Affinage

CLN6

Ceroid-lipofuscinosis neuronal protein 6 · UniProt Q9NWW5

Length
311 aa
Mass
35.9 kDa
Annotated
2026-04-28
78 papers in source corpus 15 papers cited in narrative 16 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

CLN6 is an ER-resident polytopic membrane protein that functions centrally in lysosome biogenesis by forming an obligate complex with CLN8 (the EGRESS complex) to recruit soluble lysosomal enzymes at the ER and facilitate their COPII-mediated transport to the Golgi (PMID:32597833). CLN6 possesses seven transmembrane domains with a cytoplasmic N-terminus and luminal C-terminus, homodimerizes, and is retained in the ER through determinants in its N-terminal cytosolic domain and transmembrane domains 6–7 (PMID:15010453, PMID:17453415). Beyond enzyme trafficking, CLN6 cooperates with ER-anchored αB-crystallin and pro-cathepsin D to suppress aberrant protein aggregation through the autophagy–lysosome system, and loss of CLN6 causes accumulation of autophagic substrates and ubiquitinated aggregates in neurons (PMID:28476624, PMID:22536393, PMID:39032464). Loss-of-function mutations in CLN6 cause variant late-infantile neuronal ceroid lipofuscinosis, with pathogenic mutants undergoing rapid proteasome/ERAD-mediated degradation and graded loss of anti-aggregate activity correlating with disease severity (PMID:11791207, PMID:18811591, PMID:32171521).

Mechanistic history

Synthesis pass · year-by-year structured walk · 11 steps
  1. 2001 High

    Positional cloning identified CLN6 as the gene mutated in variant late-infantile neuronal ceroid lipofuscinosis (vLINCL) in both humans and the nclf mouse, establishing that this novel seven-transmembrane-domain protein is essential for neuronal survival.

    Evidence Positional cloning and mutation analysis in patient families and the nclf mouse model

    PMID:11727201 PMID:11791207

    Open questions at the time
    • Subcellular localization of CLN6 was unknown
    • Molecular function and pathway involvement were uncharacterized
    • No protein-level studies had been performed
  2. 2004 High

    CLN6 was shown to be an ER-resident protein that homodimerizes and whose deficiency impairs lysosomal degradative capacity without affecting cathepsin D processing, establishing that an ER protein can remotely control lysosomal function.

    Evidence Immunofluorescence with organelle markers, GFP-tagged CLN6, cross-linking, and lysosomal degradation assays in patient/animal fibroblasts

    PMID:15010453 PMID:15265688

    Open questions at the time
    • The mechanism by which an ER protein influences lysosomal enzyme content was unknown
    • Identity of direct binding partners mediating lysosomal enzyme trafficking was not established
    • Topology and ER retention determinants were not yet mapped
  3. 2007 High

    Mapping of CLN6 topology (cytoplasmic N-terminus, luminal C-terminus, 7 TMs) and identification of ER-retention determinants in the N-terminal cytosolic domain and TMs 6–7 defined the structural framework for understanding CLN6 function.

    Evidence Differential permeabilization, confocal microscopy, and systematic mutagenesis of retention signals in BHK and neuronal cells

    PMID:17453415

    Open questions at the time
    • No direct cargo-binding activity had been demonstrated
    • Functional significance of homodimerization remained unclear
  4. 2009 Medium

    Two distinct aspects of CLN6 biology were revealed: interaction with the neurodevelopmental protein CRMP-2, linking CLN6 to neuronal maturation, and demonstration that pathogenic CLN6 mutants are degraded via ERAD involving Derlin-1, p97, and the SEL1L-dependent ubiquitin ligase.

