LGR4
Chr 11ADleucine rich repeat containing G protein-coupled receptor 4
Also known as: BNMD17, DPSL, GPR48
This G-protein coupled receptor binds R-spondins and potentiates the canonical Wnt signaling pathway, which is essential for development of multiple organs including liver, kidney, intestine, bone, reproductive tract, and eye. Mutations cause autosomal dominant delayed puberty (self-limited) and susceptibility to low bone mineral density. The gene is highly constrained against loss-of-function variants (LOEUF 0.382), reflecting its critical role in organ development and hormonal regulation.
Primary Disease Associations & Inheritance
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
More LoF-intolerant than ~75% of genes
Mild missense constraint
This gene has evidence for multiple mechanisms of pathogenicity (gain-of-function and dominant-negative). Both the Badonyi & Marsh prediction and the broader genomic evidence point to gain-of-function as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.
Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.
Literature Evidence
Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.
ClinVar Variant Classifications
172 submitted variants in ClinVar
Classification Summary
Curated Variants Distribution
Classified variants from ClinVar · 5 ACMG categories
| Classification | LoF | Missense + Inframe | Non-coding | Synonymous | Total |
|---|---|---|---|---|---|
Pathogenic | 0 | 2 | 19 | 0 | 21 |
Likely Pathogenic | 0 | 0 | 1 | 0 | 1 |
VUS | 0 | 104 | 4 | 0 | 108 |
Likely Benign | 0 | 5 | 1 | 9 | 15 |
Benign | 0 | 4 | 1 | 1 | 6 |
| Total | 0 | 115 | 26 | 10 | 151 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
LGR4 · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
External Resources
Links to major genomics databases and tools
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
No active trials found for this gene.
Search ClinicalTrials.gov →External Resources
Links to major genomics databases and tools