LAG3 lymphocyte activating 3 [Homo sapiens (human)] - Gene

Summary

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

Location:: 12p13.31

Exon count:: 8

Annotation release	Status	Assembly	Chr	Location
RS_2025_08	current	GRCh38.p14 (GCF_000001405.40)	12	NC_000012.12 (6772520..6778455)
RS_2025_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_000012.12 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

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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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

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.
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.
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.
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.
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.
Aplp1 interacts with Lag3 to facilitate transmission of pathologic alpha-synuclein.
Title: Aplp1 interacts with Lag3 to facilitate transmission of pathologic α-synuclein.
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.
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.
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.
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)

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

RH71279 (e-PCR)
- UniSTS:72972

RH44859 (e-PCR)
- UniSTS:14905

A21356 (e-PCR)
- UniSTS:40117

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables MHC class II protein binding	IDA Inferred from Direct Assay more info	PubMed
enables MHC class II protein binding	IEA Inferred from Electronic Annotation more info
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
enables transmembrane signaling receptor activity	IEA Inferred from Electronic Annotation more info

Process	Evidence Code	Pubs
acts_upstream_of 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
acts_upstream_of_or_within cell surface receptor signaling pathway	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 immune system process	IEA Inferred from Electronic Annotation more info
involved_in innate immune response	IBA Inferred from Biological aspect of Ancestor more info
acts_upstream_of natural killer cell mediated cytotoxicity	IEA Inferred from Electronic Annotation more info
acts_upstream_of_or_within negative regulation of T cell activation	IEA Inferred from Electronic Annotation more info
acts_upstream_of_or_within negative regulation of interleukin-2 production	IEA Inferred from Electronic Annotation more info
involved_in negative regulation of regulatory T cell differentiation	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	IEA Inferred from Electronic Annotation more info
involved_in plasmacytoid dendritic cell activation	ISS Inferred from Sequence or Structural Similarity more info
acts_upstream_of_or_within positive regulation of natural killer cell mediated cytotoxicity	IEA Inferred from Electronic Annotation more info
involved_in regulation of immune response	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
located_in membrane	IEA Inferred from Electronic Annotation more info
is_active_in plasma membrane	IBA Inferred from Biological aspect of Ancestor more info
located_in plasma membrane	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)

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

Status: REVIEWED

Source sequence(s)

AC125494
NM_001414177.1 → NP_001401106.1 lymphocyte activation gene 3 protein isoform 3 precursor

Status: REVIEWED

Source sequence(s)

AC125494

Related

ENSP00000557856.1, ENST00000887797.1
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