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CYP3A43

gene
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Summary

CYP3A43 (cytochrome P450 family 3 subfamily A member 43, HGNC:17450) is a protein-coding gene on chromosome 7q22.1, encoding Cytochrome P450 3A43 (Q9HB55). Exhibits low testosterone 6-beta-hydroxylase activity.

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. The encoded protein has a low level of testosterone hydroxylase activity, and may play a role in aging mechanisms and cancer progression. This gene is part of a cluster of cytochrome P450 genes on chromosome 7q21.1. Alternate splicing results in multiple transcript variants encoding different isoforms.

Source: NCBI Gene 64816 — RefSeq curated summary.

At a glance

  • GWAS associations: 4
  • Clinical variants (ClinVar): 67 total
  • Druggable target: yes — 9 molecules with ChEMBL bioactivity
  • Dosage sensitivity (ClinGen): haploinsufficiency dosage sensitivity unlikely, triplosensitivity no evidence
  • MANE Select transcript: NM_057095

Identifiers

Gene identifiers

FieldValue
HGNC IDHGNC:17450
Approved symbolCYP3A43
Namecytochrome P450 family 3 subfamily A member 43
Location7q22.1
Locus typegene with protein product
StatusApproved
Ensembl geneENSG00000021461
Ensembl biotypeprotein_coding
OMIM606534
Entrez64816

Gene structure

Transcript identifiers

Ensembl transcripts: 22 — 13 protein_coding, 4 protein_coding_CDS_not_defined, 3 nonsense_mediated_decay, 2 retained_intron

ENST00000222382, ENST00000312017, ENST00000354829, ENST00000415413, ENST00000417625, ENST00000433277, ENST00000434806, ENST00000436834, ENST00000444905, ENST00000463915, ENST00000472352, ENST00000477658, ENST00000481362, ENST00000491648, ENST00000495115, ENST00000631161, ENST00000874622, ENST00000874623, ENST00000874624, ENST00000874625, ENST00000874626, ENST00000874627

RefSeq mRNA: 4 — MANE Select: NM_057095 NM_001278921, NM_022820, NM_057095, NM_057096

CCDS: CCDS5675, CCDS5676, CCDS5677, CCDS64723

Canonical transcript exons

ENST00000354829 — 13 exons

ExonStartEnd
ENSE000012481169984414399844242
ENSE000015919379986590699866093
ENSE000034605929983645399836546
ENSE000034776869984748899847601
ENSE000034867939985559199855718
ENSE000034907219985683399856899
ENSE000035052689983912099839172
ENSE000035956379984954699849694
ENSE000036168299986161399861839
ENSE000036353639984816699848254
ENSE000036580709986353799863699
ENSE000036931379985983099859990
ENSE000038995789982801399828186

Expression profiles

Bgee: expression breadth ubiquitous, 148 present calls, max score 83.84.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.1154 / max 71.1704, expressed in 11 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter IDTPM avgSamples expressed
799020.115411

Top tissues by expression

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

TissueAnatomy IDExpression scoreQuality
liverUBERON:000210783.84gold quality
right lobe of liverUBERON:000111482.20gold quality
male germ line stem cell (sensu Vertebrata) in testisCL:0000089 ∩ UBERON:000047380.89gold quality
ileal mucosaUBERON:000033177.47gold quality
body of pancreasUBERON:000115077.11gold quality
jejunal mucosaUBERON:000039975.41silver quality
spermCL:000001973.85silver quality
pancreatic ductal cellCL:000207973.80silver quality
male germ cellCL:000001573.41silver quality
epithelial cell of pancreasCL:000008370.64gold quality
oocyteCL:000002368.79gold quality
cervix squamous epitheliumUBERON:000692267.38gold quality
tongue squamous epitheliumUBERON:000691967.09gold quality
skeletal muscle tissue of biceps brachiiUBERON:000450266.74gold quality
olfactory bulbUBERON:000226466.64gold quality
type B pancreatic cellCL:000016966.45gold quality
upper leg skinUBERON:000426265.64silver quality
jejunumUBERON:000211565.37silver quality
buccal mucosa cellCL:000233664.82silver quality
tibialis anteriorUBERON:000138564.55silver quality
quadriceps femorisUBERON:000137764.10gold quality
vastus lateralisUBERON:000137963.45gold quality
triceps brachiiUBERON:000150962.75gold quality
gluteal muscleUBERON:000200062.73gold quality
upper arm skinUBERON:000426362.68gold quality
pancreasUBERON:000126461.94gold quality
diaphragmUBERON:000110361.24gold quality
skin of hipUBERON:000155461.22silver quality
skeletal muscle tissueUBERON:000113459.90silver quality
mucosa of sigmoid colonUBERON:000499359.78gold quality

Single-cell (SCXA)

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

ExperimentMarker?Max mean expression
E-ANND-3yes5.20

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

9 targeting CYP3A43, 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-4682100.0068.891258
HSA-MIR-425599.7267.701541
HSA-MIR-1211799.5067.57868
HSA-MIR-3160-5P99.2869.071938
HSA-MIR-6506-5P99.0465.661386
HSA-MIR-520G-3P98.9167.381914
HSA-MIR-520H98.9167.381914
HSA-MIR-619-5P98.5764.971988
HSA-MIR-431497.5067.301369

Functional genomics

ClinGen dosage: haploinsufficiency 40 (dosage sensitivity unlikely), triplosensitivity 0 (no evidence). ClinGen Gene Dosage Map

Literature-anchored findings (GeneRIF, showing 9)

  • Finds CYP3A43-Pro(340)Ala polymorphism prevalence differs by race and contributes to prostate cancer risk in African Americans. (PMID:15894682)
  • analysis of the restriction fragment length polymorphism CYP3A43 gene c1047 > T in europeoid residents of West Siberia (PMID:16848237)
  • No differences in genotype frequencies between cases and controls were observed, indicating that CYP3A43_74_delA is not associated with breast cancer risk. (PMID:20715157)
  • CYP3A43 rs472660 is not likely to be a major contributor towards variability in systemic OLA exposure among White patients (PMID:24595013)
  • This review support the notion that the SNP CYP3A43this may play a role in antipsychotic response. (PMID:25150845)
  • Mutations in CYP3A43 gene is associated with prostate cancer. (PMID:26585945)
  • We investigated the association between genetic polymorphisms in VDR, cytochrome P450 (CYP2R1, CYP24A1, and the CYP3A family) with plasma concentrations of vitamin D metabolites (25-hydroxyvitamin D3 (25(OH)D3) and proportion 24,25-dihydroxyvitamin D3 (24,25(OH)2D3)) among individuals of sub-Saharan African and European ancestry. Only CYP3A43 and VDR polymorphisms were associated with proportion 24,25(OH)2D. (PMID:28673024)
  • Cis-acting regulatory elements regulating CYP3A4 transcription in human liver. (PMID:32301865)
  • Effects of CYP3A43 Expression on Cell Proliferation and Migration of Lung Adenocarcinoma and Its Clinical Significance. (PMID:36613552)

Cross-species orthologs

20 orthologs

OrganismSymbolGene ID
danio_reriocyp3c1ENSDARG00000015575
danio_reriocyp3c3ENSDARG00000037873
danio_reriocyp3c2ENSDARG00000037874
danio_reriocyp3c4ENSDARG00000070021
danio_reriocyp3a65ENSDARG00000103295
mus_musculusCyp3a25ENSMUSG00000029630
mus_musculusCyp3a13ENSMUSG00000029727
mus_musculusCyp3a16ENSMUSG00000038656
mus_musculusCyp3a44ENSMUSG00000054417
mus_musculusCyp3a11ENSMUSG00000056035
mus_musculusCyp3a59ENSMUSG00000061292
mus_musculusCyp3a57ENSMUSG00000070419
mus_musculusCyp3a41aENSMUSG00000075551
mus_musculusCyp3a41bENSMUSG00000075552
rattus_norvegicusCyp3a18ENSRNOG00000000969
rattus_norvegicusCyp3a73ENSRNOG00000000978
rattus_norvegicusCyp3a62ENSRNOG00000001379
rattus_norvegicusCyp3a23-3a1ENSRNOG00000032560
rattus_norvegicusCyp3a9ENSRNOG00000046643
rattus_norvegicusCyp3a23-3a1ENSRNOG00000067532

Paralogs (3): CYP3A5 (ENSG00000106258), CYP3A4 (ENSG00000160868), CYP3A7 (ENSG00000160870)

Protein

Protein identifiers

Cytochrome P450 3A43 — Q9HB55 (reviewed: Q9HB55)

All UniProt accessions (6): C9JA26, E7EMH4, E9PDL8, E9PG90, Q9HB50, Q9HB55

UniProt curated annotations — full annotation on UniProt →

Function. Exhibits low testosterone 6-beta-hydroxylase activity.

Subcellular location. Endoplasmic reticulum membrane. Microsome membrane.

Tissue specificity. Highest expression level in prostate. Also expressed in liver, kidney, pancreas, fetal liver and fetal skeletal muscle.

Induction. By rifampicin.

Polymorphism. At protein level, three alleles are known: CYP3A431, CYP3A432 and CYP3A433. The sequence shown is that of CYP3A431, which is the most frequent allele. The allele CYP3A43*2 is likely to be non-functional.

Miscellaneous. Chimeric transcripts, characterized by CYP3A43 exon 1 joined at canonical splice sites to distinct sets of CYP3A4 or CYP3A5 exons, have been detected. All are possibly produced by trans-splicing. CYP3A43-CYP3A4 chimeric transcripts exist in 3 different combinations: CYP3A43 exon 1 joined in frame to CYP3A4 exons 2-13, CYP3A43 exon 1 joined in frame to CYP3A4 exons 4-13 and CYP3A43 exon 1 joined in frame to CYP3A4 exon 7-13. The longest chimeric isoform (CYP3A43 exon 1 joined to CYP3A4 exons 2-13) exhibits 6-beta-hydroxylase activity, while a shorter isoform (CYP3A43 exon 1 joined to CYP3A4 exons 4-13) does not. CYP3A43-CYP3A5 chimeric transcripts exist in 2 different combinations: CYP3A43 exon 1 joined in frame to CYP3A5 exon 11-13 and CYP3A43 exon 1 joined in frame to CYP3A5 exon 12-13. All chimeric transcripts are expressed at very low levels in the liver. May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay.

Similarity. Belongs to the cytochrome P450 family.

Isoforms (5)

UniProt IDNamesCanonical?
Q9HB55-11yes
Q9HB55-22
Q9HB55-33
Q9HB55-44
Q9HB55-67

RefSeq proteins (4): NP_001265850, NP_073731, NP_476436, NP_476437 (=MANE)

Domains & families (InterPro)

IDNameType
IPR001128Cyt_P450Family
IPR002402Cyt_P450_E_grp-IIFamily
IPR008072Cyt_P450_E_CYP3AFamily
IPR017972Cyt_P450_CSConserved_site
IPR036396Cyt_P450_sfHomologous_superfamily
IPR050705Cytochrome_P450_3AFamily

Pfam: PF00067

Catalyzed reactions (Rhea), 1 shown:

  • an organic molecule + reduced [NADPH–hemoprotein reductase] + O2 = an alcohol + oxidized [NADPH–hemoprotein reductase] + H2O + H(+) (RHEA:17149)

UniProt features (14 total): sequence variant 6, splice variant 6, chain 1, binding site 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

ModelpLDDTFraction very-high
AF-Q9HB55-F191.890.78

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): 442 (axial binding residue)

Function

Pathways and Gene Ontology

Reactome pathways

2 pathways

IDPathway
R-HSA-211958Miscellaneous substrates
R-HSA-211981Xenobiotics

MSigDB gene sets: 86 (showing top): REACTOME_BIOLOGICAL_OXIDATIONS, GOMF_OXIDOREDUCTASE_ACTIVITY_ACTING_ON_PAIRED_DONORS_WITH_INCORPORATION_OR_REDUCTION_OF_MOLECULAR_OXYGEN, GOBP_OXIDATIVE_DEMETHYLATION, GOBP_DEMETHYLATION, GOBP_LIPID_METABOLIC_PROCESS, KEGG_STEROID_HORMONE_BIOSYNTHESIS, GOBP_STEROID_METABOLIC_PROCESS, KEGG_METABOLISM_OF_XENOBIOTICS_BY_CYTOCHROME_P450, CHIANG_LIVER_CANCER_SUBCLASS_PROLIFERATION_DN, GOCC_NUCLEAR_OUTER_MEMBRANE_ENDOPLASMIC_RETICULUM_MEMBRANE_NETWORK, KEGG_DRUG_METABOLISM_OTHER_ENZYMES, GOCC_ORGANELLE_SUBCOMPARTMENT, GOMF_TETRAPYRROLE_BINDING, GOMF_IRON_ION_BINDING, GOMF_STEROID_HYDROXYLASE_ACTIVITY

GO Biological Process (9): steroid metabolic process (GO:0008202), oxidative demethylation (GO:0070989), cytochrome metabolic process (GO:1903604), lipid hydroxylation (GO:0002933), estrogen metabolic process (GO:0008210), alkaloid catabolic process (GO:0009822), xenobiotic catabolic process (GO:0042178), retinoic acid metabolic process (GO:0042573), aflatoxin metabolic process (GO:0046222)

GO Molecular Function (11): monooxygenase activity (GO:0004497), iron ion binding (GO:0005506), heme binding (GO:0020037), testosterone 6-beta-hydroxylase activity (GO:0050649), estrogen 16-alpha-hydroxylase activity (GO:0101020), retinoic acid 4-hydroxylase activity (GO:0008401), oxidoreductase activity (GO:0016491), oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen (GO:0016705), oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, reduced flavin or flavoprotein as one donor, and incorporation of one atom of oxygen (GO:0016712), oxygen binding (GO:0019825), metal ion binding (GO:0046872)

GO Cellular Component (3): endoplasmic reticulum membrane (GO:0005789), endoplasmic reticulum (GO:0005783), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-1 pathways:

CategoryPathways
Cytochrome P450 - arranged by substrate type2

GO top-level categories

Rollup of top GO terms by namespace:

CategoryTerms
hormone metabolic process2
catabolic process2
oxidoreductase activity2
steroid hydroxylase activity2
monooxygenase activity2
oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen2
lipid metabolic process1
demethylation1
protein metabolic process1
lipid modification1
steroid metabolic process1
alkaloid metabolic process1
xenobiotic metabolic process1
retinoid metabolic process1
monocarboxylic acid metabolic process1
mycotoxin metabolic process1
transition metal ion binding1
tetrapyrrole binding1
oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, reduced flavin or flavoprotein as one donor, and incorporation of one atom of oxygen1
catalytic activity1
small molecule binding1
cation binding1
organelle membrane1
nuclear outer membrane-endoplasmic reticulum membrane network1
endoplasmic reticulum subcompartment1
cytoplasm1
endomembrane system1
intracellular membrane-bounded organelle1
cellular anatomical structure1

