CLN3 (battenin) is a multipass endolysosomal membrane protein whose loss causes juvenile neuronal ceroid lipofuscinosis. It conducts chloride and contributes to lysosomal ion balance and degradative function. A detailed trafficking study identified cytosolic-region binding to active Rab7 and RILP, linking CLN3 to the positioning and trafficking of late endosomal compartments. CLN3 deficiency also disrupts lipid distribution, lysosomal metabolite clearance and neuronal physiology. Cellular lipid-binding and transport observations complement these roles, while the exact mechanism of glycerophosphodiester clearance and proposed soluble glycolipid transfer remains unresolved.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0000139 Golgi membrane | IDA PMID:10191111 Intracellular trafficking of the JNCL protein CLN3. | KEEP AS NON CORE | Summary: Retain construct-dependent Golgi localization. Reason: The original abstract reports Golgi localization of an N-terminal GFP fusion and ER retention after C-terminal tagging. The Golgi signal is positive evidence but does not replace the predominant endolysosomal localization; tag position affects trafficking. Supporting Evidence: |
| GO:0000139 Golgi membrane | IDA PMID:9949212 The Batten disease gene product (CLN3p) is a Golgi integral ... | KEEP AS NON CORE | Summary: Retain the original Golgi membrane observation. Reason: The source reports membrane-associated GFP-tagged CLN3 and Golgi localization, including a stable low-copy construct. This is a secondary trafficking compartment rather than the sole native location. Supporting Evidence: |
| GO:0000139 Golgi membrane | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: Retain the Golgi membrane mapping as secondary localization. Reason: The authenticated UniProt subcellular-location mapping agrees with reported Golgi trafficking. Direct lysosomal and endosomal localization is more representative of its molecular work. |
| GO:0000139 Golgi membrane | TAS Reactome:R-HSA-9844955 | KEEP AS NON CORE | Summary: Retain the explicitly modeled Golgi membrane compartment. Reason: Reactome catalyst R-HSA-9844953 points to physical entity R-HSA-9844960, whose reference entity is human Q13286 in the Golgi membrane. This location is distinguishable from the uncertain carrier mechanism modeled in the same event. Supporting Evidence: Reactome:R-HSA-9844955 |
| GO:0001508 action potential | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Retain the mouse-supported electrical phenotype as contextual. Reason: Current mouse Q61124 GOA links this term to IMP in the authenticated donor record with acts_upstream_of_or_within. This supports a physiological consequence of Cln3 deficiency, not a direct demonstration that human CLN3 generates neuronal action potentials. The original ISS assertion is retained with that scope. Supporting Evidence: GO_REF:0000024 |
| GO:0005515 protein binding | IPI PMID:12134079 Neuronal ceroid lipofuscinoses are connected at molecular le... | KEEP AS NON CORE | Summary: Retain experimentally supported CLN5 association. Reason: Human CLN3/CLN5 association is supported by COS1 co-immunoprecipitation and GST-CLN5 pull-down of in-vitro-translated CLN3 with controls. Two exact IntAct records authenticate the pair. This does not establish a native stoichiometric complex or an additional defining CLN3 activity. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:14699076 Two motifs target Batten disease protein CLN3 to lysosomes i... | KEEP AS NON CORE | Summary: Retain the independently measured CLN5 association. Reason: The full source reports CLN5 co-immunoprecipitation with wild-type and targeting-motif-mutant CLN3 in transfected cells. Trafficking changes do not eliminate the association; a purified native complex was not established. The separately attributed original-text excerpt makes this full-source result checkable without replacing the abstract cache. Supporting Evidence: file:human/CLN3/CLN3-primary-excerpts.md the two NCL proteins were able to retain their physical interaction |
| GO:0005515 protein binding | IPI PMID:15471887 Interconnections of CLN3, Hook1 and Rab proteins link Batten... | KEEP AS NON CORE | Summary: Retain the mapped HOOK1 interaction. Reason: Actual Results report weak, reproducible binding of in-vitro-translated HOOK1 to GST-CLN3 cytosolic fragments, with GST and luminal-fragment controls. This supports the pair; it does not establish CLN3 motor activity or prove that the assayed partner is a structural cytoskeletal component. Supporting Evidence: PMID:15471887 a weak interaction between Hook1 and the cytoplasmic segments of CLN3 |
| GO:0005515 protein binding | IPI PMID:15598649 AP-1 and AP-3 facilitate lysosomal targeting of Batten disea... | MODIFY | Summary: Specify AP-3 adaptor complex binding. Reason: The original abstract explicitly reports in-vitro binding of the CLN3 dileucine motif to AP-3 and sorting effects in adaptor-deficient fibroblasts. The verified AP3D1 partner belongs to this complex. This binding refinement does not assign the adaptor activity itself to its CLN3 cargo. Full Methods were not recovered. Proposed replacements: AP-3 adaptor complex binding Supporting Evidence: PMID:15598649 bound both AP-1 and AP-3 |
| GO:0005515 protein binding | IPI PMID:15598649 AP-1 and AP-3 facilitate lysosomal targeting of Batten disea... | MODIFY | Summary: Specify AP-1 adaptor complex binding. Reason: The original abstract explicitly reports in-vitro binding of the CLN3 dileucine motif to AP-1 and sorting effects in adaptor-deficient fibroblasts. The verified AP1G1 partner belongs to this complex. This represents cargo recognition, not intrinsic clathrin-adaptor activity of CLN3. Full Methods were not recovered. Proposed replacements: AP-1 adaptor complex binding Supporting Evidence: PMID:15598649 bound both AP-1 and AP-3 |
| GO:0005515 protein binding | IPI PMID:15598649 AP-1 and AP-3 facilitate lysosomal targeting of Batten disea... | UNDECIDED | Summary: The exact AP2A2 experiment remains unresolved. Reason: The original abstract directly names AP-1 and AP-3, while the preserved assertion names AP2A2. The authenticated UniProt record also reports this interaction, but the original full assay and an exact interaction-provider record were not recovered. Retain the source assertion pending verification; absence from the abstract is not evidence against the pair. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:17189291 Neuronal vulnerability of CLN3 deletion to calcium-induced c... | MODIFY | Summary: Specify binding to the DNA-binding transcription factor KCNIP3. Reason: The original abstract reports in-vitro binding and co-immunoprecipitation with the CLN3 C-terminal region. Authenticated human KCNIP3 is a DNA-binding transcriptional repressor as well as a channel regulator. The partner-class term describes the measured association without assigning transcriptional regulation to CLN3. Increased calcium dissociates this interaction. Proposed replacements: DNA-binding transcription factor binding Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:17237713 Neuronal ceroid lipofuscinosis: a common pathway? | KEEP AS NON CORE | Summary: Retain the reported associations with other NCL proteins. Reason: Full Results describe endogenous human lymphoblast association with TPP1 and CLN3 detection after CLN6/CLN8 immunoprecipitation, with reciprocal overexpression experiments where endogenous signal was limiting. These are complex-association assays, not purified binary binding for every pair. Supporting Evidence: PMID:17237713 CLN2, CLN3, CLN6, and CLN8 proteins co-immunoprecipitate |
| GO:0005515 protein binding | IPI PMID:19941651 Novel interactions of CLN5 support molecular networking betw... | KEEP AS NON CORE | Summary: Retain the mouse CLN5 association at its tested scope. Reason: Mouse GST-CLN5 residues26–341 pull down CLN3 from transfected COS1 lysates; the paper also reports endogenous cellular association. This supports the historical mixed-species pair without assigning CLN5 enzymatic chemistry to CLN3. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:20015955 Interaction between Sdo1p and Btn1p in the Saccharomyces cer... | KEEP AS NON CORE | Summary: Retain the C-terminal SBDS interaction. Reason: Human CLN3 C-terminal bait identified an SBDS fragment in Cytotrap screening; tagged proteins were co-immunoprecipitated in NIH3T3 cells. Yeast ortholog observations are separate. This does not establish a ribosome-biogenesis activity of CLN3. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:20850431 A novel interaction of CLN3 with nonmuscle myosin-IIB and de... | MODIFY | Summary: Specify the experimentally bound myosin partner. Reason: The study maps a human CLN3 C-terminal interaction with a MYH10 fragment and co-immunoprecipitates endogenous mouse myosin IIB with tagged CLN3 in NIH3T3 cells. The specific binding class fits this pair; it does not confer myosin motor catalysis on CLN3. Proposed replacements: myosin binding Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:22261744 Neuronal ceroid lipofuscinosis protein CLN3 interacts with m... | MODIFY | Summary: Specify small GTPase binding through Rab7. Reason: Purified CLN3 N-terminal fragments bind active Rab7Q67L weakly but reproducibly, and cellular co-immunoprecipitation corroborates association. This is a directly performed binding activity implicated in endolysosomal positioning; no guanine-nucleotide exchange or GTPase-activating reaction is shown. Proposed replacements: small GTPase binding Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:22261744 Neuronal ceroid lipofuscinosis protein CLN3 interacts with m... | MODIFY | Summary: Specify binding to the dynactin cytoskeletal component. Reason: Tagged CLN3 co-immunoprecipitates endogenous DCTN1/p150Glued, a component of the dynactin motor-associated complex. The specific partner class is informative at this assay scope; the experiment does not establish CLN3 force generation or a purified direct interface. Proposed replacements: cytoskeletal protein binding Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:22261744 Neuronal ceroid lipofuscinosis protein CLN3 interacts with m... | KEEP AS NON CORE | Summary: Retain the mapped RILP interaction. Reason: The cytosolic CLN3 loop binds RILP in purified-fragment assays, separately from the Rab7-binding N-terminus. Cellular associations support trafficking context, but simultaneous assembly of a defined CLN3–Rab7–RILP–motor complex was not demonstrated. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:22261744 Neuronal ceroid lipofuscinosis protein CLN3 interacts with m... | MODIFY | Summary: Specify binding to the kinesin partner KIF3A. Reason: Tagged CLN3 co-immunoprecipitates endogenous KIF3A in the original cellular assay. The verified motor identity supports kinesin binding; this does not make CLN3 a kinesin or show autonomous motor activity. Proposed replacements: kinesin binding Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:32814053 Interactome Mapping Provides a Network of Neurodegenerative ... | MODIFY | Summary: Specify the measured cadherin partner class. Reason: Three exact neurodegenerative-disease interaction screen records link CLN3 and human CDHR3 in array, prey-pooling and validated yeast two-hybrid assays. CDHR3 is an authenticated cadherin-family membrane adhesion protein. The term specifies the tested partner class without asserting a native CLN3 adhesion mechanism. Proposed replacements: cadherin binding Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:32814053 Interactome Mapping Provides a Network of Neurodegenerative ... | KEEP AS NON CORE | Summary: Retain the exact IFT20 isoform interaction as non-core. Reason: Three exact neurodegenerative-disease interaction screen records support the pair with Q8IY31-3, rather than an unspecified IFT20 product. Yeast two-hybrid evidence supports association, not a demonstrated ciliary transport mechanism or activity shared by every CLN3 product. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:32814053 Interactome Mapping Provides a Network of Neurodegenerative ... | KEEP AS NON CORE | Summary: Retain the exact MAGEB6 screen interaction. Reason: Three exact neurodegenerative-disease interaction screen records support this human pair in yeast two-hybrid formats. No target-specific native mechanism or informative established partner class was demonstrated in the inspected evidence; the positive interaction is preserved. Supporting Evidence: |
| GO:0005634 nucleus | IDA PMID:10191116 Tissue expression and subcellular localization of CLN3, the ... | KEEP AS NON CORE | Summary: Retain the reported nuclear signal as secondary localization. Reason: The original abstract explicitly reports native human tissue immunolocalization, including nuclear signal, using multiple epitope antibodies. Predominant lysosomal localization does not by itself refute this observation; its physiological nuclear role remains unresolved. Supporting Evidence: |
| GO:0005737 cytoplasm | IDA PMID:10191116 Tissue expression and subcellular localization of CLN3, the ... | KEEP AS NON CORE | Summary: Retain the broad cytoplasmic localization. Reason: The original human tissue immunolocalization reports cytoplasmic signal. Cytoplasm includes CLN3-containing organelles and is less informative than the endolysosomal membrane compartments. Supporting Evidence: |
| GO:0005764 lysosome | EXP PMID:9949212 The Batten disease gene product (CLN3p) is a Golgi integral ... | ACCEPT | Summary: Retain lysosomal localization with a source-scope qualification. Reason: The original cached abstract emphasizes tagged-protein Golgi localization, so its exact lysosome experiment was not independently resolved. Multiple other direct human localization studies establish the gene-level lysosomal capability; this acceptance does not claim inspection of an unreported original assay. |
| GO:0005764 lysosome | IBA GO_REF:0000033 | ACCEPT | Summary: Retain phylogenetically inferred lysosomal localization. Reason: Current target and donor experimental records provide positive grounding for the inherited compartment. Target self-inclusion in the donor set is legitimate; the historical IBD placement and alignment were not reconstructed. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN000861897 SUPPORTS TRANSFER Qualified support combines the current PAINT assertion, authentic current target/donor evidence and the source-specific functional assessment. The historical IBD placement, tree and alignment were not reconstructed. Target self-inclusion is legitimate experimental grounding; donor count is not used as a strength or failure score. |
| GO:0005764 lysosome | IDA PMID:10332042 Defective intracellular transport of CLN3 is the molecular b... | ACCEPT | Summary: Retain the experimentally supported lysosomal compartment. Reason: The original source reports CLN3 in the lysosomal trafficking system. Human immunolocalization, targeting-motif experiments and independent endolysosomal electrophysiology corroborate this defining compartment; tagged expression, cell-type differences and the exact assayed construct remain relevant. |
| GO:0005764 lysosome | IDA PMID:10924275 CLN3 protein regulates lysosomal pH and alters intracellular... | ACCEPT | Summary: Retain the experimentally supported lysosomal compartment. Reason: The original source reports CLN3 in the lysosomal trafficking system. Human immunolocalization, targeting-motif experiments and independent endolysosomal electrophysiology corroborate this defining compartment; tagged expression, cell-type differences and the exact assayed construct remain relevant. |
| GO:0005764 lysosome | IDA PMID:14699076 Two motifs target Batten disease protein CLN3 to lysosomes i... | ACCEPT | Summary: Retain the experimentally supported lysosomal compartment. Reason: The original source reports CLN3 in the lysosomal trafficking system. Human immunolocalization, targeting-motif experiments and independent endolysosomal electrophysiology corroborate this defining compartment; tagged expression, cell-type differences and the exact assayed construct remain relevant. |
| GO:0005764 lysosome | IDA PMID:15471887 Interconnections of CLN3, Hook1 and Rab proteins link Batten... | ACCEPT | Summary: Retain the experimentally supported lysosomal compartment. Reason: The original source reports CLN3 in the lysosomal trafficking system. Human immunolocalization, targeting-motif experiments and independent endolysosomal electrophysiology corroborate this defining compartment; tagged expression, cell-type differences and the exact assayed construct remain relevant. |
| GO:0005764 lysosome | IDA PMID:19941651 Novel interactions of CLN5 support molecular networking betw... | ACCEPT | Summary: Retain the experimentally supported lysosomal compartment. Reason: The original source reports CLN3 in the lysosomal trafficking system. Human immunolocalization, targeting-motif experiments and independent endolysosomal electrophysiology corroborate this defining compartment; tagged expression, cell-type differences and the exact assayed construct remain relevant. |
| GO:0005764 lysosome | IEA GO_REF:0000120 | ACCEPT | Summary: Retain the combined lysosomal location inference. Reason: The authenticated mouse donor has experimental lysosomal records, and independent human targeting/localization supports the same compartment. The current donor and UniProt mapping are verified without reconstructing the historical Ensembl transfer. |
| GO:0005764 lysosome | IMP PMID:14644441 Intracellular trafficking of CLN3, the protein underlying th... | ACCEPT | Summary: Retain the experimentally supported lysosomal compartment. Reason: The original source reports CLN3 in the lysosomal trafficking system. Human immunolocalization, targeting-motif experiments and independent endolysosomal electrophysiology corroborate this defining compartment; tagged expression, cell-type differences and the exact assayed construct remain relevant. |
| GO:0005765 lysosomal membrane | EXP PMID:14644441 Intracellular trafficking of CLN3, the protein underlying th... | ACCEPT | Summary: Retain CLN3 in the lysosomal membrane. Reason: Integral-membrane CLN3 localization and trafficking are supported by the original source and independent human experiments. Source-specific tagging, motif mutations or osmotic treatment explain assay context rather than establishing this compartment for every alternative product. |
| GO:0005765 lysosomal membrane | EXP PMID:15471887 Interconnections of CLN3, Hook1 and Rab proteins link Batten... | ACCEPT | Summary: Retain CLN3 in the lysosomal membrane. Reason: Integral-membrane CLN3 localization and trafficking are supported by the original source and independent human experiments. Source-specific tagging, motif mutations or osmotic treatment explain assay context rather than establishing this compartment for every alternative product. |
| GO:0005765 lysosomal membrane | EXP PMID:17286803 C-terminal prenylation of the CLN3 membrane glycoprotein is ... | ACCEPT | Summary: Retain CLN3 in the lysosomal membrane. Reason: Integral-membrane CLN3 localization and trafficking are supported by the original source and independent human experiments. Source-specific tagging, motif mutations or osmotic treatment explain assay context rather than establishing this compartment for every alternative product. |
| GO:0005765 lysosomal membrane | HDA PMID:17897319 Integral and associated lysosomal membrane proteins. | ACCEPT | Summary: Retain lysosomal membrane proteomic detection. Reason: Original human placental lysosomal proteomics Table1 contains CLN3 isoform1, IPI00012448, 438 residues, eight peptides and22.8% coverage, with significant enrichment. This supports detection in the enriched membrane preparation, not a functional assay or resolution of all seven products. Supporting Evidence: |
| GO:0005765 lysosomal membrane | IDA PMID:10332042 Defective intracellular transport of CLN3 is the molecular b... | ACCEPT | Summary: Retain CLN3 in the lysosomal membrane. Reason: Integral-membrane CLN3 localization and trafficking are supported by the original source and independent human experiments. Source-specific tagging, motif mutations or osmotic treatment explain assay context rather than establishing this compartment for every alternative product. |
| GO:0005765 lysosomal membrane | IDA PMID:9384607 Biosynthesis and intracellular targeting of the CLN3 protein... | ACCEPT | Summary: Retain CLN3 in the lysosomal membrane. Reason: Integral-membrane CLN3 localization and trafficking are supported by the original source and independent human experiments. Source-specific tagging, motif mutations or osmotic treatment explain assay context rather than establishing this compartment for every alternative product. |
| GO:0005765 lysosomal membrane | IEA GO_REF:0000120 | ACCEPT | Summary: Retain the lysosomal membrane electronic mapping. Reason: The original ARBA and UniProt subcellular identifiers are preserved. Independent human membrane-localization and channel experiments corroborate the location; complete historical rule execution was not reconstructed. |
| GO:0005765 lysosomal membrane | IMP PMID:15598649 AP-1 and AP-3 facilitate lysosomal targeting of Batten disea... | ACCEPT | Summary: Retain CLN3 in the lysosomal membrane. Reason: Integral-membrane CLN3 localization and trafficking are supported by the original source and independent human experiments. Source-specific tagging, motif mutations or osmotic treatment explain assay context rather than establishing this compartment for every alternative product. |
| GO:0005765 lysosomal membrane | IMP PMID:23840424 Osmotic stress changes the expression and subcellular locali... | ACCEPT | Summary: Retain CLN3 in the lysosomal membrane. Reason: Integral-membrane CLN3 localization and trafficking are supported by the original source and independent human experiments. Source-specific tagging, motif mutations or osmotic treatment explain assay context rather than establishing this compartment for every alternative product. |
| GO:0005769 early endosome | IDA PMID:15240864 A galactosylceramide binding domain is involved in trafficki... | KEEP AS NON CORE | Summary: Retain early-endosomal localization as trafficking context. Reason: The original abstract reports CLN3 in early/recycling endosomes in several cell systems. This is a supported secondary compartment, not evidence that CLN3 is exclusively early-endosomal. Supporting Evidence: |
| GO:0005769 early endosome | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Retain the mouse-grounded early-endosomal location. Reason: Current Q61124 records include direct early-endosome localization in a mouse cerebellar precursor model. Human transfer is retained as a secondary compartment, with no reconstruction of the historical Ensembl transfer. |
| GO:0005770 late endosome | EXP PMID:17286803 C-terminal prenylation of the CLN3 membrane glycoprotein is ... | ACCEPT | Summary: Retain the late-endosomal compartment. Reason: Original localization and trafficking observations place CLN3 in late endosomes; human endolysosomal recordings provide independent functional context. The location does not imply that every construct has identical compartmental distribution. |
| GO:0005770 late endosome | IBA GO_REF:0000033 | ACCEPT | Summary: Retain inherited late-endosomal localization. Reason: Current experimental target and donor records agree with late-endosomal CLN3 activity. The historical PAINT node was not reconstructed; target self-inclusion is expected evidence, not circularity. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN000104831 SUPPORTS TRANSFER Qualified support combines the current PAINT assertion, authentic current target/donor evidence and the source-specific functional assessment. The historical IBD placement, tree and alignment were not reconstructed. Target self-inclusion is legitimate experimental grounding; donor count is not used as a strength or failure score. |
| GO:0005770 late endosome | IDA PMID:10332042 Defective intracellular transport of CLN3 is the molecular b... | ACCEPT | Summary: Retain the late-endosomal compartment. Reason: Original localization and trafficking observations place CLN3 in late endosomes; human endolysosomal recordings provide independent functional context. The location does not imply that every construct has identical compartmental distribution. |
| GO:0005770 late endosome | IDA PMID:15471887 Interconnections of CLN3, Hook1 and Rab proteins link Batten... | ACCEPT | Summary: Retain the late-endosomal compartment. Reason: Original localization and trafficking observations place CLN3 in late endosomes; human endolysosomal recordings provide independent functional context. The location does not imply that every construct has identical compartmental distribution. |
| GO:0005770 late endosome | IDA PMID:22261744 Neuronal ceroid lipofuscinosis protein CLN3 interacts with m... | ACCEPT | Summary: Retain the late-endosomal compartment. Reason: Original localization and trafficking observations place CLN3 in late endosomes; human endolysosomal recordings provide independent functional context. The location does not imply that every construct has identical compartmental distribution. |
| GO:0005770 late endosome | IEA GO_REF:0000120 | ACCEPT | Summary: Retain mouse-supported late-endosomal localization. Reason: The current mouse donor has direct endosomal localization, independently consistent with human CLN3 observations. Electronic/sequence-transfer provenance is retained separately from the direct human assays. |
| GO:0005770 late endosome | IMP PMID:23840424 Osmotic stress changes the expression and subcellular locali... | ACCEPT | Summary: Retain the late-endosomal compartment. Reason: Original localization and trafficking observations place CLN3 in late endosomes; human endolysosomal recordings provide independent functional context. The location does not imply that every construct has identical compartmental distribution. |
| GO:0005770 late endosome | ISS GO_REF:0000024 | ACCEPT | Summary: Retain mouse-supported late-endosomal localization. Reason: The current mouse donor has direct endosomal localization, independently consistent with human CLN3 observations. Electronic/sequence-transfer provenance is retained separately from the direct human assays. |
| GO:0005776 autophagosome | IEA GO_REF:0000120 | KEEP AS NON CORE | Summary: Retain autophagosomal localization as contextual. Reason: The current mouse donor contains the experimental localization assertion associated with PMID:16714284. The recovered source is abstract-only and supports autophagic maturation context; detailed compartment-assignment experiments were not independently read. This is not promoted to a defining human location. Supporting Evidence: GO_REF:0000120 |
| GO:0005776 autophagosome | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Retain autophagosomal localization as contextual. Reason: The current mouse donor contains the experimental localization assertion associated with PMID:16714284. The recovered source is abstract-only and supports autophagic maturation context; detailed compartment-assignment experiments were not independently read. This is not promoted to a defining human location. Supporting Evidence: GO_REF:0000024 |
| GO:0005783 endoplasmic reticulum | IDA PMID:10191111 Intracellular trafficking of the JNCL protein CLN3. | KEEP AS NON CORE | Summary: Retain construct-associated ER localization. Reason: The original abstract reports ER retention after C-terminal tagging, while the N-terminal GFP fusion reaches Golgi. The ER observation is real assay context but is not used as the predominant native location. Supporting Evidence: |
| GO:0005789 endoplasmic reticulum membrane | IDA PMID:12706816 Membrane topology of CLN3, the protein underlying Batten dis... | KEEP AS NON CORE | Summary: Retain the membrane-insertion experiment with its limits. Reason: The original abstract describes in-vitro-translated CLN3 with canine microsomes and topology/glycosylation assays. This establishes membrane insertion in that system, not sustained native ER residence or an invariant topology for all products. Supporting Evidence: |
| GO:0005794 Golgi apparatus | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: Retain the inherited Golgi compartment as secondary. Reason: Human localization and current mouse/Dictyostelium records ground Golgi trafficking. The exact historical PAINT placement was not reconstructed, and the donor diversity is neither a failure criterion nor proof of the ancestral node. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: PANTHER:PTN008509420 SUPPORTS TRANSFER Qualified support combines the current PAINT assertion, authentic current target/donor evidence and the source-specific functional assessment. The historical IBD placement, tree and alignment were not reconstructed. Target self-inclusion is legitimate experimental grounding; donor count is not used as a strength or failure score. |
| GO:0005794 Golgi apparatus | IDA PMID:10332042 Defective intracellular transport of CLN3 is the molecular b... | KEEP AS NON CORE | Summary: Retain source-specific Golgi trafficking localization. Reason: The original source supports CLN3 within Golgi/TGN trafficking or its relevant subcompartment. This complements rather than replaces the well-supported endolysosomal membrane location; expression system and tag-dependent distributions are retained as limits. Supporting Evidence: |
| GO:0005794 Golgi apparatus | IDA PMID:15240864 A galactosylceramide binding domain is involved in trafficki... | KEEP AS NON CORE | Summary: Retain source-specific Golgi trafficking localization. Reason: The original source supports CLN3 within Golgi/TGN trafficking or its relevant subcompartment. This complements rather than replaces the well-supported endolysosomal membrane location; expression system and tag-dependent distributions are retained as limits. Supporting Evidence: |
| GO:0005794 Golgi apparatus | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: Retain the mapped Golgi subcompartment as secondary. Reason: The authenticated UniProt subcellular mapping agrees with published Golgi trafficking observations. It does not establish a separate defining molecular function. |
| GO:0005794 Golgi apparatus | IMP PMID:23840424 Osmotic stress changes the expression and subcellular locali... | KEEP AS NON CORE | Summary: Retain source-specific Golgi trafficking localization. Reason: The original source supports CLN3 within Golgi/TGN trafficking or its relevant subcompartment. This complements rather than replaces the well-supported endolysosomal membrane location; expression system and tag-dependent distributions are retained as limits. Supporting Evidence: |
| GO:0005795 Golgi stack | IDA PMID:15240864 A galactosylceramide binding domain is involved in trafficki... | KEEP AS NON CORE | Summary: Retain source-specific Golgi trafficking localization. Reason: The original source supports CLN3 within Golgi/TGN trafficking or its relevant subcompartment. This complements rather than replaces the well-supported endolysosomal membrane location; expression system and tag-dependent distributions are retained as limits. Supporting Evidence: |
| GO:0005795 Golgi stack | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: Retain the mapped Golgi subcompartment as secondary. Reason: The authenticated UniProt subcellular mapping agrees with published Golgi trafficking observations. It does not establish a separate defining molecular function. |
| GO:0005802 trans-Golgi network | IDA PMID:10332042 Defective intracellular transport of CLN3 is the molecular b... | KEEP AS NON CORE | Summary: Retain source-specific Golgi trafficking localization. Reason: The original source supports CLN3 within Golgi/TGN trafficking or its relevant subcompartment. This complements rather than replaces the well-supported endolysosomal membrane location; expression system and tag-dependent distributions are retained as limits. Supporting Evidence: |
| GO:0005802 trans-Golgi network | IDA PMID:15240864 A galactosylceramide binding domain is involved in trafficki... | KEEP AS NON CORE | Summary: Retain source-specific Golgi trafficking localization. Reason: The original source supports CLN3 within Golgi/TGN trafficking or its relevant subcompartment. This complements rather than replaces the well-supported endolysosomal membrane location; expression system and tag-dependent distributions are retained as limits. Supporting Evidence: |
| GO:0005802 trans-Golgi network | IEA GO_REF:0000120 | KEEP AS NON CORE | Summary: Retain the transferred TGN location. Reason: Current mouse localization includes transfected Cln3 in TGN/post-TGN membrane domains. The historical rule/Ensembl execution is uninspected; the current source and its expression-system limits are explicit. |
| GO:0005829 cytosol | IEA GO_REF:0000108 | MARK AS OVER ANNOTATED | Summary: The process-to-cytosol extension overstates protein location. Reason: This electronic assertion is inferred from Golgi-to-lysosome transport, not a soluble-cytosol localization assay. CLN3 is an integral endomembrane protein with cytosol-facing regions; cytoplasmic transport does not establish its location in the aqueous cytosol. |
| GO:0005886 plasma membrane | IDA PMID:10191116 Tissue expression and subcellular localization of CLN3, the ... | KEEP AS NON CORE | Summary: Retain the reported plasma-membrane pool. Reason: The original source supports surface localization or surface-to-endosome trafficking. This is a secondary or transit pool; experimentally retargeted channel constructs are not substituted for the original native-location evidence. Supporting Evidence: |
| GO:0005886 plasma membrane | IDA PMID:15240864 A galactosylceramide binding domain is involved in trafficki... | KEEP AS NON CORE | Summary: Retain the reported plasma-membrane pool. Reason: The original source supports surface localization or surface-to-endosome trafficking. This is a secondary or transit pool; experimentally retargeted channel constructs are not substituted for the original native-location evidence. Supporting Evidence: |
| GO:0005886 plasma membrane | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: Retain the plasma-membrane location mapping. Reason: The UniProt subcellular mapping agrees with native surface-labeling and trafficking observations. This does not imply that the principal wild-type pool is at the cell surface. |
| GO:0005886 plasma membrane | IMP PMID:14644441 Intracellular trafficking of CLN3, the protein underlying th... | KEEP AS NON CORE | Summary: Retain the reported plasma-membrane pool. Reason: The original source supports surface localization or surface-to-endosome trafficking. This is a secondary or transit pool; experimentally retargeted channel constructs are not substituted for the original native-location evidence. Supporting Evidence: |
| GO:0005901 caveola | IDA PMID:15240864 A galactosylceramide binding domain is involved in trafficki... | KEEP AS NON CORE | Summary: Retain caveolar localization at the original assay scope. Reason: The source associates CLN3 with plasma-membrane microdomains/caveolar fractions or markers. This contextual localization is not taken as proof that CLN3 builds caveolae or that every membrane raft is a caveola. Supporting Evidence: |
| GO:0005901 caveola | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: Retain the mapped caveolar compartment as secondary. Reason: The authenticated subcellular-location mapping reflects the reported microdomain-associated trafficking context. It is not a separate core location. |
| GO:0005901 caveola | IMP PMID:23840424 Osmotic stress changes the expression and subcellular locali... | KEEP AS NON CORE | Summary: Retain caveolar localization at the original assay scope. Reason: The source associates CLN3 with plasma-membrane microdomains/caveolar fractions or markers. This contextual localization is not taken as proof that CLN3 builds caveolae or that every membrane raft is a caveola. Supporting Evidence: |
| GO:0006865 amino acid transport | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: Retain inherited amino-acid transport involvement. Reason: The current PAINT assertion has target, mouse and yeast experimental grounding. Human lysosomal arginine uptake/rescue supports a cellular role, while the original transport study explicitly leaves an interacting transporter or regulatory mechanism possible. No autonomous amino-acid transporter activity is inferred. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: PANTHER:PTN000104831 SUPPORTS TRANSFER Qualified support combines the current PAINT assertion, authentic current target/donor evidence and the source-specific functional assessment. The historical IBD placement, tree and alignment were not reconstructed. Target self-inclusion is legitimate experimental grounding; donor count is not used as a strength or failure score. |
| GO:0006865 amino acid transport | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: Retain broad amino-acid transport involvement. Reason: The ARBA assertion is consistent with human lysosomal arginine-uptake and rescue evidence. It is retained as cellular transport context rather than a substrate-specific intrinsic transporter activity; historical rule execution was not reconstructed. |
| GO:0006897 endocytosis | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: Retain endocytic trafficking involvement. Reason: The electronic process is consistent with altered receptor cargo handling in human mutant fibroblasts and caveolar endocytosis in mouse endothelium. It does not specify the molecular step performed by CLN3. |
| GO:0006898 receptor-mediated endocytosis | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: Retain inherited receptor-mediated trafficking involvement. Reason: The target itself has experimental grounding for altered transferrin/LDL handling. The inherited assertion is retained without reconstructing the PAINT node or treating target self-inclusion as circularity. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: PANTHER:PTN000104831 SUPPORTS TRANSFER Qualified support combines the current PAINT assertion, authentic current target/donor evidence and the source-specific functional assessment. The historical IBD placement, tree and alignment were not reconstructed. Target self-inclusion is legitimate experimental grounding; donor count is not used as a strength or failure score. |
| GO:0006898 receptor-mediated endocytosis | IMP PMID:15471887 Interconnections of CLN3, Hook1 and Rab proteins link Batten... | KEEP AS NON CORE | Summary: Retain receptor-mediated endocytic trafficking context. Reason: Actual human fibroblast experiments show altered transferrin recycling and delayed LDL passage from early to later endosomes; initial transferrin uptake was unchanged. This supports endocytic-pathway involvement without claiming CLN3 is a ligand receptor or endocytic coat component. Supporting Evidence: |
| GO:0007040 lysosome organization | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Retain mouse-supported lysosome organization. Reason: Current mouse IMP records and the inspected cerebellar precursor study show altered lysosome distribution and morphology before storage accumulation. These support contextual organization involvement, not a direct human organelle-building enzyme. |
| GO:0007042 lysosomal lumen acidification | IMP PMID:11722572 Elevated lysosomal pH in neuronal ceroid lipofuscinoses (NCL... | KEEP AS NON CORE | Summary: Retain the patient-fibroblast result with its directional interpretation explicitly disputed. Reason: The original study measured elevated lysosomal pH in one CLN3-deletion patient fibroblast line compared with a control (4.74 versus 4.02), consistent with an acidification defect in that disease-cell comparison. The later human HEK293T knockout/rescue study in PMID:41558486 instead finds that CLN3 loss lowers lysosomal pH, supporting the opposite functional direction. It therefore does not corroborate this acidification assertion. Retain the original observation as a non-core, source-scoped phenotype; the general acidifying interpretation is DISPUTED in the reference finding. Different cell backgrounds and perturbations have not been shown to explain the conflict, and neither study establishes CLN3 proton-pump activity. |
| GO:0007611 learning or memory | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Retain mouse learning and memory involvement. Reason: Current donor records are supported by Cln3-deficient mouse fear-conditioning and circuit experiments. Actual 14-month-old mutant mice have impaired cued/contextual recall; this is a physiological consequence, not a direct human cognitive mechanism. |
| GO:0007611 learning or memory | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Retain mouse learning and memory involvement. Reason: Current donor records are supported by Cln3-deficient mouse fear-conditioning and circuit experiments. Actual 14-month-old mutant mice have impaired cued/contextual recall; this is a physiological consequence, not a direct human cognitive mechanism. |
| GO:0008021 synaptic vesicle | IDA PMID:10332042 Defective intracellular transport of CLN3 is the molecular b... | MODIFY | Summary: Use the supported synaptic compartment. Reason: The original abstract reports overlap with a synaptic-vesicle marker in neuronal projections. Later primary fractionation places native mouse Cln3 in synaptosomes but virtually excludes it from purified synaptic vesicles; human transgene localization is separately tested in mouse retinal neurons. Synapse preserves the supported location without asserting purified-vesicle residence. Proposed replacements: synapse |
| GO:0008021 synaptic vesicle | IDA PMID:11590129 CLN3 protein is targeted to neuronal synapses but excluded f... | MODIFY | Summary: Correct the compartment to the demonstrated synaptic location. Reason: Actual Results distinguish synaptosomal association from absence in purified mouse synaptic-vesicle fractions, with synaptophysin and preimmune controls. Human CLN3 expressed in mouse retinal neurons shows partial synaptic-marker overlap. The broader synapse compartment fits these positive observations; no universal absence claim for every human product is made. Proposed replacements: synapse Supporting Evidence: PMID:11590129 It is localized in the synaptosomes |
| GO:0008306 associative learning | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Retain the mouse associative-learning phenotype. Reason: Current Q61124 GOA carries IMP in the authenticated donor record with an upstream-or-within qualifier. This is retained as a contextual organismal phenotype; later fear-conditioning evidence corroborates the domain without converting it into direct human synaptic chemistry. |
