{"entity":{"id":"gprc5d","kind":"target","name":"GPRC5D","aka":[],"tldr":"GPRC5D is a second myeloma target used when BCMA-directed drugs stop working.","summary":"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.","asOf":"2026-09-04","wikipedia":"https://en.wikipedia.org/wiki/GPRC5D","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/GPRC5D"}],"tags":["t-cell-engager-target"],"related":["gprc5d-expression"],"cancers":["multiple-myeloma"],"sections":[],"technologies":[],"targets":[],"drugs":["arlocabtagene-autoleucel"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"symbol":"GPRC5D","role":[],"sources":[],"specificity":"tumour-associated","distribution":"one-type","specificityNote":"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.)","specificitySources":[{"label":"Human Protein Atlas GPRC5D tissue","url":"https://www.proteinatlas.org/ENSG00000111291-GPRC5D/tissue","note":"RNA tissue and blood lineage specificity, normal tissue antibody staining (version 25.1, CC BY-SA 3.0)"},{"label":"Human Protein Atlas GPRC5D pathology","url":"https://www.proteinatlas.org/ENSG00000111291-GPRC5D/pathology","note":"patients per staining level per cancer type (version 25.1, CC BY-SA 3.0)"},{"label":"Open Targets ENSG00000111291 associations","url":"https://platform.opentargets.org/target/ENSG00000111291/associations","note":"cancer associations at or above 0.5 (CC0)"}],"hgnc":"HGNC:13310","ensembl":"ENSG00000111291","uniprot":"Q9NZD1","entrez":"55507","firstDescribed":2001,"firstDescribedBasis":"sequence","firstDescribedNote":"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\".","firstDescribedSource":"https://pubmed.ncbi.nlm.nih.gov/11311935/","biology":"GPRC5D is an orphan class C GPCR.","whereFound":["Multiple myeloma"],"targetClass":"surface-antigen","prevalence":[{"cancerId":"multiple-myeloma","pct":"60-80","measure":"High expression by IHC/RNA","source":"https://en.wikipedia.org/wiki/GPRC5D","note":"Expression correlates with high risk"}]},"route":"/targets/gprc5d/","neighbours":{"biomarker":[{"id":"gprc5d-expression","kind":"biomarker","name":"GPRC5D expression","route":"/biomarkers/gprc5d-expression/"}],"cancer":[{"id":"multiple-myeloma","kind":"cancer","name":"Multiple myeloma","route":"/cancers/multiple-myeloma/"},{"id":"myeloma-relapsed-refractory","kind":"cancer","name":"Relapsed or refractory multiple myeloma","route":"/cancers/myeloma-relapsed-refractory/"}],"drug":[{"id":"arlocabtagene-autoleucel","kind":"drug","name":"Arlocabtagene Autoleucel","route":"/drugs/arlocabtagene-autoleucel/"},{"id":"talquetamab","kind":"drug","name":"Talquetamab","route":"/drugs/talquetamab/"}],"pairing":[{"id":"bcma-then-gprc5d","kind":"pairing","name":"BCMA-directed therapy → GPRC5D-directed therapy","route":"/pairings/bcma-then-gprc5d/"}],"technology":[{"id":"car-t","kind":"technology","name":"CAR-T cell therapy","route":"/technologies/car-t/"},{"id":"t-cell-engager","kind":"technology","name":"T-cell engagers (bispecific)","route":"/technologies/t-cell-engager/"}],"person":[{"id":"ajai-chari","kind":"person","name":"Ajai Chari","route":"/people/ajai-chari/"}],"idea":[{"id":"idea-bio1-adaptive-car-antigen-switch","kind":"idea","name":"Plan the second CAR-T target before the first one is lost","route":"/ideas/idea-bio1-adaptive-car-antigen-switch/"}],"collection":[{"id":"mmrf","kind":"collection","name":"Multiple Myeloma Research Foundation (MMRF)","route":"/collections/mmrf/"}],"paper":[{"id":"paper-magnetismm-3-elranatamab-natmed-2023","kind":"paper","name":"MagnetisMM-3: elranatamab, a second BCMA bispecific, with a switch to fortnightly dosing after response","route":"/key-papers/paper-magnetismm-3-elranatamab-natmed-2023/"}],"institution":[{"id":"ccc-wuerzburg","kind":"institution","name":"Comprehensive Cancer Center Mainfranken, University Hospital Würzburg","route":"/institutions/ccc-wuerzburg/"}]}}