# RSPO3

Source: https://onco.cc/targets/rspo3/  
OnCo record `rspo3` (Target). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

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.

Open 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).

## Fields

- Kind: Target
- Last checked: 2026-09-23
- Also known as: R-spondin 3; R-spondin-3; FLJ14440; THSD2
- Tags: cancer-genes-wave
- Symbol: RSPO3
- Class: other
- 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).
- Where found: 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)

## 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.

## Sources

- HGNC HGNC:20866: https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:20866
- UniProt Q9BXY4: https://www.uniprot.org/uniprotkb/Q9BXY4/entry
- NCBI Gene 84870: https://www.ncbi.nlm.nih.gov/gene/84870
- Ensembl ENSG00000146374: https://www.ensembl.org/Homo_sapiens/Gene/Summary?g=ENSG00000146374

## Connected records

- collections: [Open Targets Platform](https://onco.cc/collections/open-targets/)
- cancers: [Breast cancer (all types)](https://onco.cc/cancers/breast-cancer/), [Colorectal cancer](https://onco.cc/cancers/colorectal/), [Lung cancer (all types)](https://onco.cc/cancers/lung-cancer/)

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JSON: https://onco.cc/api/v1/entities/rspo3.json