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GeneE
10 sources retrieved Β· Most recent: April 2026 Β· Index updated 14 days ago
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CLN8
CLN8 transmembrane ER and ERGIC protein
Chromosome 8 Β· 8p23.3
NCBI Gene: 2055Ensembl: ENSG00000182372.11HGNC: HGNC:2079UniProt: Q9UBY8
39PubMed Papers
22Diseases
0Drugs
89Pathogenic Variants
RESEARCH IMPACT
Variant-Rich
CLINICAL
OMIM Disease Gene
DATA QUALITY
βœ“ Experimental GO Evidenceβœ“ Swiss-Prot Reviewed
ceramide metabolic processceramide bindingprotein bindingendoplasmic reticulumCLN8 diseaseneuronal ceroid lipofuscinosis 8neuronal ceroid lipofuscinosis 8 northern epilepsy variantProgressive epilepsy - intellectual disability, Finnish type
✦AI Summary

CLN8 is a transmembrane endoplasmic reticulum and ERGIC protein that functions as a lysophosphatidylglycerol acyltransferase catalyzing essential steps in bis(monoacylglycero)phosphate biosynthesis, a phospholipid critical for lysosome function 1. CLN8 belongs to the TRAM-LAG1-CLN8 domain protein family involved in phospholipid remodeling and membrane homeostasis 1. The protein is developmentally regulated in the CNS, with highest expression in cortex and hippocampus, suggesting roles in neuronal maturation and survival 2. CLN8 is involved in trafficking of lysosomal enzymes and regulation of cellular phospholipid composition 3. Biallelic mutations in CLN8 cause neuronal ceroid lipofuscinosis (Batten disease), the most common childhood neurodegenerative disease, characterized by progressive seizures, cognitive decline, motor dysfunction, visual loss, and intraneuronal accumulation of autofluorescent lipid-protein deposits 45. Clinical phenotype varies from mild progressive epilepsy with mental retardation (Northern epilepsy/EPMR) to severe late infantile variants 46. A single neonatal intracerebroventricular AAV9 gene therapy delivery in CLN8-disease mice restored lifespan from 10 months to beyond 24 months, reducing pathological hallmarks and behavioral abnormalities 3, supporting therapeutic development for this currently incurable disorder.

Sources cited
1
CLN8 is a lysophosphatidylglycerol acyltransferase regulating phospholipid composition and bis(monoacylglycero)phosphate biosynthesis critical for lysosome function
PMID: 39970228
2
CLN8 is a transmembrane ER protein involved in trafficking of lysosomal enzymes; biallelic mutations cause Batten disease with seizures, cognitive/motor decline, and premature death; AAV9 gene therapy extends survival and reduces pathological features
PMID: 33010819
3
CLN8 mutations underlie neuronal ceroid lipofuscinoses; different CLN8 mutations cause variable severity phenotypes including mild EPMR and severe late infantile variants
PMID: 21990111
4
CLN8 mRNA is developmentally regulated in CNS with highest expression in cortex and hippocampus, suggesting roles in neuronal maturation and survival; expression is upregulated in hippocampal kindling epilepsy model
PMID: 15826318
5
CLN8 disease presents with progressive neurological deterioration including seizures, dementia, ataxia, visual failure, and abnormal movements; compound heterozygous variants can cause mild protracted phenotypes
PMID: 36011304
6
Northern epilepsy (CLN8/EPMR) is characterized by onset of seizures ages 5-10 with subsequent progressive mental retardation; neuronal storage of autofluorescent granules with rectilinear and fingerprint profiles
PMID: 11332769
7
CLN8 belongs to TRAM-LAG1-CLN8 family of membrane-associated proteins with potential implications for ceramide synthesis, lipid regulation, and protein translocation in ER
PMID: 12151215
8
CLN8 is a candidate gene in 8p23.3 critical region associated with developmental delay, intellectual disability, language/speech delay, motor impairment, behavioral anomalies, autism spectrum disorder, and epilepsy
PMID: 33925474
Disease Associationsβ“˜22
CLN8 diseaseOpen Targets
0.77Strong
neuronal ceroid lipofuscinosis 8Open Targets
0.76Strong
neuronal ceroid lipofuscinosis 8 northern epilepsy variantOpen Targets
0.74Strong
Progressive epilepsy - intellectual disability, Finnish typeOpen Targets
0.73Strong
neuronal ceroid lipofuscinosisOpen Targets
0.71Strong
genetic disorderOpen Targets
0.50Moderate
hypertensionOpen Targets
0.44Moderate
eye diseaseOpen Targets
0.37Weak
essential hypertensionOpen Targets
0.32Weak
neurodegenerative diseaseOpen Targets
0.30Weak
cartilage diseaseOpen Targets
0.27Weak
SeizureOpen Targets
0.27Weak
tooth diseaseOpen Targets
0.16Weak
Abruptio PlacentaeOpen Targets
0.16Weak
rectosigmoid junction neoplasmOpen Targets
0.14Weak
complex regional pain syndromeOpen Targets
0.14Weak
placental retentionOpen Targets
0.14Weak
pyogenic granulomaOpen Targets
0.14Weak
Intellectual disabilityOpen Targets
0.14Weak
severe acute respiratory syndromeOpen Targets
0.13Weak
Ceroid lipofuscinosis, neuronal, 8UniProt
Ceroid lipofuscinosis, neuronal, 8, Northern epilepsy variantUniProt
Pathogenic Variants89
NM_018941.4(CLN8):c.611G>A (p.Arg204His)Likely pathogenic
Neuronal ceroid lipofuscinosis 8|Neuronal ceroid lipofuscinosis
β˜…β˜…β˜†β˜†2026β†’ Residue 204
NM_018941.4(CLN8):c.1A>G (p.Met1Val)Pathogenic
Neuronal ceroid lipofuscinosis 8|Neuronal ceroid lipofuscinosis|not provided
β˜…β˜…β˜†β˜†2026β†’ Residue 1
NM_018941.4(CLN8):c.499G>T (p.Glu167Ter)Pathogenic
not provided|Neuronal ceroid lipofuscinosis|Neuronal ceroid lipofuscinosis 8|Inborn genetic diseases|Neuronal ceroid lipofuscinosis 8 northern epilepsy variant;Neuronal ceroid lipofuscinosis 8
β˜…β˜…β˜†β˜†2025β†’ Residue 167
NM_018941.4(CLN8):c.29C>G (p.Ser10Ter)Pathogenic
Neuronal ceroid lipofuscinosis|Neuronal ceroid lipofuscinosis 8
β˜…β˜…β˜†β˜†2025β†’ Residue 10
NM_018941.4(CLN8):c.473A>G (p.Tyr158Cys)Pathogenic
Neuronal ceroid lipofuscinosis 8|Neuronal ceroid lipofuscinosis|Neuronal ceroid lipofuscinosis 8;Neuronal ceroid lipofuscinosis 8 northern epilepsy variant|Inborn genetic diseases
β˜…β˜…β˜†β˜†2025β†’ Residue 158
NM_018941.4(CLN8):c.208C>T (p.Arg70Cys)Likely pathogenic
Neuronal ceroid lipofuscinosis|Neuronal ceroid lipofuscinosis 8
β˜…β˜…β˜†β˜†2025β†’ Residue 70
NM_018941.4(CLN8):c.620T>G (p.Leu207Arg)Likely pathogenic
Neuronal ceroid lipofuscinosis
β˜…β˜…β˜†β˜†2025β†’ Residue 207
NM_018941.4(CLN8):c.209G>A (p.Arg70His)Pathogenic
Neuronal ceroid lipofuscinosis 8|Neuronal ceroid lipofuscinosis|Inborn genetic diseases|not provided
β˜…β˜…β˜†β˜†2025β†’ Residue 70
NM_018941.4(CLN8):c.709G>A (p.Gly237Arg)Pathogenic
Neuronal ceroid lipofuscinosis 8|not provided|Neuronal ceroid lipofuscinosis
β˜…β˜…β˜†β˜†2025β†’ Residue 237
NM_018941.4(CLN8):c.295C>T (p.Gln99Ter)Pathogenic
Neuronal ceroid lipofuscinosis|Neuronal ceroid lipofuscinosis 8 northern epilepsy variant;Neuronal ceroid lipofuscinosis 8|not provided|Neuronal ceroid lipofuscinosis 8
β˜…β˜…β˜†β˜†2025β†’ Residue 99
NM_018941.4(CLN8):c.610C>T (p.Arg204Cys)Pathogenic
Neuronal ceroid lipofuscinosis 8|Neuronal ceroid lipofuscinosis 8 northern epilepsy variant;Neuronal ceroid lipofuscinosis 8|Neuronal ceroid lipofuscinosis|not provided|CLN8-related disorder
β˜…β˜…β˜†β˜†2025β†’ Residue 204
NM_018941.4(CLN8):c.703del (p.Val236fs)Pathogenic
Neuronal ceroid lipofuscinosis|Inborn genetic diseases
β˜…β˜…β˜†β˜†2025β†’ Residue 236
NM_018941.4(CLN8):c.398T>A (p.Leu133Ter)Pathogenic
Neuronal ceroid lipofuscinosis 8|Neuronal ceroid lipofuscinosis
β˜…β˜…β˜†β˜†2024β†’ Residue 133
NM_018941.4(CLN8):c.763C>T (p.Gln255Ter)Pathogenic
Neuronal ceroid lipofuscinosis 8|Neuronal ceroid lipofuscinosis
β˜…β˜…β˜†β˜†2024β†’ Residue 255
NM_018941.4(CLN8):c.70C>G (p.Arg24Gly)Pathogenic
Neuronal ceroid lipofuscinosis 8 northern epilepsy variant|Neuronal ceroid lipofuscinosis 8|Neuronal ceroid lipofuscinosis|Neuronal ceroid lipofuscinosis 8 northern epilepsy variant;Neuronal ceroid lipofuscinosis 8
β˜…β˜…β˜†β˜†2024β†’ Residue 24
NM_018941.4(CLN8):c.562_563del (p.Leu188fs)Pathogenic
Neuronal ceroid lipofuscinosis 8|Neuronal ceroid lipofuscinosis
β˜…β˜…β˜†β˜†2023β†’ Residue 188
NM_018941.4(CLN8):c.789G>C (p.Trp263Cys)Pathogenic
Neuronal ceroid lipofuscinosis 8|not provided|Neuronal ceroid lipofuscinosis
β˜…β˜…β˜†β˜†2023β†’ Residue 263
NM_018941.4(CLN8):c.593_596dup (p.Met200fs)Pathogenic
Neuronal ceroid lipofuscinosis|Neuronal ceroid lipofuscinosis 8
β˜…β˜…β˜†β˜†2022β†’ Residue 200
NM_018941.4(CLN8):c.298C>T (p.Gln100Ter)Pathogenic
Neuronal ceroid lipofuscinosis
β˜…β˜†β˜†β˜†2025β†’ Residue 100
NM_018941.4(CLN8):c.1A>C (p.Met1Leu)Pathogenic
Neuronal ceroid lipofuscinosis
β˜…β˜†β˜†β˜†2025β†’ Residue 1
View on ClinVar β†—
Related Genes
PPT1Protein interaction84%CERS1Protein interaction82%KCTD7Protein interaction80%MFSD8Protein interaction79%TPP1Protein interaction76%CTSDProtein interaction76%
Tissue Expression6 tissues
Brain
100%
Bone Marrow
85%
Liver
83%
Lung
83%
Heart
62%
Ovary
25%
Gene Interaction Network
Click a node to explore
CLN8PPT1CERS1KCTD7MFSD8TPP1CTSD
PROTEIN STRUCTURE
Preparing viewer…
AlphaFoldAI-predicted Β· UniProt Q9UBY8
View on AlphaFold β†—
Constraintβ“˜
LOEUFβ“˜
1.18LoF Tolerant
pLIβ“˜
0.00Tolerant
Observed/Expected LoF0.81 [0.57–1.18]
RankingsWhere CLN8 stands among ~20K protein-coding genes
  • #10,296of 20,598
    Most Researched39
  • #852of 5,498
    Most Pathogenic Variants89 Β· top quartile
  • #12,415of 17,882
    Most Constrained (LOEUF)1.18
Genes detectedCLN8
Sources retrieved10 papers
Response timeβ€”
πŸ“„ Sources
10β–Ό
1
8p23.2-pter Microdeletions: Seven New Cases Narrowing the Candidate Region and Review of the Literature.
PMID: 33925474
Genes (Basel) Β· 2021
1.00
2
Update of the mutation spectrum and clinical correlations of over 360 mutations in eight genes that underlie the neuronal ceroid lipofuscinoses.
PMID: 21990111
Hum Mutat Β· 2012
0.90
3
PMID: 39637217
0.80
4
TRAM-LAG1-CLN8 family proteins are acyltransferases regulating phospholipid composition.
PMID: 39970228
Sci Adv Β· 2025
0.70
5
PMID: 36011304
Genes (Basel) Β· 2022
0.60