TRIT1

Chr 1AR

tRNA isopentenyltransferase 1

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

NCBI Gene: 54802 ENSG00000043514 UniProt: Q9H3H1 OMIM: 617840

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.

OMIM ResearchSummary from RefSeq, OMIM, UniProt, Mechanism

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]

OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Combined oxidative phosphorylation deficiency 35MIM #617873

Clinical highlights

Gene–disease validity (ClinGen)

Definitive · mitochondrial disease · AR · ClinGen 2022

Interpreting a novel variant

Loss of function is the curated mechanism (Gene2Phenotype), though the gene is not strongly LoF-constrained in the population — weigh truncating variants against that tolerance.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.14

LOEUF

LOF

Mechanism· G2P

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

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?

0.78Z-score

OE missense 0.86 (0.78–0.96)

227 obs / 262.7 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.78 (0.54–1.14)

0≤0.351.4

Missense OE?0.86 (0.78–0.96)

0≤0.61.4

Synonymous OE?0.87

0≤1.21.6

LoF obs/exp: 19 / 24.4Missense obs/exp: 227 / 262.7Syn Z: 0.98

Background carrier burden — how many people carry a rare variant somewhere in TRIT1?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 100

569 rare PASS variants

Rare truncating (LoF)

1 in 250

107 rare PASS variants

Rare synonymous (reference)

1 in 630

197 rare PASS variants

Rare missense and truncating variants are carried at similar rates in TRIT1; this gene does not show strong loss-of-function constraint by this measure. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 170	1 in 230
South Asian	~43k	1 in 130	1 in 490
Remaining (unassigned)	~30k	1 in 90	1 in 350
European (Finnish)	~27k	1 in 290	1 in 500
Admixed American	~22k	1 in 120	1 in 480
African / African American	~21k	1 in 100	1 in 560
East Asian	~20k	1 in 130	1 in 870
Ashkenazi Jewish	~13k	1 in 240	1 in 470
Middle Eastern	~2,884	1 in 140	≈ 1 in 2,900

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): All 11 coding exons well covered in gnomAD exomes and genomes.? see exons ↓