{"entity":{"id":"rspo3","kind":"target","name":"RSPO3","aka":["R-spondin 3","R-spondin-3","FLJ14440","THSD2"],"tldr":"RSPO3 (R-spondin-3) is a gene. The public catalogues list it as a drug target, and clinical evidence ties its variants to diagnosis, prognosis or drug response. Tied to Colorectal cancer, Breast cancer and Lung cancer.","summary":"Activator of the canonical Wnt signalling pathway by acting as a ligand for LGR4-6 receptors, which acts as a key regulator of angiogenesis. Upon binding to LGR4-6 (LGR4, LGR5 or LGR6), LGR4-6 associate with phosphorylated LRP6 and frizzled receptors that are activated by extracellular Wnt receptors, triggering the canonical Wnt signalling pathway to increase expression of target genes. Also regulates the canonical Wnt/beta-catenin-dependent pathway and non-canonical Wnt signalling by acting as an inhibitor of ZNRF3, an important regulator of the Wnt signalling pathway.\n\nOpen Targets scores its association with cancer at 0.64 (direct and indirect evidence; datatypes literature 0.96, genetic association 0.17, somatic mutation 0.97, clinical 0.08).","asOf":"2026-09-23","links":[{"label":"HGNC HGNC:20866","url":"https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:20866"},{"label":"UniProt Q9BXY4","url":"https://www.uniprot.org/uniprotkb/Q9BXY4/entry"},{"label":"NCBI Gene 84870","url":"https://www.ncbi.nlm.nih.gov/gene/84870"},{"label":"Ensembl ENSG00000146374","url":"https://www.ensembl.org/Homo_sapiens/Gene/Summary?g=ENSG00000146374"}],"tags":["cancer-genes-wave"],"related":["open-targets"],"cancers":["colorectal","breast-cancer","lung-cancer"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":["wnt"],"terms":["gene-fusion"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":["paper-seshagiri-rspo-fusions-colon-nature-2012"],"journals":[],"dependsOn":[],"notes":["Written by scripts/fetch-cancer-genes.ts from CIViC, Open Targets, IntOGen, HGNC and UniProt; the function text is UniProt's, condensed and in UK spelling. Roles: Open Targets known-drug datatype score 0.08. Evidence tier \"clinical-evidence\" is the strongest of those signals.","Prevalence not recorded: none of the sources gives a positivity rate.","Colorectal cancer: PTPRK-RSPO3 fusions were found, with RSPO2 fusions, in 10% of more than 70 colon tumours by transcriptome sequencing, mutually exclusive with APC mutation and able to potentiate WNT signalling (Seshagiri 2012). DNA panels find far fewer (32 of 7,237, 0.44%, in crc_msk_2026) because intron coverage is partial. An RSPO fusion is an APC-wild-type way of switching WNT on, and it is the selection criterion for porcupine and RSPO3 inhibitors in trials."],"provenance":{"editedBy":"scripts/fetch-cancer-genes.ts (CIViC, Open Targets, IntOGen, HGNC, UniProt)","editedOn":"2026-09-23"},"symbol":"RSPO3","role":["drug-target"],"evidenceTier":"clinical-evidence","sources":[{"label":"HGNC HGNC:20866","url":"https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:20866","note":"approved symbol, name, aliases, locus and cross-references (hgnc_complete_set.txt)"},{"label":"UniProt Q9BXY4","url":"https://www.uniprot.org/uniprotkb/Q9BXY4/entry","note":"protein name, function text, keywords and locations (REST API)"},{"label":"Open Targets ENSG00000146374","url":"https://platform.opentargets.org/target/ENSG00000146374/associations","note":"association with cancer (MONDO_0004992) 0.64; per-cancer scores at or above 0.5: colorectal cancer 0.53, breast cancer 0.51, lung cancer 0.51 (GraphQL API, CC0)"}],"distribution":"few-types","specificityNote":"Specificity not established: no corpus medicine is aimed at it and the catalogues give it only the role drug-target; HPA finds the RNA tissue enhanced, which says where the protein sits but not whether the tumour differs from normal tissue. HPA RSPO3: RNA tissue enhanced (smooth muscle 45 nTPM); no normal tissue stained high; highest cancer staining lymphoma (2 of 12 