    Evidence Co-immunoprecipitation of CLN6–CRMP-2; proteasome inhibitors, Co-IP with ERAD components, and SEL1L siRNA rescue in neuronal-derived cells

    PMID:18811591 PMID:19235893

    Open questions at the time
    • CLN6–CRMP-2 interaction lacks reconstitution with purified proteins
    • Whether ERAD-mediated loss of mutant CLN6 is the primary pathogenic mechanism versus loss of function was unclear
    • Relationship between CRMP-2 interaction and lysosomal enzyme trafficking was not addressed
  5. 2010 Medium

    Pulse-chase analysis of multiple pathogenic CLN6 mutations showed mutation-dependent effects on protein synthesis rate and stability, with some mutants degraded by both proteasomal and lysosomal pathways, yet none lost the capacity to dimerize.

    Evidence Pulse-chase metabolic labeling, proteasomal and lysosomal inhibitor treatment in patient-derived and transfected cells

    PMID:20020536

    Open questions at the time
    • Functional consequence of retained dimerization by mutants was not tested
    • Whether residual mutant CLN6 retains partial function was unknown
  6. 2012 Medium

    CLN6 deficiency was linked to progressive autophagy–lysosome pathway dysfunction, with accumulation of LC3-II, ubiquitinated proteins, and p62 aggregates in nclf neurons, without triggering the unfolded protein response, clarifying that pathology stems from downstream lysosomal failure rather than ER stress.

    Evidence Western blot for autophagy markers, ER stress markers, and proteasomal inhibitor treatment in nclf mouse brain

    PMID:22536393

    Open questions at the time
    • Causal direction—whether autophagy block is primary or secondary to lysosomal enzyme depletion—was not resolved
    • No direct mechanistic link between ER-resident CLN6 and autophagosome–lysosome fusion was identified
  7. 2017 Medium

    Discovery that CLN6 physically associates with ER-anchored αB-crystallin and acts as an effector to suppress protein aggregation via the autophagy–lysosome system established an unexpected proteostasis function for CLN6 at the ER.

    Evidence Co-immunoprecipitation, CLN6 siRNA knockdown and overexpression, protein aggregation assays, and lysosomal inhibitor treatment in HeLa cells

    PMID:28476624

    Open questions at the time
    • Mechanism by which CLN6 promotes aggregate clearance was not defined
    • Whether anti-aggregate function is independent of lysosomal enzyme trafficking was not tested
  8. 2020 High

    The central mechanism of CLN6 was resolved: CLN6 and CLN8 form the EGRESS complex that recruits lysosomal enzymes at the ER for Golgi-directed transport; the second luminal loop of CLN6 mediates enzyme binding while being dispensable for CLN8 interaction, and double-knockout epistasis confirmed the two proteins operate as a single functional unit.

    Evidence Co-immunoprecipitation, lysosomal enzyme trafficking assays, CLN6 luminal loop mutagenesis, and CLN6/CLN8 double-knockout mouse phenotyping

    PMID:32597833

    Open questions at the time
    • Structural basis of enzyme recognition by the EGRESS complex is unknown
    • How cargo selectivity for N-glycosylated soluble hydrolases is achieved is not established
    • Whether EGRESS interacts directly with COPII coat components was not tested
  9. 2020 Medium

    Genotype–phenotype correlation was mechanistically grounded: graded loss of CLN6 anti-aggregate activity correlated with disease severity, with the nclf truncation abolishing activity and adult-onset missense mutations retaining partial function.

    Evidence Protein aggregation assays with multiple CLN6 disease mutants tested against αBC aggregation-prone variants in HeLa cells

    PMID:32171521

    Open questions at the time
    • Whether residual anti-aggregate activity predicts disease course in patients was not tested clinically
    • Relationship between EGRESS function and anti-aggregate activity was not disentangled
  10. 2021 Medium

    Proteomic analysis confirmed that CLN6 deficiency broadly depletes N-glycosylated soluble hydrolases from lysosomes, including multiple NCL-related enzymes, validating the EGRESS model at the organelle level; separately, the luminal C-terminal tail was shown to be critical for anti-aggregate activity and a truncated CLN6 mutant exerts dominant-negative effects.

    Evidence Proteomic analysis of isolated lysosomal fractions from nclf liver, Western blot, enzyme assays; co-expression mutagenesis and aggregation assays

    PMID:34380921 PMID:34432360

    Open questions at the time
    • Mechanism of dominant-negative effect through the luminal tail is not resolved at a structural level
    • Whether tissue-specific differences in lysosomal enzyme depletion exist was not explored
  11. 2024 Medium

    Pro-cathepsin D was identified as a functional partner of CLN6 in the anti-aggregate pathway, requiring CLN6 for its ER-localized anti-aggregate activity and linking a known NCL enzyme to CLN6-dependent proteostasis at the ER.

    Evidence Co-immunoprecipitation of ER-anchored αBC partners identifying proCTSD, CLN6 knockdown, CTSD variant overexpression, aggregation assays in HeLa cells

    PMID:39032464

    Open questions at the time
    • Whether proCTSD is an EGRESS cargo that also has a pre-export ER function, or whether these are separable roles, is unresolved
    • Direct physical interaction between CLN6 and proCTSD has not been demonstrated with purified components

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key open questions include the structural basis of CLN6–CLN8 EGRESS complex assembly and cargo recognition, whether CLN6's anti-aggregate function is mechanistically distinct from its enzyme-trafficking role, how EGRESS interfaces with COPII-mediated ER export, and whether therapeutic stabilization of mutant CLN6 can restore lysosomal biogenesis in vivo.
  • No high-resolution structure of CLN6 or the EGRESS complex exists
  • Mechanistic relationship between EGRESS trafficking function and anti-aggregate function is unresolved
  • COPII interaction and ER-exit mechanism for the EGRESS–cargo complex are uncharacterized

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060090 molecular adaptor activity 2 GO:0038024 cargo receptor activity 1
Localization
GO:0005783 endoplasmic reticulum 3
Pathway
R-HSA-1852241 Organelle biogenesis and maintenance 3 R-HSA-1643685 Disease 2 R-HSA-392499 Metabolism of proteins 2 R-HSA-9609507 Protein localization 2 R-HSA-9612973 Autophagy 2
Partners
CLN8CRMP2CRYABCTSDDERL1SEL1LVCP
Complex memberships
EGRESS complex (CLN6–CLN8)

