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RSPO4 gene

R-spondin 4
From Genetics Home Reference. Learn more

Normal Function

The RSPO4 gene provides instructions for making a protein called R-spondin-4. R-spondin-4 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. The role of R-spondin-4 is to increase Wnt signaling.

During early development, Wnt signaling plays a critical role in the growth and development of nails. R-spondin-4 is active in the skeleton and contributes to limb formation, particularly at the ends of the fingers and toes, where nail development occurs.

Different regions (domains) of R-spondin-4 have different functions; two regions known as furin-like domains are required for turning on (activating) and stabilizing proteins that play integral roles in the Wnt pathway.

Health Conditions Related to Genetic Changes

Anonychia congenita

At least 17 mutations in the RSPO4 gene have been found to cause anonychia congenita. This condition is characterized by the absence of fingernails and toenails (anonychia) from birth. Nearly all of the RSPO4 gene mutations that cause this condition affect the furin-like domains, impairing protein function. Some mutations disrupt the structure of the furin-like domains, and others lead to the production of an abnormally short protein that does not contain these domains. As a result, R-spondin-4 cannot participate in the Wnt signaling pathway and nails develop improperly or not at all.

More About This Health Condition

Other Names for This Gene

  • C20orf182
  • CRISTIN4
  • dJ824F16.3
  • hRspo4
  • R-spondin family, member 4
  • roof plate-specific spondin-4

Additional Information & Resources

Tests Listed in the Genetic Testing Registry

Scientific Articles on PubMed

Catalog of Genes and Diseases from OMIM

Research Resources

References

  • Blaydon DC, Ishii Y, O'Toole EA, Unsworth HC, Teh MT, Rüschendorf F, Sinclair C, Hopsu-Havu VK, Tidman N, Moss C, Watson R, de Berker D, Wajid M, Christiano AM, Kelsell DP. The gene encoding R-spondin 4 (RSPO4), a secreted protein implicated in Wnt signaling, is mutated in inherited anonychia. Nat Genet. 2006 Nov;38(11):1245-7. Epub 2006 Oct 15. Citation on PubMed
  • Brüchle NO, Frank J, Frank V, Senderek J, Akar A, Koc E, Rigopoulos D, van Steensel M, Zerres K, Bergmann C. RSPO4 is the major gene in autosomal-recessive anonychia and mutations cluster in the furin-like cysteine-rich domains of the Wnt signaling ligand R-spondin 4. J Invest Dermatol. 2008 Apr;128(4):791-6. Epub 2007 Oct 4. Citation on PubMed
  • de Lau WB, Snel B, Clevers HC. The R-spondin protein family. Genome Biol. 2012;13(3):242. doi: 10.1186/gb-2012-13-3-242. Review. Citation on PubMed or Free article on PubMed Central
  • Knight MN, Hankenson KD. R-spondins: novel matricellular regulators of the skeleton. Matrix Biol. 2014 Jul;37:157-61. doi: 10.1016/j.matbio.2014.06.003. Epub 2014 Jun 27. Review. Citation on PubMed
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