Multimodal mechanisms of pathogenic variants in the signal peptide of FIX leading to hemophilia B.

ABSTRACT:

Abstract

Signal peptide (SP) is essential for protein secretion, and pathogenic variants in the SP of factor IX (FIX) have been identified in hemophilia B (HB). However, the underlying mechanism for the genotype-phenotype correlation of these variants has not been well studied. Here, we systematically examined the effects of 13 pathogenic point variants in the SP of FIX using different approaches. Our results showed that these point variants lead to HB by missense variants and/or aberrant premessenger RNA (pre-mRNA) splicing. The missense variants in a hydrophobic core (h-region) mainly affected the cotranslational translocation function of the SP, and those in C-terminal containing cleavage site (c-region) caused FIX deficiency mainly by disturbing the cotranslational translocatio

SUBMITTER: Gao M 

PROVIDER: S-EPMC11321298 | biostudies-literature | 2024 Aug

REPOSITORIES: biostudies-literature