Affinage

CYP3A5

Cytochrome P450 3A5 · UniProt P20815

Length
502 aa
Mass
57.1 kDa
Annotated
2026-06-09
100 papers in source corpus 26 papers cited in narrative 26 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 7/7 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

CYP3A5 is a cytochrome P450 monooxygenase that hydroxylates and demethylates a broad range of drugs and steroids, with catalytic efficiencies and positional selectivities that distinguish it from the closely related CYP3A4 (PMID:15951320, PMID:16501005, PMID:31408697). Its expression in the population is governed primarily by the intronic CYP3A5*3 splice-site variant (g.6986G>A), which introduces aberrant exon 3B into the transcript; the resulting premature termination codons trigger UPF1-dependent nonsense-mediated decay, abolishing functional protein in *3/*3 individuals while *1 carriers retain expression (PMID:11740341, PMID:15955870). In expressors, CYP3A5 can constitute more than half of total hepatic CYP3A and accounts for a substantial fraction of CYP3A-mediated drug metabolism (PMID:12065767). Functionally, CYP3A5 metabolizes tacrolimus, cyclosporine-derived metabolites, and vincristine with markedly higher intrinsic clearance than CYP3A4 (PMID:15951320, PMID:16501005, PMID:17272675, PMID:23354298), produces distinct metabolite patterns for substrates such as quetiapine, vinorelbine, and eplerenone (PMID:19022943, PMID:23780963, PMID:31408697), and is relatively resistant to the mechanism-based inhibition that verapamil exerts on CYP3A4 (PMID:15689501). Its enlarged, open active site and distinct helix F-F' geometry provide a structural basis for these isoform-specific catalytic behaviors (PMID:30926609). Beyond constitutive hepatic and extrahepatic expression, CYP3A5 transcription is cooperatively driven by NF-Y and Sp1/Sp3 at the proximal promoter (PMID:11485307), by HNF-4α and PXR:RXRα in a sex-dependent manner (PMID:22994453), and by a shared distal enhancer and an antisense lncRNA (AC069294.1) (PMID:36045613, PMID:34320606). CYP3A5 also participates in cell-autonomous roles: it bioactivates compounds such as tetrandrine and lapatinib to reactive intermediates (PMID:26302866, PMID:27450182), confers PXR-driven drug resistance in pancreatic tumors by inactivating chemotherapeutics (PMID:26855150), and in prostate cells facilitates androgen receptor nuclear translocation while being itself androgen-inducible through a promoter ARE (PMID:17116727, PMID:25586052).

Mechanistic history

Synthesis pass · year-by-year structured walk · 13 steps
  1. 2001 High

    Established the genetic basis of the CYP3A5 expression polymorphism, answering why only a subset of individuals express functional protein.

    Evidence High-density SNP mapping correlated with protein expression in 183 liver samples

    PMID:11740341

    Open questions at the time
    • Did not establish the molecular fate of the aberrant transcript
    • Did not address regulation in expressors
  2. 2001 High

    Identified the core transcription factors driving CYP3A5 basal promoter activity, defining how the gene is expressed when permitted.

    Evidence Promoter-luciferase truncations, EMSA, and site-directed mutagenesis in HepG2 cells

    PMID:11485307

    Open questions at the time
    • Did not address inducible or nuclear-receptor-mediated regulation
    • No distal regulatory elements examined
  3. 2002 High

    Quantified the contribution of CYP3A5 to hepatic CYP3A activity, showing it is a major determinant of midazolam hydroxylation variability in expressors.

    Evidence Genotype-stratified protein/mRNA quantification and microsomal activity assays in liver and jejunum

    PMID:12065767

    Open questions at the time
    • Did not explain why *3 transcripts are absent at the protein level
    • Substrate range beyond midazolam not defined
  4. 2005 High

    Resolved the post-transcriptional mechanism by which CYP3A5*3 abolishes expression, showing aberrant exon 3B transcripts are eliminated by NMD.

    Evidence Minigene transfection, UPF1 siRNA, cycloheximide, and PTC mutagenesis in MCF7/HepG2 cells

    PMID:15955870

    Open questions at the time
    • Did not quantify residual leaky expression
    • Inducibility in *3/*3 carriers shown negative but mechanism of non-response not dissected
  5. 2005 High

    Demonstrated CYP3A5 resistance to mechanism-based inhibition, distinguishing its inactivation behavior from CYP3A4.

    Evidence Recombinant enzyme assays, MIC spectrophotometry, and time-dependent inhibition kinetics with verapamil metabolites

    PMID:15689501

    Open questions at the time
    • Structural basis of differential MIC formation not resolved at this stage
    • Limited to verapamil-class inhibitors
  6. 2006 High

    Characterized CYP3A5 as a high-efficiency tacrolimus-metabolizing enzyme in liver and kidney, explaining genotype-dependent immunosuppressant clearance.

    Evidence Recombinant enzyme kinetics and genotyped liver/kidney microsomes with LC-MS/MS metabolite quantification

    PMID:15951320 PMID:16501005

    Open questions at the time
    • In vivo clinical dosing consequences not addressed mechanistically here
    • Structural determinant of efficiency unknown
  7. 2007 High

    Showed CYP3A5 is the dominant catalyst of vincristine metabolism in expressers, extending its substrate scope to anticancer drugs.

    Evidence cDNA-expressed enzyme kinetics, genotyped microsomes, and protein-correlation regression

    PMID:17272675

    Open questions at the time
    • Clinical neurotoxicity link not established here
    • Single-lab dataset
  8. 2013 Medium

    Revealed sex-dependent transcriptional control of CYP3A5 via differential nuclear-receptor activation, explaining female-biased expression.

    Evidence Sex-stratified primary hepatocytes, nuclear translocation, EMSA, HNF-4α siRNA, and reporter assays

    PMID:22994453

    Open questions at the time
    • Hormonal upstream signals not fully defined
    • Single lab; in vivo relevance not tested
  9. 2013 High

    Extended CYP3A5 metabolism to cyclosporine secondary metabolites and intrarenal disposition, with in vivo genotype-dependent PK consequences.

    Evidence Controlled human PK study with genotype stratification plus recombinant enzyme incubations

    PMID:23354298

    Open questions at the time
    • Clinical nephrotoxicity link not mechanistically closed
    • Tissue-specific metabolite distribution not mapped
  10. 2016 High

    Defined a cell-autonomous oncologic role for CYP3A5 as a tumor drug-detoxification enzyme driving resistance, with HNF4A controlling basal and PXR controlling induced expression.

    Evidence Patient-derived pancreatic tumor models, shRNA knockdown, pharmacological inhibition, and transcription factor dissection

    PMID:26855150

    Open questions at the time
    • Generality across tumor types not established
    • Direct PXR binding sites on the CYP3A5 locus not mapped here
  11. 2015 Medium

    Implicated CYP3A5 in androgen receptor signaling, showing it promotes AR nuclear translocation and prostate cancer cell growth.

    Evidence siRNA, azamulin inhibition, rifampicin induction, cell fractionation, and AR target gene readouts in prostate cancer lines

    PMID:25586052

    Open questions at the time
    • Whether the effect requires catalytic activity vs a non-catalytic role is unresolved
    • Direct AR-CYP3A5 physical interaction not demonstrated
  12. 2019 High

    Provided the structural explanation for CYP3A5's distinct substrate handling via crystallographic comparison with CYP3A4.

    Evidence 2.20 Å X-ray structure of substrate-free CYP3A5 and comparison with CYP3A5-ritonavir and CYP3A4 structures

    PMID:30926609

    Open questions at the time
    • Substrate-bound complexes for clinically relevant drugs not solved
    • Dynamics linking structure to catalytic efficiency not directly measured
  13. 2022 High

    Identified distal cis-regulatory inputs (a shared enhancer and an antisense lncRNA) that fine-tune CYP3A5 expression beyond the proximal promoter.

    Evidence 4C, CRISPR enhancer deletion, reporter assays, lncRNA knockdown/overexpression, and liver eQTL correlation

    PMID:34320606 PMID:36045613

    Open questions at the time
    • Mechanism of lncRNA-mediated repression not resolved
    • Interaction of distal enhancer with the core promoter factors not integrated

Open questions

Synthesis pass · forward-looking unresolved questions
  • How tissue-specific extrahepatic expression (lung, blood, skin, kidney, fetal liver) and the catalytic versus non-catalytic roles of CYP3A5 in AR signaling integrate into a unified physiological function remains unresolved.
  • No single model links drug metabolism, AR translocation, and tumor resistance
  • Endogenous physiological substrate(s) not definitively established

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0016491 oxidoreductase activity 6 GO:0016787 hydrolase activity 2
Localization
GO:0005783 endoplasmic reticulum 2
Pathway
R-HSA-9748784 Drug ADME 4 R-HSA-74160 Gene expression (Transcription) 3 R-HSA-1430728 Metabolism 2
Partners
ARCYB5AHNF4APORPXRRXRA

Evidence

Reading pass · 26 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2001 A SNP within intron 3 (g.6986G>A, CYP3A5*3) is the primary genetic cause of the CYP3A5 protein polymorphism; the *3 allele leads to improper mRNA splicing and consequent loss of CYP3A5 protein expression, while the *1 allele permits normal splicing and protein expression. High-density SNP mapping of CYP3A5 variants in 183 Caucasian liver samples correlated with CYP3A5 protein expression; ethnic allele frequency analysis Pharmacogenetics High 11740341
2002 CYP3A5 protein contributes substantially (~31%) to the variability in hepatic midazolam 1'-hydroxylation activity; in livers carrying at least one CYP3A5*1 allele, CYP3A5 represented >50% of total CYP3A content, and improperly spliced mRNA (SV1-CYP3A5) was found only in tissues carrying a CYP3A5*3 allele. Quantitative protein and mRNA analysis of a panel of human liver and jejunal samples with genotype stratification; midazolam hydroxylation activity assays in liver microsomes Molecular pharmacology High 12065767
2005 CYP3A5 mRNA splice variants containing exon 3B (arising from the CYP3A5*3 allele) are degraded by nonsense-mediated mRNA decay (NMD) due to premature termination codons in exon 3B; cycloheximide (ribosome inhibitor) and UPF1 siRNA both reduced decay of these splice variants, confirming NMD involvement. Barbiturate or steroid induction did not switch on CYP3A5 phenotypic expression in *3/*3 carriers. CYP3A5 minigene transfection in MCF7 cells; endogenous gene in HepG2 cells; cycloheximide treatment; UPF1 siRNA knockdown; PTC mutagenesis of exon 3B Molecular pharmacology High 15955870
2006 CYP3A5 metabolizes tacrolimus with a catalytic efficiency (Vmax/Km) approximately 64% higher than CYP3A4 for 13-O-demethyltacrolimus formation; CYP3A5 contributes 1.5–40% (median 18.8%) of total hepatic 13-O-demethylation of tacrolimus, and mean in vivo hepatic clearance is approximately 2.4-fold higher in CYP3A5 expressors versus non-expressors. In vitro kinetics with cDNA-expressed CYP3A4, CYP3A5, and CYP3A7; human liver microsomes stratified by CYP3A5 genotype; LC-MS/MS metabolite quantification; parallel-tube liver model scaling Clinical chemistry High 15951320 16501005
2006 Recombinant CYP3A5 generates tacrolimus metabolites 13-O-desmethyl tacrolimus (major), 15-O-desmethyl tacrolimus, 31-O-desmethyl tacrolimus, and 12-hydroxy tacrolimus with an intrinsic clearance twice that of CYP3A4; formation of 13-DMT, 31-DMT, and 12-HT was ≥1.7-fold higher in CYP3A5*1/*3 microsomes than in *3/*3 microsomes. CYP3A5 also contributes substantially to renal tacrolimus metabolism (13-DMT formation 13.5-fold higher in *1/*3 kidney microsomes). In vitro enzyme kinetics with heterologously expressed CYP3A4 and CYP3A5; genotyped human liver and kidney microsomes; metabolite identification and quantification Drug metabolism and disposition High 16501005
2007 CYP3A5 preferentially metabolizes vincristine to a secondary amine metabolite (M1) with 9- to 14-fold higher intrinsic clearance than CYP3A4 using cDNA-expressed enzymes; in CYP3A5 high-expressers, CYP3A5 accounts for 54–95% of total M1 formation activity, and the rate of M1 formation correlates tightly with CYP3A5 protein content (r²=0.95). Estimated hepatic clearance is ~5-fold higher in CYP3A5 high-expressers. cDNA-expressed enzyme kinetics; genotyped human liver microsome bank; Western blot protein quantification; selective chemical inhibition; linear regression analysis The Journal of pharmacology and experimental therapeutics High 17272675
2005 Verapamil and its metabolite N-desalkylverapamil (D617) have little inhibitory effect on CYP3A5 and do not form a metabolic-intermediate complex (MIC) with CYP3A5, in contrast to their potent mechanism-based inhibition of CYP3A4. Norverapamil causes only modest time-dependent inhibition of CYP3A5 (30% at 50 µM) versus 80% for CYP3A4, with inactivation efficiency ~45-fold lower for CYP3A5. Human liver microsomes expressing CYP3A5 are correspondingly less inhibited by verapamil. cDNA-expressed CYP3A4 and CYP3A5 enzyme assays; dual-beam spectrophotometry for MIC detection; time-dependent inhibition kinetics (kinact, KI determination); genotyped human liver microsomes Drug metabolism and disposition High 15689501
2008 CYP3A5 metabolizes quetiapine with an intrinsic clearance <35% of CYP3A4; CYP3A5 produces a different metabolite pattern (higher proportion of O-desalkylquetiapine relative to CYP3A4); cytochrome b5 co-expression increases CYP3A4 CL_int ~3-fold but has no effect on CYP3A5 CL_int, revealing a distinct interaction of CYP3A5 with cytochrome b5. Substrate depletion kinetics in insect cell microsomes expressing CYP3A4 or CYP3A5 ± cytochrome b5; metabolite profiling Drug metabolism and disposition Medium 19022943
2013 CYP3A5 contributes to the formation of secondary cyclosporine A metabolites AM19 and AM1c9 (from AM1 and AM1c precursors); CYP3A5 expressors have ~47–51% higher AUC for AM19 and AM1c9 versus non-expressors in vivo, and ~20% lower apparent urinary CsA clearance, indicating CYP3A5-dependent intrarenal CsA metabolism. Oral CsA administration to 24 healthy volunteers stratified by CYP3A5 genotype; whole blood/urine metabolite measurement by LC-MS; in vitro incubations of CsA metabolites with recombinant CYP3A4 and CYP3A5 Transplantation High 23354298
2016 CYP3A5 mediates intrinsic and acquired drug resistance in pancreatic ductal adenocarcinoma by metabolically inactivating tyrosine kinase inhibitors and paclitaxel; CYP3A5 basal expression is controlled by HNF4A, while drug-induced upregulation is mediated by nuclear receptor NR1I2 (PXR); shRNA or pharmacological CYP3A5 inhibition re-sensitizes resistant tumor cells to these drugs. Patient-derived tumor cell models; shRNA knockdown; pharmacological inhibition; mechanistic dissection of HNF4A and NR1I2 regulation; drug sensitivity assays Nature medicine High 26855150
2001 Transcription of the CYP3A5 gene is cooperatively regulated by NF-Y (binding CCAAT box at -78/-68) and Sp1/Sp3 (binding the basic transcription element BTE at -67/-46) in HepG2 cells; mutation of either element alone decreases transcriptional activity to 10–21% of wild-type, while mutation of both reduces it to 4%. 5'-truncated promoter-luciferase chimeric gene transfection in HepG2 cells; gel shift assays (EMSA) with nuclear extracts; site-directed mutagenesis of CCAAT box and BTE Biochemical and biophysical research communications High 11485307
2006 CYP3A5 expression in human prostate is androgen-regulated: an androgen response element (ARE) in the CYP3A5 proximal promoter binds the androgen receptor (AR) as shown by EMSA, and androgen induction is abolished by mutation of this element. CYP3A5 mRNA is induced in LNCaP cells by androgen, suggesting CYP3A5 participates in an autoregulatory feedback loop controlling prostate cell androgen exposure by metabolizing testosterone. GeneChip analysis of prostate tissue after castration; RT-PCR of LNCaP cells; EMSA with ARE and AR; promoter mutation analysis; immunoblotting; immunohistochemistry; in situ hybridization Carcinogenesis High 17116727
2013 CYP3A5 expression in human hepatocytes is sexually dimorphic (women > men), attributable to ~2-fold greater hormone-induced activation and nuclear accumulation of HNF-4α, PXR, and RXRα in female hepatocytes; PXR:RXRα shows higher DNA binding to its motif on the CYP3A5 promoter in female hepatocytes; HNF-4α siRNA knockdown and luciferase reporter assays confirmed this mechanism. Primary human hepatocyte cultures from male and female donors; nuclear translocation assays; EMSA/promoter binding assays; HNF-4α siRNA knockdown; CYP3A5 promoter-luciferase reporter in HepG2 cells British journal of pharmacology Medium 22994453
2015 CYP3A5 regulates androgen receptor (AR) nuclear translocation in prostate cancer cells; CYP3A5 siRNA or the CYP3A5 inhibitor azamulin reduced growth of LNCaP, C4-2, and 22RV1 cells by 30–60%, decreased AR nuclear localization in response to DHT/R1881, and diminished PSA and TMPRSS2 expression. Conversely, the CYP3A5 inducer rifampicin enhanced AR nuclear localization. CYP3A5 siRNA knockdown; pharmacological inhibition (azamulin); CYP3A5 induction (rifampicin); cell fractionation; immunocytochemistry; growth assays; downstream AR target gene expression The Prostate Medium 25586052
2015 CYP3A5 mediates the bioactivation and cytotoxicity of the bisbenzylisoquinoline alkaloid tetrandrine by generating a reactive quinone methide intermediate; a WI-38 cell line transgenically expressing Cyp3a5 showed higher ROS, higher LDH release, lower GSH, and more apoptosis (elevated caspase-3, reduced Bcl-2) than vector-transfected controls after tetrandrine treatment. Cyp3a5-transgenic WI-38 cell line; ROS measurement; LDH assay; GSH assay; caspase-3 and Bcl-2 Western blot; apoptosis flow cytometry Archives of toxicology Medium 26302866
2016 Both CYP3A4 and CYP3A5 bioactivate lapatinib via O-dealkylation to a reactive quinoneimine that forms glutathione adducts, but CYP3A4 is ~4–5-fold more efficient (kcat/Km) than CYP3A5 for both O-dealkylation and GSH adduct formation; CYP3A4-selective inhibitors reduced GSH adduct formation by 72–78% versus >90% for pan-CYP3A inhibition, indicating the remaining 16–22% is CYP3A5-mediated. cDNA-expressed recombinant P450 panel; Km/kcat kinetics; LC-MS/MS metabolite and GSH adduct quantification; CYP3A4-selective inhibitors (SR-9186, CYP3cide) in pooled human liver microsomes Drug metabolism and disposition High 27450182
2013 CYP3A4 and CYP3A5 both oxidize vinorelbine with equivalent Michaelis-Menten constants in recombinant systems (Km ~2.6 vs 3.6 µM; common Vmax ~1.4 pmol/min/pmol), but produce qualitatively different metabolite patterns; in human liver microsomes, intrinsic clearance correlates with CYP3A4 activity and does not significantly differ between CYP3A5 high and low expressers, indicating minimal contribution of polymorphic CYP3A5 to systemic vinorelbine clearance. cDNA-expressed CYP3A4+b5 and CYP3A5+b5 kinetics; radiolabeled vinorelbine; NMR and mass spectrometry metabolite characterization; genotyped human liver microsomes; CYP3A4 activity correlation Drug metabolism and disposition High 23780963
