LAG3

protein-coding

lymphocyte activating 3, the group of CD molecules|Immunoglobulin like domain containing

Gene 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]

MANE transcript

NM_002286.6

Inheritance

—

ClinVar variants

U:104B:13

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.24

Max pathogenic AF

—

Genomic locus

chr12:6,772,512-6,778,455

External References & Databases

Ensembl (ENSG00000089692)

Transcript & Mutation Effects

hg38 • Region Span ~5.9 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to LAG3 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 112

not providedTotal: 4

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_002286.6. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous				1 clinvar		1
missense			104 clinvar	10 clinvar	2 clinvar	116
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)						0
Total	0	0	104	11	2	117

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 14 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_002286.6	RefSeq	NP_002277.4	8	MANE Select
ENST00000203629.3	Ensembl	ENSP00000203629.2	8	MANE Select
NM_001414176.1	RefSeq	NP_001401105.1	8	Standard
NM_001414177.1	RefSeq	NP_001401106.1	7	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

MHC class II antigen presentation
Immune System
Adaptive Immune System

Biological Process

cell surface receptor signaling pathway
antigen processing and presentation of exogenous peptide antigen via MHC class II
negative regulation of interleukin-2 biosynthetic process
positive regulation of natural killer cell mediated cytotoxicity
negative regulation of T cell activation

Molecular Function

antigen binding
transmembrane signaling receptor activity
MHC class II protein binding

Cellular Component

plasma membrane
external side of plasma membrane
integral component of membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000203629
Coding exons: 8
Length: 5944
Individuals with no LoFs: 125738
Homozygous LoFs: 0
Heterozygous LoFs: 10
Defined: 125748
p: 0.0000398

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.512	246	270	0.912	0.0000150	3277
Missense (PolyPhen)		51	66.113	0.7714		808
Synonymous	-0.887	127	115	1.11	0.00000638	1173
Loss of Function	3.24	5	21.0	0.238	0.00000114	209

Population LoF Frequency

Population	CAF	p-value	Status
African	0.000062	0.000062	rare
Latino/Admixed American	0.000058	0.000058	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.000054	0.000054	rare
Finnish	0.000046	0.000046	rare
European (Non-Finnish)	0.000035	0.000035	rare
South Asian	0.000033	0.000033	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Involved in lymphocyte activation. Binds to HLA class-II antigens.;

Recessive Scores

pRec: 0.152

Intolerance Scores

LoFtool: 0.399
RVIS EVS: 0.33
RVIS percentile EVS: 73.54

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.299

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium