HELZ2 Gene: Function, Expression, Mutations, and Disease Associations | Biomedical Resource

HELZ2 (Helicase With Zinc Finger 2) is a protein-coding gene located on chromosome 20q13.33. It encodes a member of the UPF1-like family of RNA helicases, characterized by a helicase core domain and a zinc finger motif. HELZ2 functions as a transcriptional coactivator, interacting with nuclear receptors such as PPARα and PPARγ, and is involved in RNA processing, ribosome biogenesis, and cellular stress responses. Its expression is widespread, with notable levels in tissues with high metabolic activity. Alterations in HELZ2 have been implicated in various cancers and metabolic disorders, though its precise pathological roles are still under investigation.

Tissue Expression

Cell Line Expression

Hotspot Mutations

Mutation functional classification

• PPAR signaling pathway

• RNA degradation

• Ribosome biogenesis in eukaryotes

• Transcriptional regulation by nuclear receptors

• Wnt signaling pathway (in cancer context)

The HELZ2 protein is a 160 kDa RNA helicase that belongs to the UPF1-like family. It contains a conserved helicase core with ATP-binding and hydrolysis domains, as well as a CCHC-type zinc finger motif. HELZ2 is predominantly localized in the nucleus and nucleolus, where it participates in transcription coactivation, particularly for nuclear receptors like PPARα and PPARγ. It also plays roles in RNA processing, ribosome biogenesis, and cellular stress responses. Structurally, it has been shown to interact with multiple proteins, including PDIP1 and PRIC complex components. Post-translational modifications such as phosphorylation may regulate its activity. Its expression is ubiquitous but enriched in metabolically active tissues. In cancer, HELZ2 overexpression is linked to tumor progression, while in metabolic diseases, it modulates lipid and glucose metabolism. Further studies are needed to fully elucidate its molecular mechanisms and therapeutic potential.