Affinage

ATN1

Atrophin-1 · UniProt P54259

Length
1190 aa
Mass
125.4 kDa
Annotated
2026-06-09
97 papers in source corpus 24 papers cited in narrative 24 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 9/9 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

ATN1/atrophin-1 is a ubiquitously expressed nuclear protein whose polyglutamine-expanded form causes the neurodegenerative disorder dentatorubral-pallidoluysian atrophy (DRPLA) through a gain-of-toxic-function mechanism (PMID:7842016, PMID:41624332). The protein carries a polyglutamine tract beginning at residue 484 flanked by proline-rich and arginine-glutamic acid (RE) dipeptide repeat motifs that organize its protein interactions (PMID:7842016). Full-length atrophin-1 localizes predominantly to the nucleus, and a caspase-3 cleavage event near the N-terminus (at 106DSLDG110) liberates a polyQ-containing fragment that partitions between nucleus and cytoplasm (PMID:9361003, PMID:9705838). Nuclear accumulation of the mutant protein is the principal driver of pathology: disrupting its nuclear export signal increases nuclear burden and worsens lifespan, locomotor, and neuropathological phenotypes in vivo (PMID:40263757). Within the nucleus the expanded protein acts as a transcriptional regulator, producing histone H3 hypoacetylation, global transcriptional repression, and age-dependent downregulation of synaptic and CREB-dependent genes that drives neuronal dysfunction prior to overt cell loss (PMID:16407196, PMID:19039037). Atrophin-1 engages defined partners through the regions surrounding its repeats — the RE-repeat protein RERE, which is recruited into nuclear aggregates by expanded polyQ (PMID:10814707); WW-domain proteins including HECT-domain ubiquitin ligases (PMID:9647693); IRSp53 via a proline-rich/SH3 contact diminished by polyQ expansion (PMID:10222779); and GAPDH (PMID:8612237). Expansion promotes transglutaminase-dependent aggregation, disulfide-linked and ubiquitinated cytoplasmic inclusions, and neuronal intranuclear inclusions (PMID:9462738, PMID:9735324, PMID:10381356). Downstream, the mutant protein causes lysosomal/autophagic flux blockade and mitochondrial dysfunction with oxidative stress (PMID:20543566). ASO-mediated knockdown of human ATN1 rescues behavioral and transcriptional phenotypes in a humanized DRPLA mouse model, confirming that lowering the mutant protein is sufficient to reverse pathology (PMID:41624332).

Mechanistic history

Synthesis pass · year-by-year structured walk · 14 steps
  1. 1994 High

    Cloning the DRPLA gene defined ATN1 as the molecular cause of the disease and revealed the polyglutamine tract and flanking repeat architecture that would frame all subsequent mechanistic work.

    Evidence cDNA cloning, sequencing, and Northern blot of the ubiquitously expressed 4.5 kb transcript

    PMID:7842016

    Open questions at the time
    • Sequence alone did not establish a molecular function or localization
    • No interacting partners or enzymatic activity identified
  2. 1995 High

    Identifying the endogenous ~190 kDa protein and its larger expanded counterpart in patient brain established that the disease form is an enlarged polyQ protein expressed in neurons.

    Evidence Immunoblotting and immunohistochemistry of normal and DRPLA human brain with C-terminal antibodies

    PMID:7647802

    Open questions at the time
    • Reported cytoplasmic localization in normal brain conflicted with later nuclear data
    • Did not address how expansion confers toxicity
  3. 1997 High

    Mapping a caspase-3 cleavage site at residue 106 showed ATN1 is a physiological protease substrate, providing a mechanism to generate the toxic polyQ-bearing fragment independent of repeat length.

    Evidence In vitro cleavage with recombinant caspase-3 and site-directed mutagenesis in apoptotic cells

    PMID:9361003

    Open questions at the time
    • Did not establish whether cleavage is required for in vivo toxicity
    • In vivo relevance of the fragment to DRPLA pathology untested at this stage
  4. 1998 High

    Localization and aggregation studies linked the caspase-3 fragment and polyQ expansion to nuclear/cytoplasmic aggregate formation and transglutaminase-dependent apoptosis, building the first toxic-fragment model.

    Evidence GFP-fusion localization, truncation constructs, and transglutaminase-inhibitor rescue in COS-7 cells

    PMID:9462738 PMID:9705838

    Open questions at the time
    • Cell-line overexpression may not reflect neuronal context
    • Whether aggregation is causal or a bystander of toxicity unresolved
  5. 1998 Medium

    Yeast two-hybrid and binding assays defined a set of physical partners (WW-domain HECT ubiquitin ligases and MAGUK/PDZ proteins) acting through regions near the polyQ tract, suggesting ATN1 operates in protein-interaction networks linked to ubiquitination.

