5(CYP24A1):c.491del (p.Lys164fs)Pathogenic
3708845NM_000782.5(CYP24A1):c.1199del (p.Lys400fs)Pathogenic
4074266NM_000782.5(CYP24A1):c.1339dup (p.Ile447fs)Pathogenic
4294430NM_000782.5(CYP24A1):c.1410dup (p.Gln471fs)Pathogenic

SpliceAI

1723 predictions. Top by Δscore:

VariantEffectΔscore
20:54157163:GCTCA:Gdonor_loss1.0000
20:54157164:CTCA:Cdonor_loss1.0000
20:54157165:TCACC:Tdonor_loss1.0000
20:54157166:CACCT:Cdonor_loss1.0000
20:54157167:A:AGdonor_loss1.0000
20:54157168:C:Tdonor_loss1.0000
20:54157286:CAAT:Cacceptor_gain1.0000
20:54157288:ATC:Aacceptor_loss1.0000
20:54157290:C:CCacceptor_gain1.0000
20:54157290:C:CGacceptor_loss1.0000
20:54157291:T:Gacceptor_loss1.0000
20:54157295:A:ACacceptor_gain1.0000
20:54158080:ACTTA:Adonor_loss1.0000
20:54158082:TTA:Tdonor_loss1.0000
20:54158084:A:ACdonor_gain1.0000
20:54158084:A:Cdonor_loss1.0000
20:54158084:ACT:Adonor_gain1.0000
20:54158084:ACTC:Adonor_gain1.0000
20:54158085:C:CTdonor_gain1.0000
20:54158085:CT:Cdonor_gain1.0000
20:54158085:CTC:Cdonor_gain1.0000
20:54158085:CTCC:Cdonor_gain1.0000
20:54158085:CTCCT:Cdonor_gain1.0000
20:54158160:TAAGC:Tacceptor_gain1.0000
20:54158162:AGC:Aacceptor_gain1.0000
20:54158163:GC:Gacceptor_gain1.0000
20:54158163:GCCT:Gacceptor_loss1.0000
20:54158164:CC:Cacceptor_gain1.0000
20:54158164:CCTGA:Cacceptor_loss1.0000
20:54158165:C:CCacceptor_gain1.0000

AlphaMissense

3371 scored. Top likely-pathogenic:

VariantProtein changeam_pathogenicity
20:54172945:C:GR138P0.996
20:54172958:A:GW134R0.995
20:54172958:A:TW134R0.995
20:54158135:C:GR396P0.994
20:54157457:A:CF455L0.991
20:54157457:A:TF455L0.991
20:54157459:A:GF455L0.991
20:54169604:A:GW210R0.991
20:54169604:A:TW210R0.991
20:54171644:C:GR159P0.991
20:54164473:A:GW275R0.990
20:54164473:A:TW275R0.990
20:54172946:G:TR138S0.990
20:54157442:T:AR460S0.988
20:54157442:T:GR460S0.988
20:54158957:C:GR386T0.988
20:54164494:A:GW268R0.988
20:54164494:A:TW268R0.988
20:54171657:A:GW155R0.988
20:54171657:A:TW155R0.988
20:54158164:C:AR386S0.987
20:54158164:C:GR386S0.987
20:54171655:C:AW155C0.987
20:54171655:C:GW155C0.987
20:54157436:G:CC462W0.986
20:54165832:A:CS214R0.986
20:54165832:A:TS214R0.986
20:54169592:T:GS214R0.986
20:54157428:C:GR465P0.985
20:54159112:A:CS334R0.985

dbSNP variants (sampled 300 via entrez): RS1000010588 (20:54152489 G>A), RS1000127032 (20:54159103 C>A,T), RS1000176915 (20:54159667 G>C), RS1000190807 (20:54146530 C>T), RS1000293051 (20:54152717 GA>G), RS1000537278 (20:54174149 G>A), RS1000612850 (20:54163298 T>C), RS1000649174 (20:54153974 C>A), RS1000895799 (20:54163613 G>C), RS1001012457 (20:54164182 C>G,T), RS1001078060 (20:54174411 C>A,T), RS1001152932 (20:54158238 A>G), RS1001184296 (20:54158533 T>A,C), RS1001351315 (20:54146300 G>A,T), RS1001379856 (20:54163916 A>C)

Disease associations

OMIM: gene MIM:126065 | disease phenotypes: MIM:143880

GenCC curated gene-disease

DiseaseClassificationInheritance
hypercalcemia, infantile, 1StrongAutosomal recessive
autosomal recessive infantile hypercalcemiaSupportiveAutosomal recessive

Mondo (2): hypercalcemia, infantile, 1 (MONDO:0020739), (MONDO:0007749)

Orphanet (1): Autosomal recessive infantile hypercalcemia (Orphanet:300547)

HPO phenotypes

15 total (15 of 15 shown, HPO-id order):

HPOTerm
HP:0000007Autosomal recessive inheritance
HP:0000103Polyuria
HP:0000121Nephrocalcinosis
HP:0000787Nephrolithiasis
HP:0001252Hypotonia
HP:0001254Lethargy
HP:0001508Failure to thrive
HP:0001824Weight loss
HP:0001944Dehydration
HP:0002013Vomiting
HP:0002150Hypercalciuria
HP:0003072Hypercalcemia
HP:0003593Infantile onset
HP:0012408Medullary nephrocalcinosis
HP:0031817Decreased circulating parathyroid hormone level

GWAS associations

27 associations (top):

StudyTraitp-value
GCST001198_43Multiple sclerosis3.000000e-11
GCST001709_17Atopic dermatitis2.000000e-08
GCST002201_7Calcium levels9.000000e-12
GCST003262_352Post bronchodilator FEV13.000000e-06
GCST003386_1Colorectal cancer (oestrogen-progestogen hormone therapy interaction)5.000000e-09
GCST003879_1Serum parathyroid hormone levels2.000000e-10
GCST003879_2Serum parathyroid hormone levels2.000000e-72
GCST005366_4Vitamin D levels (dietary vitamin D intake interaction)1.000000e-14
GCST005367_6Vitamin D levels8.000000e-23
GCST005531_70Multiple sclerosis2.000000e-13
GCST005982_15Calcium levels1.000000e-09
GCST006491_19Circulating fibroblast growth factor 23 levels3.000000e-24
GCST007876_52Estimated glomerular filtration rate1.000000e-17
GCST007877_24Creatinine levels1.000000e-08
GCST008058_160Estimated glomerular filtration rate2.000000e-46
GCST008059_121Estimated glomerular filtration rate4.000000e-50
GCST008062_130Blood urea nitrogen levels6.000000e-08
GCST008369_19Plasma anti-thyroglobulin levels2.000000e-06
GCST008745_29Estimated glomerular filtration rate in non-diabetics1.000000e-14
GCST008747_121Estimated glomerular filtration rate3.000000e-25
GCST008747_92Estimated glomerular filtration rate1.000000e-36
GCST009597_52Multiple sclerosis2.000000e-19
GCST009597_92Multiple sclerosis2.000000e-06
GCST009598_18Kidney stones8.000000e-18
GCST009599_12Kidney stones1.000000e-11
GCST010219_21Attention deficit hyperactivity disorder (inattention symptoms)3.000000e-07
GCST90011900_10Serum alkaline phosphatase levels7.000000e-09

EFO canonical traits (5, from GWAS)

EFO IDTrait name
EFO:0004838calcium measurement
EFO:0004314forced expiratory volume
EFO:0003961hormone replacement therapy
EFO:0008539vitamin D dietary intake measurement
EFO:0004533alkaline phosphatase measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4521 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

4 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 119,592 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

MoleculeNamePhasePatents
CHEMBL157101KETOCONAZOLE475,361
CHEMBL846CALCITRIOL429,522
CHEMBL2105705LUNACALCIPOL273
CHEMBL389433LIAROZOLE214,636

PharmGKB: 1 entry (VIP=true, CPIC=false)

PharmGKB clinical annotations

5 annotations.

VariantTypeLevelDrugsPhenotypes
rs2248359Metabolism/PK3deferasiroxBeta-thalassemia and related diseases
rs2248359Toxicity3tenofovir disoproxil fumarateHIV infectious disease;Nephrotoxicity
rs2585428Metabolism/PK3telaprevirHepatitis C virus infection
rs2585428Metabolism/PK3deferasiroxBeta-thalassemia and related diseases
rs927650Metabolism/PK3deferasiroxBeta-thalassemia and related diseases

PharmGKB variants

6 variants.

VariantGenesLevelScore#Clin annotsDrugs
rs2585428CYP24A132.002deferasirox;telaprevir
rs2762939CYP24A10.000
rs3787554CYP24A10.000
rs4809957CYP24A10.000
rs2248359CYP24A132.252tenofovir disoproxil fumarate;deferasirox
rs927650CYP24A131.251deferasirox

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: enzyme — CYP24, CYP26 and CYP27 families

Most potent curated ligand interactions (3 total), top 3:

LigandActionAffinityParameter
CTA091Inhibition8.2pIC50
lunacalcipolInhibition7.6pIC50
compound 4d [PMID: 20655626]Inhibition4.79pIC50

Binding affinities (BindingDB)

6 measured of 6 human assays (6 total across all organisms); most potent 6 below. Values come from heterogeneous assays and are not directly comparable.

LigandMeasureValue
AB47KI21 nM
VIMIKI21 nM
24F2-1,25(OH)D3KI24 nM
TS17KI39 nM
CPA1KI42 nM
24COOH-25(OH)D3KI90 nM

ChEMBL bioactivities

117 potent at pChembl≥5 of 128 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChemblTypeValueUnitMolecule
8.64IC502.3nMLIAROZOLE
8.53EC502.96nMCHEMBL5182683
8.52EC503.02nMCALCITRIOL
8.25EC505.6nMCHEMBL5175578
8.19IC506.5nMCHEMBL389014
8.13IC507.4nMCHEMBL389014
8.13IC507.4nMCHEMBL255088
8.11Ki7.8nMCHEMBL3329769
8.01Ki9.7nMCHEMBL3329770
8.01IC509.7nMCHEMBL1627206
7.96Ki11nMCHEMBL3329774
7.89Ki13nMCHEMBL3329778
7.89IC5013nMCHEMBL1627206
7.85Ki14nMCHEMBL3344394
7.85Ki14nMCHEMBL3344395
7.82IC5015nMCHEMBL1170908
7.82IC5015.2nMCHEMBL1170908
7.82IC5015nMCHEMBL253613
7.82IC5015.1nMCHEMBL1170908
7.72Ki19nMCHEMBL3329767
7.69IC5020.5nMCHEMBL1627203
7.68Ki21nMCHEMBL3360784
7.62Ki24nMCHEMBL3329768
7.58Ki26nMCHEMBL3344392
7.57IC5027nMLUNACALCIPOL
7.57IC5027nMCHEMBL4797263
7.55Ki28nMCHEMBL1171494
7.55IC5028nMCHEMBL224719
7.55IC5028nMCHEMBL1627207
7.55IC5028nMCHEMBL389014
7.51Ki31nMCHEMBL3344393
7.48Ki33nMKETOCONAZOLE
7.46Ki35nMKETOCONAZOLE
7.44Ki36nMCHEMBL3329771
7.43Ki37nMCHEMBL3344396
7.43Ki37nMCHEMBL3344397
7.41Ki39nMCHEMBL3360783
7.38Ki42nMCHEMBL3329779
7.38Ki42nMCHEMBL3360785
7.36IC5044nMCHEMBL1627207
7.30IC5050nMCHEMBL1627203
7.12IC5075nMCHEMBL1627204
7.04Ki91nMCHEMBL3329772
6.96IC50110nMCHEMBL3329769
6.96IC50110nMCHEMBL4105510
6.92IC50120nMCHEMBL4080128
6.90IC50126nMKETOCONAZOLE
6.85IC50140nMCHEMBL3329770
6.82Ki150nMCHEMBL3329773
6.82IC50150nMCHEMBL4066700

PubChem BioAssay actives

124 with measured affinity, of 176 total; 50 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

CompoundAssayTypeValueUnit
6-[(3-chlorophenyl)-imidazol-1-ylmethyl]-1H-benzimidazole1160913: Inhibition of human MBP-tagged CYP24A1 expressed in Escherichia coli using 1,25(OH)2D3 substrate in presence of bovine adrenodoxin, adrenodoxin reductase and NADPH incubated at 37 degC for 25 mins by HPLC methodic500.0023uM
trans-(1R,3S,5Z)-5-[(E)-3-[3,5-bis(6-hydroxy-6-methylheptyl)phenyl]prop-2-enylidene]-4-methylidenecyclohexane-1,3-diol1852313: Induction of CYP24A1 (unknown orgin) transcriptional activity trasfected in human MCF7 cells incuabted for 48 hrs by luciferase reporter gene assayec500.0030uM
Calcitriol1852313: Induction of CYP24A1 (unknown orgin) transcriptional activity trasfected in human MCF7 cells incuabted for 48 hrs by luciferase reporter gene assayec500.0030uM
trans-(1R,3S,5Z)-5-[(E)-9-hydroxy-3-[3-(6-hydroxy-6-methylheptyl)phenyl]-9-methyldec-2-enylidene]-4-methylidenecyclohexane-1,3-diol1852313: Induction of CYP24A1 (unknown orgin) transcriptional activity trasfected in human MCF7 cells incuabted for 48 hrs by luciferase reporter gene assayec500.0056uM
trans-(1R,3S,5Z)-5-[(2E)-2-[(1R,3aS,7aR)-7a-methyl-1-[(2R)-4-(phenylsulfonimidoyl)butan-2-yl]-2,3,3a,5,6,7-hexahydro-1H-inden-4-ylidene]ethylidene]-4-methylidenecyclohexane-1,3-diol1160913: Inhibition of human MBP-tagged CYP24A1 expressed in Escherichia coli using 1,25(OH)2D3 substrate in presence of bovine adrenodoxin, adrenodoxin reductase and NADPH incubated at 37 degC for 25 mins by HPLC methodic500.0065uM
trans-(1R,3S,5Z)-5-[(2E)-2-[(7aS)-7a-methyl-1-[(2R)-4-(phenylsulfonimidoyl)butan-2-yl]-3a,5,6,7-tetrahydro-3H-inden-4-ylidene]ethylidene]-4-methylidenecyclohexane-1,3-diol311066: Inhibition of CYP24ic500.0074uM
4-[(E)-2-(3,5-dimethoxyphenyl)ethenyl]-N-(2-imidazol-1-yl-2-phenylethyl)benzamide1160913: Inhibition of human MBP-tagged CYP24A1 expressed in Escherichia coli using 1,25(OH)2D3 substrate in presence of bovine adrenodoxin, adrenodoxin reductase and NADPH incubated at 37 degC for 25 mins by HPLC methodki0.0078uM
trans-(1R,3R)-5-[(2E)-2-[(1R,3aS,7aR)-7a-methyl-1-[(2R)-4-(phenylsulfonimidoyl)butan-2-yl]-2,3,3a,5,6,7-hexahydro-1H-inden-4-ylidene]ethylidene]cyclohexane-1,3-diol282480: Inhibition of human CYP24 hydroxylase expressed in V79 cellsic500.0097uM
N-(2-imidazol-1-yl-2-phenylethyl)-4-[(E)-2-(3,4,5-trimethoxyphenyl)ethenyl]benzamide1160913: Inhibition of human MBP-tagged CYP24A1 expressed in Escherichia coli using 1,25(OH)2D3 substrate in presence of bovine adrenodoxin, adrenodoxin reductase and NADPH incubated at 37 degC for 25 mins by HPLC methodki0.0097uM
[1-[4-[(E)-2-(3,5-dimethoxyphenyl)ethenyl]phenyl]-4,4-dimethylpentan-3-yl] imidazole-1-carboxylate1160913: Inhibition of human MBP-tagged CYP24A1 expressed in Escherichia coli using 1,25(OH)2D3 substrate in presence of bovine adrenodoxin, adrenodoxin reductase and NADPH incubated at 37 degC for 25 mins by HPLC methodki0.0110uM
(Z)-2-imidazol-1-yl-4,4-dimethyl-1-[4-[(E)-2-phenylethenyl]phenyl]pent-1-en-3-one1160913: Inhibition of human MBP-tagged CYP24A1 expressed in Escherichia coli using 1,25(OH)2D3 substrate in presence of bovine adrenodoxin, adrenodoxin reductase and NADPH incubated at 37 degC for 25 mins by HPLC methodki0.0130uM
1-(4-imidazol-1-ylbutyl)-4-[(E)-2-phenylethenyl]indole1165071: Inhibition of N-terminally MBP-fused human CYP24A1 by cell-free assayki0.0140uM
4-[(E)-2-(3,5-dimethoxyphenyl)ethenyl]-1-(4-imidazol-1-ylbutyl)indole1165071: Inhibition of N-terminally MBP-fused human CYP24A1 by cell-free assayki0.0140uM
