KDM4C Gene: Function, Mutations, and Role in Cancer | Biomedical SEO

KDM4C (lysine demethylase 4C) encodes a member of the Jumonji domain 2 (JMJD2) family of histone demethylases. The protein specifically demethylates di- and tri-methylated lysine 9 and lysine 36 on histone H3 (H3K9me2/me3 and H3K36me2/me3), acting as a key epigenetic regulator of gene expression. KDM4C is involved in chromatin remodeling, transcriptional activation, and cellular differentiation. Overexpression and amplification of KDM4C are frequently observed in various cancers, including breast cancer, esophageal squamous cell carcinoma, and lymphoma, where it promotes oncogenesis by altering histone methylation patterns.

Tissue Expression

Cell Line Expression

Hotspot Mutations

Mutation functional classification

• Epigenetic regulation of gene expression

• JAK-STAT signaling pathway (via H3K9 demethylation)

• MYC transcriptional activation

• p53 signaling pathway (negative regulation)

KDM4C is a 1056-amino acid protein containing a JmjN domain, a JmjC domain (catalytic), two PHD-type zinc fingers, and two Tudor domains. The JmjC domain mediates Fe(II)- and α-ketoglutarate-dependent demethylation of H3K9me2/me3 and H3K36me2/me3. The Tudor domains recognize methylated histones, facilitating chromatin targeting. KDM4C is predominantly nuclear and interacts with transcription factors such as MYC and androgen receptor. Its overexpression is oncogenic in multiple cancer types.