ArticleJCI insight2021
Characterization of HNRNPA1 mutations defines diversity in pathogenic mechanisms and clinical presentation.
Article in JCI insight, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT02450851 (Clinical and Genetic Evaluation of Patients With Undiagnosed Disorders Through the Undiagnosed Diseases Network), which is not on this map. Cited by 45 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.
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.
Clinical and Genetic Evaluation of Patients With Undiagnosed Disorders Through the Undiagnosed Diseases Network
Who cites it
45 citing papers in PubMed, 69 citations in OpenAlex.
- Assessment of Aggregation- and Condensation-Prone Regions of Proteins Involved in Neurodegenerative, Neurological and Mental-State Diseases.Biomolecules · 2026Article
- YTHDC1 functions as a molecular chaperone to suppress ALS-linked hnRNPA1 mutants from aggregation.Nature communications · 2026Article
- Expansion of the Clinical and Genetic Spectra of hnRNPA1-Associated Distal Myopathy in Two Korean Families.Journal of clinical neurology (Seoul, Korea) · 2026Article
- Isoform-specific steric zippers drive aberrant assembly and mislocalization of shortened TDP-43.Science advances · 2026Article
- Heterogeneous nuclear ribonucleoprotein A1 (hnRNPA1) maintains muscle progenitor identity by stabilizing the Ppp1r1b-lncRNA-PRC2 complex.Nucleic acids research · 2026Article
- hnRNPA1-SF3B3 interaction drives radioresistance in oral squamous cell carcinoma by modulating MARF1 alternative splicing isoforms.Journal of experimental & clinical cancer research : CR · 2026Article
- In-Cell Proteomics Enables High-Resolution Spatial and Temporal Mapping of Early Xenopus tropicalis Embryos.Molecular & cellular proteomics : MCP · 2026Article
- Defining RNA oligonucleotides that reverse deleterious phase transitions of RNA-binding proteins with prion-like domains.Molecular cell · 2026Article
- Nuclear-import receptors remodel the dilute phase to suppress phase transitions of RNA-binding proteins with prion-like domains.bioRxiv : the preprint server for biology · 2025Article
- ALS-associated RNA-binding proteins promote UNC13A transcription through REST downregulation.The EMBO journal · 2025Article
- Nuclear Protein Aggregates Disrupt RNA Processing and Alter Biomechanics in a Muscle Cell Model of OPMD.Aging and disease · 2025Article
- Neuroaxonal Degeneration as a Converging Mechanism in Motor Neuron Diseases (MNDs): Molecular Insights into RNA Dysregulation and Emerging Therapeutic Targets.International journal of molecular sciences · 2025Review
- In vivo self-renewal and expansion of quiescent stem cells from a non-human primate.Nature communications · 2025Article
- Tunable metastability of condensates reconciles their dual roles in amyloid fibril formation.Molecular cell · 2025Article
- Stress granules: emerging players in neurodegenerative diseases.Translational neurodegeneration · 2025Review
- Oxidative stress-induced stress granules: a central link to protein aggregation in neurodegenerative diseases.Frontiers in neuroscience · 2025Article
- Review
- Nuclear functions regulated by the VRK1 kinase.Nucleus (Austin, Tex.) · 2024Review
- Nuclear pore dysfunction and disease: a complex opportunity.Nucleus (Austin, Tex.) · 2024Review
- Axonopathy Underlying Amyotrophic Lateral Sclerosis: Unraveling Complex Pathways and Therapeutic Insights.Neuroscience bulletin · 2024Review
Corrections and comments
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Authors and funding
26 authors at 10 institutions in 4 countries.
Funding
Abstract
Mutations in HNRNPA1 encoding heterogeneous nuclear ribonucleoprotein (hnRNP) A1 are a rare cause of amyotrophic lateral sclerosis (ALS) and multisystem proteinopathy (MSP). hnRNPA1 is part of the group of RNA-binding proteins (RBPs) that assemble with RNA to form RNPs. hnRNPs are concentrated in the nucleus and function in pre-mRNA splicing, mRNA stability, and the regulation of transcription and translation. During stress, hnRNPs, mRNA, and other RBPs condense in the cytoplasm to form stress granules (SGs). SGs are implicated in the pathogenesis of (neuro-)degenerative diseases, including ALS and inclusion body myopathy (IBM). Mutations in RBPs that affect SG biology, including FUS, TDP-43, hnRNPA1, hnRNPA2B1, and TIA1, underlie ALS, IBM, and other neurodegenerative diseases. Here, we characterize 4 potentially novel HNRNPA1 mutations (yielding 3 protein variants: *321Eext*6, *321Qext*6, and G304Nfs*3) and 2 known HNRNPA1 mutations (P288A and D262V), previously connected to ALS and MSP, in a broad spectrum of patients with hereditary motor neuropathy, ALS, and myopathy. We establish that the mutations can have different effects on hnRNPA1 fibrillization, liquid-liquid phase separation, and SG dynamics. P288A accelerated fibrillization and decelerated SG disassembly, whereas *321Eext*6 had no effect on fibrillization but decelerated SG disassembly. By contrast, G304Nfs*3 decelerated fibrillization and impaired liquid phase separation. Our findings suggest different underlying pathomechanisms for HNRNPA1 mutations with a possible link to clinical phenotypes.
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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.