RSPO4 gene

R-spondin 4

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.

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.

Cytogenetic Location: 20p13, which is the short (p) arm of chromosome 20 at position 13

Molecular Location: base pairs 958,452 to 1,002,311 on chromosome 20 (Homo sapiens Updated Annotation Release 109.20200522, GRCh38.p13) (NCBI)

Cytogenetic Location: 20p13, which is the short (p) arm of chromosome 20 at position 13
  • C20orf182
  • dJ824F16.3
  • hRspo4
  • R-spondin family, member 4
  • roof plate-specific spondin-4