CLN8 Gene

Name	ceroid-lipofuscinosis, neuronal 8 (epilepsy, progressive with mental retardation)
Description	This gene encodes a transmembrane protein belonging to a family of proteins containing TLC domains, which are postulated to function in lipid synthesis, transport, or sensing. The protein localizes to the endoplasmic reticulum (ER), and may recycle between the ER and ER-Golgi intermediate compartment. Mutations in this gene are associated with a disorder characterized by progressive epilepsy with cognitive disabilities (EPMR), which is a subtype of neuronal ceroid lipofuscinoses (NCL). Patients with mutations in this gene have altered levels of sphingolipid and phospholipids in the brain. [provided by RefSeq, Jul 2017]
Summary	{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n CLN8 is a novel transmembrane protein that plays a central role in maintaining lysosomal homeostasis and cellular lipid balance. Although primarily localized to the endoplasmic reticulum (ER), CLN8 cycles between the ER and the ER–Golgi intermediate compartment (ERGIC) to regulate the trafficking of lysosomal enzymes. In particular, CLN8 forms a functional complex with CLN6—referred to as the EGRESS complex—that recruits lysosomal proteins at the ER to promote their efficient export and subsequent delivery to the Golgi, thereby enabling proper lysosome biogenesis and function."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n In addition to its role in lysosomal enzyme trafficking, CLN8 has been implicated in the regulation of lipid metabolism. Studies have shown that CLN8 directly or indirectly modulates ceramide levels and signaling pathways by interacting with key regulators such as the serine/threonine phosphatase PP2A and its inhibitor I2PP2A. These interactions suggest that CLN8 may function as a sphingolipid sensor and contribute to glycosphingolipid trafficking, a process that appears to be protective against severe phenotypes in disorders such as Gaucher disease."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Furthermore, investigations in neuronal cell models indicate that CLN8 is expressed in a polarized fashion and is present in distinct membranous compartments in neurons, which underscores its potential role in regulating cell proliferation and protecting against cell death during neuronal differentiation."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n In summary, CLN8 functions at the intersection of lysosomal biogenesis and lipid metabolism. Its ability to facilitate the ER-to-Golgi transport of lysosomal enzymes and to modulate ceramide-dependent signaling pathways is essential for maintaining cellular homeostasis. Defects in CLN8 are therefore linked to neurodegenerative lysosomal storage disorders, highlighting its critical function in neuronal survival.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Sara E Mole, Gregoire Michaux, Sandra Codlin, et al. "}, {"type": "b", "children": [{"type": "t", "text": "CLN6, which is associated with a lysosomal storage disease, is an endoplasmic reticulum protein."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Exp Cell Res (2004)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.yexcr.2004.04.042"}], "href": "https://doi.org/10.1016/j.yexcr.2004.04.042"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15265688"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15265688"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Lakshya Bajaj, Jaiprakash Sharma, Alberto di Ronza, et al. "}, {"type": "b", "children": [{"type": "t", "text": "A CLN6-CLN8 complex recruits lysosomal enzymes at the ER for Golgi transfer."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Clin Invest (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1172/JCI130955"}], "href": "https://doi.org/10.1172/JCI130955"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "32597833"}], "href": "https://pubmed.ncbi.nlm.nih.gov/32597833"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Babita Adhikari, Bhagya De Silva, Joshua A Molina, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Neuronal ceroid lipofuscinosis related ER membrane protein CLN8 regulates PP2A activity and ceramide levels."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochim Biophys Acta Mol Basis Dis (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.bbadis.2018.11.011"}], "href": "https://doi.org/10.1016/j.bbadis.2018.11.011"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "30453012"}], "href": "https://pubmed.ncbi.nlm.nih.gov/30453012"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Clarence K Zhang, Philip B Stein, Jun Liu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Genome-wide association study of N370S homozygous Gaucher disease reveals the candidacy of CLN8 gene as a genetic modifier contributing to extreme phenotypic variation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Am J Hematol (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/ajh.23118"}], "href": "https://doi.org/10.1002/ajh.23118"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22388998"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22388998"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Liina Lonka, Tarja Salonen, Eija Siintola, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Localization of wild-type and mutant neuronal ceroid lipofuscinosis CLN8 proteins in non-neuronal and neuronal cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Neurosci Res (2004)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/jnr.20133"}], "href": "https://doi.org/10.1002/jnr.20133"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15160397"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15160397"}]}]}]}
Synonyms	EPMR, C8ORF61
Proteins	CLN8_HUMAN
NCBI Gene ID	2055
API
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Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

CLN8 has 6,197 functional associations with biological entities spanning 9 categories (molecular profile, organism, chemical, disease, phenotype or trait, functional term, phrase or reference, structural feature, cell line, cell type or tissue, gene, protein or microRNA, sequence feature) extracted from 114 datasets.

