TAMOXIFEN PHARMACOKINETICS PATHWAY (PW:0000838)
Description
Tamoxifen (TAM, TX), an non-steroidal anti-estrogen, is one of the most commonly used drugs for the treatment and prevention of breast cancer. Estrogen is involved in the growth and development of breast cancers; estrogen mediated transcription is constitutively active in more than 50% of cases. Initially considered an antagonist, TAM is currently classified as a selective estrogen receptor modulator (SERM). It binds competitively to the estrogen receptors (ERs) acting as an antagonist in breast cancer cells and as a partial agonist in bone and the cardiovascular system. Members of the cytochrome P 450 (CYP) phase I and of phase II biotransformation pathways are responsible for the metabolism of the drug in human liver microsomes (HLM) and rat hepatic cytosol. TAM is extensively metabolized and both primary and secondary metabolites have higher potencies than the parent compound. Primary metabolites include alpha-OH-TAM and DMT or 4-OH-TAM (see DMT and 4-OH-TAM CYPs, respectively - red indicates the presence of both rat and human enzymes, blue is for human only). DMT and 4-OH-TAM are further metabolized to the secondary metabolite endoxifen (see endoxifen CYPs). TAM metabolites are substrates for several phase II conjugating enzymes and subjects to sulfonation or glucuronidation by sulfotransferases (SULT) and UDP-glycosyltransferases (UGT), respectively, with UGT providing the major conduit. Phase II biotransformation results in more hydrophilic compounds that are easier to eliminate via the bile or urine. However, some can also form toxic DNA adducts, such as for instance the O-sulfonated alpha-OH-TAM. Sulfonation involves the conjugation of PAPS to an O-, N- or S- acceptor group with O-sulfonation being the major reaction. Glucuronidation involves the formation of O-, N-, S- or C-linked products using UDPGA as a donor and all UGT enzymes can form O-glucuronides. In humans, there are four SULT (SULT1, 2, 4 and 6) and four UGT (UGT1, 2, 3 and 8) families, respectively. SULT2A1 and SULT1A1 sulfonate alpha-OH- and 4-OH-TAM, respectively. UGT1A4 is the primary enzyme involved in the glucuronidation of TAM and 4-OH-TAM; several others are involved in the transformation of 4-OH-TAM and endoxifen (see the two UGT entries). Polymorphisms in CYP and UGTs enzymes have been reported. The impact on enzymatic activity ranges from decreased to insignificant and to increased. Recently, it has been reported that multidrug efflux transporter ABCB1 is involved in the disposition of endoxifen; higher expression of the transporter has been observed in advanced tumors.
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Pathway Diagram:
Genes in Pathway:
G
Abcb1a
ATP binding cassette subfamily B member 1A
ISO
RGD PMID:21148080 RGD:5130188
NCBI chr 4:26,312,403...26,488,456
G
Cyp1a1
cytochrome P450, family 1, subfamily a, polypeptide 1
ISO
RGD PMID:12971802 RGD:5129544
NCBI chr 8:66,991,940...66,998,014
G
Cyp1a2
cytochrome P450, family 1, subfamily a, polypeptide 2
ISO
RGD PMID:12971802 RGD:5129544
NCBI chr 8:66,971,261...66,978,149
G
Cyp2b3
cytochrome P450, family 2, subfamily b, polypeptide 3
ISO
SMPDB SMP:00606
NCBI chr 1:90,780,468...90,859,852
G
Cyp2c6
cytochrome P450, family 2, subfamily C, polypeptide 6
ISO
RGD PMID:12971802 RGD:5129544
NCBI chr 1:247,879,058...247,916,804
G
Cyp2c79
cytochrome P450, family 2, subfamily c, polypeptide 79
ISO
RGD PMID:12971802 RGD:5129544
G
Cyp2d4
cytochrome P450, family 2, subfamily d, polypeptide 4
ISO
SMPDB SMP:00606
NCBI chr 7:115,762,662...115,771,832
G
Cyp3a2
cytochrome P450, family 3, subfamily a, polypeptide 2
IDA
RGD
PMID:12971802 RGD:5129544
NCBI chr12:14,321,771...14,343,886
G
Cyp3a23-3a1
cytochrome P450, family 3, subfamily a, polypeptide 23-polypeptide 1
IDA
RGD
PMID:12971802 RGD:5129544
NCBI chr12:14,369,950...14,398,803
G
Cyp3a9
cytochrome P450, family 3, subfamily a, polypeptide 9
ISO
SMPDB SMP:00606
NCBI chr12:21,919,955...21,960,160
G
Esr1
estrogen receptor 1
ISO
SMPDB SMP:00606
NCBI chr 1:43,511,685...43,904,454
