ASGR1 (Asialoglycoprotein Receptor 1): Structure, Function, and Clinical Significance
A comprehensive biomedical overview of the ASGR1 gene, encoding the major subunit of the hepatic asialoglycoprotein receptor, with emphasis on its role in glycoprotein homeostasis, lipid metabolism, and disease associations.
Gene Information Card
| Symbol | ASGR1 |
|---|---|
| Full Name | Asialoglycoprotein receptor 1 |
| Gene Type | protein coding |
| Chromosomal Location | 17p13.1 |
| NCBI Gene ID | 432 ncbi.nlm.nih.gov/gene/432 |
| Ensembl ID | ENSG00000141577 |
| UniProt ID | P07306 |
| OMIM ID | 108360 |
| HGNC ID | HGNC:739 |
| Aliases | ASGPR1, CLEC4H1, HL-1 |
Description
The ASGR1 gene encodes the major subunit of the asialoglycoprotein receptor (ASGPR), a C-type lectin primarily expressed on hepatocytes. This receptor mediates the endocytosis and lysosomal degradation of desialylated glycoproteins, playing a critical role in serum glycoprotein homeostasis. ASGR1 has also been implicated in lipid metabolism, where loss-of-function variants are associated with reduced LDL cholesterol and cardiovascular risk. The protein is a type II transmembrane receptor that forms a hetero-oligomeric complex with ASGR2, and its extracellular carbohydrate recognition domain binds galactose and N-acetylgalactosamine residues.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Cardiovascular disease | Loss-of-function variants in ASGR1 are associated with reduced LDL cholesterol and decreased risk of coronary artery disease, likely through altered hepatic clearance of lipoproteins. | Genome-wide association studies (GWAS) and exome sequencing (e.g., Nioi et al., 2016, NEJM) |
| Non-alcoholic fatty liver disease (NAFLD) | ASGR1 expression is altered in NAFLD, potentially affecting glycoprotein clearance and lipid metabolism, though direct causality is not fully established. | Expression studies in liver tissues (e.g., GTEx, published transcriptomic analyses) |
| Hepatocellular carcinoma (HCC) | Downregulation of ASGR1 in HCC tissues correlates with tumor progression and poor prognosis, possibly due to impaired receptor-mediated endocytosis. | Immunohistochemistry and transcriptomic studies (e.g., PubMed indexed reports) |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Liver | High (e.g., 1000+ nTPM) | High |
| Kidney | Low (e.g., 10-20 nTPM) | Low |
| Small intestine | Low (e.g., 5-10 nTPM) | Low |
| Other tissues | Very low or not detected | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HepG2 (liver cancer) | High | Hepatocyte-derived cell line; used as model for ASGR1 function |
| Huh7 (liver cancer) | High | Hepatocyte-derived; similar expression to HepG2 |
| HEK293 (embryonic kidney) | Low | Often used for recombinant expression; endogenous expression low |
| HeLa (cervical cancer) | Not detected | Non-hepatic; no significant expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| rs186696265 (p.Trp158Ter) | Nonsense | Rare (MAF ~0.1% in Europeans) | Loss-of-function; associated with reduced LDL cholesterol |
| rs147188847 (p.Arg263His) | Missense | Rare (MAF <0.1%) | Likely loss-of-function; functional impact uncertain |
| rs61741902 (p.Val174Ile) | Missense | Common (MAF ~5%) | Benign; no known clinical effect |
Mutation functional classification
Loss of Function (LOF)
Loss-of-function mutations in ASGR1, such as nonsense or frameshift variants, lead to reduced receptor activity, resulting in decreased hepatic uptake of desialylated glycoproteins and altered lipid metabolism. These variants are associated with lower LDL cholesterol and reduced cardiovascular risk.
Gain of Function (GOF)
No gain-of-function mutations have been reported for ASGR1. The receptor's function is primarily dependent on its expression and complex formation with ASGR2.
Dominant Negative (DN)
No dominant-negative mutations have been described. ASGR1 functions as a hetero-oligomer with ASGR2; however, haploinsufficiency may contribute to phenotypic effects, but no clear dominant-negative mechanism is established.
View complete mutation data：
Gene Ontology (GO)
| • carbohydrate binding | • galactose binding |
| • receptor-mediated endocytosis | • integral component of membrane |
| • plasma membrane | • clathrin-coated pit |
| • endosome | • lysosome |
| • cell surface receptor signaling pathway | • response to lipopolysaccharide |
Pathways
• Asialoglycoprotein receptor-mediated endocytosis
• Scavenger receptor pathway
• Lipoprotein metabolism (LDL clearance)
• Glycoprotein catabolism
Protein Summary
The ASGR1 protein is a 291-amino acid type II transmembrane glycoprotein with a short N-terminal cytoplasmic domain, a single transmembrane helix, and a large C-terminal extracellular domain containing a carbohydrate recognition domain (CRD). It forms a hetero-oligomeric complex with ASGR2 (subunit 2) to constitute the functional asialoglycoprotein receptor. The receptor binds terminal galactose or N-acetylgalactosamine residues on desialylated glycoproteins, facilitating their internalization via clathrin-mediated endocytosis and delivery to lysosomes for degradation. ASGR1 is predominantly expressed on the sinusoidal surface of hepatocytes, where it maintains serum glycoprotein homeostasis. Recent studies have also linked ASGR1 to lipid metabolism, as loss-of-function variants are associated with reduced LDL cholesterol and cardiovascular risk, making it a potential therapeutic target.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| ASGR1 Knockout HEK293 Cell Line | EDJ-KQ2668 | Human | 432 | Details Get a Quote |
| ASGR1 Knockout A-549 Cell Line | EDJ-KQ23454 | Human | 432 | Details Get a Quote |
| ASGR1 Knockout HeLa Cell Line | EDJ-KQ77838 | Human | 432 | Details Get a Quote |
| ASGR1 Knockout HCT 116 Cell Line | EDJ-KQ77839 | Human | 432 | Details Get a Quote |
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