CLN3 Gene

Name	ceroid-lipofuscinosis, neuronal 3
Description	This gene encodes a protein that is involved in lysosomal function. Mutations in this, as well as other neuronal ceroid-lipofuscinosis (CLN) genes, cause neurodegenerative diseases commonly known as Batten disease or collectively known as neuronal ceroid lipofuscinoses (NCLs). Many alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Jul 2008]
Summary	{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n CLN3 is a highly conserved multipass transmembrane protein that predominantly localizes to the lysosomal and endosomal compartments and is essential for maintaining proper lysosomal function and intracellular membrane trafficking."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": " Studies in various models have shown that CLN3 regulates lysosomal pH and maturation and facilitates lysosomal enzyme delivery by modulating the trafficking of membrane proteins. In particular, CLN3 plays a role in the transport of basic amino acids such as arginine into lysosomes, ensuring appropriate lysosomal content and homeostasis."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n The protein contains distinct lysosomal targeting signals – notably, a dileucine motif in a cytosolic loop and an unconventional motif in its C-terminal tail – that are critical for its proper sorting to lysosomes and, in neuronal cells, also to recycling endosomes."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": " Disruption of these signals results in aberrant trafficking, as CLN3 mislocalization compromises endocytic pathways and the function of membrane‐associated processes. Moreover, CLN3 has been shown to interact with several trafficking regulators including the microtubule‐binding protein Hook1 and Rab GTPases (Rab7, Rab9, and Rab11), thereby linking it to receptor-mediated endocytosis and microdomain transport."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n In human disease, mutations in CLN3 are the primary cause of juvenile neuronal ceroid lipofuscinosis (Batten disease), a neurodegenerative lysosomal storage disorder. Loss or alteration of CLN3 function leads to the accumulation of undigested storage material (including mitochondrial ATPase subunit c), defective autophagic vacuolar maturation, and abnormal trafficking, which together contribute to neuronal degeneration in key regions such as the retina, cortex, cerebellum, and thalamus."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "9", "end_ref": "12"}]}, {"type": "t", "text": " Furthermore, even residual mutant CLN3 protein appears to exert partial function—as demonstrated by studies showing that incomplete loss of CLN3 activity may modulate lysosomal size, autophagic flux, and cell survival."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "13"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n Together, these findings indicate that CLN3 is a multifunctional protein critical for proper lysosomal homeostasis, endosomal membrane trafficking, and the regulation of intracellular transport processes. Disruption of these functions leads to the lysosomal and neurodegenerative abnormalities observed in Batten disease, establishing CLN3 as a key regulator of neuronal cell viability.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Yi Cao, Janice A Espinola, Elisa Fossale, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Autophagy is disrupted in a knock-in mouse model of juvenile neuronal ceroid lipofuscinosis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2006)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M602180200"}], "href": "https://doi.org/10.1074/jbc.M602180200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16714284"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16714284"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Seasson N Phillips, Jared W Benedict, Jill M Weimer, et al. "}, {"type": "b", "children": [{"type": "t", "text": "CLN3, the protein associated with batten disease: structure, function and localization."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Neurosci Res (2005)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/jnr.20367"}], "href": "https://doi.org/10.1002/jnr.20367"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15657902"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15657902"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Yoojin Kim, Denia Ramirez-Montealegre, David A Pearce "}, {"type": "b", "children": [{"type": "t", "text": "A role in vacuolar arginine transport for yeast Btn1p and for human CLN3, the protein defective in Batten disease."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Proc Natl Acad Sci U S A (2003)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1073/pnas.2136651100"}], "href": "https://doi.org/10.1073/pnas.2136651100"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "14660799"}], "href": "https://pubmed.ncbi.nlm.nih.gov/14660799"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Denia Ramirez-Montealegre, David A Pearce "}, {"type": "b", "children": [{"type": "t", "text": "Defective lysosomal arginine transport in juvenile Batten disease."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Hum Mol Genet (2005)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1093/hmg/ddi406"}], "href": "https://doi.org/10.1093/hmg/ddi406"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16251196"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16251196"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Aija Kyttälä, Gudrun Ihrke, Jouni Vesa, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Two motifs target Batten disease protein CLN3 to lysosomes in transfected nonneuronal and neuronal cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Biol Cell (2004)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1091/mbc.e03-02-0120"}], "href": "https://doi.org/10.1091/mbc.e03-02-0120"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "14699076"}], "href": "https://pubmed.ncbi.nlm.nih.gov/14699076"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Aija Kyttälä, Kristiina Yliannala, Peter Schu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "AP-1 and AP-3 facilitate lysosomal targeting of Batten disease protein CLN3 via its dileucine motif."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2005)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M411862200"}], "href": "https://doi.org/10.1074/jbc.M411862200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15598649"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15598649"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Kaisu Luiro, Kristiina Yliannala, Laura Ahtiainen, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Interconnections of CLN3, Hook1 and Rab proteins link Batten disease to defects in the endocytic pathway."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Hum Mol Genet (2004)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1093/hmg/ddh321"}], "href": "https://doi.org/10.1093/hmg/ddh321"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15471887"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15471887"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Luis Tecedor, Colleen S Stein, Mark L Schultz, et al. "}, {"type": "b", "children": [{"type": "t", "text": "CLN3 loss disturbs membrane microdomain properties and protein transport in brain endothelial cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Neurosci (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1523/JNEUROSCI.0498-13.2013"}], "href": "https://doi.org/10.1523/JNEUROSCI.0498-13.2013"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24227717"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24227717"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "Susan L Cotman, Vladimir Vrbanac, Lori-Anne Lebel, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Cln3(Deltaex7/8) knock-in mice with the common JNCL mutation exhibit progressive neurologic disease that begins before birth."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Hum Mol Genet (2002)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1093/hmg/11.22.2709"}], "href": "https://doi.org/10.1093/hmg/11.22.2709"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12374761"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12374761"}]}, {"type": "r", "ref": 10, "children": [{"type": "t", "text": "Charlie C Pontikis, Claire V Cella, Nisha Parihar, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Late onset neurodegeneration in the Cln3-/- mouse model of juvenile neuronal ceroid lipofuscinosis is preceded by low level glial activation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Brain Res (2004)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.brainres.2004.07.030"}], "href": "https://doi.org/10.1016/j.brainres.2004.07.030"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15374749"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15374749"}]}, {"type": "r", "ref": 11, "children": [{"type": "t", "text": "Cristy A Ku, Sarah Hull, Gavin Arno, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Detailed Clinical Phenotype and Molecular Genetic Findings in CLN3-Associated Isolated Retinal Degeneration."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "JAMA Ophthalmol (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1001/jamaophthalmol.2017.1401"}], "href": "https://doi.org/10.1001/jamaophthalmol.2017.1401"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "28542676"}], "href": "https://pubmed.ncbi.nlm.nih.gov/28542676"}]}, {"type": "r", "ref": 12, "children": [{"type": "t", "text": "Jill M Weimer, Jared W Benedict, Amanda L Getty, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Cerebellar defects in a mouse model of juvenile neuronal ceroid lipofuscinosis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Brain Res (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.brainres.2009.02.009"}], "href": "https://doi.org/10.1016/j.brainres.2009.02.009"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19230832"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19230832"}]}, {"type": "r", "ref": 13, "children": [{"type": "t", "text": "Dixie-Ann N W Persaud-Sawin, Antonius VanDongen, Rose-Mary N Boustany "}, {"type": "b", "children": [{"type": "t", "text": "Motifs within the CLN3 protein: modulation of cell growth rates and apoptosis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Hum Mol Genet (2002)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1093/hmg/11.18.2129"}], "href": "https://doi.org/10.1093/hmg/11.18.2129"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12189165"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12189165"}]}, {"type": "r", "ref": 14, "children": [{"type": "t", "text": "Charlie C Pontikis, Susan L Cotman, Marcy E MacDonald, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Thalamocortical neuron loss and localized astrocytosis in the Cln3Deltaex7/8 knock-in mouse model of Batten disease."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Neurobiol Dis (2005)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.nbd.2005.05.018"}], "href": "https://doi.org/10.1016/j.nbd.2005.05.018"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16006136"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16006136"}]}]}]}
Synonyms	BTS, JNCL
Proteins	CLN3_HUMAN
NCBI Gene ID	1201
API
Download Associations
Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

