ArticleAnnals of clinical and translational neurology2015
De novo mutations in KIF1A cause progressive encephalopathy and brain atrophy.
Article in Annals of clinical and translational neurology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 71 papers, 1 of them a synthesis that pooled it.
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Who cites it
71 citing papers in PubMed, 1 synthesis or guideline pooled it, 122 citations in OpenAlex.
- Monoallelic KIF1A-related disorders: a multicenter cross sectional study and systematic literature review.Journal of neurology · 2022Pooled it
- Pathogenic KIF1A variants differentially disrupt axonal trafficking and impede synaptic development.The Journal of cell biology · 2026Article
- Mechanistic machine learning for prediction of prime editing outcomes.Nature biotechnology · 2026Article
- KIF1A-mediated trafficking is required for neuronal autophagy in human neurons.bioRxiv : the preprint server for biology · 2026Article
- Instrumented Three-Dimensional Gait Analysis in an Adult With KIF1A-Associated Neurological Disorder: A Case Report.Cureus · 2026Article
- The Long Haul: Microtubule Motors as the Essential Supply Line for Neuronal Longevity.Journal of neurochemistry · 2026Review
- Article
- Mechanistic machine learning enables interpretable and generalizable prediction of prime editing outcomes.bioRxiv : the preprint server for biology · 2026Article
- Pathogenic KIF1A variants differentially disrupt axonal trafficking and impede synaptic development.bioRxiv : the preprint server for biology · 2026Article
- Bioinformatics analysis of de novo missense variants inAmerican journal of translational research · 2026Article
- Non-transport functions of motor proteins in corticogenesis.Frontiers in cell and developmental biology · 2026Review
- Distinct Clinical Phenotypes in KIF1A-Associated Neurological Disorders Result from Different Amino Acid Substitutions at the Same Residue in KIF1A.Biomolecules · 2025Article
- Engine breakdown of lysosomes and related organelles and the resulting physiology.Frontiers in cell and developmental biology · 2025Review
- Genotype-phenotype correlations in 18 European patients with heterozygousFrontiers in medicine · 2025Article
- Case Report: Hereditary spastic paraplegia associated with monoallelic variant in the motor domain of KIF1A.Frontiers in human neuroscience · 2025Article
- Ophthalmic Findings in the KIF1A-Associated Neurologic Disorder (KAND).American journal of ophthalmology · 2024Article
- Cryo-EM unveils kinesin KIF1A's processivity mechanism and the impact of its pathogenic variant P305L.Nature communications · 2024Article
- Article
- A Model for Chemomechanical Coupling of Kinesin-3 Motor.Cellular and molecular bioengineering · 2024Article
- Tubulin CFEOM mutations both inhibit or activate kinesin motor activity.Molecular biology of the cell · 2024Article
11 more citing papers are in PubMed but not listed here.
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Authors and funding
20 authors at 10 institutions in 3 countries.
Funding
Abstract
objectiveTo determine the cause and course of a novel syndrome with progressive encephalopathy and brain atrophy in children.
methodsClinical whole-exome sequencing was performed for global developmental delay and intellectual disability; some patients also had spastic paraparesis and evidence of clinical regression. Six patients were identified with de novo missense mutations in the kinesin gene KIF1A. The predicted functional disruption of these mutations was assessed in silico to compare the calculated conformational flexibility and estimated efficiency of ATP binding to kinesin motor domains of wild-type (WT) versus mutant alleles. Additionally, an in vitro microtubule gliding assay was performed to assess the effects of de novo dominant, inherited recessive, and polymorphic variants on KIF1A motor function.
resultsAll six subjects had severe developmental delay, hypotonia, and varying degrees of hyperreflexia and spastic paraparesis. Microcephaly, cortical visual impairment, optic neuropathy, peripheral neuropathy, ataxia, epilepsy, and movement disorders were also observed. All six patients had a degenerative neurologic course with progressive cerebral and cerebellar atrophy seen on sequential magnetic resonance imaging scans. Computational modeling of mutant protein structures when compared to WT kinesin showed substantial differences in conformational flexibility and ATP-binding efficiency. The de novo KIF1A mutants were nonmotile in the microtubule gliding assay.
interpretationDe novo mutations in KIF1A cause a degenerative neurologic syndrome with brain atrophy. Computational and in vitro assays differentiate the severity of dominant de novo heterozygous versus inherited recessive KIF1A mutations. The profound effect de novo mutations have on axonal transport is likely related to the cause of progressive neurologic impairment in these patients.
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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.