The RSPO2 gene provides instructions for making a protein called R-spondin-2. R-spondin-2 plays a role in the Wnt signaling pathway, a series of steps that affect the way cells and tissues develop. Wnt signaling is important for cell division, attachment of cells to one another (adhesion), cell movement (migration), and many other cellular activities.
During early development, Wnt signaling plays a critical role in growth and development of the skeleton and other tissues. The role of R-spondin-2 is to increase Wnt signaling. Specifically, R-spondin-2 attaches (binds) to certain proteins on the surface of cells to turn off (inactivate) proteins that block the Wnt pathway.
Health Conditions Related to Genetic Changes
Variants (also called mutations) in the RSPO2 gene have been found to cause tetra-amelia syndrome. This condition is very rare and characterized by the absence of all four limbs. RSPO2 gene variants cause a form of this condition known as tetra-amelia syndrome type 2 in which affected individuals typically have a complete absence of both lungs. Because children with this condition have such serious medical problems, most are stillborn or die shortly after birth.
In individuals with tetra-amelia syndrome, RSPO2 gene variants typically result in a complete lack of functional R-spondin-2 protein. As a result, the R-spondin-2 protein is not available on the cell surface to inactivate proteins that block the Wnt pathway, so this critical pathway is dysregulated. During early development, irregular Wnt signaling leads to poor development of the limbs, organs, and other tissues, resulting in the severe signs and symptoms of tetra-amelia syndrome type 2.More About This Health Condition
Chromosomal rearrangements (translocations) involving the RSPO2 gene on chromosome 8 have been associated with certain types of cancer. These genetic changes are somatic, which means they are acquired during a person's lifetime and are present only in certain cells. In cancer cells, translocations can disrupt the region of chromosome 8 that contains the RSPO2 gene. Researchers have found a translocation between chromosome 8 and other chromosomes in several people with a cancer of the colon, stomach, lungs, liver, or prostate.
Increased activity (overexpression) of the RSPO2 gene has also been identified in different types of cancers, including cancer of the colon, stomach, breast, liver, and pancreas. The genetic changes involved in this overexpression are somatic. Research suggests that overexpression of the RSPO2 gene leads to increased Wnt signaling. As a result, cell growth and division are increased, which can lead to cancer.
Other Names for This Gene
- R-spondin family, member 2
Additional Information & Resources
Tests Listed in the Genetic Testing Registry
Scientific Articles on PubMed
Catalog of Genes and Diseases from OMIM
- Arima M, Hasegawa D, Yoshida S, Mitarai H, Tomokiyo A, Hamano S, Sugii H, Wada N, Maeda H. R-spondin 2 promotes osteoblastic differentiation of immature human periodontal ligament cells through the Wnt/beta-catenin signaling pathway. J Periodontal Res. 2019 Apr;54(2):143-153. doi: 10.1111/jre.12611. Epub 2018 Oct 4. Citation on PubMed
- Bell SM, Schreiner CM, Wert SE, Mucenski ML, Scott WJ, Whitsett JA. R-spondin 2 is required for normal laryngeal-tracheal, lung and limb morphogenesis. Development. 2008 Mar;135(6):1049-58. doi: 10.1242/dev.013359. Epub 2008 Feb 6. Citation on PubMed
- Kim KA, Zhao J, Andarmani S, Kakitani M, Oshima T, Binnerts ME, Abo A, Tomizuka K, Funk WD. R-Spondin proteins: a novel link to beta-catenin activation. Cell Cycle. 2006 Jan;5(1):23-6. doi: 10.4161/cc.5.1.2305. Epub 2006 Jan 8. Citation on PubMed
- Szenker-Ravi E, Altunoglu U, Leushacke M, Bosso-Lefevre C, Khatoo M, Thi Tran H, Naert T, Noelanders R, Hajamohideen A, Beneteau C, de Sousa SB, Karaman B, Latypova X, Basaran S, Yucel EB, Tan TT, Vlaminck L, Nayak SS, Shukla A, Girisha KM, Le Caignec C, Soshnikova N, Uyguner ZO, Vleminckx K, Barker N, Kayserili H, Reversade B. RSPO2 inhibition of RNF43 and ZNRF3 governs limb development independently of LGR4/5/6. Nature. 2018 May;557(7706):564-569. doi: 10.1038/s41586-018-0118-y. Epub 2018 May 16. Erratum In: Nature. 2018 Sep;561(7722):E7. Citation on PubMed
- Ter Steege EJ, Bakker ERM. The role of R-spondin proteins in cancer biology. Oncogene. 2021 Nov;40(47):6469-6478. doi: 10.1038/s41388-021-02059-y. Epub 2021 Oct 18. Citation on PubMed
The information on this site should not be used as a substitute for professional medical care or advice. Contact a health care provider if you have questions about your health.