Affinage

CLN3

Battenin · UniProt Q13286

Length
438 aa
Mass
47.6 kDa
Annotated
2026-06-09
100 papers in source corpus 30 papers cited in narrative 30 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

CLN3 (battenin) is a multi-pass, N-glycosylated lysosomal/endosomal membrane protein whose loss causes juvenile neuronal ceroid lipofuscinosis (Batten disease), established by the identification of a recurrent ~1 kb genomic deletion in patients (PMID:7553855). Topologically it spans the membrane five times with a luminal N-terminus and a cytosolic C-terminus (PMID:12706816), and it is delivered to lysosomes through the trans-Golgi network and the plasma membrane using a dileucine motif and a novel M(X)9G motif that engage the AP-1 and AP-3 adaptor complexes for sequential sorting (PMID:10191113, PMID:14699076, PMID:15598649), a process further dependent on C-terminal farnesylation at cysteine 435 (PMID:17286803); the common 461-677del mutant fails this trafficking and is retained in the ER (PMID:10332042). At the late endosome/lysosome, CLN3 acts as a vesicular trafficking hub: it binds active GTP-bound Rab7A and RILP and engages microtubule motors to govern endosome positioning (PMID:22261744), and it controls Rab7A–effector interactions with retromer and PLEKHM1 to drive endosome-to-TGN return of sorting receptors (CI-M6PR, sortilin) and autophagosome–lysosome fusion (PMID:32034082), functioning in this capacity together with CLN5 as an endolysosomal complex (PMID:34060589). Through its interaction with CI-M6PR, CLN3 coordinates Golgi-to-lysosome enzyme delivery and autophagic lysosomal reformation (PMID:37400440). A distinct, biochemically defined transport function is the lysosomal egress of glycerophosphodiesters, the end products of glycerophospholipid catabolism, which accumulate in CLN3-deficient brain lysosomes and patient CSF (PMID:36131016). Consistent with these roles, CLN3 loss broadly disrupts lysosomal enzyme content and lipid homeostasis, including BMP synthesis and glycosphingolipid metabolism (PMID:17482562, PMID:31040178), TGN-to-plasma-membrane transport of microdomain proteins such as caveolin-1 (PMID:24227717), photoreceptor outer segment phagocytosis by retinal pigment epithelium (PMID:33547385), and intracellular Ca2+ handling (PMID:25878248). Additional reported interactions with cytoskeletal and membrane proteins—fodrin/Na+/K+-ATPase, nonmuscle myosin-IIB, and Hook1—link CLN3 to endocytosis, cell migration, and membrane microdomain organization (PMID:15471887, PMID:18621045, PMID:20850431).

Mechanistic history

Synthesis pass · year-by-year structured walk · 11 steps
  1. 1995 High

    Established the genetic basis of Batten disease by identifying CLN3 as a novel gene disrupted by a recurrent genomic deletion, defining the molecular target.

    Evidence Exon amplification and genomic deletion/mutation mapping in patient cohorts

    PMID:7553855

    Open questions at the time
    • Gene identification gave no protein function
    • No subcellular localization or biochemical activity defined
  2. 1999 High

    Resolved where CLN3 acts by confirming it as a lysosomal membrane glycoprotein and showing the common deletion mutant is ER-retained while a missense mutant traffics normally, linking trafficking failure to disease.

    Evidence Immunoelectron microscopy, pulse-chase, and mutant comparison in BHK cells and primary neurons; monensin/tunicamycin trafficking studies

    PMID:10191113 PMID:10332042 PMID:9384607

    Open questions at the time
    • Molecular function at the lysosome not established
    • Sorting machinery not yet identified
  3. 2003 Medium

    Defined CLN3 membrane topology (five TM domains, luminal N-terminus, cytosolic C-terminus), providing the structural framework for assigning sorting and interaction surfaces.

    Evidence In vitro translation with canine microsomes plus glycosylation-site and Flag-tag mutagenesis

    PMID:12706816

    Open questions at the time
    • No high-resolution structure
    • Functional residues within TM domains not mapped
  4. 2004 High

    Identified the dileucine and M(X)9G sorting signals and showed sequential AP-1/AP-3 adaptor-dependent lysosomal delivery, explaining how CLN3 reaches its compartment.

    Evidence Targeting-motif mutagenesis, reporter chimeras, in vitro adaptor binding, and AP-1/AP-3-deficient fibroblasts

    PMID:14699076 PMID:15469932 PMID:15598649

    Open questions at the time
    • Conflicting reports on direct adaptor binding via reporter chimeras
    • Endosomal targeting independent of these motifs not fully explained
  5. 2007 Medium

    Showed CLN3 is farnesylated at C435 and that this lipid modification is required for efficient endosomal/lysosomal sorting, adding a post-translational layer to trafficking control.

    Evidence Mevalonate metabolic labeling, farnesyltransferase inhibition, and C435 mutagenesis in COS7 and neuronal cells

    PMID:17286803

    Open questions at the time
    • Mechanistic link between prenylation and sorting machinery unresolved
    • Single lab
  6. 2012 Medium

    Connected CLN3 to late-endosome dynamics by demonstrating interaction with active Rab7, RILP, and microtubule motors, with a disease mutant causing perinuclear organelle clustering.

    Evidence Co-IP, GTP-Rab7 pulldown, and mutant overexpression imaging in HeLa cells

    PMID:22261744

    Open questions at the time
    • Direct vs indirect Rab7 binding not distinguished
    • Single lab
  7. 2019 High

    Demonstrated through unbiased lysosomal proteomics that CLN3 loss broadly depletes soluble lysosomal enzymes and disrupts lipid and endosomal recycling, establishing global endolysosomal dysfunction.

    Evidence SILAC lysosome purification with mass spectrometry, enzyme activity assays, and lipid probes in CLN3 knock-in mouse cells

    PMID:31040178

    Open questions at the time
    • Did not pinpoint the primary biochemical defect upstream of enzyme loss
  8. 2020 High

    Provided the mechanistic basis for enzyme mis-sorting by showing CLN3 regulates Rab7A interactions with retromer and PLEKHM1, controlling sorting-receptor recycling and autophagosome-lysosome fusion.

    Evidence Reciprocal co-IP and functional trafficking assays in CLN3 KO and disease-mutant cells

    PMID:32034082

    Open questions at the time
    • Structural mode of CLN3 action on Rab7A effectors unknown
  9. 2021 Medium

    Placed CLN3 in a CLN3-CLN5 endolysosomal complex, showing CLN5 is needed for CLN3-Rab7A function and integrating two NCL genes into a shared trafficking pathway.

    Evidence Co-IP of the complex, Rab7A effector and autophagy/fusion assays after CLN5 depletion

    PMID:34060589

    Open questions at the time
    • Stoichiometry and direct contacts of the complex undefined
    • Single lab
  10. 2022 High

    Defined a concrete transport activity by identifying CLN3 as the lysosomal egress route for glycerophosphodiesters, with accumulation in mouse brain lysosomes and patient CSF.

    Evidence LysoTag in vivo lysosome isolation, untargeted metabolomics, and cell-based validation plus patient CSF analysis

    PMID:36131016

    Open questions at the time
    • Direct demonstration of CLN3 as the transporter vs facilitator not fully resolved
    • Relationship between GPD egress and trafficking-hub roles unclear
  11. 2023 High

    Consolidated the trafficking-hub model by showing CLN3 binds CI-M6PR to coordinate Golgi-lysosome enzyme delivery and autophagic lysosomal reformation, with overexpression driving lysosomal tubulation.

    Evidence CLN3 interactome proteomics, co-IP, CI-M6PR and enzyme sorting assays, and lysosomal tubule assays in KO and overexpressing cells

    PMID:37400440

    Open questions at the time
    • How the GPD transport function and the CI-M6PR hub function mechanistically relate is unresolved

Open questions

Synthesis pass · forward-looking unresolved questions
  • Whether CLN3's glycerophosphodiester transport activity and its Rab7A/CI-M6PR trafficking-hub functions reflect a single unified molecular mechanism or separable activities, and how either causes selective neurodegeneration, remains unresolved.
  • No structure of CLN3 in a transport or complex state
  • Primary defect underlying neuronal death not established
  • Link between metabolite accumulation and trafficking phenotypes undefined

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060090 molecular adaptor activity 2 GO:0005215 transporter activity 1
Localization
GO:0005764 lysosome 3 GO:0005768 endosome 3 GO:0005794 Golgi apparatus 3 GO:0005886 plasma membrane 1
Pathway
R-HSA-1430728 Metabolism 3 R-HSA-9612973 Autophagy 3 R-HSA-5653656 Vesicle-mediated transport 2 R-HSA-9609507 Protein localization 2
Partners
CI-M6PR (IGF2R)CLN5HOOK1MYH10PLEKHM1RAB7ARILPSPTAN1
Complex memberships
CLN3-CLN5 endolysosomal complex

