DDOST: Dolichyl-Diphosphooligosaccharide–Protein Glycosyltransferase Subunit
A key component of the oligosaccharyltransferase complex involved in N-linked glycosylation
Gene Information Card
| Symbol | DDOST |
|---|---|
| Full Name | Dolichyl-diphosphooligosaccharide–protein glycosyltransferase subunit (non-catalytic) |
| Gene Type | protein-coding |
| Chromosomal Location | 1p36.13 |
| NCBI Gene ID | 1650 ncbi.nlm.nih.gov/gene/1650 |
| Ensembl ID | ENSG00000117569 |
| UniProt ID | P39656 |
| OMIM ID | 602202 |
| HGNC ID | 2728 |
| Aliases | OST48, WBP1, CDG1R |
Description
DDOST encodes the non-catalytic subunit of the oligosaccharyltransferase (OST) complex, which catalyzes the transfer of a high-mannose oligosaccharide from dolichol to asparagine residues of nascent polypeptides in the endoplasmic reticulum. This step is essential for proper N-linked glycosylation of proteins. Mutations in DDOST cause congenital disorder of glycosylation type I (CDG-I) with multisystem involvement.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Congenital disorder of glycosylation type I (CDG1R) | Loss-of-function mutations impair N-glycosylation, leading to misfolded proteins and ER stress | OMIM #602202; ClinVar pathogenic variants |
| Colorectal cancer | DDOST overexpression correlates with poor prognosis; altered glycosylation promotes metastasis | COSMIC; PMID: 31289453 |
| Hepatocellular carcinoma | Upregulation of DDOST associated with aggressive tumor phenotype | COSMIC; PMID: 29891937 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Liver | 18.5 | High |
| Pancreas | 15.2 | High |
| Kidney | 12.8 | Medium |
| Brain | 8.3 | Medium |
| Heart | 6.1 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HepG2 | 22.1 | Hepatocellular carcinoma cell line |
| HeLa | 14.7 | Cervical adenocarcinoma |
| A549 | 11.3 | Lung carcinoma |
| K562 | 9.5 | Chronic myeloid leukemia |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1075C>T (p.Arg359Trp) | Missense | <0.01% | Loss of function; causes CDG1R |
| c.1A>G (p.Met1Val) | Start loss | <0.01% | Loss of function; causes CDG1R |
| c.1265G>A (p.Arg422Gln) | Missense | 0.02% | Likely benign; ClinVar |
| c.1483C>T (p.Arg495Cys) | Missense | <0.01% | Uncertain significance |
Mutation functional classification
Loss of Function (LOF)
Pathogenic missense and start-loss mutations impair OST complex assembly or catalytic efficiency, leading to CDG type I.
Gain of Function (GOF)
Not reported in DDOST.
Dominant Negative (DN)
Not reported; CDG1R is autosomal recessive.
View complete mutation data：
Gene Ontology (GO)
| • oligosaccharyl transferase activity (GO:0004576) | • protein N-linked glycosylation (GO:0006487) |
| • endoplasmic reticulum membrane (GO:0005789) | • integral component of membrane (GO:0016021) |
| • oligosaccharyltransferase complex (GO:0008250) |
Pathways
• N-glycan biosynthesis (Reactome R-HSA-446203)
• Asparagine N-linked glycosylation (Reactome R-HSA-446203)
• Protein processing in endoplasmic reticulum (KEGG hsa04141)
Protein Summary
DDOST (OST48) is a 48 kDa transmembrane protein localized to the endoplasmic reticulum membrane. It is a non-catalytic subunit of the OST complex, which is essential for the first step of N-linked glycosylation. The protein contains a luminal domain that interacts with the catalytic subunit STT3A/STT3B and stabilizes the complex. Loss of DDOST function disrupts glycosylation of multiple proteins, leading to multisystem disease.
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