The literature documents several examples of similar changes in signal peptides that have been proven to affect secretion and are related to human diseases or traits: a Leu->Pro mutation in the signal peptide of COL5A1 (Alpha 1 Type V Collagen), a subunit of type V collagen, caused retention of this subunit in the endoplasmic reticulum and was associated with Ehlers-Danlos syndrome, a heritable connective tissue disease, in two unrelated families [45]. The gene discussed is COL5A1; the disease is Ehlers-Danlos syndrome.