DDX28 Gene - DEAD-Box Helicase 28 | Function, Mutations & Disease

DDX28 (DEAD-Box Helicase 28) encodes a member of the DEAD-box family of RNA helicases, characterized by the conserved motif Asp-Glu-Ala-Asp (DEAD). The protein localizes to mitochondria, specifically to mitochondrial RNA granules, where it plays a critical role in mitochondrial ribosome biogenesis and RNA metabolism. DDX28 is essential for the processing and maturation of mitochondrial ribosomal RNAs (rRNAs) and the assembly of the mitochondrial large ribosomal subunit. It interacts with other mitochondrial RNA granule components such as DHX30 and FASTKD2. Loss of DDX28 leads to impaired mitochondrial translation and respiratory chain dysfunction.

Tissue Expression

Cell Line Expression

Hotspot Mutations

Mutation functional classification

• Mitochondrial ribosome biogenesis

• Mitochondrial RNA metabolism

• Oxidative phosphorylation (indirect)

DDX28 is a 60 kDa mitochondrial DEAD-box RNA helicase (UniProt Q9NUL7) that localizes to mitochondrial RNA granules. It contains a conserved DEAD-box helicase domain and an N-terminal mitochondrial targeting sequence. The protein unwinds RNA secondary structures in an ATP-dependent manner and is essential for the processing of mitochondrial 16S rRNA and assembly of the mitochondrial large ribosomal subunit (mtLSU). DDX28 interacts with DHX30, FASTKD2, and other RNA granule components. Its expression is highest in tissues with high oxidative metabolism, such as heart and skeletal muscle. Loss of DDX28 in cellular models causes severe mitochondrial translation defects and respiratory chain dysfunction.