Click the + buttons to view associations for CLN8 from the datasets below.

If available, associations are ranked by standardized value

Harmonizome 3.0

CLN8 Gene

Functional Associations

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

	Dataset	Summary
	Achilles Cell Line Gene Essentiality Profiles	cell lines with fitness changed by CLN8 gene knockdown relative to other cell lines from the Achilles Cell Line Gene Essentiality Profiles dataset.
	Allen Brain Atlas Adult Human Brain Tissue Gene Expression Profiles	tissues with high or low expression of CLN8 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 CLN8 gene relative to other tissues from the Allen Brain Atlas Adult Mouse Brain Tissue Gene Expression Profiles dataset.
	Allen Brain Atlas Aging Dementia and Traumatic Brain Injury Tissue Sample Gene Expression Profiles	tissue samples with high or low expression of CLN8 gene relative to other tissue samples from the Allen Brain Atlas Aging Dementia and Traumatic Brain Injury Tissue Sample Gene Expression Profiles dataset.
	Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by Microarray	tissue samples with high or low expression of CLN8 gene relative to other tissue samples from the Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by Microarray dataset.
	Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by RNA-seq	tissue samples with high or low expression of CLN8 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 CLN8 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 CLN8 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 CLN8 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 CLN8 gene relative to other cell types and tissues from the BioGPS Mouse Cell Type and Tissue Gene Expression Profiles dataset.
	Carcinogenome Chemical Perturbation Carcinogenicity Signatures	small molecule perturbations changing expression of CLN8 gene from the Carcinogenome Chemical Perturbation Carcinogenicity Signatures dataset.
	CCLE Cell Line Gene CNV Profiles	cell lines with high or low copy number of CLN8 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 CLN8 gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
	CCLE Cell Line Proteomics	Cell lines associated with CLN8 protein from the CCLE Cell Line Proteomics dataset.
	CellMarker Gene-Cell Type Associations	cell types associated with CLN8 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 CLN8 gene from the CHEA Transcription Factor Binding Site Profiles dataset.
	ChEA Transcription Factor Targets	transcription factors binding the promoter of CLN8 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 CLN8 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 CLN8 gene from the curated ClinVar Gene-Phenotype Associations dataset.
	ClinVar Gene-Phenotype Associations 2025	phenotypes associated with CLN8 gene from the curated ClinVar Gene-Phenotype Associations 2025 dataset.
	CMAP Signatures of Differentially Expressed Genes for Small Molecules	small molecule perturbations changing expression of CLN8 gene from the CMAP Signatures of Differentially Expressed Genes for Small Molecules dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores	cellular components containing CLN8 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores 2025	cellular components containing CLN8 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores 2025 dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores	cellular components co-occuring with CLN8 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 CLN8 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 CLN8 gene relative to other cell lines from the COSMIC Cell Line Gene CNV Profiles dataset.
	COSMIC Cell Line Gene Mutation Profiles	cell lines with CLN8 gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
	CTD Gene-Chemical Interactions	chemicals interacting with CLN8 gene/protein from the curated CTD Gene-Chemical Interactions dataset.
	CTD Gene-Disease Associations	diseases associated with CLN8 gene/protein from the curated CTD Gene-Disease Associations dataset.
	DeepCoverMOA Drug Mechanisms of Action	small molecule perturbations with high or low expression of CLN8 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 CLN8 gene knockdown relative to other cell lines from the DepMap CRISPR Gene Dependency dataset.
	DISEASES Curated Gene-Disease Association Evidence Scores	diseases involving CLN8 gene from the DISEASES Curated Gene-Disease Assocation Evidence Scores dataset.
	DISEASES Curated Gene-Disease Association Evidence Scores 2025	diseases involving CLN8 gene from the DISEASES Curated Gene-Disease Association Evidence Scores 2025 dataset.
	DISEASES Experimental Gene-Disease Association Evidence Scores	diseases associated with CLN8 gene in GWAS datasets from the DISEASES Experimental Gene-Disease Assocation Evidence Scores dataset.
	DISEASES Text-mining Gene-Disease Association Evidence Scores	diseases co-occuring with CLN8 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 CLN8 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 CLN8 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.
	DisGeNET Gene-Phenotype Associations	phenotypes associated with CLN8 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 CLN8 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 CLN8 gene from the ENCODE Transcription Factor Binding Site Profiles dataset.