{"entity":{"id":"tph1","kind":"target","name":"Tryptophan hydroxylase 1","aka":[],"tldr":"Tryptophan hydroxylase makes serotonin, the hormone that neuroendocrine tumours pour out in carcinoid syndrome; telotristat ethyl blocks the enzyme to cut the diarrhoea that somatostatin analogues leave uncontrolled.","summary":"Tryptophan hydroxylase 1 is the rate-limiting enzyme for serotonin synthesis outside the brain, chiefly in the enterochromaffin cells of the gut. Metastatic neuroendocrine tumours that keep this machinery release large amounts of serotonin, causing the diarrhoea, flushing and eventual heart-valve fibrosis of carcinoid syndrome. Telotristat ethyl, approved in the United States and Europe in 2017, inhibits TPH1 peripherally and reduced bowel movement frequency in the TELESTAR trial when added to somatostatin analogues; it does not cross into the brain, so the brain isoform TPH2 and mood are spared.","asOf":"2026-09-04","wikipedia":"https://en.wikipedia.org/wiki/Tryptophan_hydroxylase_1","links":[{"label":"UniProt P17752: TPH1","url":"https://www.uniprot.org/uniprotkb/P17752/entry"},{"label":"HGNC:12008 TPH1","url":"https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:12008"},{"label":"ChEMBL target CHEMBL3831287","url":"https://www.ebi.ac.uk/chembl/explore/target/CHEMBL3831287"}],"tags":["chembl-gap"],"related":["sstr2"],"cancers":["neuroendocrine"],"sections":[],"technologies":[],"targets":[],"drugs":["telotristat-ethyl"],"companies":[],"institutions":[],"pathways":[],"terms":["carcinoid-syndrome"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"symbol":"TPH1","role":[],"sources":[],"specificity":"tumour-associated","distribution":"one-type","specificityNote":"Tumour-associated overexpression: HPA finds the RNA cancer enhanced in cancer (Uterine Corpus Endometrial Carcinoma (TCGA)) and group enriched in normal choroid plexus, intestine, stomach 1, so the tumour and the normal tissue it comes from share the target and the medicine relies on the difference in level. HPA TPH1: RNA group enriched (choroid plexus 6 nTPM, intestine 19 nTPM, stomach 1 15 nTPM); no normal tissue stained high; highest cancer staining colorectal cancer (8 of 12 high). Distribution: 1 cancer family in the corpus carries a prevalence row, label threshold or catalogue link for it (Neuroendocrine tumours); Open Targets associates it with 0 specific cancer types at or above 0.5. (Rule 7 of scripts/fetch-target-specificity.ts.)","specificitySources":[{"label":"Human Protein Atlas TPH1 tissue","url":"https://www.proteinatlas.org/ENSG00000129167-TPH1/tissue","note":"RNA tissue and blood lineage specificity, normal tissue antibody staining (version 25.1, CC BY-SA 3.0)"},{"label":"Human Protein Atlas TPH1 pathology","url":"https://www.proteinatlas.org/ENSG00000129167-TPH1/pathology","note":"patients per staining level per cancer type (version 25.1, CC BY-SA 3.0)"},{"label":"Open Targets ENSG00000129167 associations","url":"https://platform.opentargets.org/target/ENSG00000129167/associations","note":"cancer associations at or above 0.5 (CC0)"}],"hgnc":"HGNC:12008","ensembl":"ENSG00000129167","uniprot":"P17752","entrez":"7166","firstDescribed":1990,"firstDescribedBasis":"sequence","firstDescribedNote":"Earliest sequence paper UniProt cites for the protein: Boulalard et al, Nucleic Acids Res, 1990, \"Complete coding sequence of human tryptophan hydroxylase\".","firstDescribedSource":"https://pubmed.ncbi.nlm.nih.gov/2377472/","biology":"A cytosolic aromatic amino-acid hydroxylase requiring tetrahydrobiopterin and iron; converts tryptophan to 5-hydroxytryptophan, which is then decarboxylated to serotonin.","whereFound":["Enterochromaffin cells of the gut and pineal gland","Serotonin-secreting neuroendocrine tumours"],"targetClass":"enzyme","prevalence":[{"cancerId":"neuroendocrine","pct":"host","measure":"Host target: serotonin synthesis in enterochromaffin cells. Not a tumour alteration, so no prevalence applies; the drug acts on normal tissue or on symptoms."}]},"route":"/targets/tph1/","neighbours":{"target":[{"id":"sstr2","kind":"target","name":"Somatostatin receptor 2","route":"/targets/sstr2/"}],"cancer":[{"id":"neuroendocrine","kind":"cancer","name":"Neuroendocrine tumours","route":"/cancers/neuroendocrine/"}],"drug":[{"id":"telotristat-ethyl","kind":"drug","name":"Telotristat ethyl","route":"/drugs/telotristat-ethyl/"}],"term":[{"id":"carcinoid-syndrome","kind":"term","name":"Carcinoid syndrome and carcinoid heart disease","route":"/terms/carcinoid-syndrome/"}]}}