LAT2

Chr 7

linker for activation of T cells family member 2

Also known as: HSPC046, LAB, NTAL, WBSCR15, WBSCR5, WSCR5

LAT2 encodes a transmembrane adaptor protein that couples high-affinity immunoglobulin receptors (including IgE receptors in mast cells and IgG receptors in myeloid cells) with downstream signaling cascades through recruitment of GRB2. LAT2 is located in the 7q11.23 region commonly deleted in Williams syndrome, a multisystem developmental disorder affecting cardiovascular, neurodevelopmental, and other organ systems. The gene shows low constraint against loss-of-function variants (pLI 0.0002), and inheritance follows an autosomal dominant pattern when considering Williams syndrome deletions.

OMIMResearchSummary from RefSeq, UniProt
MultiplemechanismLOEUF 0.83
Clinical SummaryLAT2
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
0.83LOEUF
pLI 0.000
Z-score 2.09
OE 0.48 (0.290.83)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
-0.02Z-score
OE missense 1.01 (0.881.15)
145 obs / 144.2 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios
LoF OE0.48 (0.290.83)
00.351.4
Missense OE1.01 (0.881.15)
00.61.4
Synonymous OE0.77
01.21.6
LoF obs/exp: 9 / 18.8Missense obs/exp: 145 / 144.2Syn Z: 1.39
DN
0.7130th %ile
GOF
0.72top 25%
LOF
0.2288th %ile

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

GOFprediction above median
DNprediction 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

LAT2 · 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

No active trials found for this gene.

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Clinical Literature
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