Affinage

SPG7

Mitochondrial inner membrane m-AAA protease component paraplegin · UniProt Q9UQ90

Length
795 aa
Mass
88.2 kDa
Annotated
2026-06-10
60 papers in source corpus 12 papers cited in narrative 12 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 5/6 claims corpus-supported (83%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

SPG7 (paraplegin) is a mitochondrial inner-membrane protein that assembles with AFG3L2 into the ATP-dependent m-AAA metalloprotease, which performs membrane protein quality control and substrate processing essential for mitochondrial integrity (PMID:24767997, PMID:30252181). Its AAA+ ATPase domain, crystallized in an ADP-bound state, drives conformational cycling that delivers substrate peptides to its protease domain within a hexameric assembly (PMID:19841671), and SPG7 itself is matured by AFG3L2-mediated cleavage that is gated by AFG3L2 tyrosine phosphorylation—an arginine-688-to-glutamine variant bypasses this control to yield constitutive activation, elevated ATP and ROS, and increased proliferation (PMID:24767997). Through the m-AAA complex SPG7 governs processing of key substrates: it directs association with the mitochondrial Ca2+ uniporter (MCU) to regulate higher-order MCU complex assembly and basal mitochondrial Ca2+ uptake (PMID:31097542), and together with AFG3L2 it is required for normal OPA1 processing and mitochondrial network integrity (PMID:30252181). SPG7 controls the mitochondrial permeability transition pore (mPTP): early work placed it in a heterooligomeric pore with VDAC and cyclophilin D (PMID:26387735), while subsequent analysis recast it as an indirect, Ca2+-dependent modulator of pore opening (PMID:31097542), and it is specifically required for efficient transient (flickering) mPTP opening, which loss of SPG7 impairs via increased SIRT3 activity and cyclophilin D deacetylation, disrupting presynaptic neurotransmitter release (PMID:33045469). Loss of SPG7 produces respiratory chain defects, disordered mitochondrial DNA maintenance, and a remodeled mitochondrial proteome marked by depleted mito-ribosomal subunits, ultimately driving axonal degeneration in patient and mouse neurons that is rescued pharmacologically by the mPTP modulator Bz-423 (PMID:33045469, PMID:24727571, PMID:14985266, PMID:37086482, PMID:37766787). SPG7 mutations cause hereditary spastic paraplegia and progressive external ophthalmoplegia with multiple mitochondrial DNA deletions (PMID:24727571).

Mechanistic history

Synthesis pass · year-by-year structured walk · 11 steps
  1. 2004 Medium

    Establishing the cellular consequence of paraplegin loss showed that SPG7 dysfunction compromises oxidative phosphorylation, anchoring the disease to a mitochondrial bioenergetic defect.

    Evidence Respiratory chain enzyme activity assays in patient muscle biopsies and cultured myoblast mitochondrial fractions

    PMID:14985266

    Open questions at the time
    • Does not identify which substrates or complexes SPG7 directly processes
    • Correlative tissue assay does not establish the molecular mechanism linking SPG7 loss to complex I/II/III deficits
  2. 2009 High

    Determining the structure of the SPG7 AAA+ ATPase domain provided the mechanistic basis for how the protein couples ATP hydrolysis to substrate handling and how disease mutations disrupt catalysis.

    Evidence X-ray crystallography of the ADP-bound ATPase domain at 2.2 A resolution

    PMID:19841671

    Open questions at the time
    • Structure is of an isolated domain, not the assembled hexameric protease or the full m-AAA complex
    • Does not visualize substrate engagement or the protease domain
  3. 2012 Medium

    Discovery of an ER-targeted splice isoform revealed that the SPG7 locus produces more than the canonical mitochondrial protease, complicating interpretation of the existing knockout mouse.

