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FLASH GENE

Symbol

LAG3

contributors: mct - updated : 26-03-2024

HGNC name	lymphocyte-activation gene 3
HGNC id	6476

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

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

identification nb exons type bp product Protein kDa AA specific expression Year Pubmed NM_002286 8 - 1995 NP_002277 - 525 - 1997 9159144 NM_001414176 8 - 2062 NP_001401105 - 514 - 1997 9159144 NM_001414177 7 - 1733 NP_001401106 - 444 - 1997 9159144

EXPRESSION

Type	restricted

expressed in	(based on citations)
organ(s)	System Organ level 1 Organ level 2 Organ level 3 Organ level 4 Level Pubmed Species Stage Rna symbol Digestive intestine small intestine       Lymphoid/Immune spleen         Reproductive female system uterus       Respiratory respiratory tract trachea

tissue

System Tissue Tissue level 1 Tissue level 2 Level Pubmed Species Stage Rna symbol Lymphoid

cells

System Cell Pubmed Species Stage Rna symbol Lymphoid/Immune B cell Homo sapiens Lymphoid/Immune dendritic cell Lymphoid/Immune lymphocyte Lymphoid/Immune natural killer Homo sapiens Lymphoid/Immune T 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)

Type Gene Modification Chromosome rearrangement Protein expression Protein 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
	System Type Disorder Pubmed immunology infectious   LAG3, either alone or in combination with other immune checkpoints, is an ideal target for immunotherapy in COVID19

ANIMAL & CELL MODELS