Protein interactions and networks

STRING

1460 interactions, top by confidence (×1000):

Protein AProtein BPartner UniProtScore
CYP3A43PPIGQ13427583
CYP3A43CYP1A1P04798506
CYP3A43CYP2B6P20813505
CYP3A43OR52E8Q6IFG1498
CYP3A43CYP2E1P05181482
CYP3A43NR1I2O75469471
CYP3A43NR1I3Q14994442
CYP3A43CYB5BO43169424
CYP3A43SLC30A9Q6PML9408
CYP3A43SRD5A2P31213406
CYP3A43HS3ST3B1Q9Y662406
CYP3A43ADAM2P78326391
CYP3A43DMBT1Q9UGM3391
CYP3A43NDC80O14777386
CYP3A43CYB5R2Q6BCY4371

IntAct

3 interactions, top by confidence:

ABTypeScore
CYP3A43OCIAD2psi-mi:“MI:0915”(physical association)0.400
CYP3A43HPpsi-mi:“MI:0914”(association)0.350

BioGRID (21): CYP3A43 (Proximity Label-MS), BPIFB1 (Affinity Capture-MS), CTSG (Affinity Capture-MS), HSP90AA4P (Affinity Capture-MS), LCP1 (Affinity Capture-MS), MPO (Affinity Capture-MS), VIM (Affinity Capture-MS), FGG (Affinity Capture-MS), KPRP (Affinity Capture-MS), HP (Affinity Capture-MS), LCN2 (Affinity Capture-MS), MNDA (Affinity Capture-MS), PRTN3 (Affinity Capture-MS), HIST1H1B (Affinity Capture-MS), FGB (Affinity Capture-MS)

ESM2 similar proteins: O09158, O16805, O18993, O42563, O61387, O70537, P04800, P05183, P08684, P11707, P13527, P20815, P24462, P24463, P29981, P33268, P33269, P51538, P79102, P79401, Q04552, Q27593, Q27594, Q27664, Q27902, Q29496, Q64148, Q64406, Q64409, Q64417, Q64459, Q64464, Q64481, Q64581, Q8AXY5, Q92088, Q95031, Q95036, Q964R0, Q964R1

Diamond homologs: A0A0C2W6G6, A0A1L9WQK2, A0A1V0QSE7, A0A2H3CSA7, A0A2H3CZX2, A0A3G9HRC2, A0A3S5HYN5, A0A8K1AW54, A2A974, A2RRT9, A8NCK6, B0XZV0, B8QHP5, F1SY62, F1SY74, F1SYB6, F1SYH7, F2K081, F2ZAF9, I1RE80, I1S2J5, I3PLR1, L7X3S1, O08336, O17624, O18993, O43174, O44221, O48786, O49396, O55127, O70537, O88833, P05183, P08684, P0DKI7, P0DOX0, P11372, P11707, P13584

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

ClassificationCount (floor)
Pathogenic0
Likely pathogenic0
Uncertain significance51
Likely benign9
Benign3

Top pathogenic / likely-pathogenic (0)

SpliceAI

1717 predictions. Top by Δscore:

VariantEffectΔscore
7:99848255:G:GGdonor_gain1.0000
7:99849695:G:GGdonor_gain1.0000
7:99856831:A:AGacceptor_gain1.0000
7:99856832:G:GGacceptor_gain1.0000
7:99859827:CAGC:Cacceptor_loss1.0000
7:99859828:A:ACacceptor_loss1.0000
7:99859828:A:AGacceptor_gain1.0000
7:99859829:G:GTacceptor_gain1.0000
7:99859829:GC:Gacceptor_gain1.0000
7:99859829:GCT:Gacceptor_gain1.0000
7:99859829:GCTC:Gacceptor_gain1.0000
7:99859829:GCTCT:Gacceptor_gain1.0000
7:99859961:G:GTdonor_gain1.0000
7:99828187:G:GGdonor_gain0.9900
7:99839118:AG:Aacceptor_gain0.9900
7:99839119:GG:Gacceptor_gain0.9900
7:99839169:GGGG:Gdonor_gain0.9900
7:99839170:GGGG:Gdonor_gain0.9900
7:99839171:GG:Gdonor_gain0.9900
7:99839172:GG:Gdonor_gain0.9900
7:99848164:A:AGacceptor_gain0.9900
7:99848164:AGAT:Aacceptor_gain0.9900
7:99848165:G:GGacceptor_gain0.9900
7:99848165:GATG:Gacceptor_gain0.9900
7:99848251:AAGAG:Adonor_loss0.9900
7:99848253:GA:Gdonor_gain0.9900
7:99848254:AGTAA:Adonor_loss0.9900
7:99848255:GT:Gdonor_loss0.9900
7:99848256:TAA:Tdonor_loss0.9900
7:99848257:AAGTA:Adonor_loss0.9900

