SET domain-containing protein 5 (SETD5) (SETD5)

SET domain-containing protein 5 (SETD5) is a critical epigenetic regulator that modulates gene transcription and chromatin architecture. Although it contains a SET domain typically associated with histone lysine methyltransferase activity, SETD5 is often characterized as a pseudo-enzyme that primarily functions as a molecular scaffold (Osipovich et al., 2016). It facilitates the recruitment of the NCoR-HDAC3 corepressor complex to specific genomic loci, thereby regulating RNA polymerase II elongation and gene silencing (Deliu et al., 2018). SETD5 is essential for normal embryonic development and neurogenesis, and its haploinsufficiency is a primary cause of autosomal dominant intellectual disability-23 and is strongly associated with autism spectrum disorders (UniProt, 2024). In the field of oncology, SETD5 is frequently overexpressed in various cancers, including pancreatic ductal adenocarcinoma and certain leukemias, where it promotes tumor cell survival, proliferation, and resistance to chemotherapy (Wang et al., 2022). While no specific small-molecule inhibitors of SETD5 are currently in clinical use, its role in maintaining cancer cell stemness and its involvement in DNA damage repair pathways make it an attractive candidate for therapeutic intervention.

Other names

SETD5Mental retardation autosomal dominant 23MRD23SET domain containing 5

Regulation of gene transcription through recruitment of the NCoR-HDAC3 corepressor complex and modulation of RNA polymerase II elongation (Osipovich et al., 2016).