4-(4-chlorophenyl)-N-[(2R)-2-imidazol-1-yl-2-phenylethyl]benzamide1160913: Inhibition of human MBP-tagged CYP24A1 expressed in Escherichia coli using 1,25(OH)2D3 substrate in presence of bovine adrenodoxin, adrenodoxin reductase and NADPH incubated at 37 degC for 25 mins by HPLC methodic500.0150uM
4-(4-chlorophenyl)-N-(2-imidazol-1-yl-2-phenylethyl)benzamide311064: Inhibition of CYP24 in human keratinocytesic500.0150uM
4-[(E)-2-(4-fluorophenyl)ethenyl]-N-(2-imidazol-1-yl-2-phenylethyl)benzamide1160913: Inhibition of human MBP-tagged CYP24A1 expressed in Escherichia coli using 1,25(OH)2D3 substrate in presence of bovine adrenodoxin, adrenodoxin reductase and NADPH incubated at 37 degC for 25 mins by HPLC methodki0.0190uM
trans-(1R,3S,5Z)-5-[(2E)-2-[(1R,3aS,7aR)-7a-methyl-1-[(2R)-1-[1-(phenylsulfonimidoyl)cyclopropyl]propan-2-yl]-2,3,3a,5,6,7-hexahydro-1H-inden-4-ylidene]ethylidene]-4-methylidenecyclohexane-1,3-diol282480: Inhibition of human CYP24 hydroxylase expressed in V79 cellsic500.0205uM
trans-(1R,3R)-5-[(2E)-2-[(1R,3aS,7aR)-1-[(2S)-1-imidazol-1-ylpropan-2-yl]-7a-methyl-2,3,3a,5,6,7-hexahydro-1H-inden-4-ylidene]ethylidene]-2-methylidenecyclohexane-1,3-diol1160913: Inhibition of human MBP-tagged CYP24A1 expressed in Escherichia coli using 1,25(OH)2D3 substrate in presence of bovine adrenodoxin, adrenodoxin reductase and NADPH incubated at 37 degC for 25 mins by HPLC methodki0.0210uM
[(2R)-2-[(4E,7aR)-4-[(2Z)-2-[(5R)-5-hydroxy-2-methylidenecyclohexylidene]ethylidene]-7a-methyl-2,3,3a,5,6,7-hexahydro-1H-inden-1-yl]propyl] 2-bromoacetate1799837: CYP24A1Inhibition Assay from Article 10.1021/bi101488p: “Screening of selective inhibitors of 1a,25-dihydroxyvitamin D3 24-hydroxylase using recombinant human enzyme expressed in Escherichia coli.”ki0.0210uM
cis-(1S,3R)-5-[(2E)-2-[(7aR)-1-[(2R)-1-imidazol-1-ylpropan-2-yl]-7a-methyl-2,3,3a,5,6,7-hexahydro-1H-inden-4-ylidene]ethylidene]-2-methylidenecyclohexane-1,3-diol1799837: CYP24A1Inhibition Assay from Article 10.1021/bi101488p: “Screening of selective inhibitors of 1a,25-dihydroxyvitamin D3 24-hydroxylase using recombinant human enzyme expressed in Escherichia coli.”ki0.0210uM
N-(2-imidazol-1-yl-2-phenylethyl)-4-[(E)-2-(4-methoxyphenyl)ethenyl]benzamide1160913: Inhibition of human MBP-tagged CYP24A1 expressed in Escherichia coli using 1,25(OH)2D3 substrate in presence of bovine adrenodoxin, adrenodoxin reductase and NADPH incubated at 37 degC for 25 mins by HPLC methodki0.0240uM
1-[4-[4-[[(2R,4S)-2-(2,4-dichlorophenyl)-2-(imidazol-1-ylmethyl)-1,3-dioxolan-4-yl]methoxy]phenyl]piperazin-1-yl]ethanone1799837: CYP24A1Inhibition Assay from Article 10.1021/bi101488p: “Screening of selective inhibitors of 1a,25-dihydroxyvitamin D3 24-hydroxylase using recombinant human enzyme expressed in Escherichia coli.”ki0.0240uM
1-(3-imidazol-1-ylpropyl)-4-[(E)-2-phenylethenyl]indole1165071: Inhibition of N-terminally MBP-fused human CYP24A1 by cell-free assayki0.0260uM
trans-(1R,3S,5Z)-5-[(2E)-2-[(3aS,7aS)-1-[(E,2R)-5-tert-butylsulfonylpent-4-en-2-yl]-7a-methyl-3a,5,6,7-tetrahydro-3H-inden-4-ylidene]ethylidene]-4-methylidenecyclohexane-1,3-diol1160913: Inhibition of human MBP-tagged CYP24A1 expressed in Escherichia coli using 1,25(OH)2D3 substrate in presence of bovine adrenodoxin, adrenodoxin reductase and NADPH incubated at 37 degC for 25 mins by HPLC methodic500.0270uM
trans-(1R,3S,5Z)-5-[(2E)-2-[(3aS,7aS)-1-[(E,2R)-4-tert-butylsulfonylbut-3-en-2-yl]-7a-methyl-3a,5,6,7-tetrahydro-3H-inden-4-ylidene]ethylidene]-4-methylidenecyclohexane-1,3-diol1704649: Inhibition of CYP24A1 (unknown origin) expressed in Chinese hamster V79 cells using [3H-1beta]-1alpha,25(OH)2D3 as substrate preincubated for 30 mins followed by substrate addition and measured after 2 hrs by scintillation counting methodic500.0270uM
