TRAT1

Chr 3

T cell receptor associated transmembrane adaptor 1

Also known as: HSPC062, TCRIM, TRIM, pp29/30

NCBI Gene: 50852 ENSG00000163519 UniProt: Q6PIZ9 OMIM: 604962

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.

OMIM ResearchSummary from RefSeq, UniProt

Predicted to enable transmembrane receptor protein tyrosine kinase adaptor activity. Acts upstream of or within negative regulation of receptor recycling; negative regulation of transport; and positive regulation of signal transduction. Located in centriolar satellite; mitotic spindle; and plasma membrane. Part of T cell receptor complex. [provided by Alliance of Genome Resources, Jul 2025]

OMIM ResearchGenerating clinical summary…

MultiplemechanismLOEUF 0.78

Clinical Summary— TRAT1

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Population Constraint (gnomAD)

Constrained for loss-of-function variants (OE-LoF 0.34) despite low pLI — interpret in context.

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ClinVar Variants

28 VUS of 34 total submissions

Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.78LOEUF

pLI 0.056

Z-score 2.09

OE 0.34 (0.17–0.78)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

-0.36Z-score

OE missense 1.10 (0.94–1.29)

112 obs / 101.7 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?0.34 (0.17–0.78)

0≤0.351.4

Missense OE?1.10 (0.94–1.29)

0≤0.61.4

Synonymous OE?1.20

0≤1.21.6

LoF obs/exp: 4 / 11.7Missense obs/exp: 112 / 101.7Syn Z: -0.94

This gene — mechanism propensity

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

34 submitted variants in ClinVar

ClinVar

Classification Summary

VUS28

Likely Benign3

Benign1

VUS

Likely Benign

Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Non-coding	Total
Pathogenic	0	0	0
Likely Pathogenic	0	0	0
VUS	27	1	28
Likely Benign	3	0	3
Benign	1	0	1
Total	31	1	32

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

View in ClinVar →

16 pathogenic / likely-pathogenic (of 22) ClinVar copy-number / structural variants overlap TRAT1 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →