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    LAG3 lymphocyte activating 3 [ Homo sapiens (human) ]

    Gene ID: 3902, updated on 10-Dec-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_2024_08 current GRCh38.p14 (GCF_000001405.40) 12 NC_000012.12 (6772520..6778455)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 12 NC_060936.1 (6782086..6788021)
    RS_2024_09 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: Tissue-specific circular RNA induction during human fetal development
    • Description: 35 human fetal samples from 6 tissues (3 - 7 replicates per tissue) collected between 10 and 20 weeks gestational time were sequenced using Illumina TruSeq Stranded Total RNA
    • BioProject: PRJNA270632
    • Publication: PMID 26076956
    • Analysis date: Mon Apr 2 22:54:59 2018

    Bibliography

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    Related articles in PubMed

    1. Molecular, clinicopathological, and immune correlates of LAG3 promoter DNA methylation in melanoma. Fröhlich A, et al. EBioMedicine, 2020 Sep. PMID 32861198, Free PMC Article
    2. Elevated LAG-3 on CD4(+) T cells negatively correlates with neutralizing antibody response during HCV infection. Zhang J, et al. Immunol Lett, 2019 Aug. PMID 31216427
    3. LAG3 in Solid Tumors as a Potential Novel Immunotherapy Target. Lee SJ, et al. J Immunother, 2019 Oct. PMID 31219974
    4. Lag3(+) regulatory T lymphocytes in critical carotid artery stenosis. Del Porto F, et al. Clin Exp Med, 2019 Nov. PMID 31302842
    5. T Cell Transcriptional Profiling and Immunophenotyping Uncover LAG3 as a Potential Significant Target of Immune Modulation in Multiple Myeloma. Lucas F, et al. Biol Blood Marrow Transplant, 2020 Jan. PMID 31445183, Free PMC Article

    See all (160) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. Indirect suppression of CD4 T cell activation through LAG-3-mediated trans-endocytosis of MHC class II.
      Title: Indirect suppression of CD4 T cell activation through LAG-3-mediated trans-endocytosis of MHC class II.
    2. Prognostic effect of CTLA4/LAG3 Expression by T-Cells Subsets on Acute Myeloid Leukemia Patients.
      Title: Prognostic effect of CTLA4/LAG3 Expression by T-Cells Subsets on Acute Myeloid Leukemia Patients.
    3. Expression and Prognostic Significance of LAG-3, TIGIT, VISTA, and IDO1 in Endometrial Serous Carcinoma.
      Title: Expression and Prognostic Significance of LAG-3, TIGIT, VISTA, and IDO1 in Endometrial Serous Carcinoma.
    4. TIGIT expression in renal cell carcinoma infiltrating T cells is variable and inversely correlated with PD-1 and LAG3.
      Title: TIGIT expression in renal cell carcinoma infiltrating T cells is variable and inversely correlated with PD-1 and LAG3.
    5. Start codon variant in LAG3 is associated with decreased LAG-3 expression and increased risk of autoimmune thyroid disease.
      Title: Start codon variant in LAG3 is associated with decreased LAG-3 expression and increased risk of autoimmune thyroid disease.
    6. Aplp1 interacts with Lag3 to facilitate transmission of pathologic alpha-synuclein.
      Title: Aplp1 interacts with Lag3 to facilitate transmission of pathologic α-synuclein.
    7. Association of Polymorphisms in PD-1 and LAG-3 Genes with Acute Myeloid Leukemia.
      Title: Association of Polymorphisms in PD-1 and LAG-3 Genes with Acute Myeloid Leukemia.
    8. Implications of LAG3 and CTLA4 immune checkpoints beyond PD-1/PD-L1 as a potential target in determining the prognosis of uveal melanoma patients.
      Title: Implications of LAG3 and CTLA4 immune checkpoints beyond PD-1/PD-L1 as a potential target in determining the prognosis of uveal melanoma patients.
    9. 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.
    10. 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.
    Submit: New GeneRIF Correction See all GeneRIFs (142)

    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)

    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 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 IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in cell surface receptor signaling pathway ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    involved_in innate immune response IBA
    Inferred from Biological aspect of Ancestor
    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
    is_active_in cell surface IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    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 extracellular region ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    is_active_in plasma membrane IBA
    Inferred from Biological aspect of Ancestor
    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_2024_08

    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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