trans-(1R,3S,5Z)-5-[(2E)-2-[(1R,3aS,7aR)-1-[(2R)-4-[(4-fluorophenyl)sulfonimidoyl]butan-2-yl]-7a-methyl-2,3,3a,5,6,7-hexahydro-1H-inden-4-ylidene]ethylidene]-4-methylidenecyclohexane-1,3-diol282480: Inhibition of human CYP24 hydroxylase expressed in V79 cellsic500.0280uM
trans-(1R,3S,5Z)-5-[(2E)-2-[(1R,3aS,7aR)-1-[(2R)-4-(benzenesulfonyl)butan-2-yl]-7a-methyl-2,3,3a,5,6,7-hexahydro-1H-inden-4-ylidene]ethylidene]-4-methylidenecyclohexane-1,3-diol1704644: Inhibition of human CYP24A1 expressed in Chinese hamster V79 cells using [3H-1beta]-1alpha,25(OH)2D3 as substrate preincubated for 10 mins followed by substrate addition and measured after 2 hrs by scintillation counting methodic500.0280uM
N-(2-imidazol-1-yl-2-phenylethyl)-4-[(E)-2-phenylethenyl]benzamide1160913: Inhibition of human MBP-tagged CYP24A1 expressed in Escherichia coli using 1,25(OH)2D3 substrate in presence of bovine adrenodoxin, adrenodoxin reductase and NADPH incubated at 37 degC for 25 mins by HPLC methodki0.0280uM
4-[(E)-2-(3,5-dimethoxyphenyl)ethenyl]-1-(3-imidazol-1-ylpropyl)indole1165071: Inhibition of N-terminally MBP-fused human CYP24A1 by cell-free assayki0.0310uM
1-[4-[4-[[2-(2,4-dichlorophenyl)-2-(imidazol-1-ylmethyl)-1,3-dioxolan-4-yl]methoxy]phenyl]piperazin-1-yl]ethanone1160913: Inhibition of human MBP-tagged CYP24A1 expressed in Escherichia coli using 1,25(OH)2D3 substrate in presence of bovine adrenodoxin, adrenodoxin reductase and NADPH incubated at 37 degC for 25 mins by HPLC methodki0.0330uM
4-[2-(4-fluorophenyl)ethyl]-N-(2-imidazol-1-yl-2-phenylethyl)benzamide1160913: Inhibition of human MBP-tagged CYP24A1 expressed in Escherichia coli using 1,25(OH)2D3 substrate in presence of bovine adrenodoxin, adrenodoxin reductase and NADPH incubated at 37 degC for 25 mins by HPLC methodki0.0360uM
1-(3-imidazol-1-ylpropyl)-5-[(E)-2-phenylethenyl]indole1165071: Inhibition of N-terminally MBP-fused human CYP24A1 by cell-free assayki0.0370uM
1-(4-imidazol-1-ylbutyl)-5-[(E)-2-phenylethenyl]indole1165071: Inhibition of N-terminally MBP-fused human CYP24A1 by cell-free assayki0.0370uM
[(4R)-4-[(1R,3aS,4E,7aR)-4-[(2Z)-2-[(5S)-5-hydroxy-2-methylidenecyclohexylidene]ethylidene]-7a-methyl-2,3,3a,5,6,7-hexahydro-1H-inden-1-yl]pentyl] 4-methylbenzenesulfonate1160913: Inhibition of human MBP-tagged CYP24A1 expressed in Escherichia coli using 1,25(OH)2D3 substrate in presence of bovine adrenodoxin, adrenodoxin reductase and NADPH incubated at 37 degC for 25 mins by HPLC methodki0.0390uM
[(4S)-4-[(4E,7aR)-4-[(2Z)-2-[(5R)-5-hydroxy-2-methylidenecyclohexylidene]ethylidene]-7a-methyl-2,3,3a,5,6,7-hexahydro-1H-inden-1-yl]pentyl] 4-methylbenzenesulfonate1799837: CYP24A1Inhibition Assay from Article 10.1021/bi101488p: “Screening of selective inhibitors of 1a,25-dihydroxyvitamin D3 24-hydroxylase using recombinant human enzyme expressed in Escherichia coli.”ki0.0390uM
2-imidazol-1-yl-4,4-dimethyl-1-[4-(2-phenylethyl)phenyl]pentan-3-one1160913: Inhibition of human MBP-tagged CYP24A1 expressed in Escherichia coli using 1,25(OH)2D3 substrate in presence of bovine adrenodoxin, adrenodoxin reductase and NADPH incubated at 37 degC for 25 mins by HPLC methodki0.0420uM
cis-(1R,3S)-5-[(2E)-2-[(7aR)-1-[(2S)-5-(cyclopropylamino)pentan-2-yl]-7a-methyl-2,3,3a,5,6,7-hexahydro-1H-inden-4-ylidene]ethylidene]-2-methylidenecyclohexane-1,3-diol1799837: CYP24A1Inhibition Assay from Article 10.1021/bi101488p: “Screening of selective inhibitors of 1a,25-dihydroxyvitamin D3 24-hydroxylase using recombinant human enzyme expressed in Escherichia coli.”ki0.0420uM
trans-(1R,3R)-5-[(2E)-2-[(1R,3aS,7aR)-1-[(2R)-5-(cyclopropylamino)pentan-2-yl]-7a-methyl-2,3,3a,5,6,7-hexahydro-1H-inden-4-ylidene]ethylidene]-2-methylidenecyclohexane-1,3-diol1160913: Inhibition of human MBP-tagged CYP24A1 expressed in Escherichia coli using 1,25(OH)2D3 substrate in presence of bovine adrenodoxin, adrenodoxin reductase and NADPH incubated at 37 degC for 25 mins by HPLC methodki0.0420uM
(1S,3Z)-3-[(2E)-2-[(1R,3aS,7aR)-7a-methyl-1-[(2R)-4-(phenylsulfonimidoyl)butan-2-yl]-2,3,3a,5,6,7-hexahydro-1H-inden-4-ylidene]ethylidene]-4-methylidenecyclohexan-1-ol282480: Inhibition of human CYP24 hydroxylase expressed in V79 cellsic500.0750uM
(4S)-4-[(4E,7aR)-4-[(2Z)-2-[(5R)-5-hydroxy-2-methylidenecyclohexylidene]ethylidene]-7a-methyl-2,3,3a,5,6,7-hexahydro-1H-inden-1-yl]pentanoic acid1799837: CYP24A1Inhibition Assay from Article 10.1021/bi101488p: “Screening of selective inhibitors of 1a,25-dihydroxyvitamin D3 24-hydroxylase using recombinant human enzyme expressed in Escherichia coli.”ki0.0900uM
N-(2-imidazol-1-yl-2-phenylethyl)-4-(phenylsulfamoyl)benzamide1160913: Inhibition of human MBP-tagged CYP24A1 expressed in Escherichia coli using 1,25(OH)2D3 substrate in presence of bovine adrenodoxin, adrenodoxin reductase and NADPH incubated at 37 degC for 25 mins by HPLC methodki0.0910uM
N-[2-imidazol-1-yl-2-(4-methoxyphenyl)ethyl]-4-[(E)-2-phenylethenyl]benzamide1486357: Inhibition of MBP-tagged human CYP24A1 expressed Escherichia coli BL21-Gold(DE3) incubated for 25 mins in presence of Adx, AdR 1,25(OH)2D3 and NADPH by HPLC methodic500.1100uM
N-[2-(4-chlorophenyl)-2-imidazol-1-ylethyl]-4-[(E)-2-(3,4-dimethoxyphenyl)ethenyl]benzamide1486357: Inhibition of MBP-tagged human CYP24A1 expressed Escherichia coli BL21-Gold(DE3) incubated for 25 mins in presence of Adx, AdR 1,25(OH)2D3 and NADPH by HPLC methodic500.1200uM
1-[4-[(E)-2-(3,5-dimethoxyphenyl)ethenyl]phenyl]-4,4-dimethylpentan-3-one1160913: Inhibition of human MBP-tagged CYP24A1 expressed in Escherichia coli using 1,25(OH)2D3 substrate in presence of bovine adrenodoxin, adrenodoxin reductase and NADPH incubated at 37 degC for 25 mins by HPLC methodki0.1500uM
N-[2-imidazol-1-yl-2-[4-(trifluoromethyl)phenyl]ethyl]-3-[(E)-2-phenylethenyl]benzamide1486357: Inhibition of MBP-tagged human CYP24A1 expressed Escherichia coli BL21-Gold(DE3) incubated for 25 mins in presence of Adx, AdR 1,25(OH)2D3 and NADPH by HPLC methodic500.1500uM
N-[2-(4-chlorophenyl)-2-imidazol-1-ylethyl]-3-[(E)-2-phenylethenyl]benzamide1486357: Inhibition of MBP-tagged human CYP24A1 expressed Escherichia coli BL21-Gold(DE3) incubated for 25 mins in presence of Adx, AdR 1,25(OH)2D3 and NADPH by HPLC methodic500.1600uM
N-[2-imidazol-1-yl-2-[4-(trifluoromethyl)phenyl]ethyl]-4-[(E)-2-phenylethenyl]benzamide1486357: Inhibition of MBP-tagged human CYP24A1 expressed Escherichia coli BL21-Gold(DE3) incubated for 25 mins in presence of Adx, AdR 1,25(OH)2D3 and NADPH by HPLC methodic500.1800uM
N-(2-imidazol-1-yl-2-phenylethyl)-3-[(E)-2-phenylethenyl]benzamide1486357: Inhibition of MBP-tagged human CYP24A1 expressed Escherichia coli BL21-Gold(DE3) incubated for 25 mins in presence of Adx, AdR 1,25(OH)2D3 and NADPH by HPLC methodic500.1900uM
[1-[4-[(E)-2-(3,5-dimethoxyphenyl)ethenyl]phenyl]-4,4-dimethylpentan-3-yl] 4-methylbenzenesulfonate1160913: Inhibition of human MBP-tagged CYP24A1 expressed in Escherichia coli using 1,25(OH)2D3 substrate in presence of bovine adrenodoxin, adrenodoxin reductase and NADPH incubated at 37 degC for 25 mins by HPLC methodki0.2100uM
N-[2-(4-chlorophenyl)-2-imidazol-1-ylethyl]-4-[(E)-2-phenylethenyl]benzamide1486357: Inhibition of MBP-tagged human CYP24A1 expressed Escherichia coli BL21-Gold(DE3) incubated for 25 mins in presence of Adx, AdR 1,25(OH)2D3 and NADPH by HPLC methodic500.2100uM

CTD chemical–gene interactions

133 total (human), top 30 by PubMed support.

ChemicalActions (top 5)PubMed papers
Calcitriolincreases activity, decreases metabolic processing, increases abundance, decreases response to substance, affects binding (+6 more)37
Benzo(a)pyreneincreases degradation, increases methylation, affects binding, decreases reaction, increases reaction (+2 more)8
Lithocholic Acidincreases expression, increases reaction, decreases reaction, affects binding, increases activity6
sodium arseniteincreases expression, affects methylation, decreases expression, affects cotreatment, increases abundance5
Estradiolaffects cotreatment, decreases expression, increases expression5
Valproic Acidincreases reaction, affects cotreatment, increases expression5
lithocholic acid acetatedecreases reaction, increases expression, affects binding, increases activity, increases reaction (+1 more)4
Calcifediolincreases expression, decreases reaction4
Tetrachlorodibenzodioxinincreases reaction, increases expression4
Cyclosporinedecreases expression, increases expression4
trichostatin Aaffects expression, decreases reaction, increases expression, increases reaction3
Ketoconazoleincreases expression, increases reaction, decreases activity, decreases expression, decreases metabolic processing3
arseniteincreases methylation2
perfluorooctanoic acidincreases expression, decreases reaction2
seocalcitolincreases expression2
paricalcitoldecreases expression, increases activity, affects cotreatment, increases expression2
U 0126increases expression, affects binding, increases reaction, decreases reaction2
monomethylarsonous aciddecreases expression, increases methylation2
Arsenic Trioxidedecreases reaction, increases expression, decreases expression, increases activity2
Leflunomideincreases expression2
Arsenicincreases abundance, increases expression, affects cotreatment, decreases expression2
Cholecalciferolincreases expression, decreases reaction2
Lipopolysaccharidesaffects response to substance, increases expression, affects expression2
Quercetindecreases expression, increases expression, increases reaction2
Rifampinincreases reaction, affects binding, increases activity, increases expression2
Dihydrotestosteronedecreases reaction, increases expression2
Tobacco Smoke Pollutiondecreases expression, increases expression2
Tretinoindecreases reaction, increases expression2
Vitamin Ddecreases reaction, increases expression, affects binding, increases reaction2
Cadmium Chloridedecreases expression, increases expression2

ChEMBL screening assays

35 unique, capped per target: 28 binding, 7 admet

Representative assays (with source publication via chembl_document):

Assay IDTypeDescriptionSource paper
CHEMBL1055571BindingBinding affinity to human CYP24A1 expressed in Escherichia coli assessed as catalytic efficiency after 60 mins relative 1-alpha,25-dihydroxyvitamin D3Synthesis of 2alpha-propoxy-1alpha,25-dihydroxyvitamin D3 and comparison of its metabolism by human CYP24A1 and rat CYP24A1. — Bioorg Med Chem
CHEMBL1177226ADMETInhibition of CYP24A1Synthesis and CYP24A1 inhibitory activity of N-(2-(1H-imidazol-1-yl)-2-phenylethyl)arylamides. — Bioorg Med Chem

Cellosaurus cell lines

1 cell lines: 1 cancer cell line

First 10 cell lines (id-ordered, not curated):

CellosaurusNameCategorySex
CVCL_B2MIAbcam A-549 CYP24A1 KOCancer cell lineMale

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.