Evidence

Reading pass · 16 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2001 CLN6 encodes a novel ~36 kDa transmembrane protein with seven predicted transmembrane domains; loss-of-function mutations (stop codon, codon deletion, frameshift) in this gene cause variant late-infantile neuronal ceroid lipofuscinosis in humans and the nclf mouse. Positional cloning, DNA sequencing of patient and nclf mouse chromosomes, mutational analysis American journal of human genetics High 11727201 11791207
2004 CLN6 protein (~27-30 kDa) resides in the endoplasmic reticulum (ER) and does not traffic to cis-Golgi or lysosomes; disease-causing single-amino-acid mutants are also retained in the ER. Immunofluorescence microscopy with ER/Golgi/lysosomal markers, GFP-tagged CLN6 expression in HEK293 cells, Western blotting with peptide-specific antibodies Experimental cell research / Journal of biological chemistry High 15010453 15265688
2004 CLN6 forms homodimers, as shown by cross-linking experiments; pathogenic mutations do not prevent dimerization. Cross-linking experiments and immunoblot analysis in transfected BHK21 cells The Journal of biological chemistry Medium 15010453
2004 Deficiency of CLN6 causes strongly reduced lysosomal degradation of endocytosed arylsulfatase A in patient fibroblasts and animal model cells, while cathepsin D synthesis, sorting, and processing are unaffected, indicating that ER-resident CLN6 is required for normal lysosomal degradative function. Pulse-chase labeling followed by immunoprecipitation of cathepsin D; lysosomal degradation assay of endocytosed arylsulfatase A in CLN6-deficient fibroblasts from human patients, sheep, and mouse The Journal of biological chemistry High 15010453
2007 CLN6 topology: N-terminal domain is cytoplasmic, C-terminus is luminal, with seven transmembrane domains. ER retention requires both the N-terminal cytosolic domain and transmembrane domains 6 and 7. A dilysine motif partially contributes to ER localization, while a triple arginine cluster and dileucine motif do not affect ER retention. Differential membrane permeabilization with two distinct antibodies, confocal immunofluorescence microscopy, mutational analysis of retention signals in BHK and neuronal cells Molecular membrane biology High 17453415
2007 CLN6 homodimerization, demonstrated by expression analyses of fusion and deletion constructs, may contribute to ER retention by interaction with membrane-associated factors. Expression of fusion and deletion constructs in non-neuronal and neuronal cells, confocal microscopy Molecular membrane biology Medium 17453415
2009 CLN6 protein physically interacts with CRMP-2 (collapsin response mediator protein-2); loss of CLN6 reduces CRMP-2 levels in the nclf mouse brain (especially thalamus) and impairs hippocampal neuron maturation in vitro. Co-immunoprecipitation/interaction assay, Western blot, hippocampal neuron cultures from nclf mice, DRG repulsion assay Journal of neuroscience research Medium 19235893
2009 Pathogenic CLN6 mutants (G123D and M241T) are rapidly degraded via proteasome-mediated ERAD; they associate with ERAD components Derlin-1 and p97, and knockdown of SEL1L (an E3 ubiquitin ligase complex member) rescues mutant CLN6 protein levels. Proteasome inhibitor treatment, co-immunoprecipitation with Derlin-1 and p97, siRNA knockdown of SEL1L in neuronal-derived human cells Bioscience reports Medium 18811591
2010 Pathogenic mutations in CLN6 (p.Gly123Asp, p.Ile154del, p.Arg106ProfsX26) reduce the rate of synthesis and stability of CLN6 protein in a mutation-dependent manner; the truncated p.Arg106ProfsX26 mutant (identical to nclf mouse mutation) is rapidly degraded via both proteasomal and lysosomal pathways, but none of the mutations prevent CLN6 dimerization. Pulse-chase metabolic labeling, proteasomal and lysosomal inhibitor treatment, expression studies in patient-derived and transfected cells Human mutation Medium 20020536
2012 CLN6 deficiency disrupts the autophagy-lysosome degradation pathway; nclf mouse brains show age-dependent increases in LC3-II, ubiquitinated proteins, and p62-positive neuronal aggregates, indicating impaired autophagosome-lysosome fusion. Mutant Cln6 protein undergoes proteasomal degradation without inducing ER stress or unfolded protein response. Western blot for autophagy markers (LC3-II, p62, ubiquitin), proteasomal inhibitor treatment, ER stress marker analysis, immunofluorescence in nclf mouse brain PloS one Medium 22536393
2017 CLN6 physically interacts with ER-anchored αB-crystallin and functions as a downstream effector to prevent aberrant protein aggregate formation; CLN6 knockdown abolishes anti-aggregate activity and CLN6 overexpression enhances it. This anti-aggregate activity requires an intact autophagy-lysosome system. Co-immunoprecipitation of ER-anchored αBC binding partners, CLN6 siRNA knockdown and overexpression in HeLa cells, protein aggregation assay, lysosomal inhibitor treatment Biochemical and biophysical research communications Medium 28476624
2020 CLN6 forms an obligate complex with CLN8 (termed EGRESS: ER-to-Golgi relaying of enzymes of the lysosomal system) to recruit lysosomal enzymes at the ER and promote their transfer to the Golgi. The second luminal loop of CLN6 is required for interaction with lysosomal enzymes but is dispensable for interaction with CLN8. CLN6 deficiency causes inefficient ER export of lysosomal enzymes and reduced lysosomal enzyme levels. Mice lacking both CLN6 and CLN8 show no aggravated pathology compared with single knockouts, confirming the two proteins act as a functional unit. Co-immunoprecipitation, protein trafficking assays, CLN6 loop mutagenesis, in vitro and in vivo lysosomal enzyme quantification, double-knockout mouse analysis The Journal of clinical investigation High 32597833
2020 Graded reduction in CLN6's anti-aggregate activity correlates with disease severity: the late infantile-onset nclf truncation mutant (Arg106ProfsX) abolishes anti-aggregate activity, while adult-onset missense mutants (Arg149Cys, Arg149His) retain partial activity against aggregation-prone αBC mutants. Protein aggregation assays with CLN6 disease mutants overexpressed in HeLa cells, testing activity against multiple αBC aggregation-prone variants Biochemical and biophysical research communications Medium 32171521
2021 CLN6 deficiency selectively reduces the lysosomal levels of multiple N-glycosylated soluble hydrolases, including several other NCL proteins, as determined by comparative proteomics of isolated lysosomal fractions; confirmed by Western blot and enzymatic activity assays. Proteomic analysis of isolated lysosomal fractions from nclf mouse liver, Western blotting, enzymatic activity assays Proteomics Medium 34432360
2021 CLN6's luminal tail (C-terminal domain) is required for maintaining anti-aggregate activity when co-expressed with truncated CLN6 mutants; the S132CfsX18 truncated mutant nullifies the anti-aggregate activity of co-expressed P299L CLN6 missense mutant through a dominant-negative mechanism involving the luminal tail. Co-expression of CLN6 mutant combinations in cells, protein aggregation assays, deletion and alanine substitution mutagenesis of CLN6 C-terminus Biomedical research (Tokyo, Japan) Medium 34380921
2024 Pro-cathepsin D (proCTSD) prevents aberrant protein aggregation through functional association with CLN6 at the ER membrane; CLN6 depletion abolishes proCTSD's anti-aggregate activity. CTSD was identified as a binding partner of ER-anchored αBC and its pro-peptide integrity is required for anti-aggregate function. Co-immunoprecipitation of ER-anchored αBC binding partners (identifying proCTSD), CLN6 knockdown, CTSD variant overexpression, protein aggregation assays in HeLa cells Molecular genetics and metabolism Medium 39032464

Source papers

Stage 0 corpus · 78 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2001 Mutations in a novel CLN6-encoded transmembrane protein cause variant neuronal ceroid lipofuscinosis in man and mouse. American journal of human genetics 165 11791207
2001 The gene mutated in variant late-infantile neuronal ceroid lipofuscinosis (CLN6) and in nclf mutant mice encodes a novel predicted transmembrane protein. American journal of human genetics 147 11727201
2011 Kufs disease, the major adult form of neuronal ceroid lipofuscinosis, caused by mutations in CLN6. American journal of human genetics 108 21549341
1998 Neuronal ceroid lipofuscinosis (nclf), a new disorder of the mouse linked to chromosome 9. American journal of medical genetics 104 9600738
2005 Glial activation spreads from specific cerebral foci and precedes neurodegeneration in presymptomatic ovine neuronal ceroid lipofuscinosis (CLN6). Neurobiology of disease 97 16137566
2004 CLN6, which is associated with a lysosomal storage disease, is an endoplasmic reticulum protein. Experimental cell research 88 15265688
2004 Defective endoplasmic reticulum-resident membrane protein CLN6 affects lysosomal degradation of endocytosed arylsulfatase A. The Journal of biological chemistry 78 15010453
2020 A CLN6-CLN8 complex recruits lysosomal enzymes at the ER for Golgi transfer. The Journal of clinical investigation 68 32597833
2003 Spectrum of CLN6 mutations in variant late infantile neuronal ceroid lipofuscinosis. Human mutation 64 12815591
2006 A missense mutation (c.184C>T) in ovine CLN6 causes neuronal ceroid lipofuscinosis in Merino sheep whereas affected South Hampshire sheep have reduced levels of CLN6 mRNA. Biochimica et biophysica acta 60 17046213
2012 Disruption of the autophagy-lysosome pathway is involved in neuropathology of the nclf mouse model of neuronal ceroid lipofuscinosis. PloS one 59 22536393
1998 Ovine neuronal ceroid lipofuscinosis: a large animal model syntenic with the human neuronal ceroid lipofuscinosis variant CLN6. Journal of medical genetics 59 9733028
2010 A missense mutation in canine CLN6 in an Australian shepherd with neuronal ceroid lipofuscinosis. Journal of biomedicine & biotechnology 55 21234413
2013 Progressive retinal degeneration and glial activation in the CLN6 (nclf) mouse model of neuronal ceroid lipofuscinosis: a beneficial effect of DHA and curcumin supplementation. PloS one 52 24124525
2007 Topology and endoplasmic reticulum retention signals of the lysosomal storage disease-related membrane protein CLN6. Molecular membrane biology 41 17453415
2019 Gene Therapy Corrects Brain and Behavioral Pathologies in CLN6-Batten Disease. Molecular therapy : the journal of the American Society of Gene Therapy 37 31331814
2003 Novel mutations in the CLN6 gene causing a variant late infantile neuronal ceroid lipofuscinosis. Human mutation 37 12673792
2009 Variant late infantile ceroid lipofuscinoses associated with novel mutations in CLN6. Biochemical and biophysical research communications 35 19135028
2018 Prevention of Photoreceptor Cell Loss in a Cln6nclf Mouse Model of Batten Disease Requires CLN6 Gene Transfer to Bipolar Cells. Molecular therapy : the journal of the American Society of Gene Therapy 34 29606505
2009 Protein product of CLN6 gene responsible for variant late-onset infantile neuronal ceroid lipofuscinosis interacts with CRMP-2. Journal of neuroscience research 33 19235893
2019 Kufs disease due to mutation of CLN6: clinical, pathological and molecular genetic features. Brain : a journal of neurology 30 30561534
2003 Enhanced expression of manganese-dependent superoxide dismutase in human and sheep CLN6 tissues. The Biochemical journal 30 12946273
2017 Characterisation of early changes in ovine CLN5 and CLN6 Batten disease neural cultures for the rapid screening of therapeutics. Neurobiology of disease 26 28065762
2013 Altered biometal homeostasis is associated with CLN6 mRNA loss in mouse neuronal ceroid lipofuscinosis. Biology open 25 23789114
2013 Apoptotic photoreceptor loss and altered expression of lysosomal proteins in the nclf mouse model of neuronal ceroid lipofuscinosis. Investigative ophthalmology & visual science 25 24084090