G
Fmo1
flavin containing dimethylaniline monoxygenase 1
ISO
SMPDB SMP:00606
NCBI chr13:77,715,405...77,747,666
G
Fmo3
flavin containing dimethylaniline monoxygenase 3
ISO
SMPDB SMP:00606
NCBI chr13:77,838,899...77,868,869
G
Sult1a1
sulfotransferase family 1A member 1
ISO
SMPDB SMP:00606
NCBI chr 1:190,702,592...190,706,112
G
Sult2a1
sulfotransferase family 2A member 1
IDA
RGD
PMID:16099924 RGD:5129555
NCBI chr 1:84,582,011...84,639,001
G
Ugt1a1
UDP glucuronosyltransferase family 1 member A1
ISO
RGD PMID:19250197 RGD:5129558
NCBI chr 9:96,249,143...96,256,264
G
Ugt1a2
UDP glucuronosyltransferase 1 family, polypeptide A2
ISO
RGD PMID:19250197 RGD:5129558
NCBI chr 9:96,239,019...96,256,264
G
Ugt1a5
UDP glucuronosyltransferase family 1 member A5
ISO
SMPDB SMP:00606
NCBI chr 9:96,210,053...96,256,264
G
Ugt1a9
UDP glucuronosyltransferase family 1 member A9
ISO
RGD PMID:19250197 RGD:5129558
NCBI chr 9:96,144,786...96,256,264
G
Ugt2b7
UDP glucuronosyltransferase family 2 member B7
ISO
RGD PMID:19250197 RGD:5129558
NCBI chr14:21,251,535...21,274,451
Additional Elements in Pathway: (includes Gene Groups, Small Molecules, Other Pathways..etc.) Small Molecule PAPS 3'-phosphoadenosine-5'-phosphosulfate Small Molecule DMT N-desmethyltamoxifen Gene Group endoxifen CYPs the set of human cytochrome P450 enzymes involved in the conversion of DMT and 4-OH-DMT to tamoxifen Gene Group 4-OH-TAM CYPs the set of human cytochrome P450 enzymes involved in the conversion of tamoxifen to 4-OH-TAM Gene Group 4-OH-TAM UGTs the set of human UDP-glucuronosyltransferase enzymes involved in the conjugation of 4-OH-TAM metabolites Gene Group endoxifen UGTs the set of human UDP-glucuronosyltransferase enzymes involved in the conjugation of endoxifen metabolites Gene Group DMT CYPs the set of rat and human cytochrome P450 enzymes involved in the conversion of tamoxifen to DMT Small Molecule UDPGA uridine diphosphate glucuronic acid
Pathway Gene Annotations
Disease Annotations Associated with Genes in the tamoxifen pharmacokinetics pathway
Abcb1a acquired immunodeficiency syndrome , acute lymphoblastic leukemia , adrenocortical carcinoma , allergic rhinitis , Alzheimer's disease , Anthracycline-induced Cardiotoxicity , antisocial personality disorder , asthma , Audiogenic Epilepsy , autism spectrum disorder , Behcet's disease , Breast Neoplasms , cannabis abuse , cannabis dependence , carcinoma , cardiomyopathy , Chemical and Drug Induced Liver Injury , Chronic Hepatitis C , chronic myeloid leukemia , colorectal adenocarcinoma , Colorectal Neoplasms , congenital heart disease , COVID-19 , Critical Illness , Crohn's disease , cryoglobulinemia , diarrhea , diffuse large B-cell lymphoma , disease of cellular proliferation , disease of mental health , Disease Progression , drug dependence , Drug Overdose , Drug-induced Neutropenia , Drug-Related Side Effects and Adverse Reactions , encephalitis , ENCEPHALOPATHY, ACUTE TRANSIENT , end stage renal disease , Endotoxemia , Eosinophilia , epilepsy , Escherichia Coli Infections , Esophageal Neoplasms , Experimental Arthritis , Experimental Diabetes Mellitus , Experimental Liver Cirrhosis , Experimental Mammary Neoplasms , familial adenomatous polyposis , familial hyperlipidemia , familial Mediterranean fever , familial temporal lobe epilepsy 3 , Femur Head Necrosis , Fetal Growth Retardation , Genetic Predisposition to Disease , Genetic Translocation , Germ Cell and Embryonal Neoplasms , head and neck squamous cell carcinoma , heart disease , Helicobacter Infections , Hematologic Neoplasms , hepatocellular carcinoma , hereditary breast ovarian cancer syndrome , heroin dependence , human immunodeficiency virus infectious disease , Idiopathic Generalized Epilepsy , Inflammation , inflammatory bowel disease 13 , invasive ductal carcinoma , kidney disease , Kidney Neoplasms , Latent Tuberculosis , lung non-small cell carcinoma , malaria , metabolic dysfunction-associated steatotic liver disease , Nasal Polyps , nasal type extranodal NK/T-cell lymphoma , Nausea , Neoplasm Metastasis , nephroblastoma , nervous system disease , neuroblastoma , neutropenia , obstructive sleep apnea , opiate dependence , Orthostatic Hypotension , ovarian cancer , Pain , Parkinson's disease , perinatal necrotizing enterocolitis , peripheral nervous system disease , Poisoning , Postoperative Pain , pulmonary tuberculosis , renal cell carcinoma , Reperfusion Injury , rheumatoid arthritis , secondary Parkinson disease , ST Elevation Myocardial Infarction , status epilepticus , temporal lobe epilepsy , toxic encephalopathy , type 2 diabetes mellitus , ulcerative colitis , Vomiting Cyp1a1 acute kidney failure , Acute Lung Injury , acute lymphoblastic leukemia , acute myeloid leukemia , allergic contact dermatitis , allergic disease , ankylosing spondylitis , Arteritis , asthma , atopic dermatitis , autism spectrum disorder , Behcet's disease , biliary tract cancer , Birth Weight , Bradycardia , breast cancer , Breast Neoplasms , bronchitis , Cardiac Fibrosis , Cardiomegaly , Chemical and Drug Induced Liver Injury , Chronic Bronchitis , Chronic Intermittent Hypoxia , chronic myeloid leukemia , chronic obstructive pulmonary disease , clubfoot , colitis , contact dermatitis , cystic fibrosis , diabetes mellitus , Digestive System Neoplasms , dilated cardiomyopathy , Drug Eruptions , end stage renal disease , endometrial cancer , endometriosis , esophageal cancer , esophagus squamous cell carcinoma , Experimental Diabetes Mellitus , Experimental Liver Neoplasms , Fetal Growth Retardation , gallbladder cancer , Graves' disease , hamartoma , head and neck cancer , heart disease , Hematuria , hepatocellular carcinoma , Hepatomegaly , Hyperoxia , Hyperoxic Lung Injury , hypertension , Hypertriglyceridemia , hypertrophic cardiomyopathy , hypospadias , Inflammation , Jaundice , Keshan disease , Kidney Neoplasms , Liver Reperfusion Injury , long QT syndrome , lung cancer , Lung Injury , male infertility , Metabolic Side Effects of Drugs and Substances , Micronuclei, Chromosome-Defective , multiple myeloma , Nematode Infections , nephritis , Occupational Diseases , oral cavity cancer , oral squamous cell carcinoma , Parkinson's disease , Parkinsonism , periodontitis , peripheral vascular disease , pneumonia , polycystic ovary syndrome , porphyria cutanea tarda , Prenatal Exposure Delayed Effects , prostate cancer , Prostatic Neoplasms , psoriasis , psoriatic arthritis , pulmonary hypertension , Pulmonary Hypertension, Hypoxia-Induced , reactive arthritis , renal cell carcinoma , Sepsis , Sinus Tachycardia , Sjogren's syndrome , Spontaneous Abortions , stomach cancer , systemic lupus erythematosus , type 2 diabetes mellitus , urinary bladder cancer , Ventricular Remodeling Cyp1a2 acute kidney failure , acute lymphoblastic leukemia , Atrophy , autism spectrum disorder , breast cancer , Chemical and Drug Induced Liver Injury , cholestasis , chronic obstructive pulmonary disease , Colorectal Neoplasms , congestive heart failure , depressive disorder , Drug-Related Side Effects and Adverse Reactions , endometrial cancer , Experimental Liver Cirrhosis , Experimental Liver Neoplasms , Growth Disorders , hepatocellular carcinoma , Hepatomegaly , Intestinal Reperfusion Injury , Jaundice , liver cirrhosis , liver disease , Liver Injury , Lung Injury , Lung Neoplasms , metabolic dysfunction-associated steatotic liver disease , Metabolic Side Effects of Drugs and Substances , methemoglobinemia , neural tube defect , Phenacetin O-Deethylase, Deficiency of , porphyria cutanea tarda , Sepsis , splenic disease , Splenomegaly , squamous cell carcinoma , Tardive Dyskinesia , type 2 diabetes mellitus , Vitamin E Deficiency Cyp2b3 Acute Lymphoblastic Leukemia, with Lymphomatous Features , acute myeloid leukemia , autism spectrum disorder , Chemical and Drug Induced Liver Injury , cholestasis , drug dependence , Drug Overdose , Efavirenz central nervous system toxicity , end stage renal disease , Experimental Diabetes Mellitus , gliosarcoma , hepatocellular carcinoma , heroin dependence , human immunodeficiency virus infectious disease , Metabolic Side Effects of Drugs and Substances , neonatal abstinence syndrome , nicotine dependence , tuberculosis Cyp2c6 Acute Coronary Syndrome , acute kidney failure , alcohol withdrawal syndrome , Allergic Rhinoconjunctivitis , atrial fibrillation , autism spectrum disorder , breast cancer , cardiovascular system disease , Chemical and Drug Induced Liver Injury , dilated cardiomyopathy , Drug Eruptions , Dyslipidemias , end stage renal disease , eosinophilic esophagitis , Experimental Liver Neoplasms , Gastrointestinal Hemorrhage , Genetic Predisposition to Disease , head and neck squamous cell carcinoma , Helicobacter Infections , Hematologic Neoplasms , hepatocellular carcinoma , heroin dependence , invasive aspergillosis , Invasive Fungal Infections , Keshan disease , multiple chemical sensitivity , multiple myeloma , peptic ulcer disease , Plasmodium falciparum malaria , Poor Drug Metabolism, CYP2C19-Related , Poor Metabolism of Proguanil , primary ovarian insufficiency , Prostatic Neoplasms , sickle cell anemia , thrombosis , tuberculosis , type 2 diabetes mellitus Cyp2c79 acute lymphoblastic leukemia , autism spectrum disorder , chronic obstructive pulmonary disease , Drug-Induced Leukopenia , Drug-induced Neutropenia , Drug-Related Side Effects and Adverse Reactions , end stage renal disease , hepatocellular carcinoma , kidney disease , nervous system disease , peripheral nervous system disease , renal hypertension , Rhabdomyolysis , Rhabdomyolysis, Cerivastatin-Induced Cyp2d4 acute kidney failure , acute lymphoblastic leukemia , acute myeloid leukemia , alcohol dependence , Alzheimer's disease , amphetamine abuse , asthma , autism spectrum disorder , autoimmune hepatitis , basal ganglia disease , Bradycardia , Breast Neoplasms , Chemical and Drug Induced Liver Injury , Chronic Hepatitis C , cognitive disorder , Coma , Drug Overdose , Drug-Induced Dyskinesia , Drug-Related Side Effects and Adverse Reactions , Dysmenorrhea , dystonia , epilepsy with generalized tonic-clonic seizures , Experimental Liver Cirrhosis , extrapyramidal and movement disease , head and neck squamous cell carcinoma , interstitial nephritis , major depressive disorder , Manganese Poisoning , multiple myeloma , Muscle Rigidity , Occupational Diseases , opiate dependence , Parkinson's disease , Poor Drug Metabolism, CYP2D6-Related , Prenatal Exposure Delayed Effects , Prostatic Neoplasms , rhinitis , sexual health disorder , substance-related disorder , traumatic brain injury , Tremor , Weight Gain Cyp3a2 alcohol dependence , alcohol-associated liver disease , anxiety disorder , breast cancer , Breast Neoplasms , Chemical and Drug Induced Liver Injury , cholestasis , end stage renal disease , familial Mediterranean fever , Familial Prostate Cancer , hepatitis C , Inflammation , osteosarcoma , ovarian carcinoma , Prostatic Neoplasms , Subarachnoid Hemorrhage , Torsades de Pointes , type 2 diabetes mellitus , VITAMIN D-DEPENDENT RICKETS, TYPE 3 Cyp3a23-3a1 acute kidney failure , alcohol dependence , Chemical and Drug Induced Liver Injury , cholestasis , depressive disorder , hepatocellular adenoma , Inflammation , type 2 diabetes mellitus Cyp3a9 acute lymphoblastic leukemia , autism spectrum disorder , B-lymphoblastic leukemia/lymphoma , Chemotherapy-Induced Febrile Neutropenia , chronic myeloid leukemia , Drug-Induced Leukopenia , Drug-induced Neutropenia , essential hypertension , Experimental Liver Cirrhosis , kidney disease , liver cirrhosis , Myeloid Leukemia, Chronic-Phase , nephrosis , oral submucous fibrosis , Pediatric Crohn's Disease , Prostatic Neoplasms , Reperfusion Injury , thrombosis , toxic encephalopathy Esr1 adenocarcinoma , Alzheimer's disease , Animal Disease Models , Animal Mammary Neoplasms , arteriosclerosis , atherosclerosis , bone disease , Bone Fractures , breast cancer , Breast Cancer, Familial , breast carcinoma , Breast Neoplasms , Bronchial Hyperreactivity , carcinoma , cataract 33 , Chronic Periodontitis , coronary artery disease , cryptorchidism , Diabetic Nephropathies , Disease