ArticleEMBO reports2022
ALS-linked KIF5A ΔExon27 mutant causes neuronal toxicity through gain-of-function.
Article in EMBO reports, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 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.
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Who cites it
40 citing papers in PubMed, 70 citations in OpenAlex.
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- The Long Haul: Microtubule Motors as the Essential Supply Line for Neuronal Longevity.Journal of neurochemistry · 2026Review
- Consequences of the Novel ALS-AssociatedNeurology. Genetics · 2026Article
- Kinesin-1 is highly flexible and adopts an open conformation in the absence of cargo.iScience · 2026Article
- KIF5A and ALS: a clinical and genetic description of a case series and review of literature.Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · 2026Review
- Rules of the road: how to turn off kinesin motors.The Biochemical journal · 2026Review
- Targeted plasma proteomics uncover proteins associated with KIF5A-linked SPG10 and ALS spectrum disorders.HGG advances · 2026Article
- Functional validation of the novel KIF5A p.R17Q VUS reveals defective axonal transport in iPSC-motoneurons from a SPG10 patient.Frontiers in genetics · 2026Article
- Genome annotations matter: characterizing Ensembl hg38 annotations from 2014 to 2023.BMC genomics · 2025Article
- Joubert syndrome 26 protein enforces compartmentalized motility of a ciliary kinesin.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Kinesins inOpen biology · 2025Review
- DNA tensiometer reveals catch-bond detachment kinetics of kinesin-1, -2 and -3.bioRxiv : the preprint server for biology · 2025Article
- Amyotrophic Lateral Sclerosis: Focus on Cytoplasmic Trafficking and Proteostasis.Molecular neurobiology · 2025Review
- ALS Mutations Shift the Isoelectric Point of the KIF5A C Terminal Inducing Protein Aggregation and TDP-43 Mislocalization.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2025Article
- Article
- One gene, many phenotypes: the role of KIF5A in neurodegenerative and neurodevelopmental diseases.Cell communication and signaling : CCS · 2025Review
- Using ALS to understand profilin 1's diverse roles in cellular physiology.Cytoskeleton (Hoboken, N.J.) · 2025Review
- The role of autophagy in the pathogenesis and treatment of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD).Autophagy reports · 2025Review
- Research progress of kinesin family in neurological diseases.Frontiers in cellular neuroscience · 2025Review
Corrections and comments
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Authors and funding
14 authors at 3 institutions in 2 countries.
Funding
Abstract
Mutations in the human kinesin family member 5A (KIF5A) gene were recently identified as a genetic cause of amyotrophic lateral sclerosis (ALS). Several KIF5A ALS variants cause exon 27 skipping and are predicted to produce motor proteins with an altered C-terminal tail (referred to as ΔExon27). However, the underlying pathogenic mechanism is still unknown. Here, we confirm the expression of KIF5A mutant proteins in patient iPSC-derived motor neurons. We perform a comprehensive analysis of ΔExon27 at the single-molecule, cellular, and organism levels. Our results show that ΔExon27 is prone to form cytoplasmic aggregates and is neurotoxic. The mutation relieves motor autoinhibition and increases motor self-association, leading to drastically enhanced processivity on microtubules. Finally, ectopic expression of ΔExon27 in Drosophila melanogaster causes wing defects, motor impairment, paralysis, and premature death. Our results suggest gain-of-function as an underlying disease mechanism in KIF5A-associated ALS.
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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.