Glycosylation and related congenital defects (WP4521)

Homo sapiens

Glycosylation is the most common postranslational modification. Defects in this pathway lead to autosomal recessive disorders, called congenital disorders of glycosylation (CDG). Up to date about 50 CDGs have been identified and more are expected to be discovered. This category of metabolic disorders can be divided into four basic groups depending on where the glycosylation process occurs on the molecule. The depicts pathway depicts the group of N-glycosylation. Generally, N-glycosylation processes spread over three cellular compartments - cytosol, endoplasmic reticulum and Golgi apparatus. The associated mortality rate in combination with the limited treatment options for CDG, points out the relevance for further investigations of this pathway. Disorders resulting from an enzyme defect are highlighted in pink. This pathway was inspired by Chapter 30 of the book of Blau (ISBN 3642403360 (978-3642403361)).


Eveline Schoenmaker , Denise Slenter , Britt Pieters , Lauren J. Dupuis , Irene Hemel , Egon Willighagen , Friederike Ehrhart , Finterly Hu , and Eric Weitz


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Homo sapiens


Inherited Metabolic Disorders (IMD) Pathways Rare Diseases


Pathway Ontology

altered carbohydrate metabolic pathway N-acetylglucosamine, N-acetylmannosamine and N-acetylneuraminic acid dissimilation pathway disease pathway

Disease Ontology

autosomal recessive disease inherited metabolic disorder congenital disorder of glycosylation


