Defective GALNT12 does not transfer GalNAc to mucins

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
The family of UDP-GalNAc:polypeptide N-acetylgalactosaminyltransferases (GalNAc-transferases, GALNTs) carry out the addition of N-acetylgalactosamine (GalNAc) on serine or threonine residues of proteins, especially mucins. This is the initial reaction in the formation of O-linked oligosaccharide biosynthesis (Guo et al. 2002). Defects in one of the GALNT family, GALNT12, can result in decreased glycosylation of mucins, mainly expressed in the digestive organs such as the stomach, small intestine and colon, and may play a role in colorectal cancer 1 (CRCS1; MIM:608812). CRCS1 is a complex disease characterised by malignant lesions arising from the inner walls of the colon and rectum. Mutations implicated in CRCS1 are M1I, T491M, Y395* (Guda et al. 2009), D303N and Y396C (Clarke et al. 2012).
Literature References
PubMed ID Title Journal Year
22183981 Control of mucin-type O-glycosylation: a classification of the polypeptide GalNAc-transferase gene family

Fritz, TA, Mandel, U, Bennett, EP, Tabak, LA, Gerken, TA, Clausen, H

Glycobiology 2012
9394011 Localization of three human polypeptide GalNAc-transferases in HeLa cells suggests initiation of O-linked glycosylation throughout the Golgi apparatus

Whitehouse, C, White, J, Bennett, EP, Olivo, JC, Röttger, S, Berger, EG, Nilsson, T, Stark, A, Wandall, HH, Clausen, H

J Cell Sci 1998
22461326 Inherited deleterious variants in GALNT12 are associated with CRC susceptibility

Parfrey, PS, Younghusband, HB, Clarke, E, Mahoney, K, Green, RC, Green, JS, Woods, MO

Hum. Mutat. 2012
19617566 Inactivating germ-line and somatic mutations in polypeptide N-acetylgalactosaminyltransferase 12 in human colon cancers

Papadopoulos, N, Lowe, JB, Lawrence, E, Wiesner, GL, Willis, J, Moinova, H, Dawson, DW, Ravi, L, Jamison, O, Lewis, S, Lutterbaugh, J, Markowitz, SD, Gerken, TA, Barnholtz-Sloan, J, Kinzler, KW, Vogelstein, B, Natale, L, He, J, Velculescu, VE, Willson, JK, Parmigiani, G, Guda, K

Proc. Natl. Acad. Sci. U.S.A. 2009
9295285 Substrate specificities of three members of the human UDP-N-acetyl-alpha-D-galactosamine:Polypeptide N-acetylgalactosaminyltransferase family, GalNAc-T1, -T2, and -T3

Burchell, J, Bennett, EP, Hassan, H, Taylor-Papadimitriou, J, Roepstorff, P, Hollingsworth, MA, Kristensen, AK, Nielsen, PA, Mirgorodskaya, E, Wandall, HH, Clausen, H

J Biol Chem 1997
Catalyst Activity

polypeptide N-acetylgalactosaminyltransferase activity of GALNT12 mutants [Golgi membrane]

Normal reaction
Functional status

Loss of function of GALNT12 mutants [Golgi membrane]

Name Identifier Synonyms
colorectal cancer DOID:9256
Cite Us!