Affinage

ATXN7

Ataxin-7 · UniProt O15265

Length
892 aa
Mass
95.5 kDa
Annotated
2026-04-28
94 papers in source corpus 23 papers cited in narrative 23 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

ATXN7 is a subunit of the SAGA transcriptional coactivator complex that anchors the histone H2B deubiquitination module (DUBm), coupling chromatin remodeling to gene expression control. Loss of ATXN7/Sgf73 disrupts DUBm incorporation into SAGA, elevating H2B monoubiquitination at target promoters such as reelin and photoreceptor genes, while its proteasomal turnover fine-tunes TBP recruitment and transcription elongation (PMID:19226466, PMID:23236151, PMID:37075097). ATXN7 interacts with the photoreceptor transcription factor CRX and participates in a miR-124-dependent autoregulatory circuit that controls its own mRNA levels in neurons (PMID:11580893, PMID:25306109). Polyglutamine expansion in ATXN7 causes spinocerebellar ataxia type 7 (SCA7), in which caspase-7 cleavage at Asp266 generates toxic N-terminal fragments, the mutant protein sequesters p53 and FIP200 to impair autophagy, and SAGA-dependent epigenetic dysregulation preferentially silences Purkinje-cell identity genes; SUMO2/RNF4-mediated ubiquitination promotes clearance of misfolded polyQ-ATXN7 (PMID:25859008, PMID:23592174, PMID:33888607, PMID:30559154).

Mechanistic history

Synthesis pass · year-by-year structured walk · 14 steps
  1. 2001 High

    Establishing that ATXN7 is a transcriptional co-regulator: its direct interaction with CRX and the ability of polyQ-expanded ATXN7 to suppress CRX transactivation and DNA binding provided the first mechanistic link between ATXN7 and photoreceptor gene regulation.

    Evidence Yeast two-hybrid, co-IP, EMSA, and RT-PCR in SCA7 transgenic mice

    PMID:11580893

    Open questions at the time
    • Whether ATXN7-CRX interaction occurs within or outside the SAGA complex was not determined
    • Direct transcriptional targets beyond photoreceptor genes were unknown
  2. 2001 Medium

    Demonstrating that mutant ATXN7 undergoes cytoplasm-to-nucleus translocation and is selectively stabilized as N-terminal fragments that recruit TFIID subunits into inclusions revealed the pathogenic importance of nuclear accumulation and general transcription machinery sequestration.

    Evidence Multiple SCA7 transgenic mouse lines, immunohistochemistry, Western blot, mRNA vs. protein level analysis

    PMID:11487572

    Open questions at the time
    • The protease responsible for N-terminal fragment generation was unidentified
    • Functional consequence of TFIID recruitment to inclusions was not tested
  3. 2009 High

    Defining ATXN7's molecular function within SAGA: the yeast ortholog Sgf73 was shown to be the anchor subunit that recruits the DUBm into both SAGA and SLIK complexes, directly linking ATXN7 to histone H2B deubiquitination and transcriptional regulation.

    Evidence Genetic deletion, biochemical fractionation, and histone modification assays in yeast

    PMID:19226466

    Open questions at the time
    • Whether the anchoring function is fully conserved in human SAGA was inferred but not directly reconstituted
    • Structural basis of DUBm attachment was unknown
  4. 2006 Medium

    Identifying a stress signaling axis downstream of polyQ-ATXN7: genetic reduction of c-Jun activity partially rescued SCA7 retinopathy and restored Nrl expression, establishing the JNK/c-Jun pathway as a mediator of photoreceptor degeneration distinct from direct SAGA dysfunction.

    Evidence Genetic epistasis using JunAA knock-in crossed with R7E SCA7 mice, retinal phenotyping and gene expression analysis

    PMID:17189700

    Open questions at the time
    • How polyQ-ATXN7 activates JNK was not resolved
    • Whether JNK inhibition is additive with SAGA restoration was untested
  5. 2011 High

    Establishing that SAGA HAT activity modulates polyQ-ATXN7 neurotoxicity: reducing Gcn5 in SCA7 mice worsened cerebellar and retinal degeneration, proving that loss of SAGA enzymatic function contributes to — rather than merely accompanies — disease progression.

    Evidence Conditional Gcn5 knockout in Purkinje cells of SCA7 transgenic mice with behavioral and histological analysis

    PMID:22002997

    Open questions at the time
    • Relative contributions of HAT vs. DUB dysfunction within SAGA were not separated
    • Whether Gcn5 loss sensitizes non-neuronal cells similarly was unknown
  6. 2012 Medium

    Showing that polyQ-ATXN7 reduces its occupancy at the reelin promoter with concomitant H2B monoubiquitination increase linked ATXN7's DUBm-anchoring role to specific target-gene epigenetic dysregulation in human astrocytes.

    Evidence ChIP in human astrocyte culture, pharmacological rescue with trichostatin A

    PMID:23236151

    Open questions at the time
    • Genome-wide identification of ATXN7-occupied loci was lacking
    • TSA rescue may reflect HDAC-dependent rather than DUB-specific effects
  7. 2012 High

    Conditional reduction of mutant ATXN7 expression by ~50% halted and partially reversed motor symptoms, aggregation, and synapse loss, demonstrating that disease phenotypes require ongoing mutant protein expression and are not irreversible once initiated.

    Evidence Tamoxifen-inducible Cre-mediated transgene excision in SCA7 mice, behavioral and histological rescue

    PMID:23197655

    Open questions at the time
    • Threshold of reduction needed for clinical benefit was not defined
    • Long-term durability of rescue was not assessed
  8. 2013 Medium

    Revealing that polyQ-ATXN7 impairs autophagy by co-aggregating with p53 and FIP200, thereby depleting soluble FIP200 and destabilizing the ULK1 initiation complex, identified a non-transcriptional gain-of-function toxicity mechanism.

    Evidence Stable inducible SCA7 cell model, co-IP, filter trap assay, pharmacological rescue of p53 and aggregation

    PMID:23592174

    Open questions at the time
    • In vivo validation of p53-FIP200 co-aggregation was not performed
    • Relative contribution of autophagy impairment vs. transcriptional dysregulation to disease was untested
  9. 2014 High

    Discovery of a miR-124-mediated autoregulatory circuit: the SAGA complex drives miR-124 transcription, which post-transcriptionally represses ATXN7 mRNA via lnc-SCA7 cross-talk; polyQ disruption of this circuit causes neuron-specific ATXN7 overaccumulation, explaining tissue selectivity of SCA7.

    Evidence ChIP, RNA knockdown/overexpression, luciferase reporters, mouse retina and cerebellum analysis

    PMID:25306109

    Open questions at the time
    • Whether restoring miR-124 is therapeutically sufficient was not tested
    • Mechanism by which polyQ-ATXN7 disrupts miR-124 transcription was not detailed
  10. 2015 High

    Identification of caspase-7 cleavage at Asp266 as a critical step in ATXN7 neurotoxicity: blocking this site (D266N) in SCA7 mice improved motor function, reduced neurodegeneration, and extended lifespan, establishing proteolytic processing as a therapeutic target.

    Evidence Site-directed mutagenesis, transgenic mouse behavioral and histological comparison

    PMID:25859008

    Open questions at the time
    • Whether the N-terminal fragment itself is toxic or whether cleavage destabilizes the full-length protein was not resolved
    • Caspase-7 activation mechanism in SCA7 neurons was not defined
  11. 2019 High

    Demonstrating that SUMO2/RNF4-mediated ubiquitination targets polyQ-ATXN7 for proteasomal clearance revealed an endogenous quality-control pathway for misfolded ATXN7 and a potential therapeutic axis.

    Evidence Co-IP, proximity ligation assay, immunofluorescence, overexpression of RNF4/SUMO2 in SCA7 knock-in mouse model and cell culture

    PMID:30559154

    Open questions at the time
    • Specific SUMO2 attachment sites on ATXN7 were not mapped
    • Whether RNF4 pathway is saturated in disease was unknown
  12. 2019 Medium

    Loss of ATXN7 in zebrafish caused ocular coloboma via elevated Hedgehog signaling and later disrupted photoreceptor outer segment formation with altered crx expression, establishing a developmental (non-polyQ) requirement for ATXN7 in eye morphogenesis.

    Evidence Zebrafish atxn7 knockdown/knockout, Hedgehog pathway and crx expression analysis

    PMID:30445451

    Open questions at the time
    • Whether SAGA integrity is required for Hedgehog pathway regulation was not tested
    • Relevance to mammalian eye development was not demonstrated
  13. 2021 Medium

    Transcriptomic analysis of SCA7 knock-in Purkinje cells showed that 83 cell-type identity genes (synaptic and firing genes) are preferentially downregulated before morphological changes, with correlated changes in SAGA-dependent histone marks, providing a direct link between SAGA epigenetic dysfunction and early disease.

    Evidence RNA-seq, cell-type gene assignment, epigenetic mark analysis in SCA7-140Q/5Q knock-in mouse cerebellum

    PMID:33888607

    Open questions at the time
    • Causal direction — whether histone mark changes drive or follow transcriptional downregulation — was not established
    • Whether these identity genes are direct ATXN7/SAGA-occupied targets was not confirmed by ChIP
  14. 2023 Medium

    Ubiquitin-proteasome regulation of ATXN7/Sgf73 abundance was shown to fine-tune SAGA transcriptional output: impaired degradation increased Sgf73 levels, boosting TBP recruitment but impairing elongation, revealing that ATXN7 turnover is integral to the SAGA transcription cycle.

    Evidence Ubiquitylation assays, proteasome inhibition, ChIP for promoter occupancy, and transcription assays in yeast with mammalian cell validation

    PMID:37075097

    Open questions at the time
    • The E3 ligase responsible for wild-type ATXN7 turnover was not identified
    • How polyQ expansion affects this turnover pathway specifically was not tested

Open questions

Synthesis pass · forward-looking unresolved questions
  • Major unresolved questions include the structural basis of ATXN7-mediated DUBm anchoring in human SAGA, the identity of the E3 ubiquitin ligase controlling wild-type ATXN7 turnover, the relative in vivo contributions of SAGA transcriptional dysfunction versus autophagy impairment and proteolytic toxicity in SCA7, and whether restoring the miR-124 autoregulatory circuit or RNF4/SUMO2 clearance pathway is therapeutically viable.
  • No structural model of human ATXN7 within the DUBm
  • Relative contribution of HAT vs. DUB dysfunction to SCA7 pathology not separated in vivo
  • Therapeutic potential of SUMO2/RNF4 or miR-124 restoration not validated in mammalian disease models

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0042393 histone binding 3 GO:0098772 molecular function regulator activity 2
Localization
GO:0005634 nucleus 2 GO:0005654 nucleoplasm 2
Pathway
R-HSA-4839726 Chromatin organization 4 R-HSA-1643685 Disease 3 R-HSA-74160 Gene expression (Transcription) 3 R-HSA-9612973 Autophagy 2
Partners
APLP2CASP7CRXFIP200GCN5RNF4SUMO2TP53
Complex memberships
SAGASAGA DUB module

Evidence

Reading pass · 23 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2001 Ataxin-7 interacts with the cone-rod homeobox protein CRX (yeast two-hybrid, co-immunoprecipitation, colocalization), and polyglutamine-expanded ataxin-7 suppresses CRX transactivation activity, leading to reduced CRX DNA-binding and decreased expression of CRX-regulated photoreceptor genes in SCA7 transgenic mice. Yeast two-hybrid, co-immunoprecipitation, electrophoretic mobility shift assay, RT-PCR in transgenic mice Neuron High 11580893
2009 Yeast Sgf73 (ortholog of human ataxin-7/ATXN7) is required to recruit the histone deubiquitination module (DUBm) into both the SAGA and Slik(SALSA) HAT complexes; loss of Sgf73 disrupts histone H2B deubiquitination and alters transcription at multiple genes. Genetic deletion, biochemical fractionation, histone modification assays in yeast Epigenetics & chromatin High 19226466
2014 STAGA complex (containing ATXN7) is required for transcription initiation of miR-124, which mediates post-transcriptional cross-talk between lnc-SCA7 (a conserved long noncoding RNA) and ATXN7 mRNA; polyQ expansion in ATXN7 disrupts this regulatory feedback, causing neuron-specific increase in ATXN7 expression most prominent in retina and cerebellum. ChIP, RNA knockdown/overexpression, luciferase reporter assays, mouse model analysis Nature structural & molecular biology High 25306109
2011 Reducing Gcn5 (the HAT catalytic subunit of SAGA) expression accelerates both cerebellar and retinal degeneration in a SCA7 mouse model, demonstrating that Gcn5 HAT function within the SAGA complex contributes to the severity of ATXN7-driven neurodegeneration. Conditional Gcn5 knockout in Purkinje cells in SCA7 transgenic mice, behavioral and histological analysis Human molecular genetics High 22002997
2012 Polyglutamine-expanded ATXN7 decreases ATXN7 occupancy at the reelin promoter, correlating with increased histone H2B monoubiquitination at that locus; trichostatin A treatment partially restores reelin transcription, identifying reelin as an ATXN7 target gene in human astrocytes. ChIP, human astrocyte cell culture model, pharmacological rescue with TSA Proceedings of the National Academy of Sciences of the United States of America Medium 23236151
2015 Caspase-7 cleaves ataxin-7 at aspartate 266; blocking this cleavage (D266N mutation) in transgenic SCA7 mice improves motor performance, reduces neurodegeneration, and extends lifespan, establishing proteolysis at D266 as a critical mediator of ataxin-7 neurotoxicity. Site-directed mutagenesis (D266N), transgenic mouse comparison, behavioral tests, histology Human molecular genetics High 25859008
2019 Endogenous ATXN7 is modified by SUMO2/3; polyQ-ATXN7 co-localizes and interacts with SUMO2 in inclusions, and RNF4 (a SUMO-targeted ubiquitin ligase) is recruited to SUMO2/3-decorated inclusions, leading to polyubiquitination and proteasomal degradation of polyQ-ATXN7; overexpression of RNF4 and/or SUMO2 significantly decreases polyQ-ATXN7 levels. Co-immunoprecipitation, proximity ligation assay, immunofluorescence, overexpression, SCA7 knock-in mouse model Disease models & mechanisms High 30559154
2013 Mutant ATXN7 (polyQ-expanded) reduces autophagic activity through a p53-mediated mechanism: increased p53-FIP200 interaction and co-aggregation into ATXN7 aggregates deplete soluble FIP200, destabilizing ULK1 and impairing ULK1-FIP200-Atg13-Atg101 complex-mediated autophagy initiation; p53 inhibition or ATXN7 aggregation blockers restore FIP200/ULK1 levels and autophagic flux. Stable inducible SCA7 cell model, co-immunoprecipitation, filter trap, pharmacological rescue Journal of molecular neuroscience : MN Medium 23592174
2012 Polyglutamine-expanded ATXN7 causes oxidative stress by increasing superoxide anion production from NADPH oxidase (NOX) complexes and reducing catalase levels; NOX inhibition or antioxidant treatment reduces both ATXN7 aggregation and toxicity. Stable inducible SCA7 cell model, ROS measurement, NOX inhibition, antioxidant treatment BMC neuroscience Medium 22827889
2013 Interferon beta induces PML protein expression and PML nuclear body formation, which mediates clearance of mutant ataxin-7 (polyQ-ATXN7) in SCA7 knock-in mice; IFN-β treatment reduces ATXN7-positive neuronal intranuclear inclusions and improves motor function. SCA7 knock-in mouse model, immunohistochemistry, behavioral testing, cell culture Brain : a journal of neurology Medium 23518714
2002 Ataxin-7 is primarily nuclear in most brain regions, but in cerebellar Purkinje cells, subcellular distribution differs between SCA7 patients and controls of different ages, suggesting that nuclear localization is linked to its pathological function; ataxin-7 expression is not restricted to regions of pathology. Immunohistochemistry, fractionation in CNS tissue from SCA7 patients and controls Acta neuropathologica Medium 12070661
2001 In SCA7 transgenic mice, mutant ataxin-7 undergoes cytoplasm-to-nucleus translocation and accumulates as N-terminal fragments; mutant ataxin-7 is selectively stabilized compared to wild-type protein (based on discrepancy between mRNA and protein levels only in mutant-expressing mice), and nuclear inclusions recruit TAF(II)30 (a TFIID subunit) even though it lacks a polyglutamine stretch. Transgenic mouse models, immunohistochemistry, Western blot, mRNA/protein level comparison Human molecular genetics Medium 11487572
2006 Polyglutamine-ataxin-7 activates the JNK/c-Jun stress pathway in rod photoreceptors; genetic reduction of c-Jun activation (JunAA knock-in) improves SCA7 retinopathy and partially restores expression of Nrl and its downstream phototransduction targets; c-Jun can directly repress Nrl transcription. Genetic epistasis (JunAA x R7E SCA7 mice), gene expression analysis, retinal phenotyping Neurobiology of disease Medium 17189700
2014 The autophagy/lysosome pathway is impaired in SCA7: mutant ataxin-7 accumulates with autophagy markers (mTOR, beclin-1, p62, ubiquitin, LC3, LAMP-1, LAMP-2, cathepsin-D) in cerebellar neurons of SCA7 knock-in mice; autophagic flux is impaired in cells overexpressing full-length mutant ataxin-7. Immunohistochemistry in knock-in mouse and patient tissue, autophagic flux assays in cell culture Acta neuropathologica Medium 24859968
2010 Amyloid precursor-like protein 2 (APLP2) is a binding partner of ataxin-7; caspase-3 cleavage of APLP2 releases intracellular C-terminal domains (ICDs) that translocate to the nucleus and accumulate in neuronal intranuclear inclusions in SCA7 brain; co-expression of APLP2 ICD with mutant ataxin-7 produces cumulative toxicity. Co-immunoprecipitation, immunohistochemistry in SCA7 brain, co-expression toxicity assay Neurobiology of disease Medium 20732423
2011 In SCA7 rod photoreceptor nuclei, the linker histone H1c is strongly reduced in nuclear extracts and its distribution is altered specifically in the facultative heterochromatin compartment, causing chromatin decondensation (fragmentation of the outer heterochromatin ring); acetylated histone H3/H4 levels are unchanged. Immunogold labeling, stereology, electron tomography, Western blot of nuclear extracts from SCA7 retinas Nucleus (Austin, Tex.) Medium 21970987
2023 Ataxin-7 (and its yeast homolog Sgf73) undergo ubiquitylation and proteasomal degradation; impaired Sgf73 degradation increases its abundance, enhancing TBP recruitment to promoters but impairing transcription elongation; decreased Sgf73 reduces PIC (preinitiation complex) formation. This UPS regulation fine-tunes SAGA complex activity in transcription. Ubiquitylation assays, proteasome inhibition, promoter occupancy (ChIP), transcription assays in yeast; ataxin-7 validation in mammalian cells Genetics Medium 37075097
2012 Reduction of mutant ataxin-7 expression by ~50% (via tamoxifen-induced Cre-mediated excision) in SCA7 mice halts or reverses motor symptoms, reduces ataxin-7 aggregation in Purkinje cells, and prevents loss of climbing fiber-Purkinje cell synapses, demonstrating that ongoing mutant gene expression is required to maintain disease phenotypes. Conditional transgenic mouse model with tamoxifen-inducible Cre, behavioral testing, histology Human molecular genetics High 23197655
2019 Loss of ATXN7 (an SAGA subunit) in zebrafish causes ocular coloboma via elevated Hedgehog signaling in the forebrain, altering proximo-distal patterning of the optic vesicle; at later stages, photoreceptor outer segment formation is incomplete, correlating with altered expression of crx (a transcription factor for photoreceptor outer segment formation). Zebrafish atxn7 knockdown/knockout, immunofluorescence, Hedgehog pathway analysis, crx expression analysis Human molecular genetics Medium 30445451
2021 In the SCA7-140Q/5Q knock-in mouse, Purkinje cells show preferential downregulation of 83 cell-type identity genes (involved in spontaneous firing and synaptic function) that precedes morphological changes and motor symptoms; gene deregulation correlates with alterations in SAGA-dependent epigenetic marks (histone modifications). Cerebellar transcriptome analysis by RNA-seq, cell-type assignment, epigenetic mark analysis, behavioral phenotyping in knock-in mouse The Journal of neuroscience : the official journal of the Society for Neuroscience Medium 33888607
2015 Polyglutamine-expanded ATXN7 co-aggregates with p53, reducing p53 transcriptional activity and decreasing p53 target proteins (AIF, TIGAR) by ~50%, while increasing NOX1 expression ~2-fold; together these alterations decrease respiratory capacity, increase glycolytic dependence, and reduce ATP by ~20% in SCA7 cells; restoring p53 function or suppressing NOX1 reverses metabolic dysfunction and reduces mutant ATXN7 toxicity. Stable inducible PC12 SCA7 model, co-immunoprecipitation/aggregation assays, metabolic flux assays, pharmacological rescue Biochimica et biophysica acta Medium 25647692
2005 A novel SCA7 isoform (ataxin-7b) contains an alternative exon (12b) encoding a different C-terminus; insertion of exon 12b shifts the reading frame to produce an alternative C-terminus that directs the protein to a more cytoplasmic localization compared to the canonical nuclear ataxin-7. Northern blot, quantitative RT-PCR, subcellular localization by immunofluorescence in mice Biochimica et biophysica acta Low 16297465
2022 Key stress granule modulators TDP-43 and TIA1 are sequestered into aggregates formed by polyQ-expanded ATXN7 in SCA7 cells; mutant ATXN7 also localizes to induced stress granules and alters their shape; mutant ATXN7 expression increases speckling of the SG-nucleating protein G3BP1. Immunofluorescence, co-localization, filter trap assay in SCA7 cell models Molecular neurobiology Low 35689166

