Importantly, according to the Catalogue of Somatic Mutations in Cancer (COSMIC) database44, cancer-associated mutations are prevalent on the ligand-binding interface, the LBD and the CRD oligomerization interfaces of EphB6, including R112W/G/Q, E126K and V294A (Fig. 5d and Supplementary Fig. 1d). Here, EPHB6 is linked to cancer.