GPR161 G protein-coupled receptor 161
ENSG00000143147 · protein coding · Open Targets profile
G protein-coupled receptor that acts as a key inhibitor of the smoothened signaling pathway in primary cilia (PubMed:38326651). Inhibits the smoothened signaling pathway in absence of hedgehog (DHH, IHH or SHH) by promoting formation of the transcription repressor form of GLI2 and GLI3 transcription factors (PubMed:38326651). GPR161 activation triggers signaling via guanine nucleotide-binding protein G(s)/GNAS, mediating activation of adenylate cyclase activity and production of cAMP (PubMed:38326651). Increased cAMP levels activate PKA, promoting PKA-dependent processing of GLI2 and GLI3 transcription factors, leading to formation of transcription repressor GLI2R and GLI3R, which repress expression of target genes (PubMed:38326651). GPR161 also activates PKA by acting as a PKA-anchoring protein, which directly associates with type I PKA regulatory subunits (PRKAR1A and/or PRKAR1B), recruiting PKA followed by PKA-dependent processing of GLI2 and GLI3 transcription factors (PubMed:38326651). In presence of hedgehog, GPR161 is removed from primary cilia by smoothened (SMO), preventing its activity and allowing activation of the smoothened signaling (By similarity). In contrast to the majority of G protein- coupled receptors, it is not activated by a ligand and it either acts as a constitutively active receptor or as a mechanosensitive receptor (PubMed:38326651). Involved in regulation of the smoothened signaling pathway during early neural tube development, forelimb formation, skeletal development, embryonic cerebellar development and forebrain development (By similarity). Involved in the saltatory migration of neurons during brain development by acting as a mechanosensitive receptor that senses mechanical forces generated by fluid shear stress (By similarity). {ECO:0000250|UniProtKB:B2RPY5, ECO:0000269|PubMed:38326651}.
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, Druggable Family
- Antibody
- UniProt loc med conf, UniProt SigP or TMHMM, GO CC med conf
- PROTAC
- Database Ubiquitination
gnomAD loss of function constraint: o/e 0.6383100152015686 (upper bound 0.8914899826049805). 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 GPR161's approved or late-stage drugs in the last three years.
No terminated, withdrawn or suspended trials of GPR161'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. | ||||