Defective POMGNT1 does not transfer GlcNAc from UDP-GlcNAc to Man-O-Ser-DAG1

Stable Identifier
Reaction [transition]
Homo sapiens
Locations in the PathwayBrowser
SVG |   | PPTX  | SBGN
Click the image above or here to open this reaction in the Pathway Browser
The layout of this reaction may differ from that in the pathway view due to the constraints in pathway layout
Protein O-linked-mannose beta-1,2-N-acetylglucosaminyltransferase 1 (POMGNT1; CAZy family GT61; MIM:606822) mediates the transfer of N-acetylglucosaminyl (GlcNAc) residues to mannosylated proteins such as mannose-O-serine-dystroglycan (man-O-Ser-DAG1). DAG1 is a cell surface protein that plays an important role in the assembly of the extracellular matrix in muscle, brain, and peripheral nerves by linking the basal lamina to cytoskeletal proteins. Defects in POMGNT1 (MIM:606822) result in disrupted glycosylation of DAG1 and can cause severe congenital muscular dystrophy-dystroglycanopathies ranging from a severe type A3 (MDDGA3; MIM:253280), through a less severe type B3 (MDDGB3; MIM:613151) to a milder type C3 (MDDGC3; MIM:613157) (Bertini et al. 2011, Wells 2013). Several mutations in POMGNT1 are known (MIM:606822) and mutations causing the severest type A3 include S550N, P493R, R605Vfs*29 (Yoshida et al. 2001), R63* (Taniguchi et al. 2003, Mercuri et al. 2009) and W475* (Godfrey et al. 2007).
Literature References
PubMed ID Title Journal Year
17878207 Refining genotype phenotype correlations in muscular dystrophies with defective glycosylation of dystroglycan

Talim, B, Smith, J, Abbs, S, Brown, SC, Clement, E, Godfrey, C, Kinali, M, Bushby, K, Brockington, M, Torelli, S, Muntoni, F, Mercuri, E, Quinlivan, R, North, K, Feng, L, Sewry, CA, Manzur, AY, Mein, R, Jimenez-Mallebrera, C, Straub, V, Topaloglu, H, Robb, S

Brain 2007
19299310 Congenital muscular dystrophies with defective glycosylation of dystroglycan: a population study

Scuderi, C, Mottarelli, E, Morandi, L, Laverda, A, Saredi, S, Moggio, M, Biancheri, R, Pichiecchio, A, Berardinelli, A, Ruggieri, A, Pane, M, Toscano, A, Pegoraro, E, Messina, S, Boffi, P, Uggetti, C, Tessa, A, Santorelli, FM, Ricci, E, Comi, GP, Pini, A, Mercuri, E, Bertini, E, Trevisan, CP, Vasco, G, D'Amico, A, Mongini, T, Moroni, I, Bruno, C, Tortorella, G, Minetti, C, Aiello, C, Pezzani, R, Mora, M, Cassandrini, D

Neurology 2009
23329833 The o-mannosylation pathway: glycosyltransferases and proteins implicated in congenital muscular dystrophy

Wells, L

J. Biol. Chem. 2013
12588800 Worldwide distribution and broader clinical spectrum of muscle-eye-brain disease

Talim, B, Endo, T, Yamanouchi, H, Taniguchi, K, Saito, K, Kobayashi, K, Toda, T, Parano, E, Pavone, P, Nishino, I, Jin, DK, Ohnuma, A, Steinbrecher, A, Hayashi, YK, Van Coster, R, Voit, T, Lee, M, Falsaperla, R, Straub, V, Manya, H, Topaloglu, H

Hum. Mol. Genet. 2003
22172424 Congenital muscular dystrophies: a brief review

Gualandi, F, D'Amico, A, Petrini, S, Bertini, E

Semin Pediatr Neurol 2011
11709191 Muscular dystrophy and neuronal migration disorder caused by mutations in a glycosyltransferase, POMGnT1

Inazu, T, Kano, H, Kobayashi, K, Voit, T, Endo, T, Manya, H, Topaloglu, H, Straub, V, Mizuno, M, Toda, T, Mitsuhashi, H, Yoshida, A, Takahashi, S, Talim, B, Herrmann, R, Takeuchi, M, Taniguchi, K

Dev. Cell 2001
Catalyst Activity

beta-1,3-galactosyl-O-glycosyl-glycoprotein beta-1,3-N-acetylglucosaminyltransferase activity of POMGNT1 mutants [Golgi membrane]

Normal reaction
Functional status

Loss of function of POMGNT1 mutants [Golgi membrane]

Cite Us!