ArticleHuman mutation2014
VARS2 and TARS2 mutations in patients with mitochondrial encephalomyopathies.
Article in Human mutation, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 72 papers, 2 of them syntheses that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
72 citing papers in PubMed, 2 syntheses or guidelines pooled it, 95 citations in OpenAlex.
- Epigenetic signatures relating to disease-associated genotypic burden in familial risk of bipolar disorder.Translational psychiatry · 2022Pooled it
- GWAS of clinically defined gout and subtypes identifies multiple susceptibility loci that include urate transporter genes.Annals of the rheumatic diseases · 2017Pooled it
- White matter disorders at the intersection of transcription, RNA processing and translation.Nature reviews. Neurology · 2026Review
- Identification of novel NDUFA3 variants in a patient with mitochondrial disorders.Pediatric research · 2026Article
- Novel Variants in VARS2 Demonstrate the Phenotypic Variability of a Rare Mitochondriopathy That Responds to Valine Supplementation.Journal of inherited metabolic disease · 2025Article
- A homozygous TARS2 variant is a novel cause of syndromic neonatal diabetes.Diabetic medicine : a journal of the British Diabetic Association · 2025Article
- Simultaneous determination of cytosolic aminoacyl-tRNA synthetase activities by LC-MS/MS.Nucleic acids research · 2024Article
- TARS2 c.470 C > G is a chinese-specific founder mutation in three unrelated families with mitochondrial encephalomyopathy.Orphanet journal of rare diseases · 2024Article
- Identification of Four Novel Candidate Genes for Non-syndromic Intellectual Disability in Pakistani Families.Biochemical genetics · 2024Article
- Association between de novo variants of nuclear-encoded mitochondrial-related genes and undiagnosed developmental disorder and autism.QJM : monthly journal of the Association of Physicians · 2024Article
- Genetic modifiers of cognitive decline in PSEN1 E280A Alzheimer's disease.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2024Article
- Expanding the Phenotypic Spectrum: Chronic Kidney Disease in a Patient with Combined Oxidative Phosphorylation Defect 21.Balkan journal of medical genetics : BJMG · 2023Article
- Clinical, neuroradiological, and molecular characterization of mitochondrial threonyl-tRNA-synthetase (TARS2)-related disorder.Genetics in medicine : official journal of the American College of Medical Genetics · 2023Article
- Mammalian mitochondrial translation infidelity leads to oxidative stress-induced cell cycle arrest and cardiomyopathy.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- The Role of Nuclear-Encoded Mitochondrial tRNA Charging Enzymes in Human Inherited Disease.Genes · 2022Review
- Mitochondrial Epilepsy, a Challenge for Neurologists.International journal of molecular sciences · 2022Review
- Article
- VARS2 Depletion Leads to Activation of the Integrated Stress Response and Disruptions in Mitochondrial Fatty Acid Oxidation.International journal of molecular sciences · 2022Article
- Knockdown of mitochondrial threonyl-tRNA synthetase 2 inhibits lung adenocarcinoma cell proliferation and induces apoptosis.Bioengineered · 2022Article
- Aminoacyl-tRNA synthetases in human health and disease.Frontiers in physiology · 2022Review
12 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
20 authors at 6 institutions in 3 countries.
Funding
Abstract
By way of whole-exome sequencing, we identified a homozygous missense mutation in VARS2 in one subject with microcephaly and epilepsy associated with isolated deficiency of the mitochondrial respiratory chain (MRC) complex I and compound heterozygous mutations in TARS2 in two siblings presenting with axial hypotonia and severe psychomotor delay associated with multiple MRC defects. The nucleotide variants segregated within the families, were absent in Single Nucleotide Polymorphism (SNP) databases and are predicted to be deleterious. The amount of VARS2 and TARS2 proteins and valyl-tRNA and threonyl-tRNA levels were decreased in samples of afflicted patients according to the genetic defect. Expression of the corresponding wild-type transcripts in immortalized mutant fibroblasts rescued the biochemical impairment of mitochondrial respiration and yeast modeling of the VARS2 mutation confirmed its pathogenic role. Taken together, these data demonstrate the role of the identified mutations for these mitochondriopathies. Our study reports the first mutations in the VARS2 and TARS2 genes, which encode two mitochondrial aminoacyl-tRNA synthetases, as causes of clinically distinct, early-onset mitochondrial encephalopathies.
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What OpenQuestion holds
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.