Rare germline loss-of-function variants in SERPINH1 (HSP47) are associated with increased risk of thrombosis

Amelia Haj, M.D., Ph.D.
Massachusetts General Hospital
Boston, MA, U.S.

Downregulation of the chaperone protein HSP47 has recently been suggested to protect against venous thromboembolism. This study assesses the clinical impact of decreased levels of HSP47 caused by inherited genetic mutations in the HSP47 gene (SERPINH1). Specifically, the authors evaluated the association between function-altering genetic variants in SERPINH1 and four thrombotic disorders (venous thromboembolism, ischemic stroke, myocardial infarction, and peripheral arterial disease). The authors found that loss of function in SERPINH1 is associated with increased risk of all four forms of thrombosis. This work demonstrates the value of using large-scale genomic datasets to rapidly vet potential drug targets and suggests that calls for development of therapeutic HSP47 inhibitors are premature.