RSPO4

This gene encodes a member of the R-spondin family of proteins that share a common domain organization consisting of a signal peptide, cysteine-rich/furin-like domain, thrombospondin domain and a C-terminal basic region. The encoded protein may be involved in activation of Wnt/beta-catenin signaling pathways. Mutations in this gene are associated with anonychia congenital. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Sep 2009]

Full Name

R-Spondin 4

Function

Activator of the canonical Wnt signaling pathway by acting as a ligand for LGR4-6 receptors (PubMed:29769720).
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 signaling pathway to increase expression of target genes. Also regulates the canonical Wnt/beta-catenin-dependent pathway and non-canonical Wnt signaling by acting as an inhibitor of ZNRF3, an important regulator of the Wnt signaling pathway (PubMed:21727895, PubMed:21909076).

Biological Process

Biological Process nail developmentManual Assertion Based On ExperimentIMP:MGI
Biological Process positive regulation of Wnt signaling pathwayManual Assertion Based On ExperimentIDA:UniProtKB
Biological Process Wnt signaling pathwayIEA:UniProtKB-KW

Cellular Location

Secreted

Involvement in disease

Nail disorder, non-syndromic congenital, 4 (NDNC4):
A nail disorder characterized by congenital anonychia or its milder phenotypic variant hyponychia. Anonychia/hyponychia is the absence or severe hypoplasia of all fingernails and toenails without significant bone anomalies.

PTM

Tyr-112 may be phosphorylated; however as this position is probably extracellular, the vivo relevance is not proven.