    Evidence Yeast two-hybrid screen with in vitro binding confirmation of 4 of 5 interactors

    PMID:9647693

    Open questions at the time
    • Functional consequence of each interaction undefined
    • No demonstration of in vivo ubiquitination through these ligases at this stage
  6. 1999 Medium

    Demonstration of disulfide-linked, pathologically ubiquitinated cytoplasmic inclusions in DRPLA brain connected expanded ATN1 to aberrant protein complexes in affected lesions.

    Evidence Reducing/non-reducing immunoblotting and double-label immunohistochemistry with anti-ubiquitin in human brain

    PMID:10381356 PMID:9735324

    Open questions at the time
    • Ubiquitination machinery responsible not identified
    • Causal link between inclusions and neuronal dysfunction not shown
  7. 1999 Medium

    Comparing neuronal and non-neuronal cells showed full-length mutant ATN1 aggregates preferentially in neuronal nuclei and that intranuclear aggregation alone is insufficient for apoptosis, refining the toxicity model toward neuron-specific nuclear processes.

    Evidence Adenoviral expression of full-length and truncated Q82 constructs in PC12 cells versus fibroblasts with apoptosis readouts

    PMID:10332031

    Open questions at the time
    • Molecular basis of neuron-specific nuclear targeting undefined
    • Dissociated aggregation from death without identifying the toxic species
  8. 2000 Medium

    Identification of RERE as an RE-repeat-dependent partner whose binding is enhanced by polyQ expansion, plus recruitment of RERE into ATN1 nuclear aggregates, placed atrophin-1 in a nuclear protein network altered by expansion.

    Evidence Reciprocal immunoprecipitation, in vitro binding, and co-localization microscopy

    PMID:10814707

    Open questions at the time
    • Transcriptional or functional output of the ATN1-RERE complex not defined
    • Single lab without orthogonal in vivo validation
  9. 2001 Medium

    Transgenic mice showed mutant atrophin-1 accumulates exclusively in neuronal nuclei, distinguishing its localization behavior from huntingtin and tying nuclear inclusions to behavioral phenotypes.

    Evidence Neuropathology, immunohistochemistry, and behavioral testing in transgenic mice

    PMID:11442350

    Open questions at the time
    • Did not isolate which nuclear function drives behavior
    • Correlative association between inclusions and phenotype
  10. 2005 High

    Demonstrating histone H3 hypoacetylation and failure of wild-type rescue established a chromatin-level transcriptional repression mechanism that is a gain of toxic function rather than simple dominant-negative loss.

    Evidence Histone acetylation biochemistry, genetic and HDAC-inhibitor rescue, and behavior/survival assays in Q118 mice

    PMID:16407196

    Open questions at the time
    • Direct genomic targets of repression not mapped
    • Mechanism connecting ATN1 to HDAC activity unresolved
  11. 2008 High

    Linking age-dependent nuclear accumulation to electrophysiological and synaptic deficits and downregulation of CREB-dependent genes established neuronal dysfunction—not loss—as the primary pathophysiological process.

    Evidence Electrophysiology, morphology, and expression profiling in Q129 transgenic mice

    PMID:19039037

    Open questions at the time
    • Direct CREB-pathway mechanism not biochemically dissected
    • Reversibility of dysfunction not tested
  12. 2010 Medium

    Drosophila work identified lysosomal dysfunction and a post-fusion autophagic flux block as a clearance defect contributing to neurodegeneration, and showed boosting autophagy is detrimental in this context.

    Evidence Drosophila genetics with autophagy pathway and lysosomal function assays

    PMID:20543566

    Open questions at the time
    • Molecular step at which flux is blocked not defined
    • Relevance to mammalian neurons untested in this study
  13. 2025 High

    Selective NES mutation versus NLS mutation in transgenic mice causally demonstrated that nuclear localization of mutant ATN1 drives pathology, converting correlative localization data into a mechanism.

    Evidence Site-directed mutagenesis of NLS/NES in transgenic mice with behavioral and neuropathological readouts

    PMID:40263757

    Open questions at the time
    • Nuclear effector mechanism downstream of accumulation not pinpointed
    • Contribution of cleavage fragment versus full-length not separated
  14. 2025 High

    Allele-specific ASO knockdown rescue in a fully humanized knock-in model provided definitive evidence that DRPLA is a gain-of-function disease and that lowering mutant ATN1 is therapeutically sufficient.

    Evidence Human-specific ASO in Atn1 112-CAG knock-in mice with behavioral and RNA-seq endpoints

    PMID:41624332

    Open questions at the time
    • Durability and CNS-wide distribution of rescue not fully characterized
    • Does not identify the molecular toxic species being lowered

Open questions

Synthesis pass · forward-looking unresolved questions
  • The direct nuclear effector mechanism by which expanded ATN1 represses transcription—the chromatin-modifying complex it engages and its genomic binding sites—remains undefined, as does how nuclear repression, mitochondrial stress, and autophagic blockade are causally ordered.
  • No mapped genomic targets or defined repressive complex
  • Causal hierarchy among transcriptional, mitochondrial, and lysosomal phenotypes unresolved
  • Role of the caspase-3 fragment versus full-length protein in vivo unsettled

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060089 molecular transducer activity 3 GO:0140110 transcription regulator activity 2
Localization
GO:0005634 nucleus 4 GO:0005829 cytosol 3 GO:0005635 nuclear envelope 1
Pathway
R-HSA-5357801 Programmed Cell Death 2 R-HSA-74160 Gene expression (Transcription) 2 R-HSA-9612973 Autophagy 1
Partners
GAPDHIRSP53REREWWP1WWP2

Evidence

Reading pass · 24 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1994 ATN1 (DRPLA gene) encodes a 1184-amino acid protein containing a polyglutamine tract starting at amino acid 484, along with a homo-proline track, two stretches of arginine-glutamic acid dipeptide repeats, and a stretch of alternating histidine residues. The gene is ubiquitously expressed as a single 4.5 kb transcript. cDNA cloning, sequencing, and Northern blot analysis Nature genetics High 7842016
1995 The ATN1/DRPLA gene product is a ~190 kDa protein localized predominantly in neuronal cytoplasm in normal human brain; DRPLA patient brains contain a larger ~205 kDa protein corresponding to the expanded polyglutamine form. Immunoblotting with antibodies against DRPLA C-terminus peptide; immunohistochemistry of human brain sections Nature genetics High 7647802
1996 ATN1/atrophin-1 protein selectively interacts with GAPDH, an interaction mediated by the polyglutamine domain. Protein–protein binding assays identifying GAPDH as a polyglutamine-domain interacting protein in brain Nature medicine Medium 8612237
1997 ATN1/DRPLA protein is cleaved by caspase-3 during apoptosis at the site 106DSLDG110 near the N-terminus. The cleavage is not modulated by polyglutamine length. This identifies ATN1 as a physiological substrate of caspase-3. In vitro cleavage assay with recombinant caspase-3; site-directed mutagenesis of cleavage site; apoptosis induction by VP-16, staurosporine, or glucocorticoid in cells The Journal of biological chemistry High 9361003
1998 Truncated ATN1 protein with an expanded polyglutamine stretch forms filamentous peri- and intranuclear aggregates and induces apoptosis when expressed in COS-7 cells. Apoptotic cell death is partially suppressed by transglutaminase inhibitors cystamine and monodansyl cadaverine, implicating a transglutaminase reaction in aggregate formation and toxicity. Cell transfection with truncated/full-length DRPLA cDNA constructs; pharmacological inhibition with transglutaminase inhibitors; apoptosis assays Nature genetics High 9462738
1998 Full-length ATN1 protein localizes predominantly in the nucleus regardless of polyglutamine length. The N-terminal-deleted caspase-3 cleavage fragment containing the polyQ domain localizes both in the nucleus and cytoplasm, and with expanded polyQ forms aggregates associated with apoptosis. GFP-fusion protein subcellular localization in transfected cells; fluorescence microscopy Biochemical and biophysical research communications Medium 9705838
1998 ATN1 interacts with five proteins containing WW domains via regions near the polyglutamine tract. Four interactions were confirmed by in vitro binding assays. Two classes of interactors were identified: (1) MAGUK-like proteins with PDZ domains (AIP1, AIP3/WWP3), and (2) ubiquitin ligases with HECT domains (AIP2/WWP2, AIP4, AIP5/WWP1). Yeast two-hybrid screen; in vitro binding assays (4 of 5 interactions confirmed) Molecular and cellular neurosciences Medium 9647693
1998 ATN1 protein forms disulfide-bond complexes in human brain, and this complex formation is enhanced in DRPLA brains with expanded polyglutamine. The complex is found in the neuronal cytoplasm. Immunoblotting under reducing and non-reducing conditions; immunohistochemistry of human brain tissue Biochemical and biophysical research communications Medium 9735324
1999 ATN1 protein complex in DRPLA brains is pathologically ubiquitinated specifically in affected lesions. Ubiquitinated ATN1 forms neuronal cytoplasmic inclusions. Complex formation is enhanced by the expanded glutamine repeat. Immunoblotting with and without reduction; double-labeling immunohistochemistry with anti-DRPLA and anti-ubiquitin antibodies Biochemical and biophysical research communications Medium 10381356
1999 ATN1/DRPLA protein binds to IRSp53 (insulin receptor substrate protein of 53 kDa). The binding involves a proline-rich region near the polyglutamine domain of ATN1 and the SH3 domain of IRSp53. Extended polyglutamine significantly reduces this binding. Yeast two-hybrid screen; co-immunoprecipitation; co-localization studies Nihon rinsho. Japanese journal of clinical medicine Medium 10222779
2000 ATN1 protein binds to RERE (a protein sharing the arginine-glutamic acid dipeptide repeat motif), with the RE repeat having a primary role in binding. Extended polyglutamine enhances this interaction. When RERE is overexpressed, endogenous ATN1 distribution changes from diffuse to speckled nuclear pattern, co-localizing with RERE. More RERE is recruited into nuclear aggregates of ATN1 with expanded polyQ. Immunoprecipitation; in vitro binding assays; transfection and co-localization microscopy Human molecular genetics Medium 10814707
