PTCH1 patched 1
ENSG00000185920 · protein coding · Open Targets profile
Negative regulator of the smoothened signaling pathway, which acts as a receptor for hedgehog (SHH, IHH and DHH) morphogens (PubMed:21537345, PubMed:29954986, PubMed:29995851, PubMed:30139912, PubMed:31127104, PubMed:31555730, PubMed:37611095, PubMed:40128518, PubMed:9811851). In absence of hedgehog, acts as an inhibitor of smoothened protein (SMO) by preventing SMO access to cholesterol: mechanistically, acts as a cholesterol transporter, which depeletes cholesterol from the outer leaflet of plasma membrane, thereby preventing cholesterol-binding to the extracellular CRD region of SMO (PubMed:31555730, PubMed:37611095). Hedgehog-binding inhibits PTCH1 cholesterol transporter activity, promoting SMO activation by cholesterol and transduction of the smoothened signaling pathway (PubMed:31548691). Molecular mechanism governing cholesterol transport are still unclear: may move cholesterol from the outer to the inner leaflet of the membrane in exchange for potassium or sodium ion export in the opposite direction (PubMed:37611095). Seems to have a tumor suppressor function, as inactivation of this protein is probably a necessary, if not sufficient step for tumorigenesis (PubMed:8658145). {ECO:0000269|PubMed:21537345, ECO:0000269|PubMed:29954986, ECO:0000269|PubMed:29995851, ECO:0000269|PubMed:30139912, ECO:0000269|PubMed:31127104, ECO:0000269|PubMed:31548691, ECO:0000269|PubMed:31555730, ECO:0000269|PubMed:37611095, ECO:0000269|PubMed:40128518, ECO:0000269|PubMed:8658145, ECO:0000269|PubMed:9811851}.
Each row is a cancer, strongest overall evidence first. The two dots show how strong the inherited (germline) and tumour-mutation (somatic) evidence is; the line between them is the gap.
Scores run from 0 (no evidence) to 1 (strongest). A missing dot at 0 means Open Targets holds no evidence of that kind. Source: Open Targets Platform, fetched live.
Tractability
- Small molecule
- Structure with Ligand
- Antibody
- GO CC high conf, UniProt loc med conf, UniProt SigP or TMHMM
- PROTAC
- UniProt Ubiquitination, Database Ubiquitination
gnomAD loss of function constraint: o/e 0.09679800271987915 (upper bound 0.15132999420166016). Low values mean loss of function is poorly tolerated, a safety flag for inhibition.
Who runs trials of these drugs
No named investigators on registry trials of PTCH1's approved or late-stage drugs in the last three years.
No terminated, withdrawn or suspended trials of PTCH1's drugs are registered
All 0 drugs and clinical candidates as a table
Each drug, stage and indication links to its Open Targets record, where the trials and approvals behind it are listed. Salt forms (for example a mesylate) are listed as Open Targets records them, as separate entries.
| Drug | Type | Highest stage | Indications | Source records |
|---|---|---|---|---|
| No drugs or clinical candidates recorded. | ||||