TRARG1

Chr 17

trafficking regulator of GLUT4 (SLC2A4) 1 (gene/pseudogene)

Also known as: BEC-1, DSPB1, IFITMD3, LOST1, TUSC5

NCBI Gene: 286753 ENSG00000184811 UniProt: Q8IXB3 OMIM: 612211

The protein regulates insulin-mediated glucose uptake in adipose tissue by modulating SLC2A4 (GLUT4) recycling during prolonged insulin stimulation. Loss-of-function mutations in TRARG1 cause autosomal recessive intellectual disability with seizures and growth retardation. The gene shows tolerance to loss-of-function variation (pLI 0.0005, LOEUF 1.75), consistent with recessive inheritance.

OMIM ResearchSummary from RefSeq, UniProt

Predicted to be involved in endosome to plasma membrane protein transport and glucose import in response to insulin stimulus. Predicted to act upstream of or within establishment of localization in cell and vesicle fusion to plasma membrane. Predicted to be located in cytoplasmic vesicle membrane and plasma membrane. Predicted to be active in membrane. [provided by Alliance of Genome Resources, Jul 2025]

OMIM ResearchGenerating clinical summary…

MultiplemechanismLOEUF 1.75

Clinical Summary— TRARG1

⚡

Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

📋

ClinVar Variants

2 unique Pathogenic / Likely Pathogenic· 34 VUS of 41 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?

1.75LOEUF

pLI 0.001

Z-score 0.17

OE 0.92 (0.48–1.75)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

-0.44Z-score

OE missense 1.11 (0.96–1.29)

129 obs / 115.8 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?0.92 (0.48–1.75)

0≤0.351.4

Missense OE?1.11 (0.96–1.29)

0≤0.61.4

Synonymous OE?1.19

0≤1.21.6

LoF obs/exp: 5 / 5.4Missense obs/exp: 129 / 115.8Syn Z: -1.13

This gene — mechanism propensity

0.81top 10%

GOF

0.80top 10%

LOF

0.2776th %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

41 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic2

VUS34

Likely Benign4

Pathogenic

VUS

Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Non-coding	Total
Pathogenic	0	2	2
Likely Pathogenic	0	0	0
VUS	33	1	34
Likely Benign	4	0	4
Benign	0	0	0
Total	37	3	40

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

View in ClinVar →

113 pathogenic / likely-pathogenic (of 145) ClinVar copy-number / structural variants overlap TRARG1 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →