POU class 2 homeobox associating factor 3 (POU2AF3)

POU class 2 homeobox associating factor 3 (POU2AF3), also known as COLCA2, is a protein-coding gene encoding a transcriptional coactivator that specifically associates with the transcription factor POU2F3. This complex is critical for the development of tuft cells, which are rare chemosensory cells coordinating immune and neural functions within mucosal epithelial tissues, such as the gastrointestinal and respiratory tracts. POU2AF3 enables DNA binding and contributes to positive regulation of DNA-templated transcription. Gene fusions involving POU2AF3 (notably EWSR1::POU2AF3) have been identified as oncogenic drivers in a recently defined and aggressive subtype of round/spindle cell sarcoma of sinonasal and head/neck origin, with rapid progression and poor outcome. The gene was initially linked to colorectal cancer susceptibility and has since been implicated in primary biliary cholangitis and certain subtypes of small-cell lung cancer. Currently, there are no approved targeted drugs against POU2AF3; however, irinotecan, doxorubicin, and PARP inhibitors are being studied for their activity against POU2AF3-fusion sarcoma models. Safety concerns include resistance to chemotherapy, aggressive metastatic behavior, and treatment-associated toxicities. Biomarkers such as SLFN11 and PD-L1 have potential utility in efficacy monitoring and patient selection.

Other names

COLCA2CASC13C11orf93Cancer susceptibility candidate protein 13Colorectal cancer-associated protein 2Protein OCA-T2LOH11CR1GOCA-T2cancer susceptibility candidate 13colorectal cancer-associated protein 2

DNA damage (irinotecan, doxorubicin), PARP inhibition (olaparib), combinatorial approaches to induce cell death and cell cycle arrest in fusion-driven sarcomas