SORT1 (Sortilin 1): A Multifunctional Receptor in Lipid Metabolism, Neurobiology, and Disease
Explore the SORT1 gene, its protein product sortilin, associated diseases, expression patterns, mutations, and molecular functions.
Gene Information Card
| Symbol | SORT1 |
|---|---|
| Full Name | Sortilin 1 |
| Gene Type | Protein coding |
| Chromosomal Location | 1p13.3 |
| NCBI Gene ID | 6272 ncbi.nlm.nih.gov/gene/6272 |
| Ensembl ID | ENSG00000134243 |
| UniProt ID | Q99523 |
| OMIM ID | 602458 |
| HGNC ID | 11186 |
| Aliases | GMRP, LDLCQ6, NT3, NTR3, Sortilin |
Description
SORT1 encodes sortilin, a type I transmembrane receptor belonging to the Vps10 family. It is involved in intracellular trafficking, lipid metabolism, and neurotrophin signaling. Sortilin regulates progranulin levels, LDL metabolism, and glucose homeostasis, and has been implicated in cardiovascular and neurodegenerative diseases.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Alzheimer's disease | Sortilin modulates progranulin levels, affecting neuroinflammation and neurodegeneration | GWAS and functional studies (PMID: 22019782) |
| Cardiovascular disease | SORT1 variants affect LDL cholesterol levels and risk of myocardial infarction | GWAS (PMID: 20031578) |
| Type 2 diabetes | Sortilin influences insulin sensitivity and glucose metabolism | Association studies (PMID: 25064392) |
| Frontotemporal dementia | Reduced sortilin expression leads to progranulin haploinsufficiency | Functional studies (PMID: 22019782) |
| Obesity | Sortilin regulates adiponectin secretion and lipid storage | Mouse models (PMID: 26023105) |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Liver | 12.4 | Medium |
| Brain | 8.7 | Low |
| Adipose tissue | 6.2 | Low |
| Muscle | 3.1 | Low |
| Kidney | 2.5 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HepG2 | 15.3 | Hepatocellular carcinoma cell line |
| SH-SY5Y | 10.2 | Neuroblastoma cell line |
| A549 | 5.4 | Lung carcinoma cell line |
| MCF7 | 3.8 | Breast cancer cell line |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| rs599839 | SNP (intronic) | ~20% allele frequency | Associated with reduced LDL cholesterol and cardiovascular risk |
| rs646776 | SNP (intergenic) | ~30% allele frequency | Associated with SORT1 expression and lipid levels |
| c.214G>A (p.Val72Met) | Missense | Rare | Potential effect on protein function, not well characterized |
| c.1123C>T (p.Arg375Trp) | Missense | Rare | Reported in neurodevelopmental disorders, functional impact unknown |
Mutation functional classification
Loss of Function (LOF)
Loss-of-function mutations in SORT1 lead to reduced sortilin protein levels, resulting in increased progranulin secretion and altered lipid metabolism. This may contribute to neurodegeneration and cardiovascular risk.
Gain of Function (GOF)
Gain-of-function mutations are rare and not well documented. Overexpression of sortilin can enhance LDL uptake and progranulin degradation, potentially affecting cellular homeostasis.
Dominant Negative (DN)
No dominant-negative mutations have been reported for SORT1.
View complete mutation data：
Gene Ontology (GO)
| • neurotrophin receptor activity | • protein binding |
| • lipoprotein particle binding | • signaling receptor activity |
| • endosome membrane | • plasma membrane |
| • Golgi apparatus | • lysosome |
| • intracellular protein transport | • regulation of lipid metabolic process |
Pathways
• Neurotrophin signaling pathway
• LDL clearance pathway
• Progranulin trafficking
• Insulin signaling
• Vps10 family receptor signaling
Protein Summary
Sortilin is a 100 kDa type I transmembrane protein with a large N-terminal extracellular domain containing a Vps10 domain, a single transmembrane helix, and a short cytoplasmic tail. It functions as a sorting receptor, trafficking ligands between the Golgi, endosomes, lysosomes, and plasma membrane. Sortilin binds progranulin, neurotrophins, and lipoproteins, regulating their levels and signaling. It is widely expressed in liver, brain, and adipose tissue, and plays critical roles in lipid metabolism, neuronal survival, and glucose homeostasis.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| SORT1 Knockout HEK293 Cell Line | EDJ-KQ2463 | Human | 6272 | Details Get a Quote |
| SORT1 Knockout A-549 Cell Line | EDJ-KQ23014 | Human | 6272 | Details Get a Quote |
| SORT1 Knockout HCT 116 Cell Line | EDJ-KQ23015 | Human | 6272 | Details Get a Quote |
| SORT1 Knockout HeLa Cell Line | EDJ-KQ23016 | Human | 6272 | Details Get a Quote |
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