# RSPO2

Source: https://onco.cc/targets/rspo2/  
OnCo record `rspo2` (Target). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

RSPO2 (R-spondin-2) is a gene that drives cell growth when it is altered. The public catalogues list it as an oncogene driver, and it is called a cancer driver by mutation analysis of patient cohorts. Tied to Prostate cancer, Breast cancer and Colorectal cancer.

## Summary

Activator of the canonical Wnt signalling pathway by acting as a ligand for LGR4-6 receptors. 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 0.74 (direct and indirect evidence; datatypes literature 0.94, animal model 0.55, genetic association 0.62, somatic mutation 0.82). IntOGen calls it a driver in 1 cohort (1 activating, 0 loss-of-function), covering Colorectal Adenocarcinoma.

## Fields

- Kind: Target
- Last checked: 2026-09-23
- Also known as: R-spondin 2; R-spondin-2; MGC35555
- Tags: cancer-genes-wave
- Symbol: RSPO2
- Class: oncogene
- Biology: Activator of the canonical Wnt signalling pathway by acting as a ligand for LGR4-6 receptors. 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. During embryonic development, plays a crucial role in limb specification, amplifying the Wnt signalling pathway independently of LGR4-6 receptors, possibly by acting as a direct antagonistic ligand to RNF43 and ZNRF3, hence governing the number of limbs an embryo should form. Location: Secreted (UniProt). Locus 8q23.1 (HGNC).
- Where found: Prostate cancer: Open Targets association 0.58 with prostate cancer (MONDO_0008315); Breast cancer: Open Targets association 0.57 with breast cancer (MONDO_0007254); Colorectal cancer: Open Targets association 0.52 with colorectal cancer (MONDO_0005575); IntOGen driver in 1 cohort (COADREAD)

## 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: IntOGen calls it an activating (Act) driver in 1 cohort. Evidence tier "cohort-driver" is the strongest of those signals.
- Prevalence not recorded: none of the sources gives a positivity rate.

## Sources

- HGNC HGNC:28583: https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:28583
- UniProt Q6UXX9: https://www.uniprot.org/uniprotkb/Q6UXX9/entry
- NCBI Gene 340419: https://www.ncbi.nlm.nih.gov/gene/340419
- Ensembl ENSG00000147655: https://www.ensembl.org/Homo_sapiens/Gene/Summary?g=ENSG00000147655

## Connected records

- collections: [IntOGen](https://onco.cc/collections/intogen/), [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/), [Prostate cancer](https://onco.cc/cancers/prostate/)

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JSON: https://onco.cc/api/v1/entities/rspo2.json