DHX9 Gene - DEAH-Box Helicase 9: Function, Mutations, and Disease Associations

DHX9 (DEAH-box helicase 9) encodes a multifunctional ATP-dependent RNA helicase belonging to the DEAH-box family. The protein is involved in a wide range of cellular processes including transcription regulation, pre-mRNA splicing, RNA export, translation, and maintenance of genomic stability. DHX9 interacts with RNA polymerase II, transcription factors, and other helicases to modulate gene expression. It also plays a role in resolving R-loops and DNA:RNA hybrids, thereby preventing replication stress and DNA damage. Dysregulation of DHX9 has been implicated in various cancers and genetic disorders.

Tissue Expression

Cell Line Expression

Hotspot Mutations

Mutation functional classification

• Spliceosome

• Transcription regulation by RNA polymerase II

• R-loop resolution

• DNA damage response

• mRNA surveillance

The DHX9 protein (UniProt Q08211) is a 1,270-amino acid DEAH-box RNA helicase. It contains a conserved helicase domain with ATP-binding and RNA unwinding activities, as well as a double-stranded RNA-binding domain (dsRBD) and a nuclear localization signal. DHX9 forms homodimers and interacts with multiple partners including RNA polymerase II, transcription factors, and other helicases (e.g., BLM, WRN). It localizes to both the nucleus and cytoplasm, shuttling between compartments to regulate RNA metabolism. The protein is essential for embryonic development and cellular proliferation.