Affinage

ATP1A2

Sodium/potassium-transporting ATPase subunit alpha-2 · UniProt P50993

Length
1020 aa
Mass
112.3 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: 6/7 claims corpus-supported (86%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

ATP1A2 encodes the α2 catalytic subunit of the Na+/K+-ATPase, an ion pump whose function in the central nervous system supports clearance of extracellular K+ and neurotransmitters and thereby constrains neural excitability (PMID:12805306, PMID:23838748). Heterozygous loss-of-function mutations cause familial hemiplegic migraine type 2 (FHM2) through haploinsufficiency: a single inactivated allele is sufficient to trigger pathology (PMID:12539047, PMID:16437583). Distinct mutations impair pump function by distinct routes — defective plasma-membrane targeting (R908Q), temperature-sensitive protein instability (P979L), outright abolition of catalytic activity (G301R, G615R, C515Y), or altered voltage dependence and reduced extracellular K+ affinity (R1007W) — yet converge on reduced pump output (PMID:19372756, PMID:21398422, PMID:23838748, PMID:16437583, PMID:16110494). The depth of biochemical impairment scales with clinical severity, with the most damaging variants producing intellectual disability, polymicrogyria, and early lethality (PMID:33880529, PMID:34384358). In mouse models, reduced α2 activity lowers the threshold for cortical spreading depression and epileptiform activity, drives astrocyte Ca2+ hyperactivity during CSD, and produces region-specific synaptic abnormalities including enhanced dentate gyrus LTP and enlarged inhibitory currents in the amygdala that are abolished by hyperthermia — linking fever to symptomatic episodes (PMID:30446731, PMID:30922082, PMID:32237043, PMID:40465487). Biallelic truncating loss in humans yields a lethal syndromic polymicrogyria with complete absence of brain ATP1A2 protein, establishing that the pump is essential for brain morphogenesis (PMID:31608932). Beyond ion transport, ATP1A2 abundance is regulated by Parkin-dependent ubiquitylation, which modulates noradrenergic neuron pacemaking (PMID:30763678).

Mechanistic history

Synthesis pass · year-by-year structured walk · 18 steps
  1. 2003 High

    Established that ATP1A2 dysfunction causes human disease and defined the genetic mechanism — haploinsufficiency of the Na+/K+ pump α2 subunit underlies familial hemiplegic migraine type 2.

    Evidence Genetic linkage, mutation analysis, and functional loss-of-function assays in cellular models

    PMID:12539047

    Open questions at the time
    • Did not resolve which cell type (astrocyte vs neuron) drives pathology
    • No in vivo demonstration of the migraine-triggering mechanism
  2. 2003 High

    Defined the in vivo role of α2 in neurotransmitter clearance and neural activity control, showing homozygous loss causes selective neuronal apoptosis and impaired glutamate/GABA re-uptake.

    Evidence Atp1a2 knockout mice with c-Fos immunostaining, synaptosomal uptake assays, and behavioral testing

    PMID:12805306

    Open questions at the time
    • Mechanism linking impaired uptake to apoptosis not fully resolved
    • Did not address cortical spreading depression directly
  3. 2005 Medium

    Demonstrated that disease variants can be cleanly distinguished from neutral ones at the functional level, establishing complete loss of pump function as the pathogenic readout.

    Evidence Two-electrode voltage clamp in Xenopus oocytes and radiochemical ATPase assays comparing C515Y vs E174K

    PMID:16110494

    Open questions at the time
    • Single lab
    • Functional assays in heterologous systems may not capture astrocytic context
  4. 2006 Medium

    Linked the depth of functional loss to clinical severity, showing complete loss of function in the most severe FHM2 phenotypes with intellectual disability.

    Evidence Cellular survival assays of G615R in a heterologous expression system

    PMID:16437583

    Open questions at the time
    • Single functional assay type
    • No structural rationale for severity in this study
  5. 2009 Medium

    Revealed that FHM2 mutations act through mechanistically distinct routes beyond simple catalytic loss — namely defective membrane trafficking and temperature-sensitive instability.

    Evidence Xenopus oocyte voltage clamp plus HEK293FT transfection with immunofluorescence/Western blot at 28°C and 37°C

    PMID:19372756

    Open questions at the time
    • Did not test trafficking in neural cell types
    • Temperature sensitivity not validated in vivo
  6. 2010 Medium

    Placed the α subunit in a defined presynaptic signaling pathway, showing the ortholog modulates neurotransmitter release downstream of Gαq/PLC/BK-channel signaling.

    Evidence C. elegans eat-6 genetics, aldicarb and serotonin behavioral assays, synaptic-vesicle EM, and epistasis with EGL-30/EGL-8/SLO-1

    PMID:20442779

    Open questions at the time
    • Ortholog study; conservation of this pathway in mammalian ATP1A2 not established
    • Single lab
  7. 2011 Medium

    Confirmed at physiological temperature that a key FHM2 mutation abolishes pump function and mapped it to a structurally critical residue.

    Evidence Cell viability, Western blot, immunocytochemistry, and homology modeling of G301R in COS-1/HeLa at 37°C

    PMID:21398422

    Open questions at the time
    • Single mutation, single lab
    • Structural model not experimentally validated
  8. 2013 Medium

    Identified a voltage-dependent mechanism of loss — reduced K+ affinity at resting potential — directly linking mutant biophysics to impaired extracellular K+ clearance.

    Evidence Two-electrode voltage clamp of R1007W in Xenopus oocytes

    PMID:23838748

    Open questions at the time
    • Single mutation
    • No demonstration of impaired K+ clearance in tissue
  9. 2018 Medium

    Provided in vivo causal proof that reduced astrocytic α2 function lowers the threshold for cortical spreading depression and epileptiform activity.

    Evidence G301R knock-in heterozygous mice with cortical KCl application and electrocorticography

    PMID:30446731

    Open questions at the time
    • Single mutation knock-in
    • Astrocyte-specific causality inferred rather than cell-type-restricted manipulation
  10. 2018 Medium

    Broadened the phenotypic spectrum by showing α2 dysfunction in skeletal muscle can generate a depolarizing leak current causing hypokalaemic periodic paralysis.

    Evidence Two-electrode voltage clamp of a novel mutation in Xenopus oocytes under varying K+

    PMID:30423015

    Open questions at the time
    • Leak-current mechanism not confirmed in native muscle
    • Single mutation
  11. 2018 Medium

    Identified Parkin-dependent ubiquitylation as an upstream regulator of ATP1A2 turnover that shapes neuronal pacemaking.

    Evidence Ubiquitylome mass spectrometry, quantitative immunoblot, and patch-clamp in Parkin-KO mouse brain slices

    PMID:30763678

    Open questions at the time
    • Direct ubiquitylation of ATP1A2 not demonstrated
    • Causal link between abundance change and electrophysiology indirect
  12. 2019 Medium

    Established that biallelic loss of ATP1A2 is incompatible with brain morphogenesis and survival, defining the most severe end of the disease spectrum.

    Evidence Whole exome sequencing and immunohistochemistry showing absent ATP1A2 protein in post-mortem brain from two families

    PMID:31608932

    Open questions at the time
    • Developmental mechanism of polymicrogyria not resolved
    • No model recapitulating the human phenotype
  13. 2019 Medium

    Showed haploinsufficiency produces region-specific synaptic plasticity defects, with abnormal LTP confined to the dentate gyrus.

    Evidence Ex vivo field-recording LTP in dentate gyrus and CA1 of W887R/+ knock-in mice

    PMID:30922082

    Open questions at the time
    • Basis of regional selectivity unexplained
    • Single lab
  14. 2020 Medium

    Demonstrated that α2 haploinsufficiency causes astrocyte hyperactivity during CSD, providing a cellular correlate of lowered CSD threshold.

    Evidence In vivo G-CaMP7 calcium imaging of astrocytes and neurons during KCl-induced CSD in Atp1a2+/- mice

    PMID:32237043

    Open questions at the time
    • Link between astrocyte Ca2+ waves and migraine symptoms not directly tested
    • Single lab
  15. 2021 Medium

    Systematically correlated degree of pump impairment with clinical severity, including disruption of brain morphogenesis at the most severe end.

    Evidence Functional and survival assays of 14 ATP1A2/A3 variants in transfected COS-1 cells with genotype-phenotype analysis

    PMID:33880529

    Open questions at the time
    • Survival assay is an indirect proxy for in vivo function
    • Combined ATP1A2/A3 dataset
  16. 2021 Medium

    Refined the severity gradient, showing FHM-with-intellectual-disability mutations impair pump biochemistry more profoundly than pure FHM variants.

    Evidence Survival assays, Na+/K+-ATPase activity assays, whole-cell patch clamp, and homology modeling of multiple mutations in HEK293T/HeLa

    PMID:34384358

    Open questions at the time
    • Heterologous cell context
    • Some variants behaved like wild-type, limiting genotype-phenotype generalization
  17. 2023 Medium

    Revealed a non-canonical role in protein-aggregation control, showing astrocytic ATP1A2 knockdown reduces SOD1 aggregation yet worsens ALS progression.

    Evidence ASO-mediated astrocytic Atp1a2 knockdown in SOD1*G93A mice with aggregation Western blot, survival, and transcriptomics

    PMID:38015828

    Open questions at the time
    • Mechanism linking pump to aggregation unresolved
    • Dissociation between aggregation reduction and disease worsening unexplained
  18. 2025 Medium

    Provided a mechanism for fever-triggered episodes, showing haploinsufficiency enhances inhibitory neurotransmission that is abolished by hyperthermic stress.

