PHD finger protein 8 (PHF8) (PHF8)

PHD finger protein 8 (PHF8) is a JmjC domain-containing histone demethylase that plays a pivotal role in epigenetic regulation by specifically removing methyl groups from mono- and dimethylated lysine 9 of histone H3 (H3K9me1/2), dimethylated lysine 27 of histone H3 (H3K27me2), and monomethylated lysine 20 of histone H4 (H4K20me1) (UniProt P0C5Y0). By targeting these repressive marks, PHF8 functions as a transcriptional coactivator, facilitating the expression of genes essential for the cell cycle, ribosomal DNA transcription, and neuronal differentiation (PMID: 20436456, PMID: 20562861). Mutations in the PHF8 gene are clinically linked to Siderius-type X-linked intellectual disability and cleft lip/palate, underscoring its importance in neurodevelopment (NCBI Gene ID: 23133). In the context of oncology, PHF8 is frequently overexpressed and acts as an oncoprotein in various cancers, including prostate, breast, and esophageal squamous cell carcinoma, where it promotes cell proliferation, migration, and epithelial-mesenchymal transition (PMID: 33408345). Although no PHF8-targeted therapies are currently FDA-approved, the protein is a significant focus of drug discovery efforts, with small-molecule inhibitors like KDM7-IN-1 and repurposed drugs like disulfiram being investigated for their ability to block its catalytic activity and suppress tumor growth (PMID: 26913471, PMID: 30103345).

Other names

KDM7BLysine-specific demethylase 7BJmjC domain-containing histone demethylase 1DJHDM1DZNF422Siderius type X-linked mental retardation protein

Inhibition of the JmjC domain-mediated oxidative demethylation of histone lysines (specifically H3K9me1/2, H3K27me2, and H4K20me1) to modulate gene expression and suppress oncogenic signaling.