Trial reportProceedings of the National Academy of Sciences of the United States of America2013
Inhibition of TFG function causes hereditary axon degeneration by impairing endoplasmic reticulum structure.
Trial report in Proceedings of the National Academy of Sciences of the United States of America, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 50 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
50 citing papers in PubMed, 104 citations in OpenAlex.
- The Identification of Proteolytic Substrates of Calpain-5 with N-Terminomics.International journal of molecular sciences · 2025Article
- Article
- Dramatic response to crizotinib through MET phosphorylation inhibition in rare TFG-MET fusion advanced squamous cell lung cancer.The oncologist · 2025Article
- Venetoclax combined with ATRA shows promising therapeutic potential for TFG:: RARA variant APL: a case report.Frontiers in oncology · 2025Article
- Cell type-specific gene therapy confers protection against motor neuron disease caused by a TFG variant.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Review
- Characterization of a novel TFG variant causing autosomal recessive pure hereditary spastic paraplegia.Annals of clinical and translational neurology · 2024Article
- Pluripotent Stem Cells as a Preclinical Cellular Model for Studying Hereditary Spastic Paraplegias.International journal of molecular sciences · 2024Review
- A novel TFG variant of uncertain significance in amyotrophic lateral sclerosis: A case report and review of literature.Annals of medicine and surgery (2012) · 2022Article
- TFG regulates secretory and endosomal sorting pathways in neurons to promote their activity and maintenance.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Sclerosing Polycystic Adenoma: Conclusive Clinical and Molecular Evidence of Its Neoplastic Nature.Head and neck pathology · 2022Article
- Involvement of neuronal and muscular Trk-fused gene (TFG) defects in the development of neurodegenerative diseases.Scientific reports · 2022Article
- TRK-fused gene (TFG) regulates ULK1 stability via TRAF3-mediated ubiquitination and protects macrophages from LPS-induced pyroptosis.Cell death & disease · 2022Article
- Review
- Homozygous TFG gene variants expanding the mutational and clinical spectrum of hereditary spastic paraplegia 57 and a review of literature.Journal of human genetics · 2021Article
- Autophagy in major human diseases.The EMBO journal · 2021Review
- TFG is required for autophagy flux and to prevent endoplasmic reticulum stress in CH12 B lymphoma cells.Autophagy · 2021Article
- Deregulation of CLTC interacts with TFG, facilitating osteosarcoma via the TGF-beta and AKT/mTOR signaling pathways.Clinical and translational medicine · 2021Article
- TFG binds LC3C to regulate ULK1 localization and autophagosome formation.The EMBO journal · 2021Article
- Importance of lipids for upper motor neuron health and disease.Seminars in cell & developmental biology · 2021Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
16 authors at 6 institutions in 3 countries.
Funding
Abstract
Hereditary spastic paraplegias are a clinically and genetically heterogeneous group of gait disorders. Their pathological hallmark is a length-dependent distal axonopathy of nerve fibers in the corticospinal tract. Involvement of other neurons can cause additional neurological symptoms, which define a diverse set of complex hereditary spastic paraplegias. We present two siblings who have the unusual combination of early-onset spastic paraplegia, optic atrophy, and neuropathy. Genome-wide SNP-typing, linkage analysis, and exome sequencing revealed a homozygous c.316C>T (p.R106C) variant in the Trk-fused gene (TFG) as the only plausible mutation. Biochemical characterization of the mutant protein demonstrated a defect in its ability to self-assemble into an oligomeric complex, which is critical for normal TFG function. In cell lines, TFG inhibition slows protein secretion from the endoplasmic reticulum (ER) and alters ER morphology, disrupting organization of peripheral ER tubules and causing collapse of the ER network onto the underlying microtubule cytoskeleton. The present study provides a unique link between altered ER architecture and neurodegeneration.
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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.