Affinage

ATP1A3

Sodium/potassium-transporting ATPase subunit alpha-3 · UniProt P13637

Length
1013 aa
Mass
111.7 kDa
Annotated
2026-06-09
100 papers in source corpus 20 papers cited in narrative 20 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 7/7 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

ATP1A3 encodes the neuron-specific α3 catalytic subunit of the Na+/K+-ATPase, the active ion pump whose ouabain-sensitive ATPase activity maintains transmembrane Na+/K+ gradients required for neuronal excitability, and its expression is restricted to neuronal tissue of the brain and spinal cord (PMID:28465228, PMID:24236096). The pump assembles into cell-type-specific heteromeric complexes, pairing α3 with β1 in excitatory neurons and with β2 in inhibitory interneurons (PMID:34161264). Heterozygous and missense loss-of-function alleles cause a spectrum of dominant neurological disease — rapid-onset dystonia-parkinsonism (RDP/DYT12), alternating hemiplegia of childhood (AHC), and CAPOS — through several distinct biophysical lesions: reduction of catalytic ATPase activity (PMID:15260953, PMID:22842232, PMID:25656163, PMID:32653672), loss of Na+ affinity at the third (sodium-specific) ion-binding site via C-terminal perturbation (PMID:19351654, PMID:29305691), pathological cation leak of Na+ and protons (PMID:37043503), and temperature-dependent structural destabilization that triggers fever-induced surface loss of α3 (PMID:36462665). The most severe alleles act through a biogenesis defect: misfolded nascent α3 is retained in the ER, undergoes ERAD, activates the unfolded protein response via eIF2α, exerts a dominant-negative effect on endogenous α1 distribution, and sensitizes cells to apoptosis, a phenotype reversible by the chemical chaperone 4-phenylbutyrate (PMID:31425744, PMID:33144327). At the circuit level α3 dysfunction abolishes Na+/K+-ATPase-mediated afterhyperpolarization in motor neurons and dysregulates inhibitory transmission, producing hyperexcitability and dystonia (PMID:23652595, PMID:39533828), while complete loss is incompatible with normal respiratory rhythm and monoamine homeostasis (PMID:28465228). Beyond ion transport, the α3 intracellular loop binds the RNA-binding proteins Eif4g1, Pabpc1, and Fmrp to restrain ribosomal S6 phosphorylation and protein synthesis under stress (PMID:38804677). α3 dysfunction also impairs cardiac repolarization, causing short-QT and arrhythmic susceptibility (PMID:40029639). Restoring wild-type α3 pump activity by AAV9 gene delivery rescues disease phenotypes in mutant mice, establishing reduced pump function as the proximate cause (PMID:33577387).

Mechanistic history

Synthesis pass · year-by-year structured walk · 17 steps
  1. 2004 High

    Established ATP1A3 as a disease gene by linking missense mutations to rapid-onset dystonia-parkinsonism and tying them to impaired pump enzyme activity/stability.

    Evidence Mutation identification in RDP families with functional and structural analysis

    PMID:15260953

    Open questions at the time
    • Did not resolve which biophysical step of the pump cycle each mutation impairs
    • No in vivo circuit-level mechanism
  2. 2009 High

    Resolved one biophysical lesion: a C-terminal insertion reduces Na+ affinity at the third Na+ site without affecting biogenesis or membrane targeting, implicating the C-terminus in stabilizing E1/E2 conformations.

    Evidence Heterologous expression, Na+ affinity assays, structural modelling, ouabain survival assay

    PMID:19351654

    Open questions at the time
    • Generalizability to other RDP mutations unaddressed
    • No direct structure of mutant pump
  3. 2012 High

    Distinguished AHC from RDP mechanistically by showing AHC de novo mutations reduce ATPase activity without altering protein expression level.

    Evidence Exome sequencing plus ATPase activity and expression assays in patient cells

    PMID:22842232

    Open questions at the time
    • Did not explain phenotypic divergence given shared activity loss
    • No structural mapping of severity
  4. 2013 High

    Defined the cellular and synaptic consequences of α3 loss in vivo, localizing the subunit presynaptically and linking haploinsufficiency to enhanced inhibition and dystonia.

    Evidence Atp1a3 heterozygous KO mouse, immunohistochemistry, cerebellar slice electrophysiology, behavioral dystonia assay

    PMID:23652595

    Open questions at the time
    • Presynaptic mechanism for enhanced inhibition not fully resolved
    • Cerebellar focus leaves other circuits open
  5. 2013 Medium

    Extended pathology beyond ion transport, showing patient cells carry lysosomal granule defects and elevated cathepsin B driving apoptosis.

    Evidence Patient platelet/fibroblast morphology, CD63 flow cytometry, proteomics, cathepsin B and apoptosis assays

    PMID:23681173

    Open questions at the time
    • Causal link from pump dysfunction to lysosomal phenotype not established
    • Two cell types, single lab
  6. 2017 High

    Demonstrated α3 is essential for life by showing complete knockout causes perinatal lethality, respiratory rhythm failure, and monoamine dysregulation.

    Evidence Atp1a3 knockout mouse, c-Fos IHC, monoamine HPLC, brainstem electrophysiology

    PMID:28465228

    Open questions at the time
    • Cell-autonomous vs network origin of respiratory failure unresolved
    • Monoamine changes mechanism unclear
  7. 2018 High

    Provided direct biophysical evidence that the CAPOS mutation specifically disrupts Na+ binding/release at the third ion site through C-terminal perturbation.

    Evidence Heterologous expression, pump current electrophysiology, molecular dynamics simulation

    PMID:29305691

    Open questions at the time
    • Link from biophysical defect to CAPOS-specific clinical features not established
  8. 2019 Medium

    Identified protein misfolding and trafficking failure as the lesion behind the most severe phenotypes, with mutant α3 competing with α1 to set a fixed total subunit pool.

    Evidence Isogenic inducible HEK-293 lines, fractionation, ER/Golgi immunofluorescence, Western blot

    PMID:31425744

    Open questions at the time
    • In vivo relevance of competition model untested
    • Single cell system
  9. 2020 High

    Detailed the biogenesis defect mechanistically (ER retention, ERAD, UPR via eIF2α, dominant-negative effect on α1, apoptotic sensitization) and showed pharmacological correction by 4-PBA.

    Evidence Isogenic inducible cell lines, fractionation, UPR pathway analysis, 4-PBA rescue

    PMID:33144327

    Open questions at the time
    • Whether 4-PBA rescues function in neurons untested
    • Single lab cell model
  10. 2020 High

    Tested whether magnitude of pump dysfunction explains phenotype severity and found it does not, decoupling activity loss from RDP-vs-AHC outcome.

    Evidence 12 mutations in HEK cells and Xenopus oocytes, pump current and survival assays

    PMID:32653672

    Open questions at the time
    • What does determine severity remains unidentified
    • In vitro systems lack neuronal context
  11. 2021 High

    Mapped cell-type-specific subunit pairing, showing α3-β1 in excitatory and α3-β2 in inhibitory neurons and developmental shifts in expression.

    Evidence Single-cell RNA-seq of ~125,000 fetal cortical cells with in situ hybridization validation

    PMID:34161264

    Open questions at the time
    • Functional consequence of isoform pairing untested
    • Transcript-level pairing not validated at protein-complex level
  12. 2021 Medium

    Established that supplementing wild-type α3 pump activity is therapeutic, providing causal proof that pump deficiency drives disease.

    Evidence AAV9-Synapsin ATP1A3 delivery in D801N mice, ATPase assay, behavior, survival

    PMID:33577387

    Open questions at the time
    • Durability and translatability untested
    • Did not address dominant-negative alleles
  13. 2022 High

    Explained fever-triggered episodes by showing a mutation confers temperature-dependent destabilization with surface internalization and lysosomal routing at 39°C.

    Evidence Isogenic cells, transport assays at 37/39°C, LAMP1 immunofluorescence, cycloheximide chase, in vitro thermal stability

    PMID:36462665

    Open questions at the time
    • In vivo confirmation in neurons during fever lacking
    • Trafficking machinery mediating internalization unidentified
  14. 2023 High

    Identified cation leak as a distinct disease mechanism, with a variant allowing Na+ and proton leak associated with a milder phenotype.

    Evidence Electrophysiological ion transport kinetics and occlusion analysis in heterologous expression

    PMID:37043503

    Open questions at the time
    • Cellular consequences of leak in neurons untested
    • Single lab
  15. 2024 Medium

    Revealed a non-pumping moonlighting function: the α3 intracellular loop binds RNA-binding proteins to regulate translation and stress responses.

    Evidence Co-IP for Eif4g1/Pabpc1/Fmr1, siRNA, ICL ectopic expression, S6 phosphorylation, heat stress, iPSC neuron calcium imaging

    PMID:38804677

    Open questions at the time
    • Direct vs indirect binding not resolved by single Co-IP-based study
    • Physiological relevance of translation control in vivo untested
  16. 2025 High

    Connected α3 dysfunction to a circuit-level dystonia mechanism: loss of pump-mediated afterhyperpolarization and impaired Na+ extrusion produce motor neuron hyperexcitability.

    Evidence D801N knock-in mouse, motor neuron intracellular electrophysiology, sodium imaging, spinal network recordings

    PMID:39533828

    Open questions at the time
    • Translation to human motor circuits untested
    • Therapeutic correction at this level not shown
  17. 2025 High

    Extended α3 function to cardiac repolarization, showing the D801N variant shortens action potentials and causes afterdepolarizations underlying short-QT arrhythmia risk.

    Evidence Patient iPSC-derived cardiomyocytes, action potential recordings, cryo-EM domain mapping, clinical QTc

    PMID:40029639

    Open questions at the time
    • Mechanism linking K+-binding-domain variants to repolarization not fully resolved
    • In vivo arrhythmia modeling lacking

Open questions

Synthesis pass · forward-looking unresolved questions
  • What determines the divergent clinical phenotypes (RDP, AHC, CAPOS, spasticity, short-QT) given that activity-loss magnitude alone does not predict severity remains unresolved.
  • No unifying genotype-phenotype mechanistic model
  • Relative contribution of pump-loss, cation leak, misfolding, and moonlighting functions to specific syndromes unquantified

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140657 ATP-dependent activity 4 GO:0005215 transporter activity 3 GO:0016787 hydrolase activity 3 GO:0060089 molecular transducer activity 2 GO:0003723 RNA binding 1
Localization
GO:0005764 lysosome 2 GO:0005783 endoplasmic reticulum 2 GO:0005886 plasma membrane 2 GO:0005794 Golgi apparatus 1
Pathway
R-HSA-112316 Neuronal System 3 R-HSA-382551 Transport of small molecules 3 R-HSA-1643685 Disease 2 R-HSA-8953897 Cellular responses to stimuli 2
Partners
ATP1A1ATP1B1ATP1B2EIF4G1FMR1PABPC1
Complex memberships
Na+/K+-ATPase (α3-β1 / α3-β2 heteromer)

Evidence

Reading pass · 20 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2004 Six missense mutations in ATP1A3 (encoding the Na+/K+-ATPase α3 subunit) were identified in rapid-onset dystonia-parkinsonism (RDP/DYT12) families; functional studies and structural analysis indicated these mutations impair enzyme activity or stability of the Na+/K+ pump. Missense mutation identification, functional studies, structural analysis Neuron High 15260953
2012 De novo nonsynonymous ATP1A3 mutations in alternating hemiplegia of childhood (AHC) cause consistent reductions in ATPase activity without affecting protein expression level, distinguishing them mechanistically from RDP mutations which impair enzyme activity or stability. Exome sequencing, ATPase activity assays in patient-derived cells, protein expression analysis Nature genetics High 22842232
2009 An in-frame C-terminal insertion mutation in ATP1A3 causes RDP by drastically reducing Na+ affinity at the third Na+ binding site, without defects in protein biogenesis or plasma membrane targeting; structural modelling demonstrated the C-terminus interacts with the third Na+ binding site to stabilize E1/E2 conformations. Expression studies, functional Na+ affinity analysis, structural modelling, ouabain challenge survival assay Human molecular genetics High 19351654
2015 Novel ATP1A3 mutations (p.Gly358Val and p.Ile363Asn) localizing to the P domain result in significant reduction of Na,K-ATPase activity in vitro; ATP1A3 immunofluorescence in human brain tissue is prominently associated with interneurons in the cortex. In vitro ATPase activity assay, immunofluorescence in human brain tissue Epilepsia Medium 25656163
2013 In Atp1a3 heterozygous knockout mice, the α3 subunit is concentrated presynaptically at Purkinje cell soma (co-localizing with VGAT), and loss of one Atp1a3 allele enhances inhibitory neurotransmission at molecular-layer interneuron–Purkinje cell synapses via a presynaptic mechanism, leading to increased dystonia symptoms after cerebellar kainate injection. Immunohistochemistry, electrophysiology (patch-clamp of cerebellar slices), Atp1a3 heterozygous knockout mouse, behavioral dystonia assay The Journal of physiology High 23652595
2019 ATP1A3 mutations causing severe phenotypes (microcephaly, brain atrophy) produce protein misfolding during biosynthesis, resulting in impaired trafficking of the α3β complex from ER through Golgi to plasma membrane; additionally, exogenous mutant α3 competes with endogenous α1 such that their total is constant, predicting variable ratios of normal to mutant protein in patients. Tetracycline-inducible isogenic HEK-293 cell lines, subcellular fractionation, immunofluorescence for Golgi/ER markers, Western blotting, cell survival assays Neurobiology of disease Medium 31425744
2020 Severe ATP1A3 mutations (e.g., L924P) cause greater ER retention of nascent α3, more ER-associated degradation (ERAD), larger perturbation of Na,K-ATPase subunit subcellular distribution, greater eIF2α inactivation (unfolded protein response), altered distribution of endogenous α1 (dominant-negative-like effect), and pro-apoptotic sensitization via reduced BAD phosphorylation; the pharmacological corrector 4-phenylbutyrate reduces L924P ER retention and restores morphology. Isogenic inducible cell lines, subcellular fractionation, Western blotting, UPR pathway analysis, pharmacological rescue with 4-PBA The Journal of biological chemistry High 33144327
2018 The CAPOS mutation p.Glu818Lys in ATP1A3 specifically affects sodium binding to and release from the third (sodium-specific) ion-binding site of the pump, as demonstrated by in vitro electrophysiological studies; molecular dynamics simulations confirm structural perturbation of the C-terminal region. Heterologous expression, in vitro electrophysiology (pump current measurements), molecular dynamics simulation Human genetics High 29305691
2021 ATP1A3 is expressed in fetal cortical subplate excitatory neurons and postnatal inhibitory neurons (including parvalbumin interneurons); the Na+/K+-ATPase pump complex forms cell-type-specific α-β isoform combinations: α3-β1 in excitatory neurons and α3-β2 in inhibitory neurons, as shown by single-cell RNA sequencing of ~125,000 fetal cortical cells. mRNA in situ hybridization, single-cell RNA sequencing (Drop-seq) of ~125,000 fetal cortical cells and ~52,000 infant cortical nuclei Proceedings of the National Academy of Sciences of the United States of America High 34161264
2022 The p.Arg756His mutation in ATP1A3 reduces protein turnover rate and Na+ affinity and increases K+ affinity; at 39°C (fever), α3 protein level drops due to internalization from the cell surface and lysosomal/endosomal routing, without loss of β subunit; recovery requires new protein synthesis; heating in vitro causes activity loss 20-30-fold faster than wildtype, demonstrating temperature-dependent structural destabilization. Arg756 normally forms hydrogen bonds anchoring four linearly distant structural regions. Isogenic mammalian cell lines, transport activity assays at 37°C and 39°C, immunofluorescence for subcellular localization (LAMP1 marker), cycloheximide chase, in vitro heating activity assays The Journal of biological chemistry High 36462665
2020 Twelve RDP and AHC-specific ATP1A3 mutations expressed in HEK cells and Xenopus oocytes all showed functional impairment (lower cell survival and reduced pump current), but no difference in extent of impairment or expression level was found between RDP and AHC phenotypes, indicating that pump dysfunction magnitude alone does not determine disease severity. Transfected HEK cells, Xenopus oocyte electrophysiology (pump current measurement), cell survival assay Neurobiology of disease High 32653672
2017 Complete knockout of Atp1a3 (Atp1a3-/-) in mice results in perinatal seizures, failure of effective breathing, and death; knockout brains show elevated c-Fos expression in multiple regions (with unique cerebellar distribution) and higher dopamine and noradrenaline contents; brainstem preparations show abnormal respiratory rhythms, demonstrating α3 is required for normal respiratory rhythm generation and monoamine homeostasis. Atp1a3 knockout mouse, c-Fos immunohistochemistry, monoamine HPLC measurement, brainstem preparation electrophysiology, behavioral observation Brain research High 28465228
2023 The recurrent ATP1A3 p.Pro775Leu variant uniquely causes leakage of sodium ions and protons into the cell (cation leak), associated with impaired sodium binding/occlusion kinetics favouring states with fewer bound ions, producing a mild spasticity/intellectual disability phenotype distinct from other ATP1A3-related syndromes. Electrophysiological characterization of ion transport kinetics in heterologous expression system, biophysical analysis of sodium occlusion Brain : a journal of neurology High 37043503
2024 The intracellular loop (ICL) of ATP1A3 interacts with RNA-binding proteins Eif4g (Eif4g1), Pabpc1, and Fmrp (Fmr1) in mouse Neuro2a cells; siRNA depletion of Atp1a3 or expression of p.R756C ATP1A3-ICL causes excessive phosphorylation of ribosomal protein S6 and increased susceptibility to heat stress; patient iPSC-derived neurons with p.R756C showed reduced calcium influx in response to ATP stimulation. Co-immunoprecipitation/pulldown for RNA-binding protein interaction, siRNA knockdown, ectopic expression of ICL domain, S6 phosphorylation Western blotting, heat stress assay, iPSC-derived neurons, calcium imaging Disease models & mechanisms Medium 38804677
2025 In Atp1a3 mutant mice (D801N), motor neurons exhibit loss of Na+/K+-ATPase-mediated afterhyperpolarization and impaired intracellular sodium extrusion, resulting in reduced responsiveness of the spinal motor network to activity-dependent sodium rises and a hyperexcitable motor phenotype compatible with dystonia. Atp1a3 mutant mouse (D801N knock-in), intracellular electrophysiology of motor neurons, sodium imaging, spinal motor network recordings Brain : a journal of neurology High 39533828
2021 AAV9-mediated delivery of human ATP1A3 under the Synapsin promoter into Atp1a3 D801N mutant mice increased ouabain-sensitive ATPase activity in brain regions, reduced inducible hemiplegia spells, improved balance beam performance, and prolonged survival, demonstrating that supplementing wild-type α3 pump activity can rescue disease phenotypes. AAV9 gene delivery (intracerebroventricular and intracisterna magna injection), ATPase activity assay, behavioral testing, survival analysis in knock-in mice Human gene therapy Medium 33577387
2013 Platelets and fibroblasts from AHC patients with ATP1A3 mutations (D801N or E815K) show lysosomal granule structural and functional abnormalities (CD63+ granule defects) and significantly increased activated cathepsin B levels, leading to enhanced intrinsic apoptosis. Platelet and fibroblast morphology, flow cytometry (CD63), proteomic analysis (TMT), cathepsin B activity assay, apoptosis assay Journal of proteomics Medium 23681173
2025 In iPSC-derived cardiomyocytes from D801N ATP1A3 patients, the D801N variant shortens action potential duration, increases mean diastolic potential, and causes delayed afterdepolarizations compared to controls, consistent with short QT interval and arrhythmic susceptibility observed clinically; the D801N variant and other short-QT-associated variants localize to the potassium-binding domain of ATP1A3. iPSC-derived cardiomyocytes, action potential recordings, cryo-EM structure mapping, clinical QTc measurements JAMA pediatrics High 40029639
2016 The ATP1A3 G316S mutation modelled in C. elegans eat-6 (orthologue of ATP1A3) via CRISPR/Cas9 knock-in causes dominant loss-of-function at the neuromuscular junction: decreased pharyngeal pumping rate and hypersensitivity to aldicarb (acetylcholinesterase inhibitor), demonstrating impaired neuromuscular function. CRISPR/Cas9 knock-in in C. elegans, pharyngeal pumping assay, aldicarb sensitivity assay PloS one Medium 27936181
2013 The porcine ATP1A3 promoter drives expression specifically in embryonic brain and spinal cord neurons in transgenic zebrafish, confirming neuron-specific transcriptional activity; ATP1A3 mRNA expression is confined to neuronal tissue with expression detectable in embryonic porcine brain from 60 days of gestation. Transgenic zebrafish reporter assay, qRT-PCR tissue expression profiling, protein immunoblotting PloS one Medium 24236096

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2004 Mutations in the Na+/K+ -ATPase alpha3 gene ATP1A3 are associated with rapid-onset dystonia parkinsonism. Neuron 365 15260953
2012 De novo mutations in ATP1A3 cause alternating hemiplegia of childhood. Nature genetics 333 22842232
2012 Heterozygous de-novo mutations in ATP1A3 in patients with alternating hemiplegia of childhood: a whole-exome sequencing gene-identification study. The Lancet. Neurology 204 22850527
2014 Distinct neurological disorders with ATP1A3 mutations. The Lancet. Neurology 200 24739246
2007 The phenotypic spectrum of rapid-onset dystonia-parkinsonism (RDP) and mutations in the ATP1A3 gene. Brain : a journal of neurology 180 17282997
2014 A novel recurrent mutation in ATP1A3 causes CAPOS syndrome. Orphanet journal of rare diseases 151 24468074
2015 Clinical profile of patients with ATP1A3 mutations in Alternating Hemiplegia of Childhood-a study of 155 patients. Orphanet journal of rare diseases 126 26410222
2015 Novel mutations in ATP1A3 associated with catastrophic early life epilepsy, episodic prolonged apnea, and postnatal microcephaly. Epilepsia 105 25656163
2014 The expanding spectrum of neurological phenotypes in children with ATP1A3 mutations, Alternating Hemiplegia of Childhood, Rapid-onset Dystonia-Parkinsonism, CAPOS and beyond. Pediatric neurology 105 25447930
2014 The expanding clinical and genetic spectrum of ATP1A3-related disorders. Neurology 95 24523486
2015 Relapsing encephalopathy with cerebellar ataxia related to an ATP1A3 mutation. Developmental medicine and child neurology 79 26400718
2013 Identification of ATP1A3 mutations by exome sequencing as the cause of alternating hemiplegia of childhood in Japanese patients. PloS one 77 23409136
2012 ATP1A3 mutations in infants: a new rapid-onset dystonia-Parkinsonism phenotype characterized by motor delay and ataxia. Developmental medicine and child neurology 72 22924536
2010 Characterization of Atp1a3 mutant mice as a model of rapid-onset dystonia with parkinsonism. Behavioural brain research 70 20850480
2011 Decreased neuronal Na+, K+ -ATPase activity in Atp1a3 heterozygous mice increases susceptibility to depression-like endophenotypes by chronic variable stress. Genes, brain, and behavior 68 21418141
1998 Evidence for an allelic association between bipolar disorder and a Na+, K+ adenosine triphosphatase alpha subunit gene (ATP1A3). Biological psychiatry 67 9646882
2013 Enhanced inhibitory neurotransmission in the cerebellar cortex of Atp1a3-deficient heterozygous mice. The Journal of physiology 59 23652595
2020 TMT-based quantitative proteomics reveals suppression of SLC3A2 and ATP1A3 expression contributes to the inhibitory role of acupuncture on airway inflammation in an OVA-induced mouse asthma model. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 58 33341053
2014 ATP1A3 mutations and genotype-phenotype correlation of alternating hemiplegia of childhood in Chinese patients. PloS one 57 24842602
2022 The Phenotypic Continuum of ATP1A3-Related Disorders. Neurology 55 36192182
2017 Fever-Induced Paroxysmal Weakness and Encephalopathy, a New Phenotype of ATP1A3 Mutation. Pediatric neurology 54 28647130
2009 A C-terminal mutation of ATP1A3 underscores the crucial role of sodium affinity in the pathophysiology of rapid-onset dystonia-parkinsonism. Human molecular genetics 52 19351654
2021 ATP1A2- and ATP1A3-associated early profound epileptic encephalopathy and polymicrogyria. Brain : a journal of neurology 50 33880529
2017 ATP1A3-related disorders: An update. European journal of paediatric neurology : EJPN : official journal of the European Paediatric Neurology Society 49 29291920
2017 ATP1A3 mutations can cause progressive auditory neuropathy: a new gene of auditory synaptopathy. Scientific reports 48 29184165
2021 ATP1A3-Related Disorders: An Ever-Expanding Clinical Spectrum. Frontiers in neurology 47 33868146
2016 A novel de novo mutation in ATP1A3 and childhood-onset schizophrenia. Cold Spring Harbor molecular case studies 46 27626066
2021 Early role for a Na+,K+-ATPase (ATP1A3) in brain development. Proceedings of the National Academy of Sciences of the United States of America 44 34161264
2015 CAOS-Episodic Cerebellar Ataxia, Areflexia, Optic Atrophy, and Sensorineural Hearing Loss: A Third Allelic Disorder of the ATP1A3 Gene. Journal of child neurology 41 25895915
2019 Factors in the disease severity of ATP1A3 mutations: Impairment, misfolding, and allele competition. Neurobiology of disease 39 31425744
2013 Alternating hemiplegia of childhood in Denmark: clinical manifestations and ATP1A3 mutation status. European journal of paediatric neurology : EJPN : official journal of the European Paediatric Neurology Society 39 24100174
2019 Genotype-structure-phenotype relationships diverge in paralogs ATP1A1, ATP1A2, and ATP1A3. Neurology. Genetics 38 30842972
2014 Rapid-onset dystonia-parkinsonism associated with the I758S mutation of the ATP1A3 gene: a neuropathologic and neuroanatomical study of four siblings. Acta neuropathologica 38 24803225
2019 Revising rapid-onset dystonia-parkinsonism: Broadening indications for ATP1A3 testing. Movement disorders : official journal of the Movement Disorder Society 36 31361359
2018 Missense variants in ATP1A3 and FXYD gene family are associated with childhood-onset schizophrenia. Molecular psychiatry 34 29895895
2016 ATP1A3 Mutation in Adult Rapid-Onset Ataxia. PloS one 34 26990090
2016 The Genetic Homogeneity of CAPOS Syndrome: Four New Patients With the c.2452G>A (p.Glu818Lys) Mutation in the ATP1A3 Gene. Pediatric neurology 34 27091223
2020 Alternating Hemiplegia of Childhood: Understanding the Genotype-Phenotype Relationship of ATP1A3 Variations. The application of clinical genetics 31 32280259
2020 Misfolding, altered membrane distributions, and the unfolded protein response contribute to pathogenicity differences in Na,K-ATPase ATP1A3 mutations. The Journal of biological chemistry 28 33144327
2018 The CAPOS mutation in ATP1A3 alters Na/K-ATPase function and results in auditory neuropathy which has implications for management. Human genetics 28 29305691
2014 Heterozygous mice deficient in Atp1a3 exhibit motor deficits by chronic restraint stress. Behavioural brain research 26 24983657
2013 Molecular cloning and characterization of porcine Na⁺/K⁺-ATPase isoforms α1, α2, α3 and the ATP1A3 promoter. PloS one 25 24236096
2019 Gamabufotalin induces a negative feedback loop connecting ATP1A3 expression and the AQP4 pathway to promote temozolomide sensitivity in glioblastoma cells by targeting the amino acid Thr794. Cell proliferation 24 31746080
2015 CAPOS syndrome and hemiplegic migraine in a novel pedigree with the specific ATP1A3 mutation. Journal of the neurological sciences 24 26453127
2014 A novel ATP1A3 mutation with unique clinical presentation. Journal of the neurological sciences 24 24713507
2013 Alternating hemiplegia of childhood with a de novo mutation in ATP1A3 and changes in SLC2A1 responsive to a ketogenic diet. Pediatric neurology 24 24491413
2020 D-DEMØ, a distinct phenotype caused by ATP1A3 mutations. Neurology. Genetics 23 32802951
2015 Intermediate Phenotypes of ATP1A3 Mutations: Phenotype-Genotype Correlations. Tremor and other hyperkinetic movements (New York, N.Y.) 23 26417536
2019 Recessive Inheritance of Congenital Hydrocephalus With Other Structural Brain Abnormalities Caused by Compound Heterozygous Mutations in ATP1A3. Frontiers in cellular neuroscience 22 31616254
2018 ATP1A3-related epileptic encephalopathy responding to ketogenic diet. Brain & development 22 29395663
2018 Early-onset encephalopathy with paroxysmal movement disorders and epileptic seizures without hemiplegic attacks: About three children with novel ATP1A3 mutations. Brain & development 22 29861155
2017 Knockout of sodium pump α3 subunit gene (Atp1a3-/-) results in perinatal seizure and defective respiratory rhythm generation. Brain research 22 28465228
2016 De novo p.Arg756Cys mutation of ATP1A3 causes an atypical form of alternating hemiplegia of childhood with prolonged paralysis and choreoathetosis. BMC neurology 22 27634470
2014 Identical ATP1A3 mutation causes alternating hemiplegia of childhood and rapid-onset dystonia parkinsonism phenotypes. Pediatric neurology 20 25439493
2007 ATP1A3 mutation in the first asian case of rapid-onset dystonia-parkinsonism. Movement disorders : official journal of the Movement Disorder Society 20 17595045
2020 Comparative analysis of alternating hemiplegia of childhood and rapid-onset dystonia-parkinsonism ATP1A3 mutations reveals functional deficits, which do not correlate with disease severity. Neurobiology of disease 18 32653672
2021 Adeno-Associated Virus-Mediated Gene Therapy in the Mashlool, Atp1a3, Mouse Model of Alternating Hemiplegia of Childhood. Human gene therapy 16 33577387
2016 Treatment with Oral ATP decreases alternating hemiplegia of childhood with de novo ATP1A3 Mutation. Orphanet journal of rare diseases 16 27146299
2013 Functional studies and proteomics in platelets and fibroblasts reveal a lysosomal defect with increased cathepsin-dependent apoptosis in ATP1A3 defective alternating hemiplegia of childhood. Journal of proteomics 15 23681173
2020 ATP1A3-related epilepsy: Report of seven cases and literature-based analysis of treatment response. Journal of clinical neuroscience : official journal of the Neurosurgical Society of Australasia 14 31959558
2016 Beyond Dystonia-Parkinsonism: Chorea and Ataxia with ATP1A3 Mutations. Movement disorders clinical practice 14 30363590
2013 Asystole in alternating hemiplegia with de novo ATP1A3 mutation. European journal of medical genetics 14 24291144
2023 The role of ATP1A3 gene in epilepsy: We need to know more. Frontiers in cellular neuroscience 13 36866063
2021 Variants of ATP1A3 in residue 756 cause a separate phenotype of relapsing encephalopathy with cerebellar ataxia (RECA)-Report of two cases and literature review. Molecular genetics & genomic medicine 13 34342181
2018 De novo ATP1A3 and compound heterozygous NLRP3 mutations in a child with autism spectrum disorder, episodic fatigue and somnolence, and muckle-wells syndrome. Molecular genetics and metabolism reports 13 29922587
2021 Genetically altered animal models for ATP1A3-related disorders. Disease models & mechanisms 12 34612482
2017 Atp1a3-deficient heterozygous mice show lower rank in the hierarchy and altered social behavior. Genes, brain, and behavior 12 29057568
