TUBB3 and cholangiocarcinoma: Applying the full multi-omics workflow to all recurrent, pathogenic variants highlighted MAP2K1, FLNC, TUBB3, and ABCA1 as the most compelling driver candidates; we therefore integrate our structural, epigenetic and transcriptomic findings with the mechanistic and clinical literature for each gene to delineate their individual and collective contributions to CCA pathogenesis.