2019 The X-ray crystal structure of substrate-free CYP3A5 (2.20 Å) reveals a larger active site and an open substrate access channel compared with substrate-free CYP3A4, arising partly from a higher trajectory of the helix F-F' connector and fewer π-CH interactions between phenylalanine residues forming the active-site roof in CYP3A5; comparison with the CYP3A5-ritonavir complex confirmed conserved structural features and differential plasticity that favors alternative ritonavir conformations compared with CYP3A4. X-ray crystallography of substrate-free CYP3A5 (2.20 Å); structural comparison with CYP3A5-ritonavir complex and CYP3A4 structures The Journal of biological chemistry High 30926609
2019 The relative contribution of CYP3A5 to 21-hydroxyeplerenone formation (Vmax/KM = 3.3) exceeds that of CYP3A4 (Vmax/KM = 1.9), while the 6β-hydroxyeplerenone metabolite is formed preferentially by CYP3A4, establishing eplerenone as a substrate with differential positional selectivity between the two CYP3A isoforms. In vitro microsomal incubations with recombinant CYP3A4 and CYP3A5; metabolite identification and kinetic parameter determination Toxicology letters Medium 31408697
1997 CYP3A5 is the predominant CYP3A form expressed in human lung (mRNA detected in all 8 samples by RT-PCR), localized by immunohistochemistry to ciliated and mucous bronchial cells, bronchial glands, bronchiolar epithelium, alveolar type I and II epithelium, vascular and capillary endothelium, and alveolar macrophages, whereas CYP3A4 is expressed in only ~20% of individuals and in fewer cell types. Immunohistochemistry with CYP3A4- and CYP3A5-specific antipeptide antibodies; RT-PCR with gene-specific primers in human lung tissue American journal of respiratory cell and molecular biology Medium 9070608
1996 CYP3A5 is selectively expressed in human peripheral blood, specifically in neutrophils (PMNs) but not in other blood cells; CYP3A4 is not detected in peripheral blood by PCR or immunoblot. Despite CYP3A5 protein presence in white cell homogenates, midazolam metabolism could not be detected in granulocyte or whole WBC preparations. Immunostaining of peripheral blood smears; RT-PCR with CYP3A-specific primers on PMN and mononuclear cell cDNA; immunoblotting with anti-CYP3A and anti-CYP3A5 antibodies; midazolam metabolism assay in WBC preparations Pharmacogenetics Medium 8946469
2022 A distal regulatory region (DRR) ~several kb from CYP3A4 physically contacts the CYP3A4 promoter (detected by 4C chromatin conformation capture), acts as a shared transcriptional enhancer for CYP3A4, CYP3A5, and CYP3A7 (CRISPR deletion decreases expression of all three genes); SNPs rs776744/rs776742 within the DRR increase enhancer-driven reporter expression and are associated with 1.39-fold increased CYP3A5 mRNA in human liver. 4C chromatin conformation capture; enhancer reporter assays; CRISPR-mediated DRR deletion; liver cohort (n=246) genotype-expression correlation; clinical cohort validation Clinical and translational science High 36045613
2022 A lncRNA (AC069294.1) generated antisense to CYP3A4 negatively regulates both CYP3A4 and CYP3A5 expression; knockdown of AC069294.1 in Huh7 cells increased CYP3A4 mRNA ~3-fold, while overexpression decreased CYP3A4 mRNA by 89% and also reduced CYP3A5 expression; the CYP3A4*1G SNP (rs2242480) is associated with increased AC069294.1 expression and decreased CYP3A5 mRNA by 39%. siRNA knockdown and overexpression of AC069294.1 in Huh7 cells; mRNA quantification; liver eQTL analysis; linkage disequilibrium analysis Pharmacogenetics and genomics Medium 34320606
2015 CYP3A5 expression in human fetal liver (7–32 weeks postconception) is highly variable (235-fold for normally spliced mRNA); alternative splicing due to the CYP3A5*3 allele occurs in fetal liver as in adults; formation of 1'-OH midazolam varies 79-fold and the 1'-OH/4-OH MDZ ratio depends on CYP3A5*3 genotype, confirming functional CYP3A5 activity in fetal liver. Genotyping of fetal liver bank; RT-PCR quantification of normal and SV1 CYP3A5 mRNA; midazolam 1'- and 4-hydroxylation activity assays in fetal liver microsomes Drug metabolism and disposition Medium 25979262
2011 CYP3A5 protein expression in renal tubular cells (assessed by immunohistochemistry of renal allograft biopsies) is associated with calcineurin inhibitor nephrotoxicity (CNIT): CYP3A5 positivity at the brush border of proximal tubules was present in 47% of CNIT biopsies versus 14% of controls, while distal tubule staining was reduced in CNIT (10% vs 39%), suggesting altered localization/expression pattern is linked to nephrotoxicity. Immunohistochemistry of renal allograft biopsies (n=103); genotyping for CYP3A5 and ABCB1 SNPs; correlation of protein expression with histological CNIT diagnosis Transplantation Low 21544031
1999 CYP3A5 protein expression is detected in human skin (and tissue-engineered skin equivalents) by gene and protein expression methods; functional testosterone metabolism (confirmed by mass spectrometry of metabolites) was demonstrated in tissue-engineered skin equivalents, establishing that CYP3A5 is enzymatically active in skin. RT-PCR and protein expression in human skin and tissue-engineered skin equivalents (TESEs); enzyme activity assay with fluorescent substrate; mass spectrometric analysis of testosterone metabolites in TESE lysates Experimental dermatology Medium 29227563

