HGNC Family | Immunoglobulin superfamily domain containing, CD molecules (CD) |
Name | lymphocyte-activation gene 3 |
Description | Lymphocyte-activation protein 3 belongs to Ig superfamily and contains 4 extracellular Ig-like domains. The LAG3 gene contains 8 exons. The sequence data, exon/intron organization, and chromosomal localization all indicate a close relationship of LAG3 to CD4. [provided by RefSeq, Jul 2008] |
Summary |
{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nLymphocyte‐activation gene‐3 (LAG3) is a critical immune checkpoint receptor widely expressed on activated T cells and natural killer cells that plays a central role in dampening immune responses within the tumor microenvironment. Multiple studies in cancer settings—including ovarian cancer, non–small cell lung cancer, melanoma, Hodgkin lymphoma, and other malignancies—have demonstrated that LAG3 is frequently co‐expressed with other inhibitory receptors such as PD‐1 on tumor‐infiltrating lymphocytes. This coexpression is associated with T cell exhaustion, impaired cytokine production, reduced proliferative capacity, and the enrichment of regulatory T cell subsets, all of which contribute to tumor immune evasion. In addition, LAG3 engagement via its natural ligands (for example, stable peptide–MHC class II complexes) or through soluble forms modulates antigen presentation by dendritic cells and even can directly protect tumor cells from apoptosis. Together, these findings not only reinforce the negative regulatory function of LAG3 but also underscore its prognostic significance in several cancers and its potential as a therapeutic target, as demonstrated by dual blockade strategies that enhance antitumor immunity."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "24"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond oncology, LAG3 has been implicated in the context of neurodegenerative and infectious diseases as well as autoimmune disorders. In early studies of Parkinson’s disease, LAG3 was reported to bind α‐synuclein fibrils and mediate their endocytosis, a process initially proposed to contribute to the spread of pathology; however, subsequent investigations have raised questions regarding its neuronal expression and direct involvement in neurodegeneration. In chronic viral infections such as HIV and hepatitis B, the upregulation of LAG3 is associated with T cell dysfunction and impaired pathogen‐specific immune responses. In parallel, genetic studies linking LAG3 variants to an increased risk of multiple sclerosis and type 1 diabetes highlight its broader role in maintaining immune tolerance and homeostasis."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "25", "end_ref": "31"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nAt the molecular level, LAG3 exhibits a unique signaling mode compared with other co‐inhibitory receptors. It preferentially binds stable peptide–MHC class II complexes without overtly competing with the CD4 co‐receptor, and its intracellular domain transmits inhibitory signals that curtail T cell activation. The regulation of LAG3 surface expression involves intricate trafficking from lysosomal compartments to the plasma membrane—a process governed by protein kinase C signaling and specific cytoplasmic motifs. Moreover, engagement of LAG3 on antigen-presenting cells, such as dendritic cells, can trigger rapid maturation and the upregulation of costimulatory molecules, thereby influencing the balance between activation and tolerance."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "32", "end_ref": "34"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nThese mechanistic insights have spurred the development of innovative therapeutic approaches targeting the LAG3 pathway. Clinical strategies now include the use of LAG3‐blocking antibodies—often in combination with PD‐1 inhibitors—to reinvigorate T cell responses in cancers such as renal cell carcinoma, breast cancer, and multiple myeloma. Furthermore, soluble LAG3 fusion proteins are under evaluation as novel immunostimulatory agents, while alterations in LAG3 processing (for example, noncleavable mutants) have been implicated in resistance to checkpoint blockade therapies. Epigenetic regulation of LAG3 expression, along with its emerging role as a predictive biomarker, supports its incorporation into next‐generation immuno‐oncology regimens and highlights its potential in overcoming tumor-induced immune tolerance."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "35", "end_ref": "39"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Junko Matsuzaki, Sacha Gnjatic, Paulette Mhawech-Fauceglia, et al. 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Synonyms | CD223 |
Proteins | LAG3_HUMAN |
NCBI Gene ID | 3902 |
API | |
Download Associations | |
Predicted Functions |
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Co-expressed Genes |
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Expression in Tissues and Cell Lines |
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LAG3 has 5,849 functional associations with biological entities spanning 8 categories (molecular profile, organism, chemical, functional term, phrase or reference, disease, phenotype or trait, structural feature, cell line, cell type or tissue, gene, protein or microRNA) extracted from 98 datasets.
Click the + buttons to view associations for LAG3 from the datasets below.
