LRP4 Gene (LDL Receptor Related Protein 4)
Key regulator of neuromuscular junction formation and bone development
Gene Information Card
| Symbol | LRP4 |
|---|---|
| Full Name | LDL Receptor Related Protein 4 |
| Gene Type | protein-coding |
| Chromosomal Location | 11p11.2 |
| NCBI Gene ID | 4038 ncbi.nlm.nih.gov/gene/4038 |
| Ensembl ID | ENSG00000134569 |
| UniProt ID | O75096 |
| OMIM ID | 604270 |
| HGNC ID | 6696 |
| Aliases | CLSS, LRP-4, MEGF7, SOST2 |
Description
LRP4 encodes a member of the low-density lipoprotein receptor (LDLR) family. The protein functions as a receptor for agrin and is critical for neuromuscular junction formation. It also acts as a negative regulator of bone growth by binding sclerostin and facilitating its inhibitory effect on Wnt signaling. Mutations in LRP4 cause Cenani-Lenz syndactyly syndrome and sclerosteosis 2, and variants are associated with myasthenia gravis.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Cenani-Lenz syndactyly syndrome | Loss-of-function mutations disrupt limb development | OMIM #212780 |
| Sclerosteosis 2 | Loss-of-function mutations impair sclerostin binding, leading to increased bone density | OMIM #614305 |
| Congenital myasthenic syndrome | Mutations impair agrin-LRP4 signaling at the neuromuscular junction | ClinVar, PubMed |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Skeletal muscle | 12.5 | Medium |
| Bone | 8.3 | Medium |
| Kidney | 6.1 | Low |
| Liver | 4.2 | Low |
| Brain | 3.8 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK 293 | 15.2 | High expression in recombinant systems |
| C2C12 (myoblast) | 10.1 | Endogenous expression |
| HepG2 | 5.4 | Moderate expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.350C>T (p.Pro117Leu) | Missense | Rare | Loss of function; associated with Cenani-Lenz syndrome |
| c.499G>A (p.Gly167Arg) | Missense | Rare | Loss of function; associated with sclerosteosis 2 |
| c.1195C>T (p.Arg399Trp) | Missense | Rare | Impaired agrin binding; associated with myasthenia gravis |
Mutation functional classification
Loss of Function (LOF)
Most LRP4 mutations are loss-of-function, leading to impaired agrin signaling (neuromuscular junction) or reduced sclerostin binding (bone overgrowth).
Gain of Function (GOF)
No gain-of-function mutations reported in LRP4.
Dominant Negative (DN)
Some missense mutations may exert dominant-negative effects by disrupting receptor dimerization, but evidence is limited.
View complete mutation data：
Gene Ontology (GO)
Pathways
• Agrin-LRP4-MuSK signaling in neuromuscular junction
• Wnt signaling pathway (regulation by sclerostin)
• LDL receptor family member signaling
Protein Summary
LRP4 is a single-pass transmembrane protein of the LDL receptor family. It contains multiple ligand-binding repeats and is essential for agrin-induced clustering of acetylcholine receptors at the neuromuscular junction. In bone, LRP4 binds sclerostin (SOST) to inhibit Wnt signaling, thereby regulating bone mass. The protein is expressed in skeletal muscle, bone, kidney, and liver. Mutations cause skeletal and neuromuscular disorders.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| LRP4 Knockout HEK293 Cell Line | EDJ-KQ2606 | Human | 4038 | Details Get a Quote |
| NLRP4 Knockout HEK293 Cell Line | EDJ-KQ9990 | Human | 147945 | Details Get a Quote |
| LRP4 Knockout A-549 Cell Line | EDJ-KQ21946 | Human | 4038 | Details Get a Quote |
| LRP4 Knockout HCT 116 Cell Line | EDJ-KQ23315 | Human | 4038 | Details Get a Quote |
| LRP4 Knockout HeLa Cell Line | EDJ-KQ23316 | Human | 4038 | Details Get a Quote |
| NLRP4 Knockout HeLa Cell Line | EDJ-KQ58591 | Human | 147945 | Details Get a Quote |
| NLRP4 Knockout A-549 Cell Line | EDJ-KQ67078 | Human | 147945 | Details Get a Quote |
| NLRP4 Knockout HCT 116 Cell Line | EDJ-KQ75483 | Human | 147945 | Details Get a Quote |
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