Evidence

Reading pass · 30 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1995 CLN3 encodes a novel 438 amino acid protein; a ~1 kb genomic deletion disrupting CLN3 was identified in Batten disease patients, confirming it as the disease gene. Exon amplification, genomic deletion mapping, mutation identification in patient cohorts Cell High 7553855
1998 CLN3 protein (battenin) is a highly glycosylated lysosomal membrane protein that is processed proteolytically in acidic compartments; confirmed by in vitro translation, immunoprecipitation, Western blotting, and Percoll density gradient fractionation. In vitro translation, Western blotting, Percoll density gradient fractionation, Triton X-114 extraction, GFP fusion expression in mammalian cells Molecular genetics and metabolism High 10191115 9384607
1998 CLN3 protein localizes to the lysosomal compartment; pulse-chase experiments showed it is synthesized as an N-glycosylated ~43 kDa polypeptide not secreted into growth medium. Pulse-chase labeling, immunoprecipitation, confocal immunofluorescence microscopy in COS-1 and HeLa cells Human molecular genetics High 9384607
1999 CLN3 protein is confirmed as a lysosomal membrane protein by immunoelectron microscopy co-localization with lysosomal markers; the common 461-677del mutant is retained in the ER and cannot reach lysosomes, while the E295K missense mutant reaches lysosomes similarly to wild-type. Immunoelectron microscopy, pulse-chase labeling, immunoprecipitation, transient expression in BHK cells and mouse primary neurons Human molecular genetics High 10332042
1999 CLN3 protein is targeted to lysosomal compartments via the trans-Golgi apparatus; monensin treatment causes retention in Golgi vesicular structures, indicating trafficking through the trans-Golgi network to lysosomes. GFP fusion expression, confocal laser scanning microscopy, monensin treatment, tunicamycin treatment in CHO and human neuroblastoma cells Molecular genetics and metabolism Medium 10191113
1999 CLN3 protein suppresses apoptosis and enhances growth in NT2 neuronal precursor cells; CLN3 overexpression modulates endogenous ceramide levels, acting upstream of ceramide generation to suppress apoptosis. CLN3 overexpression in NT2 cells, apoptosis assays (vincristine, staurosporine, etoposide treatment), ceramide measurement Molecular genetics and metabolism Medium 10191118
2000 CLN3 protein modulates lysosomal pH homeostasis: CLN3 overexpression increases lysosomal pH in human embryonal kidney cells, while antisense inhibition acidifies lysosomal compartments. These pH changes alter intracellular processing of amyloid-beta precursor protein and cathepsin D. Mutant CLN3 (R334C) lacked these activities. CLN3 overexpression, antisense inhibition, lysosomal pH measurement, Western blotting of APP and cathepsin D processing in HEK293 cells Molecular genetics and metabolism Medium 10924275
2001 In neurons, CLN3 is not exclusively lysosomal; it localizes to synaptosomes but is excluded from synaptic vesicles, suggesting a role at the synapse distinct from its lysosomal function. In situ hybridization, immunohistochemistry, Western blot of subcellular fractions, immunofluorescence in mouse brain sections and primary retinal cultures Human molecular genetics Medium 11590129
2002 CLN3 interacts with antisense-mediated knockdown pathway; blocking CLN3 expression in postmitotic hNT neurons causes apoptosis, demonstrating CLN3 is required for neuronal survival. Adenoviral antisense-CLN3 construct delivery to human postmitotic hNT neurons, apoptosis assays Annals of neurology Medium 11921051
2002 The common CLN3 1.02 kb deletion results in a truncated protein missing amino acids 154-438; specific CLN3 motifs (exons 11 and 13; conserved stretches 184WSSGTGGAGLLG195, 291VYFAE295, 330VFASRSSL337) and glycosylation sites (71NQSH74 and 310NTSL313) are required for CLN3's anti-apoptotic function and normal cell growth rate. JNCL lymphoblast cell lines, transfection with mutant CLN3 cDNA constructs, cell growth rate assays, etoposide-induced apoptosis assays Human molecular genetics Medium 12189165
2003 CLN3 contains five transmembrane domains, with an extracellular/intraluminal amino-terminus and a cytoplasmic carboxy-terminus, as determined by in vitro translation with glycosylation site mutagenesis. In vitro translation with canine pancreatic microsomes, Flag epitope tagging, glycosylation site mutagenesis, immunoprecipitation FEBS letters Medium 12706816
2003 CLN3 traffics to the lysosome via the plasma membrane (cell surface); inhibition of the AP-3 adaptor protein complex subunit micro3A increased CLN3 at the cell surface, demonstrating AP-3 involvement in CLN3 lysosomal trafficking. Surface biotinylation, antibody trapping, AP-3 subunit knockdown in NCCIT cells FEBS letters Medium 14644441
2003 CLN3 has two lysosomal targeting motifs: a novel M(X)9G motif in the C-terminal cytosolic tail and a dileucine motif in the large cytosolic loop domain (preceded by an acidic patch). Each motif alone is sufficient for lysosomal targeting; in neurons, CLN3 also localizes to early endosomes via an endosomal association independent of these targeting motifs. Mutagenesis of targeting motifs, transfection in nonneuronal and neuronal cells, immunofluorescence confocal microscopy Molecular biology of the cell High 14699076
2004 The dileucine-based motif EEEX(8)LI in the second cytoplasmic domain of CLN3 is necessary and sufficient for lysosomal targeting; the C-terminal domain and first cytoplasmic domain are less efficient. No interaction of CLN3 cytoplasmic domains with AP-1, AP-3, or GGA3 adaptor complexes was detected using chimeric reporter proteins. Chimeric CLN3/LAMP-1/lysosomal acid phosphatase reporter constructs, cell transfection, lysosomal targeting assays, adaptor binding assays The Journal of biological chemistry Medium 15469932
2004 The dileucine motif of CLN3 binds both AP-1 and AP-3 adaptor complexes in vitro; expression in AP-1– or AP-3–deficient mouse fibroblasts showed both adaptor complexes are required for sequential lysosomal sorting of CLN3 via this motif. Biochemical binding assays (in vitro), immunofluorescence in AP-1– and AP-3–deficient mouse fibroblasts The Journal of biological chemistry High 15598649
2004 CLN3 overexpression induces aggregation of the microtubule-binding protein Hook1, potentially by mediating its dissociation from microtubules; a weak interaction between Hook1 and cytoplasmic segments of CLN3 was demonstrated by in vitro binding assay. Receptor-mediated endocytosis is defective in CLN3-deficient JNCL fibroblasts. In vitro binding assay, CLN3 overexpression, receptor-mediated endocytosis assay in JNCL fibroblasts, co-immunoprecipitation for Hook1-Rab interactions Human molecular genetics Medium 15471887
2007 CLN3 is prenylated (most likely farnesylated) at cysteine 435 via its C-terminal CAAX motif; this prenylation is required for efficient sorting in early endosomal structures and lysosomal delivery, particularly in neuronal cells. Farnesyltransferase inhibition increased CLN3 at the cell surface. Mevalonate incorporation, farnesyltransferase inhibitor treatment, C435 mutagenesis, immunofluorescence in COS7 and neuronal cells Traffic Medium 17286803
2007 CLN3 is required for synthesis of bis(monoacylglycerol)phosphate (BMP) in lysosomes; metabolic labeling showed reduced BMP synthesis in JNCL fibroblasts and brain, restored by wild-type CLN3 complementation. CLN3 overexpression increased BMP synthesis; mutant CLN3-L170P decreased it. BMP isolation from brain detergent-resistant membranes, metabolic labeling of JNCL fibroblasts and CLN3-overexpressing cell lines, wild-type CLN3 complementation Biochemical and biophysical research communications Medium 17482562
2008 CLN3 physically interacts with the plasma membrane cytoskeletal protein fodrin (alpha-spectrin) and with Na+/K+-ATPase; loss of CLN3 disrupts fodrin distribution and impairs ouabain-induced endocytosis and subcellular distribution of neuron-specific Na+/K+-ATPase in Cln3-/- mouse primary neurons, while pump activity itself is unchanged. Co-immunoprecipitation, immunostaining of fodrin in JNCL fibroblasts and Cln3-/- brain, Na+/K+-ATPase activity assay, ouabain-induced endocytosis assay in primary neurons Experimental cell research Medium 18621045
2011 CLN3 is required for the response to oxidative stress; Drosophila lacking CLN3 function are hypersensitive to oxidative stress and fail to detoxify reactive oxygen species. CLN3 overexpression confers increased resistance to oxidative stress. Genetic interaction screen identified connections between CLN3 and core stress signalling pathways and stress granule components. Drosophila gain-of-function modifier screen, CLN3 loss-of-function, oxidative stress survival assays, ROS detoxification assays Human molecular genetics Medium 21372148
2012 CLN3 interacts with motor components of both plus-end and minus-end microtubular trafficking (tubulin, dynactin, dynein, kinesin-2); CLN3 directly interacts with active GTP-bound Rab7 and with RILP (Rab7-interacting lysosomal protein that anchors dynein motor). The disease-causing CLN3E295K mutant induces perinuclear clustering of late endosomes/lysosomes. Co-immunoprecipitation, GTP-Rab7 pulldown, overexpression of CLN3 mutants in HeLa cells, immunofluorescence of late endosome markers Cellular and molecular life sciences Medium 22261744
2013 CLN3 is required for normal trafficking of microdomain-associated proteins caveolin-1, syntaxin-6, and MDR1 from the trans-Golgi network (TGN) to the plasma membrane in brain endothelial cells. CLN3-null cells have reduced caveolae, impaired caveolae-mediated endocytosis, drug efflux, and cell volume regulation. CLN3 localizes to the TGN and partitions with buoyant microdomain fractions. Application of lactosylceramide rescues protein transport and caveolar endocytosis in CLN3-deficient cells. CLN3 KO brain endothelial cells, immunofluorescence, caveolae quantification by EM, drug efflux assay, volume regulation assay, fluorescent sphingolipid probes, glycosphingolipid rescue The Journal of neuroscience High 24227717
2015 CLN3 protein is involved in intracellular Ca2+ handling; JNCL cells bearing the common CLN3 mutation show alterations in ER, mitochondrial, and lysosomal Ca2+ pools and in store-operated Ca2+ uptake, and display autophagosome accumulation reversible by Ca2+ chelation. GFP-LC3 autophagy screening assay in JNCL mouse and iPSC-derived neural progenitor cells, thapsigargin sensitivity assay, Ca2+ chelation rescue, Ca2+ pool measurements The Journal of biological chemistry Medium 25878248
2019 CLN3-defective cells have multiple lysosomal enzyme deficiencies (28 soluble lysosomal proteins reduced); CLN3 deficiency also impairs lipid droplet degradation, alters lactosylceramide and glycosphingolipid levels, and disrupts recycling endosome/exocytic transferrin receptor trafficking. SILAC-labeled lysosome purification by magnetic separation, mass spectrometry proteomics, immunoblotting, enzyme activity assays, fluorescent lipid probes in CLN3 knock-in mouse cerebellar cell lines The Journal of biological chemistry High 31040178
2020 CLN3 regulates Rab7A-effector interactions at late endosomes: CLN3 is required for efficient endosome-to-TGN trafficking of lysosomal sorting receptors (CI-M6PR, sortilin) because it regulates the Rab7A interaction with retromer. CLN3 is also required for the Rab7A-PLEKHM1 interaction, which mediates autophagosome-to-lysosome fusion. Co-immunoprecipitation of Rab7A effector interactions in CLN3 KO and CLN3-disease-mutant cells, live-cell imaging, sorting receptor degradation assays Journal of cell science High 32034082
2021 CLN3 and CLN5 function as an endolysosomal complex: CLN5 depletion results in impaired CLN3-Rab7A interactions and downstream effector interactions; CLN3 and CLN5 together regulate endolysosome fusion, autophagy, and retromer function. Co-immunoprecipitation of CLN3-CLN5 complex, Rab7A effector interaction assays after CLN5 depletion, endolysosomal fusion assays, autophagy flux assays The Biochemical journal Medium 34060589
2021 CLN3 is required for phagocytosis of photoreceptor outer segments (POS) by retinal pigment epithelium (RPE); a proportion of CLN3 localizes to RPE microvilli. CLN3-disease iPSC-RPE cells show decreased microvilli density and reduced POS binding and ingestion, rescued by wild-type CLN3 gene supplementation. iPSC-RPE from CLN3-disease patients, POS phagocytosis assay (binding and ingestion), immunofluorescence of RPE microvilli, wild-type CLN3 gene rescue Communications biology High 33547385
2022 CLN3 is required for lysosomal egress of glycerophosphodiesters (GPDs), the end products of glycerophospholipid catabolism. Loss of CLN3 causes massive accumulation of GPDs in brain lysosomes of mice and elevated glycerophosphoinositol in CSF of Batten disease patients. CLN3 deficiency also disrupts glycerophospholipid catabolism. LysoTag mouse for tissue-specific lysosome isolation, untargeted metabolite profiling of brain lysosomes by mass spectrometry, CLN3-deficient cultured cells, CSF metabolite analysis from Batten disease patients Nature High 36131016
2023 CLN3 functions as a vesicular trafficking hub between Golgi and lysosome compartments: CLN3 interacts with the cation-independent mannose 6-phosphate receptor (CI-M6PR) and multiple endo-lysosomal trafficking proteins. CLN3 depletion causes mis-trafficking of CI-M6PR, mis-sorting of lysosomal enzymes, and defective autophagic lysosomal reformation. CLN3 overexpression promotes formation of multiple lysosomal tubules in a CI-M6PR– and autophagy-dependent manner. Proteomics (CLN3 interactome), co-immunoprecipitation, CI-M6PR trafficking assays, lysosomal enzyme sorting assays, lysosomal tubule formation assays in CLN3 KO and overexpressing cells Nature communications High 37400440
2010 CLN3 physically interacts with nonmuscle myosin-IIB; loss of CLN3 in Cln3-/- cells causes myosin-IIB distribution abnormalities and a cell migration defect that mimics myosin-II inhibition by blebbistatin. Co-immunoprecipitation of CLN3 and myosin-IIB, scratch assay and transwell migration assay in Cln3-/- cells, blebbistatin inhibition comparison, immunofluorescence of myosin-IIB Experimental cell research Medium 20850431

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1995 Isolation of a novel gene underlying Batten disease, CLN3. The International Batten Disease Consortium. Cell 462 7553855
1992 The Cln3-Cdc28 kinase complex of S. cerevisiae is regulated by proteolysis and phosphorylation. The EMBO journal 386 1316273
2004 Cln3 activates G1-specific transcription via phosphorylation of the SBF bound repressor Whi5. Cell 318 15210110
1995 p34Cdc28-mediated control of Cln3 cyclin degradation. Molecular and cellular biology 271 7823941
1997 Coupling of cell division to cell growth by translational control of the G1 cyclin CLN3 in yeast. Genes & development 248 9334317
1997 Spectrum of mutations in the Batten disease gene, CLN3. American journal of human genetics 178 9311735
1998 Biosynthesis and intracellular targeting of the CLN3 protein defective in Batten disease. Human molecular genetics 164 9384607
2002 Cln3(Deltaex7/8) knock-in mice with the common JNCL mutation exhibit progressive neurologic disease that begins before birth. Human molecular genetics 162 12374761
2004 Interconnections of CLN3, Hook1 and Rab proteins link Batten disease to defects in the endocytic pathway. Human molecular genetics 122 15471887
2022 CLN3 is required for the clearance of glycerophosphodiesters from lysosomes. Nature 117 36131016
2005 Production, purification, and characterization of lipase from thermophilic and alkaliphilic Bacillus coagulans BTS-3. Protein expression and purification 108 15802219
2005 CLN3, the protein associated with batten disease: structure, function and localization. Journal of neuroscience research 100 15657902
2001 CLN3 protein is targeted to neuronal synapses but excluded from synaptic vesicles: new clues to Batten disease. Human molecular genetics 99 11590129
1999 Defective intracellular transport of CLN3 is the molecular basis of Batten disease (JNCL). Human molecular genetics 99 10332042
2003 Two motifs target Batten disease protein CLN3 to lysosomes in transfected nonneuronal and neuronal cells. Molecular biology of the cell 97 14699076
2000 CLN3 protein regulates lysosomal pH and alters intracellular processing of Alzheimer's amyloid-beta protein precursor and cathepsin D in human cells. Molecular genetics and metabolism 96 10924275
1998 Regulation of the Cln3-Cdc28 kinase by cAMP in Saccharomyces cerevisiae. The EMBO journal 96 9687505
2007 Cyclin Cln3 is retained at the ER and released by the J chaperone Ydj1 in late G1 to trigger cell cycle entry. Molecular cell 90 17560371
1999 CLN3 defines a novel antiapoptotic pathway operative in neurodegeneration and mediated by ceramide. Molecular genetics and metabolism 87 10191118
2009 Recruitment of Cln3 cyclin to promoters controls cell cycle entry via histone deacetylase and other targets. PLoS biology 85 19823669
2005 New assays for detection and localization of endogenous lipid peroxidation products in living boar sperm after BTS dilution or after freeze-thawing. Theriogenology 85 15626411
2013 Alterations in ROS activity and lysosomal pH account for distinct patterns of macroautophagy in LINCL and JNCL fibroblasts. PloS one 83 23408996
2000 Batten disease: evaluation of CLN3 mutations on protein localization and function. Human molecular genetics 79 10749980
2002 The G(1) cyclin Cln3 promotes cell cycle entry via the transcription factor Swi6. Molecular and cellular biology 78 12024050
1993 The yeast Cln3 protein is an unstable activator of Cdc28. Molecular and cellular biology 75 8497251
2015 Unbiased Cell-based Screening in a Neuronal Cell Model of Batten Disease Highlights an Interaction between Ca2+ Homeostasis, Autophagy, and CLN3 Protein Function. The Journal of biological chemistry 69 25878248
2012 The juvenile Batten disease protein, CLN3, and its role in regulating anterograde and retrograde post-Golgi trafficking. Clinical lipidology 69 22545070
2019 The CLN3 gene and protein: What we know. Molecular genetics & genomic medicine 66 31568712
2012 Neuronal ceroid lipofuscinosis protein CLN3 interacts with motor proteins and modifies location of late endosomal compartments. Cellular and molecular life sciences : CMLS 66 22261744
2001 Osmotic stress causes a G1 cell cycle delay and downregulation of Cln3/Cdc28 activity in Saccharomyces cerevisiae. Molecular microbiology 64 11251821
2006 Batten disease (JNCL) is linked to disturbances in mitochondrial, cytoskeletal, and synaptic compartments. Journal of neuroscience research 62 16941499
2016 Self-Complementary AAV9 Gene Delivery Partially Corrects Pathology Associated with Juvenile Neuronal Ceroid Lipofuscinosis (CLN3). The Journal of neuroscience : the official journal of the Society for Neuroscience 59 27629717
2005 The G1 cyclin Cln3 regulates morphogenesis in Candida albicans. Eukaryotic cell 59 15643064
2002 Motifs within the CLN3 protein: modulation of cell growth rates and apoptosis. Human molecular genetics 58 12189165
