Affinage

SPG11

Spatacsin · UniProt Q96JI7

Length
2443 aa
Mass
278.9 kDa
Annotated
2026-06-10
93 papers in source corpus 15 papers cited in narrative 15 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 7/7 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

Spatacsin (SPG11) is a large scaffolding protein that organizes a coat-like assembly on late endosomes/lysosomes to drive lysosome reformation, and its loss produces a spectrum of neurodevelopmental and neurodegenerative phenotypes (PMID:23825025, PMID:26284655). Spatacsin and spastizin (SPG15) bind all four subunits of the AP-5 adaptor complex in fixed stoichiometry, with the N-terminal β-propeller-like domain of SPG11 mediating the AP-5 interaction; the two proteins are mutually stabilizing and co-localize with AP-5 on a late endosomal/lysosomal compartment (PMID:23825025, PMID:24999486). Cryo-EM shows SPG11 and SPG15 form a W-shaped head-to-head heterodimer that holds AP-5 in a super-open conformation, binds PI3P, senses membrane curvature, and initiates membrane tubulation in vitro (PMID:40175557). The complex is recruited to lysosomes by coincidence detection of PI3P (via the SPG15 FYVE domain) and GDP-locked RagC, an interplay with mTORC1 signaling that is enhanced upon starvation (PMID:33464297). Functionally, this activity is required for autophagic lysosome reformation: Spg11 loss depletes lysosomes, impairs their recovery during starvation, and elevates lipidated LC3, while leaving lysosomal enzymatic function intact (PMID:26284655). Loss of spatacsin disrupts neuronal homeostasis through multiple downstream routes — lysosomal accumulation of gangliosides and cholesterol with resulting axonal spheroids and impaired axonal transport (PMID:38876323, PMID:37709208), GSK3β hyperactivation impairing neural progenitor proliferation and driving premature neurogenesis (PMID:26971897, PMID:30476097, PMID:30574063), a lysosomal calcium–PI4K2A–mTOR axis that perturbs cortical development (PMID:42049147), and hyperactivation of the non-canonical inflammasome in microglia via increased STAT1 signaling (PMID:38305941). SPG11 mutations underlie an autosomal recessive hereditary spastic paraplegia, modeled in patient-derived neurons and organoids (PMID:24794856, PMID:30476097).

Mechanistic history

Synthesis pass · year-by-year structured walk · 14 steps
  1. 2010 Medium

    Established that spatacsin is required for early neural development in vivo, before any molecular function was known.

    Evidence Morpholino knockdown of spg11 in zebrafish embryos with axon pathway immunostaining

    PMID:20390432

    Open questions at the time
    • No molecular mechanism for the developmental defect
    • Morpholino specificity not addressed by genetic rescue
    • Single model organism
  2. 2013 High

    Defined the core molecular identity of spatacsin as a stoichiometric partner of SPG15 and the AP-5 adaptor complex, establishing a coat-like sorting machinery on late endosomes/lysosomes.

    Evidence Reciprocal Co-IP with stoichiometry, in vitro domain binding of the SPG11 N-terminus to AP-5, knockdown epistasis on CI-M6PR sorting, and colocalization imaging

    PMID:23825025

    Open questions at the time
    • Structural basis of the assembly not resolved
    • Functional consequence for lysosome biology not yet defined
  3. 2014 High

    Connected spatacsin loss to neuronal axonal pathology and to lysosomal enlargement, and showed SPG11/SPG15 protein stability is interdependent.

    Evidence iPSC patient neurons and mouse cortical neuron knockdown with vesicle trafficking imaging and cytoskeletal markers; patient fibroblast LAMP1 imaging, EM, and protein stability westerns

    PMID:24794856 PMID:24999486

    Open questions at the time
    • Mechanism linking lysosomal defect to axonal transport not established
    • Cargo whose mistrafficking drives axonal instability unknown
  4. 2015 High

    Identified the cell-biological function of spatacsin as autophagic lysosome reformation, explaining lysosome depletion as the proximate consequence of its loss.

    Evidence Spg11 knockout mouse with lysosome quantification in MEFs and neurons, starvation-recovery assay, LC3 lipidation, and preserved cathepsin D processing/pH

    PMID:26284655

    Open questions at the time
    • How the complex physically reforms lysosomes not yet shown
    • Recruitment signals to lysosomes undefined
  5. 2016 Medium

    Revealed that spatacsin loss impairs neural progenitor proliferation through GSK3β hyperactivation, a pharmacologically reversible mechanism.

    Evidence iPSC-derived NPCs from three SPG11 patients with transcriptome profiling, proliferation assays, and GSK3 inhibitor rescue

    PMID:26971897

    Open questions at the time
    • Link between lysosomal dysfunction and GSK3β activation not mechanistically connected
    • Single lab
  6. 2018 Medium

    Distinguished SPG11 from SPG15 function, showing both are required for ALR but only SPG15 acts at the autophagy-endocytosis intersection via RAB regulation.

    Evidence Patient cells with SPG11 or SPG15 mutations, RAB5A/RAB11 Co-IP and activation assays, autophagosome-endosome fusion and ALR assays with RAB5A rescue

    PMID:30081747

    Open questions at the time
    • Why SPG11 produces a milder defect than its partner unclear
    • Single lab
  7. 2018 Medium

    Confirmed GSK3β/β-catenin dysregulation as a driver of neuronal pathology in mature neurons using both patient and isogenic knockout lines.

    Evidence SPG11 patient iPSC cortical neurons and a CRISPR-Cas9 knockout line with tideglusib rescue of neurite, death, and inclusion phenotypes

    PMID:30574063

    Open questions at the time
    • Upstream trigger of GSK3β hyperactivation still not identified
  8. 2019 Medium

    Demonstrated that GSK3β dysregulation causes a developmental phenotype — premature neurogenesis from altered NPC division mode — reversible by an FDA-approved GSK3 inhibitor.

    Evidence SPG11 patient iPSC cortical organoids with division mode quantification and tideglusib rescue

    PMID:30476097

    Open questions at the time
    • Molecular path from spatacsin to division asymmetry not resolved
  9. 2021 High

    Solved how the complex is targeted to lysosomes, defining coincidence detection of PI3P and Rag GTPase state as the recruitment switch and linking it to mTORC1.

    Evidence Cell-based recruitment assays with Rag GTPase mutants, PI3P manipulation, and starvation conditions

    PMID:33464297

    Open questions at the time
    • Direct contact between the complex and Rag GTPases not structurally defined
  10. 2023 Medium

    Identified impaired cholesterol trafficking as a distinct lysosomal consequence of SPG11 loss, with axonal phenotypes rescuable by LXR agonists.

    Evidence hESC SPG11 knockdown and disease-mutation knock-in cortical neurons with cholesterol distribution imaging, LXR agonist treatment, axonal outgrowth and transport assays

    PMID:37709208

    Open questions at the time
    • Whether cholesterol and ganglioside accumulation share a common upstream lysosomal defect unclear
    • Single lab
  11. 2024 High

    Showed ganglioside accumulation in lysosomes is a causal driver of axonal pathology in vivo, reversible by reducing glycosphingolipid synthesis.

    Evidence Spg11 knockout mice with AAV miRNA knockdown of St3gal5 and venglustat treatment, ganglioside quantification, behavior, serum NfL, and axonal spheroid counts plus human neuron validation

    PMID:38876323

    Open questions at the time
    • Mechanism by which ganglioside buildup generates spheroids not detailed
  12. 2024 High

    Extended spatacsin function to innate immunity, showing its loss destabilizes AP5 in immune cells and hyperactivates the non-canonical inflammasome through increased STAT1 signaling.

    Evidence Spg11 KO mouse microglia/BMDMs and patient MDMs, LPS challenge in vivo, mass spectrometry, STAT1 phospho westerns, STAT1 inhibitor rescue of neuronal toxicity

    PMID:38305941

    Open questions at the time
    • How lysosomal/AP5 dysfunction mechanistically elevates STAT1 phosphorylation not resolved
  13. 2025 High

    Provided the structural basis for the complex and reconstituted its membrane-remodeling activity, unifying the recruitment and ALR observations into a physical mechanism.

    Evidence Cryo-EM of AP5-SPG11-SPG15, PI3P binding and in vitro membrane tubulation assays, and domain deletion constructs

    PMID:40175557

    Open questions at the time
    • Structure of the membrane-engaged, curvature-sensing state not captured
    • In vivo tubulation dynamics not visualized
  14. 2025 High

    Defined a lysosomal calcium–PI4K2A–PI(4)P–mTOR axis through which spatacsin loss disrupts cortical development, with TRPML1 modulation as a corrective intervention.

    Evidence Spg11 KO mouse and iPSC cortical organoids with lysosomal calcium measurement, PI4K2A localization, PI(4)P and mTOR assays, RNA-seq, and TRPML1 pharmacological rescue

    PMID:42049147

    Open questions at the time
    • Relationship between this axis and the GSK3β pathway in NPCs not integrated

Open questions

Synthesis pass · forward-looking unresolved questions
  • How a single lysosomal reformation defect bifurcates into distinct downstream cascades — GSK3β, lysosomal Ca2+/PI4K2A/mTOR, lipid accumulation, and STAT1-driven inflammation — and whether they converge on a common proximal lesion remains unresolved.
  • No unifying model linking the four downstream pathways
  • Cell-type specificity of each cascade not systematically compared
  • Cargo whose mistrafficking initiates each cascade unidentified

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0008289 lipid binding 2 GO:0060090 molecular adaptor activity 2
Localization
GO:0005764 lysosome 4 GO:0005768 endosome 2 GO:0005829 cytosol 1
Pathway
R-HSA-9612973 Autophagy 2 R-HSA-5653656 Vesicle-mediated transport 1 R-HSA-9609507 Protein localization 1
Partners
AP5B1AP5M1AP5S1AP5Z1RAB11RAB5ASPG15
Complex memberships
AP5-SPG11-SPG15 complex

Evidence

Reading pass · 15 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2013 SPG11 (spatacsin) and SPG15 (spastizin) physically interact with all four subunits of the AP-5 adaptor protein complex in a ~1:1:1:1:1:1 stoichiometry, as shown by co-immunoprecipitation from both cytosol and detergent-extracted membranes. The N-terminal β-propeller-like domain of SPG11 interacts in vitro with AP-5. All six knockdowns (AP-5 subunits, SPG11, SPG15) phenocopy each other, causing cation-independent mannose-6-phosphate receptor trapping in early endosome clusters. AP-5, SPG11, and SPG15 co-localize on a late endosomal/lysosomal compartment, suggesting they form a coat-like complex involved in protein sorting. Co-immunoprecipitation (reciprocal, from cytosol and membranes), in vitro binding assay, siRNA knockdown with CI-M6PR localization readout, co-localization imaging, secondary structure prediction Molecular biology of the cell High 23825025
2015 Loss of spatacsin (Spg11 knockout) in mice causes lysosome depletion: lysosome numbers are reduced in knockout MEFs and in cortical neurons and Purkinje cells in vivo. Recovery of lysosomes during sustained starvation is impaired, consistent with a defect in autophagic lysosome reformation (ALR). Lipidated LC3 levels are increased in knockout MEFs indicating a generalized autophagy defect. Degenerating neurons accumulate autofluorescent material positive for LAMP1 and p62. Cathepsin D processing and lysosomal pH are preserved, indicating the defect is specific to lysosome biogenesis/reformation rather than bulk lysosomal enzymatic function. Spg11 knockout mouse model; lysosome quantification by immunofluorescence in MEFs and neurons in vivo; LC3 lipidation western blot; cathepsin D processing assay; lysosomal pH measurement; starvation-recovery assay PLoS genetics High 26284655
2014 Spatacsin localizes to axons and dendrites of human and mouse neurons, co-localizes with cytoskeletal and synaptic vesicle markers, and is present in synaptosomes. Loss of spatacsin (SPG11 patient-derived neurons or siRNA knockdown in mouse cortical neurons) leads to: downregulation of axonal genes, decreased neurite complexity, accumulation of membranous bodies in axonal processes, reduced acetylated tubulin (axonal instability), and reduced anterograde vesicle trafficking as shown by time-lapse imaging. iPSC-derived neurons from SPG11 patients; siRNA knockdown in mouse cortical neurons; immunofluorescence co-localization; synaptosome fractionation; time-lapse live imaging of vesicle trafficking; acetylated tubulin western blot Human molecular genetics High 24794856
2014 Fibroblasts from SPG11 patients show selective enlargement of LAMP1-positive lysosomal structures. The stabilities of SPG15 (spastizin) and SPG11 (spatacsin) proteins are interdependent: loss of one destabilizes the other. Patient-derived fibroblast analysis; immunofluorescence for LAMP1; electron microscopy for lysosomal storage; western blot for protein stability in SPG11 and SPG15 patient cells Annals of clinical and translational neurology Medium 24999486
2018 SPG11 mutations cause a milder autophagy defect than SPG15 mutations. Both SPG11 and SPG15 interact with RAB5A and RAB11 (endosome trafficking regulators), but only SPG15 mutations affect RAB protein interactions and activation. SPG15 mutations disrupt fusion between autophagosomes and endosomes, while SPG11 mutations do not affect this step. Both proteins are required for autophagic lysosome reformation (ALR), but SPG15 additionally acts at the autophagy–endocytosis intersection. Patient-derived cells with SPG11 or SPG15 mutations; co-immunoprecipitation for RAB5A/RAB11 interactions; RAB activation assays; autophagosome–endosome fusion assays; ALR assays; constitutively active RAB5A rescue experiment Autophagy Medium 30081747
2021 Recruitment of the AP-5/SPG11/SPG15 complex to late endosomes/lysosomes requires coincidence detection of two signals: phosphatidylinositol 3-phosphate (PI3P, via the SPG15 FYVE domain) and Rag GTPases. GDP-locked RagC promotes complex recruitment while GTP-locked RagA prevents it. Recruitment is enhanced in starved cells, revealing an interplay between this complex and the mTORC1 pathway. Cell-based recruitment assays with dominant-negative/constitutively active Rag GTPase mutants; PI3P manipulation; localization imaging; starvation conditions The Journal of cell biology High 33464297
2016 SPG11 patient-derived neural progenitor cells (NPCs) show dysregulation of the GSK3β-signaling pathway. GSK3β hyperactivation in SPG11-NPCs impairs proliferation, reducing neural cell numbers. Pharmacological GSK3 modulation rescues the NPC proliferation defect. Gene expression profiling revealed alterations in cell-cycle, neurogenesis, cortical development, and autophagy pathways. iPSC-derived NPCs from 3 SPG11 patients; transcriptome profiling; proliferation assays; GSK3 inhibitor rescue (pharmacological modulation); pathway analysis Annals of neurology Medium 26971897
