| DNAJC6 Gene | |
|---|---|
| Gene Symbol | DNAJC6 |
| Full Name | DNAJ Heat Shock Protein Family (Hsp40) Member C6 |
| Chromosomal Location | 1p31.3 |
| NCBI Gene ID | 9837 |
| OMIM | 618375 |
| Ensembl ID | ENSG00000138231 |
| UniProt ID | O75037 |
| Associated Diseases | Early-Onset Parkinson's Disease, Atypical Parkinsonism, Juvenile Parkinsonism |
DNAJC6 (DNAJ Heat Shock Protein Family (Hsp40) Member C6) is a gene located on chromosome 1p31.3 that encodes a member of the DNAJ/Hsp40 family of co-chaperones. This gene is also known as DnaJ homolog subfamily C member 6 or Auxilin (for its role in clathrin uncoating). DNAJC6 is expressed in neuronal tissues and has been implicated in synaptic vesicle recycling and neurodegenerative processes[1][2].
The protein encoded by DNAJC6 functions as a co-chaperone that assists Hsp70 proteins in protein folding and refolding processes. Mutations in DNAJC6 have been associated with early-onset Parkinson's disease, making it a gene of interest in understanding the molecular mechanisms of neurodegeneration[^3].
DNAJC6 encodes a molecular co-chaperone of the Hsp40 family, also known as auxilin-1. The protein contains a J domain that stimulates the ATPase activity of Hsp70 chaperones, facilitating protein folding, refolding, and degradation. DNAJC6 is specifically involved in clathrin-mediated endocytosis by uncoating clathrin-coated vesicles. It is highly expressed in neurons and localizes to synaptic terminals, where it plays critical roles in synaptic vesicle recycling and protein quality control.
| Disease | Inheritance | Pathogenic Variants | Mechanism |
|---|---|---|---|
| Early-Onset Parkinson's Disease | Autosomal Recessive | Nonsense, frameshift, splice-site | Loss of function leading to endocytic dysfunction |
| Juvenile Parkinsonism | Autosomal Recessive | Homozygous/compound heterozygous | Impaired synaptic vesicle recycling |
| Atypical Parkinsonism | Susceptibility | Heterozygous variants | Reduced protein function |
Recessive mutations in DNAJC6 cause a form of early-onset parkinsonism with excellent response to levodopa. The disease typically presents before age 20 and is characterized by progressive parkinsonism with dystonia.
DNAJC6 shows high expression in:
The protein localizes to: