DNAJC15 Gene - Function, Mutations, and Disease Associations

DNAJC15 (DnaJ Heat Shock Protein Family (Hsp40) Member C15) encodes a mitochondrial co-chaperone belonging to the Hsp40/DnaJ family. The protein contains a J-domain that stimulates the ATPase activity of Hsp70 chaperones, facilitating protein folding and import into mitochondria. DNAJC15 is also known as MCJ (Methylation-Controlled J protein) and acts as a negative regulator of mitochondrial respiration and apoptosis. Its expression is frequently silenced by promoter methylation in various cancers, suggesting a tumor suppressor role. The gene is located on chromosome 13q14.3, a region commonly deleted in hematological malignancies.

Tissue Expression

Cell Line Expression

Hotspot Mutations

Mutation functional classification

• Protein processing in endoplasmic reticulum (KEGG: hsa04141)

• Apoptosis (KEGG: hsa04210)

• Cellular response to heat stress (Reactome: R-HSA-3371556)

DNAJC15 is a 150-amino acid mitochondrial co-chaperone with a conserved J-domain. It interacts with Hsp70 chaperones to facilitate protein import and folding within mitochondria. The protein negatively regulates mitochondrial respiration and sensitizes cells to apoptosis by modulating the mitochondrial permeability transition pore. Loss of DNAJC15 expression, often through promoter methylation, is observed in multiple cancers and contributes to chemoresistance and tumor progression.