2000 ATN1 protein complex in DRPLA brains is aberrantly phosphorylated. Both ubiquitinated cytoplasmic inclusions and the nuclear membrane show aberrant phosphorylation in DRPLA-affected neurons, suggesting the nuclear membrane is an additional pathological focus. Immunochemical methods; enzymatic dephosphorylation; immunohistochemistry The Biochemical journal Medium 11042112
2001 In transgenic mouse models expressing mutant atrophin-1, the protein accumulates/aggregates exclusively in the nucleus (neuronal intranuclear inclusions), whereas mutant huntingtin also forms cytoplasmic aggregates. This differential localization corresponds to distinct behavioral phenotypes. Neuropathological analysis of transgenic mice; immunohistochemistry; behavioral testing Neurobiology of disease Medium 11442350
2005 Mutant ATN1 with expanded polyglutamine (118Q) causes histone H3 hypoacetylation in brain tissue, indicating global transcriptional repression. Overexpression of wild-type ATN1 does not rescue the motor/survival defects in Q118 mice, indicating the mutant does not act in a simple dominant-negative manner. Biochemical analysis of histone acetylation in transgenic mouse brain; motor behavior and survival assays; rescue experiment with wild-type ATN1 overexpression; sodium butyrate (HDAC inhibitor) treatment The Journal of biological chemistry High 16407196
2005 Alternative splicing of ATN1 generates two protein isoforms differing by a single glutamine residue encoded by an alternative CAG exon. The glutamine-included isoform localizes more predominantly in the nucleus. The CAG-included mRNA form is the major isoform expressed in tissues. RT-PCR confirmation of splice isoforms; transfection and subcellular localization studies Journal of human genetics Medium 16091834
2008 In Q129 DRPLA transgenic mice, age-dependent neuronal intranuclear accumulation (NIA) of mutant atrophin-1 is associated with presynaptic dysfunction in the globus pallidus and cerebellum, progressive shrinkage of Purkinje cell distal dendrites, decreased AMPA and GABA-A receptor currents in CA1 neurons, and age-dependent downregulation of synaptic and CREB-dependent genes—without overt neuronal loss, indicating neuronal dysfunction as the primary pathophysiological process. Electrophysiology; neuropathology; immunohistochemistry; expression profiling in transgenic mice Human molecular genetics High 19039037
2025 Mutation of the nuclear export signal (NES) of mutant atrophin-1 (65Q) increases nuclear accumulation of ATN1 and fragments, shortens lifespan, and worsens locomotor defects and brain pathology compared to NLS mutation. This demonstrates that nuclear localization of mutant ATN1 enhances neuropathology. Site-directed mutagenesis of NLS and NES; transgenic mice; behavioral testing; neuropathological analysis; protein localization Human molecular genetics High 40263757
2010 In Drosophila models of DRPLA, atrophin protein causes lysosomal dysfunction and blocks autophagic flux after autophagosome-lysosome fusion, leading to clearance defects. Further induction of autophagy does not rescue neurodegeneration and is instead detrimental in this context. Drosophila genetics; autophagy pathway analysis; lysosomal function assays Autophagy Medium 20543566
2005 Apoptosis-inducing-signal kinase 1 (ASK1) activation is implicated in polyQ-expanded ATN1-induced apoptosis in PC12 cells. Humanin (HN), which inhibits ASK1, partially suppresses apoptotic cell death and aggregate formation induced by expanded polyQ ATN1. Tet-Off inducible expression in PC12 cells; humanin peptide treatment; apoptosis and aggregate formation assays Journal of molecular neuroscience : MN Low 15784964
1999 When full-length mutant ATN1 protein (Q82) is expressed, aggregates form exclusively in the nuclei of neuronally differentiated PC12 cells, but in the cytoplasm of fibroblasts. Truncated ATN1-Q82 forms intranuclear inclusions preferentially in neuronally differentiated cells (>97%) versus fibroblasts (31%). Intranuclear aggregate formation alone is not sufficient to induce apoptosis with full-length ATN1. Adenovirus-mediated expression of truncated and full-length DRPLA constructs in PC12 cells and fibroblasts; fluorescence microscopy; apoptosis assays Human molecular genetics Medium 10332031
2025 In DRPLA patient-derived cortical glutamatergic neurons, mitochondrial dysfunction and oxidative stress occur before overt neuronal loss. Phenylbutyrate treatment improved neuronal survival and reduced mitochondrial ROS, identifying mitochondrial stress as an early driver of neurodegeneration in ATN1 CAG expansion disease. iPSC differentiation into cortical neurons; mitochondrial function assays; pharmacological treatment; survival assays bioRxivpreprint Low bio_10.1101_2025.09.02.673807
2025 In a Drosophila model expressing full-length human ATN1 with Q88, protein quality control pathways are disrupted. Genetic experiments identified Hsc70-3 (a chaperone) as a suppressor of ATN1 toxicity, while VCP (proteasome-related AAA ATPase), Rpn11 (proteasome-related deubiquitinase), and select DnaJ co-chaperones had variable/context-dependent protective effects. RNA-seq identified altered immune and protein quality control pathways. Drosophila transgenic model; RNA-seq; genetic epistasis experiments; behavioral assays bioRxivpreprint Low bio_10.1101_2024.12.05.627083
2025 RNA-seq of HEK293T cells stably expressing polyQ-expanded ATN1 revealed disrupted transcriptional networks including synaptic organization, extracellular matrix remodeling, ion channel expression, inflammation, chromatin remodeling, stress responses, and redox imbalance. Heat shock protein expression changes suggest proteotoxic stress and impaired protein quality control. Stable cell line generation; RNA-seq transcriptomic profiling bioRxivpreprint Low bio_10.1101_2025.08.08.669318
2025 An antisense oligonucleotide targeting human ATN1 (but not mouse Atn1) provides robust protection from behavioral phenotypes and transcriptional dysregulation in the cerebellum of a fully humanized DRPLA mouse model (Atn1 knock-in with 112 CAG repeats), demonstrating that ATN1 knockdown is sufficient to rescue pathology and that disease arises from a gain-of-function mechanism. Humanized knock-in mouse model; ASO treatment; behavioral assays; RNA-seq Molecular therapy. Nucleic acids High 41624332

Source papers

Stage 0 corpus · 97 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1994 Unstable expansion of CAG repeat in hereditary dentatorubral-pallidoluysian atrophy (DRPLA). Nature genetics 1014 8136840
1996 Huntingtin and DRPLA proteins selectively interact with the enzyme GAPDH. Nature medicine 382 8612237
1998 Suppression of aggregate formation and apoptosis by transglutaminase inhibitors in cells expressing truncated DRPLA protein with an expanded polyglutamine stretch. Nature genetics 303 9462738
1994 Structure and expression of the gene responsible for the triplet repeat disorder, dentatorubral and pallidoluysian atrophy (DRPLA). Nature genetics 184 7842016
1994 The Haw River syndrome: dentatorubropallidoluysian atrophy (DRPLA) in an African-American family. Nature genetics 175 7951323
1998 Atrophin-1, the DRPLA gene product, interacts with two families of WW domain-containing proteins. Molecular and cellular neurosciences 147 9647693
1995 Abnormal gene product identified in hereditary dentatorubral-pallidoluysian atrophy (DRPLA) brain. Nature genetics 143 7647802
2000 Frequency of SCA1, SCA2, SCA3/MJD, SCA6, SCA7, and DRPLA CAG trinucleotide repeat expansion in patients with hereditary spinocerebellar ataxia from Chinese kindreds. Archives of neurology 141 10768629
1999 Transgenic mice harboring a full-length human mutant DRPLA gene exhibit age-dependent intergenerational and somatic instabilities of CAG repeats comparable with those in DRPLA patients. Human molecular genetics 93 9887337
2005 Sodium butyrate ameliorates histone hypoacetylation and neurodegenerative phenotypes in a mouse model for DRPLA. The Journal of biological chemistry 78 16407196
1997 Dentatorubral and pallidoluysian atrophy (DRPLA). Clinical and neuropathological findings in genetically confirmed North American and European pedigrees. Movement disorders : official journal of the Movement Disorder Society 72 9251070
1995 Somatic mosaicism of CAG repeat in dentatorubral-pallidoluysian atrophy (DRPLA). Human molecular genetics 72 7633415
1997 Dentatorubral pallidoluysian atrophy (DRPLA) protein is cleaved by caspase-3 during apoptosis. The Journal of biological chemistry 69 9361003
2000 Protein binding of a DRPLA family through arginine-glutamic acid dipeptide repeats is enhanced by extended polyglutamine. Human molecular genetics 58 10814707
1998 Analysis of SCA1, DRPLA, MJD, SCA2, and SCA6 CAG repeats in 48 Portuguese ataxia families. American journal of medical genetics 53 9613852
2005 Frequent occurrence of protein isoforms with or without a single amino acid residue by subtle alternative splicing: the case of Gln in DRPLA affects subcellular localization of the products. Journal of human genetics 52 16091834
1996 A unique origin and multistep process for the generation of expanded DRPLA triplet repeats. Human molecular genetics 50 8852663
2001 Distinct behavioral and neuropathological abnormalities in transgenic mouse models of HD and DRPLA. Neurobiology of disease 44 11442350
1995 Dentatorubral-pallidoluysian atrophy (DRPLA): close correlation of CAG repeat expansions with the wide spectrum of clinical presentations and prominent anticipation. Seminars in cell biology 44 7620120
2001 Single cell analysis of CAG repeat in brains of dentatorubral-pallidoluysian atrophy (DRPLA). Journal of the neurological sciences 37 11574112
1999 Adenovirus-mediated expression of mutant DRPLA proteins with expanded polyglutamine stretches in neuronally differentiated PC12 cells. Preferential intranuclear aggregate formation and apoptosis. Human molecular genetics 35 10332031
2000 Differential somatic CAG repeat instability in variable brain cell lineage in dentatorubral pallidoluysian atrophy (DRPLA): a laser-captured microdissection (LCM)-based analysis. Human genetics 33 11140942
2003 Portuguese families with dentatorubropallidoluysian atrophy (DRPLA) share a common haplotype of Asian origin. European journal of human genetics : EJHG 32 14512972
2008 Severe neurological phenotypes of Q129 DRPLA transgenic mice serendipitously created by en masse expansion of CAG repeats in Q76 DRPLA mice. Human molecular genetics 31 19039037
1997 Frequency of the different mutations causing spinocerebellar ataxia (SCA1, SCA2, MJD/SCA3 and DRPLA) in a large group of Brazilian patients. Arquivos de neuro-psiquiatria 31 9629399
2005 Humanin attenuates apoptosis induced by DRPLA proteins with expanded polyglutamine stretches. Journal of molecular neuroscience : MN 30 15784964
1998 Intracellular aggregate formation of dentatorubral-pallidoluysian atrophy (DRPLA) protein with the extended polyglutamine. Biochemical and biophysical research communications 30 9705838
1996 DRPLA gene (atrophin-1) sequence and mRNA expression in human brain. Brain research. Molecular brain research 29 8965642
2008 TADH, the thermostable alcohol dehydrogenase from Thermus sp. ATN1: a versatile new biocatalyst for organic synthesis. Applied microbiology and biotechnology 27 18704396
2017 Efficacy of perampanel for controlling seizures and improving neurological dysfunction in a patient with dentatorubral-pallidoluysian atrophy (DRPLA). Epilepsy & behavior case reports 26 28856097
2003 Searching for modulating effects of SCA2, SCA6 and DRPLA CAG tracts on the Machado-Joseph disease (SCA3) phenotype. Acta neurologica Scandinavica 26 12614315
1994 Triplet repeats in clinical subtypes of schizophrenia: variation at the DRPLA (B 37 CAG repeat) locus is not associated with periodic catatonia. Journal of neural transmission. General section 25 7734112
1999 Single sperm analysis of the CAG repeats in the gene for dentatorubral-pallidoluysian atrophy (DRPLA): the instability of the CAG repeats in the DRPLA gene is prominent among the CAG repeat diseases. Human molecular genetics 24 9949204
2010 Dentatorubral-pallidoluysian atrophy (DRPLA): The 50th Anniversary of Japanese Society of Neuropathology. Neuropathology : official journal of the Japanese Society of Neuropathology 23 20500452
2020 Maternal sevoflurane exposure affects differentiation of hippocampal neural stem cells by regulating miR-410-3p and ATN1. Stem cell research & therapy 22 32993796
2006 Exclusion of mutations in the PRNP, JPH3, TBP, ATN1, CREBBP, POU3F2 and FTL genes as a cause of disease in Portuguese patients with a Huntington-like phenotype. Journal of human genetics 22 16858508
1988 Cytogenetic characterization of a T-cell line, ATN-1, derived from adult T-cell leukemia cells. Cancer genetics and cytogenetics 22 3260813
1998 Somatic mosaicism of the expanded CAG trinucleotide repeat in mRNAs for the responsible gene of Machado-Joseph disease (MJD), dentatorubral-pallidoluysian atrophy (DRPLA), and spinal and bulbar muscular atrophy (SBMA). Neurochemical research 21 9482263
1995 Dentatorubral-pallidoluysian atrophy (DRPLA). Molecular basis for wide clinical features of DRPLA. Clinical neuroscience (New York, N.Y.) 21 7614090
1995 Predominant neuronal expression of the gene responsible for dentatorubral-pallidoluysian atrophy (DRPLA) in rat. Human molecular genetics 21 8541849
2020 DRPLA: understanding the natural history and developing biomarkers to accelerate therapeutic trials in a globally rare repeat expansion disorder. Journal of neurology 20 33106889
1999 Abnormal dentatorubral-pallidoluysian atrophy (DRPLA) protein complex is pathologically ubiquitinated in DRPLA brains. Biochemical and biophysical research communications 16 10381356
1997 Homozygosity for an allele carrying intermediate CAG repeats in the dentatorubral-pallidoluysian atrophy (DRPLA) gene results in spastic paraplegia. Neurology 16 9109905
1996 Benign adult familial myoclonus epilepsy (BAFME): an autosomal dominant form not linked to the dentatorubral pallidoluysian atrophy (DRPLA) gene. Journal of medical genetics 15 8825056
2001 Dentatorubral-pallidoluysian atrophy (DRPLA) presenting with psychosis. The Journal of neuropsychiatry and clinical neurosciences 14 11449034
2017 Dentatorubro-Pallidoluysian Atrophy (DRPLA) among 700 Families with Ataxia in Brazil. Cerebellum (London, England) 13 28432641
