LRP6: Low-Density Lipoprotein Receptor-Related Protein 6
Key Wnt Signaling Co-Receptor in Development and Disease
Gene Information Card
| Symbol | LRP6 |
|---|---|
| Full Name | Low Density Lipoprotein Receptor-Related Protein 6 |
| Gene Type | Protein coding |
| Chromosomal Location | 12p13.2 |
| NCBI Gene ID | 4040 ncbi.nlm.nih.gov/gene/4040 |
| Ensembl ID | ENSG00000070018 |
| UniProt ID | O75581 |
| OMIM ID | 603507 |
| HGNC ID | 6698 |
| Aliases | ADCAD2, LRP-6, LRP6_HUMAN |
Description
LRP6 encodes a transmembrane protein that functions as a co-receptor for Wnt ligands, essential for canonical Wnt/β-catenin signaling. It plays critical roles in embryonic development, cell proliferation, and differentiation. Mutations in LRP6 are associated with coronary artery disease, neural tube defects, and various cancers.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Coronary artery disease (ADCAD2) | Impaired Wnt signaling due to LRP6 loss-of-function variants reduces osteoblast activity and increases vascular calcification | OMIM #610947 |
| Neural tube defects | Disrupted Wnt/β-catenin signaling during neurulation | ClinVar, PMID: 20602914 |
| Osteoporosis | Reduced bone formation via attenuated Wnt signaling | OMIM, PMID: 21909107 |
| Colorectal cancer | Aberrant Wnt pathway activation through LRP6 overexpression or mutation | COSMIC, PMID: 17667926 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Liver | 14.2 | Medium |
| Kidney | 11.8 | Medium |
| Heart | 9.5 | Low |
| Brain | 7.3 | Low |
| Lung | 6.1 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK 293 | 18.5 | High expression in embryonic kidney cells |
| HepG2 | 12.1 | Hepatocellular carcinoma line |
| MCF7 | 8.9 | Breast cancer line |
| A549 | 6.4 | Lung carcinoma line |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| R611C | Missense | Rare | Impaired Wnt signaling, associated with coronary artery disease |
| V1062I | Missense | Rare | Reduced β-catenin activation, linked to neural tube defects |
| N433S | Missense | Rare | Decreased Wnt3a binding, associated with osteoporosis |
| Glu1357* | Nonsense | Very rare | Truncated protein, loss of function |
Mutation functional classification
Loss of Function (LOF)
Missense variants (e.g., R611C, V1062I) impair Wnt co-receptor activity, reducing β-catenin signaling and contributing to developmental and metabolic disorders.
Gain of Function (GOF)
Amplification or overexpression of LRP6 in cancers (e.g., colorectal) enhances Wnt signaling, promoting proliferation and tumorigenesis.
Dominant Negative (DN)
Truncated or misfolded LRP6 variants can interfere with wild-type receptor function, though dominant-negative effects are not well-documented in LRP6.
View complete mutation data：
Gene Ontology (GO)
| • GO:0017147 - Wnt-protein binding | • GO:0005109 - frizzled binding |
| • GO:0007165 - signal transduction | • GO:0060070 - canonical Wnt signaling pathway |
| • GO:0005886 - plasma membrane |
Pathways
• Wnt signaling pathway (KEGG: hsa04310)
• Hippo signaling pathway (KEGG: hsa04390)
• Signaling by WNT (Reactome: R-HSA-195721)
Protein Summary
LRP6 is a 1613-amino-acid single-pass transmembrane protein with extracellular LDL-receptor class A repeats and YWTD propeller domains, and an intracellular domain containing PPPSP motifs that recruit axin upon Wnt stimulation. It forms a complex with Frizzled receptors to transduce Wnt signals, stabilizing β-catenin and activating target gene transcription.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| NLRP6 Knockout HCT 116 Cell Line | EDJ-KQ21 | Human | 171389 | Details Get a Quote |
| LRP6 Knockout HEK293T Cell Line | EDJ-KQ94 | Human | 4040 | Details Get a Quote |
| LRP6 Knockout HEK293 Cell Line | EDJ-KQ314 | Human | 4040 | Details Get a Quote |
| NLRP6 Knockout HEK293 Cell Line | EDJ-KQ1132 | Human | 171389 | Details Get a Quote |
| LRP6 Knockout A-549 Cell Line | EDJ-KQ18451 | Human | 4040 | Details Get a Quote |
| LRP6 Knockout HCT 116 Cell Line | EDJ-KQ18452 | Human | 4040 | Details Get a Quote |
| LRP6 Knockout HeLa Cell Line | EDJ-KQ18453 | Human | 4040 | Details Get a Quote |
| NLRP6 Knockout HeLa Cell Line | EDJ-KQ58953 | Human | 171389 | Details Get a Quote |
| NLRP6 Knockout A-549 Cell Line | EDJ-KQ67440 | Human | 171389 | Details Get a Quote |
| LRP6 Knockout HAP1 Cell Line | EDC08284 | Human | 4040 | Details Get a Quote |
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