2011 Distinct early molecular responses to mutations causing vLINCL and JNCL presage ATP synthase subunit C accumulation in cerebellar cells. PloS one 56 21359198
2012 Large-scale phenotyping of an accurate genetic mouse model of JNCL identifies novel early pathology outside the central nervous system. PloS one 54 22701626
2002 Flupirtine blocks apoptosis in batten patient lymphoblasts and in human postmitotic CLN3- and CLN2-deficient neurons. Annals of neurology 54 11921051
2002 AZF1 is a glucose-dependent positive regulator of CLN3 transcription in Saccharomyces cerevisiae. Molecular and cellular biology 52 11839825
2013 CLN3 loss disturbs membrane microdomain properties and protein transport in brain endothelial cells. The Journal of neuroscience : the official journal of the Society for Neuroscience 51 24227717
2004 A dileucine motif and a cluster of acidic amino acids in the second cytoplasmic domain of the batten disease-related CLN3 protein are required for efficient lysosomal targeting. The Journal of biological chemistry 51 15469932
2004 AP-1 and AP-3 facilitate lysosomal targeting of Batten disease protein CLN3 via its dileucine motif. The Journal of biological chemistry 50 15598649
1999 Molecular basis of the neuronal ceroid lipofuscinoses: mutations in CLN1, CLN2, CLN3, and CLN5. Human mutation 50 10477428
1995 Batten disease gene, CLN3: linkage disequilibrium mapping in the Finnish population, and analysis of European haplotypes. American journal of human genetics 50 7887419
2019 Lysosomal proteome analysis reveals that CLN3-defective cells have multiple enzyme deficiencies associated with changes in intracellular trafficking. The Journal of biological chemistry 49 31040178
2014 Evidence for aberrant astrocyte hemichannel activity in Juvenile Neuronal Ceroid Lipofuscinosis (JNCL). PloS one 49 24736558
1999 Tissue expression and subcellular localization of CLN3, the Batten disease protein. Molecular genetics and metabolism 49 10191116
1991 Regional mapping of the Batten disease locus (CLN3) to human chromosome 16p12. American journal of human genetics 49 1746562
2019 Juvenile Batten Disease (CLN3): Detailed Ocular Phenotype, Novel Observations, Delayed Diagnosis, Masquerades, and Prospects for Therapy. Ophthalmology. Retina 47 31926949
2011 The Batten disease gene CLN3 is required for the response to oxidative stress. Human molecular genetics 47 21372148
2004 Boar sperm storage capacity of BTS and Androhep Plus: viability, motility, capacitation, and tyrosine phosphorylation. Theriogenology 47 15251239
2020 Therapeutic efficacy of antisense oligonucleotides in mouse models of CLN3 Batten disease. Nature medicine 45 32719489
2011 Analysis of potential biomarkers and modifier genes affecting the clinical course of CLN3 disease. Molecular medicine (Cambridge, Mass.) 45 21863212
2004 A cell sizer network involving Cln3 and Far1 controls entrance into S phase in the mitotic cycle of budding yeast. The Journal of cell biology 45 15520229
2002 The CLN3 gene is a novel molecular target for cancer drug discovery. Cancer research 45 11830536
2001 Early cell cycle box-mediated transcription of CLN3 and SWI4 contributes to the proper timing of the G(1)-to-S transition in budding yeast. Molecular and cellular biology 45 11390643
1998 Cln3-associated kinase activity in Saccharomyces cerevisiae is regulated by the mating factor pathway. Molecular and cellular biology 45 9418890
2019 Knockdown of BTS may provide a new strategy to improve cadmium-phytoremediation efficiency by improving iron status in plants. Journal of hazardous materials 44 31676164
2008 Novel interactions of CLN3 protein link Batten disease to dysregulation of fodrin-Na+, K+ ATPase complex. Experimental cell research 42 18621045
1997 Genomic structure and complete nucleotide sequence of the Batten disease gene, CLN3. Genomics 42 9119403
2023 Loss of the batten disease protein CLN3 leads to mis-trafficking of M6PR and defective autophagic-lysosomal reformation. Nature communications 41 37400440
2003 Membrane topology of CLN3, the protein underlying Batten disease. FEBS letters 41 12706816
1998 Growth-independent regulation of CLN3 mRNA levels by nutrients in Saccharomyces cerevisiae. Journal of bacteriology 41 9440509
2021 Repurposing of tamoxifen ameliorates CLN3 and CLN7 disease phenotype. EMBO molecular medicine 40 34411438
2007 A novel role of the Batten disease gene CLN3: association with BMP synthesis. Biochemical and biophysical research communications 40 17482562
2002 The CLN3/SWI6/CLN2 pathway and SNF1 act sequentially to regulate meiotic initiation in Saccharomyces cerevisiae. Genes to cells : devoted to molecular & cellular mechanisms 40 12081645
2010 A novel interaction of CLN3 with nonmuscle myosin-IIB and defects in cell motility of Cln3(-/-) cells. Experimental cell research 39 20850431
2008 Interactions between the juvenile Batten disease gene, CLN3, and the Notch and JNK signalling pathways. Human molecular genetics 39 19028667
