ASGR2 (Asialoglycoprotein Receptor 2): Gene, Function, and Clinical Relevance
A comprehensive overview of the ASGR2 gene, including its genomic context, protein function, expression patterns, associated diseases, and mutation landscape.
Gene Information Card
| Symbol | ASGR2 |
|---|---|
| Full Name | Asialoglycoprotein receptor 2 |
| Gene Type | protein coding |
| Chromosomal Location | 17p13.1 |
| NCBI Gene ID | 433 ncbi.nlm.nih.gov/gene/433 |
| Ensembl ID | ENSG00000161944 |
| UniProt ID | P07307 |
| OMIM ID | 108360 |
| HGNC ID | 740 |
| Aliases | CLEC4H2, HL-2, ASGP-R2, C-type lectin domain family 4 member H2 |
Description
The ASGR2 gene encodes the asialoglycoprotein receptor 2, a subunit of the hepatic asialoglycoprotein receptor (ASGPR). This receptor is primarily expressed on the sinusoidal surface of hepatocytes and mediates the endocytosis of circulating glycoproteins with exposed terminal galactose or N-acetylgalactosamine residues. ASGR2 is a type II transmembrane protein that contains a C-type lectin domain. It forms a hetero-oligomeric complex with ASGR1, which is essential for high-affinity ligand binding and internalization. The receptor plays a critical role in serum glycoprotein homeostasis and has been implicated in viral entry (e.g., hepatitis B and C viruses) and liver cancer.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Hepatocellular carcinoma | Altered ASGR2 expression may affect receptor-mediated endocytosis and signaling, potentially influencing tumor progression. | Expression studies in HCC tissues show downregulation; functional studies suggest a tumor-suppressive role (PMID: 31211834). |
| Hepatitis B virus infection | ASGR2 is a putative receptor for HBV entry; binding of HBV preS1 domain to ASGPR facilitates viral uptake into hepatocytes. | In vitro studies using HepG2 cells demonstrate that ASGR2 mediates HBV entry (PMID: 28381556). |
| Hepatitis C virus infection | ASGR2 interacts with HCV E2 glycoprotein, potentially contributing to viral attachment and entry. | Co-immunoprecipitation assays show binding between ASGR2 and HCV E2 (PMID: 15194770). |
| Liver cirrhosis | Reduced ASGR2 expression in cirrhotic liver may impair clearance of desialylated glycoproteins, contributing to systemic changes. | Immunohistochemistry of cirrhotic liver samples shows decreased ASGR2 staining (PMID: 2444944). |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Liver | 12.4 | High |
| Kidney | 1.2 | Low |
| Small intestine | 0.8 | Low |
| Spleen | 0.5 | Low |
| Lung | 0.3 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HepG2 | 15.2 | Hepatocellular carcinoma cell line; high expression |
| Huh7 | 12.8 | Hepatoma cell line; high expression |
| HEK293 | 0.1 | Embryonic kidney; very low expression |
| HeLa | 0.0 | Cervical carcinoma; no expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1A>G (p.Met1Val) | Missense | Rare | Potential loss of start codon, leading to truncated protein |
| c.244C>T (p.Arg82Cys) | Missense | Rare | Disrupts disulfide bond, affecting protein folding |
| c.565G>A (p.Gly189Ser) | Missense | Rare | Alters ligand-binding domain, reducing receptor function |
Mutation functional classification
Loss of Function (LOF)
Mutations that impair protein synthesis, folding, or ligand binding are likely loss-of-function, reducing receptor activity.
Gain of Function (GOF)
No gain-of-function mutations have been reported for ASGR2.
Dominant Negative (DN)
No dominant-negative mutations have been characterized; however, mutations in one allele could potentially interfere with hetero-oligomer formation.
View complete mutation data：
Gene Ontology (GO)
| • carbohydrate binding | • receptor activity |
| • endocytosis | • cell surface receptor signaling pathway |
| • integral component of membrane |
Pathways
• Asialoglycoprotein receptor-mediated endocytosis
• Viral entry into host cell (HBV
• HCV)
Protein Summary
ASGR2 is a 311-amino acid type II transmembrane protein with a short N-terminal cytoplasmic domain, a single transmembrane helix, and a large extracellular C-type lectin domain. It forms a hetero-oligomeric complex with ASGR1, which is required for high-affinity binding of desialylated glycoproteins. The protein is predominantly expressed in hepatocytes and is involved in receptor-mediated endocytosis. It also serves as a co-receptor for hepatitis B and C viruses. Post-translational modifications include glycosylation, which is essential for proper trafficking and function.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| ASGR2 Knockout HEK293 Cell Line | EDJ-KQ3087 | Human | 433 | Details Get a Quote |
| ASGR2 Knockout HeLa Cell Line | EDJ-KQ52671 | Human | 433 | Details Get a Quote |
| ASGR2 Knockout A-549 Cell Line | EDJ-KQ61143 | Human | 433 | Details Get a Quote |
| ASGR2 Knockout HCT 116 Cell Line | EDJ-KQ69631 | Human | 433 | Details Get a Quote |
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