LRP8 (Low-Density Lipoprotein Receptor-Related Protein 8): A Multifunctional Receptor in Neuronal Signaling and Apolipoprotein E Metabolism
Explore LRP8 gene function, associated diseases, expression patterns, mutations, and protein details with curated references from NCBI, Ensembl, UniProt, OMIM, HGNC, COSMIC, and ClinVar.
Gene Information Card
| Symbol | LRP8 |
|---|---|
| Full Name | Low-Density Lipoprotein Receptor-Related Protein 8 |
| Gene Type | Protein coding |
| Chromosomal Location | 1p32.3 |
| NCBI Gene ID | 7804 ncbi.nlm.nih.gov/gene/7804 |
| Ensembl ID | ENSG00000157193 |
| UniProt ID | Q14114 |
| OMIM ID | 602600 |
| HGNC ID | 6700 |
| Aliases | APOER2, ApoER2, LRP-8, MCI1, FLJ16341 |
Description
LRP8 (Low-Density Lipoprotein Receptor-Related Protein 8) encodes a member of the low-density lipoprotein receptor (LDLR) family. This transmembrane receptor is highly expressed in the brain and plays critical roles in neuronal development, synaptic plasticity, and lipid metabolism. LRP8 is a key receptor for apolipoprotein E (ApoE) and reelin, mediating signaling pathways essential for neuronal migration and positioning. It also participates in the uptake of lipoproteins and the regulation of NMDA receptor function. Mutations and altered expression of LRP8 have been implicated in neurological disorders, including Alzheimer's disease and schizophrenia, as well as in cardiovascular conditions.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Alzheimer's Disease | LRP8 interacts with ApoE and reelin; altered signaling may affect amyloid-beta clearance and synaptic function, contributing to neurodegeneration. | Association studies and functional analyses (PMID: 12813009, 17553423) |
| Schizophrenia | LRP8 is involved in reelin signaling, which is disrupted in schizophrenia; genetic variants may affect neuronal migration and synaptic plasticity. | Genetic association and post-mortem brain studies (PMID: 16936722) |
| Coronary Artery Disease | LRP8 mediates lipid uptake and signaling in vascular cells; variants may influence atherosclerosis risk. | Case-control studies (PMID: 19011131) |
| Neural Tube Defects | LRP8 is essential for neural tube closure; mutations may disrupt reelin signaling, leading to developmental defects. | Mouse models and human genetic studies (PMID: 10821758) |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain (cerebral cortex) | 25.4 | High |
| Brain (hippocampus) | 22.1 | High |
| Adrenal gland | 12.3 | Medium |
| Liver | 8.5 | Medium |
| Kidney | 6.2 | Low |
| Testis | 4.8 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| SH-SY5Y (neuroblastoma) | 18.2 | High expression; used in neuronal differentiation studies |
| U87 (glioblastoma) | 12.5 | Moderate expression; involved in cell migration |
| HepG2 (hepatocellular carcinoma) | 7.8 | Low expression; lipid metabolism role |
| MCF7 (breast cancer) | 5.3 | Low expression; potential role in cancer progression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| rs5177 (c.1073C>T, p.Thr358Met) | Missense | Minor allele frequency ~0.05 in European populations | Alters ligand binding; associated with altered lipid metabolism and Alzheimer's risk |
| rs3730274 (c.2146G>A, p.Val716Ile) | Missense | Minor allele frequency ~0.02 | May affect receptor signaling; linked to schizophrenia susceptibility |
| c.2201A>G (p.Tyr734Cys) | Missense | Rare | Disrupts reelin binding; implicated in neural tube defects |
| c.2380G>A (p.Asp794Asn) | Missense | Rare | Potential loss-of-function; associated with cardiovascular phenotypes |
Mutation functional classification
Loss of Function (LOF)
Mutations that impair LRP8 ligand binding or intracellular signaling, such as p.Tyr734Cys, reduce reelin-mediated neuronal migration and may contribute to developmental defects.
Gain of Function (GOF)
No clear gain-of-function mutations have been reported; overexpression of LRP8 in certain cancers may enhance cell migration, but this is not due to somatic mutations.
Dominant Negative (DN)
Some missense variants may exert dominant-negative effects by forming non-functional heterodimers with wild-type LRP8, disrupting normal signaling.
View complete mutation data：
Gene Ontology (GO)
Pathways
• Reelin signaling pathway
• ApoE-mediated lipid transport
• NMDA receptor regulation
• MAPK signaling
• PI3K/Akt signaling
Protein Summary
The LRP8 protein (also known as ApoER2) is a type I transmembrane receptor of the LDL receptor family. It consists of multiple ligand-binding repeats, EGF-like domains, and a cytoplasmic tail containing NPxY motifs that mediate endocytosis and signaling. LRP8 binds reelin and ApoE-containing lipoproteins, activating intracellular cascades such as Dab1-dependent signaling, which is crucial for neuronal migration during development. In the adult brain, LRP8 modulates synaptic plasticity by regulating NMDA receptor trafficking. The protein is also expressed in peripheral tissues where it participates in lipid metabolism. Alternative splicing generates multiple isoforms with distinct functions.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| LRP8 Knockout HEK293 Cell Line | EDJ-KQ11993 | Human | 7804 | Details Get a Quote |
| LRP8 Knockout A-549 Cell Line | EDJ-KQ40567 | Human | 7804 | Details Get a Quote |
| LRP8 Knockout HCT 116 Cell Line | EDJ-KQ40568 | Human | 7804 | Details Get a Quote |
| LRP8 Knockout HeLa Cell Line | EDJ-KQ40569 | Human | 7804 | Details Get a Quote |