1999 Analysis of intracellular distribution and trafficking of the CLN3 protein in fusion with the green fluorescent protein in vitro. Molecular genetics and metabolism 39 10191113
2000 Localization and processing of CLN3, the protein associated to Batten disease: where is it and what does it do? Journal of neuroscience research 37 10658181
2017 Homeostatic control of START through negative feedback between Cln3-Cdk1 and Rim15/Greatwall kinase in budding yeast. eLife 36 28600888
2013 Effects of the yeast RNA-binding protein Whi3 on the half-life and abundance of CLN3 mRNA and other targets. PloS one 36 24386402
2020 CLN3 regulates endosomal function by modulating Rab7A-effector interactions. Journal of cell science 35 32034082
2016 Vision loss in juvenile neuronal ceroid lipofuscinosis (CLN3 disease). Annals of the New York Academy of Sciences 35 26748992
2021 A human model of Batten disease shows role of CLN3 in phagocytosis at the photoreceptor-RPE interface. Communications biology 34 33547385
2016 Efficacy of phosphodiesterase-4 inhibitors in juvenile Batten disease (CLN3). Annals of neurology 33 27804148
2007 C-terminal prenylation of the CLN3 membrane glycoprotein is required for efficient endosomal sorting to lysosomes. Traffic (Copenhagen, Denmark) 33 17286803
1999 Expression studies of CLN3 protein (battenin) in fusion with the green fluorescent protein in mammalian cells in vitro. Molecular genetics and metabolism 33 10191115
1998 Transcriptional regulation of CLN3 expression by glucose in Saccharomyces cerevisiae. Journal of bacteriology 33 9721289
2020 Loss of CLN3, the gene mutated in juvenile neuronal ceroid lipofuscinosis, leads to metabolic impairment and autophagy induction in retinal pigment epithelium. Biochimica et biophysica acta. Molecular basis of disease 32 32592935
2017 Loss of Cln3 impacts protein secretion in the social amoeba Dictyostelium. Cellular signalling 31 28365442
2008 Transcript and in silico analysis of CLN3 in juvenile neuronal ceroid lipofuscinosis and associated mouse models. Human molecular genetics 31 18678598
2007 Increased expression of lysosomal acid phosphatase in CLN3-defective cells and mouse brain tissue. Journal of neurochemistry 31 17868323
2016 Using Patient-Specific Induced Pluripotent Stem Cells and Wild-Type Mice to Develop a Gene Augmentation-Based Strategy to Treat CLN3-Associated Retinal Degeneration. Human gene therapy 29 27400765
2014 Novel CLN3 mutation causing autophagic vacuolar myopathy. Neurology 29 24827497
2006 The F-box protein Grr1 regulates the stability of Ccn1, Cln3 and Hof1 and cell morphogenesis in Candida albicans. Molecular microbiology 29 16987179
2018 Cln3 function is linked to osmoregulation in a Dictyostelium model of Batten disease. Biochimica et biophysica acta. Molecular basis of disease 28 30251676
2021 CLN3, at the crossroads of endocytic trafficking. Neuroscience letters 27 34274435
2013 Osmotic stress changes the expression and subcellular localization of the Batten disease protein CLN3. PloS one 27 23840424
1996 Isolation and chromosomal mapping of a mouse homolog of the Batten disease gene CLN3. Genomics 27 8812504
2021 CLN5 and CLN3 function as a complex to regulate endolysosome function. The Biochemical journal 26 34060589
2016 Neurodegeneration and Epilepsy in a Zebrafish Model of CLN3 Disease (Batten Disease). PloS one 26 27327661
2003 Intracellular trafficking of CLN3, the protein underlying the childhood neurodegenerative disease, Batten disease. FEBS letters 25 14644441
1996 Mitochondrial abnormalities in CLN2 and CLN3 forms of Batten disease. Molecular and chemical neuropathology 25 8971698
2018 Astrocytes in juvenile neuronal ceroid lipofuscinosis (CLN3) display metabolic and calcium signaling abnormalities. Journal of neurochemistry 24 29964296
2013 Methodology of clinical research in rare diseases: development of a research program in juvenile neuronal ceroid lipofuscinosis (JNCL) via creation of a patient registry and collaboration with patient advocates. Contemporary clinical trials 24 23628560
2000 Neural and extraneural expression of the neuronal ceroid lipofuscinoses genes CLN1, CLN2, and CLN3: functional implications for CLN3. Molecular genetics and metabolism 24 11001812
1998 Studies of atypical JNCL suggest overlapping with other NCL forms. Pediatric neurology 23 9492089
2020 An iPSC-Derived Neuron Model of CLN3 Disease Facilitates Small Molecule Phenotypic Screening. ACS pharmacology & translational science 22 33073192
2018 Clinical and molecular characterization of non-syndromic retinal dystrophy due to c.175G>A mutation in ceroid lipofuscinosis neuronal 3 (CLN3). Documenta ophthalmologica. Advances in ophthalmology 22 30446867
2019 Comparative transcriptomics reveals mechanisms underlying cln3-deficiency phenotypes in Dictyostelium. Cellular signalling 21 30771446

Missed literature

Know a paper Affinage missed for CLN3? Flag it for the maintainers and the community.

No submissions yet.