Progression , Endometrial Neoplasms , Endometrioid Carcinomas , endometriosis , Estrogen Resistance , Experimental Arthritis , Experimental Diabetes Mellitus , Experimental Liver Neoplasms , Experimental Mammary Neoplasms , Female Infertility , Female Urogenital Diseases , Feminization , Genetic Predisposition to Disease , glomerulonephritis , Hand Osteoarthritis , Hemorrhagic Shock , hepatocellular carcinoma , Hyperalgesia , idiopathic pulmonary fibrosis , in situ carcinoma , infertility , Insulin Resistance , Knee Osteoarthritis , leiomyoma , leukemia , Leydig cell tumor , Liver Neoplasms , Lung Neoplasms , lung non-small cell carcinoma , lymphangioleiomyomatosis , macular degeneration , male infertility , malignant astrocytoma , melanoma , Mesothelioma , Metabolic Bone Diseases , metabolic dysfunction-associated steatotic liver disease , migraine , mitochondrial metabolism disease , Musculoskeletal Pain , myocardial infarction , Myocardial Reperfusion Injury , Neoplasm Invasiveness , Neoplasm Metastasis , Neoplasm Recurrence, Local , Neoplastic Cell Transformation , neuroblastoma , obesity , oligospermia , osteoarthritis , Osteoarthritis, Hip , osteoporosis , Osteoporotic Fractures , ovarian cancer , Parkinsonism , peritonitis , pleurisy , Postmenopausal Osteoporosis , prostate cancer , prostate carcinoma in situ , prostatic hypertrophy , Prostatic Neoplasms , pulmonary hypertension , Spinal Cord Injuries , Spinal Fractures , sporadic breast cancer , Subarachnoid Hemorrhage , substance-induced psychosis , systemic scleroderma , transient cerebral ischemia , type 2 diabetes mellitus , urinary bladder cancer , Urination Disorders , Varicose Ulcer , vitiligo , Vulvar Lichen Sclerosus Fmo1 amyotrophic lateral sclerosis type 1 , autism spectrum disorder , Experimental Liver Cirrhosis Fmo3 autism spectrum disorder , Chemical and Drug Induced Liver Injury , familial adenomatous polyposis , genetic disease , hypertension , inherited metabolic disorder , trimethylaminuria Sult1a1 benign neoplasm , breast cancer , Breast Neoplasms , Chromosome Aberrations , Colonic Neoplasms , Colorectal Neoplasms , COVID-19 , endometrial cancer , Endometrial Neoplasms , esophagus squamous cell carcinoma , Genomic Instability , Hypotension , lung adenocarcinoma , lung cancer , lung squamous cell carcinoma , Myocardial Ischemia , neural tube defect , Ovarian Neoplasms , prostate cancer , Prostatic Neoplasms , Recurrence , stomach cancer , urinary bladder cancer , Urologic Neoplasms Sult2a1 Experimental Liver Cirrhosis , prostate cancer , Prostatic Neoplasms Ugt1a1 acute kidney failure , Acute Liver Failure , autism spectrum disorder , bilirubin metabolic disorder , breast cancer , Chemical and Drug Induced Liver Injury , cholecystolithiasis , cholelithiasis , cholestasis , contact dermatitis , Crigler Najjar Syndrome, Type 1 , Crigler Najjar Syndrome, Type 2 , Crigler-Najjar syndrome , Crohn's disease , Drug-induced Neutropenia , Drug-Related Side Effects and Adverse Reactions , endometrial cancer , Gallstones , Gilbert syndrome , Gram-Negative Bacterial Infections , hematopoietic system disease , hepatitis B , Hereditary Hyperbilirubinemia , Hodgkin's lymphoma , Hyperbilirubinemia, Transient Familial Neonatal , hyperthyroidism , Inflammation , Jaundice , kernicterus , lung non-small cell carcinoma , myeloid leukemia , Neonatal Hyperbilirubinemia , neutropenia , ovarian cancer , Polyuria , small cell carcinoma , Starvation , type 1 diabetes mellitus , type 2 diabetes mellitus Ugt1a2 Crigler-Najjar syndrome , Gilbert syndrome , schizophrenia Ugt1a5 celiac disease , Crigler-Najjar syndrome Ugt1a9 acute kidney failure , Chemical and Drug Induced Liver Injury , cholangiocarcinoma , Crigler-Najjar syndrome , Gilbert syndrome , Leber congenital amaurosis Ugt2b7 autism spectrum disorder , urinary bladder cancer
