ArticleHuman genetics2016
De novo RRAGC mutation activates mTORC1 signaling in syndromic fetal dilated cardiomyopathy.
Article in Human genetics, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
What it found
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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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
23 citing papers in PubMed, 50 citations in OpenAlex.
- Interpreting human genetic variation at atomic resolution.Nature genetics · 2026Review
- Rapidly Progressive Infantile Dilated Cardiomyopathy in Long-Olsen-Distelmaier Syndrome Associated withGenes · 2026Article
- G3BP1 Succinylation at K413 is Critical for Cardiac Function by Modulating PI3K-AKT-mTOR Signal Axis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- mTOR signaling networks: mechanistic insights and translational frontiers in disease therapeutics.Signal transduction and targeted therapy · 2025Review
- Transcriptional reprogramming in oral squamous cell carcinoma.Scientific reports · 2025Article
- Ragopathies and the rising influence of RagGTPases on human diseases.Nature communications · 2024Review
- Raptor mediates the selective inhibitory effect of cardamonin on RRAGC-mutant B cell lymphoma.BMC complementary medicine and therapies · 2023Article
- RagD auto-activating mutations impair MiT/TFE activity in kidney tubulopathy and cardiomyopathy syndrome.Nature communications · 2023Article
- Regulation of mTORC1 by the Rag GTPases.Biochemical Society transactions · 2023Review
- The complex network of mTOR signalling in the heart.Cardiovascular research · 2022Review
- Next-Generation Sequencing Reveals Novel Genetic Variants for Dilated Cardiomyopathy in Pediatric Chinese Patients.Pediatric cardiology · 2022Article
- Structural bioinformatics enhances mechanistic interpretation of genomic variation, demonstrated through the analyses of 935 distinct RAS family mutations.Bioinformatics (Oxford, England) · 2021Article
- TFEB Overexpression, Not mTOR Inhibition, Ameliorates RagCInternational journal of molecular sciences · 2021Article
- The Roles of Post-Translational Modifications on mTOR Signaling.International journal of molecular sciences · 2021Review
- Analysis ofJournal of clinical medicine · 2020Article
- Architecture of human Rag GTPase heterodimers and their complex with mTORC1.Science (New York, N.Y.) · 2019Article
- RNA-seq as a tool for evaluating human embryo competence.Genome research · 2019Article
- Human Induced Pluripotent Stem-Cell-Derived Cardiomyocytes as Models for Genetic Cardiomyopathies.International journal of molecular sciences · 2019Review
- Whole-Exome Sequencing Reveals Novel Genetic Variation for Dilated Cardiomyopathy in Pediatric Chinese Patients.Pediatric cardiology · 2019Article
- New Insights Into the Role of mTOR Signaling in the Cardiovascular System.Circulation research · 2018Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
Idiopathic dilated cardiomyopathy (DCM) is a heritable, genetically heterogeneous disorder with variable age-dependent penetrance. We sought to identify the genetic underpinnings of syndromic, sporadic DCM in a newborn female diagnosed in utero. Postnatal evaluation revealed ventricular dilation and systolic dysfunction, bilateral cataracts, and mild facial dysmorphisms. Comprehensive metabolic and genetic testing, including chromosomal microarray, mitochondrial DNA and targeted RASopathy gene sequencing, and clinical whole exome sequencing for known cardiomyopathy genes was non-diagnostic. Following exclusion of asymptomatic DCM in the parents, trio-based whole exome sequencing was carried out on a research basis, filtering for rare, predicted deleterious de novo and recessive variants. An unreported de novo S75Y mutation was discovered in RRAGC, encoding Ras-related GTP binding C, an essential GTPase in nutrient-activated mechanistic target of rapamycin complex 1 (mTORC1) signaling. In silico protein modeling and molecular dynamics simulation predicted the mutation to disrupt ligand interactions and increase the GDP-bound state. Overexpression of RagC(S75Y) rendered AD293 cells partially insensitive to amino acid deprivation, resulting in increased mTORC1 signaling compared to wild-type RagC. These findings implicate mTORC1 dysregulation through a gain-of-function mutation in RagC as a novel molecular basis for syndromic forms of pediatric heart failure, and expand genotype-phenotype correlation in RASopathy-related syndromes.
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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.