TRPC6 N338S is a gain-of-function mutant identified in patient with doxorubicin-induced cardiotoxicity.

ABSTRACT: The canonical transient receptor potential 6 gene, TRPC6, has been implicated as a putative risk gene for chemotherapy-induced congestive heart failure, but knowledge of specific risk variants is lacking. Following our genome-wide association study and subsequent fine-mapping, a rare missense mutant of TRPC6 N338S, was identified in a breast cancer patient who received anthracycline-containing chemotherapy regiments and developed congestive heart failure. However, the function of N338S mutant has not been examined. Using intracellular Ca²⁺ imaging, patch clamp recording and molecular docking techniques, we assessed the function of N338S mutant heterologously expressed in HEK293 cells and HL-1 cardiac cells. We found that expression of TRPC6 N338S significantly increased intracel

SUBMITTER: Lu T 

PROVIDER: S-EPMC10858733 | biostudies-literature | 2022 Nov

REPOSITORIES: biostudies-literature