APEX1 Gene: Function, Mutations, and Disease Associations | Biomedical Resource

The APEX1 gene encodes a multifunctional protein involved in DNA base excision repair (BER) and redox regulation of transcription factors. It is essential for repairing apurinic/apyrimidinic (AP) sites in DNA, which are generated by spontaneous depurination or by DNA glycosylases during BER. APEX1 also functions as a redox factor (Ref-1) that maintains transcription factors such as p53, AP-1, and NF-κB in an active reduced state. The protein is ubiquitously expressed and plays a critical role in maintaining genomic stability. Mutations and altered expression of APEX1 have been linked to various cancers and neurodegenerative disorders.

Tissue Expression

Cell Line Expression

Hotspot Mutations

Mutation functional classification

• Base excision repair

• APE1-mediated DNA repair

• p53 signaling pathway

• NF-κB signaling pathway

APEX1 is a 318-amino acid protein with two main functional domains: an N-terminal redox domain and a C-terminal endonuclease domain. The protein is predominantly nuclear but can translocate to mitochondria under stress. It recognizes AP sites in DNA and cleaves the phosphodiester backbone, creating a single-strand break that is further processed by other BER enzymes. As a redox factor, APEX1 reduces cysteine residues in transcription factors, enhancing their DNA-binding activity. Post-translational modifications such as acetylation and phosphorylation regulate its subcellular localization and activity. APEX1 is essential for cell survival, and its dysregulation is implicated in cancer and neurodegeneration.