Details of Drug-Metabolizing Enzyme (DME)

General Information of Drug-Metabolizing Enzyme (DME) (ID: DEP5BDK)

DME Name Tryptophan 5-hydroxylase 1 (TPH1)
Synonyms Tryptophan 5-monooxygenase 1; Normal tryptophan hydroxylase; TPH; TPH1; TPRH; TRPH
Gene Name TPH1
UniProt ID
TPH1_HUMAN
INTEDE ID
DME0173
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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Gene ID
7166
EC Number EC: 1.14.16.4
Oxidoreductase
Oxygen paired donor oxidoreductase
Pteridine donor oxidoreductase
EC: 1.14.16.4
Lineage Species: Homo sapiens
Kingdom: Metazoa
Phylum: Chordata
Class: Mammalia
Order: Primates
Family: Hominidae
Genus: Homo
Species: Homo sapiens
Sequence
MIEDNKENKDHSLERGRASLIFSLKNEVGGLIKALKIFQEKHVNLLHIESRKSKRRNSEF
EIFVDCDINREQLNDIFHLLKSHTNVLSVNLPDNFTLKEDGMETVPWFPKKISDLDHCAN
RVLMYGSELDADHPGFKDNVYRKRRKYFADLAMNYKHGDPIPKVEFTEEEIKTWGTVFQE
LNKLYPTHACREYLKNLPLLSKYCGYREDNIPQLEDVSNFLKERTGFSIRPVAGYLSPRD
FLSGLAFRVFHCTQYVRHSSDPFYTPEPDTCHELLGHVPLLAEPSFAQFSQEIGLASLGA
SEEAVQKLATCYFFTVEFGLCKQDGQLRVFGAGLLSSISELKHALSGHAKVKPFDPKITC
KQECLITTFQDVYFVSESFEDAKEKMREFTKTIKRPFGVKYNPYTRSIQILKDTKSITSA
MNELQHDLDVVSDALAKVSRKPSI
Function This enzyme catalyzes the formation of 5-hydroxytryptophan, a precursor to the neurotransmitter serotonin.
KEGG Pathway
Folate biosynthesis (hsa00790 )
Metabolic pathways (hsa01100 )
Serotonergic synapse (hsa04726 )
Tryptophan metabolism (hsa00380 )
Reactome Pathway
Serotonin and melatonin biosynthesis (R-HSA-209931 )

Molecular Interaction Atlas (MIA) of This DME

Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DME
1 Approved Drug(s) Metabolized by This DME
Drug Name Drug ID Indication ICD 11 Highest Status REF
L-Tryptophan DMIBH7M Depression 6A70-6A7Z Approved [5]

Molecular Expression Atlas (MEA) of This DME

Molecular Expression Atlas (MEA) Jump to Detail Molecular Expression Atlas of This DME
Disease Name ICD 11 Studied Tissue p-value Fold-Change Z-score
Acute myelocytic leukaemia 2B33.1 Bone marrow 4.68E-03 5.47E-02 3.67E-01
Alopecia ED70 Skin from scalp 3.03E-01 -1.27E-01 -3.98E-01
Alzheimer's disease 8A20 Entorhinal cortex 2.75E-01 -2.24E-02 -1.85E-01
Ankylosing spondylitis FA92.0 Pheripheral blood 2.15E-01 1.50E-01 1.53E+00
Aortic stenosis BB70 Calcified aortic valve 9.07E-01 -2.03E-01 -5.49E-01
Apnea 7A40 Hyperplastic tonsil 6.32E-01 -5.21E-02 -6.87E-01
Arthropathy FA00-FA5Z Peripheral blood 1.14E-01 -8.92E-02 -8.72E-01
Asthma CA23 Nasal and bronchial airway 1.79E-06 -1.69E-01 -3.41E-01
Atopic dermatitis EA80 Skin 8.58E-01 -6.71E-02 -5.89E-01
Autism 6A02 Whole blood 9.60E-01 8.22E-02 4.15E-01
Autoimmune uveitis 9A96 Peripheral monocyte 7.21E-02 -1.47E-01 -1.24E+00
Autosomal dominant monocytopenia 4B04 Whole blood 4.64E-01 -2.85E-03 -1.92E-02
Bacterial infection of gingival 1C1H Gingival tissue 3.00E-01 2.74E-02 1.98E-01
Batten disease 5C56.1 Whole blood 1.79E-01 9.53E-03 9.16E-02
Behcet's disease 4A62 Peripheral blood 5.76E-01 6.26E-04 4.98E-03
Bipolar disorder 6A60-6A6Z Prefrontal cortex 2.98E-01 -3.03E-02 -2.17E-01
Bladder cancer 2C94 Bladder tissue 3.16E-02 1.12E-01 5.97E-01
Breast cancer 2C60-2C6Z Breast tissue 1.42E-07 -8.72E-03 -4.18E-02
Cardioembolic stroke 8B11.20 Whole blood 1.31E-01 -7.72E-02 -3.76E-01
Cervical cancer 2C77 Cervical tissue 2.13E-01 -7.75E-02 -6.35E-01
Childhood onset rheumatic disease FA20.Z Peripheral blood 2.21E-01 4.77E-02 3.98E-01
Chronic hepatitis C 1E51.1 Whole blood 4.68E-01 1.02E-02 3.36E-02
Chronic obstructive pulmonary disease CA22 Lung tissue 3.32E-01 2.87E-02 1.94E-01
Chronic obstructive pulmonary disease CA22 Small airway epithelium 8.27E-01 1.40E-02 7.97E-02
Chronic rhinosinusitis CA0A Sinus mucosa tissue 2.98E-01 5.11E-03 5.14E-02
Colon cancer 2B90 Colon tissue 8.54E-54 -2.57E+00 -2.10E+00
Coronary artery disease BA80-BA8Z Peripheral blood 7.18E-01 -2.75E-03 -1.80E-02
Diffuse large B-cell lymphoma 2A81 Tonsil tissue 4.24E-01 -4.65E-02 -2.07E-01
Endometriosis GA10 Endometrium tissue 3.57E-01 -1.64E-02 -9.74E-02
Familial hypercholesterolemia 5C80.00 Peripheral blood 1.97E-01 -6.37E-02 -5.13E-01
Familial hypercholesterolemia 5C80.00 Whole blood 3.05E-03 -1.75E-01 -1.35E+00
Gastric cancer 2B72 Gastric tissue 4.19E-01 -6.77E-01 -8.79E-01
Glioblastopma 2A00.00 Nervous tissue 4.50E-14 5.56E-02 2.48E-01
Glioma 2A00.0Y-2A00.0Z Brain stem tissue 6.26E-01 3.01E-02 6.55E-01
Glioma 2A00.0Y-2A00.0Z White matter tissue 2.64E-04 -5.85E-01 -2.63E+00
Head and neck cancer 2D42 Head and neck tissue 8.58E-07 -7.68E-02 -5.01E-01
HIV-associated neurocognitive impairment 8A2Y-8A2Z White matter tissue 3.76E-01 -4.21E-02 -2.96E-01
Huntington's disease 8A01.10 Whole blood 1.85E-01 1.15E-02 1.34E-01
Idiopathic pulmonary fibrosis CB03.4 Lung tissue 4.26E-01 3.49E-02 2.32E-01
Immunodeficiency 4A00-4A20 Peripheral blood 5.38E-03 -2.19E-01 -1.05E+00
Influenza 1E30 Whole blood 4.06E-01 3.89E-03 4.25E-02
Interstitial cystitis GC00.3 Bladder tissue 2.25E-01 3.09E-02 3.43E-01
Intracranial aneurysm 8B01.0 Intracranial artery 1.24E-01 -1.06E-04 -3.13E-04
Irritable bowel syndrome DD91.0 Rectal colon tissue 3.58E-01 -1.36E-01 -1.74E-01
Ischemic stroke 8B11 Peripheral blood 7.23E-02 7.17E-02 4.52E-01
Juvenile idiopathic arthritis FA24 Peripheral blood 9.38E-01 6.99E-03 2.87E-02
Lateral sclerosis 8B60.4 Skin 1.44E-01 -8.10E-02 -8.64E-01
Lateral sclerosis 8B60.4 Cervical spinal cord 6.11E-01 3.22E-02 2.43E-01
Liver cancer 2C12.0 Liver tissue 2.42E-01 -4.41E-02 -2.70E-01
Liver failure DB99.7-DB99.8 Liver tissue 4.68E-02 -1.69E-01 -1.10E+00
Lung cancer 2C25 Lung tissue 9.31E-06 -2.91E-02 -1.05E-01
Lupus erythematosus 4A40 Whole blood 1.64E-01 1.18E-02 5.26E-02
Major depressive disorder 6A70-6A7Z Hippocampus 9.20E-01 -5.55E-03 -4.01E-02
Major depressive disorder 6A70-6A7Z Whole blood 7.38E-01 4.41E-03 1.53E-02
Melanoma 2C30 Skin 5.38E-01 -6.38E-02 -2.86E-01
Multiple myeloma 2A83.1 Peripheral blood 1.87E-01 3.25E-02 3.61E-01
Multiple myeloma 2A83.1 Bone marrow 6.23E-02 1.02E-01 9.78E-01
Multiple sclerosis 8A40 Plasmacytoid dendritic cells 4.35E-02 -1.90E-01 -5.98E-01
Myelodysplastic syndrome 2A36-2A3Z Bone marrow 5.57E-03 -4.59E-02 -4.70E-01
Myelofibrosis 2A20.2 Whole blood 4.58E-01 -3.34E-02 -1.94E-01
Myocardial infarction BA41-BA50 Peripheral blood 5.59E-01 1.59E-02 2.54E-02
Myopathy 8C70.6 Muscle tissue 4.40E-01 -3.91E-02 -2.82E-01
Neonatal sepsis KA60 Whole blood 2.66E-04 -6.46E-02 -4.52E-01
Neuroectodermal tumour 2A00.11 Brain stem tissue 5.07E-02 -2.45E-01 -1.28E+00
Non-alcoholic fatty liver disease DB92 Liver tissue 8.70E-01 1.25E-02 1.21E-01
Obesity related type 2 diabetes 5A11 Omental adipose tissue 5.73E-01 4.10E-03 6.11E-02
Olive pollen allergy CA08.00 Peripheral blood 4.41E-01 -1.39E-01 -7.44E-01
Oral cancer 2B6E Oral tissue 2.97E-03 -9.90E-02 -5.74E-01
Osteoarthritis FA00-FA0Z Synovial tissue 5.93E-01 -1.51E-01 -6.62E-01
Osteoporosis FB83.1 Bone marrow 6.90E-02 1.71E-01 3.18E+00
Ovarian cancer 2C73 Ovarian tissue 5.48E-01 -3.93E-02 -1.96E-01
Pancreatic cancer 2C10 Pancreas 4.93E-01 -1.51E-01 -6.44E-01
Parkinson's disease 8A00.0 Substantia nigra tissue 2.36E-01 -6.85E-02 -6.51E-01
Pediatric respiratory syncytial virus infection CA40.11 Peripheral blood 1.68E-03 -1.47E-01 -1.19E+00
Pituitary cancer 2D12 Pituitary tissue 7.61E-01 -3.46E-01 -3.69E-01
Pituitary gonadotrope tumour 2D12 Pituitary tissue 8.76E-01 1.51E-01 1.42E-01
Polycystic ovary syndrome 5A80.1 Vastus lateralis muscle 2.03E-02 -6.79E-02 -7.70E-01
Polycythemia vera 2A20.4 Whole blood 8.05E-01 -1.80E-02 -1.00E-01
Pompe disease 5C51.3 Biceps muscle 5.99E-01 -9.81E-02 -5.86E-01
Preterm birth KA21.4Z Myometrium 9.75E-02 -1.02E-01 -1.49E+00
Prostate cancer 2C82 Prostate 1.45E-01 1.84E-01 3.91E-01
Psoriasis EA90 Skin 3.06E-02 -5.97E-02 -2.62E-01
Rectal cancer 2B92 Rectal colon tissue 1.67E-04 -3.97E+00 -4.17E+00
Renal cancer 2C90-2C91 Kidney 2.43E-02 -9.59E-02 -7.40E-01
Retinoblastoma 2D02.2 Uvea 2.98E-02 -1.11E-01 -1.17E+00
Rheumatoid arthritis FA20 Synovial tissue 8.42E-01 4.39E-02 2.03E-01
Rhinovirus infection CA42.1 Nasal epithelium tissue 6.99E-01 -1.48E-02 -1.41E-01
Schizophrenia 6A20 Prefrontal cortex 1.77E-01 -2.74E-02 -1.66E-01
Schizophrenia 6A20 Superior temporal cortex 8.56E-01 4.09E-02 2.94E-01
Scleroderma 4A42.Z Whole blood 5.96E-01 -1.08E-01 -6.82E-01
Seizure 8A60-8A6Z Whole blood 8.95E-01 5.97E-02 4.05E-01
Sensitive skin EK0Z Skin 1.20E-01 -8.79E-02 -5.54E-01
Sepsis with septic shock 1G41 Whole blood 1.71E-04 -8.00E-02 -4.55E-01
Shwachman-Diamond syndrome 3A70.0 Bone marrow 3.24E-01 5.99E-03 2.14E-02
Sickle cell disease 3A51.0-3A51.3 Peripheral blood 2.18E-01 9.08E-02 5.23E-01
Simpson golabi behmel syndrome LD2C Adipose tissue 2.29E-01 -1.25E-01 -2.05E+00
Sjogren's syndrome 4A43.2 Salivary gland tissue 4.38E-01 3.14E-02 6.68E-01
Skin cancer 2C30-2C3Z Skin 3.95E-02 -8.98E-02 -3.27E-01
Thrombocythemia 3B63 Whole blood 7.24E-01 -4.98E-02 -2.85E-01
Thrombocytopenia 3B64 Whole blood 8.34E-01 -7.32E-02 -4.89E-01
Thyroid cancer 2D10 Thyroid 7.54E-09 1.22E-01 5.09E-01
Tibial muscular dystrophy 8C75 Muscle tissue 6.00E-07 -3.03E-01 -2.10E+00
Tuberous sclerosis complex LD2D.2 Perituberal tissue 5.71E-04 1.73E-01 6.64E+00
Type 2 diabetes 5A11 Liver tissue 4.04E-01 -3.53E-02 -3.33E-01
Ureter cancer 2C92 Urothelium 2.67E-01 9.97E-03 9.88E-02
Uterine cancer 2C78 Endometrium tissue 8.12E-04 1.24E-02 6.43E-02
Vitiligo ED63.0 Skin 4.94E-01 -5.93E-02 -3.11E-01
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⏷ Show the Full List of DME Expression Under 107 Diseases

The Drug Therapeutic Target (DTT) Role of This DME

DME DTT Name Tryptophan 5-hydroxylase 1 (TPH1) DTT Info
DME DTT Type Clinical trial
2 Clinical Trial Drug(s) Targeting This DTT
Drug Name Drug ID Indication ICD 11 Highest Status REF
AGN-2979 DMLQRFO Psychotic disorder 6A20-6A25 Phase 2 [1]
KAR5585 DMXYN1H Pulmonary arterial hypertension BB01.0 Phase 1 [2]
3 Investigative Drug(s) Targeting This DTT
Drug Name Drug ID Indication ICD 11 Highest Status REF
6-fluorotryptophan DM6YD3U Discovery agent N.A. Investigative [3]
alpha-propyldopacetamide DMQKMX3 Discovery agent N.A. Investigative [4]
fenclonine DMUBO3E Discovery agent N.A. Investigative [4]

References

1 Antidepressant-like action of AGN 2979, a tryptophan hydroxylase activation inhibitor, in a chronic mild stress model of depression in rats. Eur Neuropsychopharmacol. 2001 Oct;11(5):351-7.
2 Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
3 (+)-6-fluorotryptophan, an inhibitor of tryptophan hydroxylase: sleep and wakefulness in the rat. Neuropharmacology. 1981 Apr;20(4):335-9.
4 URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Target id: 1241).
5 Developmental role of tryptophan hydroxylase in the nervous system. Mol Neurobiol. 2007 Feb;35(1):45-54.