RSPO1

Chr 1p34.3

R-spondin 1

Aliases:: FLJ40906, RSPONDIN
MANE:: ENST00000356545.7

OMIM: 609595 ↗NCBI: 284654 ↗Ensembl ↗

Annotations refreshed 9 hours ago.

Predicted protein structure

AlphaFold predicted structure

RSPO1 · Q2MKA7

v62025-08-01

Predicted Aligned Error matrix for RSPO1 — diagonal shows residue index, colour shows pairwise prediction confidence (lower is better) — Predicted Aligned Error

Mean pLDDT

74.7/ 100

Confident

263 residues

Confidence breakdown

Very high(≥ 90)40%
Confident(70–90)19%
Low(50–70)25%
Very low(< 50)16%

Open interactive 3D viewer

AlphaFold (Jumper et al., 2021) · CC BY 4.0

Clinical relevance (Genomics England PanelApp)

Diagnostic Grade (Green)

Differences in sex development
BIALLELIC, autosomal or pseudoautosomal
Ichthyosis and erythrokeratoderma
BIALLELIC, autosomal or pseudoautosomal
Palmoplantar keratoderma and erythrokeratodermas
BIALLELIC, autosomal or pseudoautosomal
Palmoplantar keratodermas
BIALLELIC, autosomal or pseudoautosomal

Disease associations (Open Targets)

palmoplantar keratoderma-XX sex reversal-predisposition to squamous cell carcinoma syndrome
0.73
Palmoplantar keratoderma - XX sex reversal - predisposition to squamous cell carcinoma
0.68
Palmoplantar hyperkeratosis
0.59
epidermolytic palmoplantar keratoderma, 1
0.47
Palmoplantar keratoderma
0.47
hereditary palmoplantar keratoderma
0.47
open-angle glaucoma
0.36
high grade ovarian serous adenocarcinoma
0.27
diaphragm disorder
0.25
hereditary disease
0.19

Score is the Open Targets composite evidence score (0-1). Higher = stronger gene-disease association.

Protein function (UniProt)

R-spondin-1

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. Acts as a ligand for frizzled FZD8 and LRP6. May negatively regulate the TGF-beta pathway. Has a essential roles in ovary determination. Regulates Wnt signaling by antagonizing DKK1/KREM1-mediated internalization of LRP6 through an interaction with KREM1 (PubMed:17804805)