Defective GALNT3 causes familial hyperphosphatemic tumoral calcinosis (HFTC)

Stable Identifier
Homo sapiens
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The family of UDP GalNAc:polypeptide N acetylgalactosaminyltransferases (GalNAc transferases, GALNTs) carry out the addition of N acetylgalactosamine (GalNAc) on serine, threonine or possibly tyrosine residues on a wide variety of proteins, most commonly associated with mucins. This is the initial reaction in the biosynthesis of GalNAc-type O linked oligosaccharides (Wandall et al. 1997). This reaction takes place in the Golgi apparatus (Rottger et al. 1998). There are 20 known members of the GALNT family, 15 of which have been characterised and 5 candidate members which are thought to belong to this family based on sequence similarity (Bennett et al. 2012). The GALNT-family is classified as belonging to CAZy family GT27. Defects in one of the GALNT family genes, GALNT3 (MIM:601756), can cause familial hyperphosphatemic tumoral calcinosis (HFTC; MIM:211900). HFTC is a rare autosomal recessive severe metabolic disorder characterised by the progressive deposition of calcium phosphate crystals in the skin, soft tissues and sometimes bone (Chefetz et al. 2005). The biochemical observation is hyperphosphatemia, caused by increased renal absorption of phosphate (Chefetz et al. 2005, Ichikawa et al. 2005). Some patients manifest recurrent, transient, painful swellings of the long bones with radiological evidence of periosteal reaction and cortical hyperostosis (Frishberg et al. 2005).

Literature References
PubMed ID Title Journal Year
9394011 Localization of three human polypeptide GalNAc-transferases in HeLa cells suggests initiation of O-linked glycosylation throughout the Golgi apparatus

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

J Cell Sci 1998
22183981 Control of mucin-type O-glycosylation: a classification of the polypeptide GalNAc-transferase gene family

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

Glycobiology 2012
16151858 A novel homozygous missense mutation in FGF23 causes Familial Tumoral Calcinosis associated with disseminated visceral calcification

Chefetz, I, Heller, R, Galli-Tsinopoulou, A, Richard, G, Wollnik, B, Indelman, M, Koerber, F, Topaz, O, Bergman, R, Sprecher, E, Schoenau, E

Hum. Genet. 2005
9295285 Substrate specificities of three members of the human UDP-N-acetyl-alpha-D-galactosamine:Polypeptide N-acetylgalactosaminyltransferase family, GalNAc-T1, -T2, and -T3

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

J Biol Chem 1997
15687324 A novel GALNT3 mutation in a pseudoautosomal dominant form of tumoral calcinosis: evidence that the disorder is autosomal recessive

Ichikawa, S, Lyles, KW, Econs, MJ

J. Clin. Endocrinol. Metab. 2005
15599692 Identification of a recurrent mutation in GALNT3 demonstrates that hyperostosis-hyperphosphatemia syndrome and familial tumoral calcinosis are allelic disorders

Frishberg, Y, Topaz, O, Bergman, R, Behar, D, Fisher, D, Gordon, D, Richard, G, Sprecher, E

J. Mol. Med. 2005
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Name Identifier Synonyms
hyperphosphatemia 0050459