AlphaMissense

3355 scored. Top likely-pathogenic:

VariantProtein changeam_pathogenicity
7:99863538:T:CF419L0.992
7:99863540:C:AF419L0.992
7:99863540:C:GF419L0.992
7:99861671:A:TE362V0.991
7:99861826:T:CF414L0.990
7:99861828:C:AF414L0.990
7:99861828:C:GF414L0.990
7:99859956:T:CL331P0.989
7:99859928:G:CA322P0.988
7:99863586:T:CF435L0.987
7:99863588:T:AF435L0.987
7:99863588:T:GF435L0.987
7:99844228:T:CF102L0.984
7:99844230:C:AF102L0.984
7:99844230:C:GF102L0.984
7:99859926:T:CL321P0.981
7:99859929:C:AA322D0.978
7:99861827:T:CF414S0.978
7:99863642:A:CK453N0.978
7:99863642:A:TK453N0.978
7:99863647:C:AA455D0.978
7:99847558:G:CR130P0.977
7:99863662:T:CL460P0.977
7:99861717:C:GC377W0.976
7:99848212:T:CL160P0.975
7:99861671:A:CE362A0.975
7:99847545:T:AW126R0.974
7:99847545:T:CW126R0.974
7:99861672:A:CE362D0.974
7:99861672:A:TE362D0.974

dbSNP variants (sampled 300 via entrez): RS1000030886 (7:99831932 G>A), RS1000040878 (7:99830441 C>T), RS1000066249 (7:99861006 TG>T,TGGG), RS1000182365 (7:99843222 T>C,G), RS1000296903 (7:99856722 T>C), RS1000360365 (7:99836700 T>C), RS1000369004 (7:99844072 A>G), RS1000420018 (7:99830696 A>G,T), RS1000440550 (7:99850197 C>A,G,T), RS1000450318 (7:99836398 C>A,G,T), RS1000589947 (7:99854448 A>C,G,T), RS1000668940 (7:99856158 G>A), RS1000692380 (7:99835548 C>G), RS1000707514 (7:99862906 C>G,T), RS1000722385 (7:99842947 A>T)

Disease associations

OMIM: gene MIM:606534 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

4 associations (top):

StudyTraitp-value
GCST001038_4Dehydroepiandrosterone sulphate levels2.000000e-11
GCST002882_1Ticagrelor levels in individuals with acute coronary syndromes treated with ticagrelor1.000000e-14
GCST005144_1Tacrolimus trough concentration in kidney transplant patients2.000000e-17
GCST006249_49Serum metabolite levels1.000000e-11

EFO canonical traits (3, from GWAS)

EFO IDTrait name
EFO:0004730hormone measurement
EFO:0007007ticagrelor measurement
EFO:0008458tacrolimus measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (3): CHEMBL2364675 (PROTEIN FAMILY), CHEMBL4523986 (PROTEIN FAMILY), CHEMBL5792 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

9 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 459,636 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

MoleculeNamePhasePatents
CHEMBL1136TELITHROMYCIN415,927
CHEMBL157101KETOCONAZOLE475,361
CHEMBL160CYCLOSPORINE4168,247
CHEMBL163RITONAVIR453,773
CHEMBL269732TACROLIMUS ANHYDROUS495,168
CHEMBL451887CARFILZOMIB412,508
CHEMBL638VORICONAZOLE423,088
CHEMBL477772PAZOPANIB415,540
CHEMBL5314518GLECIRASIB224

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

PharmGKB clinical annotations

2 annotations.

VariantTypeLevelDrugsPhenotypes
rs472660Metabolism/PK3olanzapineSchizophrenia
rs62471956Metabolism/PK3ticagrelorAcute coronary syndrome

PharmGKB variants

7 variants.

VariantGenesLevelScore#Clin annotsDrugs
rs472660CYP3A4330.251olanzapine
rs651430CYP3A430.000
rs680055CYP3A430.000
rs12535293CYP3A430.000
rs17161981CYP3A430.000
rs17161983CYP3A430.000
rs62471956CYP3A4330.001ticagrelor

