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LAG3 lymphocyte activating 3 [ Homo sapiens (human) ]

Gene ID: 3902, updated on 2-Nov-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: HPA RNA-seq normal tissues 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. 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)

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 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

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