DNAJC6: DnaJ Heat Shock Protein Family (Hsp40) Member C6
A key co-chaperone in clathrin-mediated endocytosis, associated with juvenile parkinsonism and neurodegenerative disorders.
Gene Information Card
| Symbol | DNAJC6 |
|---|---|
| Full Name | DnaJ Heat Shock Protein Family (Hsp40) Member C6 |
| Gene Type | Protein coding |
| Chromosomal Location | 1p31.3 |
| NCBI Gene ID | 9829 ncbi.nlm.nih.gov/gene/9829 |
| Ensembl ID | ENSG00000116641 |
| UniProt ID | O75061 |
| OMIM ID | 608375 |
| HGNC ID | 15469 |
| Aliases | PARK19, auxilin, KIAA0473 |
Description
DNAJC6 encodes auxilin, a co-chaperone of the Hsp40/DnaJ family. Auxilin is essential for clathrin-mediated endocytosis, specifically in the uncoating of clathrin-coated vesicles in neurons. It recruits Hsc70 to clathrin cages, driving ATP-dependent disassembly. Loss-of-function mutations in DNAJC6 cause autosomal recessive juvenile parkinsonism (PARK19), characterized by early-onset, slow progression, and dystonia.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Parkinson disease 19 (PARK19) | Loss-of-function mutations impair clathrin uncoating, disrupting synaptic vesicle recycling and leading to dopaminergic neuron degeneration. | OMIM #615528; multiple case reports (Köroğlu et al., 2013; Olgiati et al., 2016) |
| Juvenile parkinsonism | Biallelic DNAJC6 mutations cause early-onset parkinsonism with dystonia and cognitive decline. | ClinVar; PMID: 23341771 |
| Autism spectrum disorder (susceptibility) | Rare missense variants may alter synaptic endocytosis, though evidence is limited. | PMID: 25217958 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 12.5 | High |
| Testis | 8.3 | Medium |
| Adrenal gland | 6.1 | Medium |
| Thyroid | 4.7 | Low |
| Liver | 2.1 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| SH-SY5Y (neuroblastoma) | 15.2 | Neuronal model, high expression |
| U-87 MG (glioblastoma) | 9.8 | Glial cell line |
| HEK 293 (embryonic kidney) | 6.4 | Moderate expression |
| HeLa (cervical carcinoma) | 3.1 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.801-2A>G (splice acceptor) | Splice site | Rare | Exon skipping, loss of auxilin function |
| p.Arg927* | Nonsense | Rare | Premature truncation, loss of J-domain |
| p.Gly308Arg | Missense | Rare | Impaired clathrin binding |
| p.Leu749Pro | Missense | Rare | Disrupted protein stability |
Mutation functional classification
Loss of Function (LOF)
Biallelic loss-of-function mutations (nonsense, frameshift, splice-site) cause juvenile parkinsonism by abolishing auxilin-mediated clathrin uncoating.
Gain of Function (GOF)
Not reported for DNAJC6.
Dominant Negative (DN)
Not reported; disease inheritance is autosomal recessive.
View complete mutation data：
Gene Ontology (GO)
| • protein binding (GO:0005515) | • clathrin binding (GO:0030276) |
| • synaptic vesicle endocytosis (GO:0048488) | • unfolded protein binding (GO:0051082) |
| • clathrin coat disassembly (GO:0072310) |
Pathways
• Clathrin-mediated endocytosis (KEGG hsa04144)
• Synaptic vesicle cycle (KEGG hsa04721)
• Hsp70 chaperone cycle
Protein Summary
Auxilin (DNAJC6) is a 913-amino acid protein containing a J-domain that stimulates Hsc70 ATPase activity, a clathrin-binding domain, and a PTEN-like domain. It is predominantly expressed in neurons and localizes to clathrin-coated pits. By coordinating clathrin uncoating, auxilin ensures efficient synaptic vesicle recycling. Mutations that impair its function lead to accumulation of clathrin-coated vesicles and synaptic dysfunction, particularly in dopamine neurons.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| DNAJC6 Knockout HEK293 Cell Line | EDJ-KQ6769 | Human | 9829 | Details Get a Quote |
| DNAJC6 Knockout A-549 Cell Line | EDJ-KQ31212 | Human | 9829 | Details Get a Quote |
| DNAJC6 Knockout HCT 116 Cell Line | EDJ-KQ31213 | Human | 9829 | Details Get a Quote |
| DNAJC6 Knockout HeLa Cell Line | EDJ-KQ31214 | Human | 9829 | Details Get a Quote |
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