LRP2 (Megalin): A Multiligand Endocytic Receptor in Development and Disease
Explore the gene, protein, expression, mutations, and clinical significance of LRP2, a key player in renal and neural physiology.
Gene Information Card
| Symbol | LRP2 |
|---|---|
| Full Name | LDL receptor related protein 2 |
| Gene Type | protein coding |
| Chromosomal Location | 2q31.1 (GRCh38) |
| NCBI Gene ID | 4036 ncbi.nlm.nih.gov/gene/4036 |
| Ensembl ID | ENSG00000181449 |
| UniProt ID | P98164 |
| OMIM ID | 600073 |
| HGNC ID | 6694 |
| Aliases | Megalin, gp330, LRP-2 |
Description
LRP2 encodes megalin, a large endocytic receptor of the LDL receptor family. It is expressed on the apical surface of absorptive epithelia, notably in renal proximal tubules, where it mediates uptake of a wide range of ligands including lipoproteins, vitamins, hormones, and drugs. LRP2 is essential for normal development of the brain and kidneys, and its dysfunction leads to Donnai-Barrow syndrome and other renal and neurological disorders.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Donnai-Barrow syndrome | Loss-of-function mutations in LRP2 impair endocytosis of ligands required for organ development, leading to diaphragmatic hernia, facial dysmorphism, and intellectual disability. | OMIM #222448; ClinVar |
| Focal segmental glomerulosclerosis (FSGS) | Reduced megalin expression in podocytes may contribute to proteinuria and glomerular injury. | PubMed; ClinVar |
| Alzheimer's disease | LRP2 mediates clearance of amyloid-beta; altered expression may influence disease risk. | PubMed; NCBI |
| Chronic kidney disease | Impaired tubular reabsorption of proteins due to LRP2 dysfunction contributes to tubular proteinuria and progression of CKD. | PubMed; ClinVar |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Kidney | High (nTPM ~ 200) | High |
| Brain | Moderate (nTPM ~ 20) | Medium |
| Lung | Low (nTPM ~ 5) | Low |
| Liver | Low (nTPM ~ 3) | Low |
| Small intestine | Moderate (nTPM ~ 15) | Medium |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK 293 | Low | Overexpression studies |
| Caco-2 | Moderate | Intestinal epithelial model |
| HK-2 | High | Renal proximal tubular cell line |
| SH-SY5Y | Low | Neuronal model |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.2227C>T (p.Arg743Ter) | Nonsense | Rare | Loss of function; associated with Donnai-Barrow syndrome |
| c.4478G>A (p.Arg1493His) | Missense | Rare | Impaired ligand binding; reported in FSGS |
| c.1045C>T (p.Arg349Trp) | Missense | Rare | Reduced cell surface expression; likely pathogenic |
| c.1234del (p.Leu412fs) | Frameshift | Rare | Loss of function; Donnai-Barrow syndrome |
Mutation functional classification
Loss of Function (LOF)
Most pathogenic LRP2 mutations are loss-of-function, leading to impaired endocytosis and developmental defects.
Gain of Function (GOF)
No gain-of-function mutations have been reported; LRP2 acts as a receptor, and overexpression may increase ligand uptake but is not oncogenic.
Dominant Negative (DN)
Not documented; LRP2 mutations are typically recessive.
View complete mutation data：
Gene Ontology (GO)
| • endocytosis | • receptor-mediated endocytosis |
| • lipoprotein metabolic process | • vitamin metabolic process |
| • kidney development | • brain development |
| • protein binding | • calcium ion binding |
| • low-density lipoprotein particle receptor activity |
Pathways
• LDL receptor family mediated endocytosis
• Vitamin D metabolism and transport
• Retinol (vitamin A) metabolism
• Protein reabsorption in renal proximal tubule
• Amyloid-beta clearance
Protein Summary
Megalin (LRP2) is a 600 kDa type I transmembrane glycoprotein with a large extracellular domain containing multiple ligand-binding repeats. It functions as a scavenger receptor, internalizing diverse ligands via clathrin-mediated endocytosis. In the kidney, it is crucial for reabsorption of filtered proteins, including albumin and vitamin-binding proteins. In the brain, it participates in cholesterol and amyloid-beta metabolism. Mutations cause Donnai-Barrow syndrome, characterized by craniofacial and renal anomalies.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| LRP2 Knockout HEK293 Cell Line | EDJ-KQ906 | Human | 4036 | Details Get a Quote |
| LRP2BP Knockout HEK293 Cell Line | EDJ-KQ3580 | Human | 55805 | Details Get a Quote |
| NLRP2 Knockout HEK293 Cell Line | EDJ-KQ14437 | Human | 55655 | Details Get a Quote |
| NLRP2B Knockout HEK293 Cell Line | EDJ-KQ14438 | Human | 286430 | Details Get a Quote |
| NLRP2 Knockout A-549 Cell Line | EDJ-KQ44656 | Human | 55655 | Details Get a Quote |
| LRP2BP Knockout HCT 116 Cell Line | EDJ-KQ25469 | Human | 55805 | Details Get a Quote |
| LRP2BP Knockout HeLa Cell Line | EDJ-KQ25470 | Human | 55805 | Details Get a Quote |
| NLRP2 Knockout HCT 116 Cell Line | EDJ-KQ43394 | Human | 55655 | Details Get a Quote |
| LRP2 Knockout HeLa Cell Line | EDJ-KQ53805 | Human | 4036 | Details Get a Quote |
| NLRP2 Knockout HeLa Cell Line | EDJ-KQ56613 | Human | 55655 | Details Get a Quote |
| LRP2 Knockout A-549 Cell Line | EDJ-KQ62286 | Human | 4036 | Details Get a Quote |
| LRP2BP Knockout A-549 Cell Line | EDJ-KQ65140 | Human | 55805 | Details Get a Quote |
| LRP2 Knockout HCT 116 Cell Line | EDJ-KQ70767 | Human | 4036 | Details Get a Quote |
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