LAT

Chr 16AR

linker for activation of T cells

Also known as: IMD52, LAT1, pp36

NCBI Gene: 27040ENSG00000213658UniProt: O43561

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]

Primary Disease Associations & Inheritance

Immunodeficiency 52MIM #617514
AR
389
ClinVar variants
123
Pathogenic / LP
0.01
pLI score
8
Active trials
Clinical Summary— LAT
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.01) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
123 Pathogenic / Likely Pathogenic· 111 VUS of 389 total submissions
💊
Clinical Trials
8 active or recruiting trials — potential therapeutic options may be available

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.66LOEUF
pLI 0.009
Z-score 2.68
OE 0.35 (0.20–0.66)
Tolerant

Typical tolerance to LoF variation

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
0.63Z-score
OE missense 0.86 (0.75–0.99)
143 obs / 165.8 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.35 (0.20–0.66)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.86 (0.75–0.99)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.0.98
0≤1.21.6
LoF obs/exp: 7 / 19.9Missense obs/exp: 143 / 165.8Syn Z: 0.16

ClinVar Variant Classifications

389 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic112
Likely Pathogenic11
VUS111
Likely Benign126
Benign14
Conflicting3
112
Pathogenic
11
Likely Pathogenic
111
VUS
126
Likely Benign
14
Benign
3
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
6
0
106
0
112
Likely Pathogenic
1
0
10
0
11
VUS
1
68
40
2
111
Likely Benign
0
7
59
60
126
Benign
0
3
10
1
14
Conflicting
—3
Total87822563377

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in 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.

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Immunodeficiency 52

MIM #617514

Molecular basis of disorder known

Autosomal recessive
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Local Ablative Therapy in Oligometastatic NSCLC.
Li X et al.·Semin Radiat Oncol
2021Review
Identification of key genes and immune infiltration in peripheral blood biomarker analysis of delayed cerebral ischemia: Valproic acid as a potential therapeutic drug.
Wu Z et al.·Int Immunopharmacol
2024
Publication trends in ligament augmentation techniques: current concepts.
Alexeev SO et al.·J ISAKOS
2023Review
Mechanical stretch promotes the migration of mesenchymal stem cells via Piezo1/F-actin/YAP axis.
Ma N et al.·Exp Cell Res
2025
GLP-1 analogs and regional adiposity: A systematic review and meta-analysis.
Akoumianakis I et al.·Obes Rev
2023Meta-analysis
Higher volume resistance training enhances whole-body muscle hypertrophy in postmenopausal and older females: A secondary analysis of systematic review and meta-analysis of randomized clinical trials.
Nunes PRP et al.·Arch Gerontol Geriatr
2024Meta-analysis
Frequency and Prognostic Impact of Local Ablation Therapy for Oligoprogression in Non-Small Cell Lung Cancer.
Morinaga D et al.·Thorac Cancer
2025
Advances in basic and clinical immunology in 2016.
Chinen J et al.·J Allergy Clin Immunol
2017Review
Current perspectives on lacertus syndrome: clinical features, diagnosis, and treatment.
Jerome JTJ et al.·Int Orthop
2025Review
Advances in ultrasound-guided thermal ablation for symptomatic benign thyroid nodules.
Cheng Z et al.·Adv Clin Exp Med
2020Review
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Traditional Medicine Extracts of Gnidia sericocephala and Product Nkabinde in HIV-1 Latency Reversal: Insights from J-Lat Subtype B and J-Lat Subtype C Models.
Mngomezulu K et al.·Int J Mol Sci
2026🔓 Open AccessFunctional
Transcriptomic profiling reveals T cell-mediated Glutamine immunomodulation via CD8A / LCK / LAT signaling in the liver model of piglets.
Liu G et al.·J Nutr Biochem
2026Functional
Bayesian Framework for Atrial LAT Estimation in ECGI.
Fambuena-Santos C et al.·IEEE Trans Med Imaging
2026
DNA-PKcs controls the cytotoxic T cell response to cancer and transplant allograft through regulating LAT-dependent signaling.
Rainwater RR et al.·Cell Rep
2026
Low Levels of Mouse γδ T Cell Development Persist in the Presence of Null Mutants of the LAT Adaptor.
Arbulo-Echevarria MM et al.·Int J Mol Sci
2025🔓 Open AccessFunctional
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov
Dyslexia, DevelopmentalLanguage Development DisordersLanguage Development

Language Development Deficits and Early Interactive Music Intervention

RECRUITING
NCT06261307Phase NAUniversity of HelsinkiStarted 2024-03-11
Music interventionCircus intervention
Hearing Loss

Natural History of Autosomal Dominant Hearing Loss

RECRUITING
NCT04501081National Institute on Deafness and Other Communication Disorders (NIDCD)Started 2021-02-09
Prediabetes

Training Induced Muscle-Adipose EV Communication

NOT YET RECRUITING
NCT07106450Phase NAYuan WenStarted 2026-02
Acute Resistance Exercise
Hip Replacement in Osteoarthritis PatientsOsteoarthritis, Hip

Prehabilitation in Older People Undergoing Total Hip Replacement

NOT YET RECRUITING
NCT07048080Phase NAUniversidad de La FronteraStarted 2025-08
(P)rehabilitation Progresive Resistance Exercise TrainingPrehabilitation Group Deuterated WaterUsual Care Group Deuterated Water
Biliary Atresia

Mapping Disease Pathways for Biliary Atresia

RECRUITING
NCT03273049University of PittsburghStarted 2016-07-21
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
Glioblastoma IDH (Isocitrate Dehydrogenase) Wildtype

Feasibility of ONCOhabitats for Surgical and Treatment Planning in IDH-Wildtype Glioblastoma (SINUE)

RECRUITING
NCT07111195Juan M Garcia-GomezStarted 2024-07-16
The ONCOhabitats software for MRI-based habitat segmentation
Histiocytosis

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

RECRUITING
NCT04943224Phase PHASE2Anna RaciborskaStarted 2021-04-01
Trametinib

External Resources

Links to major genomics databases and tools