2008 Searching for mutation in the JPH3, ATN1 and TBP genes in Polish patients suspected of Huntington's disease and without mutation in the IT15 gene. Neurologia i neurochirurgia polska 13 18651325
1996 Reduction of CAG expansions in cerebellar cortex and spinal cord of DRPLA. Clinical genetics 12 9001798
1995 Cloning and expression of the rat atrophin-I (DRPLA disease gene) homologue. Neurobiology of disease 12 9173996
2017 Co-expression Patterns between ATN1 and ATXN2 Coincide with Brain Regions Affected in Huntington's Disease. Frontiers in molecular neuroscience 11 29249939
1997 Expression of dentatorubral-pallidoluysian atrophy (DRPLA) proteins in patients. Neuroscience letters 11 9143016
1996 Analysis of the DRPLA triplet repeat in brain tissue and leukocytes from schizophrenics. Psychiatric genetics 11 8925251
1996 cDNA cloning and characterization of an atrophin-1 (DRPLA disease gene)-related protein. Neurobiology of disease 11 9173919
2000 Aberrant phosphorylation of dentatorubral-pallidoluysian atrophy (DRPLA) protein complex in brain tissue. The Biochemical journal 10 11042112
1998 Expanded glutamine repeat enhances complex formation of dentatorubral-pallidoluysian atrophy (DRPLA) protein in human brains. Biochemical and biophysical research communications 10 9735324
1996 The relationship between (CAG)n repeat number and age of onset in a family with dentatorubral-pallidoluysian atrophy (DRPLA): diagnostic implications of confirmatory and predictive testing. Journal of medical genetics 10 8929958
2019 Generation of induced pluripotent stem cell line CSSi008-A (4698) from a patient affected by advanced stage of Dentato-Rubral-Pallidoluysian atrophy (DRPLA). Stem cell research 9 31493762
1998 Clinical and electroencephalographic findings in juvenile type DRPLA. Pediatric neurology 9 9568927
1996 Precise chromosomal locations of the genes for dentatorubral-pallidoluysian atrophy (DRPLA), von Willebrand factor (F8vWF) and parathyroid hormone-like hormone (PTHLH) in human chromosome 12p by deletion mapping. Human genetics 9 8557270
1996 Proton magnetic resonance spectroscopy on childhood-onset dentatorubral-pallidoluysian atrophy (DRPLA). Brain & development 9 8733908
1999 Differences in evoked potential characteristics between DRPLA patients and patients with progressive myoclonic epilepsy: preliminary findings indicating usefulness for differential diagnosis. Epilepsy research 8 10515170
2013 DRPLA: recent advances in research using transgenic mouse models. Methods in molecular biology (Clifton, N.J.) 7 23754232
2002 Late onset ataxia phenotype in dentatorubro-pallidoluysian atrophy (DRPLA). Journal of neurology 7 11967648
2021 CHEDDA syndrome is an underrecognized neurodevelopmental disorder with a highly restricted ATN1 mutation spectrum. Clinical genetics 6 34212383
2014 A shared haplotype for dentatorubropallidoluysian atrophy (DRPLA) in Italian families testifies of the recent introduction of the mutation. Journal of human genetics 6 24401908
2010 The fine line between waste disposal and recycling: DRPLA fly models illustrate the importance of completing the autophagy cycle for rescuing neurodegeneration. Autophagy 6 20543566
2021 DRPLA: An unusual disease or an underestimated cause of ataxia in Brazil? Parkinsonism & related disorders 5 34700111
2015 Case report of optic atrophy in Dentatorubropallidoluysian Atrophy (DRPLA). BMC neurology 5 26679169
1998 Different complex formations of dentatorubral-pallidoluysian atrophy (DRPLA) protein in human and rat neurons. Biochemical and biophysical research communications 5 9878517
2021 The rare and the common: An Austrian DRPLA family harboring the European haplotype. Parkinsonism & related disorders 4 34022586
1999 [Cloning and characterization of cDNA for DRPLA interacting protein]. Nihon rinsho. Japanese journal of clinical medicine 4 10222779
1995 [Does the ataxo-choreic form of DRPLA exist in Europe? Search of mutation in 120 families]. Revue neurologique 4 8745629
2024 ATN1-related infantile developmental and epileptic encephalopathy responding to Ketogenic diet. Seizure 3 38262122
