LAT

Chr 16AR

linker for activation of T cells

Also known as: IMD52, LAT1, pp36

NCBI Gene: 27040 ENSG00000213658 UniProt: O43561 OMIM: 602354

LAT encodes a transmembrane adaptor protein that serves as a critical docking site for signaling molecules downstream of T-cell antigen receptor activation and is essential for T-cell development and function. Mutations cause autosomal recessive immunodeficiency 52, a primary immunodeficiency affecting T-cell signaling. The gene shows moderate constraint against loss-of-function variants (LOEUF 0.66), consistent with its role in immune system development.

GeneReviews OMIM ResearchSummary from RefSeq, OMIM, UniProt

The protein encoded by this gene is phosphorylated by ZAP-70/Syk protein tyrosine kinases following activation of the T-cell antigen receptor (TCR) signal transduction pathway. This transmembrane protein localizes to lipid rafts and acts as a docking site for SH2 domain-containing proteins. Upon phosphorylation, this protein recruits multiple adaptor proteins and downstream signaling molecules into multimolecular signaling complexes located near the site of TCR engagement. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Jul 2008]

GeneReviews OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Immunodeficiency 52MIM #617514

Clinical highlights

Gene–disease validity (ClinGen)

Definitive · severe combined immunodeficiency due to LAT deficiency · AR · ClinGen 2025

Active trials

546

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.66

LOEUF

Multiple*

Mechanism· predicted

📖

GeneReview available — LAT

Authoritative clinical overview · Recommended first read

Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.66LOEUF

pLI 0.009

Z-score 2.68

OE 0.35 (0.20–0.66)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

0.63Z-score

OE missense 0.86 (0.75–0.99)

143 obs / 165.8 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.35 (0.20–0.66)

0≤0.351.4

Missense OE?0.86 (0.75–0.99)

0≤0.61.4

Synonymous OE?0.98

0≤1.21.6

LoF obs/exp: 7 / 19.9Missense obs/exp: 143 / 165.8Syn Z: 0.16

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

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 110

386 rare PASS variants

Rare truncating (LoF)

1 in 3,000

42 rare PASS variants

Rare synonymous (reference)

1 in 200

175 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for LAT. 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 140	1 in 4,000
South Asian	~43k	1 in 100	1 in 1,500
Remaining (unassigned)	~30k	1 in 92	1 in 2,500
European (Finnish)	~27k	1 in 340	1 in 700
Admixed American	~22k	1 in 150	1 in 2,000
African / African American	~21k	1 in 100	1 in 1,800
East Asian	~20k	1 in 110	1 in 2,100
Ashkenazi Jewish	~13k	1 in 430	1 in 2,500
Middle Eastern	~2,884	1 in 130	none seen

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): All 11 coding exons well covered in gnomAD exomes and genomes.? see exons ↓

ClinVar Variant Classifications

0 submitted variants in ClinVar

ClinVar

Protein Context — Lollipop Plot

LAT · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

External Resources

Links to major genomics databases and tools

Franklin by Genoox

AI-powered variant curation and clinical analysis

DECIPHER

Genomic variants and phenotypes in rare disease patients

📖

GeneReview available — LAT

Authoritative clinical overview · NCBI Bookshelf · Recommended first read

Open GeneReview ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

NSCLC

Trial for Local Ablative Treatment (LAT) Optimization in Patients With Advanced Non-Small Cells Lung Cancer (NSCLC) Presenting an Anaplastic Lymphoma Kinase (ALK) Rearrangement Treated by Brigatinib

RECRUITING

NCT06620835Phase PHASE2Groupe Francais De Pneumo-CancerologieStarted 2025-06-19

Blood samples for HematologyBlood samples for ChemistryBlood sample for liver function tests

Clinical Literature

Open Research Assistant →

Landmark / reviewRecent case evidence

Full-Text Mentions

NLP-detected gene mentions in article bodies · via PubTator3

PubTator3

Manifold Approximating Graph Interpolation of Cardiac Local Activation Time

Hellar J et al.·IEEE Trans Biomed Eng

2022