Label Type Compact URI Comment
dolichyl phosphate Metabolite chebi:57683
UDP Metabolite chebi:58223
beta-D-glucose Metabolite chebi:15903
UDP-N-acetylalpha-D-glucosamine Metabolite chebi:57705
GlcNAc-PP-Dol Metabolite chebi:58427 In RHEA: N-acetyl-α-D-glucosaminyl-diphosphodolichol
dolichyl beta-D-mannosyl phosphate Metabolite chebi:58211
Dolichyl phosphate Metabolite chebi:57683
GDP Metabolite chebi:58189
Man5-GlcNac2-PP-Dol Metabolite chebi:132516
Man8-GlcNac2-PP-Dol Metabolite chebi:132519
Man7-GlcNac2-PP-Dol Metabolite chebi:132517
Man9-GlcNac2-PP-Dol Metabolite chebi:132520
Glc2Man9-GlcNac2-PP-Dol Metabolite chebi:132522
GlcMan9-GlcNac2-PP-Dol Metabolite chebi:132521
Glc2Man9-GlcNac2-Prot Metabolite chebi:59082
Glc3Man9-GlcNac2-Prot Metabolite chebi:132537
Man3-GlcNac4-Prot Metabolite chebi:60615
Man3-GlcNac3-Prot Metabolite chebi:60615
GDP-mannose Metabolite chebi:57527
Dol-P-Man Metabolite chebi:58211
Mannose 6-phosphate Metabolite chebi:58735
Mannose 1-phosphate Metabolite chebi:58409
Fructose 6-phosphate Metabolite chebi:61527
Man5GIcNAc2-PP-Dol Metabolite chebi:132515
Dolichol phosphate Metabolite chebi:57683 In RHEA stated as dolichyl phosphate, and in this reaction it results in a -2 charge.
Dolichol-PP Metabolite chebi:15750 In CheBi known as Dolichol diphosphate
Man3GIcNAc2-PP-Dol Metabolite chebi:132511
Dolichol Metabolite chebi:16091 Full name in RHEA: di-trans,poly-cis-dolichol
Polyprenol Metabolite chebi:67132 In RHEA and UniProt known as di-trans,cis-polyprenol.
Man2GIcNAc2PP-Dol Metabolite chebi:132510
Mevalonate Metabolite chebi:17710
ManGlcNAc2-PP-Dol Metabolite chebi:58472
GlcNAc2-PP-Dol Metabolite chebi:57269 Aka N-acetylglucosamine
dolichyl phosphate Metabolite chebi:57683
dolichyl beta-D-mannosyl phosphate Metabolite chebi:58211
DOLK Protein uniprot:Q9UPQ8 Dolichol kinase, Book label: 30.38
ALG13 Protein uniprot:Q9NP73 Labelled in UniProt as Putative bifunctional UDP-N-acetylglucosamine transferase and deubiquitinase ALG13.
Found manually through RHEA identifier. This enzyme was not indicated in the Blau Book, but it catalyzes this exact reaction.
DPAGT1 Protein uniprot:Q9H3H5 In UniProt described as UDP-N-acetylglucosamine--dolichyl-phosphate N-acetylglucosaminephosphotransferase.
Found manually through RHEA identifier reaction. Not indicated in the Blau Book Chapter 30.
GMPPB Protein uniprot:Q9Y5P6 AKA mannose-1-phosphate guanylyltransferase []
B4GALT1 Protein uniprot:P15291 AKA B4GALT1; beta-1,4-galactosyltransferase 1; book label: 30.34
DPM2 Protein uniprot:O94777
MGAT2 Protein uniprot:Q10469 AKA MGAT2; N-acetylglucosaminyltransferase 2; book label: 30.13
Function'Plays an essential role in protein N-glycosylation. Catalyzes the transfer of N-acetylglucosamine (GlcNAc) onto the free terminal mannose moiety in the core structure of the nascent N-linked glycan chain, giving rise to the second branch in complex glycans.' []
MOGS Protein uniprot:Q13724 AKA GCS1; Glucosidase 1; book label: 30.14
Function:'Cleaves the distal alpha 1,2-linked glucose residue from the Glc3Man9GlcNAc2 oligosaccharide precursor in a highly specific manner.' []
TUSC3 Protein uniprot:Q13454 AKA TUSC3; oligosaccharyltransferase subunit tusc 3; book label: 30.15
30.16 Protein uniprot:Q9H0U3 Aka MAGT1; magnesium transporter 1
ALG8 Protein uniprot:Q9BVK2 AKA ALG8; Glucosyltransferase 2; book label: 30.6
ALG6 Protein uniprot:Q9Y672 Aka ALG6; glucosyltransferase 1; book label: 30.3
ALG9 Protein uniprot:Q9H6U8 book label: 30.10
ALG12 Protein uniprot:Q9BV10 AKA ALG12, Mannosyltransferase 8; book label: 30.5
ALG9 Protein uniprot:Q9H6U8 Aka ;mannosyltransferase 7-9; Book label: 30.10
MPDU1 Protein uniprot:O75352 AKA MPDU1; Dol-P-Man utilization 1; Book label: 30.33
ALG3 Protein uniprot:Q92685 AKA ALG3, mannosyltransferase 6; Book label: 30.4
Function:'Adds the first Dol-P-Man derived mannose in an alpha-1,3 linkage to Man5GlcNAc2-PP-Dol' []
MPI Protein uniprot:P34949 AKA MPI, phosphomannose isomerase; Book label: 30.2
PMM2 Protein uniprot:O15305 AKA PMM, phosphomannomutase 2; book label: 30.1
DPM1 Protein uniprot:O60762 AKA DPM1, GDP-Man:Dol-P mannosyltransferase subunit 1; book label: 30.31
DPM3 Protein uniprot:Q9P2X0 AKA DPM3, GDP-Man:Dol-P mannosyltransferase 3; book label: 30.32
'Stabilizer subunit of the dolichol-phosphate mannose (DPM) synthase complex; tethers catalytic subunit DPM1 to the ER' []
SRD5A3 Protein uniprot:Q9H8P0 Known as polyprenol reductase, which catalyzes reduction of the alpha-isoprene subunit of polyprenol. But also known to have steroid dehydrogenase activity. Book label:30.39
ALG1 Protein uniprot:Q9BT22 Chitobiosyldiphosphodolichol beta-mannosyltransferase mediates the hexosyl group transfer.
In Blau Book known as Mannosyltransferase 1, label: 30.9
DPAGT1 Protein uniprot:Q9H3H5 Also known as UDP-N-acetylglucosamine-dolichyl-phosphate N-acetylglucosaminephosphotransferase, which transfers the hexosyl group. Book label: 30.8
ALG11 Protein uniprot:Q2TAA5 GDP-Man:Man(3)GlcNAc(2)-PP- Dol alpha-1,2-mannosyltransferase; Book label: 30.11
ALG2 Protein uniprot:Q9H553 Alpha-1,3/1,6- mannosyltransferase ALG2; Book label: 30.7
ALG14 Protein ncbigene:199857 ALG14


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