2022 A novel variant in the HX repeat motif of ATN1 in a Chinese patient with CHEDDA syndrome and literature review. Molecular genetics & genomic medicine 3 36251950
2001 [Molecular mechanisms of neurodegeneration in dentatorubral-pallidoluysian atrophy (DRPLA)]. Rinsho shinkeigaku = Clinical neurology 3 12235796
2000 Dentatorubral-pallidoluysian atrophy (DRPLA). Journal of neural transmission. Supplementum 3 11128606
2000 [Dentatorubral-pallidoluysian atrophy (DRPLA)--discovery of the disease, DRPLA gene and the pathophysiology]. Rinsho shinkeigaku = Clinical neurology 3 11464481
2024 IRF2BPL-Related Disorder, Causing Neurodevelopmental Disorder with Regression, Abnormal Movements, Loss of Speech and Seizures (NEDAMSS) Is Characterized by Pathology Consistent with DRPLA. Movement disorders : official journal of the Movement Disorder Society 2 39224955
1998 The DRPLA CAG repeats in an Italian population sample: evaluation of the polymorphism for forensic applications. Journal of forensic sciences 2 9544554
1998 [A case of juvenile type dentatorubral-pallidoluysian atrophy (DRPLA) with psychomotor retardation since infancy]. No to hattatsu = Brain and development 2 9844421
1996 [A sporadic case of dentatorubral-pallidoluysian atrophy (DRPLA) having an elderly age of onset]. Rinsho shinkeigaku = Clinical neurology 2 8810854
1995 [A sporadic dentatorubral-pallidoluysian atrophy (DRPLA) diagnosed by gene analysis]. Rinsho shinkeigaku = Clinical neurology 2 7781240
2025 The nuclear export signal mediates mutant atrophin-1-induced neuropathology in a mouse model of DRPLA. Human molecular genetics 1 40263757
2024 Overexpanded CAG repeats in ATN1 cause an Early-Onset Case of Dentatorubral-Pallidoluysian atrophy with novel phenotypes and a literature Review of Chinese patients. Gene 1 39181274
2023 A Case of Congenital Hypotonia and Developmental Delay in an Individual with a De Novo Variant Outside of the Canonical HX-Motif of ATN1. Case reports in genetics 1 36660549
2007 [Electroencephalographic changes in sisters with infantile-onset dentatorubral-pallidoluysian atrophy (DRPLA)]. No to hattatsu = Brain and development 1 18027567
2002 [Analysis of the allele polymorphism of (CTG)n and (GAG)n triplet repeats in DM, DRPLA, and SCA1 genes in various populations of Russia]. Genetika 1 12500681
2000 [A family with DRPLA and chronic renal failure]. Rinsho shinkeigaku = Clinical neurology 1 10967659
1999 [Somatic mosaicism of CAG repeats size in the nervous system of dentatorubral-pallidoluysian atrophy (DRPLA)]. Nihon rinsho. Japanese journal of clinical medicine 1 10222778
2025 A DRPLA-Affected Family: Clinical Course and Autopsy Findings in a Long-Surviving Case. Neuropathology : official journal of the Japanese Society of Neuropathology 0 40203874
2025 Atrophin-1 antisense oligonucleotide provides robust protection from pathology in a fully humanized DRPLA model. Molecular therapy. Nucleic acids 0 41624332
2023 The relationship between the number of CAG repeats and clinical manifestations: a survey of Chinese DRPLA family. Acta neurologica Belgica 0 37243799
2014 Juvenile myoclonic epilepsy is not associated with the DRPLA gene in a European population. In vivo (Athens, Greece) 0 25398822
2000 Distribution of CAG repeat size in the dentatorubral and pallidoluysian atrophy (DRPLA) gene in a normal population in Taiwan. Proceedings of the National Science Council, Republic of China. Part B, Life sciences 0 10809084
1998 [A case of late adult-onset dentatorubral-pallidoluysian atrophy (DRPLA) successfully treated with V-P shunt operation]. Rinsho shinkeigaku = Clinical neurology 0 9847669
1995 [Triplet repeat disorder, dentatorubral and pallidoluysian atrophy DRPLA)]. Nihon rinsho. Japanese journal of clinical medicine 0 7752462
1994 [Molecular basis of heterogeneities of clinical presentation of dentatorubral pallidoluysian atrophy (DRPLA)]. Rinsho shinkeigaku = Clinical neurology 0 7774119

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