Defective B3GALT6 does not transfer Gal to the tetrasaccharide linker

Stable Identifier
R-HSA-4420365
Type
Reaction [transition]
Species
Homo sapiens
Compartment
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Beta-1,3-galactosyltransferase 6 (B3GALT6) normally transfers a second galactose to the tetrasaccharide linker, an initiator sequence required for the biosynthesis of chondroitin sulfate, dermatan sulfate and heparans. Defects in B3GALT6 cause Ehlers-Danlos syndrome progeroid type 2 (EDSP2; MIM:615349), resulting in a broad range of skeletal and connective tissue disorders characterised by loose skin, spinal deformaty, muscle hypotonia, impaired wound healing and joint dislocation (Okajima et al. 1999, Nakajima et al. 2013, Malfait et al. 2013). Defects in B3GALT6 can also cause spondyloepimetaphyseal dysplasia with joint laxity type 1 (SEMDJL1; MIM:271640), characterised by spinal deformaty and lax joints, especially of the hands and respiratory compromise resulting in early death (Nakajima et al. 2013, Malfait et al. 2013). Mutations causing EDSP2 include S309T and R6W and the frameshift mutations R197Afs*81 and D118Afs*160 (Nakajima et al. 2013, Malfait et al. 2013). Mutations causing SEMDJL1 include M1?, R232C, D156N, C300S, S56G, P67L, D207H and G217S (Nakajima et al. 2013, Malfait et al. 2013).

Literature References
PubMed ID Title Journal Year
23664118 Defective Initiation of Glycosaminoglycan Synthesis due to B3GALT6 Mutations Causes a Pleiotropic Ehlers-Danlos Syndrome-like Connective Tissue Disorder

Malfait, F, Kariminejad, A, Van Damme, T, Gauche, C, Syx, D, Merhi-Soussi, F, Gulberti, S, Symoens, S, Vanhauwaert, S, Willaert, A, Bozorgmehr, B, Kariminejad, MH, Ebrahimiadib, N, Hausser, I, Huysseune, A, Fournel-Gigleux, S, De Paepe, A

Am. J. Hum. Genet. 2013
10506123 Molecular basis for the progeroid variant of Ehlers-Danlos syndrome. Identification and characterization of two mutations in galactosyltransferase I gene

Okajima, T, Fukumoto, S, Furukawa, K, Urano, T

J Biol Chem 1999
23664117 Mutations in B3GALT6, which Encodes a Glycosaminoglycan Linker Region Enzyme, Cause a Spectrum of Skeletal and Connective Tissue Disorders

Nakajima, M, Mizumoto, S, Miyake, N, Kogawa, R, Iida, A, Ito, H, Kitoh, H, Hirayama, A, Mitsubuchi, H, Miyazaki, O, Kosaki, R, Horikawa, R, Lai, A, Mendoza-Londono, R, Dupuis, L, Chitayat, D, Howard, A, Leal, GF, Cavalcanti, D, Tsurusaki, Y, Saitsu, H, Watanabe, S, Lausch, E, Unger, S, Bonafe, L, Ohashi, H, Superti-Furga, A, Matsumoto, N, Sugahara, K, Nishimura, G, Ikegawa, S

Am. J. Hum. Genet. 2013
Participants
Participant Of
Catalyst Activity
Catalyst Activity
Title
galactosylxylosylprotein 3-beta-galactosyltransferase activity of B3GALT6 mutants [Golgi membrane]
Physical Entity
Activity
Normal reaction
Disease
Name Identifier Synonyms
spondyloepimetaphyseal dysplasia 0080027
Ehlers-Danlos syndrome 13359 Cutis hyperelastica, elastic skin
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