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2015 Clinical Pharmacogenetics Implementation Consortium (CPIC) Guidelines for CYP3A5 Genotype and Tacrolimus Dosing. Clinical pharmacology and therapeutics 565 25801146
2001 The genetic determinants of the CYP3A5 polymorphism. Pharmacogenetics 563 11740341
2002 Co-regulation of CYP3A4 and CYP3A5 and contribution to hepatic and intestinal midazolam metabolism. Molecular pharmacology 366 12065767
2006 Effect of CYP3A5 polymorphism on tacrolimus metabolic clearance in vitro. Drug metabolism and disposition: the biological fate of chemicals 251 16501005
2004 Genetic variability in CYP3A5 and its possible consequences. Pharmacogenomics 214 15102541
2005 Contribution of CYP3A5 to the in vitro hepatic clearance of tacrolimus. Clinical chemistry 188 15951320
2016 CYP3A5 mediates basal and acquired therapy resistance in different subtypes of pancreatic ductal adenocarcinoma. Nature medicine 173 26855150
2004 CYP3A5 and MDR1 genetic polymorphisms and cyclosporine pharmacokinetics after renal transplantation. Clinical pharmacology and therapeutics 160 15116055
2006 CYP3A5 and ABCB1 polymorphisms and tacrolimus pharmacokinetics in renal transplant candidates: guidelines from an experimental study. American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons 144 17049058
2003 The effect of CYP3A5 and MDR1 polymorphic expression on cyclosporine oral disposition in renal transplant patients. Journal of clinical pharmacology 136 12817518
2005 CYP3A5 genetic polymorphisms in different ethnic populations. Drug metabolism and disposition: the biological fate of chemicals 133 15833928
1997 Expression and localization of CYP3A4 and CYP3A5 in human lung. American journal of respiratory cell and molecular biology 133 9070608
2007 Effect of CYP3A5 expression on vincristine metabolism with human liver microsomes. The Journal of pharmacology and experimental therapeutics 112 17272675
2004 CYP3A4, CYP3A5, and CYP3A43 genotypes and haplotypes in the etiology and severity of prostate cancer. Cancer research 111 15548719
2003 CYP3A4 and CYP3A5 genotypes, haplotypes, and risk of prostate cancer. Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology 94 14504207
2010 CYP3A5 and ABCB1 polymorphisms influence tacrolimus concentrations in peripheral blood mononuclear cells after renal transplantation. Pharmacogenomics 88 20415563
1996 Expression of CYP3A4, CYP3A5 and CYP3A7 in human duodenal tissue. British journal of clinical pharmacology 84 8877031
2005 CYP3A5*3 and CYP3A4*18 single nucleotide polymorphisms in a Chinese population. Clinica chimica acta; international journal of clinical chemistry 82 15698606
2019 CYP2C9, CYP2C19, CYP2D6 and CYP3A5 polymorphisms in South-East and East Asian populations: A systematic review. Journal of clinical pharmacy and therapeutics 79 30980418
2015 CYP3A5 and ABCB1 polymorphisms as predictors for sunitinib outcome in metastatic renal cell carcinoma. European urology 76 25930089
2005 Genetic polymorphisms of CYP3A5 genes and concentration of the cyclosporine and tacrolimus. Transplantation proceedings 74 15808586
2018 CYP3A5 polymorphisms in renal transplant recipients: influence on tacrolimus treatment. Pharmacogenomics and personalized medicine 72 29563827
2012 Impact of CYP3A5 and ABCB1 gene polymorphisms on fentanyl pharmacokinetics and clinical responses in cancer patients undergoing conversion to a transdermal system. Drug metabolism and pharmacokinetics 70 22277678
2008 CYP3A7, CYP3A5, CYP3A4, and ABCB1 genetic polymorphisms, cyclosporine concentration, and dose requirement in transplant recipients. Therapeutic drug monitoring 69 18978522
2024 CYP3A4 and CYP3A5: the crucial roles in clinical drug metabolism and the significant implications of genetic polymorphisms. PeerJ 68 39650550
2018 Influence of CYP2D6, CYP3A4, CYP3A5 and ABCB1 Polymorphisms on Pharmacokinetics and Safety of Aripiprazole in Healthy Volunteers. Basic & clinical pharmacology & toxicology 68 29325225
2017 Differential Regulation of CYP3A4 and CYP3A5 and its Implication in Drug Discovery. Current drug metabolism 66 28558634
2005 Differential mechanism-based inhibition of CYP3A4 and CYP3A5 by verapamil. Drug metabolism and disposition: the biological fate of chemicals 61 15689501
2001 CYP3A4, CYP3A5, and MDR1 in human small and large intestinal cell lines suitable for drug transport studies. Journal of pharmaceutical sciences 57 11745731
2011 Influence of CYP3A5 and ABCB1 gene polymorphisms and other factors on tacrolimus dosing in Caucasian liver and kidney transplant patients. International journal of molecular medicine 55 21922127
2005 CYP3A4 and CYP3A5 genotyping by Pyrosequencing. BMC medical genetics 55 15882469
2008 Metabolism of quetiapine by CYP3A4 and CYP3A5 in presence or absence of cytochrome B5. Drug metabolism and disposition: the biological fate of chemicals 54 19022943
2003 CYP3A5 phenotype-genotype correlations in a British population. British journal of clinical pharmacology 52 12814460
2009 Genetic variants of CYP3A4 and CYP3A5 in cynomolgus and rhesus macaques. Drug metabolism and disposition: the biological fate of chemicals 51 19910514
