The effect of mutations on functional subdomains of FIX signal peptide and propeptide. The signal peptide consists of 2 subdomains: the hydrophobic region and the signal peptidase recognition site. The hydrophobic region is recognized by signal recognition particles that assist in cotranslational translocation of FIX into the ER; mutations in the region lead to a lower MW. Mutations in the signal peptidase recognition site interfere with protein secretion, expression, and γ-carboxylation efficiency by preventing signal peptide cleavage. The propeptide region includes 2 subdomains: the GGCX recognition site and the propeptidase recognition site. Mutations in the GGCX recognition site affect protein secretion, protein expression, or γ-carboxylation efficiency. Mutations in the propeptidase recognition site lead to unremoved propeptide and destroy the specific conformation of the Gla domain.