2015 Common variants of ATP1A3 but not ATP1A2 are associated with Chinese genetic generalized epilepsies. Journal of the neurological sciences 12 26003227
2023 Cation leak through the ATP1A3 pump causes spasticity and intellectual disability. Brain : a journal of neurology 11 37043503
2022 Molecular and clinical characteristics of ATP1A3-related diseases. Frontiers in neurology 11 35968298
2018 ATP1A3 spectrum disorders: A video-documented history of 7 genetically confirmed early onset cases. European journal of paediatric neurology : EJPN : official journal of the European Paediatric Neurology Society 11 29396171
2017 A de novo p.Arg756Cys mutation in ATP1A3 causes a distinct phenotype with prolonged weakness and encephalopathy triggered by fever. Brain & development 11 29066118
2016 In Vivo Modelling of ATP1A3 G316S-Induced Ataxia in C. elegans Using CRISPR/Cas9-Mediated Homologous Recombination Reveals Dominant Loss of Function Defects. PloS one 11 27936181
2020 Mutational and phenotypic expansion of ATP1A3-related disorders: Report of nine cases. Gene 10 32339621
2020 Long-term follow-up and novel genotype-phenotype analysis of monozygotic twins with ATP1A3 mutation in Alternating Hemiplegia of Childhood-2. European journal of medical genetics 10 32454213
2025 ATP1A3 Variants, Variably Penetrant Short QT Intervals, and Lethal Ventricular Arrhythmias. JAMA pediatrics 9 40029639
2022 Temperature instability of a mutation at a multidomain junction in Na,K-ATPase isoform ATP1A3 (p.Arg756His) produces a fever-induced neurological syndrome. The Journal of biological chemistry 9 36462665
2020 ATP1A3 mutation as a candidate cause of autosomal dominant cone-rod dystrophy. Human genetics 9 32440726
2022 ATP1A3 mutation in rapid-onset dystonia parkinsonism: New data and genotype-phenotype correlation analysis. Frontiers in aging neuroscience 8 35978945
2018 A case of early onset life-threatening epilepsy associated with a novel ATP1A3 gene variant. Brain & development 8 30392841
2024 ATP1A3 regulates protein synthesis for mitochondrial stability under heat stress. Disease models & mechanisms 7 38804677
2020 Epileptic encephalopathy with features of rapid-onset dystonia Parkinsonism and alternating hemiplegia of childhood: a novel combination phenotype associated with ATP1A3 mutation. Epileptic disorders : international epilepsy journal with videotape 7 32043468
2018 Long-term follow up of an adult with alternating hemiplegia of childhood and a p.Gly755Ser mutation in the ATP1A3 gene. Brain & development 7 29269014
2018 Further characterization of CAPOS/CAOS syndrome with the Glu818Lys mutation in the ATP1A3 gene: A case report. Brain & development 7 29625811
2018 Variants in the ATP1A3 Gene Mutations within Severe Apnea Starting in Early Infancy: An Observational Study of Two Cases with a Possible Relation to Epileptic Activity. Neuropediatrics 7 29801192
2018 Early Life Epilepsy and Episodic Apnea Revealing an ATP1A3 Mutation: Report of a Pediatric Case and Literature Review. Neuropediatrics 7 30011403
2001 Absence of a significant linkage between Na(+),K(+)-ATPase subunit (ATP1A3 and ATP1B3) genotypes and bipolar affective disorder in the old-order Amish. American journal of medical genetics 7 11353452
2025 Progressive central cardiorespiratory rate downregulation and intensifying epilepsy lead to sudden unexpected death in epilepsy in mouse model of the most common human ATP1A3 mutation. Epilepsia 6 39797721
2024 Childhood-related neural genotype-phenotype in ATP1A3 mutations: comprehensive analysis. Genes & genomics 6 38243045
2021 Auditory Neuropathy as the Initial Phenotype for Patients With ATP1A3 c.2452 G > A: Genotype-Phenotype Study and CI Management. Frontiers in cell and developmental biology 6 34692702
2020 Effect of Flunarizine on Alternating Hemiplegia of Childhood in a Patient with the p.E815K Mutation in ATP1A3: A Case Report. Case reports in neurology 6 33082768
2020 The Expanding Phenotypic Spectrums Associated with ATP1A3 Mutation in a Family with Rapid-Onset Dystonia Parkinsonism. Neuro-degenerative diseases 6 33326973
2015 ATP1A3 mutation in a Chinese girl with alternating hemiplegia of childhood--Potential target of treatment? Brain & development 6 25662428
2014 Genome sequencing identifies a novel mutation in ATP1A3 in a family with dystonia in females only. Journal of neurology 6 25359261
2023 Epilepsy with eyelid myoclonia in the setting of de novo pathogenic variant in ATP1A3. Epileptic disorders : international epilepsy journal with videotape 5 37293976
2022 ATP1A3-related phenotypes in Chinese children: AHC, CAPOS, and RECA. European journal of pediatrics 5 36484864
2021 Rapid-onset dystonia-parkinsonism with ATP1A3 mutation and left lower limb paroxysmal dystonia. Brain & development 5 33451880
2004 Refined linkage to the RDP/DYT12 locus on 19q13.2 and evaluation of GRIK5 as a candidate gene. Movement disorders : official journal of the Movement Disorder Society 5 15254951
2025 ATP1A3 dysfunction causes motor hyperexcitability and afterhyperpolarization loss in a dystonia model. Brain : a journal of neurology 4 39533828
2022 Chinese patients with p.Arg756 mutations of ATP1A3: Clinical manifestations, treatment, and follow-up. Pediatric investigation 4 35382416

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