2019 SPG11 patient-derived cortical organoids are smaller than controls, with larger ventricles and thinner germinal walls, caused by increased asymmetric divisions of NPCs leading to premature neurogenesis. GSK3 inhibitors including FDA-approved tideglusib rescue organoid size and premature neurogenesis. 3D brain organoids from SPG11 patient iPSCs; 2D NPC cultures; division mode quantification; GSK3 inhibitor (tideglusib) rescue Human molecular genetics Medium 30476097
2018 GSK3β inhibitor tideglusib rescues neurite pathology (shorter, less complex neurites), increased cell death, and membranous inclusions in SPG11 iPSC-derived cortical neurons and in a CRISPR-Cas9 SPG11 knockout line, confirming GSK3β/βCatenin pathway dysregulation as a mechanistic basis for neurodegeneration. SPG11 patient iPSC-derived cortical neurons; CRISPR-Cas9 SPG11 knockout iPSC line; tideglusib treatment; neurite morphometry; cell death assays; membrane inclusion quantification Frontiers in neuroscience Medium 30574063
2025 Cryo-EM structure of the AP5-SPG11-SPG15 complex reveals: SPG11-SPG15 form a W-shaped intertwined head-to-head heterodimer; the N-terminal region of SPG11 is required for AP5 complex interaction and assembly; AP5 adopts a super-open conformation. The AP5-SPG11-SPG15 complex binds PI3P, senses membrane curvature, and drives membrane remodeling (tubulation initiation) in vitro. Cryo-electron microscopy; in silico structural prediction; PI3P binding assay; in vitro membrane remodeling/tubulation assay; domain deletion constructs Nature structural & molecular biology High 40175557
2024 SPG11 loss of function causes accumulation of gangliosides in lysosomes of Spg11 knockout mouse neurons. Reducing ganglioside synthesis by AAV-mediated miRNA knockdown of St3gal5 or pharmacological inhibition of glucosylceramide synthase (venglustat) prevents ganglioside accumulation, delays motor and cognitive symptom onset, prevents neurofilament light chain elevation, and strongly reduces axonal spheroid formation. Venglustat also reduced axonal spheroids in cultured human SPG11 neurons, linking ganglioside trafficking to axonal pathology. Spg11 knockout mice; AAV-PHP.eB viral miRNA delivery targeting St3gal5; venglustat pharmacological treatment; ganglioside quantification; behavioral testing; serum NfL measurement; axonal spheroid counting in mouse and human SPG11 cultured neurons Neurobiology of disease High 38876323
2023 SPG11 deficiency in human cortical projection neurons (from hESC-derived knockdown and disease-mutation knock-in lines) causes cholesterol accumulation in lysosomes with reduction at the plasma membrane, indicating impaired cholesterol trafficking. LXR agonists restore cholesterol homeostasis and rescue axonal outgrowth defects, impaired axonal transport, and axonal swellings. hESC SPG11 knockdown; disease-mutation knock-in hESC cortical neurons; cholesterol subcellular distribution imaging; LXR agonist treatment; axonal outgrowth and transport assays Neurobiology of disease Medium 37709208
2024 Loss of SPG11 function in microglia/macrophages causes hyperactivation of the non-canonical inflammasome, resulting in stronger inflammatory responses. LPS challenge triggers markedly increased lethality and inflammatory response in Spg11 KO mice in vivo. Mass spectrometry of activated BMDMs from Spg11 KO mice reveals massive downregulation of AP5 subunits upon Spg11 disruption, linking spatacsin to AP5 stability in immune cells. STAT1 phosphorylation is increased as the molecular mechanism connecting IFNγ-mediated immune hyperactivation and SPG11 loss of function; STAT1 inhibition decreases CXCL10 production and rescues toxic effects on SPG11 neurons. Spg11 KO mouse primary microglia and BMDMs; patient-derived MDMs; LPS challenge in vivo; mass spectrometry of activated BMDMs; STAT1 phosphorylation western blot; STAT1 inhibitor rescue; CXCL10 ELISA; IFNγ stimulation of patient iPSC-derived microglia-like cells Acta neuropathologica High 38305941
2025 SPG11 mutations cause lysosomal calcium accumulation in neural progenitor cells (NPCs), which reduces NPC proliferation and diminishes apical tight junctions during cortical development. This is mechanistically linked to lysosomal recruitment of PI4K2A (phosphatidylinositol 4-kinase type 2 alpha), resulting in elevated PI(4)P levels that hypoactivate mTOR signaling. Pharmacological modulation of the lysosomal calcium channel TRPML1 corrects all developmental phenotypes in cortical organoids. Spg11 knockout mouse; iPSC-derived cortical organoids from SPG11 models; lysosomal calcium measurement; PI4K2A localization by imaging; PI(4)P quantification; mTOR activity assays; RNA sequencing; TRPML1 agonist/antagonist pharmacological rescue; tight junction imaging Neurobiology of disease High 42049147
2010 Morpholino-mediated knockdown of spatacsin (spg11) in zebrafish embryos causes CNS developmental defects and an overall perturbation of neuronal differentiation with disruption of axon pathway formation, identifying a critical role for spatacsin in early neural development in vivo. Morpholino antisense oligonucleotide knockdown in zebrafish; whole-mount in situ hybridization for transcript distribution; axon pathway immunostaining Neurogenetics Medium 20390432

