Defective LFNG causes SCDO3

Stable Identifier
R-HSA-5083630
Type
Pathway
Species
Homo sapiens
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The Fringe family (CAZy family GT31) of glycosyltransferases in mammals includes LFNG (lunatic fringe; MIM:602576), MFNG (manic fringe; MIM:602577) and RFNG (radical fringe; MIM:602578). Fringe enzymes function in the Golgi apparatus where they initiate the elongation of O-linked fucose on fucosylated peptides by the addition of a beta 1,3 N-acetylglucosaminyl group (GlcNAc) (Moloney et al. 2000). Fringe enzymes elongate conserved O fucosyl residues conjugated to EGF repeats of NOTCH, modulating NOTCH activity (Cohen et al. 1997, Johnston et al. 1997) by decreasing the affinity of NOTCH extracellular domain for JAG ligands (Bruckner et al. 2000).

The spondylocostal dysostoses (SCDs) are a group of disorders that arise during embryonic development by a disruption of somitogenesis. The Notch signalling pathway is essential for somitogenesis, the precursors of vertebra and associated musculature. Defects in one of the Fringe enzymes, beta-1,3-N-acetylglucosaminyltransferase lunatic fringe (LFNG), can cause spondylocostal dysostosis, autosomal recessive 3 (SCDO3, MIM:609813), a condition of variable severity associated with vertebral and rib segmentation defects (Sparrow et al. 2006).

Literature References
PubMed ID Title Journal Year
10935637 Glycosyltransferase activity of Fringe modulates Notch-Delta interactions

Br├╝ckner, K, Perez, L, Clausen, H, Cohen, S

Nature 2000
16385447 Mutation of the LUNATIC FRINGE gene in humans causes spondylocostal dysostosis with a severe vertebral phenotype

Sparrow, DB, Chapman, G, Wouters, MA, Whittock, NV, Ellard, S, Fatkin, D, Turnpenny, PD, Kusumi, K, Sillence, D, Dunwoodie, SL

Am. J. Hum. Genet. 2006
9207795 Fringe boundaries coincide with Notch-dependent patterning centres in mammals and alter Notch-dependent development in Drosophila

Cohen, B, Bashirullah, A, Dagnino, L, Campbell, C, Fisher, WW, Leow, CC, Whiting, E, Ryan, D, Zinyk, D, Boulianne, G, Hui, CC, Gallie, B, Phillips, RA, Lipshitz, HD, Egan, SE

Nat Genet 1997
9187150 A family of mammalian Fringe genes implicated in boundary determination and the Notch pathway

Johnston, SH, Rauskolb, C, Wilson, R, Prabhakaran, B, Irvine, KD, Vogt, TF

Development 1997
Participants
Participant Of
Disease
Name Identifier Synonyms
spondylocostal dysostosis 0050568 SPONDYLOTHORACIC DYSPLASIA, JARCHO-LEVIN SYNDROME, SPONDYLOTHORACIC DYSOSTOSIS
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