Details for: ASGR2

Gene ID: 433

Gene Type:  Protein-coding  - A gene that serves as a template for producing a messenger RNA (mRNA) molecule, which is then translated into a functional protein.

Symbol: ASGR2

Ensembl ID: ENSG00000161944

Description: asialoglycoprotein receptor 2

Selected Context(s):  Overall

Cell Significance Landscape

Contexts:

Associated with

Significant Cells

Cell Significance Index (CSI) scores for the chosen context(s)

  • hepatocyte CL0000182
    CSI 28.4
    rCSI 50.83%
    PRS 84.48
  • midzonal region hepatocyte CL0019028
    CSI 17.95
    rCSI 42.12%
    PRS 84.13
  • intrahepatic cholangiocyte CL0002538
    CSI 10.79
    rCSI 25.9%
    PRS 87.48
  • promonocyte CL0000559
    CSI 9.13
    rCSI 15.64%
    PRS 89.39
  • centrilobular region hepatocyte CL0019029
    CSI 7.94
    rCSI 20.72%
    PRS 82.61
  • hepatic stellate cell CL0000632
    CSI 7.05
    rCSI 26.41%
    PRS 78.82
  • CD14-positive monocyte CL0001054
    CSI 5.01
    rCSI 6.24%
    PRS 92.47
  • Kupffer cell CL0000091
    CSI 3.37
    rCSI 7.7%
    PRS 86.2
  • CD14-positive, CD16-positive monocyte CL0002397
    CSI 2.97
    rCSI 3.89%
    PRS 93.35
  • periportal region hepatocyte CL0019026
    CSI 2.6
    rCSI 10.1%
    PRS 83.51
  • basal cell of epidermis CL0002187
    CSI 2.43
    rCSI 4.31%
    PRS 54.7
  • Langerhans cell CL0000453
    CSI 1.58
    rCSI 2.42%
    PRS 93.53
  • suprabasal keratinocyte CL4033013
    CSI 1.11
    rCSI 1.81%
    PRS 53.47
  • cholangiocyte CL1000488
    CSI 1.01
    rCSI 6.04%
    PRS 86.01
  • intermediate monocyte CL0002393
    CSI 1
    rCSI 1.5%
    PRS 89.94
  • CD14-positive, CD16-negative classical monocyte CL0002057
    CSI 0.53
    rCSI 3.18%
    PRS 93.23

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this specific cell.

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this cell type. Calculated using techniques like effect size estimation and bootstrapping for reliability.

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this cell type. Calculated using techniques like effect size estimation and bootstrapping for reliability.
Network Configuration

Explore relationships of the current gene. Select an Interaction Source: 'ONTOLOGY' for shared pathways (GO/Reactome) or 'STRING' for protein-protein interactions. Further refine by selecting context genes and comparing Cell Significance Index (CSI) scores between baseline and target cell types and their specific contexts.

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  • Query Gene
  • Node Color (Target Cell CSI, relative to current network):
    • Very High
    • High
    • Medium
    • Low
    • Very Low
    • CSI N/A
  • Node Size: Proportional to Target Cell CSI magnitude
  • STRING PPI Edge
  • Shared Pathway Edge (ONTOLOGY)

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Other Information

This section provides additional information about the gene, including a description generated by an AI language model and details about associated proteins.

## Summary Asialoglycoprotein receptor 2, encoded by the [ASGR2](/details-gene/433) gene, is a subunit of the hepatic asialoglycoprotein receptor (ASGPR). This receptor is a C-type lectin that plays a crucial role in serum glycoprotein homeostasis by mediating the endocytosis and subsequent lysosomal degradation of glycoproteins that have exposed terminal galactose or N-acetylgalactosamine residues. **Overall**, expression data reveals that [ASGR2](/details-gene/433) is a highly specific marker for liver cells, with its most significant expression observed in [hepatocytes](/details-cell/CL0000182). Its function is primarily associated with protein metabolism, particularly the clearance of circulating glycoproteins, and it has been implicated as a potential host factor in viral infections [Link](https://doi.org/10.1002/jmv.24570). ## Cellular Roles and Expression Landscape The expression profile of [ASGR2](/details-gene/433) firmly establishes it as a key component of liver biology. It shows the highest significance in [hepatocytes](/details-cell/CL0000182) (CSI: 28.40), including those in specific liver zones such as [midzonal region hepatocytes](/details-cell/CL0019028) (CSI: 17.95) and [centrilobular region hepatocytes](/details-cell/CL0019029) (CSI: 7.94). This highlights its integral role in the primary metabolic functions of these cells. Significant expression is also noted in other liver-resident cells, including [intrahepatic cholangiocytes](/details-cell/CL0002538) (CSI: 10.79) and [hepatic stellate cells](/details-cell/CL0000632) (CSI: 7.05), suggesting a broader role in hepatic cell function beyond just hepatocytes. Beyond the liver, [ASGR2](/details-gene/433) displays a notable, albeit lower, significance in certain myeloid lineage cells. This includes [promonocytes](/details-cell/CL0000559) (CSI: 9.13), [CD14-positive monocytes](/details-cell/CL0001054) (CSI: 5.01), and the liver-resident macrophages known as [Kupffer cells](/details-cell/CL0000091) (CSI: 3.37). This expression pattern suggests a potential secondary role in the innate immune system, possibly related to the recognition and clearance of glycosylated pathogens or cellular debris within the bloodstream and liver sinusoids. ## Pathways and Molecular Function The functions of [ASGR2](/details-gene/433) are deeply rooted in protein processing and cell surface signaling. Gene Ontology annotations confirm its role in the [cell surface receptor signaling pathway](/details-cell/GO:0007166) and [endocytosis](/details-cell/GO:0006897). Its molecular function is defined by its [asialoglycoprotein receptor activity](/details-cell/GO:0004873), which involves binding to specific carbohydrate structures such as D-mannose ([GO:0005537](https://www.ebi.ac.uk/QuickGO/term/GO:0005537)) and fucose ([GO:0042806](https://www.ebi.ac.uk/QuickGO/term/GO:0042806)). This is consistent with its location on the [external side of the plasma membrane](/details-cell/GO:0009897). Reactome pathway analysis further places [ASGR2](/details-gene/433) within the broader context of protein life cycles, including [Metabolism of proteins](/details-cell/R-HSA-392499) and [Post-translational protein modification](/details-cell/R-HSA-597592). This functional profile aligns perfectly with its high expression in [hepatocytes](/details-cell/CL0000182), the primary site for clearing desialylated glycoproteins from the circulation, thereby maintaining serum protein quality control. Its annotation as a [pattern recognition receptor](/details-cell/GO:0038187) supports the hypothesis of an immune surveillance function in myeloid cells. ## Research Directions The highly specific expression of [ASGR2](/details-gene/433) in the liver, combined with its function as an endocytic receptor, opens several avenues for future research. ### Proposed Hypotheses: 1. Given that the ASGPR complex facilitates Hepatitis E virus entry into hepatic cells [Link](https://doi.org/10.1002/jmv.24570), [ASGR2](/details-gene/433) may function as a more general co-receptor for other hepatotropic pathogens whose surface proteins are glycosylated. Its role in mediating the entry of other viruses (e.g., Hepatitis B variants) or even bacterial pathogens that target the liver warrants investigation. 2. The expression of [ASGR2](/details-gene/433) in [Kupffer cells](/details-cell/CL0000091) and other monocytes suggests a role in hepatic innate immunity. It may act as a pattern recognition receptor specializing in the clearance of glycosylated PAMPs (Pathogen-Associated Molecular Patterns) or DAMPs (Damage-Associated Molecular Patterns), thereby contributing to the inflammatory response or tolerance induction within the liver microenvironment. ### Experimental Approach: To test the second hypothesis regarding its immune function, a compelling experiment would be to use CRISPR-Cas9 to knock out [ASGR2](/details-gene/433) in a human monocyte-derived macrophage cell line (e.g., THP-1) or in primary human [Kupffer cells](/details-cell/CL0000091). These knockout and wild-type cells could then be challenged with various stimuli, such as galactosylated bacterial lipopolysaccharide (LPS) or yeast-derived zymosan. The cellular response could be quantified by measuring phagocytic uptake via flow cytometry and the secretion of key cytokines (e.g., TNF-alpha, IL-6, IL-10) using ELISA. A significant reduction in phagocytosis or an altered cytokine profile in the knockout cells would provide direct evidence for its role in innate immune recognition. ### Therapeutic Potential: The remarkable tissue specificity of [ASGR2](/details-gene/433) for liver cells makes it an exceptionally attractive target for therapeutic delivery. Rather than inhibiting or activating the receptor itself, its natural endocytic function can be exploited. This strategy, known as receptor-mediated targeting, involves conjugating therapeutic agents (such as small molecules, siRNAs, or oligonucleotides) to ligands recognized by the ASGPR complex, like N-acetylgalactosamine (GalNAc). This approach allows for the highly efficient and specific delivery of drugs to [hepatocytes](/details-cell/CL0000182), minimizing off-target toxicity and increasing therapeutic efficacy for a wide range of liver diseases, including chronic hepatitis, genetic metabolic disorders, and hepatocellular carcinoma.

Genular Protein ID: 846854115

Symbol: ASGR2_HUMAN

Name: Asialoglycoprotein receptor 2

UniProtKB Accession Codes:

P07307 A6NLV8 A8MT12 D3DTM9 D3DTN0 O00448 Q03969

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 Bgee 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 3 CDD 1 CPTAC 1 CTD 1 ChiTaRS 1 DMDM 1 DNASU 1 DisGeNET 1 DrugBank 3 EMBL 9 Ensembl 3 ExpressionAtlas 1 GO 9 Gene3D 1 GeneCards 1 GeneTree 1 GenomeRNAi 1 GlyConnect 1 GlyCosmos 1 GlyGen 1 HGNC 1 HOGENOM 1 HPA 1 InParanoid 1 IntAct 1 InterPro 6 KEGG 1 MIM 1 MassIVE 1 NCBI Taxonomy 1 OMA 1 OpenTargets 1 OrthoDB 1 PANTHER 2 PDB 1 PDBsum 1 PIR 1 PRO 1 PROSITE 2 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 Pfam 2 PharmGKB 1 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 ProteomicsDB 3 RNAct 1 Reactome 1 RefSeq 10 SMART 1 SMR 1 STRING 1 SUPFAM 1 SignaLink 1 SwissPalm 1 TreeFam 1 UCSC 1 VEuPathDB 1 eggNOG 1 iPTMnet 1 jPOST 1 neXtProt 1

Citations:

PubMed ID: 3863106

Title: Sequence of a second human asialoglycoprotein receptor: conservation of two receptor genes during evolution.

PubMed ID: 3863106

DOI: 10.1073/pnas.82.19.6465

PubMed ID: 1371982

Title: Differences in the abundance of variably spliced transcripts for the second asialoglycoprotein receptor polypeptide, H2, in normal and transformed human liver.

PubMed ID: 1371982

DOI: 10.1002/hep.1840150307

PubMed ID: 16625196

Title: DNA sequence of human chromosome 17 and analysis of rearrangement in the human lineage.

PubMed ID: 16625196

DOI: 10.1038/nature04689

PubMed ID: 15489334

Title: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).

PubMed ID: 15489334

DOI: 10.1101/gr.2596504

PubMed ID: 11543633

Title: Cloning, mapping, and characterization of a human homologue of the yeast longevity assurance gene LAG1.

PubMed ID: 11543633

DOI: 10.1006/geno.2001.6614

PubMed ID: 16335952

Title: Human plasma N-glycoproteome analysis by immunoaffinity subtraction, hydrazide chemistry, and mass spectrometry.

PubMed ID: 16335952

DOI: 10.1021/pr0502065

PubMed ID: 19159218

Title: Glycoproteomics analysis of human liver tissue by combination of multiple enzyme digestion and hydrazide chemistry.

PubMed ID: 19159218

DOI: 10.1021/pr8008012

PubMed ID: 24275569

Title: An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome.

PubMed ID: 24275569

DOI: 10.1016/j.jprot.2013.11.014

PubMed ID: 27155063

Title: Asialoglycoprotein receptor facilitates infection of PLC/PRF/5 cells by HEV through interaction with ORF2.

PubMed ID: 27155063

DOI: 10.1002/jmv.24570

Sequence Information:

  • Length: 311
  • Mass: 35092
  • Checksum: C86D2247FFF604DC
  • Sequence:
    • MAKDFQDIQQ LSSEENDHPF HQGEGPGTRR LNPRRGNPFL KGPPPAQPLA QRLCSMVCFS 
LLALSFNILL LVVICVTGSQ SEGHGGAQLQ AELRSLKEAF SNFSSSTLTE VQAISTHGGS 
VGDKITSLGA KLEKQQQDLK ADHDALLFHL KHFPVDLRFV ACQMELLHSN GSQRTCCPVN 
WVEHQGSCYW FSHSGKAWAE AEKYCQLENA HLVVINSWEE QKFIVQHTNP FNTWIGLTDS 
DGSWKWVDGT DYRHNYKNWA VTQPDNWHGH ELGGSEDCVE VQPDGRWNDD FCLQVYRWVC 
EKRRNATGEV A

Genular Protein ID: 3136938886

Symbol: Q7Z4G9_HUMAN

Name: N/A

UniProtKB Accession Codes:

Q7Z4G9

Database IDs:

ARBA 3 BioGRID-ORCS 1 CDD 1 CTD 1 ChiTaRS 1 DNASU 1 DisGeNET 1 EMBL 3 Ensembl 2 GO 6 Gene3D 1 GeneTree 1 HGNC 1 InterPro 6 MANE-Select 1 NCBI Taxonomy 1 OrthoDB 1 PANTHER 2 PROSITE 3 PeptideAtlas 1 Pfam 2 Proteomes 2 ProteomicsDB 1 RefSeq 1 SAM 2 SMART 1 SUPFAM 1

Citations:

PubMed ID: 11237011

Title: Initial sequencing and analysis of the human genome.

PubMed ID: 11237011

DOI: 10.1038/35057062

PubMed ID: 15496913

Title: Finishing the euchromatic sequence of the human genome.

PubMed ID: 15496913

DOI: 10.1038/nature03001

PubMed ID: 16625196

Title: DNA sequence of human chromosome 17 and analysis of rearrangement in the human lineage.

PubMed ID: 16625196

DOI: 10.1038/nature04689

Sequence Information:

  • Length: 306
  • Mass: 34655
  • Checksum: F53B06C41AE80D03
  • Sequence:
    • MAKDFQDIQQ LSSEENDHPF HQGEGPGTRR LNPRRGNPFL KGPPPAQPLA QRLCSMVCFS 
LLALSFNILL LVVICVTGSQ SAQLQAELRS LKEAFSNFSS STLTEVQAIS THGGSVGDKI 
TSLGAKLEKQ QQDLKADHDA LLFHLKHFPV DLRFVACQME LLHSNGSQRT CCPVNWVEHQ 
GSCYWFSHSG KAWAEAEKYC QLENAHLVVI NSWEEQKFIV QHTNPFNTWI GLTDSDGSWK 
WVDGTDYRHN YKNWAVTQPD NWHGHELGGS EDCVEVQPDG RWNDDFCLQV YRWVCEKRRN 
ATGEVA