GtoPdb / IUPHAR curated pharmacology

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

Target class: enzyme — CYP3 family

ChEMBL bioactivities

49 potent at pChembl≥5 of 58 total, top 49 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChemblTypeValueUnitMolecule
8.92Ki1.2nMCHEMBL583090
8.62Ki2.4nMTELITHROMYCIN
8.28Ki5.3nMCHEMBL583093
8.25Ki5.6nMCHEMBL583091
7.89Ki13nMRITONAVIR
7.62Ki24nMCHEMBL583299
7.60Ki25nMCHEMBL583298
6.96IC50110nMKETOCONAZOLE
6.85IC50140nMRITONAVIR
6.80IC50160nMCHEMBL3527048
6.80IC50160nMKETOCONAZOLE
6.60IC50251.2nMCHEMBL601428
6.48IC50330nMCHEMBL3527048
6.44Ki360nMTACROLIMUS ANHYDROUS
6.31IC50490nMCARFILZOMIB
6.24IC50570nMCHEMBL5435851
6.21Ki610nMTACROLIMUS ANHYDROUS
6.18Ki660nMVORICONAZOLE
6.16IC50700nMCHEMBL3330409
6.13IC50740nMTACROLIMUS ANHYDROUS
6.05IC50900nMCHEMBL3330410
6.03IC50940nMTACROLIMUS ANHYDROUS
6.01Ki980nMCYCLOSPORINE
5.96IC501100nMCHEMBL2130955
5.96IC501100nMRITONAVIR
5.91IC501240nMCYCLOSPORINE
5.85IC501400nMCHEMBL3527048
5.84IC501450nMGLECIRASIB
5.83IC501470nMCYCLOSPORINE
5.75IC501800nMCHEMBL3542335
5.72IC501900nMCHEMBL495075
5.72IC501900nMCHEMBL2130955
5.60IC502500nMCHEMBL5612347
5.55IC502800nMCHEMBL2130955
5.54IC502900nMVORICONAZOLE
5.53Ki2970nMVORICONAZOLE
5.43IC503700nMCHEMBL5406721
5.43IC503700nMCHEMBL46909
5.42IC503800nMCHEMBL5418617
5.41IC503900nMCHEMBL5429178
5.34IC504600nMRITONAVIR
5.31IC504900nMCHEMBL2130955
5.23IC505900nMCHEMBL5406218
5.22IC506053nMCHEMBL65590
5.17IC506830nMGLECIRASIB
5.14IC507300nMCHEMBL6190745
5.10IC507900nMPAZOPANIB
5.03IC509300nMCHEMBL5771742
5.00IC501e+04nMCHEMBL5395150

PubChem BioAssay actives

45 with measured affinity, of 617 total; 30 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

