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FLASH GENE
Symbol LAG3 contributors: mct - updated : 26-03-2024
HGNC name lymphocyte-activation gene 3
HGNC id 6476
Location 12p13.31      Physical location : 6.881.669 - 6.887.619
Synonym name
  • protein FDC
  • CD223 antigen
  • Synonym symbol(s) CD223, FDC, LAG-3
    DNA
    TYPE functioning gene
    STRUCTURE 5.95 kb     8 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    text structure three transcriptional initiation sites
    MAPPING cloned Y linked   status confirmed
    regionally located close to CD4
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    8 - 1995 - 525 - 1997 9159144
    8 - 2062 - 514 - 1997 9159144
    7 - 1733 - 444 - 1997 9159144
    EXPRESSION
    Type restricted
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Digestiveintestinesmall intestine   
    Lymphoid/Immunespleen    
    Reproductivefemale systemuterus   
    Respiratoryrespiratory tracttrachea   
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Lymphoid    
    cells
    SystemCellPubmedSpeciesStageRna symbol
    Lymphoid/ImmuneB cell Homo sapiens
    Lymphoid/Immunedendritic cell
    Lymphoid/Immunelymphocyte
    Lymphoid/Immunenatural killer Homo sapiens
    Lymphoid/ImmuneT cell Homo sapiens
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • four extracellular Ig-like domains
  • three ig-like C2-type (immunoglobulin-like) domains
  • a Ig-like V-type (immunoglobulin-like) domain
  • HOMOLOGY
    intraspecies homolog to CD4,highly
    Homologene
    FAMILY
  • immunoglobulin superfamily
  • CATEGORY immunity/defense , signaling cytokine
    SUBCELLULAR LOCALIZATION extracellular
        plasma membrane
    basic FUNCTION
  • potentially involved in the regulation of immune response
  • involved in lymphocyte activation
  • important inhibitory molecules frequently expressed by ovarian tumor-infiltrating lymphocytes (Matsuzaki 2010)
  • negatively regulates the expansion of activated T cells and T cell homeostasis, and is required for maximal regulatory T cell function (Workman 2009)
  • may be playing an important but selective cell intrinsic and cell extrinsic role in plasmacytoid dendritic cells biology (Workman 2009)
  • key marker for the identification of exhausted T cells, it may be useful also in resolving Treg subpopulations by indicating distinct functional breadths
  • is required for optimal T cell regulation and homeostasis
  • important role of LAG3 in maintaining immune tolerance
  • LAG3 negatively regulates cellular proliferation, activation, and homeostasis of T cells
  • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS development , immunity/defense
    text maturation and activation of dentritic cells
    PATHWAY
    metabolism
    signaling
    a component
    INTERACTION
    DNA
    RNA
    small molecule
    protein
  • LAG3 trafficking from lysosomal compartments to the cell surface is dependent on the cytoplasmic domain through protein kinase C signaling in activated T cells
  • major histocompatibility complex (MHC) class 2 ligand
  • FGL1 is a newly emerging checkpoint ligand of lymphocyte activation gene 3 (LAG3)
  • is recognized as an inhibitory regulator of Tregs
  • FGL1 cross-linking induces the formation of higher-order LAG3 oligomers
  • cell & other
    REGULATION
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral     --over  
    in chronic lymphocytic leukemia cells, associated with unmutated immunoglobulin variable heavy chain region (IGHV) gene and reduced treatment-free survival (Kotaskova 2010)
    constitutional        
    undetectable in preterm neonates while resulting at a level of 176.1±112.6ng/ml in term neonates, and Th-cell polarization could also depend on gestational age
    Susceptibility to multiple sclerosis (MS)
    Variant & Polymorphism SNP
  • at least three significantly associated SNPs--conferred susceptibility to MS (Zhang 2005)
  • Candidate gene
    Marker
  • testing LAG3 DNA methylation is a predictive biomarker for response to LAG3 immune checkpoint inhibitors in in clear cell renal cell carcinoma
  • Therapy target
    SystemTypeDisorderPubmed
    immunologyinfectious 
    LAG3, either alone or in combination with other immune checkpoints, is an ideal target for immunotherapy in COVID19
    ANIMAL & CELL MODELS