Our study allowed us: i) to predict new BH3-only targets for future validation; ii) to revise the role of the invariant salt-bridge for interaction between Bcl-2 and BH3-only proteins; iii) to propose the complexes between Bcl2a1 and Hrk or Nr4a1, as new potential targets in breast cancer and iv) to identify three damaging mutations of Bcl2a1 for protein stability (L99R and M75R) or with allosteric effects (Y120C). Here, BCL2 is linked to breast cancer.