Loading
GPRC5D is an orphan class C G-protein-coupled receptor expressed on myeloma cells and on hard keratinised tissue (skin, nails, tongue), which explains the characteristic skin, nail and taste toxicity of drugs directed against it. Expression is high in roughly 60 to 80 percent of myeloma cases and correlates with high-risk disease. Because it is independent of BCMA, it offers a second surface address for patients whose disease has escaped BCMA-directed therapy. Talquetamab, a GPRC5D×CD3 bispecific, is approved; a GPRC5D CAR-T (arlocabtagene autoleucel) is in phase 3. Open questions are how to sequence GPRC5D and BCMA agents and whether antigen loss limits durability. For a newcomer: it is the backup target used when BCMA-directed myeloma drugs stop working.
In plain words · GPRC5D is a second myeloma target used when BCMA-directed drugs stop working.
Backbone ribbon from PDB 9IMA. RCSB PDB 9IMA. The ribbon widens where the chain is folded into a regular pattern and narrows where it is a loose loop.
GPRC5D is a second myeloma target used when BCMA-directed drugs stop working.
GPRC5D is an orphan class C GPCR.
2 products aim at GPRC5D: bispecific antibodies and cell therapies. Because it sits on the outside of the cell, it can be reached from the bloodstream: antibodies flag the cell, ADCs deliver a toxin, radioligands deliver radiation, and CAR-T or bispecifics bring a T cell.
Tumour-associated overexpression: 2 cell-killing or cell-finding medicines (Arlocabtagene Autoleucel, Talquetamab) aim at the antigen, which HPA finds stained high in 5 normal tissues; the medicine relies on the tumour carrying more of it than the normal tissue it shares it with. HPA GPRC5D: RNA tissue enriched (skin 1 26 nTPM); blood lineage lineage enriched (B-cells 15 nTPM); high antibody staining in 5 normal tissues; highest cancer staining lymphoma (8 of 12 high). Distribution: 1 cancer family in the corpus carries a prevalence row, label threshold or catalogue link for it (Multiple myeloma); Open Targets associates it with 1 specific cancer type at or above 0.5 (plasma cell myeloma). (Rule 5 of scripts/fetch-target-specificity.ts.)
Sources: Human Protein Atlas GPRC5D tissue; Human Protein Atlas GPRC5D pathology; Open Targets ENSG00000111291 associations
First described 2001. Earliest sequence paper UniProt cites for the protein: Braeuner-Osborne et al, Biochim. Biophys. Acta, 2001, "Cloning and characterization of a human orphan family C G-protein coupled receptor GPRC5D". Source.
What a pathology or genomic report can say about this target, each with the thresholds approvals use.
GPRC5D is an orphan class C GPCR.
RNA: tissue enriched (skin 1 26 nTPM), detected in some normal tissues. Blood: lineage enriched (B-cells 15 nTPM).
Medium: Bone marrow, Breast, Bronchus, Colon, Duodenum, Gallbladder, Kidney, Lymph node.
Medium only: carcinoid, cervical cancer, colorectal cancer, glioma.
Human Protein Atlas version 25.1, antibody staining at reliability approved, enhanced or supported; used under CC BY-SA 3.0. Staining counts are patients per level in the atlas cohort, not population prevalence.
| Cancer | Prevalence | Measure | Note | Source |
|---|---|---|---|---|
| Multiple myeloma | 60-80% | High expression by IHC/RNA | Expression correlates with high risk | Wikipedia |
Approximate, population-level figures; the measure column says what was counted. Ranges show the midpoint as a bar.
Arlocabtagene Autoleucel is an experimental CAR-T cell therapy from Juno Therapeutics, a Bristol-Myers Squibb in phase 3 trials for multiple myeloma, aimed at GPRC5D.
Talquetamab is the first drug against GPRC5D, a second myeloma target used after BCMA therapies stop working; taste and skin side effects are its signature.
Query for this target: (TITLE:"GPRC5D" OR ABSTRACT:"GPRC5D") AND (cancer OR tumor OR tumour OR oncology OR carcinoma OR lymphoma OR leukemia OR leukaemia OR myeloma OR sarcoma OR melanoma OR glioma). Results are unfiltered search hits about GPRC5D, not a curated reading list.
Shares Ajai Chari, MagnetisMM-3: elranatamab, a second BCMA bispecific, with a switch to fortnightly dosing after response, Talquetamab, T-cell engagers (bispecific) and the tag t-cell-engager-target.
Shares T-cell engagers (bispecific) and the tag t-cell-engager-target.
Shares BCMA-directed therapy → GPRC5D-directed therapy, Ajai Chari, Talquetamab, Relapsed or refractory multiple myeloma.
Shares BCMA-directed therapy → GPRC5D-directed therapy, Multiple Myeloma Research Foundation (MMRF), Plan the second CAR-T target before the first one is lost, Comprehensive Cancer Center Mainfranken, University Hospital Würzburg and the tag t-cell-engager-target.
Shares BCMA-directed therapy → GPRC5D-directed therapy, MagnetisMM-3: elranatamab, a second BCMA bispecific, with a switch to fortnightly dosing after response, Talquetamab, Relapsed or refractory multiple myeloma.
Shares Arlocabtagene Autoleucel, Relapsed or refractory multiple myeloma, Multiple myeloma.
Shares Arlocabtagene Autoleucel, Relapsed or refractory multiple myeloma, Multiple myeloma.
Shares MagnetisMM-3: elranatamab, a second BCMA bispecific, with a switch to fortnightly dosing after response, Relapsed or refractory multiple myeloma, T-cell engagers (bispecific), Multiple myeloma.