Source papers

Stage 0 corpus · 93 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2007 Mutations in SPG11, encoding spatacsin, are a major cause of spastic paraplegia with thin corpus callosum. Nature genetics 263 17322883
2007 Mutations in SPG11 are frequent in autosomal recessive spastic paraplegia with thin corpus callosum, cognitive decline and lower motor neuron degeneration. Brain : a journal of neurology 189 18079167
2014 Overlapping phenotypes in complex spastic paraplegias SPG11, SPG15, SPG35 and SPG48. Brain : a journal of neurology 132 24833714
2015 In Vivo Evidence for Lysosome Depletion and Impaired Autophagic Clearance in Hereditary Spastic Paraplegia Type SPG11. PLoS genetics 101 26284655
2013 Interaction between AP-5 and the hereditary spastic paraplegia proteins SPG11 and SPG15. Molecular biology of the cell 98 23825025
2014 Lysosomal abnormalities in hereditary spastic paraplegia types SPG15 and SPG11. Annals of clinical and translational neurology 92 24999486
2014 Dysfunction of spatacsin leads to axonal pathology in SPG11-linked hereditary spastic paraplegia. Human molecular genetics 87 24794856
2011 Exome sequencing reveals SPG11 mutations causing juvenile ALS. Neurobiology of aging 85 22154821
2015 ALS5/SPG11/KIAA1840 mutations cause autosomal recessive axonal Charcot-Marie-Tooth disease. Brain : a journal of neurology 84 26556829
2009 SPG11 spastic paraplegia. A new cause of juvenile parkinsonism. Journal of neurology 81 19224311
2008 SPG11 mutations are common in familial cases of complicated hereditary spastic paraplegia. Neurology 66 18337587
2004 Clinical progression and genetic analysis in hereditary spastic paraplegia with thin corpus callosum in spastic gait gene 11 (SPG11). Archives of neurology 62 14732628
2009 Frequency and phenotype of SPG11 and SPG15 in complicated hereditary spastic paraplegia. Journal of neurology, neurosurgery, and psychiatry 60 19917823
2019 "Ears of the Lynx" MRI Sign Is Associated with SPG11 and SPG15 Hereditary Spastic Paraplegia. AJNR. American journal of neuroradiology 57 30606727
2011 Novel mutations in SPG11 cause hereditary spastic paraplegia associated with early-onset levodopa-responsive Parkinsonism. Movement disorders : official journal of the Movement Disorder Society 54 21381113
2009 Screening of ARHSP-TCC patients expands the spectrum of SPG11 mutations and includes a large scale gene deletion. Human mutation 54 19105190
2003 Allelic variation in the contiguous loci encoding Candida albicans ALS5, ALS1 and ALS9. Microbiology (Reading, England) 51 14523127
2001 The ALS5 gene of Candida albicans and analysis of the Als5p N-terminal domain. Yeast (Chichester, England) 50 11124701
2008 Hereditary spastic paraplegia with mental impairment and thin corpus callosum in Tunisia: SPG11, SPG15, and further genetic heterogeneity. Archives of neurology 49 18332254
2018 ZFYVE26/SPASTIZIN and SPG11/SPATACSIN mutations in hereditary spastic paraplegia types AR-SPG15 and AR-SPG11 have different effects on autophagy and endocytosis. Autophagy 47 30081747
2007 Deletion of ALS5, ALS6 or ALS7 increases adhesion of Candida albicans to human vascular endothelial and buccal epithelial cells. Medical mycology 42 17654269
2016 GSK3ß-dependent dysregulation of neurodevelopment in SPG11-patient induced pluripotent stem cell model. Annals of neurology 40 26971897
2009 SPG11 mutations cause Kjellin syndrome, a hereditary spastic paraplegia with thin corpus callosum and central retinal degeneration. American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics 40 19194956
2008 Forceps minor region signal abnormality "ears of the lynx": an early MRI finding in spastic paraparesis with thin corpus callosum and mutations in the spatacsin gene (SPG11) on chromosome 15. Journal of neuroimaging : official journal of the American Society of Neuroimaging 39 19040626
2006 Spastic paraplegia with thin corpus callosum: description of 20 new families, refinement of the SPG11 locus, candidate gene analysis and evidence of genetic heterogeneity. Neurogenetics 36 16699786
2020 Janus-faced spatacsin (SPG11): involvement in neurodevelopment and multisystem neurodegeneration. Brain : a journal of neurology 35 32355960
2007 SPG11: a consistent clinical phenotype in a family with homozygous spatacsin truncating mutation. Neurogenetics 34 17717710
2007 Analysis of ALS5 and ALS6 allelic variability in a geographically diverse collection of Candida albicans isolates. Fungal genetics and biology : FG & B 33 17625934
2010 Novel SPG11 mutations in Asian kindreds and disruption of spatacsin function in the zebrafish. Neurogenetics 30 20390432
2009 Point mutations and a large intragenic deletion in SPG11 in complicated spastic paraplegia without thin corpus callosum. Journal of medical genetics 29 19196735
2019 Human SPG11 cerebral organoids reveal cortical neurogenesis impairment. Human molecular genetics 28 30476097
