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CAMIP causal chains
CAMIP stands for Causal Analysis of Mechanistic Inference in Pharmacogenomics. Each row links a pharmacogene regulated by the receptor to its inducer and the drugs taken alongside it, through a causal chain grounded in pharmacology. Affected drugs are taken from PharmGKB clinical annotations, and each chain is confirmed by a reviewing pharmacist. These receptors govern the inducible enzymes and transporters that handle a large share of clinically used drugs and their interactions. The CYP3A subfamily alone metabolizes roughly 30% of marketed drugs, as summarized in a CYP450 metabolism review, and the panel further spans CYP2C9, CYP2C19, CYP1A2, CYP2C8, CYP2A6, UGT1A1 and major hepatic transporters, covering many first line agents prone to drug interactions driven by induction. CAMIP describes mechanism only and gives no dosing, monitoring, severity, or treatment recommendations.
AhR axis
Canonical inducer: Smoking; PAHs; Experimental TCDD
| Gene | Regulatory element | Predicted effect if AhR binding is reduced | Affected substrate drugs | Refs |
|---|---|---|---|---|
| ALDH3A1 | overlapping the TSS | Reduced AhR-mediated induction of ALDH3A1 would lower ALDH3A1-mediated oxidation of aldophosphamide; increased retention of the active intermediate may sensitise tumour cells to cyclophosphamide. | cyclophosphamide; doxorubicin; fluorouracil | 24677340 |
| CYP1A1 | at promoter -276 bp | Diminished AhR-mediated transactivation of CYP1A1, reducing both basal and inducible CYP1A1 expression and thereby attenuating local bioactivation of procarcinogens such as benzo[a]pyrene. | deferasirox; carbamazepine; phenobarbital; phenytoin; valproic acid; capecitabine | 31199573, 37707797 |
| CYP1A2 | at promoter -3123 bp | Reduced receptor-mediated transactivation of CYP1A2 diminishes the inducibility of this major hepatic CYP; substrate clearance is correspondingly less enhanced in the induced state, which may raise exposure to narrow-therapeutic substrates. | clozapine; caffeine; leflunomide; paroxetine; olanzapine; escitalopram | 19961320, 37707797 |
| CYP1B1under review | overlapping TSS | Impaired receptor-mediated signaling that abolishes both the basal constitutive expression and chemical inducibility of CYP1B1 in extrahepatic tissues, perturbing the localized pathway of estradiol 4-hydroxylation and procarcinogen activation that drives tissue-specific susceptibility to malignancies. | cyclophosphamide; doxorubicin; fluorouracil; risperidone; epirubicin; paclitaxel | 10702233, 37707797 |
FXR axis
Canonical inducer: Obeticholic acid; Experimental GW4064
| Gene | Regulatory element | Predicted effect if FXR binding is reduced | Affected substrate drugs | Refs |
|---|---|---|---|---|
| ABCB11under review | overlapping TSS | Disrupted receptor-mediated transactivation via the FXR/RXRα heterodimer, abolishing the critical canalicular expression of the Bile Salt Export Pump. This directly cripples the ATP-dependent rate-limiting step of hepatic bile acid elimination, precipitating toxic intracellular bile salt accumulation and rendering hepatocytes profoundly vulnerable to severe drug-induced cholestatic liver injury under medications such as bosentan and cyclosporine. | bosentan; cyclosporine; estrogens | 11870371, 25198545 |
| ABCB4under review | at promoter -6485 bp | Disrupted receptor-mediated transactivation via the FXR/RXRα heterodimer, impairing the coordinated up-regulation of ABCB4. This leads to a deficiency in ATP-dependent phospholipid translocation across the canalicular membrane of hepatocytes, decreasing biliary phospholipid secretion and increasing the physiological susceptibility to intrahepatic cholestasis and gallstone formation. | imatinib; anthracyclines and related substances | 14527955, 25198545 |
| CYP8B1under review | in distal enhancer +19834 bp | Altered receptor-mediated feedback repression of CYP8B1, shifting the cholic acid to chenodeoxycholic acid synthesis ratio in endogenous bile acid pathways. | none in routine clinical use, endogenous or bile acid pathway | 15550563 |
| FGF19under review | at promoter -2789 bp | Attenuated receptor-mediated transcriptional activation of enterocyte FGF19, disrupting the intestinal endocrine signaling cascade required for the downstream feedback repression of hepatic bile acid biosynthesis. | none in routine clinical use, endogenous or bile acid pathway | 22561792, 25198545 |
| NR0B2under review | overlapping TSS | Blunted receptor-mediated induction of NR0B2 expression, weakening the downstream transcriptional feedback inhibition of hepatic bile acid synthesis pathways. | none in routine clinical use, endogenous or bile acid pathway | 16269825, 25198545 |
| SLC10A1 | in distal enhancer +11900 bp | Reduced FXR binding would weaken FXR-driven SHP induction; with SHP-mediated repression relieved, SLC10A1/NTCP expression would rise, thus increasing the hepatic clearance of NTCP substrates. | rosuvastatin | 23299969, 23930675 |
| SLC51Aunder review | at promoter +1088 bp | Blunted receptor-mediated induction of SLC51A expression, reducing heteromeric basolateral bile acid efflux capacity in hepatocytes and enterocytes. | none in routine clinical use, endogenous or bile acid pathway | 16269519 |
| SLC51Bunder review | overlapping TSS | Blunted receptor-mediated induction of SLC51B expression, reducing heteromeric basolateral bile acid efflux capacity in hepatocytes and enterocytes. | none in routine clinical use, endogenous or bile acid pathway | 16269519 |
PXR axis
Canonical inducer: Rifampicin
| Gene | Regulatory element | Predicted effect if PXR binding is reduced | Affected substrate drugs | Refs |
|---|---|---|---|---|
| ABCC2under review | at promoter -440 bp | Blunted receptor-mediated induction of ABCC2 expression, diminishing canalicular efflux capacity and reducing the clearance of clearance-dependent substrates. | tenofovir; methotrexate; mycophenolic acid; talinolol; lopinavir; tacrolimus | 11706036 |
| ABCC3under review | at promoter -544 bp | Blunted receptor-mediated induction of ABCC3 expression, weakening basolateral transport capacity for organic anions and drug conjugates such as methotrexate and morphine-glucuronide. | cisplatin; morphine; cyclophosphamide; doxorubicin; methotrexate; vincristine | 19593667 |
| CES2under review | at promoter -111 bp | Blunted receptor-mediated induction of CES2 expression, impairing the hydrolytic bioactivation of key prodrugs such as irinotecan. | irinotecan | 17003103 |
| CYP2A6 | in distal enhancer +21719 bp | Blunted receptor-mediated induction of CYP2A6 decreases the hepatic oxidative metabolism and clearance of its substrates such as nicotine and coumarin. | nicotine; coumarin; tegafur; efavirenz; letrozole; metronidazole | 16857725, 25275310 |
| CYP2C19 | in distal enhancer +14490 bp | Blunted receptor-mediated induction of CYP2C19 lowers antiplatelet effect of the prodrug clopidogrel, and raises exposure of voriconazole. | clopidogrel; voriconazole; omeprazole; lansoprazole; citalopram; escitalopram | 12869636, 25275310, 40301309, 38899464, 27981572 |
| CYP2C8 | at promoter -1846 bp | Blunted receptor-mediated induction of CYP2C8 reduces the inducible metabolic clearance of substrates such as repaglinide and paclitaxel. | ibuprofen; tacrolimus; rosiglitazone; pioglitazone; amodiaquine; paclitaxel | 15933212, 25275310 |
| CYP2C9 | at promoter -1557 bp | Blunted receptor-mediated induction of CYP2C9 reduces the inducible metabolism of narrow-therapeutic-index substrates such as warfarin and phenytoin. | warfarin; phenytoin; celecoxib; fluvastatin; ibuprofen; meloxicam | 25275310, 40301309 |
| CYP3A4 | at promoter -137 bp | CYP3A subfamily enzymes metabolize ~30% of clinically used drugs. Blunted receptor-mediated induction of CYP3A4 reduces its inducible metabolic capacity under PXR inducers. | quetiapine; tacrolimus; fentanyl; cyclosporine; sufentanil; simvastatin | 10570062, 23333322, 40301309 |
| CYP3A5under review | overlapping TSS | Blunted receptor-mediated induction of CYP3A5, reducing the inducible component of metabolic clearance specifically in CYP3A5-expressing individuals. | tacrolimus; cyclosporine; everolimus; sirolimus; fentanyl; carbamazepine | 15252010, 25275310 |
| CYP3A7under review | at promoter -7497 bp | Blunted receptor-mediated induction of CYP3A7, attenuating inducible developmental xenobiotic detoxification pathways. | tacrolimus | 11162490, 25275310 |
| SULT2A1under review | at promoter -63 bp | Blunted receptor-mediated induction of SULT2A1, reducing the inducible sulfonation capacity for hydroxysteroids and clinical substrates such as budesonide. | DHEA; budesonide | 17595319, 25275310 |
| UGT1A1 | at promoter -137 bp | Blunted receptor-mediated induction of UGT1A1, reducing the inducible glucuronidation capacity. For irinotecan, reduced glucuronidation of the active metabolite SN-38 may increase toxicity. | FOLFIRI; irinotecan; atazanavir; atazanavir / ritonavir; sacituzumab govitecan; SN-38 | 25275310, 40301309, 26417955, 17728214 |
| UGT1A3under review | at promoter -82 bp | Blunted receptor-mediated induction of UGT1A3, dampening the inducible glucuronidation of lipophilic clinical substrates such as atorvastatin and fibrates. | deferasirox; telmisartan; atorvastatin; montelukast; atazanavir; ritonavir | 14977869, 40301309 |
| UGT1A4under review | at promoter -22 bp | Blunted receptor-mediated induction of UGT1A4, leading to attenuated clearance and increased systemic exposure of its clinical substrates such as lamotrigine. | lamotrigine; tamoxifen; ABT-751; anastrozole; testosterone | 14977869, 40301309 |
| UGT1A6under review | overlapping TSS | Blunted receptor-mediated induction of UGT1A6, restricting the inducible glucuronidation capacity of critical small-molecule drugs. | valproic acid; aspirin; irinotecan; oxaliplatin; tegafur / gimeracil / oteracil; deferiprone | 12644700, 40301309 |
| UGT1A9under review | in distal enhancer +19740 bp | Blunted receptor-mediated induction of UGT1A9, attenuating the inducible glucuronidation capacity of critical clinical substrates such as mycophenolic acid and propofol. | SN-38; irinotecan; propofol; sorafenib; mycophenolate mofetil; cotinine glucuronide | 31611795, 40301309 |
| UGT2B7under review | in distal enhancer +14718 bp | Blunted receptor-mediated modulation of UGT2B7, altering the adaptive clearance rate of heavily utilized opioid and immunosuppressant substrates. | lamotrigine; valproic acid; morphine; oxcarbazepine; fentanyl; zidovudine | 29610665 |
Entries still under review have their predicted effect shown in gray as provisional; reviewed entries carry the reviewing pharmacist's verbatim wording and reference choices. Affected substrate drugs are mapped from PharmGKB clinical annotations, highest evidence level first; endogenous or bile acid genes with no PharmGKB drug association are labeled as such. Causal chains describe mechanism only and are scientific predictions, not medical advice.