TRIT1

Chr 1AR

tRNA isopentenyltransferase 1

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

NCBI Gene: 54802ENSG00000043514UniProt: Q9H3H1

This gene encodes a protein that that is targeted to the mitochondrion and modifies transfer RNAs (tRNAs) by adding a dimethylallyl group onto the adenine at position 37. This modification is important for maintaining the correct reading frame during protein translation. This gene is considered a tumor suppressor and its expression can decrease cell growth. Alternative splicing results in multiple transcripts variants, most of which are likely non-functional. [provided by RefSeq, Aug 2015]

Primary Disease Associations & Inheritance

Combined oxidative phosphorylation deficiency 35MIM #617873
AR
201
ClinVar variants
25
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— TRIT1
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
25 Pathogenic / Likely Pathogenic· 96 VUS of 201 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
1.14LOEUF
pLI 0.000
Z-score 1.01
OE 0.78 (0.54–1.14)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
0.78Z-score
OE missense 0.86 (0.78–0.96)
227 obs / 262.7 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.78 (0.54–1.14)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.86 (0.78–0.96)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.0.87
0≤1.21.6
LoF obs/exp: 19 / 24.4Missense obs/exp: 227 / 262.7Syn Z: 0.98

ClinVar Variant Classifications

201 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic12
Likely Pathogenic13
VUS96
Likely Benign48
Benign16
Conflicting5
12
Pathogenic
13
Likely Pathogenic
96
VUS
48
Likely Benign
16
Benign
5
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
2
0
10
0
12
Likely Pathogenic
6
3
4
0
13
VUS
0
85
11
0
96
Likely Benign
0
7
24
17
48
Benign
0
1
13
2
16
Conflicting
—5
Total8966219190

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

View 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.

Gene2Phenotype Curations

TRIT1-related tRNA isopentenyltransferase deficiency

limited
ARUndeterminedAbsent Gene Product, Altered Gene Product Structure, Decreased Gene Product Level
Dev. Disorders
G2P ↗
splice region variantframeshift variantmissense variantinframe deletioninframe insertion

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Combined oxidative phosphorylation deficiency 35

MIM #617873

Molecular basis of disorder known

Autosomal recessive
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Mevalonate pathway promotes liver cancer by suppressing ferroptosis through CoQ10 production and selenocysteine-tRNA modification.
Chen Y et al.·J Hepatol
2025
TRIT1 defect leads to a recognizable phenotype of myoclonic epilepsy, speech delay, strabismus, progressive spasticity, and normal lactate levels.
Muylle E et al.·J Inherit Metab Dis
2022Review
Targeting mitochondrial and cytosolic substrates of TRIT1 isopentenyltransferase: Specificity determinants and tRNA-i6A37 profiles.
Khalique A et al.·PLoS Genet
2020
To determine the role of TRIT1 in the diagnosis, prognosis and immunoinvasion of liver hepatocellular carcinoma.
Niu X et al.·Front Immunol
2025
TRIT1 deficiency: Two novel patients with four novel variants.
Smol T et al.·Eur J Med Genet
2022Case report
Defective i6A37 modification of mitochondrial and cytosolic tRNAs results from pathogenic mutations in TRIT1 and its substrate tRNA.
Yarham JW et al.·PLoS Genet
2014Case report
The Effect of tRNA([Ser]Sec) Isopentenylation on Selenoprotein Expression.
Fradejas-Villar N et al.·Int J Mol Sci
2021
The first Korean cases of combined oxidative phosphorylation deficiency 35 with two novel TRIT1 mutations in two siblings confirmed by clinical and molecular investigation.
Yoo S et al.·Brain Dev
2021Case report
Matchmaking facilitates the diagnosis of an autosomal-recessive mitochondrial disease caused by biallelic mutation of the tRNA isopentenyltransferase (TRIT1) gene.
Kernohan KD et al.·Hum Mutat
2017Case report
Genetic etiology of progressive pediatric neurological disorders.
Aaltio J et al.·Pediatr Res
2024
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools