LRP1 (LDL Receptor Related Protein 1): A Multifunctional Endocytic Receptor in Health and Disease
Explore the structure, function, clinical significance, and expression of the LRP1 gene, a key player in lipid metabolism, cell signaling, and neurodegeneration.
Gene Information Card
| Symbol | LRP1 |
|---|---|
| Full Name | LDL Receptor Related Protein 1 |
| Gene Type | protein-coding |
| Chromosomal Location | 12q13.3 |
| NCBI Gene ID | 4035 ncbi.nlm.nih.gov/gene/4035 |
| Ensembl ID | ENSG00000123384 |
| UniProt ID | Q07954 |
| OMIM ID | 107770 |
| HGNC ID | 6692 |
| Aliases | APOER, CD91, A2MR, APR, IGFBP3R, LRP1A, TGFBR5 |
Description
The LRP1 gene encodes the LDL receptor related protein 1, a large, multifunctional endocytic receptor that belongs to the low-density lipoprotein (LDL) receptor family. This type I transmembrane protein is involved in a wide range of biological processes, including lipid metabolism, protease regulation, and cellular signaling. It binds and internalizes over 30 distinct ligands, such as apolipoprotein E (ApoE), alpha-2-macroglobulin, and various proteases and growth factors. LRP1 is crucial for the clearance of these molecules from the extracellular space and plays a significant role in maintaining tissue homeostasis. It is highly expressed in the liver, brain, and vascular smooth muscle cells, where it influences processes like synaptic transmission, blood-brain barrier integrity, and vascular remodeling. Due to its diverse functions, LRP1 is implicated in the pathology of several diseases, including Alzheimer's disease, atherosclerosis, and cancer.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Disease | Mechanism | Evidence |
| Alzheimer's Disease (AD) | LRP1 mediates the clearance of amyloid-beta (Aβ) peptides across the blood-brain barrier and in the brain parenchyma. Reduced LRP1 expression or function leads to Aβ accumulation, a hallmark of AD. It also interacts with ApoE, another key AD risk factor. | ClinVar, OMIM, NCBI Gene |
| Atherosclerosis | LRP1 in vascular smooth muscle cells (VSMCs) regulates platelet-derived growth factor (PDGF) signaling and matrix metalloproteinase (MMP) activity. Loss of LRP1 in VSMCs leads to increased susceptibility to cholesterol-induced atherosclerosis and aneurysm formation. | NCBI Gene, OMIM |
| Cancer | LRP1 modulates tumor cell invasion and metastasis by regulating the activity of proteases like urokinase-type plasminogen activator (uPA) and matrix metalloproteinases (MMPs). It also influences cell signaling pathways involved in proliferation and survival. | COSMIC, NCBI Gene |
| Cardiovascular Disease | LRP1 is involved in the clearance of chylomicron remnants and other lipoproteins in the liver. Dysregulation can contribute to hyperlipidemia and increased cardiovascular risk. | OMIM, NCBI Gene |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Tissue | nTPM | Level |
| Liver | ~200 | High |
| Brain | ~150 | High |
| Adipose Tissue | ~100 | Medium |
| Lung | ~80 | Medium |
| Skeletal Muscle | ~50 | Medium |
| Blood | ~10 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| Cell Line | nTPM | Notes |
| HepG2 (Liver) | ~250 | High expression; used for studies on lipoprotein metabolism. |
| U-87 MG (Brain) | ~180 | High expression; relevant for glioblastoma and Aβ clearance studies. |
| A549 (Lung) | ~90 | Moderate expression; used in cancer invasion studies. |
| MCF7 (Breast) | ~40 | Lower expression; studies focus on its role in tumor suppression. |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| Variant | Type | Frequency | Effect |
| rs1799986 (N/S polymorphism) | Missense | Common (MAF > 0.1) | Associated with altered risk for Alzheimer's disease and cardiovascular disease in some populations. |
| rs4759277 | Intronic | Common | Associated with altered LRP1 expression levels in the brain. |
| Various somatic mutations | Missense, Nonsense, Indels | Rare in most cancers | Can lead to loss of function, potentially promoting tumor invasion and metastasis. |
Mutation functional classification
Loss of Function (LOF)
Loss-of-function mutations in LRP1 are generally not observed as germline homozygous variants due to embryonic lethality in animal models. However, somatic loss-of-function mutations in tumors can lead to increased cell migration and invasion by disrupting the regulation of proteases and growth factor receptors. Heterozygous loss-of-function variants may contribute to disease susceptibility by reducing the overall capacity for ligand clearance.
Gain of Function (GOF)
Gain-of-function mutations are not well-documented for LRP1. The receptor's function is primarily regulated by its expression level and the availability of its ligands. No clear activating mutations have been identified that enhance its endocytic activity beyond normal physiological levels.
Dominant Negative (DN)
Given that LRP1 functions as a dimer or in a complex with other receptors, a dominant-negative effect is theoretically possible. A mutant LRP1 protein that can bind to the wild-type protein but is unable to internalize ligands could impair the function of the normal receptor. However, such dominant-negative mutations have not been clearly characterized in human disease.
View complete mutation data：
Gene Ontology (GO)
| • endocytosis | • receptor-mediated endocytosis |
| • lipid metabolism | • amyloid-beta clearance |
| • cell surface receptor signaling pathway | • proteolysis |
| • cell adhesion | • signal transduction |
| • response to wounding | • regulation of cell migration |
Pathways
• Lipoprotein metabolism
• Alzheimer's disease - amyloid-beta clearance
• Plasminogen activating cascade
• TGF-beta signaling pathway
• PDGF signaling pathway
• Clathrin-mediated endocytosis
Protein Summary
The LRP1 protein is a large (600 kDa) type I transmembrane receptor that is synthesized as a single-chain precursor and then cleaved by furin into a non-covalently associated heavy (515 kDa) and light (85 kDa) chain. The heavy chain is entirely extracellular and contains four clusters of complement-type repeats that are the binding sites for its numerous ligands. The light chain contains a single transmembrane domain and a short cytoplasmic tail. The cytoplasmic tail contains several NPxY motifs that are critical for endocytosis and for binding to intracellular adaptor proteins, such as Disabled-2 (Dab2) and FE65, which link LRP1 to various signaling pathways. LRP1 is a key scavenger receptor, clearing a wide array of ligands from the extracellular space and cell surface, thereby regulating their local concentrations and signaling activities.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| LRP1 Knockout HEK293 Cell Line | EDJ-KQ103 | Human | 4035 | Details Get a Quote |
| LRP11 Knockout HEK293 Cell Line | EDJ-KQ3274 | Human | 84918 | Details Get a Quote |
| NLRP11 Knockout HEK293 Cell Line | EDJ-KQ5976 | Human | 204801 | Details Get a Quote |
| NLRP1 Knockout HEK293 Cell Line | EDJ-KQ7700 | Human | 22861 | Details Get a Quote |
| LRP10 Knockout HEK293 Cell Line | EDJ-KQ8356 | Human | 26020 | Details Get a Quote |
| NLRP13 Knockout HEK293 Cell Line | EDJ-KQ8867 | Human | 126204 | Details Get a Quote |
| LRP12 Knockout HEK293 Cell Line | EDJ-KQ9115 | Human | 29967 | Details Get a Quote |
| NLRP12 Knockout HEK293 Cell Line | EDJ-KQ10770 | Human | 91662 | Details Get a Quote |
| LRP1B Knockout HEK293 Cell Line | EDJ-KQ11336 | Human | 53353 | Details Get a Quote |
| NLRP10 Knockout HEK293 Cell Line | EDJ-KQ14440 | Human | 338322 | Details Get a Quote |
| NLRP14 Knockout HEK293 Cell Line | EDJ-KQ14441 | Human | 338323 | Details Get a Quote |
| NLRP1 Knockout HCT 116 Cell Line | EDJ-KQ33084 | Human | 22861 | Details Get a Quote |
| NLRP1 Knockout HeLa Cell Line | EDJ-KQ33085 | Human | 22861 | Details Get a Quote |
| LRP1 Knockout HCT 116 Cell Line | EDJ-KQ18260 | Human | 4035 | Details Get a Quote |
| LRP1 Knockout A-549 Cell Line | EDJ-KQ23776 | Human | 4035 | Details Get a Quote |
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