RSPO2

Chr 8q23.1

R-spondin 2

Aliases:: MGC35555
MANE:: ENST00000276659.10

OMIM: 610575 ↗NCBI: 340419 ↗Ensembl ↗

Annotations refreshed 10 hours ago.

Predicted protein structure

AlphaFold predicted structure

RSPO2 · Q6UXX9

v62025-08-01

Predicted Aligned Error matrix for RSPO2 — diagonal shows residue index, colour shows pairwise prediction confidence (lower is better) — Predicted Aligned Error

Mean pLDDT

81.4/ 100

Confident

243 residues

Confidence breakdown

Very high(≥ 90)52%
Confident(70–90)24%
Low(50–70)15%
Very low(< 50)9%

Open interactive 3D viewer

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

Clinical relevance (Genomics England PanelApp)

Diagnostic Grade (Green)

DDG2P
BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies
BIALLELIC, autosomal or pseudoautosomal
Clefting

Disease associations (Open Targets)

Tetraamelia - multiple malformations
0.57
prostate carcinoma
0.54
humerofemoral hypoplasia with radiotibial ray deficiency
0.50
androgenetic alopecia
0.46
hair color
0.46
tetraamelia-multiple malformations syndrome
0.45
Dupuytren Contracture
0.40
esophageal adenocarcinoma
0.37
gastric carcinoma
0.37
colon adenocarcinoma
0.37

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

Protein function (UniProt)

R-spondin-2

Activator of the canonical Wnt signaling pathway by acting as a ligand for LGR4-6 receptors. 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, PubMed:22615920). During embryonic development, plays a crucial role in limb specification, amplifying the Wnt signaling pathway independently of LGR4-6 receptors, possibly by acting as a direct antagonistic ligand to RNF43 and ZNRF3, hence governing the number of limbs an embryo should form (PubMed:29769720)