high). Distribution: 3 cancer families in the corpus carry a prevalence row, label threshold or catalogue link for it (Colorectal cancer, Breast cancer (all types), Lung cancer (all types)); Open Targets associates it with 0 specific cancer types at or above 0.5. (No rule of scripts/fetch-target-specificity.ts fired.)","specificitySources":[{"label":"Human Protein Atlas RSPO3 tissue","url":"https://www.proteinatlas.org/ENSG00000146374-RSPO3/tissue","note":"RNA tissue and blood lineage specificity, normal tissue antibody staining (version 25.1, CC BY-SA 3.0)"},{"label":"Open Targets ENSG00000146374 associations","url":"https://platform.opentargets.org/target/ENSG00000146374/associations","note":"cancer associations at or above 0.5 (CC0)"}],"hgnc":"HGNC:20866","ensembl":"ENSG00000146374","uniprot":"Q9BXY4","entrez":"84870","firstDescribed":2002,"firstDescribedBasis":"sequence","firstDescribedNote":"Earliest sequence paper UniProt cites for the protein: Chen J.-Z. et al, Mol. Biol. Rep, 2002, \"Cloning and identification of a cDNA that encodes a novel human protein with thrombospondin type I repeat domain, hPWTSR\".","firstDescribedSource":"https://pubmed.ncbi.nlm.nih.gov/12463421/","biology":"Activator of the canonical Wnt signalling pathway by acting as a ligand for LGR4-6 receptors, which acts as a key regulator of angiogenesis. Upon binding to LGR4-6 (LGR4, LGR5 or LGR6), LGR4-6 associate with phosphorylated LRP6 and frizzled receptors that are activated by extracellular Wnt receptors, triggering the canonical Wnt signalling pathway to increase expression of target genes. Also regulates the canonical Wnt/beta-catenin-dependent pathway and non-canonical Wnt signalling by acting as an inhibitor of ZNRF3, an important regulator of the Wnt signalling pathway. Acts as a ligand for frizzled FZD8 and LRP6. May negatively regulate the TGF-beta pathway. Acts as a key regulator of angiogenesis by controlling vascular stability and pruning: acts by activating the non-canonical Wnt signalling pathway in endothelial cells. Location: Secreted (UniProt). Locus 6q22.33 (HGNC).","whereFound":["Colorectal cancer: Open Targets association 0.53 with colorectal cancer (MONDO_0005575)","Breast cancer: Open Targets association 0.51 with breast cancer (MONDO_0007254)","Lung cancer: Open Targets association 0.51 with lung cancer (MONDO_0008903)","Colorectal cancer: gene fusion (ptprk-rspo3, eif3e-rspo2) 0.4-10%"],"targetClass":"other","prevalence":[{"cancerId":"colorectal","pct":"0.4-10","measure":"Gene fusion (PTPRK-RSPO3, EIF3E-RSPO2)","source":"https://doi.org/10.1038/nature11282","note":"Recurrent RSPO2 and RSPO3 fusions occurred together in 10% of more than 70 colon tumours analysed by exome, transcriptome and copy number, and were mutually exclusive with APC mutation (Seshagiri 2012; coadread_genentech). Targeted panels find far fewer because they bait the RSPO3 intron but not RSPO2: cBioPortal structural variants give PTPRK-RSPO3 in 32 of 7,237 samples, 0.44%, in crc_msk_2026 (RSPO2 3 samples) and RSPO3-PTPRK in 3 of 1,516 in crc_eo_2020."}]},"route":"/targets/rspo3/","neighbours":{"collection":[{"id":"open-targets","kind":"collection","name":"Open Targets Platform","route":"/collections/open-targets/"}],"cancer":[{"id":"breast-cancer","kind":"cancer","name":"Breast cancer (all types)","route":"/cancers/breast-cancer/"},{"id":"colorectal","kind":"cancer","name":"Colorectal cancer","route":"/cancers/colorectal/"},{"id":"lung-cancer","kind":"cancer","name":"Lung cancer (all types)","route":"/cancers/lung-cancer/"}],"pathway":[{"id":"wnt","kind":"pathway","name":"Wnt / β-catenin","route":"/pathways/wnt/"}],"term":[{"id":"gene-fusion","kind":"term","name":"Gene fusion","route":"/terms/gene-fusion/"}],"paper":[{"id":"paper-seshagiri-rspo-fusions-colon-nature-2012","kind":"paper","name":"Recurrent R-spondin fusions in colon cancer","route":"/key-papers/paper-seshagiri-rspo-fusions-colon-nature-2012/"}]}}