Whole exome sequencing of 251 individuals from 97 NPC families led to the identification of numerous rare variants possibly linked to NPC, including variants within genes involved in Notch signaling (NOTCH1, DLL3), magnesium transport (NIPAL1), EBV entry into epithelial cells (ITGB6), modulation of EBV (BCL2L12, NEDD4L), telomere biology (CLPTM1L, BRD2, HNRNPU), modulation of cAMP signaling (RAPGEF3), or DNA repair (PRKDC, MLH1). Here, PRKDC is linked to nasopharyngeal carcinoma.