acquired immunodeficiency syndrome Abcb1a Acute Coronary Syndrome Cyp2c6 acute kidney failure Cyp1a1 , Cyp1a2 , Cyp2c6 , Cyp2d4 , Cyp3a23-3a1 , Ugt1a1 , Ugt1a9 Acute Liver Failure Ugt1a1 Acute Lung Injury Cyp1a1 acute lymphoblastic leukemia Abcb1a , Cyp1a1 , Cyp1a2 , Cyp2c79 , Cyp2d4 , Cyp3a9 Acute Lymphoblastic Leukemia, with Lymphomatous Features Cyp2b3 acute myeloid leukemia Cyp1a1 , Cyp2b3 , Cyp2d4 adenocarcinoma Esr1 adrenocortical carcinoma Abcb1a alcohol dependence Cyp2d4 , Cyp3a2 , Cyp3a23-3a1 alcohol withdrawal syndrome Cyp2c6 alcohol-associated liver disease Cyp3a2 allergic contact dermatitis Cyp1a1 allergic disease Cyp1a1 allergic rhinitis Abcb1a Allergic Rhinoconjunctivitis Cyp2c6 Alzheimer's disease Abcb1a , Cyp2d4 , Esr1 amphetamine abuse Cyp2d4 amyotrophic lateral sclerosis type 1 Fmo1 Animal Disease Models Esr1 Animal Mammary Neoplasms Esr1 ankylosing spondylitis Cyp1a1 Anthracycline-induced Cardiotoxicity Abcb1a antisocial personality disorder Abcb1a anxiety disorder Cyp3a2 arteriosclerosis Esr1 Arteritis Cyp1a1 asthma Abcb1a , Cyp1a1 , Cyp2d4 atherosclerosis Esr1 atopic dermatitis Cyp1a1 atrial fibrillation Cyp2c6 Atrophy Cyp1a2 Audiogenic Epilepsy Abcb1a autism spectrum disorder Abcb1a , Cyp1a1 , Cyp1a2 , Cyp2b3 , Cyp2c6 , Cyp2c79 , Cyp2d4 , Cyp3a9 , Fmo1 , Fmo3 , Ugt1a1 , Ugt2b7 autoimmune hepatitis Cyp2d4 B-lymphoblastic leukemia/lymphoma Cyp3a9 basal ganglia disease Cyp2d4 Behcet's disease Abcb1a , Cyp1a1 benign neoplasm Sult1a1 biliary tract cancer Cyp1a1 bilirubin metabolic disorder Ugt1a1 Birth Weight Cyp1a1 bone disease Esr1 Bone Fractures Esr1 Bradycardia Cyp1a1 , Cyp2d4 breast cancer Cyp1a1 , Cyp1a2 , Cyp2c6 , Cyp3a2 , Esr1 , Sult1a1 , Ugt1a1 Breast Cancer, Familial Esr1 breast carcinoma Esr1 Breast Neoplasms Abcb1a , Cyp1a1 , Cyp2d4 , Cyp3a2 , Esr1 , Sult1a1 Bronchial Hyperreactivity Esr1 bronchitis Cyp1a1 cannabis abuse Abcb1a cannabis dependence Abcb1a carcinoma Abcb1a , Esr1 Cardiac Fibrosis Cyp1a1 Cardiomegaly Cyp1a1 cardiomyopathy Abcb1a cardiovascular system disease Cyp2c6 cataract 33 Esr1 celiac disease Ugt1a5 Chemical and Drug Induced Liver Injury Abcb1a , Cyp1a1 , Cyp1a2 , Cyp2b3 , Cyp2c6 , Cyp2d4 , Cyp3a2 , Cyp3a23-3a1 , Fmo3 , Ugt1a1 , Ugt1a9 Chemotherapy-Induced Febrile Neutropenia Cyp3a9 cholangiocarcinoma Ugt1a9 cholecystolithiasis Ugt1a1 cholelithiasis Ugt1a1 cholestasis Cyp1a2 , Cyp2b3 , Cyp3a2 , Cyp3a23-3a1 , Ugt1a1 Chromosome Aberrations Sult1a1 Chronic Bronchitis Cyp1a1 Chronic Hepatitis C Abcb1a , Cyp2d4 Chronic Intermittent Hypoxia Cyp1a1 chronic myeloid leukemia Abcb1a , Cyp1a1 , Cyp3a9 chronic obstructive pulmonary disease Cyp1a1 , Cyp1a2 , Cyp2c79 Chronic Periodontitis Esr1 clubfoot Cyp1a1 cognitive disorder Cyp2d4 colitis Cyp1a1 Colonic Neoplasms Sult1a1 colorectal adenocarcinoma Abcb1a Colorectal Neoplasms Abcb1a , Cyp1a2 , Sult1a1 Coma Cyp2d4 congenital heart disease Abcb1a congestive heart failure Cyp1a2 contact dermatitis Cyp1a1 , Ugt1a1 coronary artery disease Esr1 COVID-19 Abcb1a , Sult1a1 Crigler Najjar Syndrome, Type 1 Ugt1a1 Crigler Najjar Syndrome, Type 2 Ugt1a1 Crigler-Najjar syndrome Ugt1a1 , Ugt1a2 , Ugt1a5 , Ugt1a9 Critical Illness Abcb1a Crohn's disease Abcb1a , Ugt1a1 cryoglobulinemia Abcb1a cryptorchidism Esr1 cystic fibrosis Cyp1a1 depressive disorder Cyp1a2 , Cyp3a23-3a1 diabetes mellitus Cyp1a1 Diabetic Nephropathies Esr1 diarrhea Abcb1a diffuse large B-cell lymphoma Abcb1a Digestive System Neoplasms Cyp1a1 dilated cardiomyopathy Cyp1a1 , Cyp2c6 disease of cellular proliferation Abcb1a disease of mental health Abcb1a Disease Progression Abcb1a , Esr1 drug dependence Abcb1a , Cyp2b3 Drug Eruptions Cyp1a1 , Cyp2c6 Drug Overdose Abcb1a , Cyp2b3 , Cyp2d4 Drug-Induced Dyskinesia Cyp2d4 Drug-Induced Leukopenia Cyp2c79 , Cyp3a9 Drug-induced Neutropenia Abcb1a , Cyp2c79 , Cyp3a9 , Ugt1a1 Drug-Related Side Effects and Adverse Reactions Abcb1a , Cyp1a2 , Cyp2c79 , Cyp2d4 , Ugt1a1 Dyslipidemias Cyp2c6 Dysmenorrhea Cyp2d4 dystonia Cyp2d4 Efavirenz central nervous system toxicity Cyp2b3 encephalitis Abcb1a ENCEPHALOPATHY, ACUTE TRANSIENT Abcb1a end stage renal disease Abcb1a , Cyp1a1 , Cyp2b3 , Cyp2c6 , Cyp2c79 , Cyp3a2 endometrial cancer Cyp1a1 , Cyp1a2 , Sult1a1 , Ugt1a1 Endometrial Neoplasms Esr1 , Sult1a1 Endometrioid Carcinomas Esr1 endometriosis Cyp1a1 , Esr1 Endotoxemia Abcb1a Eosinophilia Abcb1a eosinophilic esophagitis Cyp2c6 epilepsy Abcb1a epilepsy with generalized tonic-clonic seizures Cyp2d4 Escherichia Coli Infections Abcb1a esophageal cancer Cyp1a1 Esophageal Neoplasms Abcb1a esophagus squamous cell carcinoma Cyp1a1 , Sult1a1 essential hypertension Cyp3a9 Estrogen Resistance Esr1 Experimental Arthritis Abcb1a , Esr1 Experimental Diabetes Mellitus Abcb1a , Cyp1a1 , Cyp2b3 , Esr1 Experimental Liver Cirrhosis Abcb1a , Cyp1a2 , Cyp2d4 , Cyp3a9 , Fmo1 , Sult2a1 Experimental Liver Neoplasms Cyp1a1 , Cyp1a2 , Cyp2c6 , Esr1 Experimental Mammary Neoplasms Abcb1a , Esr1 extrapyramidal and movement disease Cyp2d4 familial adenomatous polyposis Abcb1a , Fmo3 familial hyperlipidemia Abcb1a familial Mediterranean fever Abcb1a , Cyp3a2 Familial Prostate Cancer Cyp3a2 familial temporal lobe epilepsy 3 Abcb1a Female Infertility Esr1 Female Urogenital Diseases Esr1 Feminization Esr1 Femur Head Necrosis Abcb1a Fetal Growth Retardation Abcb1a , Cyp1a1 gallbladder cancer Cyp1a1 Gallstones Ugt1a1 Gastrointestinal Hemorrhage Cyp2c6 genetic disease Fmo3 Genetic Predisposition to Disease Abcb1a , Cyp2c6 , Esr1 Genetic Translocation Abcb1a Genomic Instability Sult1a1 Germ Cell and Embryonal Neoplasms Abcb1a Gilbert syndrome Ugt1a1 , Ugt1a2 , Ugt1a9 gliosarcoma Cyp2b3 glomerulonephritis Esr1 Gram-Negative Bacterial Infections Ugt1a1 Graves' disease Cyp1a1 Growth Disorders Cyp1a2 hamartoma Cyp1a1 Hand Osteoarthritis Esr1 head and neck cancer Cyp1a1 head and neck squamous cell carcinoma Abcb1a , Cyp2c6 , Cyp2d4 heart disease Abcb1a , Cyp1a1 Helicobacter Infections Abcb1a , Cyp2c6 Hematologic Neoplasms Abcb1a , Cyp2c6 hematopoietic system disease Ugt1a1 Hematuria Cyp1a1 Hemorrhagic Shock Esr1 hepatitis B Ugt1a1 hepatitis C Cyp3a2 hepatocellular adenoma Cyp3a23-3a1 hepatocellular carcinoma Abcb1a , Cyp1a1 , Cyp1a2 , Cyp2b3 , Cyp2c6 , Cyp2c79 , Esr1 Hepatomegaly Cyp1a1 , Cyp1a2 hereditary breast ovarian cancer syndrome Abcb1a Hereditary Hyperbilirubinemia Ugt1a1 heroin dependence Abcb1a , Cyp2b3 , Cyp2c6 Hodgkin's lymphoma Ugt1a1 human immunodeficiency virus infectious disease Abcb1a , Cyp2b3 Hyperalgesia Esr1 Hyperbilirubinemia, Transient Familial Neonatal Ugt1a1 Hyperoxia Cyp1a1 Hyperoxic Lung Injury Cyp1a1 hypertension Cyp1a1 , Fmo3 hyperthyroidism Ugt1a1 Hypertriglyceridemia Cyp1a1 hypertrophic cardiomyopathy Cyp1a1 hypospadias Cyp1a1 Hypotension Sult1a1 Idiopathic Generalized Epilepsy Abcb1a idiopathic pulmonary fibrosis Esr1 in situ carcinoma Esr1 infertility Esr1 Inflammation Abcb1a , Cyp1a1 , Cyp3a2 , Cyp3a23-3a1 , Ugt1a1 inflammatory bowel disease 13 Abcb1a inherited metabolic disorder Fmo3 Insulin Resistance Esr1 interstitial nephritis Cyp2d4 Intestinal Reperfusion Injury Cyp1a2 invasive aspergillosis Cyp2c6 invasive ductal carcinoma Abcb1a Invasive Fungal Infections Cyp2c6 Jaundice Cyp1a1 , Cyp1a2 , Ugt1a1 kernicterus Ugt1a1 Keshan disease Cyp1a1 , Cyp2c6 kidney disease Abcb1a , Cyp2c79 , Cyp3a9 Kidney Neoplasms Abcb1a , Cyp1a1 Knee Osteoarthritis Esr1 Latent Tuberculosis Abcb1a Leber congenital amaurosis Ugt1a9 leiomyoma Esr1 leukemia Esr1 Leydig cell tumor Esr1 liver cirrhosis Cyp1a2 , Cyp3a9 liver disease Cyp1a2 Liver Injury Cyp1a2 Liver Neoplasms Esr1 Liver Reperfusion Injury Cyp1a1 long QT syndrome Cyp1a1 lung adenocarcinoma Sult1a1 lung cancer Cyp1a1 , Sult1a1 Lung Injury Cyp1a1 , Cyp1a2 Lung Neoplasms Cyp1a2 , Esr1 lung non-small cell carcinoma Abcb1a , Esr1 , Ugt1a1 lung squamous cell carcinoma Sult1a1 lymphangioleiomyomatosis Esr1 macular degeneration Esr1 major depressive disorder Cyp2d4 malaria Abcb1a male infertility Cyp1a1 , Esr1 malignant astrocytoma Esr1 Manganese Poisoning Cyp2d4 melanoma Esr1 Mesothelioma Esr1 Metabolic Bone Diseases Esr1 metabolic dysfunction-associated steatotic liver disease Abcb1a , Cyp1a2 , Esr1 Metabolic Side Effects of Drugs and Substances Cyp1a1 , Cyp1a2 , Cyp2b3 methemoglobinemia Cyp1a2 Micronuclei, Chromosome-Defective Cyp1a1 migraine Esr1 mitochondrial metabolism disease Esr1 multiple chemical sensitivity