CLN3 has 7,267 functional associations with biological entities spanning 8 categories (molecular profile, organism, disease, phenotype or trait, chemical, functional term, phrase or reference, structural feature, cell line, cell type or tissue, gene, protein or microRNA) extracted from 117 datasets.

Click the + buttons to view associations for CLN3 from the datasets below.

If available, associations are ranked by standardized value

Harmonizome 3.0

CLN3 Gene

Functional Associations

Please acknowledge the Harmonizome in your publications by citing the following reference(s):

	Dataset	Summary
	Allen Brain Atlas Adult Human Brain Tissue Gene Expression Profiles	tissues with high or low expression of CLN3 gene relative to other tissues from the Allen Brain Atlas Adult Human Brain Tissue Gene Expression Profiles dataset.
	Allen Brain Atlas Adult Mouse Brain Tissue Gene Expression Profiles	tissues with high or low expression of CLN3 gene relative to other tissues from the Allen Brain Atlas Adult Mouse Brain Tissue Gene Expression Profiles dataset.
	Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by RNA-seq	tissue samples with high or low expression of CLN3 gene relative to other tissue samples from the Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by RNA-seq dataset.
	Allen Brain Atlas Prenatal Human Brain Tissue Gene Expression Profiles	tissues with high or low expression of CLN3 gene relative to other tissues from the Allen Brain Atlas Prenatal Human Brain Tissue Gene Expression Profiles dataset.
	BioGPS Cell Line Gene Expression Profiles	cell lines with high or low expression of CLN3 gene relative to other cell lines from the BioGPS Cell Line Gene Expression Profiles dataset.
	BioGPS Human Cell Type and Tissue Gene Expression Profiles	cell types and tissues with high or low expression of CLN3 gene relative to other cell types and tissues from the BioGPS Human Cell Type and Tissue Gene Expression Profiles dataset.
	BioGPS Mouse Cell Type and Tissue Gene Expression Profiles	cell types and tissues with high or low expression of CLN3 gene relative to other cell types and tissues from the BioGPS Mouse Cell Type and Tissue Gene Expression Profiles dataset.
	CCLE Cell Line Gene CNV Profiles	cell lines with high or low copy number of CLN3 gene relative to other cell lines from the CCLE Cell Line Gene CNV Profiles dataset.
	CCLE Cell Line Gene Expression Profiles	cell lines with high or low expression of CLN3 gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
	CCLE Cell Line Proteomics	Cell lines associated with CLN3 protein from the CCLE Cell Line Proteomics dataset.
	CellMarker Gene-Cell Type Associations	cell types associated with CLN3 gene from the CellMarker Gene-Cell Type Associations dataset.
	ChEA Transcription Factor Binding Site Profiles	transcription factor binding site profiles with transcription factor binding evidence at the promoter of CLN3 gene from the CHEA Transcription Factor Binding Site Profiles dataset.
	ChEA Transcription Factor Targets	transcription factors binding the promoter of CLN3 gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets dataset.
	ChEA Transcription Factor Targets 2022	transcription factors binding the promoter of CLN3 gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets 2022 dataset.
	ClinVar Gene-Phenotype Associations	phenotypes associated with CLN3 gene from the curated ClinVar Gene-Phenotype Associations dataset.
	CMAP Signatures of Differentially Expressed Genes for Small Molecules	small molecule perturbations changing expression of CLN3 gene from the CMAP Signatures of Differentially Expressed Genes for Small Molecules dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores	cellular components containing CLN3 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores 2025	cellular components containing CLN3 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores 2025 dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores	cellular components co-occuring with CLN3 protein in abstracts of biomedical publications from the COMPARTMENTS Text-mining Protein Localization Evidence Scores dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025	cellular components co-occuring with CLN3 protein in abstracts of biomedical publications from the COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025 dataset.
	COSMIC Cell Line Gene CNV Profiles	cell lines with high or low copy number of CLN3 gene relative to other cell lines from the COSMIC Cell Line Gene CNV Profiles dataset.
	COSMIC Cell Line Gene Mutation Profiles	cell lines with CLN3 gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
	CTD Gene-Chemical Interactions	chemicals interacting with CLN3 gene/protein from the curated CTD Gene-Chemical Interactions dataset.
	CTD Gene-Disease Associations	diseases associated with CLN3 gene/protein from the curated CTD Gene-Disease Associations dataset.
	DeepCoverMOA Drug Mechanisms of Action	small molecule perturbations with high or low expression of CLN3 protein relative to other small molecule perturbations from the DeepCoverMOA Drug Mechanisms of Action dataset.
	DepMap CRISPR Gene Dependency	cell lines with fitness changed by CLN3 gene knockdown relative to other cell lines from the DepMap CRISPR Gene Dependency dataset.
	DISEASES Curated Gene-Disease Association Evidence Scores	diseases involving CLN3 gene from the DISEASES Curated Gene-Disease Assocation Evidence Scores dataset.
	DISEASES Curated Gene-Disease Association Evidence Scores 2025	diseases involving CLN3 gene from the DISEASES Curated Gene-Disease Association Evidence Scores 2025 dataset.
	DISEASES Experimental Gene-Disease Association Evidence Scores	diseases associated with CLN3 gene in GWAS datasets from the DISEASES Experimental Gene-Disease Assocation Evidence Scores dataset.
	DISEASES Experimental Gene-Disease Association Evidence Scores 2025	diseases associated with CLN3 gene in GWAS datasets from the DISEASES Experimental Gene-Disease Assocation Evidence Scores 2025 dataset.
	DISEASES Text-mining Gene-Disease Association Evidence Scores	diseases co-occuring with CLN3 gene in abstracts of biomedical publications from the DISEASES Text-mining Gene-Disease Assocation Evidence Scores dataset.
	DISEASES Text-mining Gene-Disease Association Evidence Scores 2025	diseases co-occuring with CLN3 gene in abstracts of biomedical publications from the DISEASES Text-mining Gene-Disease Assocation Evidence Scores 2025 dataset.
	DisGeNET Gene-Disease Associations	diseases associated with CLN3 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.
	DisGeNET Gene-Phenotype Associations	phenotypes associated with CLN3 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Phenoptype Associations dataset.
	ENCODE Histone Modification Site Profiles	histone modification site profiles with high histone modification abundance at CLN3 gene from the ENCODE Histone Modification Site Profiles dataset.
	ENCODE Transcription Factor Binding Site Profiles	transcription factor binding site profiles with transcription factor binding evidence at the promoter of CLN3 gene from the ENCODE Transcription Factor Binding Site Profiles dataset.
	ENCODE Transcription Factor Targets	transcription factors binding the promoter of CLN3 gene in ChIP-seq datasets from the ENCODE Transcription Factor Targets dataset.
	ESCAPE Omics Signatures of Genes and Proteins for Stem Cells	PubMedIDs of publications reporting gene signatures containing CLN3 from the ESCAPE Omics Signatures of Genes and Proteins for Stem Cells dataset.
	GAD Gene-Disease Associations	diseases associated with CLN3 gene in GWAS and other genetic association datasets from the GAD Gene-Disease Associations dataset.
	GAD High Level Gene-Disease Associations	diseases associated with CLN3 gene in GWAS and other genetic association datasets from the GAD High Level Gene-Disease Associations dataset.