CXXC4 Gene - CXXC Finger Protein 4 | Function, Mutations & Diseases

CXXC4 (CXXC Finger Protein 4), also known as IDAX, is a protein-coding gene located on chromosome 4q24. It encodes a CXXC-type zinc finger domain-containing protein that binds to unmethylated CpG dinucleotides and is involved in the regulation of DNA methylation and Wnt signaling. CXXC4 acts as a negative regulator of the canonical Wnt/β-catenin pathway by interacting with DVL (Dishevelled) and promoting its degradation. It also recruits TET proteins to DNA, influencing epigenetic modifications. Altered expression and mutations of CXXC4 have been implicated in various cancers, including colorectal and hepatocellular carcinoma.

Tissue Expression

Cell Line Expression

Hotspot Mutations

Mutation functional classification

• Wnt signaling pathway (Reactome: R-HSA-195721)

• Regulation of beta-catenin signaling (KEGG: hsa04310)

• TET-mediated DNA demethylation (Reactome: R-HSA-212165)

CXXC4 (IDAX) is a 334-amino acid protein containing a CXXC zinc finger domain at the N-terminus and a DIX domain at the C-terminus. The CXXC domain binds specifically to unmethylated CpG dinucleotides, targeting the protein to CpG islands. The DIX domain mediates interaction with Dishevelled (DVL), leading to DVL ubiquitination and degradation, thereby negatively regulating Wnt/β-catenin signaling. CXXC4 also interacts with TET proteins, facilitating their recruitment to DNA and promoting active DNA demethylation. Subcellularly, it localizes to the nucleus and cytoplasm. Post-translational modifications include phosphorylation and ubiquitination.