RSPO4 Gene

The RSPO4 gene (RSPO4 stands for R-spondin 4) is a protein-coding gene located on chromosome 20p13. Alternative splicing results in multiple transcript variants. The RSPO4 gene encodes a member of the R-spondin family of proteins that share a common domain organization consisting of a signal peptide, a cysteine-rich/furin-like domain, a thrombospondin domain, and a C-terminal basic region.

The encoded protein is likely involved in the activation of the Wnt/beta-catenin signaling pathway, which acts as a ligand for LGR4-6 receptors. Upon binding to LGR4-6 (LGR4, LGR5, or LGR6), LGR4-6 associates with phosphorylated LRP6 and Frizzled receptors, which are activated by extracellular Wnt receptors and trigger the canonical Wnt signaling pathway to increase the expression of target genes.

Mutations in this gene are associated with anonychia congenitalis (congenital nonsyndromic nail disorder 4).

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