Mutational hotspots of HSP47 and its potential role in cancer and bone-disorders

Abstract

Heat shock protein 47 kDa (HSP47) serves as a client-specific chaperone, essential for collagen biosynthesis and its folding and structural assembly. To date, there is no comprehensive study on mutational hotspots. Using five different human mutational databases, we deduced a comprehensive list of human HSP47 mutations with 24, 67, 50, 43 and 2 deleterious mutations from the 1000 genomes data, gnomAD, COSMICv86, cBioPortal, and CanVar, respectively. We identified thirteen top-ranked missense mutations of HSP47 with the stringent cut-off of CADD score (>25) and Grantham score (≥151) as Ser76Trp, Arg103Cys, Arg116Cys, Ser159Phe, Arg167Cys, Arg280Cys, Trp293Cys, Gly323Trp, Arg339Cys, Arg373Cys, Arg377Cys, Ser399Phe, and Arg405Cys with the arginine-cysteine changes as the predominant mutations. These findings will assist in the evaluation of roles of HSP47 in collagen misfolding and human diseases such as cancer and bone disorders.

Keywords: Cancer database; Chaperone; HSP47; Missense mutation; Mutational hotspot; Variant analysis.