9.B.206 The TMEM199 (TMEM199) Family
Congenital disorders of glycosylation (CDGs) lead to diseases with aberrant protein glycosylation, some of which disturb Golgi homeostasis. TMEM199 is a human homolog of yeast V-ATPase assembly factor Vph2p (also known as Vma12p). Jansen et al. 2016 identified four people with different mutations in TMEM199. The adolescent individuals exhibited mild phenotypes of hepatic steatosis, elevated aminotransferases and alkaline phosphatase, hypercholesterolemia and low serum ceruloplasmin. Affected individuals showed abnormal N- and mucin-type O-glycosylation with reduced incorporation of galactose and sialic acid as seen in other Golgi homeostasis defects. TMEM199 localized to the endoplasmic reticulum and Golgi apparatus. Thus, TMEM199 is involved in Golgi homeostasis, and deficiency results in a hepatic abnormalities. Human TMEM199 is 208 aas long with two C-terminal TMSs.