    Evidence Patch-clamp recording of IPSCs/EPSCs in basolateral amygdala neurons of Atp1a2+/- mice at baseline and under hyperthermia

    PMID:40465487

    Open questions at the time
    • Molecular basis of hyperthermic loss of inhibition not defined
    • Single brain region

Open questions

Synthesis pass · forward-looking unresolved questions
  • It remains unresolved how reduced α2 pump activity is mechanistically transduced into cortical spreading depression and how non-canonical roles (TGF-β/Smad regulation, ER-stress protection, SOD1 aggregation) relate to the pump's transport function.
  • No unified model connecting ion-transport loss to CSD initiation
  • Non-pump functions reported only in cancer/cardiac cell lines (Low confidence) without mechanistic linkage to transport activity
  • Cell-type-specific contributions (astrocyte vs neuron vs muscle) not fully dissected

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140657 ATP-dependent activity 5 GO:0005215 transporter activity 4 GO:0016787 hydrolase activity 3
Localization
GO:0005886 plasma membrane 1
Pathway
R-HSA-112316 Neuronal System 4 R-HSA-382551 Transport of small molecules 3 R-HSA-1266738 Developmental Biology 2
Partners
PRKN
Complex memberships
Na+/K+-ATPase

Evidence

Reading pass · 20 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2003 Loss-of-function mutations in ATP1A2 (encoding the Na+/K+ pump α2 subunit) cause familial hemiplegic migraine type 2 (FHM2) via haploinsufficiency; functional data demonstrated that a single allele loss of function is sufficient to trigger the pathogenic mechanism. Genetic linkage, mutation analysis, and functional loss-of-function assays in cellular models Nature genetics High 12539047
2003 Homozygous knockout of Atp1a2 in mice causes selective neuronal apoptosis in the amygdala and piriform cortex associated with high c-Fos expression (neural hyperactivity), and impaired re-uptake of glutamate and GABA into crude synaptosome fractions (P2 fraction), indicating the α2 subunit is critical for neurotransmitter clearance and regulation of neural activity in these regions. Atp1a2 knockout mouse generation, c-Fos immunostaining, synaptosomal glutamate/GABA re-uptake assay, behavioral fear/anxiety testing in heterozygous mice The Journal of neuroscience High 12805306
2009 Certain FHM2 ATP1A2 mutations (R908Q) cause defective plasma membrane targeting rather than loss of catalytic activity; others (P979L) exhibit temperature-sensitive protein instability at 37°C but not 28°C, establishing plasma membrane mistargeting and protein instability as distinct pathophysiological mechanisms beyond simple loss of pump function. Expression in Xenopus oocytes (two-electrode voltage clamp) and transfection of HEK293FT cells with immunofluorescence and Western blot at different temperatures Channels (Austin, Tex.) Medium 19372756
2010 The C. elegans ATP1A2 homolog EAT-6 (Na+/K+-ATPase α subunit) modulates presynaptic acetylcholine neurotransmission and is required for serotonin-mediated inhibition of ACh release; genetic epistasis placed EAT-6 in a pathway with EGL-30 Gαq, EGL-8 phospholipase C, and SLO-1 BK channel signaling; eat-6 is expressed in ventral cord ACh motor neurons and its loss increases synaptic vesicle number. C. elegans genetics (eat-6 mutation and cell-specific RNAi), aldicarb paralysis assay, serotonin behavioral assay, electron microscopy of synaptic vesicles, genetic epistasis with Gαq/PLC/BK channel pathway mutants PloS one Medium 20442779
2011 The FHM2 ATP1A2 G301R mutation completely abolishes Na+/K+-ATPase function, confirmed in human cellular models at physiological temperature (37°C) by cell viability assays and Western blot; homology modeling placed G301 in a structurally critical position of the α2 subunit. Cell viability assays, Western blot, immunocytochemistry, homology modeling in COS-1/HeLa cells at 37°C Cephalalgia Medium 21398422
2013 The FHM2 ATP1A2 R1007W mutation causes loss of function via reduced ion pumping activity with more profound voltage dependence and decreased apparent affinity for extracellular K+ at resting membrane potential voltages, a mechanism distinct from other FHM2 mutations, predicted to impair K+ clearance. Two-electrode voltage clamp experiments in Xenopus oocytes Cephalalgia Medium 23838748
2018 The FHM2 ATP1A2 G301R knock-in heterozygous mouse model (α2+/G301R) shows increased susceptibility to both cortical spreading depression (CSD) and epileptiform activity in vivo, establishing that reduced α2-Na+/K+-ATPase function in astrocytes lowers the threshold for CSD and seizure-like events. In vivo cortical KCl application in awake head-restrained mice, electrocorticography recording of CSD and epileptiform activity Scientific reports Medium 30446731
2018 A novel ATP1A2 mutation causes hypokalaemic periodic paralysis with an anomalous inward leak current under hypokalaemic conditions and lower pump turnover rates under physiological K+ concentrations, demonstrating that α2-Na+/K+-ATPase dysfunction in skeletal muscle can produce depolarizing leak current sufficient to cause muscle inexcitability. Electrophysiological measurements of mutant pump activity in Xenopus oocytes (two-electrode voltage clamp under varying K+ concentrations) Brain Medium 30423015
2018 In Parkin-knockout mouse brain, ATP1A2 protein abundance is elevated (validated by quantitative immunoblot), and this is associated with altered electrophysiological properties of noradrenergic locus coeruleus neurons including accelerated pacemaker frequency and reduced slow afterhyperpolarization, suggesting Parkin-mediated ubiquitylation normally regulates ATP1A2 turnover and thereby modulates neuronal excitability. Mass spectrometry ubiquitylome profiling, quantitative immunoblot, patch-clamp electrophysiology in acute brain slices from aged Parkin-KO mice Neurobiology of disease Medium 30763678
2019 FHM2 KI mice (W887R/+) with 50% reduced α2-NKA expression show abnormally increased long-term potentiation (LTP) in the dentate gyrus but normal LTP in the CA1 hippocampal area, demonstrating region-specific synaptic plasticity abnormalities attributable to reduced astrocytic K+ and glutamate clearance. Ex vivo hippocampal slice electrophysiology (field recordings of LTP in dentate gyrus and CA1) in FHM2 W887R/+ knock-in mice Cephalalgia Medium 30922082
2020 In Atp1a2+/- heterozygous mice during cortical spreading depression, astrocytic Ca2+ wave propagation speed and the percentage of astrocytes with elevated Ca2+ were greater than in wild-type, demonstrating that haploinsufficiency of the α2 subunit leads to astrocyte hyperactivity during CSD. In vivo calcium imaging using G-CaMP7 transgenic reporter in astrocytes and neurons during KCl-induced CSD in Atp1a2+/- mice FEBS open bio Medium 32237043
2021 In vitro testing of 14 ATP1A2/A3 mutations in transfected COS-1 cells demonstrated impaired Na+/K+-ATPase pump activity (severe loss of function) for disease-associated variants; lack of cell survival in COS-1 correlated with the most severe clinical phenotypes including polymicrogyria and early lethality, establishing that severely impaired NKA pump function can disrupt brain morphogenesis. Transfection of COS-1 cells with mutant constructs, cell survival assays, in silico pathogenicity prediction Brain Medium 33880529
2021 ATP1A2 mutations causing FHM with intellectual disability (FHMEI: T378N, G615R, D718N) show more severe impairment of Na+/K+-ATPase biochemical activity than mutations causing pure FHM or FHM with epilepsy only; the ouabain-sensitive pump current of G615R was significantly reduced by whole-cell patch clamp, while G762S and R938P pump currents were comparable to wild-type, establishing a gradient of functional severity correlating with clinical phenotype. Cell survival assays, membrane protein extraction, Western blot, Na+/K+-ATPase activity assay, whole-cell patch-clamp electrophysiology in HEK293T/HeLa cells, homology modeling The journal of headache and pain Medium 34384358
2023 ASO-mediated knockdown of Atp1a2 in astrocytes of SOD1*G93A mice significantly reduced SOD1 protein aggregation in vivo, but accelerated disease onset and shortened lifespan despite no systemic toxicity; transcriptomics revealed upregulation of glutamate receptor signaling and complement activation pathways, indicating that astrocytic α2-Na+/K+-ATPase participates in SOD1 aggregation regulation but its loss worsens ALS disease progression. Antisense oligonucleotide (ASO) in vivo Atp1a2 knockdown in SOD1 mice, Western blot for SOD1 aggregation, survival analysis, transcriptomics PloS one Medium 38015828
2025 In Atp1a2+/- heterozygous mice, inhibitory postsynaptic currents (IPSCs) in the basolateral amygdala were consistently larger than in wild-type while excitatory postsynaptic currents (EPSCs) were comparable, indicating enhanced inhibitory neurotransmission due to α2-NKA haploinsufficiency; hyperthermic stress abolished this enhanced inhibition, providing a mechanism by which fever triggers neurological episodes in ATP1A2-related disorders. Acute brain slice electrophysiology (patch-clamp recording of IPSCs and EPSCs in BLA principal neurons) in Atp1a2+/- mice at baseline and under hyperthermic conditions Journal of neurophysiology Medium 40465487
2019 Homozygous truncating ATP1A2 variants in humans cause a lethal syndromic polymicrogyria with complete absence of immunodetectable ATP1A2 protein in brain, establishing that biallelic loss of function of the α2-Na+/K+-ATPase is incompatible with normal brain morphogenesis and neonatal survival. Whole exome sequencing, immunohistochemistry for ATP1A2 protein in post-mortem brain tissue from affected individuals Brain Medium 31608932
2006 The ATP1A2 G615R mutation causes complete loss of Na+/K+-ATPase function, as demonstrated by cellular survival assays, establishing haploinsufficiency as the mechanism underlying the most severe FHM2 phenotypes including permanent mental retardation. Cellular survival assays in heterologous expression system Annals of neurology Medium 16437583
2005 The ATP1A2 C515Y variant causes complete loss of Na+/K+-ATPase function comparable to known FHM mutations, as demonstrated by two-electrode voltage clamp in Xenopus oocytes and radiochemical ATPase activity measurements; by contrast, E174K showed no functional alteration in the same assays. Two-electrode voltage clamp in Xenopus oocytes, radiochemical ATPase activity assay Human mutation Medium 16110494
2018 ATP1A2 overexpression in prostate cancer cells inhibited cell proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT), and suppressed the TGF-β/Smad signaling pathway; conversely, ATP1A2 knockdown activated TGF-β/Smad signaling, and the effects of knockdown were reversed by a TGF-β/Smad pathway inhibitor (LY364947), placing ATP1A2 upstream of the TGF-β/Smad axis. ATP1A2 overexpression and siRNA knockdown in PC-3 and DU145 cells; clone formation, EdU, flow cytometry, transwell assays; Western blot for TGF-β/Smad pathway; in vivo xenograft in nude mice Translational andrology and urology Low 35242641
2018 ATP1A2 knockdown (siRNA) in rat cardiomyocytes subjected to anoxia-reoxygenation injury significantly elevated apoptosis and expression of ER stress markers CHOP, GRP78, and caspase-12, indicating that α2-Na+/K+-ATPase protects cardiomyocytes from A/R injury by inhibiting ER stress-related apoptosis. siRNA knockdown of ATP1A2 in rat cardiomyocytes, anoxia-reoxygenation injury model, flow cytometry apoptosis assay, Western blot for ER stress proteins Canadian journal of physiology and pharmacology Low 29394489

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2003 Haploinsufficiency of ATP1A2 encoding the Na+/K+ pump alpha2 subunit associated with familial hemiplegic migraine type 2. Nature genetics 701 12539047
2003 Novel mutations in the Na+, K+-ATPase pump gene ATP1A2 associated with familial hemiplegic migraine and benign familial infantile convulsions. Annals of neurology 260 12953268
2004 Alternating hemiplegia of childhood or familial hemiplegic migraine? A novel ATP1A2 mutation. Annals of neurology 127 15174025
2003 Degeneration of the amygdala/piriform cortex and enhanced fear/anxiety behaviors in sodium pump alpha2 subunit (Atp1a2)-deficient mice. The Journal of neuroscience : the official journal of the Society for Neuroscience 104 12805306
2010 De novo mutations in ATP1A2 and CACNA1A are frequent in early-onset sporadic hemiplegic migraine. Neurology 94 20837964
2007 Epilepsy as part of the phenotype associated with ATP1A2 mutations. Epilepsia 80 18028407
2005 Familial basilar migraine associated with a new mutation in the ATP1A2 gene. Neurology 77 16344534
2005 ATP1A2 mutations in 11 families with familial hemiplegic migraine. Human mutation 72 16088919
2016 ATP1A2 Mutations in Migraine: Seeing through the Facets of an Ion Pump onto the Neurobiology of Disease. Frontiers in physiology 67 27445835
2006 Severe episodic neurological deficits and permanent mental retardation in a child with a novel FHM2 ATP1A2 mutation. Annals of neurology 66 16437583
2005 Rare missense variants in ATP1A2 in families with clustering of common forms of migraine. Human mutation 60 16110494
2006 Migrainous vertigo: mutation analysis of the candidate genes CACNA1A, ATP1A2, SCN1A, and CACNB4. Headache 58 16866717
2004 No mutations in CACNA1A and ATP1A2 in probands with common types of migraine. Archives of neurology 57 15210532
2021 ATP1A2- and ATP1A3-associated early profound epileptic encephalopathy and polymicrogyria. Brain : a journal of neurology 50 33880529
2006 Two de novo mutations in the Na,K-ATPase gene ATP1A2 associated with pure familial hemiplegic migraine. European journal of human genetics : EJHG 50 16538223
2004 A novel missense ATP1A2 mutation in a Finnish family with familial hemiplegic migraine type 2. Neurogenetics 47 15133718
2013 Genetic effects of ATP1A2 in familial hemiplegic migraine type II and animal models. Human genomics 39 23561701
2019 Genotype-structure-phenotype relationships diverge in paralogs ATP1A1, ATP1A2, and ATP1A3. Neurology. Genetics 38 30842972
2018 The contribution of CACNA1A, ATP1A2 and SCN1A mutations in hemiplegic migraine: A clinical and genetic study in Finnish migraine families. Cephalalgia : an international journal of headache 38 29486580
2013 Screening of CACNA1A and ATP1A2 genes in hemiplegic migraine: clinical, genetic, and functional studies. Molecular genetics & genomic medicine 37 24498617
2007 Prolonged hemiplegic episodes in children due to mutations in ATP1A2. Journal of neurology, neurosurgery, and psychiatry 37 17435187
2006 A novel ATP1A2 mutation in a family with FHM type II. Cephalalgia : an international journal of headache 37 16472340
2011 Neurovascular changes in prolonged migraine aura in FHM with a novel ATP1A2 gene mutation. Journal of neurology, neurosurgery, and psychiatry 36 22013243
2008 Screen for CACNA1A and ATP1A2 mutations in sporadic hemiplegic migraine patients. Cephalalgia : an international journal of headache 33 18513263
2008 A novel de novo nonsense mutation in ATP1A2 associated with sporadic hemiplegic migraine and epileptic seizures. Journal of the neurological sciences 33 18644608
2018 Increased susceptibility to cortical spreading depression and epileptiform activity in a mouse model for FHM2. Scientific reports 32 30446731
2009 Impaired plasma membrane targeting or protein stability by certain ATP1A2 mutations identified in sporadic or familial hemiplegic migraine. Channels (Austin, Tex.) 32 19372756
2018 A novel ATP1A2 mutation in a patient with hypokalaemic periodic paralysis and CNS symptoms. Brain : a journal of neurology 31 30423015
2008 Severe attacks of familial hemiplegic migraine, childhood epilepsy and ATP1A2 mutation. Cephalalgia : an international journal of headache 30 18498390
1999 The Na,K-ATPase alpha4 gene (Atp1a4) encodes a ouabain-resistant alpha subunit and is tightly linked to the alpha2 gene (Atp1a2) on mouse chromosome 1. Biochemistry 29 10555956
2019 Ubiquitylome profiling of Parkin-null brain reveals dysregulation of calcium homeostasis factors ATP1A2, Hippocalcin and GNA11, reflected by altered firing of noradrenergic neurons. Neurobiology of disease 27 30763678
2006 The CACNA1A and ATP1A2 genes are not involved in dominantly inherited migraine with aura. American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics 27 16508934
2016 Recurrent coma and fever in familial hemiplegic migraine type 2. A prospective 15-year follow-up of a large family with a novel ATP1A2 mutation. Cephalalgia : an international journal of headache 26 27226003
2004 Alternating hemiplegia of childhood: no mutations in the second familial hemiplegic migraine gene ATP1A2. Neuropediatrics 26 15534763
2013 A novel ATP1A2 gene mutation in familial hemiplegic migraine and epilepsy. Cephalalgia : an international journal of headache 25 23918834
2011 A new Italian FHM2 family: clinical aspects and functional analysis of the disease-associated mutation. Cephalalgia : an international journal of headache 25 21398422
2008 A novel ATP1A2 gene mutation in an Irish familial hemiplegic migraine kindred. Headache 25 18184292
2007 Two novel functional mutations in the Na+,K+-ATPase alpha2-subunit ATP1A2 gene in patients with familial hemiplegic migraine and associated neurological phenotypes. Clinical genetics 25 18028456
2021 Early onset severe ATP1A2 epileptic encephalopathy: Clinical characteristics and underlying mutations. Epilepsy & behavior : E&B 24 33493807
2019 A novel lethal recognizable polymicrogyric syndrome caused by ATP1A2 homozygous truncating variants. Brain : a journal of neurology 24 31608932
2019 Biallelic loss of function variants in ATP1A2 cause hydrops fetalis, microcephaly, arthrogryposis and extensive cortical malformations. European journal of medical genetics 22 30690204
2017 Abnormal expression of ATP1A1 and ATP1A2 in breast cancer. F1000Research 22 28529692
2021 Functional correlation of ATP1A2 mutations with phenotypic spectrum: from pure hemiplegic migraine to its variant forms. The journal of headache and pain 21 34384358
2012 Genetic control of a central pattern generator: rhythmic oromotor movement in mice is controlled by a major locus near Atp1a2. PloS one 21 22675444
2019 Early Treatment in Acute Severe Encephalopathy Caused by ATP1A2 Mutation of Familial Hemiplegic Migraine Type 2: Case Report and Literature Review. Neuropediatrics 19 31766058
2013 Functional characterization of a novel C-terminal ATP1A2 mutation causing hemiplegic migraine and epilepsy. Cephalalgia : an international journal of headache 19 23838748
2007 First case of compound heterozygosity in Na,K-ATPase gene ATP1A2 in familial hemiplegic migraine. European journal of human genetics : EJHG 19 17473835
2000 Lack of association between temporal lobe epilepsy and a novel polymorphism in the alpha 2 subunit gene (ATP1A2) of the sodium potassium transporting ATPase. American journal of medical genetics 19 10686557
2017 An Infant With Epilepsy and Recurrent Hemiplegia due to Compound Heterozygous Variants in ATP1A2. Pediatric neurology 18 28811059
2014 A missense variant of the ATP1A2 gene is associated with a novel phenotype of progressive sensorineural hearing loss associated with migraine. European journal of human genetics : EJHG 18 25138102
2018 Clinical Benefit of NMDA Receptor Antagonists in a Patient With ATP1A2 Gene Mutation. Pediatrics 17 29610157
2013 A wide clinical phenotype spectrum in patients with ATP1A2 mutations. Journal of child neurology 17 24097848
2013 Clinical spectrum in three families with familial hemiplegic migraine type 2 including a novel mutation in the ATP1A2 gene. Cephalalgia : an international journal of headache 16 24096472
2010 A homolog of FHM2 is involved in modulation of excitatory neurotransmission by serotonin in C. elegans. PloS one 16 20442779
2010 Prolonged sporadic hemiplegic migraine associated with a novel de novo missense ATP1A2 gene mutation. Headache 15 21352219
2007 Recurrent ATP1A2 mutations in Portuguese families with familial hemiplegic migraine. Journal of human genetics 15 17952365
2018 Familial Hemiplegic Migraine With Asymmetric Encephalopathy Secondary to ATP1A2 Mutation: A Case Series. Journal of clinical neurophysiology : official publication of the American Electroencephalographic Society 14 28445178
2015 Common variants of ATP1A3 but not ATP1A2 are associated with Chinese genetic generalized epilepsies. Journal of the neurological sciences 12 26003227
2013 Acute encephalopathy in familial hemiplegic migraine with ATP1A2 mutation. BMJ case reports 12 23761507
2005 Analysis of chromosome 1 microsatellite markers and the FHM2-ATP1A2 gene mutations in migraine pedigrees. Neurological research 12 16157018
2019 Differential effect of FHM2 mutation on synaptic plasticity in distinct hippocampal regions. Cephalalgia : an international journal of headache 11 30922082
2013 Evidence for linkage of migraine in Rolandic epilepsy to known 1q23 FHM2 and novel 17q22 genetic loci. Genes, brain, and behavior 10 24286483
2012 Psychotic aura symptoms in familial hemiplegic migraine type 2 (ATP1A2). The journal of headache and pain 10 22661290
2005 No association between common variations in the human alpha 2 subunit gene (ATP1A2) of the sodium-potassium-transporting ATPase and idiopathic generalized epilepsy. Neuroscience letters 10 15911117
2022 Inhibition of the proliferation, invasion, migration, and epithelial-mesenchymal transition of prostate cancer cells through the action of ATP1A2 on the TGF-β/Smad pathway. Translational andrology and urology 9 35242641
2018 Sodium pump alpha-2 subunit (ATP1A2) alleviates cardiomyocyte anoxia-reoxygenation injury via inhibition of endoplasmic reticulum stress-related apoptosis. Canadian journal of physiology and pharmacology 9 29394489
2016 Familial Hemiplegic Migraine with Severe Attacks: A New Report with ATP1A2 Mutation. Case reports in neurological medicine 9 27818813
2013 Polymorphisms in migraine-associated gene, atp1a2, and ischemic stroke risk in a biracial population: the genetics of early onset stroke study. SpringerPlus 9 23459313
2019 Novel missense mutation in the ATP1A2 gene associated with atypical sporapedic hemiplegic migraine. BMJ case reports 8 31586957
2024 ATP1A2-related epileptic encephalopathy and movement disorder: Clinical features of three novel patients. Epileptic disorders : international epilepsy journal with videotape 7 38512072
2021 Familial hemiplegic migraine type 2 due to a novel missense mutation in ATP1A2. The journal of headache and pain 7 33711927
2019 An association analysis for 14 candidate genes mapping to meat quality quantitative trait loci in a Duroc pig population reveals that the ATP1A2 genotype is highly associated with muscle electric conductivity. Animal genetics 7 31633210
2012 A case of familial hemiplegic migraine associated with a novel ATP1A2 gene mutation. Pediatric neurology 7 22759692
2023 Targeted ASO-mediated Atp1a2 knockdown in astrocytes reduces SOD1 aggregation and accelerates disease onset in mutant SOD1 mice. PloS one 6 38015828
2021 A novel ATP1A2 variant associated with severe stepwise regression, hemiplegia, epilepsy and movement disorders in two unrelated patients. European journal of paediatric neurology : EJPN : official journal of the European Paediatric Neurology Society 6 33578253
2019 A Chinese family with familial hemiplegic migraine type 2 due to a novel missense mutation in ATP1A2. Cephalalgia : an international journal of headache 6 31053037
2017 De novo exonic duplication of ATP1A2 in Italian patient with hemiplegic migraine: a case report. The journal of headache and pain 6 28593511
2005 No evidence of ATP1A2 involvement in 12 multiplex Italian families with benign familial infantile seizures. Neuroscience letters 6 16026932
1999 Mapping of the Na+, K(+)-ATPase subunit alpha 2 (ATP1A2) and muscle phosphofructokinase (PFKM) genes in pig by somatic cell hybrid analysis. Animal genetics 6 10050286
2025 Exploring the association between familial hemiplegic migraine genes (CACNA1A, ATP1A2 and SCN1A) with migraine and epilepsy: A UK Biobank exome-wide association study. Cephalalgia : an international journal of headache 5 39781574
2022 Hemiplegic migraine type 2 with new mutation of the ATP1A2 gene in Japanese cases. Neuroscience research 5 35257835
2022 Comprehensive analysis identified a reduction in ATP1A2 mediated by ARID3A in abdominal aortic aneurysm. Journal of cellular and molecular medicine 5 35441443
2020 Astrocytes in Atp1a2-deficient heterozygous mice exhibit hyperactivity after induction of cortical spreading depression. FEBS open bio 5 32237043
2021 De novo ATP1A2 variants in two Chinese children with alternating hemiplegia of childhood upgraded the gene-disease relationship and variant classification: a case report. BMC medical genomics 4 33794876
2018 A Novel ATP1A2 Gene Variant Associated With Pure Sporadic Hemiplegic Migraine Improved After Patent Foramen Ovale Closure: A Case Report. Frontiers in neurology 4 29867740
2013 Sporadic Hemiplegic Migraine with ATP1A2 and Prothrombin Gene Mutations. Case reports in neurological medicine 3 24396618
2024 Network-based meta-analysis and confirmation of genes ATP1A2, FXYD1, and ADCY3 associated with cAMP signaling in breast tumors compared to corresponding normal marginal tissues. Cellular and molecular biology (Noisy-le-Grand, France) 2 39707785
2024 Clinical characterization of a novel ATP1A2 p.Gly615Glu mutation in nine family members with familial hemiplegic migraine. Brain communications 2 39723107
2023 A novel heterozygous ATP1A2 pathogenic variant in a Chinese child with MELAS-like alternating hemiplegia. Molecular genetics & genomic medicine 2 36749827
2016 Atp1a2 contributes modestly to alcohol-related behaviors. Alcohol (Fayetteville, N.Y.) 2 27814792
2008 Coexistence of CACNA1A, ATP1A2, and KCNN3 gene mutation in migraine patients with human platelet polymorphism. Neurosciences (Riyadh, Saudi Arabia) 2 21063360
2025 Atp1a2 and Kcnj9 Are Candidate Genes Underlying Sensitivity to Oxycodone-Induced Locomotor Activation and Withdrawal-Induced Anxiety-Like Behaviors in C57BL/6 Substrains. Genes, brain, and behavior 1 39801366
2024 Familial hemiplegic migraine type 2: a case report of an adolescent with ATP1A2 mutation. Frontiers in neurology 1 38379707
2024 Fetus with multiple congenital anomaly syndrome caused by novel variant in ATP1A2. Prenatal diagnosis 1 38549198
2024 A Case Report of Hemiplegic Migraine with Mutation in the ATP1A2 Gene. Pharmacogenomics and personalized medicine 1 39319208
2008 FHM3 in familial hemiplegic migraine is more resistant to mutation than FHM1 and FHM2. Journal of the neurological sciences 1 19007941
2026 Jujuboside A induces bladder cancer cell apoptosis by inhibiting ATP1A2-mediated mitochondrial energy metabolism regulation. Cancer biology & therapy 0 41533486
2025 Enhanced amygdala inhibitory neurotransmission and its vulnerability to hyperthermic stress in Atp1a2-deficient heterozygous mice. Journal of neurophysiology 0 40465487
2024 Atp1a2 and Kcnj9 are candidate genes underlying sensitivity to oxycodone-induced locomotor activation and withdrawal-induced anxiety-like behaviors in C57BL/6 substrains. bioRxiv : the preprint server for biology 0 38798314
2024 [Developmental and epileptic encephalopathy produced by the ATP1A2 mutation]. Zhurnal nevrologii i psikhiatrii imeni S.S. Korsakova 0 39072579

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