Ribonuclease H2 subunit A (RNASEH2A)

Ribonuclease H2 subunit A is the **catalytic subunit** of the RNase H2 complex, an essential heterotrimeric enzyme responsible for recognizing and excising ribonucleotides embedded in genomic DNA, as well as degrading the RNA component of RNA:DNA hybrids[1][3][7]. This complex is vital for the **removal of RNA primers during lagging-strand DNA synthesis (Okazaki fragment processing)** and for maintaining genomic stability by resolving R-loops and correcting misincorporated ribonucleotides[1][3][6][7]. Mutations in RNASEH2A cause **Aicardi-Goutières syndrome**, an inherited neuro-inflammatory disorder, and changes in its expression have been linked to cancer aggressiveness and prognosis—particularly in ER-positive breast cancer and aggressive prostate cancer[2][4][6]. RNASEH2A is currently considered a **potential therapeutic target** and predictive/prognostic biomarker, but no approved drugs directly target it. Inhibition could have significant safety risks due to its ubiquitous role in DNA replication and repair[2][4][6].

Other names

RNASEH2ARNASEHIRNHIARNase H2 subunit AAGS4RNase HI large subunitRNHLAicardi-Goutieres syndrome 4 proteinRibonuclease HI large subunitRibonuclease HI subunit A

Not established for clinical drugs; potential mechanisms would involve inhibition of RNA:DNA hybrid degradation, leading to DNA replication stress or synthetic lethality in cancer