If available, associations are ranked by standardized value
Dataset | Summary | |
---|---|---|
Allen Brain Atlas Adult Human Brain Tissue Gene Expression Profiles | tissues with high or low expression of LAG3 gene relative to other tissues from the Allen Brain Atlas Adult Human Brain Tissue Gene Expression Profiles dataset. | |
Allen Brain Atlas Adult Mouse Brain Tissue Gene Expression Profiles | tissues with high or low expression of LAG3 gene relative to other tissues from the Allen Brain Atlas Adult Mouse Brain Tissue Gene Expression Profiles dataset. | |
Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by Microarray | tissue samples with high or low expression of LAG3 gene relative to other tissue samples from the Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by Microarray dataset. | |
Allen Brain Atlas Prenatal Human Brain Tissue Gene Expression Profiles | tissues with high or low expression of LAG3 gene relative to other tissues from the Allen Brain Atlas Prenatal Human Brain Tissue Gene Expression Profiles dataset. | |
BioGPS Cell Line Gene Expression Profiles | cell lines with high or low expression of LAG3 gene relative to other cell lines from the BioGPS Cell Line Gene Expression Profiles dataset. | |
BioGPS Human Cell Type and Tissue Gene Expression Profiles | cell types and tissues with high or low expression of LAG3 gene relative to other cell types and tissues from the BioGPS Human Cell Type and Tissue Gene Expression Profiles dataset. | |
BioGPS Mouse Cell Type and Tissue Gene Expression Profiles | cell types and tissues with high or low expression of LAG3 gene relative to other cell types and tissues from the BioGPS Mouse Cell Type and Tissue Gene Expression Profiles dataset. | |
CCLE Cell Line Gene CNV Profiles | cell lines with high or low copy number of LAG3 gene relative to other cell lines from the CCLE Cell Line Gene CNV Profiles dataset. | |
CCLE Cell Line Gene Expression Profiles | cell lines with high or low expression of LAG3 gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset. | |
CellMarker Gene-Cell Type Associations | cell types associated with LAG3 gene from the CellMarker Gene-Cell Type Associations dataset. | |
ChEA Transcription Factor Binding Site Profiles | transcription factor binding site profiles with transcription factor binding evidence at the promoter of LAG3 gene from the CHEA Transcription Factor Binding Site Profiles dataset. | |
ChEA Transcription Factor Targets | transcription factors binding the promoter of LAG3 gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets dataset. | |
ChEA Transcription Factor Targets 2022 | transcription factors binding the promoter of LAG3 gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets 2022 dataset. | |
CMAP Signatures of Differentially Expressed Genes for Small Molecules | small molecule perturbations changing expression of LAG3 gene from the CMAP Signatures of Differentially Expressed Genes for Small Molecules dataset. | |
COMPARTMENTS Curated Protein Localization Evidence Scores | cellular components containing LAG3 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset. | |
COMPARTMENTS Curated Protein Localization Evidence Scores 2025 | cellular components containing LAG3 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores 2025 dataset. | |
COMPARTMENTS Text-mining Protein Localization Evidence Scores | cellular components co-occuring with LAG3 protein in abstracts of biomedical publications from the COMPARTMENTS Text-mining Protein Localization Evidence Scores dataset. | |
COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025 | cellular components co-occuring with LAG3 protein in abstracts of biomedical publications from the COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025 dataset. | |
COSMIC Cell Line Gene CNV Profiles | cell lines with high or low copy number of LAG3 gene relative to other cell lines from the COSMIC Cell Line Gene CNV Profiles dataset. | |
COSMIC Cell Line Gene Mutation Profiles | cell lines with LAG3 gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset. | |
CTD Gene-Disease Associations | diseases associated with LAG3 gene/protein from the curated CTD Gene-Disease Associations dataset. | |
dbGAP Gene-Trait Associations | traits associated with LAG3 gene in GWAS and other genetic association datasets from the dbGAP Gene-Trait Associations dataset. | |
DepMap CRISPR Gene Dependency | cell lines with fitness changed by LAG3 gene knockdown relative to other cell lines from the DepMap CRISPR Gene Dependency dataset. | |
DISEASES Experimental Gene-Disease Association Evidence Scores 2025 | diseases associated with LAG3 gene in GWAS datasets from the DISEASES Experimental Gene-Disease Assocation Evidence Scores 2025 dataset. | |
DISEASES Text-mining Gene-Disease Association Evidence Scores | diseases co-occuring with LAG3 gene in abstracts of biomedical publications from the DISEASES Text-mining Gene-Disease Assocation Evidence Scores dataset. | |
DISEASES Text-mining Gene-Disease Association Evidence Scores 2025 | diseases co-occuring with LAG3 gene in abstracts of biomedical publications from the DISEASES Text-mining Gene-Disease Assocation Evidence Scores 2025 dataset. | |
DisGeNET Gene-Disease Associations | diseases associated with LAG3 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset. | |
DisGeNET Gene-Phenotype Associations | phenotypes associated with LAG3 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Phenoptype Associations dataset. | |
ENCODE Histone Modification Site Profiles | histone modification site profiles with high histone modification abundance at LAG3 gene from the ENCODE Histone Modification Site Profiles dataset. | |
ENCODE Transcription Factor Binding Site Profiles | transcription factor binding site profiles with transcription factor binding evidence at the promoter of LAG3 gene from the ENCODE Transcription Factor Binding Site Profiles dataset. | |
ENCODE Transcription Factor Targets | transcription factors binding the promoter of LAG3 gene in ChIP-seq datasets from the ENCODE Transcription Factor Targets dataset. | |
ESCAPE Omics Signatures of Genes and Proteins for Stem Cells | PubMedIDs of publications reporting gene signatures containing LAG3 from the ESCAPE Omics Signatures of Genes and Proteins for Stem Cells dataset. | |
GAD Gene-Disease Associations | diseases associated with LAG3 gene in GWAS and other genetic association datasets from the GAD Gene-Disease Associations dataset. | |
GAD High Level Gene-Disease Associations | diseases associated with LAG3 gene in GWAS and other genetic association datasets from the GAD High Level Gene-Disease Associations dataset. | |
GDSC Cell Line Gene Expression Profiles | cell lines with high or low expression of LAG3 gene relative to other cell lines from the GDSC Cell Line Gene Expression Profiles dataset. | |
GeneRIF Biological Term Annotations | biological terms co-occuring with LAG3 gene in literature-supported statements describing functions of genes from the GeneRIF Biological Term Annotations dataset. | |
GeneSigDB Published Gene Signatures | PubMedIDs of publications reporting gene signatures containing LAG3 from the GeneSigDB Published Gene Signatures dataset. | |
GEO Signatures of Differentially Expressed Genes for Diseases | disease perturbations changing expression of LAG3 gene from the GEO Signatures of Differentially Expressed Genes for Diseases dataset. | |
GEO Signatures of Differentially Expressed Genes for Gene Perturbations | gene perturbations changing expression of LAG3 gene from the GEO Signatures of Differentially Expressed Genes for Gene Perturbations dataset. | |
GEO Signatures of Differentially Expressed Genes for Kinase Perturbations | kinase perturbations changing expression of LAG3 gene from the GEO Signatures of Differentially Expressed Genes for Kinase Perturbations dataset. | |
GEO Signatures of Differentially Expressed Genes for Small Molecules | small molecule perturbations changing expression of LAG3 gene from the GEO Signatures of Differentially Expressed Genes for Small Molecules dataset. | |
GEO Signatures of Differentially Expressed Genes for Transcription Factor Perturbations | transcription factor perturbations changing expression of LAG3 gene from the GEO Signatures of Differentially Expressed Genes for Transcription Factor Perturbations dataset. | |
GEO Signatures of Differentially Expressed Genes for Viral Infections | virus perturbations changing expression of LAG3 gene from the GEO Signatures of Differentially Expressed Genes for Viral Infections dataset. | |
GO Biological Process Annotations 2015 | biological processes involving LAG3 gene from the curated GO Biological Process Annotations 2015 dataset. | |
GO Biological Process Annotations 2023 | biological processes involving LAG3 gene from the curated GO Biological Process Annotations 2023 dataset. | |
GO Biological Process Annotations 2025 | biological processes involving LAG3 gene from the curated GO Biological Process Annotations2025 dataset. | |
GO Cellular Component Annotations 2015 | cellular components containing LAG3 protein from the curated GO Cellular Component Annotations 2015 dataset. | |
GO Molecular Function Annotations 2015 | molecular functions performed by LAG3 gene from the curated GO Molecular Function Annotations 2015 dataset. | |
GO Molecular Function Annotations 2023 | molecular functions performed by LAG3 gene from the curated GO Molecular Function Annotations 2023 dataset. | |
GO Molecular Function Annotations 2025 | molecular functions performed by LAG3 gene from the curated GO Molecular Function Annotations 2025 dataset. | |
GTEx Tissue Gene Expression Profiles | tissues with high or low expression of LAG3 gene relative to other tissues from the GTEx Tissue Gene Expression Profiles dataset. | |
GTEx Tissue Gene Expression Profiles 2023 | tissues with high or low expression of LAG3 gene relative to other tissues from the GTEx Tissue Gene Expression Profiles 2023 dataset. | |
GTEx Tissue Sample Gene Expression Profiles | tissue samples with high or low expression of LAG3 gene relative to other tissue samples from the GTEx Tissue Sample Gene Expression Profiles dataset. | |
GTEx Tissue-Specific Aging Signatures | tissue samples with high or low expression of LAG3 gene relative to other tissue samples from the GTEx Tissue-Specific Aging Signatures dataset. | |
Heiser et al., PNAS, 2011 Cell Line Gene Expression Profiles | cell lines with high or low expression of LAG3 gene relative to other cell lines from the Heiser et al., PNAS, 2011 Cell Line Gene Expression Profiles dataset. | |
HPA Cell Line Gene Expression Profiles | cell lines with high or low expression of LAG3 gene relative to other cell lines from the HPA Cell Line Gene Expression Profiles dataset. | |
HPA Tissue Gene Expression Profiles | tissues with high or low expression of LAG3 gene relative to other tissues from the HPA Tissue Gene Expression Profiles dataset. | |
HPA Tissue Protein Expression Profiles | tissues with high or low expression of LAG3 protein relative to other tissues from the HPA Tissue Protein Expression Profiles dataset. | |
HPA Tissue Sample Gene Expression Profiles | tissue samples with high or low expression of LAG3 gene relative to other tissue samples from the HPA Tissue Sample Gene Expression Profiles dataset. | |
HuBMAP Azimuth Cell Type Annotations | cell types associated with LAG3 gene from the HuBMAP Azimuth Cell Type Annotations dataset. | |
HuGE Navigator Gene-Phenotype Associations | phenotypes associated with LAG3 gene by text-mining GWAS publications from the HuGE Navigator Gene-Phenotype Associations dataset. | |
InterPro Predicted Protein Domain Annotations | protein domains predicted for LAG3 protein from the InterPro Predicted Protein Domain Annotations dataset. | |
JASPAR Predicted Transcription Factor Targets | transcription factors regulating expression of LAG3 gene predicted using known transcription factor binding site motifs from the JASPAR Predicted Transcription Factor Targets dataset. | |
Kinase Library Serine Threonine Kinome Atlas | kinases that phosphorylate LAG3 protein from the Kinase Library Serine Threonine Atlas dataset. | |
Klijn et al., Nat. Biotechnol., 2015 Cell Line Gene CNV Profiles | cell lines with high or low copy number of LAG3 gene relative to other cell lines from the Klijn et al., Nat. Biotechnol., 2015 Cell Line Gene CNV Profiles dataset. | |
Klijn et al., Nat. Biotechnol., 2015 Cell Line Gene Expression Profiles | cell lines with high or low expression of LAG3 gene relative to other cell lines from the Klijn et al., Nat. Biotechnol., 2015 Cell Line Gene Expression Profiles dataset. | |
Klijn et al., Nat. Biotechnol., 2015 Cell Line Gene Mutation Profiles | cell lines with LAG3 gene mutations from the Klijn et al., Nat. Biotechnol., 2015 Cell Line Gene Mutation Profiles dataset. | |
KnockTF Gene Expression Profiles with Transcription Factor Perturbations | transcription factor perturbations changing expression of LAG3 gene from the KnockTF Gene Expression Profiles with Transcription Factor Perturbations dataset. | |
LINCS L1000 CMAP Chemical Perturbation Consensus Signatures | small molecule perturbations changing expression of LAG3 gene from the LINCS L1000 CMAP Chemical Perturbations Consensus Signatures dataset. | |
LINCS L1000 CMAP CRISPR Knockout Consensus Signatures | gene perturbations changing expression of LAG3 gene from the LINCS L1000 CMAP CRISPR Knockout Consensus Signatures dataset. | |
LOCATE Curated Protein Localization Annotations | cellular components containing LAG3 protein in low- or high-throughput protein localization assays from the LOCATE Curated Protein Localization Annotations dataset. | |
LOCATE Predicted Protein Localization Annotations | cellular components predicted to contain LAG3 protein from the LOCATE Predicted Protein Localization Annotations dataset. | |
MGI Mouse Phenotype Associations 2023 | phenotypes of transgenic mice caused by LAG3 gene mutations from the MGI Mouse Phenotype Associations 2023 dataset. | |
