TRMU

Chr 22MitoAR

tRNA mitochondrial 2-thiouridylase

Also known as: LCAL3, MTO2, MTU1, TRMT

NCBI Gene: 55687ENSG00000100416UniProt: O75648

This nuclear gene encodes a mitochondrial tRNA-modifying enzyme. The encoded protein catalyzes the 2-thiolation of uridine on the wobble positions of tRNA(Lys), tRNA(Glu), and tRNA(Gln), resulting in the formation of 5-taurinomethyl-2-thiouridine moieties. Mutations in this gene may cause transient infantile liver failure. Polymorphisms in this gene may also influence the severity of deafness caused by mitochondrial 12S ribosomal RNA mutations. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Sep 2013]

Primary Disease Associations & Inheritance

{Deafness, mitochondrial, modifier of}MIM #580000
Mito
Liver failure, transient infantileMIM #613070
AR
UniProtDeafness, aminoglycoside-induced
UniProtLiver failure, infantile, transient
0
ClinVar variants
0
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— TRMU
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
Some data sources returned errors (1)

clinvarCount: Error: NCBI fetch failed: 429 https://eutils.ncbi.nlm.nih.gov/entrez/eutils/esearch.fcgi

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.
1.56LOEUF
pLI 0.000
Z-score -0.44
OE 1.10 (0.79–1.56)
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.
-0.33Z-score
OE missense 1.06 (0.96–1.18)
247 obs / 232.7 exp
Tolerant

Tolerant to missense variation

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.1.10 (0.79–1.56)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.1.06 (0.96–1.18)
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.1.42
0≤1.21.6
LoF obs/exp: 23 / 20.8Missense obs/exp: 247 / 232.7Syn Z: -3.15

ClinVar Variant Classifications

0 submitted variants in ClinVar

ClinVar

Protein Context — Lollipop Plot

TRMU · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

{Deafness, mitochondrial, modifier of}

MIM #580000

Molecular basis of disorder known

Mitochondrial

Liver failure, transient infantile

MIM #613070

Molecular basis of disorder known

Autosomal recessive
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Genotypic and phenotypic spectrum of infantile liver failure due to pathogenic TRMU variants.
Vogel GF et al.·Genet Med
2023
Reversible infantile mitochondrial diseases.
Boczonadi V et al.·J Inherit Metab Dis
2015Review
TRMU deficiency: A broad clinical spectrum responsive to cysteine supplementation.
Murali CN et al.·Mol Genet Metab
2021
Mitochondrial hepatopathies in the newborn period.
Fellman V et al.·Semin Fetal Neonatal Med
2011Review
microRNA-mediated differential expression of TRMU, GTPBP3 and MTO1 in cell models of mitochondrial-DNA diseases.
Meseguer S et al.·Sci Rep
2017Functional
Perioperative Management of Liver Retransplant in an Adult With a History of TRMU Alteration.
Matus M et al.·Exp Clin Transplant
2022Case report
Mutation in TRMU related to transfer RNA modification modulates the phenotypic expression of the deafness-associated mitochondrial 12S ribosomal RNA mutations.
Guan MX et al.·Am J Hum Genet
2006
Whole-exome sequencing identified novel compound heterozygous variants in a Chinese neonate with liver failure and review of literature.
Qin Z et al.·Mol Genet Genomic Med
2020Review
Correspondence on "Genotypic and phenotypic spectrum of infantile liver failure due to pathogenic TRMU variants" by Vogel et al.
Kulseth MA·Genet Med
2024
[TRMU MUTATIONS - REVERSIBLE INFANTILE LIVER FAILURE OR MULTISYSTEM DISORDER?].
Gil-Margolis M et al.·Harefuah
2018Case report
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.

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External Resources

Links to major genomics databases and tools