RSPO4

Chr 20p13

R-spondin 4

Aliases:: dJ824F16.3
MANE:: ENST00000217260.9

OMIM: 610573 ↗NCBI: 343637 ↗Ensembl ↗

Annotations refreshed 9 hours ago.

Predicted protein structure

AlphaFold predicted structure

RSPO4 · Q2I0M5

v62025-08-01

Predicted Aligned Error matrix for RSPO4 — diagonal shows residue index, colour shows pairwise prediction confidence (lower is better) — Predicted Aligned Error

Mean pLDDT

78.6/ 100

Confident

234 residues

Confidence breakdown

Very high(≥ 90)44%
Confident(70–90)26%
Low(50–70)18%
Very low(< 50)12%

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
Ectodermal dysplasia
BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies
BIALLELIC, autosomal or pseudoautosomal
Intellectual disability
BIALLELIC, autosomal or pseudoautosomal

Disease associations (Open Targets)

nonsyndromic congenital nail disorder 4
0.75
Anonychia congenita totalis
0.68
Congenital anonychia
0.66
hereditary disease
0.42
Genu valgum
0.28
Genu varum
0.28
neoplasm
0.27
open-angle glaucoma
0.27
glaucoma
0.26
MODY
0.08

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

Protein function (UniProt)

R-spondin-4

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)