ArticleHuman mutation2014
Impaired function is a common feature of neuropathy-associated glycyl-tRNA synthetase mutations.
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 48 papers.
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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.
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Who cites it
48 citing papers in PubMed, 61 citations in OpenAlex.
- Aminoacyl-tRNA Synthetases: Variant Classification, Functional Assays, and Emerging Therapeutic Strategies.Journal of inherited metabolic disease · 2026Review
- Recessive, pathogenic AARS1 variants display variable loss-of-function and dominant-negative effects.Disease models & mechanisms · 2025Article
- Yeast models for Charcot-Marie-Tooth disease-causing aminoacyl-tRNA synthetase alleles reveal the cellular basis of disease.IUBMB life · 2025Review
- Glycyl-tRNA sequestration is a unifying mechanism underlying GARS1-associated peripheral neuropathy.Nucleic acids research · 2025Article
- Isoleucine-to-valine substitutions support cellular physiology during isoleucine deprivation.Nucleic acids research · 2025Article
- An Adapted GeneSwitch Toolkit for Comparable Cellular and Animal Models: A Proof of Concept in Modeling Charcot-Marie-Tooth Neuropathy.International journal of molecular sciences · 2023Article
- Dominant aminoacyl-tRNA synthetase disorders: lessons learned fromFrontiers in neuroscience · 2023Review
- Genetic modifiers of synucleinopathies-lessons from experimental models.Oxford open neuroscience · 2023Review
- Pathogenic missense variants altering codon 336 of GARS1 lead to divergent dominant phenotypes.Human mutation · 2022Article
- Conformational sampling of CMT-2D associated GlyRS mutations.Brain multiphysics · 2022Article
- Review
- SIRT2-knockdown rescues GARS-induced Charcot-Marie-Tooth neuropathy.Aging cell · 2021Article
- Aminoacyl-tRNA synthetases in Charcot-Marie-Tooth disease: A gain or a loss?Journal of neurochemistry · 2021Review
- Mitochondrial Aminoacyl-tRNA Synthetase and Disease: The Yeast Contribution for Functional Analysis of Novel Variants.International journal of molecular sciences · 2021Review
- The Power of Yeast in Modelling Human Nuclear Mutations Associated with Mitochondrial Diseases.Genes · 2021Review
- An Integrated Approach to Studying Rare Neuromuscular Diseases Using Animal and Human Cell-Based Models.Frontiers in cell and developmental biology · 2021Review
- Associations between Neurological Diseases and Mutations in the Human Glycyl-tRNA Synthetase.Biochemistry. Biokhimiia · 2021Review
- Neuropathy-associated histidyl-tRNA synthetase variants attenuate protein synthesis in vitro and disrupt axon outgrowth in developing zebrafish.The FEBS journal · 2021Article
- GARS-related disease in infantile spinal muscular atrophy: Implications for diagnosis and treatment.American journal of medical genetics. Part A · 2020Article
- Overlapping spectrums: The clinicogenetic commonalities between Charcot-Marie-Tooth and other neurodegenerative diseases.Brain research · 2020Review
Corrections and comments
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Authors and funding
8 authors at 4 institutions in 1 country.
Funding
Abstract
Charcot-Marie-Tooth disease type 2D (CMT2D) is an autosomal-dominant axonal peripheral neuropathy characterized by impaired motor and sensory function in the distal extremities. Mutations in the glycyl-tRNA synthetase (GARS) gene cause CMT2D. GARS is a member of the ubiquitously expressed aminoacyl-tRNA synthetase (ARS) family and is responsible for charging tRNA with glycine. To date, 13 GARS mutations have been identified in patients with CMT disease. While functional studies have revealed loss-of-function characteristics, only four GARS mutations have been rigorously studied. Here, we report the functional evaluation of nine CMT-associated GARS mutations in tRNA charging, yeast complementation, and subcellular localization assays. Our results demonstrate that impaired function is a common characteristic of CMT-associated GARS mutations. Additionally, one mutation previously associated with CMT disease (p.Ser581Leu) does not demonstrate impaired function, was identified in the general population, and failed to segregate with disease in two newly identified families with CMT disease. Thus, we propose that this variant is not a disease-causing mutation. Together, our data indicate that impaired function is a key component of GARS-mediated CMT disease and emphasize the need for careful genetic and functional evaluation before implicating a variant in disease onset.
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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.