LAT

Chr 16AR

linker for activation of T cells

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.

OMIMResearchSummary from RefSeq, OMIM, UniProt
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.
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Clinical Trials
8 active or recruiting trials — potential therapeutic options may be available
Some data sources returned errors (1)

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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 OE0.35 (0.200.66)
00.351.4
Missense OE0.86 (0.750.99)
00.61.4
Synonymous OE0.98
01.21.6
LoF obs/exp: 7 / 19.9Missense obs/exp: 143 / 165.8Syn Z: 0.16
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

0 submitted variants 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.

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

Biliary Atresia

Mapping Disease Pathways for Biliary Atresia

RECRUITING
NCT03273049University of PittsburghStarted 2016-07-21
Histiocytosis

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

RECRUITING
NCT04943224Phase PHASE2Anna RaciborskaStarted 2021-04-01
Trametinib
Prediabetes

Training Induced Muscle-Adipose EV Communication

NOT YET RECRUITING
NCT07106450Phase NAYuan WenStarted 2026-06
Acute Resistance Exercise
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
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
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
Hearing Loss

Natural History of Autosomal Dominant Hearing Loss

RECRUITING
NCT04501081National Institute on Deafness and Other Communication Disorders (NIDCD)Started 2021-02-09
Clinical Literature
Open Research Assistant →
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
At Lats: Flow Has Come Along.
Allbritton-King JD et al.·Arterioscler Thromb Vasc Biol
2025
Rush Hour of LATs towards Their Transport Cycle
Nicolàs-Aragó A et al.·Membranes (Basel)
2021
Bayesian framework for atrial LAT estimation in ECGI.
Fambuena-Santos C et al.·IEEE Trans Med Imaging
2025
Top 5 full-text resultsSearch PubTator3 ↗