    Evidence Alternative splicing characterization, subcellular fractionation, and live-cell localization in mouse brain and retina

    PMID:22563492

    Open questions at the time
    • Function of the ER-localized paraplegin-2 isoform is undefined
    • Whether paraplegin-2 has protease activity in the ER lumen is untested
  4. 2014 Medium

    Defining how the SPG7 m-AAA protease is activated showed that AFG3L2-dependent cleavage, gated by AFG3L2 phosphorylation, controls SPG7 maturation, and that a regulatory variant uncouples this to alter cell metabolism.

    Evidence Biochemical processing and phosphorylation assays comparing wild-type versus Q688 SPG7 with ATP/ROS/proliferation readouts

    PMID:24767997

    Open questions at the time
    • The kinase responsible for AFG3L2 phosphorylation is not identified
    • Direct structural mechanism by which Q688 bypasses regulation is not resolved
  5. 2014 Medium

    Linking SPG7 mutations to progressive external ophthalmoplegia with multiple mtDNA deletions extended its role beyond protein quality control to mitochondrial DNA maintenance.

    Evidence Whole exome sequencing, proteomics, and single-fiber/deep mtDNA resequencing in patient muscle and fibroblasts

    PMID:24727571

    Open questions at the time
    • Mechanistic link between m-AAA dysfunction and mtDNA clonal expansion is not established
    • Does not identify the protease substrate mediating mtDNA instability
  6. 2015 Medium

    A targeted screen first implicated SPG7 in the permeability transition pore, proposing it as a core pore component alongside VDAC and cyclophilin D.

    Evidence RNAi screening, co-immunoprecipitation, membrane potential and Ca2+ retention capacity assays

    PMID:26387735

    Open questions at the time
    • The core-component claim was subsequently disputed
    • Co-IP does not establish a structural role within the pore
  7. 2018 Medium

    Demonstrating that combined AFG3L2/SPG7 deficiency disrupts OPA1 processing and mitochondrial network integrity defined a substrate-level role for the assembled m-AAA complex in fusion control.

    Evidence Patient fibroblast morphology and OPA1 processing western blots with yeast functional complementation

    PMID:30252181

    Open questions at the time
    • Whether SPG7 alone, versus the AFG3L2/SPG7 complex, cleaves OPA1 is not separated
    • Digenic dependency complicates assigning the defect specifically to SPG7
  8. 2019 Medium

    Reassessing the pore model showed SPG7 is not a structural pore component but an indirect modulator acting through MCU processing and basal mitochondrial Ca2+, refining the earlier mechanism.

    Evidence SPG7 knockout, cyclosporine A insensitivity testing, m-AAA/MCU co-IP and MCU complex formation assays

    PMID:31097542

    Open questions at the time
    • Directly contradicts the prior core-component model and the conflict is unresolved
    • Direct cleavage of MCU subunits by SPG7 is inferred from association rather than demonstrated proteolysis
  9. 2020 High

    Connecting SPG7 to transient mPTP flickering established a synaptic mechanism for neurodegeneration, where SPG7 loss raises SIRT3 activity to deacetylate cyclophilin D and impair neurotransmitter release.

    Evidence Live-cell mPTP flickering assays, patient fibroblasts, Spg7-/- mouse neurons, CypD acetylation analysis, and in vivo Bz-423 rescue

    PMID:33045469

    Open questions at the time
    • How SPG7 loss increases SIRT3 expression/activity is not defined
    • Link between m-AAA protease activity and flickering control is not mechanistically bridged
  10. 2023 Medium

    In vivo proteomic and epistasis studies tied SPG7-dependent mitochondrial dysfunction to mito-ribosome and transporter remodeling and to SARM1-driven axonal degeneration in a neuron-type-specific manner.

    Evidence Enhanced Spg7/Afg3l1 double-knockout mouse, proteomics, SARM1 genetic deletion, behavioral and EM analyses; complemented by iPSC-derived patient cortical neurons with Bz-423 rescue

    PMID:37086482 PMID:37766787

    Open questions at the time
    • SARM1 deletion rescues cerebellar but not long spinal axons, leaving the spinal degeneration mechanism unexplained
    • Causal chain from proteome remodeling to axonal loss is incompletely resolved
  11. 2025 Low

    Placing SPG7 downstream of PISD in keratinocytes positioned it within an upstream regulatory pathway controlling mPTP-dependent necroptosis.

    Evidence PISD and SPG7 overexpression with mPTP opening and necroptosis (p-MLKL) readouts in HaCaT cells

    PMID:40780696

    Open questions at the time
    • Single overexpression study in one cell line without loss-of-function or structural validation
    • Whether PISD regulates SPG7 directly or indirectly is not determined

Open questions

Synthesis pass · forward-looking unresolved questions
  • The conflicting models of how SPG7 controls the mPTP—direct pore component versus indirect Ca2+/MCU modulator—and the identity of the m-AAA substrates linking protease activity to mtDNA maintenance, mito-ribosome biogenesis, and flickering remain unresolved.
  • No reconciliation of the core-component versus modulator pore models
  • Direct proteolytic substrates underlying mtDNA instability and ribosome depletion not biochemically defined
  • Mechanism coupling m-AAA activity to SIRT3/CypD regulation unknown

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0016787 hydrolase activity 2 GO:0140096 catalytic activity, acting on a protein 2 GO:0140657 ATP-dependent activity 1
Localization
GO:0005739 mitochondrion 3 GO:0005783 endoplasmic reticulum 1
Pathway
R-HSA-5357801 Programmed Cell Death 3 R-HSA-392499 Metabolism of proteins 2 R-HSA-1430728 Metabolism 1
Partners
AFG3L2CYCLOPHILIN D (PPIF)MCUOPA1VDAC
Complex memberships
m-AAA proteasemitochondrial permeability transition pore

Evidence

Reading pass · 12 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2015 SPG7 (paraplegin) is a necessary and conserved core component of the mitochondrial permeability transition pore (mPTP). The PTP was identified as a heterooligomeric complex composed of VDAC, SPG7, and cyclophilin D (CypD). Loss of SPG7 resulted in higher mitochondrial Ca2+ retention and sustained mitochondrial membrane potential during Ca2+ and ROS stress, similar to CypD knockdown. Silencing or disruption of SPG7-CypD binding prevented Ca2+- and ROS-induced membrane potential depolarization and cell death. RNAi-based screening, biochemical co-immunoprecipitation, mitochondrial membrane potential assays, Ca2+ retention capacity assays Molecular cell Medium 26387735
2019 SPG7 does not constitute a core component of the mPTP itself, but modulates mPTP opening indirectly through regulation of basal mitochondrial Ca2+ concentration. SPG7 directs the m-AAA protease complex to favor association with the mitochondrial Ca2+ uniporter (MCU), and SPG7-dependent MCU processing regulates higher-order MCU complex formation. Loss of SPG7 decreased MCU complex formation, reducing mitochondrial Ca2+ uptake, which in turn increased resistance to Ca2+-induced mPTP opening independently of cyclophilin D (cyclosporine A-insensitive mechanism). SPG7 gene knockout, Ca2+-induced mPTP assays, cyclosporine A insensitivity testing, co-immunoprecipitation of m-AAA with MCU, MCU complex formation assays The Journal of biological chemistry Medium 31097542
2020 Paraplegin (SPG7) is required for efficient transient (flickering) opening of the mPTP. Loss of paraplegin impairs mPTP flickering by a mechanism involving increased expression and deacetylase activity of sirtuin3 (SIRT3), which promotes deacetylation of cyclophilin D, thereby hampering mPTP opening. Dysregulation of mPTP flickering at the pre-synaptic terminal impairs neurotransmitter release, leading to ineffective synaptic transmission. Pharmacological treatment with Bz-423 (which bypasses CypD activity) normalized synaptic transmission and rescued motor impairment in the Spg7-/- mouse model. Fluorescence-based mPTP flickering assay in live cells, SPG7 patient-derived fibroblasts, primary neurons from Spg7-/- mice, biochemical measurement of SIRT3 expression/activity and CypD acetylation status, neurotransmitter release assays, in vivo pharmacological rescue in mouse model EBioMedicine High 33045469
2014 SPG7 assembles with AFG3L2 into the m-AAA protease at the mitochondrial inner membrane. SPG7 processing and activation is regulated by tyrosine phosphorylation of AFG3L2 — SPG7 is cleaved and activated by AFG3L2 upon assembly. A variant replacing arginine 688 with glutamine (Q688) bypasses this phosphorylation-dependent regulation, resulting in constitutive processing and activation of the SPG7 m-AAA protease. Cells expressing Q688 produce higher ATP levels and reactive oxygen species (ROS), promoting cell proliferation. Biochemical processing assays, phosphorylation studies of AFG3L2, ATP and ROS measurements in cells expressing wild-type vs. Q688 variant SPG7 Cell reports Medium 24767997
2009 Crystal structure of the ATPase (AAA+) domain of human paraplegin/SPG7 bound to ADP was solved at 2.2 Å resolution, enabling assignment of specific side chain roles in the catalytic cycle and providing structural basis for understanding disease mutation mechanisms. The protein is believed to form a hexamer that uses ATPase-driven conformational changes in its AAA domain to deliver substrate peptides to its protease domain. X-ray crystallography at 2.2 Å resolution PloS one High 19841671
2012 Alternative splicing of mouse Spg7 produces a novel isoform (paraplegin-2) encoded by an alternative first exon that lacks the mitochondrial targeting sequence. Paraplegin-2 is targeted to the endoplasmic reticulum rather than mitochondria, and exposes its catalytic domains to the ER lumen. Endogenous paraplegin-2 accumulates in microsomal fractions from mouse brain and retina. The previously generated Spg7 knockout mouse model specifically ablates mitochondrial paraplegin while retaining expression of paraplegin-2. Alternative splicing characterization by RT-PCR, subcellular fractionation (microsomal fractions), live-cell localization studies, transcript analysis of existing knockout mouse model PloS one Medium 22563492
2014 SPG7 mutations cause progressive external ophthalmoplegia associated with multiple mitochondrial DNA deletions. SPG7 mutations caused increased mitochondrial biogenesis in patient muscle and mitochondrial fusion in patient fibroblasts, associated with clonal expansion of mitochondrial DNA mutations. This establishes SPG7 dysfunction as a cause of disordered mitochondrial DNA maintenance. Whole exome sequencing, transcript analysis, proteomics, mitochondrial network analysis, single-fiber mitochondrial DNA analysis, deep re-sequencing of mitochondrial DNA in patient tissue Brain : a journal of neurology Medium 24727571
2018 Concurrent heterozygous mutations in AFG3L2 and SPG7 (one allele each) result in abnormal processing of OPA1 (a dynamin-related GTPase essential for mitochondrial fusion) and severe fragmentation of the mitochondrial network in patient fibroblasts, a phenotype not observed in cells with mutations in only one of the two m-AAA subunits. Functional analysis in yeast demonstrated the pathogenic role of the AFG3L2 mutation. This establishes that the m-AAA complex (SPG7/AFG3L2 together) is required for normal OPA1 processing and mitochondrial network integrity. Patient fibroblast analysis, mitochondrial morphology assessment, OPA1 processing western blot, yeast functional complementation assay Human mutation Medium 30252181
2004 Biochemical analysis of muscle from patients with SPG7 compound heterozygous mutations revealed reduced citrate synthase-corrected complex I and complex II/III activities in muscle and complex I activity in mitochondrial-enriched fractions from cultured myoblasts, indicating that loss of paraplegin function causes a mitochondrial respiratory chain defect. Biochemical respiratory chain enzyme activity assays in patient muscle biopsies and mitochondrial fractions from cultured myoblasts Brain : a journal of neurology Medium 14985266
2023 Loss of SPG7 rewires the mitochondrial proteome in both spinal cord and cerebellar tissues, leading to early-onset decrease in mito-ribosomal subunits and remodeling of mitochondrial solute carriers and transporters. SARM1 deletion in an enhanced Spg7/Afg3l1 double-knockout mouse delays appearance of ataxic signs, rescues mitochondrial swelling and axonal degeneration of cerebellar granule cells, and dampens neuroinflammation in the cerebellum. SARM1 deletion also prevents ER abnormalities in long spinal cord axons but does not halt degeneration of these axons, establishing a neuron-specific interplay between SARM1 and SPG7-dependent mitochondrial dysfunction. Enhanced SPG7/AFG3L1 double-knockout mouse model, proteomics, behavioral assays, SARM1 genetic deletion (epistasis), histological and electron microscopy analysis of axonal degeneration and mitochondrial morphology Brain : a journal of neurology Medium 37086482
2023 In iPSC-derived cortical neurons from SPG7 patients, mitochondrial dysfunction (aberrant morphology, reduced membrane potential) is directly linked to neuronal defects including reduced neurite complexity, reduced synaptic gene/protein expression, reduced viability, and increased axonal degeneration. Treatment with Bz-423 (mPTP inducer/modulator) restored mitochondrial and neurite morphological defects and mitochondrial membrane potential to control levels, and rescued viability, confirming that mPTP dysregulation is a key pathomechanism in SPG7 disease neurons. iPSC differentiation to cortical neurons, high-throughput live-cell imaging, mitochondrial morphology and function assays, pharmacological rescue with Bz-423 Frontiers in neuroscience Medium 37766787
2025 In inflammatory HaCaT keratinocytes, PISD (phosphatidylserine decarboxylase) overexpression directly upregulates SPG7 expression, and SPG7 overexpression reverses mPTP opening and necroptosis induced by zinc oxide nanoparticles. This establishes a PISD→SPG7→mPTP pathway in which SPG7 acts downstream of PISD to regulate mPTP opening and cell death. SPG7 overexpression, PISD overexpression, mPTP opening assays, necroptosis markers (p-MLKL), mitochondrial morphology assessment in HaCaT cells Toxicology Low 40780696

Source papers

Stage 0 corpus · 60 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2015 SPG7 Is an Essential and Conserved Component of the Mitochondrial Permeability Transition Pore. Molecular cell 169 26387735
2014 Mutations in the SPG7 gene cause chronic progressive external ophthalmoplegia through disordered mitochondrial DNA maintenance. Brain : a journal of neurology 139 24727571
2012 SPG7 mutational screening in spastic paraplegia patients supports a dominant effect for some mutations and a pathogenic role for p.A510V. Clinical genetics 97 22571692
2006 Mutation analysis of the paraplegin gene (SPG7) in patients with hereditary spastic paraplegia. Neurology 90 16534102
2008 A clinical, genetic, and biochemical characterization of SPG7 mutations in a large cohort of patients with hereditary spastic paraplegia. Human mutation 80 18200586
2004 A clinical, genetic and biochemical study of SPG7 mutations in hereditary spastic paraplegia. Brain : a journal of neurology 75 14985266
2007 A novel form of autosomal recessive hereditary spastic paraplegia caused by a new SPG7 mutation. Neurology 50 17646629
2018 Novel genotype-phenotype and MRI correlations in a large cohort of patients with SPG7 mutations. Neurology. Genetics 49 30533525
2019 Loss of paraplegin drives spasticity rather than ataxia in a cohort of 241 patients with SPG7. Neurology 45 31068484
2015 SPG7 mutations explain a significant proportion of French Canadian spastic ataxia cases. European journal of human genetics : EJHG 43 26626314
2020 Mutations in the m-AAA proteases AFG3L2 and SPG7 are causing isolated dominant optic atrophy. Neurology. Genetics 40 32548275
2020 Impaired flickering of the permeability transition pore causes SPG7 spastic paraplegia. EBioMedicine 37 33045469
2012 The p.Ala510Val mutation in the SPG7 (paraplegin) gene is the most common mutation causing adult onset neurogenetic disease in patients of British ancestry. Journal of neurology 37 23269439
2018 Concurrent AFG3L2 and SPG7 mutations associated with syndromic parkinsonism and optic atrophy with aberrant OPA1 processing and mitochondrial network fragmentation. Human mutation 35 30252181
2011 Amplicon-based high-throughput pooled sequencing identifies mutations in CYP7B1 and SPG7 in sporadic spastic paraplegia patients. Clinical genetics 35 21623769
2014 SPG7 variant escapes phosphorylation-regulated processing by AFG3L2, elevates mitochondrial ROS, and is associated with multiple clinical phenotypes. Cell reports 33 24767997
2019 SPG7 targets the m-AAA protease complex to process MCU for uniporter assembly, Ca2+ influx, and regulation of mitochondrial permeability transition pore opening. The Journal of biological chemistry 29 31097542
2009 Crystal structure of the ATPase domain of the human AAA+ protein paraplegin/SPG7. PloS one 28 19841671
2010 A novel splice site mutation in the SPG7 gene causing widespread fiber damage in homozygous and heterozygous subjects. Movement disorders : official journal of the Movement Disorder Society 26 20108356
2020 SPG7 mutations in amyotrophic lateral sclerosis: a genetic link to hereditary spastic paraplegia. Journal of neurology 25 32447552
2010 Mouse brain expression patterns of Spg7, Afg3l1, and Afg3l2 transcripts, encoding for the mitochondrial m-AAA protease. BMC neuroscience 24 20426821
2008 Hereditary spastic paraplegia caused by the novel mutation 1047insC in the SPG7 gene. Journal of neurology 23 18563470
1999 Genomic structure and expression analysis of the spastic paraplegia gene, SPG7. Human genetics 23 10480368
2020 Mitochondrial Function in Hereditary Spastic Paraplegia: Deficits in SPG7 but Not SPAST Patient-Derived Stem Cells. Frontiers in neuroscience 20 32973427
2019 A deep intronic splice variant advises reexamination of presumably dominant SPG7 Cases. Annals of clinical and translational neurology 19 31854126
2015 Abnormal Paraplegin Expression in Swollen Neurites, τ- and α-Synuclein Pathology in a Case of Hereditary Spastic Paraplegia SPG7 with an Ala510Val Mutation. International journal of molecular sciences 19 26506339
2017 SPG7 and Impaired Emotional Communication. Cerebellum (London, England) 16 27557734
1997 Exclusion of BBC1 and CMAR as candidate breast tumour-suppressor genes. British journal of cancer 16 9413939
2018 Prevalence and phenotype of the c.1529C>T SPG7 variant in adult-onset cerebellar ataxia in Italy. European journal of neurology 13 30098094
2016 A founder mutation p.H701P identified as a major cause of SPG7 in Norway. European journal of neurology 11 26756429
