Histone lysine demethylase PHF8 (PHF8)

Histone lysine demethylase PHF8 (PHF8, also known as KDM7B) is an epigenetic enzyme that catalyzes the Fe(II)- and 2-oxoglutarate-dependent demethylation of mono- and dimethylated lysines on histone H3 (especially H3K9me1/2, H3K27me2, possibly H4K20me1 and H3K36me2), regulating chromatin accessibility and gene expression[2][1][5]. PHF8 contains a plant homeodomain (PHD) involved in substrate recognition and a JmjC catalytic domain for demethylase activity[2][1]. It acts both as a transcriptional coactivator and repressor, influencing cell cycle progression, DNA damage repair, and broader epigenetic regulatory programs. Mutations in PHF8 are causally linked to X-linked intellectual disability syndromes with craniofacial defects, and altered PHF8 function is associated with cancer and other diseases[1][2][5]. As an epigenetic regulator, PHF8 is under preclinical investigation as a drug target for modulators of histone methylation[5].

Other names

KDM7BJHDM1FPlant homeodomain (PHD) finger protein 8KIAA1111ZNF422Zinc finger protein 422[Histone H3]-dimethyl-L-lysine(36) demethylase PHF8[Histone H3]-dimethyl-L-lysine(9) demethylase PHF8Jumonji C domain-containing histone demethylase 1FLysine demethylase 7BMRXSSD

Small-molecule inhibitors of PHF8 (in experimental/preclinical phases) are designed to block its Fe(II)- and 2-oxoglutarate-dependent dioxygenase activity, thereby inhibiting demethylation of repressive histone marks and altering gene expression. Disruption of PHF8 activity can lead to accumulation of transcriptionally repressive histone methylation and altered cellular epigenetic state.