CLN8
CLN8 transmembrane ER and ERGIC protein
Gene Information Card
| Symbol | CLN8 |
|---|---|
| Full Name | CLN8 transmembrane ER and ERGIC protein |
| Gene Type | protein-coding |
| Chromosomal Location | 8p23.3 |
| NCBI Gene ID | 2055 ncbi.nlm.nih.gov/gene/2055 |
| Ensembl ID | ENSG00000182372 |
| UniProt ID | Q9UBY8 |
| OMIM ID | 607837 |
| HGNC ID | 2079 |
| Aliases | EPMR, FLJ39275, MGC138215 |
Description
CLN8 encodes a transmembrane protein localized to the endoplasmic reticulum (ER) and ER-Golgi intermediate compartment (ERGIC). It is involved in lysosomal biogenesis and lipid transport. Mutations in CLN8 cause neuronal ceroid lipofuscinosis type 8 (CLN8 disease), a neurodegenerative lysosomal storage disorder, and also progressive epilepsy with mental retardation (EPMR).
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Neuronal ceroid lipofuscinosis 8 (CLN8 disease) | Loss of CLN8 function disrupts lysosomal protein trafficking and lipid homeostasis, leading to accumulation of autofluorescent lipopigments in neurons. | ClinVar, OMIM |
| Progressive epilepsy with mental retardation (EPMR) | Specific missense mutations (e.g., p.Arg24Gly) impair CLN8 protein function, causing a milder form of neurodegeneration with epilepsy and cognitive decline. | OMIM, PubMed |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 12.5 | Medium |
| Testis | 8.3 | Low |
| Kidney | 6.1 | Low |
| Liver | 4.7 | Low |
| Heart | 3.9 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| SH-SY5Y (neuroblastoma) | 10.2 | Neuronal model |
| HEK293 (embryonic kidney) | 7.8 | Common overexpression system |
| U-87 MG (glioblastoma) | 6.5 | Glial model |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.70C>T (p.Arg24Gly) | Missense | Found in EPMR families | Reduced protein stability and ER retention |
| c.200C>T (p.Pro67Leu) | Missense | Rare in CLN8 disease | Impaired lysosomal targeting |
| c.1A>G (p.Met1Val) | Start loss | Very rare | Complete loss of protein expression |
| c.535C>T (p.Arg179*) | Nonsense | Reported in CLN8 disease | Premature truncation, loss of function |
Mutation functional classification
Loss of Function (LOF)
Most CLN8 disease mutations (nonsense, frameshift, splice-site) lead to loss of protein function, causing severe neurodegeneration.
Gain of Function (GOF)
No evidence for gain-of-function mutations in CLN8.
Dominant Negative (DN)
No dominant-negative mechanism reported; CLN8 disease is autosomal recessive.
View complete mutation data：
Gene Ontology (GO)
| • endoplasmic reticulum (GO:0005783) | • ER-Golgi intermediate compartment (GO:0005793) |
| • lipid metabolic process (GO:0006629) | • lysosome organization (GO:0007040) |
| • integral component of membrane (GO:0016021) |
Pathways
• Lysosome biogenesis
• Sphingolipid metabolism
• Neuronal ceroid lipofuscinosis pathway
Protein Summary
CLN8 is a 286-amino acid transmembrane protein with 5 predicted transmembrane domains. It localizes to the ER and ERGIC, where it participates in lipid transport and lysosomal enzyme trafficking. The protein is highly expressed in brain and testis. Loss of CLN8 function leads to accumulation of subunit c of mitochondrial ATP synthase and saposins in lysosomes, characteristic of CLN8 disease.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| CLN8 Knockout HEK293 Cell Line | EDJ-KQ4545 | Human | 2055 | Details Get a Quote |
| CLN8 Knockout A-549 Cell Line | EDJ-KQ27171 | Human | 2055 | Details Get a Quote |
| CLN8 Knockout HCT 116 Cell Line | EDJ-KQ27172 | Human | 2055 | Details Get a Quote |
| CLN8 Knockout HeLa Cell Line | EDJ-KQ18237 | Human | 2055 | Details Get a Quote |