CompoundAssayTypeValueUnit
(1S,2R,5R,7R,8R,9R,11R,13R,14R)-8-[(2S,3R,4S,6R)-4-(dimethylamino)-3-hydroxy-6-methyloxan-2-yl]oxy-2-ethyl-9-hydroxy-1,5,7,9,11,13-hexamethyl-15-[1-(1,5-naphthyridin-4-ylmethyl)azetidin-3-yl]-3,17-dioxa-15-azabicyclo[12.3.0]heptadecane-4,6,12,16-tetrone440648: Inhibition of CYP3A in human liver microsomes assessed as hydroxymidazolam formation by time dependent inhibition assayki0.0012uM
Telithromycin440648: Inhibition of CYP3A in human liver microsomes assessed as hydroxymidazolam formation by time dependent inhibition assayki0.0024uM
(1S,2R,5R,7R,8R,9R,11R,13R,14R)-8-[(2S,3R,4S,6R)-4-(dimethylamino)-3-hydroxy-6-methyloxan-2-yl]oxy-2-ethyl-9-hydroxy-1,5,7,9,11,13-hexamethyl-15-[1-[(1R)-1-(1,8-naphthyridin-4-yl)ethyl]azetidin-3-yl]-3,17-dioxa-15-azabicyclo[12.3.0]heptadecane-4,6,12,16-tetrone440648: Inhibition of CYP3A in human liver microsomes assessed as hydroxymidazolam formation by time dependent inhibition assayki0.0053uM
(1S,2R,5R,7R,8R,9R,11R,13R,14R)-8-[(2S,3R,4S,6R)-4-(dimethylamino)-3-hydroxy-6-methyloxan-2-yl]oxy-2-ethyl-9-hydroxy-1,5,7,9,11,13-hexamethyl-15-[1-(1,8-naphthyridin-4-ylmethyl)azetidin-3-yl]-3,17-dioxa-15-azabicyclo[12.3.0]heptadecane-4,6,12,16-tetrone440648: Inhibition of CYP3A in human liver microsomes assessed as hydroxymidazolam formation by time dependent inhibition assayki0.0056uM
Ritonavir2033231: Inhibition of CYP3A-mediated metabolism in human liver microsomeski0.0130uM
(1S,2R,5R,7R,8R,9R,11R,13R,14R)-8-[(2S,3R,4S,6R)-4-(dimethylamino)-3-hydroxy-6-methyloxan-2-yl]oxy-2-ethyl-9-hydroxy-15-[1-[(3-hydroxy-1,5-naphthyridin-4-yl)methyl]azetidin-3-yl]-1,5,7,9,11,13-hexamethyl-3,17-dioxa-15-azabicyclo[12.3.0]heptadecane-4,6,12,16-tetrone440648: Inhibition of CYP3A in human liver microsomes assessed as hydroxymidazolam formation by time dependent inhibition assayki0.0240uM
(1S,2R,5R,7R,8R,9R,11R,13R,14R)-8-[(2S,3R,4S,6R)-4-(dimethylamino)-3-hydroxy-6-methyloxan-2-yl]oxy-2-ethyl-9-hydroxy-15-[1-[(3-hydroxy-1,8-naphthyridin-4-yl)methyl]azetidin-3-yl]-1,5,7,9,11,13-hexamethyl-3,17-dioxa-15-azabicyclo[12.3.0]heptadecane-4,6,12,16-tetrone440648: Inhibition of CYP3A in human liver microsomes assessed as hydroxymidazolam formation by time dependent inhibition assayki0.0250uM
8-imidazol-1-yl-5,6,7,8-tetrahydroquinoline2022035: Inhibition of CYP450 (unknown origin)ic500.0335uM
1-methyl-3-[1-methyl-5-(4-methylphenyl)pyrazol-4-yl]-4-[(3S)-3-piperidin-1-ylpyrrolidin-1-yl]pyrazolo[5,4-d]pyrimidine1217207: Reversible inhibition of human CYP3A felodipine oxidase activityic500.1600uM
N-(4-chlorophenyl)-5-ethyl-N-methyl-3-phenyl-1,2-oxazole-4-carboxamide2108148: Inhibition of CYP450 (unknown origin)ic500.2512uM
Tacrolimus1209606: Competitive inhibition of CYP3A in human liver microsomeski0.3600uM
Carfilzomib1219229: Inhibition of CYP3A in human liver microsomes assessed as substrate metabolite formation using midazolam as substrate preincubated with microsomes for 30 mins prior to substrate addition measured after 5 mins by LC-MS/MS analysisic500.4900uM
(3S,3aS,6aR)-2-[(2S)-2-[[2-(1-adamantyl)acetyl]amino]-3,3-dimethylbutanoyl]-N-[(1S)-1-cyclohexyl-3-(cyclopropylamino)-2,3-dioxopropyl]-3,3a,4,5,6,6a-hexahydro-1H-cyclopenta[c]pyrrole-3-carboxamide2020327: Inhibition of CYP3A (unknown origin)ic500.5700uM
Voriconazole541854: Competitive inhibition of CYP3A in human liver microsomes assessed as midazolam 4-hydroxylation after 5 mins by Dixon plot analysiski0.6600uM
2-(dimethylamino)-2-(2-ethylphenyl)-N-[3-(3-sulfamoylphenyl)-1H-indazol-5-yl]acetamide2119433: Inhibition of CYP450 (unknown origin)ic500.7000uM
2-pyrrolidin-1-yl-N-[3-(3-sulfamoylphenyl)-1H-indazol-5-yl]-2-thiophen-3-ylacetamide2119433: Inhibition of CYP450 (unknown origin)ic500.9000uM
cyclosporine1209614: Reversible competitive inhibition of CYP3A-mediated 1’-OH midazolam formation in human liver microsomes after 7.5 mins by nonlinear regression studyki0.9800uM
2-[4-(trifluoromethyl)phenyl]chromen-4-one1860369: Inhibition of CYP450 in human HCT-116 cells assessed as 20-HETE formation in presence of arachidonic acid incubated for 15 mins by multi-enzyme assay based LC-MS/MS analysisic501.1000uM
N-[1-[(1,2-dihydroxy-2,6-dimethyl-3-oxoheptan-4-yl)amino]-1-oxo-3-phenylpropan-2-yl]-4-methyl-2-[[2-[(2-morpholin-4-ylacetyl)amino]-4-phenylbutanoyl]amino]pentanamide1219244: Time-dependent inhibition of CYP3A in human liver microsomes preincubated for 30 mins with carfilzomib by LC-MS/MS analysisic501.8000uM
N-[(3S)-1-[(3-bromo-4-piperidin-4-yloxyphenyl)methyl]pyrrolidin-3-yl]-3,4-dichlorobenzamide339723: Inhibition of CYP3A4ic501.9000uM
4-N-[(1S)-1,2,3,4-tetrahydronaphthalen-1-yl]-4-N-[[(7R)-5,6,7,8-tetrahydro-1,6-naphthyridin-7-yl]methyl]cyclohexane-1,4-diamine2124397: Inhibition of CYP450 (unknown origin)ic502.5000uM
1-[3-(2,4-dimethoxyphenyl)phenyl]-2,4-dimethoxybenzene1973305: Inhibition of CYP450 in pooled human liver microsomes in presence of NADPH measured every 3 mins for 120 mins by fluorescence based analysisic503.7000uM
1-[(E)-2-(2,4-dimethoxyphenyl)ethenyl]-3,5-dimethoxybenzene1973305: Inhibition of CYP450 in pooled human liver microsomes in presence of NADPH measured every 3 mins for 120 mins by fluorescence based analysisic503.7000uM
2,4-bis(3,5-dimethoxyphenyl)pyrimidine1973305: Inhibition of CYP450 in pooled human liver microsomes in presence of NADPH measured every 3 mins for 120 mins by fluorescence based analysisic503.8000uM
2,5-bis(3,5-dimethoxyphenyl)thiophene1973305: Inhibition of CYP450 in pooled human liver microsomes in presence of NADPH measured every 3 mins for 120 mins by fluorescence based analysisic503.9000uM
4-[2-(2,4-dimethoxyphenyl)-1,3-thiazol-4-yl]phenol1973305: Inhibition of CYP450 in pooled human liver microsomes in presence of NADPH measured every 3 mins for 120 mins by fluorescence based analysisic505.9000uM
1-pyridin-4-yl-1a,2,3,7b-tetrahydro-1H-cyclopropa[a]naphthalen-4-ol2022025: Inhibition of CYP450 in human liver microsomesic506.0534uM
(5R)-3-[1-(1H-indol-2-ylmethyl)piperidin-4-yl]-5-(6-methoxyquinolin-4-yl)-1,3-oxazolidin-2-one306257: Inhibition of CYP450ic507.9433uM
3-[1-[(3,4-dimethylphenyl)methyl]piperidin-4-yl]-5-(6-methoxyquinolin-4-yl)-1,3-oxazolidin-2-one306257: Inhibition of CYP450ic5010.0000uM
1-[3-(3,5-dimethoxyphenyl)phenyl]-3,5-dimethoxybenzene1973305: Inhibition of CYP450 in pooled human liver microsomes in presence of NADPH measured every 3 mins for 120 mins by fluorescence based analysisic5010.0000uM

