Details for: LRG1

Gene ID: 116844

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: LRG1

Ensembl ID: ENSG00000171236

Description: leucine rich alpha-2-glycoprotein 1

Cell Significance Landscape

Associated with

Significant Cells

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

  • hepatocyte CL0000182
    CSI 14.88
    rCSI 26.64%
    PRS 90.16
  • centrilobular region hepatocyte CL0019029
    CSI 12.92
    rCSI 33.72%
    PRS 87.68
  • goblet cell CL0000160
    CSI 8.98
    rCSI 8.48%
    PRS 89.55
  • epithelial cell of lower respiratory tract CL0002632
    CSI 7.81
    rCSI 6.06%
    PRS 93.61
  • multi-ciliated epithelial cell CL0005012
    CSI 7.21
    rCSI 7.2%
    PRS 86.29
  • colon epithelial cell CL0011108
    CSI 6.83
    rCSI 7.16%
    PRS 89.46
  • epithelial cell CL0000066
    CSI 4.99
    rCSI 7.67%
    PRS 80.41
  • club cell CL0000158
    CSI 4.94
    rCSI 7.24%
    PRS 87.66
  • periportal region hepatocyte CL0019026
    CSI 4.39
    rCSI 17.07%
    PRS 88.53
  • secretory cell CL0000151
    CSI 4.03
    rCSI 4.2%
    PRS 90.61
  • blood vessel endothelial cell CL0000071
    CSI 3.92
    rCSI 8.13%
    PRS 89.99
  • nasal mucosa goblet cell CL0002480
    CSI 3.74
    rCSI 4.34%
    PRS 91.82
  • epithelial cell of lung CL0000082
    CSI 3.44
    rCSI 2.85%
    PRS 92.36
  • pancreatic ductal cell CL0002079
    CSI 3.29
    rCSI 6.4%
    PRS 92.84
  • fallopian tube secretory epithelial cell CL4030006
    CSI 3.22
    rCSI 3.1%
    PRS 90.14
  • neutrophil CL0000775
    CSI 3.16
    rCSI 17.69%
    PRS 89.15
  • ciliated epithelial cell CL0000067
    CSI 3.12
    rCSI 2.75%
    PRS 83.37
  • CD14-positive, CD16-positive monocyte CL0002397
    CSI 2.69
    rCSI 3.53%
    PRS 96.62
  • ciliated cell CL0000064
    CSI 2.6
    rCSI 4.22%
    PRS 86.03
  • promonocyte CL0000559
    CSI 2.59
    rCSI 4.43%
    PRS 93.17
  • acinar cell CL0000622
    CSI 2.49
    rCSI 3.64%
    PRS 95.85
  • duct epithelial cell CL0000068
    CSI 2.36
    rCSI 3.46%
    PRS 94.48
  • foveolar cell of stomach CL0002179
    CSI 2.3
    rCSI 4.89%
    PRS 93.32
  • ciliated columnar cell of tracheobronchial tree CL0002145
    CSI 2.21
    rCSI 5.03%
    PRS 85.02
  • intestine goblet cell CL0019031
    CSI 2.15
    rCSI 1.91%
    PRS 89.26
  • tracheobronchial serous cell CL0019001
    CSI 2.11
    rCSI 9.12%
    PRS 93.4
  • mucous neck cell CL0000651
    CSI 2.03
    rCSI 2.92%
    PRS 93.85
  • vein endothelial cell CL0002543
    CSI 2.03
    rCSI 5.53%
    PRS 93.96
  • basal cell of prostate epithelium CL0002341
    CSI 2
    rCSI 5.78%
    PRS 93.62
  • respiratory basal cell CL0002633
    CSI 1.92
    rCSI 1.99%
    PRS 92.98
  • pancreatic acinar cell CL0002064
    CSI 1.92
    rCSI 2.55%
    PRS 93.98
  • lung ciliated cell CL1000271
    CSI 1.63
    rCSI 1.89%
    PRS 86.5
  • squamous epithelial cell CL0000076
    CSI 1.61
    rCSI 3.83%
    PRS 88.82
  • vein endothelial cell of respiratory system CL4033008
    CSI 1.59
    rCSI 10.93%
    PRS 94.35
  • intermediate monocyte CL0002393
    CSI 1.36
    rCSI 2.05%
    PRS 95.07
  • CD8-positive, alpha-beta memory T cell, CD45RO-positive CL0001203
    CSI 1.06
    rCSI 1.28%
    PRS 73.16
  • bronchial goblet cell CL1000312
    CSI 0.87
    rCSI 3.46%
    PRS 94.2
  • myelocyte CL0002193
    CSI 0.6
    rCSI 3.95%
    PRS 96.3
  • prostate gland microvascular endothelial cell CL2000059
    CSI 0.22
    rCSI 5.21%
    PRS 94.31
  • acinar cell of salivary gland CL0002623
    CSI 0.19
    rCSI 4.54%
    PRS 95.87

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.

Comma-separated if multiple.
Comma-separated if multiple.
Legend:
  • 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 [LRG1](/details-gene/116844) (Leucine Rich Alpha-2-Glycoprotein 1) is a protein-coding gene located on chromosome 19p13.3. It encodes a secreted glycoprotein characterized by a leucine-rich repeat structure. **Overall**, expression data indicates that [LRG1](/details-gene/116844) is most significantly expressed in [hepatocytes](/details-cell/CL0000182) and various types of secretory and mucosal [epithelial cells](/details-cell/CL0000066), such as [goblet cells](/details-cell/CL0000160). Functionally, [LRG1](/details-gene/116844) is implicated in the positive regulation of angiogenesis, wound healing, and epithelial cell proliferation. These functions appear to be mediated through its interaction with the transforming growth factor beta (TGF-beta) receptor signaling pathway, positioning it as a key modulator of cellular growth, differentiation, and tissue repair processes. ## Cellular Roles and Expression Landscape The expression profile of [LRG1](/details-gene/116844) highlights its predominant role in hepatic and epithelial tissues. **Overall**, the gene shows the highest significance in [hepatocytes](/details-cell/CL0000182), including both [centrilobular region hepatocytes](/details-cell/CL0019029) and [periportal region hepatocytes](/details-cell/CL0019026), establishing the liver as a primary site of its production and a likely major contributor to its circulating levels in plasma. Beyond the liver, [LRG1](/details-gene/116844) is a significant marker for a range of secretory and barrier-forming [epithelial cells](/details-cell/CL0000066). It is highly expressed in [goblet cells](/details-cell/CL0000160) of the [colon](/details-cell/CL0011108) and [nasal mucosa](/details-cell/CL0002480), as well as in [multi-ciliated epithelial cells](/details-cell/CL0005012), [club cells](/details-cell/CL0000158), and other [epithelial cells of the lower respiratory tract](/details-cell/CL0002632). This pattern suggests a crucial role in mucosal biology, potentially involving secretion, barrier maintenance, and response to environmental stimuli. The gene is also significantly expressed in [blood vessel endothelial cells](/details-cell/CL0000071), which is consistent with its established function in angiogenesis. While early studies characterized it as a marker of granulocytic differentiation ([Link](https://pubmed.ncbi.nlm.nih.gov/12223515)), and it is annotated to [neutrophil degranulation](/details-pathway/R-HSA-6798695), mature granulocytes do not appear as top expressers in this broad context, suggesting its role in hematopoiesis may be differentiation-stage specific or more nuanced than its role in epithelial and endothelial biology. ## Pathways and Molecular Function [LRG1](/details-gene/116844) is fundamentally involved in modulating cell growth and tissue remodeling, primarily through the TGF-beta signaling pathway. Its molecular function is defined by its ability to bind to type I ([GO:0034713](https://www.ebi.ac.uk/QuickGO/term/GO:0034713)) and type II ([GO:0005114](https://www.ebi.ac.uk/QuickGO/term/GO:0005114)) TGF-beta receptors, thereby positively regulating this pathway ([GO:0030511](https://www.ebi.ac.uk/QuickGO/term/GO:0030511)). This regulatory activity translates into several key biological processes. The high expression of [LRG1](/details-gene/116844) in [epithelial cells](/details-cell/CL0000066) and its role in tissue repair are supported by its involvement in the positive regulation of epithelial cell proliferation during wound healing ([GO:0060054](https://www.ebi.ac.uk/QuickGO/term/GO:0060054)) and keratinocyte migration ([GO:0051546](https://www.ebi.ac.uk/QuickGO/term/GO:0051546)). Its significance in [blood vessel endothelial cells](/details-cell/CL0000071) directly correlates with its well-documented role in promoting angiogenesis ([GO:0045766](https://www.ebi.ac.uk/QuickGO/term/GO:0045766)) and endothelial cell proliferation ([GO:0001938](https://www.ebi.ac.uk/QuickGO/term/GO:0001938)). As a secreted protein found in the extracellular space ([GO:0005615](https://www.ebi.ac.uk/QuickGO/term/GO:0005615)) and exosomes ([GO:0070062](https://www.ebi.ac.uk/QuickGO/term/GO:0070062)), [LRG1](/details-gene/116844) can act systemically or locally to influence these processes. Furthermore, its annotation to the [Innate immune system](/details-pathway/R-HSA-168249) and specifically [Neutrophil degranulation](/details-pathway/R-HSA-6798695), along with its localization to specific and tertiary granule lumens ([GO:0035580](https://www.ebi.ac.uk/QuickGO/term/GO:0035580), [GO:1904724](https://www.ebi.ac.uk/QuickGO/term/GO:1904724)), indicates a role in the inflammatory response, likely mediating crosstalk between epithelial, endothelial, and immune cells during injury or infection. ## Research Directions The data positions [LRG1](/details-gene/116844) as a secreted signaling molecule with a dual role in both homeostatic tissue maintenance and pathological processes like aberrant angiogenesis. Its high expression in the liver suggests it may be a systemic factor, while its expression at mucosal surfaces points to a local regulatory function. ### Proposed Hypotheses 1. **Systemic Angiogenic Regulator:** Given its extremely high expression in [hepatocytes](/details-cell/CL0000182) and its function in promoting angiogenesis, liver-derived [LRG1](/details-gene/116844) may function as a major endocrine factor that regulates systemic vascular health and repair. Under conditions of liver damage or metabolic stress, altered secretion of [LRG1](/details-gene/116844) could contribute to the vascular complications associated with liver disease. 2. **Mucosal Barrier Modulator:** In mucosal tissues like the gut and airways, [LRG1](/details-gene/116844) secreted by [goblet cells](/details-cell/CL0000160) and other [epithelial cells](/details-cell/CL0000066) may act locally as a critical first responder to injury or infection. By modulating TGF-beta signaling, it could orchestrate epithelial restitution, regulate local inflammation, and control leukocyte adhesion to the vascular endothelium ([GO:0061756](https://www.ebi.ac.uk/QuickGO/term/GO:0061756)). ### Key Experimental Approach To test the hypothesis that liver-derived [LRG1](/details-gene/116844) acts as a systemic regulator of angiogenesis (Hypothesis 1), a liver-specific knockout mouse model could be generated (e.g., *Lrg1fl/fl* x *Alb-Cre*). The impact of depleting the major circulating pool of [LRG1](/details-gene/116844) could be assessed in a model of pathological neovascularization, such as oxygen-induced retinopathy or tumor xenografts. Endpoints would include quantifying vessel density, branching, and leakage via immunohistochemistry and functional imaging. Conversely, a liver-specific overexpression model could be used to determine if elevated systemic [LRG1](/details-gene/116844) is sufficient to drive pathological angiogenesis in otherwise healthy tissues. ### Therapeutic Potential As a secreted protein that promotes angiogenesis and modulates TGF-beta signaling, [LRG1](/details-gene/116844) is a compelling therapeutic target, particularly in oncology and fibrotic diseases. Its pro-angiogenic role suggests that **inhibition** would be the therapeutic strategy. A monoclonal antibody designed to neutralize circulating [LRG1](/details-gene/116844) or a small molecule inhibitor blocking its interaction with TGF-beta co-receptors like endoglin could represent viable approaches. Such therapies could potentially limit tumor growth by starving them of their blood supply or reduce tissue fibrosis by dampening pro-fibrotic TGF-beta signaling. Because [LRG1](/details-gene/116844) is also involved in physiological wound healing, potential on-target side effects related to impaired tissue repair would need to be carefully evaluated.

Genular Protein ID: 1974648308

Symbol: A2GL_HUMAN

Name: Leucine-rich alpha-2-glycoprotein

UniProtKB Accession Codes:

P02750 Q8N4F5 Q96QZ4

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 Bgee 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 1 CPTAC 2 CTD 1 ChiTaRS 1 DIP 1 DMDM 1 DNASU 1 DisGeNET 1 DrugBank 1 EMBL 3 Ensembl 1 GO 21 Gene3D 1 GeneCards 1 GeneTree 1 GeneWiki 1 GenomeRNAi 1 GlyConnect 1 GlyCosmos 1 GlyGen 1 HGNC 1 HOGENOM 1 HPA 1 InParanoid 1 IntAct 1 InterPro 4 KEGG 1 MANE-Select 1 MIM 1 MassIVE 1 NCBI Taxonomy 1 OMA 1 OpenTargets 1 OrthoDB 1 PANTHER 2 PDB 2 PDBsum 2 PIR 1 PRINTS 1 PRO 1 PROSITE 1 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 Pfam 2 PharmGKB 1 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 ProteomicsDB 1 RNAct 1 Reactome 1 RefSeq 1 SMART 2 SMR 1 STRING 1 SUPFAM 1 SignaLink 1 TreeFam 1 UCSC 1 VEuPathDB 1 eggNOG 1 iPTMnet 1 jPOST 1 neXtProt 1

Citations:

PubMed ID: 12223515

Title: Molecular characterization and expression analysis of leucine-rich alpha2-glycoprotein, a novel marker of granulocytic differentiation.

