RSPO1 Gene - R-Spondin 1
Key regulator of WNT signaling, stem cell maintenance, and sexual development
Gene Information Card
| Symbol | RSPO1 |
|---|---|
| Full Name | R-spondin 1 |
| Gene Type | Protein coding |
| Chromosomal Location | 1p34.3 |
| NCBI Gene ID | 284654 ncbi.nlm.nih.gov/gene/284654 |
| Ensembl ID | ENSG00000169218 |
| UniProt ID | Q2MKA7 |
| OMIM ID | 609595 |
| HGNC ID | 24220 |
| Aliases | R-spondin, CRISTIN3, FLJ40906, hRspo1 |
Description
RSPO1 (R-spondin 1) is a protein-coding gene that encodes a secreted agonist of the canonical WNT/β-catenin signaling pathway. It plays critical roles in embryonic development, stem cell proliferation, and sex determination. RSPO1 enhances WNT signaling by binding to LGR4/5/6 receptors and ZNRF3/RNF43 E3 ubiquitin ligases, thereby stabilizing Frizzled receptors. Loss-of-function mutations in RSPO1 cause an autosomal recessive syndrome characterized by palmoplantar hyperkeratosis, predisposition to squamous cell carcinoma, and 46,XX sex reversal (female-to-male).
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Palmoplantar hyperkeratosis with squamous cell carcinoma and sex reversal (OMIM #610644) | Loss-of-function mutations in RSPO1 impair WNT signaling, disrupting keratinocyte differentiation and ovarian development, leading to hyperkeratosis, tumor susceptibility, and testicular differentiation in XX individuals. | OMIM, NCBI |
| Squamous cell carcinoma (SCC) | RSPO1 deficiency reduces WNT signaling, promoting genomic instability and malignant transformation of keratinocytes. | OMIM, NCBI |
| 46,XX sex reversal | RSPO1 is essential for ovarian development; its loss allows testis-determining pathways (e.g., SOX9) to activate, causing female-to-male sex reversal. | OMIM, NCBI |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Skin | 12.5 | Medium |
| Ovary | 8.3 | Low |
| Testis | 6.1 | Low |
| Esophagus | 10.2 | Medium |
| Placenta | 7.8 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HaCaT (keratinocyte) | 15.0 | High expression in skin-derived cells |
| MCF7 (breast cancer) | 5.2 | Moderate expression |
| HEK293 (embryonic kidney) | 3.1 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.286C>T (p.Arg96*) | Nonsense | Rare | Loss of function; truncates protein, abolishing WNT signaling enhancement |
| c.370C>T (p.Arg124*) | Nonsense | Rare | Loss of function; premature stop codon, no active protein |
| c.1A>G (p.Met1?) | Missense (start loss) | Rare | Loss of function; prevents translation initiation |
Mutation functional classification
Loss of Function (LOF)
Nonsense and start-loss mutations that truncate or abolish RSPO1 protein, leading to reduced WNT signaling and causing palmoplantar hyperkeratosis, SCC, and 46,XX sex reversal.
Gain of Function (GOF)
Not reported in germline; somatic RSPO1 fusions (e.g., with PTPRK) in colon cancer can enhance WNT signaling, but these are not germline mutations.
Dominant Negative (DN)
Not described for RSPO1; all known pathogenic mutations are recessive loss-of-function.
View complete mutation data：
Gene Ontology (GO)
| • Wnt signaling pathway (GO:0016055) | • Receptor agonist activity (GO:0048018) |
| • Extracellular region (GO:0005576) | • Cell proliferation (GO:0008283) |
| • Sex determination (GO:0007530) |
Pathways
• WNT signaling pathway (Reactome: R-HSA-195721)
• R-spondin-mediated WNT signaling (Reactome: R-HSA-5362768)
• LGR4/5/6 and RSPO1 signaling (KEGG: hsa04310)
Protein Summary
R-spondin 1 is a secreted 27 kDa protein containing a furin-like domain and a thrombospondin type 1 domain. It acts as a potent agonist of canonical WNT signaling by binding to LGR4/5/6 receptors and inhibiting ZNRF3/RNF43, thereby increasing cell surface levels of Frizzled and LRP6. RSPO1 is critical for stem cell maintenance in skin, intestine, and bone, and for ovarian development. Its deficiency leads to hyperkeratosis, cancer predisposition, and sex reversal.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| RSPO1 Knockout HEK293 Cell Line | EDJ-KQ15133 | Human | 284654 | Details Get a Quote |
| RSPO1 Knockout HeLa Cell Line | EDJ-KQ59484 | Human | 284654 | Details Get a Quote |
| RSPO1 Knockout A-549 Cell Line | EDJ-KQ67951 | Human | 284654 | Details Get a Quote |
| RSPO1 Knockout HCT 116 Cell Line | EDJ-KQ76330 | Human | 284654 | Details Get a Quote |
