However, due to the hetereozygous mutations (A171D, A171T, G201V, E204K, N209K and C324Y) in the NEDD8-binding cleft of NAEβ and the adenosine triphosphate binding pocket, these adenosine sulfamate-based NAE inhibitors partly occurred to resistance in some cancer cells. The gene discussed is NEDD8; the disease is cancer.