CLN6: Ceroid-Lipofuscinosis, Neuronal 6
Endoplasmic Reticulum Membrane Protein Associated with Neurodegenerative Lysosomal Storage Disorders
Gene Information Card
| Symbol | CLN6 |
|---|---|
| Full Name | CLN6, transmembrane ER protein |
| Gene Type | Protein coding |
| Chromosomal Location | 15q23 |
| NCBI Gene ID | 54982 ncbi.nlm.nih.gov/gene/54982 |
| Ensembl ID | ENSG00000128973 |
| UniProt ID | Q9NWW5 |
| OMIM ID | 606725 |
| HGNC ID | 2077 |
| Aliases | NCL6, CLN6A, FLJ20561 |
Description
CLN6 encodes a transmembrane protein localized to the endoplasmic reticulum (ER). It is involved in the biogenesis of lysosomal enzymes and the clearance of cellular waste. Mutations in CLN6 cause neuronal ceroid lipofuscinosis type 6 (NCL6), a progressive neurodegenerative lysosomal storage disorder characterized by accumulation of autofluorescent lipopigments in neurons and other tissues.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Neuronal Ceroid Lipofuscinosis 6 (NCL6) | Loss-of-function mutations in CLN6 impair lysosomal enzyme trafficking, leading to accumulation of ceroid lipofuscin in lysosomes and neuronal death. | ClinVar, OMIM |
| Kufs Disease Type A (Adult-Onset NCL) | Homozygous or compound heterozygous CLN6 mutations cause adult-onset NCL with progressive myoclonus epilepsy and dementia. | OMIM, PubMed |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 12.5 | Medium |
| Testis | 8.2 | Low |
| Heart | 6.1 | Low |
| Liver | 5.3 | Low |
| Kidney | 4.8 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| SH-SY5Y (neuroblastoma) | 10.1 | Neuronal model |
| HeLa (cervical carcinoma) | 7.3 | Epithelial |
| HEK293 (embryonic kidney) | 6.5 | Common expression system |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.316C>T (p.Arg106*) | Nonsense | Rare | Loss of function; truncation |
| c.535G>A (p.Gly179Arg) | Missense | Rare | Impaired ER localization |
| c.662C>T (p.Pro221Leu) | Missense | Rare | Reduced protein stability |
| c.1A>G (p.Met1?) | Start loss | Rare | No protein synthesis |
Mutation functional classification
Loss of Function (LOF)
Most CLN6 mutations are loss-of-function, leading to reduced or absent protein activity and lysosomal dysfunction.
Gain of Function (GOF)
No gain-of-function mutations reported.
Dominant Negative (DN)
No dominant-negative mutations reported; disease is autosomal recessive.
View complete mutation data：
Gene Ontology (GO)
| • endoplasmic reticulum (GO:0005783) | • lysosome organization (GO:0007040) |
| • lysosome (GO:0005764) | • integral component of membrane (GO:0016021) |
| • lipid metabolic process (GO:0006629) |
Pathways
• Lysosome (KEGG: hsa04142)
• Autophagy - animal (KEGG: hsa04140)
Protein Summary
The CLN6 protein is a 311-amino-acid transmembrane protein with 7 predicted membrane-spanning domains, localized to the endoplasmic reticulum. It is essential for proper lysosomal enzyme trafficking and function. Loss of CLN6 leads to accumulation of autofluorescent storage material, particularly subunit c of mitochondrial ATP synthase, in lysosomes, causing neurodegeneration.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| CLN6 Knockout HEK293 Cell Line | EDJ-KQ12168 | Human | 54982 | Details Get a Quote |
| CLN6 Knockout A-549 Cell Line | EDJ-KQ39623 | Human | 54982 | Details Get a Quote |
| CLN6 Knockout HCT 116 Cell Line | EDJ-KQ40870 | Human | 54982 | Details Get a Quote |
| CLN6 Knockout HeLa Cell Line | EDJ-KQ40871 | Human | 54982 | Details Get a Quote |
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