G protein-coupled receptor which associates with the patched protein (PTCH) to transduce hedgehog protein signaling. Binding of sonic hedgehog (SHH) to its receptor patched prevents inhibition of smoothened (SMO) by patched. When active, SMO binds to and sequesters protein kinase A catalytic subunit PRKACA at the cell membrane, preventing PRKACA-mediated phosphorylation of GLI transcription factors which releases the GLI proteins from PRKACA-mediated inhibition and allows for transcriptional activation of hedgehog pathway target genes (By similarity).
Required for the accumulation of KIF7, GLI2 and GLI3 in the cilia (PubMed:19592253). Interacts with DLG5 at the ciliary base to induce the accumulation of KIF7 and GLI2 at the ciliary tip for GLI2 activation (By similarity)
Homodimer (PubMed:23636324). Interacts (via C-terminus) with protein kinase A catalytic subunit PRKACA; interacts with free PRKACA subunits and the interaction leads to sequestration of PRKACA at the membrane, preventing PRKACA-mediated phosphorylation of GLI transcription factors (By similarity). Interacts with ARRB2 (By similarity).
Interacts with KIF7 (PubMed:19592253). Interacts with BBS5 and BBS7; the interactions are indicative for the association of SMO with the BBsome complex to facilitate ciliary localization of SMO (PubMed:22072986). Interacts with DLG5 and SDCBP (By similarity).
Interacts with DRC4 (PubMed:21659505)
The N-terminal extracellular domain mediates sterol-binding which is required for maximal activation of signaling (PubMed:24859340). Contains a second sterol-binding site within the seven-transmembrane pocket which is also required for activation (By similarity). The activating sterol is likely to be cholesterol (PubMed:35658032).
The extracellular site is required for SHH-induced activity while the site within the transmembrane pocket regulates basal signaling in the absence of SHH (PubMed:35658032)
A multisystem disorder characterized by patchy skin lesions, polysyndactyly, diverse cerebral malformations, unicoronal craniosynostosis, iris colobomas, microphthalmia, and intestinal malrotation with myofibromas or hamartomas.
Click a pathway to open the interactive Reactome viewer.
Genes with an experimentally identified or computationally predicted synthetic-lethal relationship to MOSMO, aggregated across our SSL data sources. Click any partner node to view that gene’s page.
Nodes and edges are coloured by the SSL data source. Partners appearing in more than one source are shown in grey.
Total Trials Found: 270
| NCT ID | Condition | Brief Title | Phase | Status |
|---|---|---|---|---|
| NCT01071564 | Estrogen Receptor Negative, HER2/Neu Negative, Progesterone Receptor Negative, Recurrent Breast Carcinoma, Stage IIIB Breast Cancer, Stage IIIC Breast Cancer, Stage IV Breast Cancer, Triple-Negative Breast Carcinoma | RO4929097 and Vismodegib in Treating Patients With Breast Cancer That is Metastatic or Cannot Be Removed By Surgery | PHASE1 | TERMINATED |
| NCT02523014 | Intracranial Meningioma, Recurrent Meningioma, NF2 Gene Mutation | Vismodegib, FAK Inhibitor GSK2256098, Capivasertib, and Abemaciclib in Treating Patients With Progressive Meningiomas | PHASE2 | RECRUITING |
| NCT03390296 | Recurrent Acute Myeloid Leukemia, Refractory Acute Myeloid Leukemia | OX40, Venetoclax, Avelumab, Glasdegib, Gemtuzumab Ozogamicin, and Azacitidine in Relapsed or Refractory Acute Myeloid Leukemia | PHASE1, PHASE2 | COMPLETED |
| NCT01842646 | Myelodysplastic Syndrome (MDS), Chronic Myelomonocytic Leukemia (CMML) | Phase II Hedgehog Inhibitor for Myelodysplastic Syndrome (MDS) | PHASE2 | COMPLETED |
| NCT02323139 | MDS | A Study of LDE255 in Combination With Azacitidine for High Risk Myelodysplastic Syndrome Patients | PHASE1 | COMPLETED |
| NCT03070691 | Basal Cell Carcinoma | Efficacy, Safety and Tolerability of Topically Applied LDE225 Cream (Hedgehog Pathway Inhibitor) in Adult Patients With Nevoid Basal Cell Carcinoma Syndrome (NBCCS) | PHASE2, PHASE3 | WITHDRAWN |
| NCT01106508 | Advanced Solid Tumors, Recurrent or Refractory Medulloblastoma, Locally Advanced or Metastatic Basal Cell Carcinoma | A Dose Finding and Safety Study of Oral LEQ506 in Patients With Advanced Solid Tumors | PHASE1 | COMPLETED |
| NCT03052478 | Stomach Neoplasms | Study of Vismodegib in Advanced Gastric Adenocarcinoma Patients With SMO Overexpression | PHASE2 | COMPLETED |
| NCT01357655 | Leukemia | Phase 2 Dasatinib Combo With Smoothened (SMO) Antagonist (BMS-833923) | PHASE2 | TERMINATED |
| NCT02002689 | PTCH1 or SMO Activated Solid and Hematologic Tumors | LDE225 for Patients With PTCH1 or SMO Mutated Tumors | PHASE2 | TERMINATED |