2008 Clinical heterogeneity and genotype-phenotype correlations in hereditary spastic paraplegia because of Spatacsin mutations (SPG11). European journal of neurology 28 18717728
2006 Hereditary spastic paraplegia with thin corpus callosum: reduction of the SPG11 interval and evidence for further genetic heterogeneity. Archives of neurology 27 16682547
2010 Kjellin syndrome: long-term neuro-ophthalmologic follow-up and novel mutations in the SPG11 gene. Ophthalmology 26 21035867
2008 SPG11 compound mutations in spastic paraparesis with thin corpus callosum. Neurology 26 18663179
2008 Novel mutations of the SPG11 gene in hereditary spastic paraplegia with thin corpus callosum. Journal of the neurological sciences 26 18835492
2021 Rag GTPases and phosphatidylinositol 3-phosphate mediate recruitment of the AP-5/SPG11/SPG15 complex. The Journal of cell biology 25 33464297
2015 SPG11 Mutations Associated With a Complex Phenotype Resembling Dopa-Responsive Dystonia. Movement disorders clinical practice 25 30363882
2012 Alu elements mediate large SPG11 gene rearrangements: further spatacsin mutations. Genetics in medicine : official journal of the American College of Medical Genetics 25 22237444
2018 Tideglusib Rescues Neurite Pathology of SPG11 iPSC Derived Cortical Neurons. Frontiers in neuroscience 24 30574063
2008 Identification of a heterozygous genomic deletion in the spatacsin gene in SPG11 patients using high-resolution comparative genomic hybridization. Neurogenetics 21 18787847
2006 Further clinical and genetic characterization of SPG11: hereditary spastic paraplegia with thin corpus callosum. Neuropediatrics 19 16773502
2011 Structural and metabolic damage in brains of patients with SPG11-related spastic paraplegia as detected by quantitative MRI. Journal of neurology 17 21625935
2015 Turkish families with juvenile motor neuron disease broaden the phenotypic spectrum of SPG11. Neurology. Genetics 15 27066562
2009 Autosomal recessive hereditary spastic paraplegia with thin corpus callosum: a novel mutation in the SPG11 gene and further evidence for genetic heterogeneity. European journal of neurology 15 19087158
2024 Neuroinflammatory disease signatures in SPG11-related hereditary spastic paraplegia patients. Acta neuropathologica 14 38305941
2017 Identification of novel SPG11 mutations in a cohort of Chinese families with hereditary spastic paraplegia. The International journal of neuroscience 14 28933964
2016 Severe axonal neuropathy is a late manifestation of SPG11. Journal of neurology 14 27544499
2010 Cognitive profile in spastic paraplegia with thin corpus callosum and mutations in SPG11. Neuropediatrics 14 20571989
2022 Structure and Conservation of Amyloid Spines From the Candida albicans Als5 Adhesin. Frontiers in molecular biosciences 13 35874616
2009 Novel compound heterozygous mutations of the SPG11 gene in Korean families with hereditary spastic paraplegia with thin corpus callosum. Journal of neurology 13 19513778
2021 Circ-SPG11 knockdown hampers IL-1β-induced osteoarthritis progression via targeting miR-337-3p/ADAMTS5. Journal of orthopaedic surgery and research 11 34140036
2020 Description of combined ARHSP/JALS phenotype in some patients with SPG11 mutations. Molecular genetics & genomic medicine 11 32383541
2016 A rare case of SPG11 mutation with multiple sclerosis. Revue neurologique 11 27180005
2012 The GPI anchor signal sequence dictates the folding and functionality of the Als5 adhesin from Candida albicans. PloS one 11 22509405
2010 Expanding the clinical spectrum of SPG11 gene mutations in recessive hereditary spastic paraplegia with thin corpus callosum. European journal of medical genetics 11 20971220
2012 Novel SPG11 mutations in Chinese families with hereditary spastic paraplegia with thin corpus callosum. Parkinsonism & related disorders 10 23121729
2012 Microstructural integrity of cerebral fiber tracts in hereditary spastic paraparesis with SPG11 mutation. AJNR. American journal of neuroradiology 9 23221952
2018 Novel SPG11 Mutations in a Patient with Symptoms Mimicking Multiple Sclerosis. Internal medicine (Tokyo, Japan) 8 29877287
2017 Monozygotic twins with a new compound heterozygous SPG11 mutation and different disease expression. Journal of the neurological sciences 8 28991695
2016 Novel Compound Heterozygous Spatacsin Mutations in a Greek Kindred with Hereditary Spastic Paraplegia SPG11 and Dementia. Neuro-degenerative diseases 7 27318863
2013 Novel mutations c.[5121_5122insAG]+[6859C>T] of the SPG11 gene associated with cerebellum hypometabolism in a Chinese case of hereditary spastic paraplegia with thin corpus callosum. Parkinsonism & related disorders 7 24315199
2022 An autopsied case report of spastic paraplegia with thin corpus callosum carrying a novel mutation in the SPG11 gene: widespread degeneration with eosinophilic inclusions. BMC neurology 6 34979968
2021 Mild cognitive impairment in novel SPG11 mutation-related sporadic hereditary spastic paraplegia with thin corpus callosum: case series. BMC neurology 6 33430805
2021 Circ_SPG11 plays contributing effects on IL-1β-induced chondrocyte apoptosis and ECM degradation via miR-665 inhibition-mediated GREM1 upregulation. Clinical immunology (Orlando, Fla.) 6 34798237
2016 Whole-genome sequencing of two probands with hereditary spastic paraplegia reveals novel splice-donor region variant and known pathogenic variant in SPG11. Cold Spring Harbor molecular case studies 6 27900367
2015 Late-onset spastic paraplegia: Aberrant SPG11 transcripts generated by a novel splice site donor mutation. Journal of the neurological sciences 6 26671123
2025 Structural basis for membrane remodeling by the AP5-SPG11-SPG15 complex. Nature structural & molecular biology 5 40175557
2024 Decreasing ganglioside synthesis delays motor and cognitive symptom onset in Spg11 knockout mice. Neurobiology of disease 5 38876323
2023 Liver-X-receptor agonists rescue axonal degeneration in SPG11-deficient neurons via regulating cholesterol trafficking. Neurobiology of disease 5 37709208
2022 Neurometabolic Dysfunction in SPG11 Hereditary Spastic Paraplegia. Nutrients 5 36432490
2022 SPG11: clinical and genetic features of seven Czech patients and literature review. Neurological research 4 35254204
2020 Chinese families with autosomal recessive hereditary spastic paraplegia caused by mutations in SPG11. BMC neurology 4 31900114
2018 Homocarnosinosis: A historical update and findings in the SPG11 gene. Acta neurologica Scandinavica 4 29732542
2018 Quantification of dysarthrοphonia in a Cypriot family with autosomal recessive hereditary spastic paraplegia associated with a homozygous SPG11 mutation. Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology 4 29804168
2013 Exome sequencing identifies novel compound heterozygous mutations in SPG11 that cause autosomal recessive hereditary spastic paraplegia. Journal of the neurological sciences 4 24090761
2022 Blended Phenotype of Prader-Willi Syndrome and HSP-SPG11 Caused by Maternal Uniparental Isodisomy. Neurology. Genetics 3 36524102
2016 A case report of SPG11 mutations in a Chinese ARHSP-TCC family. BMC neurology 3 27256065
2016 Identification of a Heterozygous SPG11 Mutation by Clinical Exome Sequencing in a Patient With Hereditary Spastic Paraplegia: A Case Report. Annals of rehabilitation medicine 3 28119845
2015 Exome sequencing reveals novel SPG11 mutation in hereditary spastic paraplegia with complicated phenotypes. Journal of clinical neuroscience : official journal of the Neurosurgical Society of Australasia 3 26003865
2024 Hereditary spastic paraplegia with thin corpus callosum and SPG11 mutation: A neuropathological evaluation. Neuropathology : official journal of the Japanese Society of Neuropathology 2 39391989
2023 Case report: Novel mutations in the SPG11 gene in a case of autosomal recessive hereditary spastic paraplegia with a thin corpus callosum. Frontiers in integrative neuroscience 2 37035454
2022 SPG11 presenting with dystonic tremor in childhood. Parkinsonism & related disorders 2 35617747
2022 Two novel mutations in ALDH18A1 and SPG11 gene found by whole-exome sequencing in spastic paraplegia disease patients in Iran. Genomics & informatics 2 36239107
2020 Identification of a Mutation in SPG11 in an Iranian Patient with Spastic Paraplegia and Ears of the Lynx Sign. Journal of molecular neuroscience : MN 2 32040826
2025 Burden of pathogenetic and likely pathogenetic variants in SPG7, SPG11 and AP4 genes in Amyotrophic Lateral Sclerosis. A case-control study. Journal of neurology 1 40498122
2025 Nutritional Approaches in Neurodegenerative Disorders: A Mini Scoping Review with Emphasis on SPG11-Related Conditions. Nutrients 1 41228418
2023 Upregulation of Heat-Shock Protein (hsp)-27 in a Patient with Heterozygous SPG11 c.1951C>T and SYNJ1 c.2614G>T Mutations Causing Clinical Spastic Paraplegia. Genes 1 37510225
2022 A complex form of hereditary spastic paraplegia harboring a novel variant, p.W1515*, in the SPG11 gene. eNeurologicalSci 1 35036589
2021 Generation and characterization of an endogenously tagged SPG11-human iPSC line by CRISPR/Cas9 mediated knock-in. Stem cell research 1 34479069
2026 SPG11 models reveal lysosomal calcium regulation of neural progenitor proliferation. Neurobiology of disease 0 42049147
2025 Hyperactivity of the non-canonical inflammasome in SPG11 and SPG48. EBioMedicine 0 41138668
2020 Homozygous frameshift mutation of SPG11 as a cause of progressive flaccid paralysis, ataxia and dysphagia. Journal of clinical neuroscience : official journal of the Neurosurgical Society of Australasia 0 33222977

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