LRP5 (O75197) variants and mutations

LRP5 (also known as O75197) is a human protein-coding gene encoding a low-density lipoprotein receptor-related protein 5 protein. It transduces canonical Wnt signals that strongly regulate bone formation and also contributes to retinal vascular development. Loss-of-function variants cause osteoporosis-pseudoglioma syndrome, while activating variants cause high-bone-mass disorders. This analysis covers 2,355 LRP5 variants and mutations. Of these, 79% have computational variant effect predictions. Disease context includes osteoporosis-pseudoglioma syndrome, Familial exudative vitreoretinopathy, and autosomal dominant osteosclerosis, Worth type. Example LRP5 variants include M1L, M1V, and E2Q.

Variant analysis overview

Gene: LRP5
Protein: O75197
UniProt accession: O75197
Organism: Homo sapiens
Variants analyzed: 2355
Variant scope: all variants
Completed: 2026-08-21

Variant and mutation evidence

Variant composition: 2,093 unspecified-consequence records; 111 missense variants; 43 frameshift variants; 6 stop-gained variants; 71 synonymous variants; 12 in-frame deletions; 12 in-frame insertions; 2 splice-region variants; 5 substitution
Prediction scores: 1,855 variants have prediction scores (79% of the analyzed set).

Clinical, disease, and population context

Disease context: 25 disease associations are represented. Top associations: osteoporosis-pseudoglioma syndrome, Familial exudative vitreoretinopathy, autosomal dominant osteosclerosis, Worth type, polycystic liver disease 4 with or without kidney cysts, osteoporosis, exudative vitreoretinopathy 4, Autosomal dominant osteopetrosis type 1, Osteoporosis - pseudoglioma, autosomal dominant osteopetrosis 1, hyperostosis corticalis generalisata, Albers-Schönberg osteopetrosis, X-linked osteoporosis with fractures.

Protein structure and variant hotspots

Protein features: 1 transmembrane segments; 7 domains; 6 post-translational modification sites.
Structural context: 417 variants have structural context.
PTM context: 7 variants overlap post-translational modification sites.

Data sources

Evidence in this analysis draws on EBI Proteins Variation, UniProt, gnomAD v4, EuropePMC, 3D Hotspot Analysis, Interaction Network Analysis, AlphaFold DB, gnomAD constraint, Open Targets, ClinGen, MaveDB, LitVar.

Notable LRP5 variants

Examples include M1L, M1V, E2Q, E2K, E2G, E2*, E2V, E2E. Listed records include available protein-change notation, database identifiers, clinical classifications, computational predictions, population evidence, experimental measurements, and disease context.

LRP5 analysis run — LRP5 (2,355 variants) — completed 2026-08-21