Source papers

Stage 0 corpus · 94 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1997 Cloning of the SCA7 gene reveals a highly unstable CAG repeat expansion. Nature genetics 636 9288099
1998 Spinocerebellar ataxia type 7 (SCA7): a neurodegenerative disorder with neuronal intranuclear inclusions. Human molecular genetics 273 9536097
1998 Molecular and clinical correlations in autosomal dominant cerebellar ataxia with progressive macular dystrophy (SCA7). Human molecular genetics 225 9425222
2001 Polyglutamine-expanded ataxin-7 antagonizes CRX function and induces cone-rod dystrophy in a mouse model of SCA7. Neuron 194 11580893
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
1998 Molecular and clinical studies in SCA-7 define a broad clinical spectrum and the infantile phenotype. Neurology 128 9781533
1998 Expanded CAG repeats in Swedish spinocerebellar ataxia type 7 (SCA7) patients: effect of CAG repeat length on the clinical manifestation. Human molecular genetics 127 9425223
2011 Zinc uptake by Streptococcus pneumoniae depends on both AdcA and AdcAII and is essential for normal bacterial morphology and virulence. Molecular microbiology 113 22023106
2014 AdcA and AdcAII employ distinct zinc acquisition mechanisms and contribute additively to zinc homeostasis in Streptococcus pneumoniae. Molecular microbiology 89 24428621
2008 AdcAII, a new pneumococcal Zn-binding protein homologous with ABC transporters: biochemical and structural analysis. Journal of molecular biology 84 18632116
2002 Spinocerebellar ataxia type 7 (SCA7) shows a cone-rod dystrophy phenotype. Experimental eye research 83 12126946
2001 SCA7 mouse models show selective stabilization of mutant ataxin-7 and similar cellular responses in different neuronal cell types. Human molecular genetics 82 11487572
2001 Similarities between spinocerebellar ataxia type 7 (SCA7) cell models and human brain: proteins recruited in inclusions and activation of caspase-3. Human molecular genetics 78 11709544
1998 Analysis of the dynamic mutation in the SCA7 gene shows marked parental effects on CAG repeat transmission. Human molecular genetics 78 9467013
2014 Cross-talking noncoding RNAs contribute to cell-specific neurodegeneration in SCA7. Nature structural & molecular biology 75 25306109
2009 Yeast Sgf73/Ataxin-7 serves to anchor the deubiquitination module into both SAGA and Slik(SALSA) HAT complexes. Epigenetics & chromatin 75 19226466
2001 A survey of spinocerebellar ataxia in South Brazil - 66 new cases with Machado-Joseph disease, SCA7, SCA8, or unidentified disease-causing mutations. Journal of neurology 70 11697524
2013 Interferon β induces clearance of mutant ataxin 7 and improves locomotion in SCA7 knock-in mice. Brain : a journal of neurology 64 23518714
2003 Genomic context drives SCA7 CAG repeat instability, while expressed SCA7 cDNAs are intergenerationally and somatically stable in transgenic mice. Human molecular genetics 58 12490531
2002 Childhood-onset ataxia: testing for large CAG-repeats in SCA2 and SCA7. American journal of medical genetics 57 12116207
2014 The autophagy/lysosome pathway is impaired in SCA7 patients and SCA7 knock-in mice. Acta neuropathologica 55 24859968
1996 The gene for autosomal dominant cerebellar ataxia type II is located in a 5-cM region in 3p12-p13: genetic and physical mapping of the SCA7 locus. American journal of human genetics 55 8940279
2002 Two populations of neuronal intranuclear inclusions in SCA7 differ in size and promyelocytic leukaemia protein content. Brain : a journal of neurology 54 12077003
1999 Spinocerebellar ataxia type 7 (SCA7) - correlations between phenotype and genotype in one large Belgian family. Journal of the neurological sciences 53 10500272
2009 Design of RNAi hairpins for mutation-specific silencing of ataxin-7 and correction of a SCA7 phenotype. PloS one 51 19789634
2003 Spinocerebellar ataxia 7 (SCA7). Cytogenetic and genome research 49 14526176
2000 Evidence for a common Spinocerebellar ataxia type 7 (SCA7) founder mutation in Scandinavia. European journal of human genetics : EJHG 49 11175279
2014 Nonallele specific silencing of ataxin-7 improves disease phenotypes in a mouse model of SCA7. Molecular therapy : the journal of the American Society of Gene Therapy 46 24930601
2011 Gcn5 loss-of-function accelerates cerebellar and retinal degeneration in a SCA7 mouse model. Human molecular genetics 43 22002997
2004 Ataxin-7 aggregation and ubiquitination in infantile SCA7 with 180 CAG repeats. Annals of neurology 43 15349877
2013 New insights into histidine triad proteins: solution structure of a Streptococcus pneumoniae PhtD domain and zinc transfer to AdcAII. PloS one 41 24312273
2012 Reduction of mutant ataxin-7 expression restores motor function and prevents cerebellar synaptic reorganization in a conditional mouse model of SCA7. Human molecular genetics 36 23197655
2012 Reelin is a target of polyglutamine expanded ataxin-7 in human spinocerebellar ataxia type 7 (SCA7) astrocytes. Proceedings of the National Academy of Sciences of the United States of America 36 23236151
2005 Spinocerebellar ataxia type 7 (SCA7): first report of a systematic neuropathological study of the brain of a patient with a very short expanded CAG-repeat. Brain pathology (Zurich, Switzerland) 35 16389941
2000 Macular degeneration associated with aberrant expansion of trinucleotide repeat of the SCA7 gene in 2 Japanese families. Archives of ophthalmology (Chicago, Ill. : 1960) 31 11030825
2021 SCA7 Mouse Cerebellar Pathology Reveals Preferential Downregulation of Key Purkinje Cell-Identity Genes and Shared Disease Signature with SCA1 and SCA2. The Journal of neuroscience : the official journal of the Society for Neuroscience 29 33888607
2014 Allele-specific silencing of mutant Ataxin-7 in SCA7 patient-derived fibroblasts. European journal of human genetics : EJHG 29 24667781
2012 Expanded ataxin-7 cause toxicity by inducing ROS production from NADPH oxidase complexes in a stable inducible Spinocerebellar ataxia type 7 (SCA7) model. BMC neuroscience 29 22827889
1999 Multiple origins of the spinocerebellar ataxia 7 (SCA7) mutation revealed by linkage disequilibrium studies with closely flanking markers, including an intragenic polymorphism (G3145TG/A3145TG). European journal of human genetics : EJHG 29 10602364
2016 AdcAII of Streptococcus pneumoniae Affects Pneumococcal Invasiveness. PloS one 27 26752283
2013 Inhibition of autophagy via p53-mediated disruption of ULK1 in a SCA7 polyglutamine disease model. Journal of molecular neuroscience : MN 27 23592174
2004 Hsp70 and Hsp40 chaperones do not modulate retinal phenotype in SCA7 mice. The Journal of biological chemistry 27 15494410
2001 Molecular analysis of Spinocerebellar ataxias in Koreans: frequencies and reference ranges of SCA1, SCA2, SCA3, SCA6, and SCA7. Molecules and cells 25 11804332
2017 Transposon mutagenesis identifies chromatin modifiers cooperating with Ras in thyroid tumorigenesis and detects ATXN7 as a cancer gene. Proceedings of the National Academy of Sciences of the United States of America 24 28584132
2020 Circular RNA ATXN7 promotes the development of gastric cancer through sponging miR-4319 and regulating ENTPD4. Cancer cell international 23 31997941
2002 Expression of ataxin-7 in CNS and non-CNS tissue of normal and SCA7 individuals. Acta neuropathologica 23 12070661
2018 The Atxn7-overexpressing mice showed hyperactivity and impulsivity which were ameliorated by atomoxetine treatment: A possible animal model of the hyperactive-impulsive phenotype of ADHD. Progress in neuro-psychopharmacology & biological psychiatry 22 30125623
2019 SUMOylation by SUMO2 is implicated in the degradation of misfolded ataxin-7 via RNF4 in SCA7 models. Disease models & mechanisms 21 30559154
2015 Proteolytic cleavage of ataxin-7 promotes SCA7 retinal degeneration and neurological dysfunction. Human molecular genetics 21 25859008
2005 A SCA7 CAG/CTG repeat expansion is stable in Drosophila melanogaster despite modulation of genomic context and gene dosage. Gene 20 15715978
2022 The AdcACB/AdcAII system is essential for zinc homeostasis and an important contributor of Enterococcus faecalis virulence. Virulence 18 35341449
2017 Large normal-range TBP and ATXN7 CAG repeat lengths are associated with increased lifetime risk of depression. Translational psychiatry 18 28585930
2011 The linker histone H1C contributes to the SCA7 nuclear phenotype. Nucleus (Austin, Tex.) 18 21970987
2002 Cloning and expression analysis of the murine homolog of the spinocerebellar ataxia type 7 (SCA7) gene. Gene 18 12039035
2013 C-terminus of the Sgf73 subunit of SAGA and SLIK is important for retention in the larger complex and for heterochromatin boundary function. Genes to cells : devoted to molecular & cellular mechanisms 17 23819448
2012 Differential degradation of full-length and cleaved ataxin-7 fragments in a novel stable inducible SCA7 model. Journal of molecular neuroscience : MN 17 22367614
2007 Massive SCA7 expansion detected in a 7-month-old male with hypotonia, cardiomegaly, and renal compromise. Developmental medicine and child neurology 16 17254003
2019 Loss of zebrafish Ataxin-7, a SAGA subunit responsible for SCA7 retinopathy, causes ocular coloboma and malformation of photoreceptors. Human molecular genetics 15 30445451
2013 Founder effect and ancestral origin of the spinocerebellar ataxia type 7 (SCA7) mutation in Mexican families. Neurogenetics 15 24374739
2017 Clinical and genetic analysis of spinocerebellar ataxia type 7 (SCA7) in Zambian families. Cerebellum & ataxias 14 29214039
1999 Genomic organisation of the spinocerebellar ataxia type 7 (SCA7) gene responsible for autosomal dominant cerebellar ataxia with retinal degeneration. Human genetics 14 10598805
2019 Circular RNA ATXN7 is upregulated in non-small cell lung cancer and promotes disease progression. Oncology letters 13 31186686
2016 Lentiviral vector-mediated overexpression of mutant ataxin-7 recapitulates SCA7 pathology and promotes accumulation of the FUS/TLS and MBNL1 RNA-binding proteins. Molecular neurodegeneration 13 27465358