2010 Influence of CYP3A5 and ABCB1 gene polymorphisms on calcineurin inhibitor-related neurotoxicity after hematopoietic stem cell transplantation. Clinical transplantation 49 20030680
2007 CYP3A5 and ABCB1 genes influence blood pressure and response to treatment, and their effect is modified by salt. Hypertension (Dallas, Tex. : 1979) 49 17372036
2007 Association of CYP3A5 polymorphisms with hypertension and antihypertensive response to verapamil. Clinical pharmacology and therapeutics 45 17339868
2017 CYP3A5 genotype and its impact on vincristine pharmacokinetics and development of neuropathy in Kenyan children with cancer. Pediatric blood & cancer 43 29115708
2017 Effect of CYP3A4*22, CYP3A5*3, and CYP3A combined genotypes on tamoxifen metabolism. European journal of clinical pharmacology 41 28849250
2009 Statin regulation of CYP3A4 and CYP3A5 expression. Pharmacogenomics 41 19530969
2018 Tacrolimus Population Pharmacokinetics and Multiple CYP3A5 Genotypes in Black and White Renal Transplant Recipients. Journal of clinical pharmacology 39 29775201
2022 PharmVar GeneFocus: CYP3A5. Clinical pharmacology and therapeutics 38 35202484
1996 Selective expression of CYP3A5 and not CYP3A4 in human blood. Pharmacogenetics 37 8946469
2016 Cytochrome P450 3A4 and CYP3A5-Catalyzed Bioactivation of Lapatinib. Drug metabolism and disposition: the biological fate of chemicals 36 27450182
2005 CYP3A5 mRNA degradation by nonsense-mediated mRNA decay. Molecular pharmacology 36 15955870
2011 Expression of CYP3A5 and P-glycoprotein in renal allografts with histological signs of calcineurin inhibitor nephrotoxicity. Transplantation 35 21544031
2019 Active-site differences between substrate-free and ritonavir-bound cytochrome P450 (CYP) 3A5 reveal plasticity differences between CYP3A5 and CYP3A4. The Journal of biological chemistry 34 30926609
2006 Characterization of androgen-regulated expression of CYP3A5 in human prostate. Carcinogenesis 32 17116727
2021 Roles of CYP3A4, CYP3A5 and CYP2C8 drug-metabolizing enzymes in cellular cytostatic resistance. Chemico-biological interactions 30 33775687
2013 Inherent sex-dependent regulation of human hepatic CYP3A5. British journal of pharmacology 29 22994453
2013 CYP3A5 gene variation influences cyclosporine A metabolite formation and renal cyclosporine disposition. Transplantation 28 23354298
2007 CYP3A5*3 and CYP3A4*1B allele distribution and genotype combinations: differences between Spaniards and Central Americans. Therapeutic drug monitoring 27 17667794
2018 Impact of SLC22A1 and CYP3A5 genotypes on imatinib response in chronic myeloid leukemia: A systematic review and meta-analysis. Pharmacological research 26 29427770
2009 CYP3A5 and ABCB1 genes and hypertension. Pharmacogenomics 26 19290795
2008 Frequencies of CYP3A5 genotypes and haplotypes in a Korean population. Journal of clinical pharmacy and therapeutics 26 18211618
2007 Pharmacokinetics and pharmacodynamics of paclitaxel with carboplatin or gemcitabine, and effects of CYP3A5 and MDR1 polymorphisms in patients with urogenital cancers. International journal of clinical oncology 26 17701008
2021 SLCO1B1 Phenotype and CYP3A5 Polymorphism Significantly Affect Atorvastatin Bioavailability. Journal of personalized medicine 25 33805706
2017 Effect of CYP3A4 and CYP3A5 Polymorphisms on Pharmacokinetics and Pharmacodynamics of Ticagrelor in Healthy Chinese Subjects. Frontiers in pharmacology 24 28408884
2013 Association of hemoglobin levels, CYP3A5, and NR1I3 gene polymorphisms with tacrolimus pharmacokinetics in liver transplant patients. Drug metabolism and pharmacokinetics 24 24351870
2011 CYP1A1, CYP3A5 and CYP3A7 polymorphisms and testicular cancer susceptibility. International journal of andrology 24 20345875
2014 Effects of combinational CYP3A5 6986A>G polymorphism in graft liver and native intestine on the pharmacokinetics of tacrolimus in liver transplant patients: a meta-analysis. Therapeutic drug monitoring 23 24378577
2019 miR‑543 acts as a novel oncogene in oral squamous cell carcinoma by targeting CYP3A5. Oncology reports 22 31322243
2015 Variability in Expression of CYP3A5 in Human Fetal Liver. Drug metabolism and disposition: the biological fate of chemicals 22 25979262
2013 The relative contributions of CYP3A4 and CYP3A5 to the metabolism of vinorelbine. Drug metabolism and disposition: the biological fate of chemicals 22 23780963
2011 CYP3A5, ABCB1, and SLCO1B1 polymorphisms and pharmacokinetics and virologic outcome of lopinavir/ritonavir in HIV-infected children. Therapeutic drug monitoring 22 21743379
2015 Effect of the CYP3A5 and ABCB1 genotype on exposure, clinical response and manifestation of toxicities from sunitinib in Asian patients. The pharmacogenomics journal 20 25778465
2015 CYP3A5 mediates bioactivation and cytotoxicity of tetrandrine. Archives of toxicology 20 26302866
2010 Analysis of CYP3A5*3 and CYP3A5*6 gene polymorphisms in Indian chronic myeloid leukemia patients. Asian Pacific journal of cancer prevention : APJCP 20 21039054
2009 Effects of CYP3A5, MDR1 and CACNA1C polymorphisms on the oral disposition and response of nimodipine in a Chinese cohort. European journal of clinical pharmacology 20 19205682
2007 Genetic variability in CYP3A4 and CYP3A5 in primary liver, gastric and colorectal cancer patients. BMC cancer 19 17605821
2015 CYP3A5 regulates prostate cancer cell growth by facilitating nuclear translocation of AR. The Prostate 18 25586052
2014 CYP3A5 genotypes affect tacrolimus pharmacokinetics and infectious complications in Chinese pediatric liver transplant patients. Pediatric transplantation 18 24438215
2013 Effects of atorvastatin on CYP3A4 and CYP3A5 mRNA expression in mononuclear cells and CYP3A activity in hypercholeresterolemic patients. Clinica chimica acta; international journal of clinical chemistry 18 23501331
2001 Cooperative regulation of CYP3A5 gene transcription by NF-Y and Sp family members. Biochemical and biophysical research communications 18 11485307
2020 CYP3A5 polymorphisms and their effects on tacrolimus exposure in an ethnically diverse South African renal transplant population. South African medical journal = Suid-Afrikaanse tydskrif vir geneeskunde 17 32657689
2019 Melding Pharmacogenomic Effect of MDR1 and CYP3A5 Gene Polymorphism on Tacrolimus Dosing in Renal Transplant Recipients in Northern India. Kidney international reports 17 31922058
2021 Associations between CYP3A4, CYP3A5 and SCN1A polymorphisms and carbamazepine metabolism in epilepsy: A meta-analysis. Epilepsy research 16 33756436
2022 Regulatory variants in a novel distal enhancer regulate the expression of CYP3A4 and CYP3A5. Clinical and translational science 15 36045613
2021 Association of CYP3A5 Gene Polymorphisms and Amlodipine-Induced Peripheral Edema in Chinese Han Patients with Essential Hypertension. Pharmacogenomics and personalized medicine 15 33564260
2017 Association of CYP3A5 Expression and Vincristine Neurotoxicity in Pediatric Malignancies in Turkish Population. Journal of pediatric hematology/oncology 15 28697165
2016 Influence of CYP3A5 polymorphism on the pharmacokinetics of psychiatric drugs. Current drug metabolism 15 26651976
2015 Polymorphism of the CYP3A5 gene and its effect on tacrolimus blood level. Experimental and clinical transplantation : official journal of the Middle East Society for Organ Transplantation 15 25894154
2014 Characterization of CYP1A2, CYP2C19, CYP3A4 and CYP3A5 polymorphisms in South Brazilians. Molecular biology reports 15 24443221
2014 Distribution of ABCB1, CYP3A5, CYP2C19, and P2RY12 gene polymorphisms in a Mexican Mestizos population. Molecular biology reports 15 25106522
2011 Association of the CYP3A5 polymorphism (6986G>A) with blood pressure and hypertension. Hypertension research : official journal of the Japanese Society of Hypertension 15 21814220
2020 CYP3A5 Gene-Guided Tacrolimus Treatment of Living-Donor Egyptian Kidney Transplanted Patients. Frontiers in pharmacology 14 32848803
2017 Effect of Age and Allele Variants of CYP3A5, CYP3A4, and POR Genes on the Pharmacokinetics of Cyclosporin A in Pediatric Renal Transplant Recipients From Serbia. Therapeutic drug monitoring 14 29135906
2015 Interactions between CYP3A5*3 and POR*28 polymorphisms and lipid lowering response with atorvastatin. Clinical drug investigation 14 26293521
2023 A systematic review and meta-analysis recite the efficacy of Tacrolimus treatment in renal transplant patients in association with genetic variants of CYP3A5 gene. American journal of clinical and experimental urology 13 37645617
2016 CYP3A5 Genotype and Time to Reach Tacrolimus Therapeutic Levels in Renal Transplant Children. Transplantation proceedings 13 27110018
2023 Genetic association in CYP3A4 and CYP3A5 genes elevate the risk of prostate cancer. Annals of human biology 12 36688864
2022 Regulation of CYP3A4 and CYP3A5 by a lncRNA: a potential underlying mechanism explaining the association between CYP3A4*1G and CYP3A metabolism. Pharmacogenetics and genomics 12 34320606
2021 Polymorphisms in the CYP3A5 gene significantly affect the pharmacokinetics of sirolimus after kidney transplantation. Pharmacogenomics 12 34523354
2020 Frequency of CYP3A5 Genetic Polymorphisms and Tacrolimus Pharmacokinetics in Pediatric Liver Transplantation. Pharmaceutics 12 32971783
2019 The relative role of CYP3A4 and CYP3A5 in eplerenone metabolism. Toxicology letters 12 31408697
2018 Expression and enzyme activity of cytochrome P450 enzymes CYP3A4 and CYP3A5 in human skin and tissue-engineered skin equivalents. Experimental dermatology 12 29227563
2015 Combinational Effect of CYP3A5 and MDR-1 Polymorphisms on Tacrolimus Pharmacokinetics in Liver Transplant Patients. Experimental and clinical transplantation : official journal of the Middle East Society for Organ Transplantation 12 26450467
2014 Interaction between ALOX5AP and CYP3A5 gene variants significantly increases the risk for cerebral infarctions in Chinese. Neuroreport 12 24368493
2011 Study the polymorphism of CYP3A5 and CYP3A4 loci in Iranian population with laryngeal squamous cell carcinoma. Molecular biology reports 12 21380731
2022 ABCG2, SCN1A and CYP3A5 genes polymorphism and drug-resistant epilepsy in children: A case-control study. Seizure 11 35338956

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