ArticleHuman genomics2019
Mutations in ATP13A2 (PARK9) are associated with an amyotrophic lateral sclerosis-like phenotype, implicating this locus in further phenotypic expansion.
Article in Human genomics, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.
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Who cites it
37 citing papers in PubMed, 50 citations in OpenAlex.
- Article
- Progress in modelling ATP13A2-linked neurodegeneration.NPJ Parkinson's disease · 2026Review
- Clinical Evaluation of Three KRS Families and Cellular Analysis of Distinct ATP13A2 Mutations Reveal Different Levels of Iron Accumulation.Journal of neurochemistry · 2026Article
- Wild-typemedRxiv : the preprint server for health sciences · 2026Article
- ATP13A2-Mediated Spermine Export Modulates Lipid Catabolism in the Endolysosomal System of SH-SY5Y Cells.International journal of molecular sciences · 2026Article
- Bridging the gap in Parkinson's disease research: from general pathophysiology to advanced 3d cell culture models.Cell communication and signaling : CCS · 2025Review
- Phenotypic characterization of an Atp13a2 knockout rat model of Parkinson's disease.NPJ Parkinson's disease · 2025Article
- Entering the era of precision medicine to treat amyotrophic lateral sclerosis.Molecular neurodegeneration · 2025Review
- Polyamine homeostasisbioRxiv : the preprint server for biology · 2025Article
- Motor Neuron Involvement in Two ATP13A2-Related Families: ALS And HSP-Like Phenotypes.Movement disorders clinical practice · 2025Article
- Genetically encoded fluorescent reporter for polyamines.Nature communications · 2025Article
- The motor neuron m6A repertoire governs neuronal homeostasis and FTO inhibition mitigates ALS symptom manifestation.Nature communications · 2025Article
- Direct measurement of ATP13A2 polyamine-dependent ATPase activity following rapid purification of lysosomes.Methods in enzymology · 2025Article
- Nigral ATP13A2 depletion induces Parkinson's disease-related neurodegeneration in a pilot study in non-human primates.NPJ Parkinson's disease · 2024Article
- Adult-onset deletion of ATP13A2 in mice induces progressive nigrostriatal pathway dopaminergic degeneration and lysosomal abnormalities.NPJ Parkinson's disease · 2024Article
- Genetic heterogeneity in epilepsy and comorbidities: insights from Pakistani families.BMC neurology · 2024Article
- Nine Hereditary Movement Disorders First Described in Asia: Their History and Evolution.Journal of movement disorders · 2023Article
- Zebrafish as a Model Organism for Studying Pathologic Mechanisms of Neurodegenerative Diseases and other Neural Disorders.Cellular and molecular neurobiology · 2023Review
- The emerging mechanisms and functions of microautophagy.Nature reviews. Molecular cell biology · 2023Review
- ATP13A2 (PARK9) and basal ganglia function.Frontiers in neurology · 2023Review
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Authors and funding
11 authors at 6 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundAmyotrophic lateral sclerosis [1] is a genetically heterogeneous neurodegenerative disorder, characterized by late-onset degeneration of motor neurons leading to progressive limb and bulbar weakness, as well as of the respiratory muscles, which is the primary cause of disease fatality. To date, over 25 genes have been implicated as causative in ALS with C9orf72, SOD1, FUS, and TARDBP accounting for the majority of genetically positive cases.
resultsWe identified two patients of Italian and French ancestry with a clinical diagnosis of juvenile-onset ALS who were mutation-negative in any of the known ALS causative genes. Starting with the index case, a consanguineous family of Italian origin, we performed whole-exome sequencing and identified candidate pathogenic mutations in 35 genes, 27 of which were homozygous. We next parsed all candidates against a cohort of 3641 ALS cases; only ATP13A2 was found to harbor recessive changes, in a patient with juvenile-onset ALS, similar to the index case. In vivo complementation of ATP13A2 using a zebrafish surrogate model that focused on the assessment of motor neuron morphology and cerebellar integrity confirmed the role of this gene in central and peripheral nervous system maintenance and corroborated the damaging direction of effect of the change detected in the index case of this study.
conclusionsWe here expand the phenotypic spectrum associated with genetic variants in ATP13A2 that previously comprised Kufor-Rakeb syndrome, spastic paraplegia 78, and neuronal ceroid lipofuscinosis type 12 (CLN12), to also include juvenile-onset ALS, as supported by both genetic and functional data. Our findings highlight the importance of establishing a complete genetic profile towards obtaining an accurate clinical diagnosis.
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