KDM5C

Description

The KDM5C (lysine demethylase 5C) is a protein-coding gene located on chromosome X.

KDM5C, encoded by the KDM5C gene in humans, is an enzyme belonging to the alpha-ketoglutarate-dependent hydroxylase superfamily. It is a member of the SMCY homolog family and contains an ARID domain, a JmjC domain, a JmjN domain, and two PHD-type zinc fingers. These domains suggest its role in regulating transcription and chromatin remodeling. Mutations in KDM5C are linked to X-linked intellectual disability. While multiple splice variants exist, only one has been fully characterized. KDM5C is involved in regulating gene expression through its demethylase activity and interactions with other proteins.

KDM5C acts as a histone demethylase, specifically targeting the 'Lys-4' residue of histone H3. This demethylation plays a crucial role in the histone code, influencing gene expression. KDM5C demethylates both trimethylated and dimethylated H3 'Lys-4', but not the monomethylated form. It does not demethylate other histone residues, such as H3 'Lys-9', H3 'Lys-27', H3 'Lys-36', H3 'Lys-79', or H4 'Lys-20'. KDM5C participates in repressing neuronal gene transcription by recruiting histone deacetylases and the REST protein to neuron-restrictive silencer elements. Additionally, it represses the CLOCK-BMAL1 heterodimer-mediated transcriptional activation of the core clock component PER2. KDM5C is part of two distinct complexes, one containing E2F6 and the other containing REST.

KDM5C is also known as DXS1272E, JARID1C, MRX13, MRXJ, MRXSCJ, MRXSJ, SMCX, XE169.

Associated Diseases

• Intellectual developmental disorder, X-linked syndromic, Claes-Jensen type
• KDM5C-related syndromic X-linked intellectual disability