CTD chemical–gene interactions

28 total (human), top 28 by PubMed support.

ChemicalActions (top 5)PubMed papers
Aflatoxin B1affects expression, decreases methylation, increases expression3
Arsenic Trioxideaffects binding, decreases reaction, increases expression2
Benzo(a)pyreneaffects methylation, decreases expression, increases methylation2
pirinixic acidaffects binding, increases activity, increases expression1
senecionineincreases expression1
4-aminophenylarsenoxideaffects binding, decreases reaction1
fipronilaffects cotreatment, increases expression1
tebuconazoleincreases expression1
cylindrospermopsindecreases expression1
CGP 52608affects binding, increases reaction1
obeticholic aciddecreases expression1
Resveratrolaffects cotreatment, decreases expression1
Troglitazoneincreases expression1
Bosentanaffects expression1
Acetaminophenincreases expression1
Biological Factorsdecreases expression1
Carbamazepineincreases expression1
Copperdecreases expression, affects cotreatment1
DEETincreases expression, affects cotreatment1
Diethylhexyl Phthalatedecreases expression1
Formaldehydedecreases expression1
N-Nitrosopyrrolidinedecreases expression1
Testosteroneaffects metabolic processing1
Tetrachlorodibenzodioxinaffects expression1
Urethanedecreases expression1
Cyclosporinedecreases expression1
beta Caroteneincreases expression1
Okadaic Aciddecreases expression1

ChEMBL screening assays

282 unique, capped per target: 279 admet, 3 binding

Representative assays (with source publication via chembl_document):

Assay IDTypeDescriptionSource paper
CHEMBL1042375ADMETInhibition of CYP3A in human liver microsomes assessed as hydroxymidazolam formation by time dependent inhibition assayDiscovery of azetidinyl ketolides for the treatment of susceptible and multidrug resistant community-acquired respiratory tract infections. — J Med Chem
CHEMBL4614611BindingDrug metabolism in human liver microsomes assessed as Cytochrome P450-mediated formation of 12-OHNVP by measuring Kcat/Km ratio in presence of NADPH regenerating reagents by uHPLC-MS/MS analysisTwelfth-Position Deuteration of Nevirapine Reduces 12-Hydroxy-Nevirapine Formation and Nevirapine-Induced Hepatocyte Death. — J Med Chem

Clinical trials (associated diseases)

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

No linked Atlas pages yet — the cross-entity mesh grows as the corpus expands.

About this page

Generated deterministically by Sugi Atlas from primary biomedical databases via BioBTree. Every record on this page traces to a primary source.

Generated
Atlas version
v1.1.4
BioBTree
v2.0.2

Sources 80

This page pulls from 80 datasets indexed by BioBTree:

alphafoldalphamissenseantibodybgeebgee_evidencebindingdbbiogrid_interactionbrendabrenda_kineticsccdscellosauruschembl_activitychembl_assaychembl_documentchembl_moleculechembl_targetciviccivic_evidenceclingen_dosageclingen_gene_validityclinical_trialsclinvarcollectrictd_gene_interactiondbsnpdepmapdiamond_similarityefoensemblentrezesm2_similarityexonfantom5_genefantom5_promotergenccgenerifgogoparentgtopdbgtopdb_interactiongwasgwas_studyhgnchpointactinterprointogenjasparmeshmimmirdbmondomsigdborphanetorthologparalogpatent_compoundpdbpfampharmgkb_clinicalpharmgkb_genepharmgkb_guidelinepharmgkb_variantpubchempubchem_activitypubchem_assaypubmedreactomereactomeparentrefseqrhearnacentralscxa_expressionscxa_gene_experimentsignorspliceaistring_interactiontranscriptufeatureuniprot