LRP5 Gene: Low-Density Lipoprotein Receptor-Related Protein 5
Key regulator of Wnt signaling, bone density, and vascular development
Gene Information Card
| Symbol | LRP5 |
|---|---|
| Full Name | Low-Density Lipoprotein Receptor-Related Protein 5 |
| Gene Type | Protein coding |
| Chromosomal Location | 11q13.2 |
| NCBI Gene ID | 4041 ncbi.nlm.nih.gov/gene/4041 |
| Ensembl ID | ENSG00000162337 |
| UniProt ID | O75197 |
| OMIM ID | 603506 |
| HGNC ID | 6697 |
| Aliases | LR3, LRP-5, LRP7, OPPG, OPTA1, VBCH2, EVR1, EVR4, HBM, LRP5_HUMAN |
Description
The LRP5 gene encodes a transmembrane low-density lipoprotein receptor-related protein that functions as a coreceptor for Wnt ligands, playing a critical role in the canonical Wnt/β-catenin signaling pathway. This protein is essential for bone mass regulation, eye development, and vascular homeostasis. Mutations in LRP5 are associated with bone density disorders, familial exudative vitreoretinopathy, and other developmental conditions.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Osteoporosis-pseudoglioma syndrome (OPPG) | Loss-of-function mutations impair Wnt signaling, reducing osteoblast activity and bone formation | OMIM #259770 |
| Familial exudative vitreoretinopathy (FEVR) | Defective Wnt signaling disrupts retinal vascular development | OMIM #133780 |
| High bone mass (HBM) phenotype | Gain-of-function mutations enhance Wnt signaling, increasing bone density | OMIM #601884 |
| Osteoporosis | Common variants in LRP5 are associated with reduced bone mineral density | ClinVar, GWAS studies |
| Autosomal dominant osteopetrosis type 1 | Gain-of-function mutations lead to increased bone density | OMIM #607634 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Bone | 12.5 | Medium |
| Liver | 8.3 | Medium |
| Kidney | 7.1 | Medium |
| Lung | 6.4 | Medium |
| Brain | 5.2 | Low |
| Heart | 4.8 | Low |
| Pancreas | 3.9 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| Osteoblasts | 15.2 | High expression; key for bone formation |
| Hepatocytes | 9.8 | Moderate expression |
| Retinal pigment epithelial cells | 7.5 | Moderate expression; relevant to FEVR |
| Endothelial cells | 6.1 | Moderate expression; vascular development |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.512G>A (p.Arg171Gln) | Missense | <0.01% | Gain-of-function; associated with high bone mass |
| c.4330C>T (p.Arg1444Ter) | Nonsense | <0.01% | Loss-of-function; causes OPPG |
| c.3559C>T (p.Arg1187Trp) | Missense | <0.01% | Loss-of-function; associated with FEVR |
| c.1067G>A (p.Arg356His) | Missense | <0.01% | Gain-of-function; linked to osteopetrosis |
Mutation functional classification
Loss of Function (LOF)
Loss-of-function mutations in LRP5 impair Wnt/β-catenin signaling, leading to reduced bone formation (OPPG) and defective retinal angiogenesis (FEVR).
Gain of Function (GOF)
Gain-of-function mutations enhance Wnt signaling, resulting in increased bone density (HBM, osteopetrosis type 1).
Dominant Negative (DN)
Dominant-negative effects have been reported for some missense mutations that disrupt receptor dimerization or ligand binding, though less common.
View complete mutation data：
Gene Ontology (GO)
| • GO:0004888 - transmembrane signaling receptor activity | • GO:0005109 - frizzled binding |
| • GO:0007165 - signal transduction | • GO:0007224 - smoothened signaling pathway |
| • GO:0016055 - Wnt signaling pathway | • GO:0030509 - BMP signaling pathway |
| • GO:0042813 - Wnt receptor activity | • GO:0060070 - canonical Wnt signaling pathway |
Pathways
• Wnt signaling pathway (KEGG: hsa04310)
• Wnt/β-catenin signaling (Reactome: R-HSA-201681)
• Regulation of bone mineralization (Reactome: R-HSA-2172127)
• Retinal vascular development (Reactome: R-HSA-9013405)
Protein Summary
LRP5 is a 1615-amino acid single-pass transmembrane protein with an extracellular domain containing multiple LDL receptor class A repeats and YWTD propeller domains, essential for ligand binding. It forms a complex with Frizzled receptors to transduce Wnt signals, stabilizing β-catenin and activating target gene transcription. The protein is critical for osteoblast function, retinal angiogenesis, and metabolic regulation.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| LRP5 Knockout HEK293 Cell Line | EDJ-KQ313 | Human | 4041 | Details Get a Quote |
| NLRP5 Knockout HEK293 Cell Line | EDJ-KQ8868 | Human | 126206 | Details Get a Quote |
| LRP5 Knockout HeLa Cell Line | EDJ-KQ17954 | Human | 4041 | Details Get a Quote |
| LRP5 Knockout A-549 Cell Line | EDJ-KQ18449 | Human | 4041 | Details Get a Quote |
| LRP5 Knockout HCT 116 Cell Line | EDJ-KQ18450 | Human | 4041 | Details Get a Quote |
| NLRP5 Knockout HeLa Cell Line | EDJ-KQ58170 | Human | 126206 | Details Get a Quote |
| NLRP5 Knockout A-549 Cell Line | EDJ-KQ66658 | Human | 126206 | Details Get a Quote |
| NLRP5 Knockout HCT 116 Cell Line | EDJ-KQ75076 | Human | 126206 | Details Get a Quote |
| LRP5 and LRP6 Knockout HCT 116 Cell Line | EDC90770 | Human | 4041 and 4040 | Details Get a Quote |
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