2013 Identification of a novel homozygous SPG7 mutation in a Japanese patient with spastic ataxia: making an efficient diagnosis using exome sequencing for autosomal recessive cerebellar ataxia and spastic paraplegia. Internal medicine (Tokyo, Japan) 10 23857099
2012 Alternative splicing of Spg7, a gene involved in hereditary spastic paraplegia, encodes a variant of paraplegin targeted to the endoplasmic reticulum. PloS one 10 22563492
2009 The cmaR gene of Corynebacterium ammoniagenes performs a novel regulatory role in the metabolism of sulfur-containing amino acids. Microbiology (Reading, England) 10 19383689
2021 Positive DAT-SCAN in SPG7: a case report mimicking possible MSA-C. BMC neurology 9 34433436
2014 Characterization of Alu and recombination-associated motifs mediating a large homozygous SPG7 gene rearrangement causing hereditary spastic paraplegia. Neurogenetics 9 25398481
2015 Predominant cerebellar phenotype in spastic paraplegia 7 (SPG7). Human genome variation 8 27081526
2025 Reduced Expression of UPRmt Proteins HSP10, HSP60, HTRA2, OMA1, SPG7, and YME1L Is Associated with Accelerated Heart Failure in Humans. Biomedicines 7 40426970
2023 Pharmacological rescue of mitochondrial and neuronal defects in SPG7 hereditary spastic paraplegia patient neurons using high throughput assays. Frontiers in neuroscience 7 37766787
2023 SARM1 deletion delays cerebellar but not spinal cord degeneration in an enhanced mouse model of SPG7 deficiency. Brain : a journal of neurology 6 37086482
2023 An SPG7 mutation as a novel cause of monogenic progressive muscular atrophy. Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology 6 37213040
2022 A novel homozygous variant in the SPG7 gene presenting with childhood optic nerve atrophy. American journal of ophthalmology case reports 6 35243150
2016 In Silico Investigation of Traditional Chinese Medicine for Potential Lead Compounds as SPG7 Inhibitors against Coronary Artery Disease. Molecules (Basel, Switzerland) 6 27164068
2015 Identification of a novel homozygous SPG7 mutation by whole exome sequencing in a Greek family with a complicated form of hereditary spastic paraplegia. European journal of medical genetics 6 26260707
2022 A Novel SPG7 Gene Pathogenic Variant in a Cypriot Family With Autosomal Recessive Spastic Ataxia. Frontiers in genetics 5 35096021
2022 Expanding SPG7 dominant optic atrophy phenotype: Infantile nystagmus and optic atrophy without spastic paraplegia. American journal of medical genetics. Part A 5 36367250
2025 Expanding the Phenotypic Spectrum of SPG7 Rare Damaging Variants: Insights From a Hungarian Cohort. Clinical genetics 4 39978794
2021 Cognitive dysfunction and psychosis: expanding the phenotype of SPG7. Neurocase 4 34003721
2021 Early Onset Degenerative Parkinsonism - Consider SPG7 Mutation. Neurology India 4 34507444
2022 A novel compound heterozygous SPG7 variant is associated with progressive spastic ataxia and persecutory delusions found in Chinese patients: two case reports. BMC neurology 3 35637455
2020 Emotional detachment, gait ataxia, and cerebellar dysconnectivity associated with compound heterozygous mutations in the SPG7 gene. Neurocase 3 32893728
2024 SPG7 mutation - Novel phenotypic presentation mimicking idiopathic Parkinson's disease. Clinical parkinsonism & related disorders 2 39624339
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
2023 Expression dynamics indicate the involvement of SPG7 in the reproduction and spermiogenesis of Phascolosoma esculenta. Gene 1 38007160
2018 Identification of novel compound heterozygous SPG7 mutations-related hereditary spastic paraplegia in a Chinese family: a case report. BMC neurology 1 30497413
2026 Identification of an additional deep intronic splice variant prompts critical evaluation of SPG7 inheritance. Neurogenetics 0 41656397
2025 Mechanism of PISD/SPG7-mediated mPTP opening in necroptosis of inflammatory HaCaT cells induced by nano-zinc oxide. Toxicology 0 40780696
2025 SPG7 p.A510V heterozygosity as a cause of adult-onset cerebellar ataxia without spasticity: longitudinal evidence from a sporadic case. Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology 0 40824590
2025 Genetic analysis of a family with skeletal muscle ion channelopathy and hereditary spastic paraplegia type 7 caused by SCN4A and SPG7 double mutations. Gene 0 40998070
2025 The Neuro-Ophthalmologic Manifestations of SPG7-Associated Disease. Journal of personalized medicine 0 41149856
2025 3-Methyl Glutaconic Aciduria and Elevated Plasma Growth Differentiation Factor 15 Level in an Adult with Monoallelic SPG7 Pathogenic Variant. Acta myologica : myopathies and cardiomyopathies : official journal of the Mediterranean Society of Myology 0 41773441

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