Cyp2c6 multiple myeloma Cyp1a1 , Cyp2c6 , Cyp2d4 Muscle Rigidity Cyp2d4 Musculoskeletal Pain Esr1 myeloid leukemia Ugt1a1 Myeloid Leukemia, Chronic-Phase Cyp3a9 myocardial infarction Esr1 Myocardial Ischemia Sult1a1 Myocardial Reperfusion Injury Esr1 Nasal Polyps Abcb1a nasal type extranodal NK/T-cell lymphoma Abcb1a Nausea Abcb1a Nematode Infections Cyp1a1 neonatal abstinence syndrome Cyp2b3 Neonatal Hyperbilirubinemia Ugt1a1 Neoplasm Invasiveness Esr1 Neoplasm Metastasis Abcb1a , Esr1 Neoplasm Recurrence, Local Esr1 Neoplastic Cell Transformation Esr1 nephritis Cyp1a1 nephroblastoma Abcb1a nephrosis Cyp3a9 nervous system disease Abcb1a , Cyp2c79 neural tube defect Cyp1a2 , Sult1a1 neuroblastoma Abcb1a , Esr1 neutropenia Abcb1a , Ugt1a1 nicotine dependence Cyp2b3 obesity Esr1 obstructive sleep apnea Abcb1a Occupational Diseases Cyp1a1 , Cyp2d4 oligospermia Esr1 opiate dependence Abcb1a , Cyp2d4 oral cavity cancer Cyp1a1 oral squamous cell carcinoma Cyp1a1 oral submucous fibrosis Cyp3a9 Orthostatic Hypotension Abcb1a osteoarthritis Esr1 Osteoarthritis, Hip Esr1 osteoporosis Esr1 Osteoporotic Fractures Esr1 osteosarcoma Cyp3a2 ovarian cancer Abcb1a , Esr1 , Ugt1a1 ovarian carcinoma Cyp3a2 Ovarian Neoplasms Sult1a1 Pain Abcb1a Parkinson's disease Abcb1a , Cyp1a1 , Cyp2d4 Parkinsonism Cyp1a1 , Esr1 Pediatric Crohn's Disease Cyp3a9 peptic ulcer disease Cyp2c6 perinatal necrotizing enterocolitis Abcb1a periodontitis Cyp1a1 peripheral nervous system disease Abcb1a , Cyp2c79 peripheral vascular disease Cyp1a1 peritonitis Esr1 Phenacetin O-Deethylase, Deficiency of Cyp1a2 Plasmodium falciparum malaria Cyp2c6 pleurisy Esr1 pneumonia Cyp1a1 Poisoning Abcb1a polycystic ovary syndrome Cyp1a1 Polyuria Ugt1a1 Poor Drug Metabolism, CYP2C19-Related Cyp2c6 Poor Drug Metabolism, CYP2D6-Related Cyp2d4 Poor Metabolism of Proguanil Cyp2c6 porphyria cutanea tarda Cyp1a1 , Cyp1a2 Postmenopausal Osteoporosis Esr1 Postoperative Pain Abcb1a Prenatal Exposure Delayed Effects Cyp1a1 , Cyp2d4 primary ovarian insufficiency Cyp2c6 prostate cancer Cyp1a1 , Esr1 , Sult1a1 , Sult2a1 prostate carcinoma in situ Esr1 prostatic hypertrophy Esr1 Prostatic Neoplasms Cyp1a1 , Cyp2c6 , Cyp2d4 , Cyp3a2 , Cyp3a9 , Esr1 , Sult1a1 , Sult2a1 psoriasis Cyp1a1 psoriatic arthritis Cyp1a1 pulmonary hypertension Cyp1a1 , Esr1 Pulmonary Hypertension, Hypoxia-Induced Cyp1a1 pulmonary tuberculosis Abcb1a reactive arthritis Cyp1a1 Recurrence Sult1a1 renal cell carcinoma Abcb1a , Cyp1a1 renal hypertension Cyp2c79 Reperfusion Injury Abcb1a , Cyp3a9 Rhabdomyolysis Cyp2c79 Rhabdomyolysis, Cerivastatin-Induced Cyp2c79 rheumatoid arthritis Abcb1a rhinitis Cyp2d4 schizophrenia Ugt1a2 secondary Parkinson disease Abcb1a Sepsis Cyp1a1 , Cyp1a2 sexual health disorder Cyp2d4 sickle cell anemia Cyp2c6 Sinus Tachycardia Cyp1a1 Sjogren's syndrome Cyp1a1 small cell carcinoma Ugt1a1 Spinal Cord Injuries Esr1 Spinal Fractures Esr1 splenic disease Cyp1a2 Splenomegaly Cyp1a2 Spontaneous Abortions Cyp1a1 sporadic breast cancer Esr1 squamous cell carcinoma Cyp1a2 ST Elevation Myocardial Infarction Abcb1a Starvation Ugt1a1 status epilepticus Abcb1a stomach cancer Cyp1a1 , Sult1a1 Subarachnoid Hemorrhage Cyp3a2 , Esr1 substance-induced psychosis Esr1 substance-related disorder Cyp2d4 systemic lupus erythematosus Cyp1a1 systemic scleroderma Esr1 Tardive Dyskinesia Cyp1a2 temporal lobe epilepsy Abcb1a thrombosis Cyp2c6 , Cyp3a9 Torsades de Pointes Cyp3a2 toxic encephalopathy Abcb1a , Cyp3a9 transient cerebral ischemia Esr1 traumatic brain injury Cyp2d4 Tremor Cyp2d4 trimethylaminuria Fmo3 tuberculosis Cyp2b3 , Cyp2c6 type 1 diabetes mellitus Ugt1a1 type 2 diabetes mellitus Abcb1a , Cyp1a1 , Cyp1a2 , Cyp2c6 , Cyp3a2 , Cyp3a23-3a1 , Esr1 , Ugt1a1 ulcerative colitis Abcb1a urinary bladder cancer Cyp1a1 , Esr1 , Sult1a1 , Ugt2b7 Urination Disorders Esr1 Urologic Neoplasms Sult1a1 Varicose Ulcer Esr1 Ventricular Remodeling Cyp1a1 VITAMIN D-DEPENDENT RICKETS, TYPE 3 Cyp3a2 Vitamin E Deficiency Cyp1a2 vitiligo Esr1 Vomiting Abcb1a Vulvar Lichen Sclerosus Esr1 Weight Gain Cyp2d4
