LAT

Chr 16AR

linker for activation of T cells

Also known as: IMD52, LAT1, pp36

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]

GeneReviewsOMIMResearchGenerating clinical summary…
MultiplemechanismARLOEUF 0.661 OMIM phenotype
Clinical SummaryLAT
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Gene-Disease Validity (ClinGen)
severe combined immunodeficiency due to LAT deficiency · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

Population Constraint (gnomAD)
Low constraint (pLI 0.01) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
11 unique Pathogenic / Likely Pathogenic· 77 VUS of 238 total submissions
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Clinical Trials
8 active or recruiting trials — potential therapeutic options may be available
📖
GeneReview available — LAT
Authoritative clinical overview · Recommended first read
Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint?
0.66LOEUF
pLI 0.009
Z-score 2.68
OE 0.35 (0.200.66)
Tolerant

Typical tolerance to LoF variation

Missense Constraint?
0.63Z-score
OE missense 0.86 (0.750.99)
143 obs / 165.8 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?
LoF OE?0.35 (0.200.66)
00.351.4
Missense OE?0.86 (0.750.99)
00.61.4
Synonymous OE?0.98
01.21.6
LoF obs/exp: 7 / 19.9Missense obs/exp: 143 / 165.8Syn Z: 0.16

This gene — mechanism propensity

DN
0.7228th %ile
GOF
0.7029th %ile
LOF
0.2287th %ile

This gene has evidence for multiple mechanisms of pathogenicity (dominant-negative and gain-of-function). Both the Badonyi & Marsh prediction and the broader genomic evidence point to dominant-negative as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

DNprediction above median
GOFprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

238 submitted variants in ClinVar

Classification Summary

Pathogenic10
Likely Pathogenic1
VUS77
Likely Benign125
Benign14
Conflicting1
10
Pathogenic
1
Likely Pathogenic
77
VUS
125
Likely Benign
14
Benign
1
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
8
0
2
0
10
Likely Pathogenic
1
0
0
0
1
VUS
2
69
4
2
77
Likely Benign
1
7
57
60
125
Benign
0
3
10
1
14
Conflicting
1
Total12797363228

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

View in ClinVar →

112 pathogenic / likely-pathogenic (of 151) ClinVar copy-number / structural variants overlap LAT — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →

Protein Context — Lollipop Plot

LAT · protein map & ClinVar variants

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

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

Histiocytosis

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

RECRUITING
NCT04943224Phase PHASE2Anna RaciborskaStarted 2021-04-01
Trametinib
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
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
(P)rehabilitation Progresive Resistance Exercise TrainingPrehabilitation Group Deuterated WaterUsual Care Group Deuterated Water
Prediabetes

Training Induced Muscle-Adipose EV Communication

NOT YET RECRUITING
NCT07106450Phase NAYuan WenStarted 2026-07
Acute Resistance Exercise
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
Hearing Loss

Natural History of Autosomal Dominant Hearing Loss

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

Mapping Disease Pathways for Biliary Atresia

RECRUITING
NCT03273049University of PittsburghStarted 2016-07-21