ArticleNature chemical biology2022
Characterization of a patient-derived variant of GPX4 for precision therapy.
Article in Nature chemical biology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 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.
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Who cites it
47 citing papers in PubMed, 93 citations in OpenAlex.
- Mechanisms underlying propagation of ferroptotic cell death.Nature cell biology · 2026Review
- Revealing interactions between glutathione peroxidase 4 and phosphoinositides.bioRxiv : the preprint server for biology · 2026Article
- Design, Synthesis, and Protective Activity against Doxorubicin-Induced Cardiotoxicity of Novel Water-Soluble Small-Molecule GPx Mimics.ACS medicinal chemistry letters · 2026Article
- Genetics of selenoproteins and selenoprotein metabolism - An overview of current concepts and emerging aspects.Redox biology · 2026Review
- Dissecting Complex Interactions Between Ferroptosis and the Proteasome.bioRxiv : the preprint server for biology · 2026Article
- Validation of ferroptosis in zebrafish as a reliable model for phenotypic studies.Scientific reports · 2026Article
- PPARa-FSP1 axis modulates lipid peroxidation-induced neuronal ferroptosis to promote functional recovery in mouse model of traumatic spinal cord injury.Cellular and molecular life sciences : CMLS · 2026Article
- Lipidomics in Melanoma: Insights into Disease Progression and Therapeutical Targets.International journal of molecular sciences · 2026Review
- Decoding ferroptosis for cancer therapy.Nature reviews. Cancer · 2025Review
- "Several birds with one stone": exploring the potential of AI methods for multi-target drug design.Molecular diversity · 2025Article
- Polyphyllin VII promotes hepatic stellate cell ferroptosis via the HIC1/CX3CL1/GPX4 axis.Journal of pharmaceutical analysis · 2025Article
- Mechanisms of ferroptosis sensitization and resistance.Developmental cell · 2025Review
- PRMT5-mediated arginine methylation stabilizes GPX4 to suppress ferroptosis in cancer.Nature cell biology · 2025Article
- Palmitoylation-dependent regulation of GPX4 suppresses ferroptosis.Nature communications · 2025Article
- Recent Progress of Glutathione Peroxidase 4 Inhibitors in Cancer Therapy.Mini reviews in medicinal chemistry · 2025Review
- Research on the function of GPX4 in tumor-targeted treatment based on its molecular structure and features.Frontiers in oncology · 2025Review
- Pulling back the mitochondria's iron curtain.npj metabolic health and disease · 2025Review
- Mapping the oxidative landscape in cystic fibrosis: methodological frontiers and application.Frontiers in pharmacology · 2025Review
- Ferroptosis: mechanisms and therapeutic targets.MedComm · 2024Review
- GPX4 Promoter Hypermethylation Induced by Ischemia/Reperfusion Injury Regulates Hepatocytic Ferroptosis.Journal of clinical and translational hepatology · 2024Article
Corrections and comments
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Authors and funding
11 authors at 7 institutions in 3 countries.
Funding
Abstract
Glutathione peroxidase 4 (GPX4), as the only enzyme in mammals capable of reducing esterified phospholipid hydroperoxides within a cellular context, protects cells from ferroptosis. We identified a homozygous point mutation in the GPX4 gene, resulting in an R152H coding mutation, in three patients with Sedaghatian-type spondylometaphyseal dysplasia. Using structure-based analyses and cell models, including patient fibroblasts, of this variant, we found that the missense variant destabilized a critical loop, which disrupted the active site and caused a substantial loss of enzymatic function. We also found that the R152H variant of GPX4 is less susceptible to degradation, revealing the degradation mechanism of the GPX4 protein. Proof-of-concept therapeutic treatments, which overcome the impaired R152H GPX4 activity, including selenium supplementation, selective antioxidants and a deuterated polyunsaturated fatty acid were identified. In addition to revealing a general approach to investigating rare genetic diseases, we demonstrate the biochemical foundations of therapeutic strategies targeting GPX4.
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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.