SORL1 (Sortilin Related Receptor 1)
A key player in Alzheimer's disease pathogenesis and endosomal trafficking
Gene Information Card
| Symbol | SORL1 |
|---|---|
| Full Name | Sortilin Related Receptor 1 |
| Gene Type | protein-coding |
| Chromosomal Location | 11q24.1 |
| NCBI Gene ID | 6653 ncbi.nlm.nih.gov/gene/6653 |
| Ensembl ID | ENSG00000137642 |
| UniProt ID | Q92673 |
| OMIM ID | 602005 |
| HGNC ID | 11185 |
| Aliases | LR11, SORLA, SorLA-1, gp250 |
Description
SORL1 encodes a mosaic protein that belongs to the vacuolar protein sorting 10 (VPS10) domain-containing receptor family. It functions as a sorting receptor in the endocytic and secretory pathways, particularly involved in the trafficking of amyloid precursor protein (APP) and other ligands. SORL1 is highly expressed in the brain and has been strongly implicated in the pathogenesis of Alzheimer's disease (AD). Loss-of-function variants increase the risk of late-onset AD.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Alzheimer's disease, late-onset | Loss-of-function variants impair APP sorting, leading to increased amyloid-beta production | Multiple GWAS and sequencing studies (e.g., Pottier et al., 2012; Rogaeva et al., 2007) |
| Alzheimer's disease, early-onset | Rare coding variants (e.g., p.Gly511Arg) disrupt protein function | Exome sequencing studies (e.g., Nicolas et al., 2016) |
| Frontotemporal dementia | Potential role via altered protein trafficking | Limited evidence; some variants reported in FTD cohorts |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain (cerebral cortex) | 28.5 | High |
| Brain (hippocampus) | 26.3 | High |
| Brain (cerebellum) | 22.1 | High |
| Testis | 15.4 | Medium |
| Adipose tissue | 10.2 | Medium |
| Liver | 5.8 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| SH-SY5Y (neuroblastoma) | 32.1 | High expression; used in APP trafficking studies |
| HEK293 (embryonic kidney) | 18.5 | Moderate expression; common for overexpression |
| H4 (neuroglioma) | 25.0 | High expression; relevant for AD research |
| HeLa (cervical carcinoma) | 12.3 | Moderate expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| p.Gly511Arg (rs201119075) | Missense | Rare (MAF <0.01%) | Loss of function; increases Aβ production |
| p.Arg953Cys (rs143571823) | Missense | Rare | Impaired APP binding |
| p.Thr947Met (rs142649917) | Missense | Rare | Reduced SORL1 expression |
| c.5779C>T (p.Arg1927*) | Nonsense | Very rare | Premature truncation; loss of function |
Mutation functional classification
Loss of Function (LOF)
Most SORL1 mutations associated with Alzheimer's disease are loss-of-function, reducing protein expression or disrupting APP sorting, leading to increased amyloid-beta production.
Gain of Function (GOF)
No well-established gain-of-function mutations reported for SORL1.
Dominant Negative (DN)
Some missense variants may exert dominant-negative effects by interfering with wild-type SORL1 function, but evidence is limited.
View complete mutation data：
Gene Ontology (GO)
Pathways
• Alzheimer's disease (KEGG: hsa05010)
• Endocytosis (KEGG: hsa04144)
• APP processing (Reactome: R-HSA-977225)
Protein Summary
SORL1 (also known as SorLA or LR11) is a 250 kDa type I transmembrane protein with multiple domains: an N-terminal VPS10 domain, a YWTD β-propeller domain, an EGF-like domain, a fibronectin type III domain, and a short cytoplasmic tail. It acts as a sorting receptor that shuttles APP from the cell surface to the Golgi and endosomes, preventing its processing into amyloid-beta. SORL1 also binds other ligands such as apolipoprotein E and growth factors. Its expression is particularly high in neurons, and reduced levels are observed in Alzheimer's disease brains.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| SORL1 Knockout HEK293 Cell Line | EDJ-KQ3028 | Human | 6653 | Details Get a Quote |
| SORL1 Knockout A-549 Cell Line | EDJ-KQ24248 | Human | 6653 | Details Get a Quote |
| SORL1 Knockout HCT 116 Cell Line | EDJ-KQ24249 | Human | 6653 | Details Get a Quote |
| SORL1 Knockout HeLa Cell Line | EDJ-KQ24250 | Human | 6653 | Details Get a Quote |
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