Molecular characteristics

COG4-CDG is caused by biallelic loss-of-function of hypomorphic mutations in COG4.

Saul-Wilson syndrome is caused by a recurrent heterozygous de novo amino acid substitution in COG4, p.Gly516Arg, associated with gain-of-function.

Both mechanisms alter vesicular trafficking, although in different ways: COG4-CDG leads to delayed retrograde Golgi-to-Endoplasmatic Reticulum traffic, while Saul-Wilson syndrome leads to accelerated retrograde trafficking.