DNAJC6
- Known as:
- DNAJC6
- Catalog number:
- Y214369
- Product Quantity:
- 200ul
- Category:
- -
- Supplier:
- ABM
- Gene target:
- DNAJC6
Related genes to: DNAJC6
- Gene:
- DNAJC6 NIH gene
- Name:
- DnaJ heat shock protein family (Hsp40) member C6
- Previous symbol:
- -
- Synonyms:
- KIAA0473, PARK19
- Chromosome:
- 1p31.3
- Locus Type:
- gene with protein product
- Date approved:
- 2001-03-30
- Date modifiied:
- 2015-11-19
Related products to: DNAJC6
Related articles to: DNAJC6
- Loss-of-function mutations in DNAJC6, encoding the co-chaperone auxilin (HSP40 family), cause familial juvenile-onset Parkinson's disease (PD). Given the chaperone role of DNAJC6 in cellular homeostasis in adult neurons, we hypothesized that DNAJC6 dysfunction may not be limited to juvenile-onset disorders but could also be associated with adult-onset brain diseases. Here, we show that DNAJC6 expression is significantly downregulated in postmortem substantia nigra tissues and transcriptomic datasets from patients with late-onset sporadic PD. Consistently, human pluripotent stem cell-derived midbrain cultures exhibited reduced DNAJC6 expression under multiple PD-associated conditions. Mechanistically, DNAJC6 loss resulted from impaired transcription mediated by midbrain-specific factors NURR1/FOXA2 and reduced protein stability regulated by LRRK2. Beyond neurons, DNAJC6 was robustly expressed in astrocytes and similarly downregulated in sporadic PD contexts. Astrocytic DNAJC6 deficiency impaired phagocytic, autolysosomal, and mitochondrial functions while promoting a pro-inflammatory phenotype, thereby exacerbating neurodegenerative pathology. Importantly, epigenetic restoration of DNAJC6 in neurons and astrocytes using a CRISPRa-AAV9 system in the substantia nigra of an α-synuclein-induced PD mouse model alleviated behavioral deficits and neuropathology. These findings provide evidence that DNAJC6 dysregulation is associated with pathogenic processes in sporadic PD and suggest that targeting neuronal and astrocytic DNAJC6 could represent a potential disease-modifying strategy. - Source: PubMed
Publication date: 2026/04/09
Darsono Wahyu Handoko WibowoHwang YeongranValencia EricaGunawan Leonardo TejoHyeon Seung JaeRyu HoonStein Thor DChang Mi-YoonWulansari NovianaLee Sang-Hun - Recent studies suggested that genetic mutations in the DNAJC family might elevate the risk of Parkinson's disease (PD). Nevertheless, the role of some DNAJC genes in PD remains controversial, and previous studies lacked downstream research. In this study, we aim to explore the relationship between DNAJC family genes and PD in a European cohort through a comprehensive method. - Source: PubMed
Publication date: 2026/04/09
Yang DehaoXu JingxuanZhu YushengLu YangguangYao RuotongYe ZihanYu BohuaiChen JiaxuanZhang TingxuanLiu BowenHuang SuwenChen Guangyong - DNAJC6 encodes auxilin, which is predominantly expressed in neurons and oligodendrocytes. It is involved in clathrin uncoating following clathrin-mediated endocytosis (CME), and loss-of-function genetic variants have been linked to juvenile- and early-onset forms of Parkinson's disease (PD). Here, we review the genetics and function of the DNAJC6 gene and discuss potential roles it may play in PD. Mechanistic studies across cellular and animal models demonstrate that loss of auxilin impairs synaptic vesicle endocytosis, disrupts endolysosomal trafficking and autophagy, alters lipid homeostasis, and leads to dopaminergic neuron degeneration, while emerging glial data hint at oligodendrocyte contributions to disease pathogenesis. - Source: PubMed
Publication date: 2026/04/04
Allen Angel GStednitz SarahLardelli MichaelBarthelson Karissa - - Source: PubMed
Publication date: 2026/04/02
Jacquemyn JulieKuenen SabineSwerts JefPavie BenjaminVijayan VinoyKilic AyseChabot DriesWang Yu-ChunSchoovaerts NilsCorthout NikkyVerstreken Patrik - Homozygous (Q789X) DNAJC6 mutation causes PARK19. Q787 of Dnajc6 corresponds to Q789 of DNAJC6. Dnajc6 mouse was utilized to elucidate pathomechanisms underlying (Q789X) DNAJC6-induced PARK19. Dnajc6 mice displayed PARK19 motor deficits and degeneration of substantia nigra (SN) dopaminergic neurons. (Q787X) Dnajc6 decreased clathrin heavy chain and lysosomal number, leading to downregulation of lysosomal cathepsin D and upregulation of α-synuclein or α-synuclein oligomers in SN dopaminergic neurons. Lysosomal biogenesis activator rapamycin precluded (Q787X) Dnajc6-induced downregulation of cathepsin D, upregulation of α-synuclein, and PARK19 phenotypes. (Q787X) Dnajc6-induced elevation of ER and mitochondrial α-synuclein excited ER stress and mitochondrial pro-apoptotic cascades. (Q787X) Dnajc6-evoked α-synuclein oligomer overexpression activated SN microglia and NLRP3 inflammasome and upregulated IL-1β, IL-18, and TNF-α, which stimulated MKK4-JNK -c-Jun/ATF-2 and RIPK1-RIPK3-MLKL death cascades. Our results suggest that PARK19 (Q789X) DNAJC6 mutation causes lysosomal deficiency and impairs cathepsin D-mediated degradation of α-synuclein, resulting in upregulated α-synuclein-induced neurodegeneration of SN dopaminergic cells. - Source: PubMed
Publication date: 2026/03/12
Wang Hung-LiChen Ying-LingChiu Tai-JuChiu Ching-ChiWeng Yi-HsinLiu Shu-YuLi Allen Hon-LunYeh Tu-Hsueh