ArticlePLoS genetics2013
tRNA methyltransferase homolog gene TRMT10A mutation in young onset diabetes and primary microcephaly in humans.
Article in PLoS genetics, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 81 papers, 2 of them syntheses that pooled it.
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Who cites it
81 citing papers in PubMed, 2 syntheses or guidelines pooled it, 123 citations in OpenAlex.
- Clinical and Molecular Heterogeneity Underlying Monogenic Causes of Pediatric Diabetes Associated to Brain Developmental Disorders.Clinical genetics · 2025Pooled it
- Emerging Role of Epitranscriptomics in Diabetes Mellitus and Its Complications.Frontiers in endocrinology · 2022Pooled it
- Trial
- Genotype-phenotype variability in TRMT10A deficiency: divergent developmental outcomes associated with biallelic loss-of-function variants.Journal of human genetics · 2026Article
- Molecular basis of tRNA substrate recognition and modification by the atypical SPOUT methyltransferase Trm10.Nucleic acids research · 2026Article
- Distinct Mitochondrial Central Dogma Gene Expression in the Buffalo Brain: A Comparative Transcriptomic Study with Metabolically Active Organs.Molecular neurobiology · 2026Article
- TRMT10A maintains lipid homeostasis independently of its tRNA mScience China. Life sciences · 2026Article
- 5'tRNA-derived fragments modulate β-cell homeostasis and islet macrophage activation in type 2 diabetes.Nature communications · 2026Article
- Update of the Methyltransferase Gene Family: Classification, Evolution and Biological Functions.Human genomics · 2026Review
- Emerging roles of tRNA modification-mediated codon-specific translational reprogramming in cancer biology.Cell death & disease · 2026Review
- Article
- Reconnaissance of the Good, the Bad, and the Ugly Role of tRNAs in Carcinogenesis and Metastasis.Experientia supplementum (2012) · 2026Review
- Characterization of the nucleolar localization signal of TRMT10A and its importance for the m1G9 methylation of tRNAs in mammalian cells.Journal of molecular cell biology · 2025Article
- Targeting tRNA methyltransferases: from molecular mechanisms to drug discovery.Science China. Life sciences · 2025Review
- The Secret Life of NJournal of molecular biology · 2025Review
- tsRNA modifications: An emerging layer of biological regulation in disease.Journal of advanced research · 2025Review
- Illness stress-induced transient hyperglycemia in a patient with a novel YIPF5 homozygous missense variant: expanding the phenotype.Hormones (Athens, Greece) · 2024Review
- TRMT10A dysfunction perturbs codon translation of initiator methionine and glutamine and impairs brain functions in mice.Nucleic acids research · 2024Article
- Roles and regulation of tRNA-derived small RNAs in animals.Nature reviews. Molecular cell biology · 2024Review
- Association of TRMT2B gene variants with juvenile amyotrophic lateral sclerosis.Frontiers of medicine · 2024Article
21 more citing papers are in PubMed but not listed here.
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Authors and funding
19 authors at 6 institutions in 4 countries.
Funding
Abstract
We describe a new syndrome of young onset diabetes, short stature and microcephaly with intellectual disability in a large consanguineous family with three affected children. Linkage analysis and whole exome sequencing were used to identify the causal nonsense mutation, which changed an arginine codon into a stop at position 127 of the tRNA methyltransferase homolog gene TRMT10A (also called RG9MTD2). TRMT10A mRNA and protein were absent in lymphoblasts from the affected siblings. TRMT10A is ubiquitously expressed but enriched in brain and pancreatic islets, consistent with the tissues affected in this syndrome. In situ hybridization studies showed that TRMT10A is expressed in human embryonic and fetal brain. TRMT10A is the mammalian ortholog of S. cerevisiae TRM10, previously shown to catalyze the methylation of guanine 9 (m(1)G9) in several tRNAs. Consistent with this putative function, in silico topology prediction indicated that TRMT10A has predominant nuclear localization, which we experimentally confirmed by immunofluorescence and confocal microscopy. TRMT10A localizes to the nucleolus of β- and non-β-cells, where tRNA modifications occur. TRMT10A silencing induces rat and human β-cell apoptosis. Taken together, we propose that TRMT10A deficiency negatively affects β-cell mass and the pool of neurons in the developing brain. This is the first study describing the impact of TRMT10A deficiency in mammals, highlighting a role in the pathogenesis of microcephaly and early onset diabetes. In light of the recent report that the type 2 diabetes candidate gene CDKAL1 is a tRNA methylthiotransferase, the findings in this family suggest broader relevance of tRNA methyltransferases in the pathogenesis of type 2 diabetes.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.