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Literature summary for 2.4.1.134 extracted from

  • 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, M.H.; Ebrahimiadib, N.; Hausser, I.; Huysseune, A.; Fournel-Gigleux, S.; De Paepe, A.
    Defective initiation of glycosaminoglycan synthesis due to B3GALT6 mutations causes a pleiotropic Ehlers-Danlos-Syndrome-like connective tissue disorder (2013), Am. J. Hum. Genet., 92, 935-945.
    View publication on PubMedView publication on EuropePMC

Cloned(Commentary)

Cloned (Comment) Organism
gene B3GALT6, homozygosity mapping and candidate gene sequence analysis in three independent families, genotyping Homo sapiens

Protein Variants

Protein Variants Comment Organism
A108G naturally occuring enzyme mutation Homo sapiens
D207H naturally occuring enzyme mutation Homo sapiens
G217S naturally occuring enzyme mutation Homo sapiens
additional information homozygosity mapping and candidate gene sequence analysis in three independent families identified biallelic gene B3GALT6 mutations, including homozygous missense mutations in family 1 (c.619G>C [p.Asp207His]) and family 3 (c.649G>A [p.Gly217Ser]) and compound heterozygous mutations in family 2 (c.323_344del [p.Ala108Glyfs*163], c.619G>C [p.Asp207His]), phenotypes overview Homo sapiens

Localization

Localization Comment Organism GeneOntology No. Textmining
Golgi apparatus
-
Homo sapiens 5794
-

Natural Substrates/ Products (Substrates)

Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
UDP-alpha-D-galactose + 4-beta-D-galactosyl-O-beta-D-xylosyl-[protein] Homo sapiens
-
UDP + 3-beta-D-galactosyl-4-beta-D-galactosyl-O-beta-D-xylosyl-[protein]
-
?

Organism

Organism UniProt Comment Textmining
Homo sapiens Q96L58
-
-
Homo sapiens Q96L58 gene B3GALT6
-

Source Tissue

Source Tissue Comment Organism Textmining
fibroblast
-
Homo sapiens
-
skin
-
Homo sapiens
-

Substrates and Products (Substrate)

Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
UDP-alpha-D-galactose + 4-beta-D-galactosyl-O-beta-D-xylosyl-[protein]
-
Homo sapiens UDP + 3-beta-D-galactosyl-4-beta-D-galactosyl-O-beta-D-xylosyl-[protein]
-
?
UDP-alpha-D-galactose + 4-methylumbelliferyl-beta-D-xylopyranoside
-
Homo sapiens UDP + ?
-
?

Synonyms

Synonyms Comment Organism
B3GALT6
-
Homo sapiens
beta3GalT6
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Homo sapiens
galactosyltransferase II
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Homo sapiens

General Information

General Information Comment Organism
malfunction enzyme deficiency alters synthesis of both main types of glycosaminoglycans and results in impaired wound repair in vivo with abnormal dermal collagen fibril architecture characterized by loosely packed collagen fibrils of variable size and shape Homo sapiens
malfunction loss of function of gene b3GalT6 causes a severe deficiency in glycosaminoglycan synthesis and results in the production of immature decorin, lacking its chondroitin sulfate/dermatan sulfate side chain, as well as reduced-to-absent heparan sulfate chains in dermal fibroblasts of affected individuals. Homozygosity mapping and candidate gene sequence analysis in three independent families identified biallelic gene B3GALT6 mutations, including homozygous missense, the families present a severe autosomal-recessive connective tissue disorder characterized by skin fragility, delayed wound healing, joint hyperlaxity and contractures, muscle hypotonia, intellectual disability, and a spondyloepimetaphyseal dysplasia with bone fragility and severe kyphoscoliosis. The phenotype overlaps with several recessive Ehlers-Danlos variants and spondyloepimetaphyseal dysplasia with joint hyperlaxity. Affected individuals' fibroblasts exhibit a large decrease in ability to prime glycosaminoglycan synthesis together with impaired glycanation of the small chondroitin/dermatan sulfate proteoglycan decorin, confirming b3GalT6 loss of function. Dermal electron microcopy discloses abnormalities in collagen fibril organization, in line with the important regulatory role of decorin in this process. A strong reduction in heparan sulfate level is also observed, indicating that enzyme b3GalT6 deficiency alters synthesis of both main types of glycosaminoglycans. In vitro wound healing assay reveals a significant delay in fibroblasts from two index individuals, pointing to a role for glycosaminoglycan defect in impaired wound repair in vivo. Genotype-Phenotype-analysis, overview Homo sapiens
metabolism the enzyme catalyzes a step in glycosaminoglycan synthesis, pathway overview Homo sapiens
physiological function proteoglycans are important components of cell plasma membranes and extracellular matrices of connective tissues. They consist of glycosaminoglycan chains attached to a core protein via a tetrasaccharide linkage, whereby addition of the third residue is catalyzed by galactosyltransferase II, encoded by gene B3GALT6. A crucial role for b3GalT6 in multiple major developmental and pathophysiological processes Homo sapiens