Estrogeh insensitivity syndrome (EIS) arises from rare mutations in ERα resulting in the inability of estrogen to exert its biological effects. Due to the rarity, mutations in ESR1 gene and the underlying molecular mechanisms of EIS have not been thoroughly studied. We used RIME (Rapid Immunoprecipitation Mass spectrometry of Endogenous proteins) analysis to compare the interactions for ER alpha between the WT ER alpha and Q375H clinical mutant in HepG2 stable cells.