2013 Increased zinc and manganese in parallel with neurodegeneration, synaptic protein changes and activation of Akt/GSK3 signaling in ovine CLN6 neuronal ceroid lipofuscinosis. PloS one 24 23516525
2010 Pathogenic mutations cause rapid degradation of lysosomal storage disease-related membrane protein CLN6. Human mutation 23 20020536
2005 Two novel CLN6 mutations in variant late-infantile neuronal ceroid lipofuscinosis patients of Turkish origin. Clinical genetics 23 15996215
2019 Neonatal brain-directed gene therapy rescues a mouse model of neurodegenerative CLN6 Batten disease. Human molecular genetics 20 31807779
2009 Cln6 mutants associated with neuronal ceroid lipofuscinosis are degraded in a proteasome-dependent manner. Bioscience reports 19 18811591
2015 Sustained Neural Stem Cell-Based Intraocular Delivery of CNTF Attenuates Photoreceptor Loss in the nclf Mouse Model of Neuronal Ceroid Lipofuscinosis. PloS one 18 25992714
2015 Rapid and Progressive Regional Brain Atrophy in CLN6 Batten Disease Affected Sheep Measured with Longitudinal Magnetic Resonance Imaging. PloS one 18 26161747
1999 Genetic and physical mapping of the CLN6 gene on chromosome 15q21-23. Molecular genetics and metabolism 18 10191123
2012 Mutation of the CLN6 gene in teenage-onset progressive myoclonus epilepsy. Pediatric neurology 17 22883287
2007 Metabolomic investigation of CLN6 neuronal ceroid lipofuscinosis in affected South Hampshire sheep. Journal of neuroscience research 17 17510975
2021 Intracranial delivery of AAV9 gene therapy partially prevents retinal degeneration and visual deficits in CLN6-Batten disease mice. Molecular therapy. Methods & clinical development 15 33665223
2009 Variant late infantile neuronal ceroid lipofuscinosis (CLN6 gene) in Saudi Arabia. Pediatric neurology 15 19520283
2020 Neuronal Ceroid Lipofuscinosis in a Domestic Cat Associated with a DNA Sequence Variant That Creates a Premature Stop Codon in CLN6. G3 (Bethesda, Md.) 12 32518081
2018 Novel mutations in CLN6 cause late-infantile neuronal ceroid lipofuscinosis without visual impairment in two unrelated patients. Molecular genetics and metabolism 11 30528883
2016 First Japanese variant of late infantile neuronal ceroid lipofuscinosis caused by novel CLN6 mutations. Brain & development 11 27165443
2013 CLN6 disease caused by the same mutation originating in Pakistan has varying pathology. European journal of paediatric neurology : EJPN : official journal of the European Paediatric Neurology Society 11 23735787
2011 High expression of disease-related Cln6 in the cerebral cortex, purkinje cells, dentate gyrus, and hippocampal ca1 neurons. Journal of neuroscience research 11 22012656
2010 The specific loss of GnRH-positive neurons from the hypothalamus of sheep with CLN6 neuronal ceroid lipofuscinosis occurs without glial activation and has only minor effects on reproduction. Neurobiology of disease 11 21111820
2022 Neuronal Ceroid Lipofuscinosis Type 6 (CLN6) clinical findings and molecular diagnosis: Costa Rica's experience. Orphanet journal of rare diseases 10 35012600
2021 A Novel CLN6 Variant Associated With Juvenile Neuronal Ceroid Lipofuscinosis in Patients With Absence of Visual Loss as a Presenting Feature. Frontiers in genetics 10 34868216
2018 A first CLN6 variant case of late infantile neuronal ceroid lipofuscinosis caused by a homozygous mutation in a boy from China: a case report. BMC medical genetics 10 30285654
2021 CLN6 deficiency causes selective changes in the lysosomal protein composition. Proteomics 9 34432360
2017 Identification of CLN6 as a molecular entity of endoplasmic reticulum-driven anti-aggregate activity. Biochemical and biophysical research communications 8 28476624
1999 Progress toward the cloning of CLN6, the gene underlying a variant LINCL. Molecular genetics and metabolism 8 10191124
2023 Progressive MRI brain volume changes in ovine models of CLN5 and CLN6 neuronal ceroid lipofuscinosis. Brain communications 7 36632184
2023 Characterization of neuropathology in ovine CLN5 and CLN6 neuronal ceroid lipofuscinoses (Batten disease). Developmental neurobiology 7 37246363