| GO:0009992 intracellular water homeostasis | IEA GO_REF:0000107 | UNDECIDED | Summary: The exact transferred process scope remains unresolved. Reason: Actual PMID:20219947 reports whole-animal polyuria and altered concentrating responses, while intracellular osmolyte accumulation and taurine uptake/efflux remain intact. These results support systemic renal physiology but do not clearly establish the precise intracellular-water-homeostasis assertion. Preserve the historical human transfer pending resolution of that scope. |
| GO:0009992 intracellular water homeostasis | ISS GO_REF:0000024 | UNDECIDED | Summary: The exact transferred process scope remains unresolved. Reason: Actual PMID:20219947 reports whole-animal polyuria and altered concentrating responses, while intracellular osmolyte accumulation and taurine uptake/efflux remain intact. These results support systemic renal physiology but do not clearly establish the precise intracellular-water-homeostasis assertion. Preserve the historical human transfer pending resolution of that scope. |
| GO:0010506 regulation of autophagy | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Retain mouse-supported autophagy regulation. Reason: The exact current donor has an IMP record in the authenticated donor record. Retain the physiological process context; neither the donor count nor the lack of a reconstructed historical transfer establishes a propagation failure. Supporting Evidence: GO_REF:0000107 |
| GO:0010762 regulation of fibroblast migration | IMP PMID:20850431 A novel interaction of CLN3 with nonmuscle myosin-IIB and de... | KEEP AS NON CORE | Summary: Retain the measured fibroblast migration phenotype. Reason: Cln3-deficient mouse fibroblasts close scratch wounds more slowly and show altered myosin-IIB distribution; blebbistatin produces a related phenotype. This is a contextual motility role, not evidence of intrinsic CLN3 motor activity. Supporting Evidence: |
| GO:0016020 membrane | IDA PMID:10191112 Studies of membrane association of CLN3 protein. | ACCEPT | Summary: Retain integral membrane association. Reason: The original membrane experiment or conserved protein-family mapping is consistent with CLN3 membrane insertion, localization and direct channel activity. More precise endolysosomal membrane locations are independently supported. |
| GO:0016020 membrane | IEA GO_REF:0000002 | ACCEPT | Summary: Retain integral membrane association. Reason: The original membrane experiment or conserved protein-family mapping is consistent with CLN3 membrane insertion, localization and direct channel activity. More precise endolysosomal membrane locations are independently supported. |
| GO:0016192 vesicle-mediated transport | IEA GO_REF:0000117 | ACCEPT | Summary: Retain vesicle-mediated trafficking involvement. Reason: The electronic process agrees with direct CLN3 interactions with Rab7/RILP and motors plus altered late-endosomal positioning. It does not imply autonomous motor action or a proven simultaneous adaptor complex. |
| GO:0016243 regulation of autophagosome size | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Retain the mouse autophagosome-size phenotype. Reason: The current Q61124 donor contains IMP in the authenticated donor record for this exact term. Retain the contextual regulation assertion, without extending size phenotypes into an intrinsic organelle-construction activity. Supporting Evidence: GO_REF:0000107 |
| GO:0016485 protein processing | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Retain the observed protein-processing role. Reason: The inspected mouse cerebellar precursor study shows altered cathepsin-D processing despite relatively unchanged total enzymatic activity. CLN3 is not assigned the protease reaction; the original upstream physiological relationship is retained. |
| GO:0017089 glycolipid transfer activity | TAS Reactome:R-HSA-9844955 | UNDECIDED | Summary: The precise aqueous-phase glycolipid carrier mechanism is unresolved. Reason: Reactome positively models Q13286-mediated GalCer transport as an uncertain BlackBoxEvent. GO:0017089 specifically requires membrane extraction and protected hydrophobic-pocket delivery through water. Full primary lipid-overlay, distribution and rescue experiments support binding/trafficking but do not distinguish that carrier mechanism from vesicular transport; the paper presents extraction-and-carriage as a proposal. |
| GO:0030003 intracellular monoatomic cation homeostasis | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: Retain broad cation-homeostasis context. Reason: The electronic assertion is compatible with lysosomal pH and calcium phenotypes. Directly demonstrated chloride conductance does not itself establish cation permeation or replace these secondary cellular effects. |
| GO:0030162 regulation of proteolysis | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: Retain regulation of proteolysis as contextual. Reason: Protein-processing and lysosomal degradation phenotypes support the broad electronic process. The proteolytic reactions are performed by lysosomal enzymes, not assigned as intrinsic CLN3 catalysis. |
| GO:0031410 cytoplasmic vesicle | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Retain broad cytoplasmic vesicle localization. Reason: The mouse donor and direct human trafficking studies support membrane-bounded cytoplasmic vesicles. Specific endosomal and lysosomal membrane terms are more informative. |
| GO:0031901 early endosome membrane | IEA GO_REF:0000120 | KEEP AS NON CORE | Summary: Retain early-endosome membrane localization as secondary. Reason: The mapping or original localization study supports an early-endosomal pool within the CLN3 trafficking itinerary. This is not taken as the exclusive location. |
| GO:0031901 early endosome membrane | IMP PMID:23840424 Osmotic stress changes the expression and subcellular locali... | KEEP AS NON CORE | Summary: Retain early-endosome membrane localization as secondary. Reason: The mapping or original localization study supports an early-endosomal pool within the CLN3 trafficking itinerary. This is not taken as the exclusive location. Supporting Evidence: |
| GO:0031902 late endosome membrane | IEA GO_REF:0000044 | ACCEPT | Summary: Retain the late-endosome membrane compartment. Reason: The UniProt mapping or mouse donor is independently corroborated by direct human endolysosomal localization and channel assays. This is a representative site of molecular activity. |
| GO:0031902 late endosome membrane | ISS GO_REF:0000024 | ACCEPT | Summary: Retain the late-endosome membrane compartment. Reason: The UniProt mapping or mouse donor is independently corroborated by direct human endolysosomal localization and channel assays. This is a representative site of molecular activity. |
| GO:0032228 regulation of synaptic transmission, GABAergic | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Retain mouse GABAergic transmission regulation. Reason: Actual Cln3-deficient mouse circuit recordings reveal changes in inhibitory synaptic currents and short-term plasticity, with interneuron loss in selected regions. The human transferred process remains contextual and does not establish direct GABA-receptor binding or transmitter synthesis. |
| GO:0032228 regulation of synaptic transmission, GABAergic | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Retain mouse GABAergic transmission regulation. Reason: Actual Cln3-deficient mouse circuit recordings reveal changes in inhibitory synaptic currents and short-term plasticity, with interneuron loss in selected regions. The human transferred process remains contextual and does not establish direct GABA-receptor binding or transmitter synthesis. |
| GO:0035235 ionotropic glutamate receptor signaling pathway | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Retain the mouse glutamatergic signaling phenotype. Reason: Current donor IMP in the authenticated donor record has an upstream-or-within qualifier. Later circuit studies support altered excitatory transmission; this does not identify CLN3 as an ionotropic glutamate receptor. |
| GO:0035627 ceramide transport | TAS Reactome:R-HSA-9845576 | MODIFY | Summary: Specify the glycolipid transport actually modeled for CLN3. Reason: Reactome:R-HSA-9845576 is the glycosphingolipid transport pathway and includes the target GalCer event Reactome:R-HSA-9844955. CLN3 participation concerns galactosylceramide, whereas GO:0035627 names ceramide itself. Glycolipid transport preserves the positive target event without inferring transport of unsubstituted ceramide or the exact aqueous-carrier mechanism. Proposed replacements: glycolipid transport |
| GO:0035752 lysosomal lumen pH elevation | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: Retain inherited lysosomal pH elevation at the target assay scope. Reason: The PAINT assertion has target experimental grounding in the human expression/antisense study of PMID:10924275: increased CLN3 raises lysosomal pH in those conditions. Human HEK293T knockout and rescue in PMID:41558486 independently support that direction. The elevated-pH CLN3-deficient patient fibroblast result in PMID:11722572 points the other way and remains explicitly disputed at the general functional-interpretation level. Retain this inherited assertion as non-core without claiming an invariant direction across models; the historical IBD placement and alignment remain uninspected. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: PANTHER:PTN000861897 SUPPORTS TRANSFER Qualified support combines the current PAINT assertion, authentic current target/donor evidence and the source-specific functional assessment. The historical IBD placement, tree and alignment were not reconstructed. Target self-inclusion is legitimate experimental grounding; donor count is not used as a strength or failure score. |
| GO:0035752 lysosomal lumen pH elevation | IDA PMID:10924275 CLN3 protein regulates lysosomal pH and alters intracellular... | KEEP AS NON CORE | Summary: Retain the measured lysosomal pH response. Reason: The authentic abstract reports that CLN3 expression raises lysosomal pH in human embryonal kidney cells, whereas antisense inhibition acidifies lysosomal compartments; R334C lacks the wild-type effect. The later HEK293T knockout/rescue measurements in PMID:41558486 corroborate this direction. The older CLN3-deficient patient fibroblast comparison in PMID:11722572 reports the opposite loss-associated change and is retained as a distinct observation, not explained away as proven context dependence. This is a source-scoped homeostatic response, not proton pumping. |
| GO:0036359 renal potassium excretion | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Retain mouse-supported renal potassium excretion. Reason: Actual Cln3-deficient mouse whole-animal measurements show reduced potassium excretion and polyuria. This supports contextual renal physiology without establishing a potassium-selective CLN3 transporter or a direct human renal mechanism. |
| GO:0036359 renal potassium excretion | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Retain mouse-supported renal potassium excretion. Reason: Actual Cln3-deficient mouse whole-animal measurements show reduced potassium excretion and polyuria. This supports contextual renal physiology without establishing a potassium-selective CLN3 transporter or a direct human renal mechanism. |
| GO:0042987 amyloid precursor protein catabolic process | IDA PMID:10924275 CLN3 protein regulates lysosomal pH and alters intracellular... | KEEP AS NON CORE | Summary: Retain the APP-processing phenotype. Reason: The original study links CLN3 perturbation to APP processing in transfected cells. This is indirect catabolic-pathway involvement, not an APP-cleaving enzymatic activity of CLN3. Supporting Evidence: |
| GO:0042998 positive regulation of Golgi to plasma membrane protein transport | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Retain positive regulation of Golgi-to-surface trafficking. Reason: The inspected mouse endothelial study uses Cln3-deficient and rescued sister lines and finds reduced surface caveolin-1 with altered TGN distribution of syntaxin-6. This supports a performed cellular trafficking role without proving a unique direct molecular cargo-transfer step. |
| GO:0042998 positive regulation of Golgi to plasma membrane protein transport | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Retain positive regulation of Golgi-to-surface trafficking. Reason: The inspected mouse endothelial study uses Cln3-deficient and rescued sister lines and finds reduced surface caveolin-1 with altered TGN distribution of syntaxin-6. This supports a performed cellular trafficking role without proving a unique direct molecular cargo-transfer step. |
| GO:0043005 neuron projection | IDA PMID:10332042 Defective intracellular transport of CLN3 is the molecular b... | KEEP AS NON CORE | Summary: Retain neuronal projection localization. Reason: Original neuronal localization and current mouse evidence support axonal/dendritic or neuritic CLN3 pools. The broad compartment is retained as context, not equated with purified synaptic vesicles. |
| GO:0043005 neuron projection | IEA GO_REF:0000120 | KEEP AS NON CORE | Summary: Retain neuronal projection localization. Reason: Original neuronal localization and current mouse evidence support axonal/dendritic or neuritic CLN3 pools. The broad compartment is retained as context, not equated with purified synaptic vesicles. |
| GO:0043066 negative regulation of apoptotic process | IEA GO_REF:0000120 | KEEP AS NON CORE | Summary: Retain anti-apoptotic cellular context. Reason: Current mouse evidence and human neuronal-cell CLN3/calsenilin perturbations support context-dependent protection from calcium-induced death. This does not establish CLN3 as a general apoptosis inhibitor in every tissue. |
| GO:0043066 negative regulation of apoptotic process | IMP PMID:15240864 A galactosylceramide binding domain is involved in trafficki... | UNDECIDED | Summary: The exact apoptosis experiment in this source remains unverified. Reason: The authentic abstract discusses prior growth/apoptosis observations but focuses on trafficking and GalCer localization. The full original apoptosis assay was not recovered. The source assertion is preserved without inferring absence or substituting a different paper as if it were the original experiment. Supporting Evidence: |
| GO:0043066 negative regulation of apoptotic process | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Retain anti-apoptotic cellular context. Reason: Current mouse evidence and human neuronal-cell CLN3/calsenilin perturbations support context-dependent protection from calcium-induced death. This does not establish CLN3 as a general apoptosis inhibitor in every tissue. |
| GO:0043524 negative regulation of neuron apoptotic process | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Retain neuron-survival regulation at its tested scope. Reason: The current mouse transfer is compatible with the original CLN3/calsenilin study, whose abstract reports neuronal-cell protection and knockdown-rescue responses to calcium perturbation. This is not a general constitutive anti-apoptotic mechanism. |
| GO:0044754 autolysosome | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Retain autolysosomal localization as contextual. Reason: The current mouse donor carries direct localization from PMID:16714284. The available abstract supports the autophagy/lysosome context, while detailed original localization Methods were not recovered; no defining human autolysosome-specific role is asserted. Supporting Evidence: GO_REF:0000107 |
| GO:0044754 autolysosome | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Retain autolysosomal localization as contextual. Reason: The current mouse donor carries direct localization from PMID:16714284. The available abstract supports the autophagy/lysosome context, while detailed original localization Methods were not recovered; no defining human autolysosome-specific role is asserted. Supporting Evidence: GO_REF:0000024 |
| GO:0044857 plasma membrane raft organization | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Retain regulation of membrane-raft organization. Reason: Actual mouse endothelial experiments show altered membrane-domain partitioning, mobility and aggregation after Cln3 loss, with rescue context. They do not identify CLN3 as an enzyme synthesizing raft lipids. |
| GO:0044857 plasma membrane raft organization | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Retain regulation of membrane-raft organization. Reason: Actual mouse endothelial experiments show altered membrane-domain partitioning, mobility and aggregation after Cln3 loss, with rescue context. They do not identify CLN3 as an enzyme synthesizing raft lipids. |
| GO:0045121 membrane raft | IDA PMID:15240864 A galactosylceramide binding domain is involved in trafficki... | KEEP AS NON CORE | Summary: Retain the experimentally reported membrane-microdomain pool. Reason: The original source associates CLN3 with raft-enriched membranes or markers. Fractionation/colocalization supports an assay-scoped secondary location without defining a stable stoichiometric raft complex. Supporting Evidence: |
| GO:0045121 membrane raft | IEA GO_REF:0000120 | KEEP AS NON CORE | Summary: Retain the combined membrane-raft location mapping. Reason: The mouse donor has direct carbonate-fractionation and GM1/TGN colocalization evidence from transfected cells. Endogenous CLN3 was not reliably detectable in that study. Original electronic source identifiers are retained. |
| GO:0045121 membrane raft | IMP PMID:23840424 Osmotic stress changes the expression and subcellular locali... | KEEP AS NON CORE | Summary: Retain the experimentally reported membrane-microdomain pool. Reason: The original source associates CLN3 with raft-enriched membranes or markers. Fractionation/colocalization supports an assay-scoped secondary location without defining a stable stoichiometric raft complex. Supporting Evidence: |
| GO:0045202 synapse | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: Retain synaptic localization as a broader compartment. Reason: The UniProt location mapping is compatible with synaptosomal fractionation and neuronal synaptic-region staining. It does not imply purified synaptic-vesicle residence. |
| GO:0045861 negative regulation of proteolysis | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Retain the mouse negative-proteolysis context. Reason: The exact current donor carries an upstream-or-within IMP assertion in the authenticated donor record. Preserve this contextual outcome without claiming CLN3 directly inhibits protease catalysis or that all lysosomal degradation changes have this direction. Supporting Evidence: GO_REF:0000024 |
| GO:0046474 glycerophospholipid biosynthetic process | IMP PMID:17482562 A novel role of the Batten disease gene CLN3: association wi... | KEEP AS NON CORE | Summary: Retain the measured glycerophospholipid biosynthetic phenotype. Reason: Human tissue, fibroblast and LA-N5 isotope-labeling experiments link CLN3 to BMP abundance/synthesis and include expression/rescue comparisons. The full Discussion explicitly leaves primary versus secondary effects unresolved; no intrinsic phospholipid-synthetic enzyme activity is established. Supporting Evidence: |
| GO:0046836 glycolipid transport | IMP PMID:18317235 CLN3p impacts galactosylceramide transport, raft morphology,... | KEEP AS NON CORE | Summary: Retain the cellular glycolipid transport contribution. Reason: Full primary lipid-overlay, GalCer distribution and CLN3 rescue experiments support cellular trafficking. They do not distinguish a soluble lipid-carrier mechanism from membrane transport pathways. Supporting Evidence: |
| GO:0047496 vesicle transport along microtubule | IBA GO_REF:0000033 | ACCEPT | Summary: Retain inherited microtubule-associated vesicle transport. Reason: Direct human CLN3–Rab7/RILP/motor interactions and late-endosomal positioning experiments support the cellular role. Target self-inclusion grounds the PAINT assertion; the historical ancestral placement was not reconstructed. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN000104831 SUPPORTS TRANSFER Qualified support combines the current PAINT assertion, authentic current target/donor evidence and the source-specific functional assessment. The historical IBD placement, tree and alignment were not reconstructed. Target self-inclusion is legitimate experimental grounding; donor count is not used as a strength or failure score. |
| GO:0047496 vesicle transport along microtubule | IMP PMID:22261744 Neuronal ceroid lipofuscinosis protein CLN3 interacts with m... | ACCEPT | Summary: Retain the measured vesicle-positioning role. Reason: The original study combines mapped Rab7/RILP interactions, motor associations and altered late-endosomal redistribution after CLN3 knockdown. This supports involvement in microtubule-associated transport, without assigning ATP-driven movement to CLN3 itself. Supporting Evidence: |
| GO:0048172 regulation of short-term neuronal synaptic plasticity | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Retain mouse short-term synaptic plasticity regulation. Reason: Actual mouse hippocampal and cerebellar recordings show altered paired-pulse behavior, including a formally tested genotype-by-calcium/stimulus interaction in the later study. The transferred process is contextual; no direct neurotransmitter-receptor mechanism is assigned. |
| GO:0048172 regulation of short-term neuronal synaptic plasticity | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Retain mouse short-term synaptic plasticity regulation. Reason: Actual mouse hippocampal and cerebellar recordings show altered paired-pulse behavior, including a formally tested genotype-by-calcium/stimulus interaction in the later study. The transferred process is contextual; no direct neurotransmitter-receptor mechanism is assigned. |
| GO:0048306 calcium-dependent protein binding | IEA GO_REF:0000107 | UNDECIDED | Summary: The calcium-dependent binding qualifier needs the original assay conditions. Reason: Current mouse GOA links the term to PMID:17189291. Its abstract reports dissociation at increased calcium. The GO definition requires binding in the presence of calcium, not necessarily monotonic enhancement, so dissociation alone does not refute the annotation. Detailed calcium concentrations and controls were not recovered, leaving this precise transferred qualifier unresolved. Supporting Evidence: GO_REF:0000107 |
| GO:0048549 positive regulation of pinocytosis | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Retain the mouse pinocytosis-regulation phenotype. Reason: The current mouse donor carries IMP in the authenticated donor record for this exact term. Preserve the source-specific cellular effect as non-core; it does not establish CLN3 as an endocytic receptor or vesicle-coat enzyme. Supporting Evidence: GO_REF:0000107 |
| GO:0048549 positive regulation of pinocytosis | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Retain the mouse pinocytosis-regulation phenotype. Reason: The current mouse donor carries IMP in the authenticated donor record for this exact term. Preserve the source-specific cellular effect as non-core; it does not establish CLN3 as an endocytic receptor or vesicle-coat enzyme. Supporting Evidence: GO_REF:0000024 |
| GO:0050885 neuromuscular process controlling balance | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Retain the mouse balance phenotype. Reason: The current mouse donor links this term to an upstream-or-within IMP assertion. It is retained as a neurological consequence rather than a direct human motor-control mechanism. Supporting Evidence: GO_REF:0000024 |
| GO:0051480 regulation of cytosolic calcium ion concentration | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Retain cytosolic calcium regulation as contextual. Reason: The current mouse donor and original CLN3/calsenilin abstract support perturbed calcium transients in mutant-expression/knockdown systems. This is not evidence that CLN3 conducts calcium. |
| GO:0051493 regulation of cytoskeleton organization | IMP PMID:20850431 A novel interaction of CLN3 with nonmuscle myosin-IIB and de... | KEEP AS NON CORE | Summary: Retain the measured cytoskeletal organization phenotype. Reason: The full source reports altered actin/myosin-IIB distribution in Cln3-deficient fibroblasts and an interaction with myosin IIB. This supports contextual organization without showing intrinsic actin polymerization or motor catalysis. Supporting Evidence: |
| GO:0051861 glycolipid binding | IDA PMID:18317235 CLN3p impacts galactosylceramide transport, raft morphology,... | KEEP AS NON CORE | Summary: Retain directly observed glycolipid binding. Reason: Original full Results and Figure2 report wild-type CLN3 association with GalCer in cell-lysate lipid-overlay assays, with mutant controls. This positive secondary capability is not a purified-affinity or aqueous lipid-transfer measurement. Supporting Evidence: PMID:18317235 WT CLN3p binds GalCer |
| GO:0051966 regulation of synaptic transmission, glutamatergic | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Retain mouse glutamatergic transmission regulation. Reason: Actual mouse recordings show altered excitatory transmission and release dynamics, with cell-type and age dependence. The human transfer remains physiological context rather than a claim of glutamate transport or receptor activity. |
| GO:0051966 regulation of synaptic transmission, glutamatergic | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Retain mouse glutamatergic transmission regulation. Reason: Actual mouse recordings show altered excitatory transmission and release dynamics, with cell-type and age dependence. The human transfer remains physiological context rather than a claim of glutamate transport or receptor activity. |
| GO:0055037 recycling endosome | IDA PMID:15240864 A galactosylceramide binding domain is involved in trafficki... | KEEP AS NON CORE | Summary: Retain the recycling-endosomal trafficking pool. Reason: The original abstract reports Rab4/Rab11-positive recycling endosomal trafficking of wild-type CLN3 and altered mutant distribution. This is a secondary location, not evidence of a separate intrinsic recycling enzyme. Supporting Evidence: |
| GO:0055037 recycling endosome | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: Retain the mapped recycling-endosome location. Reason: The authenticated UniProt subcellular mapping agrees with original Rab4/Rab11-associated trafficking observations. |
| GO:0061024 membrane organization | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: Retain membrane organization as a broad cellular role. Reason: Mouse cerebellar and endothelial studies show changes in endomembrane morphology and membrane-domain properties. These support a broad physiological context without identifying a distinct lipid-synthetic or membrane-building catalytic function. |
| GO:0061024 membrane organization | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Retain membrane organization as a broad cellular role. Reason: Mouse cerebellar and endothelial studies show changes in endomembrane morphology and membrane-domain properties. These support a broad physiological context without identifying a distinct lipid-synthetic or membrane-building catalytic function. |
| GO:0061909 autophagosome-lysosome fusion | IEA GO_REF:0000107 | UNDECIDED | Summary: The exact transferred process scope remains unresolved. Reason: Actual PMID:26450516 documents accumulation of post-fusion autophagolysosomes and explicitly states that autophagosomes can fuse with lysosomes; terminal degradation versus fusion kinetics remains unresolved. This does not refute all participation, but the precise transferred fusion assertion is not settled by the inspected experiments. |
| GO:0061909 autophagosome-lysosome fusion | ISS GO_REF:0000024 | UNDECIDED | Summary: The exact transferred process scope remains unresolved. Reason: Actual PMID:26450516 documents accumulation of post-fusion autophagolysosomes and explicitly states that autophagosomes can fuse with lysosomes; terminal degradation versus fusion kinetics remains unresolved. This does not refute all participation, but the precise transferred fusion assertion is not settled by the inspected experiments. |
| GO:0070613 regulation of protein processing | IMP PMID:10924275 CLN3 protein regulates lysosomal pH and alters intracellular... | KEEP AS NON CORE | Summary: Retain protein-processing regulation at the original cellular scope. Reason: The original CLN3 perturbation study links lysosomal pH changes with APP/cathepsin processing. This does not assign the proteolytic reaction to CLN3. Supporting Evidence: |
| GO:0090160 Golgi to lysosome transport | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: Retain inherited Golgi-to-lysosome trafficking. Reason: The current target experimental record supports altered receptor/proenzyme traffic. The PAINT source is legitimate target grounding; historical IBD placement is uninspected. The direct Rab7-associated positioning role is represented separately. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: PANTHER:PTN000861897 SUPPORTS TRANSFER Qualified support combines the current PAINT assertion, authentic current target/donor evidence and the source-specific functional assessment. The historical IBD placement, tree and alignment were not reconstructed. Target self-inclusion is legitimate experimental grounding; donor count is not used as a strength or failure score. |
| GO:0090160 Golgi to lysosome transport | IMP PMID:18817525 Loss of the Batten disease gene CLN3 prevents exit from the ... | KEEP AS NON CORE | Summary: Retain the measured Golgi-to-lysosome trafficking phenotype. Reason: The original abstract reports reduced CI-MPR exit from the TGN and altered cathepsin maturation after CLN3 loss. These are positive cellular transport observations, not proof of a purified cargo-transfer or protease activity. Supporting Evidence: |
| GO:0090385 phagosome-lysosome fusion | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Retain phagosome–lysosome fusion involvement. Reason: Actual mouse Cln3-null MEFs transfected with human Fc-gamma receptor IIA show reduced delivery of lysosomal LAMP1 and HRP to phagosomes. The significant MEF assays support this cellular fusion/traffic context; the receptor transgene is not human CLN3, and the RPE docking comparison alone is not significant. |
| GO:0090385 phagosome-lysosome fusion | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Retain phagosome–lysosome fusion involvement. Reason: Actual mouse Cln3-null MEFs transfected with human Fc-gamma receptor IIA show reduced delivery of lysosomal LAMP1 and HRP to phagosomes. The significant MEF assays support this cellular fusion/traffic context; the receptor transgene is not human CLN3, and the RPE docking comparison alone is not significant. |
| GO:0097352 autophagosome maturation | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Retain mouse autophagosome maturation involvement. Reason: The current mouse donor carries an upstream-or-within IMP assertion from PMID:16714284. Its genuine abstract supports impaired autophagic clearance; full original Methods were not recovered. This contextual process is not promoted to an autonomous maturation activity. Supporting Evidence: GO_REF:0000024 |
| GO:0106049 regulation of cellular response to osmotic stress | IMP PMID:23840424 Osmotic stress changes the expression and subcellular locali... | UNDECIDED | Summary: Keep the proposed regulatory role unresolved. Reason: The inspected Methods and Results measure increased CLN3 expression and redistribution after hyperosmotic treatment in human cells and BHK cells expressing human CLN3. The Discussion proposes an adaptive role, but the study does not establish the work CLN3 performs in adaptation or regulation of the response. These positive induction and localization observations therefore do not settle the original regulatory assertion or justify a replacement process annotation. Supporting Evidence: |
| GO:0120146 sulfatide binding | IDA PMID:18317235 CLN3p impacts galactosylceramide transport, raft morphology,... | KEEP AS NON CORE | Summary: Retain the actual sulfatide-binding result. Reason: Original full Results and Figure2 explicitly include wild-type CLN3 in the sulfatide lipid-overlay assay; mutant CLN3 lacks the observed signal. The abstract emphasis on other NCL proteins does not negate this positive target result. The assay uses lysates, not homogeneous purified CLN3. Supporting Evidence: |
| GO:1900079 regulation of arginine biosynthetic process | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Retain the mouse arginine-biosynthesis regulatory context. Reason: The current mouse donor carries IMP in the authenticated donor record for this term. Preserve the existing metabolic phenotype without assigning arginine-synthetic enzyme activity to CLN3 or confusing it with lysosomal arginine uptake. Supporting Evidence: GO_REF:0000107 |
| GO:1900079 regulation of arginine biosynthetic process | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Retain the mouse arginine-biosynthesis regulatory context. Reason: The current mouse donor carries IMP in the authenticated donor record for this term. Preserve the existing metabolic phenotype without assigning arginine-synthetic enzyme activity to CLN3 or confusing it with lysosomal arginine uptake. Supporting Evidence: GO_REF:0000024 |
| GO:1901096 regulation of autophagosome maturation | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Retain regulation of autophagosome maturation. Reason: Actual mouse experiments show accumulation of post-fusion autophagolysosomes and impaired terminal maturation/clearance. This supports contextual autophagic regulation without proving failure of the initial fusion step or intrinsic degradative catalysis. |
| GO:1901096 regulation of autophagosome maturation | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Retain regulation of autophagosome maturation. Reason: Actual mouse experiments show accumulation of post-fusion autophagolysosomes and impaired terminal maturation/clearance. This supports contextual autophagic regulation without proving failure of the initial fusion step or intrinsic degradative catalysis. |
| GO:1903076 regulation of protein localization to plasma membrane | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Retain mouse regulation of protein surface localization. Reason: The exact current donor contains IMP in the authenticated donor record. Independently, endothelial Cln3 loss/rescue alters caveolin surface delivery. This supports contextual trafficking regulation without specifying that all surface cargoes use the same direct CLN3 interaction. |
| GO:1903076 regulation of protein localization to plasma membrane | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Retain mouse regulation of protein surface localization. Reason: The exact current donor contains IMP in the authenticated donor record. Independently, endothelial Cln3 loss/rescue alters caveolin surface delivery. This supports contextual trafficking regulation without specifying that all surface cargoes use the same direct CLN3 interaction. |
| GO:1903826 L-arginine transmembrane transport | IDA PMID:16251196 Defective lysosomal arginine transport in juvenile Batten di... | KEEP AS NON CORE | Summary: Retain the measured lysosomal arginine-transport contribution. Reason: The full primary source reports defective uptake in patient fibroblast lysosomal fractions and human CLN3 re-expression rescue, with organelle-fraction and antibody controls. The discussion allows an interacting transporter or trafficking/regulatory role and does not establish autonomous CLN3 arginine permeation. Supporting Evidence: |
| GO:1905146 lysosomal protein catabolic process | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Retain lysosomal protein catabolism involvement. Reason: Current mouse IMP records and independent CLN3-deficient-cell degradation assays support a lysosomal catabolic phenotype. CLN3 supplies a membrane/channel and trafficking contribution rather than the peptide-cleaving reaction. |
| GO:1905146 lysosomal protein catabolic process | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Retain lysosomal protein catabolism involvement. Reason: Current mouse IMP records and independent CLN3-deficient-cell degradation assays support a lysosomal catabolic phenotype. CLN3 supplies a membrane/channel and trafficking contribution rather than the peptide-cleaving reaction. |
| GO:1905162 regulation of phagosome maturation | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Retain regulation of phagosome maturation. Reason: Actual mouse MEF phagosome assays show impaired lysosomal-marker and luminal-tracer delivery after Cln3 loss. These support contextual maturation regulation, without identifying CLN3 as an autonomous fusogen or assigning the effect to every human product. |
| GO:1905162 regulation of phagosome maturation | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Retain regulation of phagosome maturation. Reason: Actual mouse MEF phagosome assays show impaired lysosomal-marker and luminal-tracer delivery after Cln3 loss. These support contextual maturation regulation, without identifying CLN3 as an autonomous fusogen or assigning the effect to every human product. |
| GO:1905244 regulation of modification of synaptic structure | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Retain mouse synaptic-structure regulation. Reason: Actual cerebellar ultrastructure shows fewer presynaptic vesicles near active zones in Cln3-deficient mice, with preserved vesicle diameter and important circuit/model limits. This supports the contextual process without showing direct human synapse assembly. |
| GO:1905244 regulation of modification of synaptic structure | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Retain mouse synaptic-structure regulation. Reason: Actual cerebellar ultrastructure shows fewer presynaptic vesicles near active zones in Cln3-deficient mice, with preserved vesicle diameter and important circuit/model limits. This supports the contextual process without showing direct human synapse assembly. |
| GO:2001288 positive regulation of caveolin-mediated endocytosis | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Retain positive regulation of caveolar endocytosis. Reason: The inspected mouse endothelial loss/rescue study measures caveolin distribution and uptake defects with membrane-domain changes. This is a cellular regulatory role, not intrinsic caveola formation or proof that CLN3 is a caveolin. |
| GO:2001288 positive regulation of caveolin-mediated endocytosis | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Retain positive regulation of caveolar endocytosis. Reason: The inspected mouse endothelial loss/rescue study measures caveolin distribution and uptake defects with membrane-domain changes. This is a cellular regulatory role, not intrinsic caveola formation or proof that CLN3 is a caveolin. |
| GO:0005254 chloride channel activity | IDA PMID:41558486 CLN3 mediates chloride efflux from lysosomes. | NEW | Summary: Add directly demonstrated chloride channel activity. Reason: Human CLN3 expression produces endolysosomal chloride conductance, and plasma-membrane retargeting plus selectivity-altering mutants support a channel contribution beyond knockout necessity. The inspected pH series is mouse Neuro-2a, while rectification alone does not establish voltage gating. No narrower gating subtype or activity of every alternative product is asserted. All thirteen current chloride-channel subtype definitions and typed ancestry were checked against the seed without overlap. Supporting Evidence: PMID:41558486 CLN3 mediates an endolysosomal Cl− conductance |
| GO:1902476 chloride transmembrane transport | IDA PMID:41558486 CLN3 mediates chloride efflux from lysosomes. | NEW | Summary: CLN3 directly performs chloride permeation across the tested membranes. Reason: Human CLN3 expression produces endolysosomal chloride currents that depend on chloride substitution; retargeted CLN3 also produces plasma-membrane currents, and pore-region mutations alter the measured channel properties. CLN3 therefore performs the membrane-crossing step, rather than merely being necessary for lysosomal physiology. Official typed process coverage finds no ancestor or descendant among the existing assertions or replacements. Same-role chloride channels CLCN1 and CFTR carry experimental annotations to this process, while PACC1 carries a function-derived annotation. The current GO-CAM index has no target entry, which is not used as evidence of a gap. This assertion is limited to the tested human constructs; it does not generalize all seven products or assert a universal gating response. Supporting Evidence: |
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Download this section (compressed HTML)Q: How does CLN3 chloride conductance relate mechanistically to glycerophosphodiester clearance and lipid distribution?
Suggested experts: Lysosomal electrophysiology and lipid-transport specialists
Q: Do the alternative CLN3 products retain the membrane topology, chloride conductance and Rab7-binding regions required for the measured canonical functions?
Suggested experts: CLN3 isoform and membrane-protein specialists
Q: Does CLN3 organize simultaneous Rab7/RILP/motor contacts, or do the measured interactions occur in separate trafficking states?
Suggested experts: Endolysosomal trafficking specialists
Experiment: Compare matched-expression, correctly localized pore-selectivity mutants with wild-type CLN3 in lysosomal electrophysiology and isotope-traced metabolite-clearance assays; distinguish changes in channel function from expression, pH and organelle integrity.
Hypothesis: Chloride conductance and glycerophosphodiester clearance can be separated by selective CLN3 variants.
Type: Functional separation and rescue
Experiment: Test full-length separation-of-function substitutions that disrupt the fragment-mapped Rab7 interface while preserving localization and chloride conductance. Measure native partner association and directional late-endosomal transport; do not infer GEF/GAP activity from FRAP alone.
Hypothesis: The mapped Rab7-binding region contributes to organelle positioning independently of chloride permeation.
Type: Interaction mapping and live-cell transport
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