LAG3

Chr 12

lymphocyte activating 3

Also known as: CD223

NCBI Gene: 3902 ENSG00000089692 UniProt: P18627 OMIM: 153337

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]

OMIM Research

OMIM ResearchGenerating clinical summary…

Clinical highlights

Interpreting a novel variant

This gene is strongly intolerant of loss-of-function variation in the population, so LoF variants warrant close attention. No curated mechanism annotation is available — see the mechanism card for the computational prediction and its caveats.Based on population constraint only.

Active trials

396

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.50

LOEUF

Multiple*

Mechanism· predicted

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Moderate LoF intolerance

LoF Constraint?

0.50LOEUF

pLI 0.276

Z-score 3.24

OE 0.24 (0.12–0.50)

Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?

0.51Z-score

OE missense 0.91 (0.82–1.01)

246 obs / 269.7 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.24 (0.12–0.50)

0≤0.351.4

Missense OE?0.91 (0.82–1.01)

0≤0.61.4

Synonymous OE?1.11

0≤1.21.6

LoF obs/exp: 5 / 21.0Missense obs/exp: 246 / 269.7Syn Z: -0.89

Background carrier burden — how many people carry a rare variant somewhere in LAG3?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 71

759 rare PASS variants

Rare truncating (LoF)

1 in 1,800

86 rare PASS variants

Rare synonymous (reference)

1 in 220

351 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for LAG3. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 97	1 in 2,900
South Asian	~43k	1 in 56	1 in 2,500
Remaining (unassigned)	~30k	1 in 48	1 in 1,500
European (Finnish)	~27k	1 in 220	≈ 1 in 27,000
Admixed American	~22k	1 in 91	1 in 1,400
African / African American	~21k	1 in 63	1 in 1,700
East Asian	~20k	1 in 92	1 in 1,500
Ashkenazi Jewish	~13k	1 in 250	≈ 1 in 4,500
Middle Eastern	~2,884	1 in 73	≈ 1 in 2,900

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): 7 of 8 coding exons well covered in gnomAD exomes; exon 3 marginal. Genomes: all 8.? see exons ↓