MotifMap Predicted Transcription Factor Targets | transcription factors regulating expression of LAG3 gene predicted using known transcription factor binding site motifs from the MotifMap Predicted Transcription Factor Targets dataset. | |
MPO Gene-Phenotype Associations | phenotypes of transgenic mice caused by LAG3 gene mutations from the MPO Gene-Phenotype Associations dataset. | |
MSigDB Signatures of Differentially Expressed Genes for Cancer Gene Perturbations | gene perturbations changing expression of LAG3 gene from the MSigDB Signatures of Differentially Expressed Genes for Cancer Gene Perturbations dataset. | |
NIBR DRUG-seq U2OS MoA Box Gene Expression Profiles | drug perturbations changing expression of LAG3 gene from the NIBR DRUG-seq U2OS MoA Box dataset. | |
Pathway Commons Protein-Protein Interactions | interacting proteins for LAG3 from the Pathway Commons Protein-Protein Interactions dataset. | |
PerturbAtlas Signatures of Differentially Expressed Genes for Gene Perturbations | gene perturbations changing expression of LAG3 gene from the PerturbAtlas Signatures of Differentially Expressed Genes for Gene Perturbations dataset. | |
PerturbAtlas Signatures of Differentially Expressed Genes for Mouse Gene Perturbations | gene perturbations changing expression of LAG3 gene from the PerturbAtlas Signatures of Differentially Expressed Genes for Gene Perturbations dataset. | |
PFOCR Pathway Figure Associations 2023 | pathways involving LAG3 protein from the PFOCR Pathway Figure Associations 2023 dataset. | |
PFOCR Pathway Figure Associations 2024 | pathways involving LAG3 protein from the Wikipathways PFOCR 2024 dataset. | |
Reactome Pathways 2024 | pathways involving LAG3 protein from the Reactome Pathways 2024 dataset. | |
Roadmap Epigenomics Cell and Tissue DNA Methylation Profiles | cell types and tissues with high or low DNA methylation of LAG3 gene relative to other cell types and tissues from the Roadmap Epigenomics Cell and Tissue DNA Methylation Profiles dataset. | |
Roadmap Epigenomics Cell and Tissue Gene Expression Profiles | cell types and tissues with high or low expression of LAG3 gene relative to other cell types and tissues from the Roadmap Epigenomics Cell and Tissue Gene Expression Profiles dataset. | |
Roadmap Epigenomics Histone Modification Site Profiles | histone modification site profiles with high histone modification abundance at LAG3 gene from the Roadmap Epigenomics Histone Modification Site Profiles dataset. | |
RummaGEO Drug Perturbation Signatures | drug perturbations changing expression of LAG3 gene from the RummaGEO Drug Perturbation Signatures dataset. | |
RummaGEO Gene Perturbation Signatures | gene perturbations changing expression of LAG3 gene from the RummaGEO Gene Perturbation Signatures dataset. | |
Tabula Sapiens Gene-Cell Associations | cell types with high or low expression of LAG3 gene relative to other cell types from the Tabula Sapiens Gene-Cell Associations dataset. | |
TargetScan Predicted Conserved microRNA Targets | microRNAs regulating expression of LAG3 gene predicted using conserved miRNA seed sequences from the TargetScan Predicted Conserved microRNA Targets dataset. | |
TargetScan Predicted Nonconserved microRNA Targets | microRNAs regulating expression of LAG3 gene predicted using nonconserved miRNA seed sequences from the TargetScan Predicted Nonconserved microRNA Targets dataset. | |
TCGA Signatures of Differentially Expressed Genes for Tumors | tissue samples with high or low expression of LAG3 gene relative to other tissue samples from the TCGA Signatures of Differentially Expressed Genes for Tumors dataset. | |
TISSUES Curated Tissue Protein Expression Evidence Scores | tissues with high expression of LAG3 protein from the TISSUES Curated Tissue Protein Expression Evidence Scores dataset. | |
TISSUES Curated Tissue Protein Expression Evidence Scores 2025 | tissues with high expression of LAG3 protein from the TISSUES Curated Tissue Protein Expression Evidence Scores 2025 dataset. | |
TISSUES Experimental Tissue Protein Expression Evidence Scores 2025 | tissues with high expression of LAG3 protein in proteomics datasets from the TISSUES Experimental Tissue Protein Expression Evidence Scores 2025 dataset. | |
TISSUES Text-mining Tissue Protein Expression Evidence Scores | tissues co-occuring with LAG3 protein in abstracts of biomedical publications from the TISSUES Text-mining Tissue Protein Expression Evidence Scores dataset. | |
TISSUES Text-mining Tissue Protein Expression Evidence Scores 2025 | tissues co-occuring with LAG3 protein in abstracts of biomedical publications from the TISSUES Text-mining Tissue Protein Expression Evidence Scores 2025 dataset. | |
WikiPathways Pathways 2024 | pathways involving LAG3 protein from the WikiPathways Pathways 2024 dataset. | |