2016 Mutant CAG Repeats Effectively Targeted by RNA Interference in SCA7 Cells. Genes 13 27999335
2015 Altered p53 and NOX1 activity cause bioenergetic defects in a SCA7 polyglutamine disease model. Biochimica et biophysica acta 13 25647692
2008 Trinucleotide expansions in the SCA7 gene in a large family with spinocerebellar ataxia and craniocervical dystonia. Neuroscience letters 13 18325672
2016 ATXN7 Gene Variants and Expression Predict Post-Operative Clinical Outcomes in Hepatitis B Virus-Related Hepatocellular Carcinoma. Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology 12 27855399
2014 Uncovering the role of Sgf73 in maintaining SAGA deubiquitinating module structure and activity. Journal of molecular biology 12 25526805
2006 Preventing polyglutamine-induced activation of c-Jun delays neuronal dysfunction in a mouse model of SCA7 retinopathy. Neurobiology of disease 12 17189700
2020 Deletion of the Zinc Transporter Lipoprotein AdcAII Causes Hyperencapsulation of Streptococcus pneumoniae Associated with Distinct Alleles of the Type I Restriction-Modification System. mBio 11 32234814
2023 A novel ubiquitin-proteasome system regulation of Sgf73/ataxin-7 that maintains the integrity of the coactivator SAGA in orchestrating transcription. Genetics 10 37075097
2015 Spinocerebellar ataxia 7 (SCA7) in Indian population: predilection of ATXN7-CAG expansion mutation in an ethnic population. The Indian journal of medical research 10 25900954
2022 The AdcR-regulated AdcA and AdcAII contribute additively to zinc acquisition and virulence in Streptococcus suis. Veterinary microbiology 9 35430524
2022 Key Modulators of the Stress Granule Response TIA1, TDP-43, and G3BP1 Are Altered by Polyglutamine-Expanded ATXN7. Molecular neurobiology 9 35689166
2015 Sgf73, a subunit of SAGA complex, is required for the assembly of RITS complex in fission yeast. Scientific reports 8 26443059
2022 Novel Pseudomonas sp. SCA7 Promotes Plant Growth in Two Plant Families and Induces Systemic Resistance in Arabidopsis thaliana. Frontiers in microbiology 7 35875540
2015 Somatic instability of expanded CAG repeats of ATXN7 in Japanese patients with spinocerebellar ataxia type 7. Documenta ophthalmologica. Advances in ophthalmology 7 25643591
2023 Purkinje-Enriched snRNA-seq in SCA7 Cerebellum Reveals Zebrin Identity Loss as a Central Feature of Polyglutamine Ataxias. bioRxiv : the preprint server for biology 6 37214832
2016 Voice Alterations in Patients With Spinocerebellar Ataxia Type 7 (SCA7): Clinical-Genetic Correlations. Journal of voice : official journal of the Voice Foundation 6 26992556
2013 Genetic variation in ataxia gene ATXN7 influences cerebellar grey matter volume in healthy adults. Cerebellum (London, England) 6 23100044
2010 Solution NMR characterization of Sgf73(1-104) indicates that Zn ion is required to stabilize zinc finger motif. Biochemical and biophysical research communications 5 20510875
2010 Amyloid precursor-like protein 2 cleavage contributes to neuronal intranuclear inclusions and cytotoxicity in spinocerebellar ataxia-7 (SCA7). Neurobiology of disease 5 20732423
2024 YTHDC1-Mediated lncRNA MSC-AS1 m6A Modification Potentiates Laryngeal Squamous Cell Carcinoma Development via Repressing ATXN7 Transcription. Molecular biotechnology 4 38637450
2021 Clinical characterization and the improved molecular diagnosis of autosomal dominant cone-rod dystrophy in patients with SCA7. Molecular vision 4 34012225
2021 Conformation of the Solute-Binding Protein AdcAII Influences Zinc Uptake in Streptococcus pneumoniae. Frontiers in cellular and infection microbiology 4 34490149
2024 ATXN7-Related Cone-Rod Dystrophy: The Integrated Functional Evaluation of the Cerebellum (CERMOI) Study. JAMA ophthalmology 3 38421662
2019 Loss of function in SAGA deubiquitinating module caused by Sgf73 H93A mutation: A molecular dynamics study. Journal of molecular graphics & modelling 3 31202915
2005 Identification and characterization of Spinocerebellar Ataxia Type 7 (SCA7) isoform SCA7b in mice. Biochimica et biophysica acta 3 16297465
2024 Longitudinal MRI and 1H-MRS study of SCA7 mouse forebrain reveals progressive multiregional atrophy and early brain metabolite changes indicating early neuronal and glial dysfunction. PloS one 2 38227598
2024 The 5HT4R agonist velusetrag efficacy on neuropathic chronic intestinal pseudo-obstruction in PrP-SCA7-92Q transgenic mice. Frontiers in pharmacology 2 39139632
2019 A SCA7 premutation may be a novel Mendelian modifier of MS course: A case report. Multiple sclerosis and related disorders 2 30999137
2014 Large scale screening of genetic interaction with sgf73(+) in fission yeast. Yi chuan = Hereditas 1 25076038
2005 [SCA-7. Cone-rod dystrophy in the context of an hereditary ataxia]. Archivos de la Sociedad Espanola de Oftalmologia 1 16311960
2021 Amyotrophic lateral sclerosis associated with a pathological expansion in the ATXN7 gene. Amyotrophic lateral sclerosis & frontotemporal degeneration 0 34870541