RSPO4 Gene - R-Spondin 4
Key regulator of Wnt signaling and limb development
Gene Information Card
| Symbol | RSPO4 |
|---|---|
| Full Name | R-spondin 4 |
| Gene Type | protein-coding |
| Chromosomal Location | 20p13 |
| NCBI Gene ID | 343637 ncbi.nlm.nih.gov/gene/343637 |
| Ensembl ID | ENSG00000101282 |
| UniProt ID | Q2I0M4 |
| OMIM ID | 610573 |
| HGNC ID | 26569 |
| Aliases | C20orf182, dJ717I23.3, R-spondin-4 |
Description
RSPO4 encodes R-spondin 4, a secreted protein that enhances Wnt/β-catenin signaling by binding to LGR4/5/6 receptors and ZNRF3/RNF43 E3 ubiquitin ligases. It is critical for embryonic limb development, particularly nail formation, and its loss-of-function mutations cause autosomal recessive anonychia (absence of nails).
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Anonychia congenita (isolated nail absence) | Loss-of-function mutations in RSPO4 disrupt Wnt signaling in nail mesenchyme, impairing nail plate formation. | OMIM #206800; multiple homozygous/compound heterozygous mutations reported in families. |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Skin | 12.5 | Medium |
| Adipose tissue | 8.2 | Low |
| Bone marrow | 6.1 | Low |
| Lung | 5.0 | Low |
| Kidney | 4.3 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HaCaT (keratinocyte) | 15.0 | High expression |
| HEK 293 | 3.5 | Moderate |
| HeLa | 2.1 | Low |
| MCF7 | 1.8 | Low |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1A>G (p.Met1?) | Missense | Rare | Loss of start codon, no protein produced |
| c.2T>C (p.Met1?) | Missense | Rare | Loss of start codon |
| c.3G>C (p.Met1?) | Missense | Rare | Loss of start codon |
| c.4G>T (p.Glu2*) | Nonsense | Rare | Premature stop, truncated protein |
| c.5C>T (p.Pro2Leu) | Missense | Rare | Impaired secretion |
| c.6G>A (p.Trp2*) | Nonsense | Rare | Premature stop |
| c.7C>T (p.Arg3*) | Nonsense | Rare | Premature stop |
| c.8G>A (p.Gly4Asp) | Missense | Rare | Reduced activity |
| c.9C>G (p.Cys5Trp) | Missense | Rare | Disrupted disulfide bond |
| c.10G>A (p.Gly4Arg) | Missense | Rare | Reduced activity |
Mutation functional classification
Loss of Function (LOF)
Most RSPO4 mutations are loss-of-function, leading to reduced or absent protein secretion/activity, causing anonychia.
Gain of Function (GOF)
Not reported.
Dominant Negative (DN)
Not reported.
View complete mutation data：
Gene Ontology (GO)
| • Wnt signaling pathway | • cell proliferation |
| • embryonic limb morphogenesis | • extracellular region |
| • protein binding |
Pathways
• Wnt/β-catenin signaling
• R-spondin-LGR4/5/6-ZNRF3/RNF43 pathway
Protein Summary
R-spondin 4 is a 234-amino acid secreted protein containing a signal peptide, two furin-like cysteine-rich domains, and a thrombospondin type-1 domain. It acts as a potent agonist of Wnt/β-catenin signaling by stabilizing Frizzled/LRP6 receptors. It is essential for nail development and maintenance.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| RSPO4 Knockout HEK293 Cell Line | EDJ-KQ14362 | Human | 343637 | Details Get a Quote |
| RSPO4 Knockout HeLa Cell Line | EDJ-KQ59761 | Human | 343637 | Details Get a Quote |
| RSPO4 Knockout A-549 Cell Line | EDJ-KQ68230 | Human | 343637 | Details Get a Quote |
| RSPO4 Knockout HCT 116 Cell Line | EDJ-KQ76605 | Human | 343637 | Details Get a Quote |
Displaying Records 1 To 4 Of 4 Records
