SETD2

The protein encoded by SETD2, known as SET domain-containing protein 2, is a histone methyltransferase that catalyzes the trimethylation of histone H3 at lysine 36 (H3K36me3). It plays a critical role in transcriptional regulation, DNA repair, and genome stability by marking active gene regions and facilitating error-free homologous recombination.
SETD2 is frequently mutated in various cancers, including renal cell carcinoma, leukemia, and glioblastoma, where loss-of-function alterations disrupt H3K36me3 patterns and promote genomic instability. Current research focuses on developing small-molecule inhibitors targeting its methyltransferase activity, with preclinical studies exploring their efficacy in tumors harboring SETD2 mutations.