TRIT1

Chr 1AR

tRNA isopentenyltransferase 1

Also known as: COXPD35, GRO1, IPPT, IPT, IPTase, MOD5, hGRO1

This protein catalyzes the transfer of a dimethylallyl group onto adenine at position 37 of specific cytosolic and mitochondrial tRNAs, forming N6-(dimethylallyl)adenosine (i6A37), which is essential for maintaining proper reading frame during protein translation and for selenoprotein expression. Biallelic mutations cause combined oxidative phosphorylation deficiency 35 through autosomal recessive inheritance. The pathogenic mechanism involves loss of tRNA modification function, leading to impaired mitochondrial protein synthesis and oxidative phosphorylation defects.

OMIMResearchSummary from RefSeq, OMIM, UniProt, Mechanism
DNmechanismARLOEUF 1.141 OMIM phenotype
Clinical SummaryTRIT1
🧬
Gene-Disease Validity (ClinGen)
mitochondrial disease · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

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
1.14LOEUF
pLI 0.000
Z-score 1.01
OE 0.78 (0.541.14)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
0.78Z-score
OE missense 0.86 (0.780.96)
227 obs / 262.7 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.78 (0.541.14)
00.351.4
Missense OE0.86 (0.780.96)
00.61.4
Synonymous OE0.87
01.21.6
LoF obs/exp: 19 / 24.4Missense obs/exp: 227 / 262.7Syn Z: 0.98
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
limitedTRIT1-related tRNA isopentenyltransferase deficiencyOTHERAR

Predictions shown for reference only — model trained on dominant genes, not applicable to AR conditions.

DN
0.6842th %ile
GOF
0.5170th %ile
LOF
0.3066th %ile

The Badonyi & Marsh prediction model was trained exclusively on dominant disease genes. Predictions are not reliable for genes with autosomal recessive inheritance and are shown at reduced opacity for reference only.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

TRIT1 · 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.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →