PHD finger protein 2 (PHF2) (PHF2)

PHD finger protein 2 (PHF2), also known as KDM7C, is a JmjC domain-containing histone demethylase that plays a critical role in epigenetic regulation by specifically removing repressive methyl marks from histone H3 lysine 9 (H3K9me1/2) and histone H4 lysine 20 (H4K20me3). It functions as a transcriptional coactivator for various transcription factors, including ChREBP and HNF4A, and is essential for processes such as cell cycle progression, DNA repair, and metabolic homeostasis. In the context of disease, PHF2 has been implicated in several cancers, where it can act as either a tumor suppressor or an oncogene depending on the tissue type. For instance, it acts as a tumor suppressor in colorectal and hepatocellular carcinomas by promoting p53-mediated gene expression, while its deregulation is linked to aggressive features in other malignancies. Beyond oncology, PHF2 is a key regulator in metabolic disorders like non-alcoholic fatty liver disease (NAFLD), where its activation by glucose-responsive pathways promotes lipogenic gene expression. It also plays a significant role in neurodevelopment and neurodegeneration, with its depletion linked to cognitive deficits and neuroinflammation in Alzheimer's disease models. While no specific drugs targeting PHF2 are currently FDA-approved, it is an active area of research for small-molecule inhibitors and RNA-targeting strategies. Experimental compounds such as KDM2A/7A-IN-1 and pan-JmjC inhibitors like JIB-04 are being studied in preclinical settings to modulate its activity. Furthermore, the anti-diabetic drug metformin has been shown to exert anti-metastatic effects through the AMPK-mediated phosphorylation and activation of PHF2, highlighting its potential as a druggable node in complex signaling networks.

Other names

KDM7CJHDM1EGRC5CENP-35Lysine-specific demethylase 7C

Demethylation of repressive histone marks H3K9me1/2 and H4K20me3 to facilitate transcriptional activation; functions as a coactivator for transcription factors such as ChREBP, HNF4A, and ARID5B.