LAT

Chr 16

linker for activation of T cells

Also known as: IMD52, LAT1, pp36

NCBI Gene: 27040 ENSG00000213658 UniProt: O43561

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 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 ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

UniProtImmunodeficiency 52

Clinical highlights

Gene-disease validity (ClinGen)

severe combined immunodeficiency due to LAT deficiency · ARDefinitivesufficient evidence for diagnostic panels

Active trials

513

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 ↗

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

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

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

Prediabetes

Training Induced Muscle-Adipose EV Communication

NOT YET RECRUITING

NCT07106450Phase NAYuan WenStarted 2026-09

Acute Resistance Exercise

Dyslexia, DevelopmentalLanguage Development DisordersLanguage Development

Language Development Deficits and Early Interactive Music Intervention

ACTIVE NOT RECRUITING

NCT06261307Phase NAUniversity of HelsinkiStarted 2024-03-11

Music interventionCircus intervention

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

Histiocytosis

Optimization of the Time and Dosage of Trametinib in BRAF Negative Juvenile Patients

RECRUITING

NCT04943224Phase PHASE2Anna RaciborskaStarted 2021-04-01

Trametinib

Hip Replacement in Osteoarthritis PatientsOsteoarthritis, Hip

Prehabilitation in Older People Undergoing Total Hip Replacement

NOT YET RECRUITING

NCT07048080Phase NAUniversidad de La FronteraStarted 2026-08-02