PubMed ID: 12223515

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: 3856868

Title: Periodicity of leucine and tandem repetition of a 24-amino acid segment in the primary structure of leucine-rich alpha 2-glycoprotein of human serum.

PubMed ID: 3856868

DOI: 10.1073/pnas.82.7.1906

PubMed ID: 14760718

Title: Screening for N-glycosylated proteins by liquid chromatography mass spectrometry.

PubMed ID: 14760718

DOI: 10.1002/pmic.200300556

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: 16740002

Title: Identification of N-linked glycoproteins in human saliva by glycoprotein capture and mass spectrometry.

PubMed ID: 16740002

DOI: 10.1021/pr050492k

PubMed ID: 18780401

Title: Identification of N-linked glycoproteins in human milk by hydrophilic interaction liquid chromatography and mass spectrometry.

PubMed ID: 18780401

DOI: 10.1002/pmic.200701057

PubMed ID: 19139490

Title: A strategy for precise and large scale identification of core fucosylated glycoproteins.

PubMed ID: 19139490

DOI: 10.1074/mcp.m800504-mcp200

PubMed ID: 19838169

Title: Enrichment of glycopeptides for glycan structure and attachment site identification.

PubMed ID: 19838169

DOI: 10.1038/nmeth.1392

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

Sequence Information:

  • Length: 347
  • Mass: 38178
  • Checksum: 20C99ED50152FA9C
  • Sequence:
    • MSSWSRQRPK SPGGIQPHVS RTLFLLLLLA ASAWGVTLSP KDCQVFRSDH GSSISCQPPA 
EIPGYLPADT VHLAVEFFNL THLPANLLQG ASKLQELHLS SNGLESLSPE FLRPVPQLRV 
LDLTRNALTG LPPGLFQASA TLDTLVLKEN QLEVLEVSWL HGLKALGHLD LSGNRLRKLP 
PGLLANFTLL RTLDLGENQL ETLPPDLLRG PLQLERLHLE GNKLQVLGKD LLLPQPDLRY 
LFLNGNKLAR VAAGAFQGLR QLDMLDLSNN SLASVPEGLW ASLGQPNWDM RDGFDISGNP 
WICDQNLSDL YRWLQAQKDK MFSQNDTRCA GPEAVKGQTL LAVAKSQ

Genular Protein ID: 2299748994

Symbol: Q68CK4_HUMAN

Name: N/A

UniProtKB Accession Codes:

Q68CK4

Database IDs:

ARBA 3 AlphaFoldDB 1 BioGRID-ORCS 1 CTD 1 ChiTaRS 1 DNASU 1 DisGeNET 1 EMBL 8 GO 1 Gene3D 1 InterPro 4 KEGG 1 NCBI Taxonomy 1 OrthoDB 1 PANTHER 2 PRINTS 1 PROSITE 1 PeptideAtlas 1 Pfam 2 PharmGKB 1 RefSeq 1 SAM 1 SMART 3 SUPFAM 1

Citations:

PubMed ID: 11181995

Title: The sequence of the human genome.

PubMed ID: 11181995

DOI: 10.1126/science.1058040

PubMed ID: 15221005

Title: Expression profiling and differential screening between hepatoblastomas and the corresponding normal livers: identification of high expression of the PLK1 oncogene as a poor-prognostic indicator of hepatoblastomas.

PubMed ID: 15221005

DOI: 10.1038/sj.onc.1207782

Sequence Information:

  • Length: 347
  • Mass: 38168
  • Checksum: 9DE57EE4FDB2CBF0
  • Sequence:
    • MSSWSRQRPK SPGGIQPHVS RTLFLLLLLA ASAWGVTLSP KDCQVFRSDH GSSISCQPPA 
EIPGYLPADT VHLAVEFFNL THLPANLLQG ASKLQELHLS SNGLESLSPE FLRPVPQLRV 
LDLTRNALTG LPSGLFQASA TLDTLVLKEN QLEVLEVSWL HGLKALGHLD LSGNRLRKLP 
PGLLANFTLL RTLDLGENQL ETLPPDLLRG PLQLERLHLE GNKLQVLGKD LLLPQPDLRY 
LFLNGNKLAR VAAGAFQGLR QLDMLDLSNN SLASVPEGLW ASLGQPNWDM RDGFDISGNP 
WICDQNLSDL YRWLQAQKDK MFSQNDTRCA GPEAVKGQTL LAVAKSQ