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    LAG3 lymphocyte activating 3 [ Homo sapiens (human) ]

    Gene ID: 3902, updated on 13-May-2024

    Summary

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    Official Symbol
    LAG3provided by HGNC
    Official Full Name
    lymphocyte activating 3provided by HGNC
    Primary source
    HGNC:HGNC:6476
    See related
    Ensembl:ENSG00000089692 MIM:153337; AllianceGenome:HGNC:6476
    Gene type
    protein coding
    RefSeq status
    REVIEWED
    Organism
    Homo sapiens
    Lineage
    Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
    Also known as
    CD223
    Summary
    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]
    Expression
    Biased expression in spleen (RPKM 15.1), lymph node (RPKM 8.3) and 12 other tissues See more
    Orthologs
    mouse all
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    Genomic context

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    See LAG3 in Genome Data Viewer
    Location:
    12p13.31
    Exon count:
    8
    Annotation release Status Assembly Chr Location
    RS_2023_10 current GRCh38.p14 (GCF_000001405.40) 12 NC_000012.12 (6772520..6778455)
    RS_2023_10 current T2T-CHM13v2.0 (GCF_009914755.1) 12 NC_060936.1 (6782086..6788021)
    105.20220307 previous assembly GRCh37.p13 (GCF_000001405.25) 12 NC_000012.11 (6881686..6887621)

    Chromosome 12 - NC_000012.12Genomic Context describing neighboring genes Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 4179 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 5879 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 5880 Neighboring gene myeloid leukemia factor 2 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 4180 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 4181 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 4182 Neighboring gene parathymosin Neighboring gene H3K4me1 hESC enhancer GRCh37_chr12:6887480-6888130 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr12:6888131-6888782 Neighboring gene Sharpr-MPRA regulatory region 1171 Neighboring gene RNA, 7SL, cytoplasmic 380, pseudogene Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr12:6898178-6898735 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 5883 Neighboring gene CD4 molecule Neighboring gene H3K4me1 hESC enhancer GRCh37_chr12:6928026-6928526 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr12:6928527-6929027

    Genomic regions, transcripts, and products

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    Go to nucleotide: Graphics FASTA GenBank

    Expression

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    • Project title: HPA RNA-seq normal tissues
    • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
    • BioProject: PRJEB4337
    • Publication: PMID 24309898
    • Analysis date: Wed Apr 4 07:08:55 2018

    Bibliography

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    Related articles in PubMed

    1. Lymphocyte activation gene 3 is increased and affects cytokine production in rheumatoid arthritis. Pedersen JM, et al. Arthritis Res Ther, 2023 Jun 7. PMID 37287025, Free PMC Article
    2. Lymphocyte-activation gene 3 protein expression in tumor-infiltrating lymphocytes is associated with a poor prognosis of ovarian clear cell carcinoma. Zaitsu S, et al. J Ovarian Res, 2023 May 13. PMID 37179337, Free PMC Article
    3. LAG-3 transcriptomic expression patterns across malignancies: Implications for precision immunotherapeutics. Adashek JJ, et al. Cancer Med, 2023 Jun. PMID 37132280, Free PMC Article
    4. The elevated expression of LAG-3 on CD8+T cells correlates with disease severity of pulmonary TB. Chen J, et al. Microb Pathog, 2023 Jun. PMID 37004963
    5. LAG-3 expression in tumor microenvironment of triple-negative breast cancer. Tahtacı G, et al. Turk J Med Sci, 2023 Feb. PMID 36945923, Free PMC Article

    See all (141) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. Multiplex immunohistochemistry elucidates increased distance between cytotoxic T cells and plasma cells in relapsed myeloma, and identifies Lag-3 as the most common checkpoint receptor on cytotoxic T cells of myeloma patients.
      Title: Multiplex immunohistochemistry elucidates increased distance between cytotoxic T cells and plasma cells in relapsed myeloma, and identifies Lag-3 as the most common checkpoint receptor on cytotoxic T cells of myeloma patients.
    2. Expression of lymphocyte activation gene-3 on CD4[+]T cells is regulated by cytokine interleukin-18 in myasthenia gravis.
      Title: Expression of lymphocyte activation gene-3 on CD4(+)T cells is regulated by cytokine interleukin-18 in myasthenia gravis.
    3. Altered immune co-inhibitory receptor expression and correlation of LAG-3 expression to disease severity in NMOSD.
      Title: Altered immune co-inhibitory receptor expression and correlation of LAG-3 expression to disease severity in NMOSD.
    4. LAG3 and TIGIT Expression on Tumor-Infiltrating Lymphocytes in Cutaneous Melanoma.
      Title: LAG3 and TIGIT Expression on Tumor-Infiltrating Lymphocytes in Cutaneous Melanoma.
    5. ATM-AMPKalpha mediated LAG-3 expression suppresses T cell function in prostate cancer.
      Title: ATM-AMPKα mediated LAG-3 expression suppresses T cell function in prostate cancer.
    6. Characterisation of the protein expression of the emerging immunotherapy targets VISTA, LAG-3 and PRAME in primary uveal melanoma: insights from a southern French patient cohort.
      Title: Characterisation of the protein expression of the emerging immunotherapy targets VISTA, LAG-3 and PRAME in primary uveal melanoma: insights from a southern French patient cohort.
    7. Comprehensive immunophenotyping of solid tumor-infiltrating immune cells reveals the expression characteristics of LAG-3 and its ligands.
      Title: Comprehensive immunophenotyping of solid tumor-infiltrating immune cells reveals the expression characteristics of LAG-3 and its ligands.
    8. Blockade of PD-1 and LAG-3 expression on CD8+ T cells promotes the tumoricidal effects of CD8+ T cells.
      Title: Blockade of PD-1 and LAG-3 expression on CD8+ T cells promotes the tumoricidal effects of CD8+ T cells.
    9. The ligand-dependent suppression of TCR signaling by the immune checkpoint receptor LAG3 depends on the cytoplasmic RRFSALE motif.
      Title: The ligand-dependent suppression of TCR signaling by the immune checkpoint receptor LAG3 depends on the cytoplasmic RRFSALE motif.
    10. A unique expression pattern of LAG3 distinct from that of other immune checkpoints in diffuse large B-cell lymphoma.
      Title: A unique expression pattern of LAG3 distinct from that of other immune checkpoints in diffuse large B-cell lymphoma.
    Submit: New GeneRIF Correction See all GeneRIFs (134)

    Phenotypes

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    Find tests for this gene in the NIH Genetic Testing Registry (GTR)

    Review eQTL and phenotype association data in this region using PheGenI

    Variation

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    See variants in ClinVar

    See studies and variants in dbVar

    See Variation Viewer (GRCh37.p13)

    See Variation Viewer (GRCh38)

    Genotypes

    Pathways from PubChem

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    Interactions

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    Products Interactant Other Gene Complex Source Pubs Description

    General gene information

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    Markers

    Homology

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    enables MHC class II protein binding IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    enables MHC class II protein binding IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables antigen binding TAS
    Traceable Author Statement
    more info
    		 PubMed 
    enables protein binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    enables transmembrane signaling receptor activity IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    Process Evidence Code Pubs
    involved_in T cell activation IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in adaptive immune response IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in cell surface receptor signaling pathway ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    involved_in natural killer cell mediated cytotoxicity IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in negative regulation of interleukin-2 production IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in negative regulation of regulatory T cell differentiation ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    involved_in plasmacytoid dendritic cell activation ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    involved_in positive regulation of natural killer cell mediated cytotoxicity IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in regulation of immune response ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    Component Evidence Code Pubs
    located_in external side of plasma membrane IEA
    Inferred from Electronic Annotation
    more info
    		  
    located_in extracellular region IEA
    Inferred from Electronic Annotation
    more info
    		  
    located_in plasma membrane TAS
    Traceable Author Statement
    more info
    		  

    General protein information

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    Preferred Names
    lymphocyte activation gene 3 protein
    Names
    lymphocyte-activation gene 3

    NCBI Reference Sequences (RefSeq)

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    RefSeqs maintained independently of Annotated Genomes

    These reference sequences exist independently of genome builds. Explain

    These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

    mRNA and Protein(s)

    1. NM_001414176.1 → NP_001401105.1  lymphocyte activation gene 3 protein isoform 2 precursor

      Status: REVIEWED

      Source sequence(s)
      AC125494

    2. NM_001414177.1 → NP_001401106.1  lymphocyte activation gene 3 protein isoform 3 precursor

      Status: REVIEWED

      Source sequence(s)
      AC125494

    3. NM_002286.6 → NP_002277.4  lymphocyte activation gene 3 protein isoform 1 precursor

      See identical proteins and their annotated locations for NP_002277.4

      Status: REVIEWED

      Source sequence(s)
      AA687676, AC125494, AI274900, X51985
      Consensus CDS
      CCDS8561.1
      UniProtKB/Swiss-Prot
      A8K7T9, P18627, Q7Z643
      Related
      ENSP00000203629.2, ENST00000203629.3
      Conserved Domains (3) summary
      smart00410
      Location:267 → 348
      IG_like; Immunoglobulin like
      pfam13895
      Location:174 → 259
      Ig_2; Immunoglobulin domain
      cl11960
      Location:263 → 336
      Ig; Immunoglobulin domain

    RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2023_10

    The following sections contain reference sequences that belong to a specific genome build. Explain

    Reference GRCh38.p14 Primary Assembly

    Genomic

    1. NC_000012.12 Reference GRCh38.p14 Primary Assembly

      Range
      6772520..6778455
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060936.1 Alternate T2T-CHM13v2.0

      Range
      6782086..6788021
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)
    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    P18627.5 GenPept UniProtKB/Swiss-Prot:P18627

    Gene LinkOut

    The following LinkOut resources are supplied by external providers. These providers are responsible for maintaining the links.

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