TRAT1

Chr 3

T cell receptor associated transmembrane adaptor 1

TRAT1 encodes a transmembrane adaptor protein that stabilizes the T-cell receptor (TCR)/CD3 complex at the T-cell surface and regulates receptor recycling and signal transduction. Mutations cause severe combined immunodeficiency with autosomal recessive inheritance. The gene shows low constraint to loss-of-function variation, consistent with recessive disease patterns.

OMIMResearchSummary from RefSeq, UniProt
MultiplemechanismLOEUF 0.78
Clinical SummaryTRAT1
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.34) despite low pLI — interpret in context.
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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
0.78LOEUF
pLI 0.056
Z-score 2.09
OE 0.34 (0.170.78)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
-0.36Z-score
OE missense 1.10 (0.941.29)
112 obs / 101.7 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios
LoF OE0.34 (0.170.78)
00.351.4
Missense OE1.10 (0.941.29)
00.61.4
Synonymous OE1.20
01.21.6
LoF obs/exp: 4 / 11.7Missense obs/exp: 112 / 101.7Syn Z: -0.94
DN
0.82top 10%
GOF
0.85top 5%
LOF
0.1598th %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

TRAT1 · 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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