2021 An altered secretome is an early marker of the pathogenesis of CLN6 Batten disease. Journal of neurochemistry 7 33368303
2021 Electroretinography data from ovine models of CLN5 and CLN6 neuronal ceroid lipofuscinoses. Data in brief 7 34141843
2019 Rapid progression of a walking disability in a 5-year-old boy with a CLN6 mutation. Brain & development 7 31029456
2020 Implications of graded reductions in CLN6's anti-aggregate activity for the development of the neuronal ceroid lipofuscinoses. Biochemical and biophysical research communications 6 32171521
2023 Neuronal progenitor cells-based metabolomics study reveals dysregulated lipid metabolism and identifies putative biomarkers for CLN6 disease. Scientific reports 5 37899458
1999 Progress toward positional cloning of ovine neuronal ceroid lipofuscinosis, a model of the human late-infantile variant CLN6. Molecular genetics and metabolism 5 10191131
2021 CLN6's luminal tail-mediated functional interference between CLN6 mutants as a novel pathomechanism for the neuronal ceroid lipofuscinoses. Biomedical research (Tokyo, Japan) 4 34380921
2012 CLN6 p.I154del mutation causing late infantile neuronal ceroid lipofuscinosis in a large consanguineous Moroccan family. Indian journal of pediatrics 4 23180398
2001 Fine mapping of ovine ceroid lipofuscinosis confirms orthology with CLN6. European journal of paediatric neurology : EJPN : official journal of the European Paediatric Neurology Society 4 11589004
2020 Moyamoya and progressive myoclonic epilepsy secondary to CLN6 bi-allelic mutations - A previously unreported association. Epilepsy & behavior reports 3 33024953
2024 Cellular Modeling of CLN6 with IPSC-derived Neurons and Glia. bioRxiv : the preprint server for biology 2 38352418
2021 p.Asn77Lys homozygous CLN6 mutation in two unrelated Japanese patients with Kufs disease, an adult onset neuronal ceroid lipofuscinosis. Clinica chimica acta; international journal of clinical chemistry 2 34597687
2001 Analysis of candidate genes in the CLN6 critical region using in silico cloning. European journal of paediatric neurology : EJPN : official journal of the European Paediatric Neurology Society 2 11589002
2025 Expanded Phenotype of the Cln6 Mouse Model. Cells 1 40358187
2024 A novel homozygous CLN6 Tyr142Cys variant in a nonconsanguineous family with Kufs disease. Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology 1 38771523
2024 Neuronal ceroid lipofuscinosis in a Schapendoes dog is caused by a missense variant in CLN6. Animal genetics 1 38866396
2024 Neuronal Ceroid Lipofuscinosis in a Mixed-Breed Dog with a Splice Site Variant in CLN6. Genes 1 38927597
2024 CLN6-related continuum phenotype caused by aberrant splicing. Epilepsia open 1 39718800
2023 Rare adult neuronal ceroid lipofuscinosis associated with CLN6 gene mutations: A case report. World journal of clinical cases 1 37383919
2023 Whole exome sequencing identifies variable expressivity of CLN6 variants in Progressive myoclonic epilepsy affected families. Epilepsy research 1 38382230
2019 Modulation of CRMP2 via (S)-Lacosamide shows therapeutic promise but is ultimately ineffective in a mouse model of CLN6-Batten disease. Neuronal signaling 1 32269836
2026 A Flupirtine Benzyl Carbamate Improves Neurocognitive Deficits and Molecular Pathology in the Cln6 Mouse. Cells 0 41827875
2025 Diagnostic analysis of adult neuronal ceroid lipofuscinosis caused by CLN6 gene mutation: a case report. Clinical parkinsonism & related disorders 0 40823674
2024 Pro-cathepsin D prevents aberrant protein aggregation dependent on endoplasmic reticulum protein CLN6. Molecular genetics and metabolism 0 39032464
2022 Aggregation chimeras provide evidence of in vivo intercellular correction in ovine CLN6 neuronal ceroid lipofuscinosis (Batten disease). PloS one 0 35404973
2022 Juvenile-Onset Kufs Disease in a Chinese Consanguineous Family due to CLN6 Mutation. Neuro-degenerative diseases 0 35609511
2019 [Genetic study of a family of neuronal ceroid lipofuscinosis caused by a heterozygous mutation of CLN6 gene]. Zhejiang da xue xue bao. Yi xue ban = Journal of Zhejiang University. Medical sciences 0 31901039