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GeneE
25 sources retrieved Β· Most recent: April 2026 Β· Index updated 14 days ago
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DDOST
dolichyl-diphosphooligosaccharide--protein glycosyltransferase non-catalytic subunit
Chromosome 1 Β· 1p36.12
NCBI Gene: 1650Ensembl: ENSG00000244038.11HGNC: HGNC:2728UniProt: P39656
218PubMed Papers
21Diseases
0Drugs
3Pathogenic Variants
RESEARCH IMPACT
Trending
CLINICAL
OMIM Disease Gene
DATA QUALITY
βœ“ Experimental GO Evidenceβœ“ Swiss-Prot Reviewed
intracellular membrane-bounded organelleoligosaccharyltransferase complex Aoligosaccharyltransferase complex Boligosaccharyltransferase complexDDOST-congenital disorder of glycosylationneurodegenerative diseasedengue diseasecongenital disorder of glycosylation
✦AI Summary

DDOST (dolichyl-diphosphooligosaccharide-protein glycosyltransferase non-catalytic subunit) is a critical non-catalytic component of the oligosaccharyltransferase (OST) complex that catalyzes N-linked protein glycosylation in the endoplasmic reticulum 1. As part of the OST complex, DDOST facilitates the cotranslational transfer of a defined N-glycan to asparagine residues within nascent polypeptide chains, a fundamental posttranslational modification required for proper protein folding and function 2. All OST subunits, including DDOST, are essential for maximal enzymatic activity and assembly of functional glycosylation complexes 3. DDOST dysregulation contributes to multiple disease pathologies. Biallelic DDOST mutations cause DDOST-congenital disorder of glycosylation (DDOST-CDG), characterized by developmental delay, failure to thrive, and abnormal transferrin glycosylation patterns 4. In cancer, DDOST is frequently upregulated and promotes oncogenic pathways. In pancreatic cancer, DDOST knockdown increases endoplasmic reticulum stress, oxidative stress, and apoptosis 1. In hepatocellular carcinoma, DDOST maintains EGFR glycosylation and downstream signaling; targeting DDOST sensitizes tumors to lenvatinib and immunotherapy 5. In colorectal cancer, DDOST regulates CTSD N-glycosylation, affecting ferroptosis-related pathways and metastasis 6. DDOST overexpression in gliomas correlates with poor prognosis and immunosuppressive microenvironments 7. These findings establish DDOST as both a disease biomarker and potential therapeutic target.

Sources cited
1
DDOST is a key component of the oligosaccharyltransferase complex catalyzing N-linked glycosylation in the ER; its knockdown induces ER stress, ROS formation, and apoptosis in pancreatic cancer
PMID: 39223141
2
DDOST and other N-glycosylation-related proteins are upregulated in brain capillaries of Alzheimer's disease patients
PMID: 35766008
3
DDOST is an important subunit of N-glycosylated oligosaccharyltransferase closely related to protein N-glycosylation and associated with congenital disorders and solid tumors
PMID: 40601285
4
DDOST-CDG caused by biallelic variants presents with developmental delay, abnormal transferrin glycosylation, and type I CDG pattern
PMID: 36214423
5
DDOST is upregulated in HCC; its depletion impairs EGFR N-glycosylation and sensitizes cells to lenvatinib and immunotherapy
PMID: 41413687
6
DDOST regulates N-glycosylation modification of CTSD, affecting ferroptosis-related proteins and colorectal cancer liver metastasis
PMID: 39716927
7
DDOST is overexpressed in high-grade gliomas and correlates with poor prognosis and immunosuppressive tumor microenvironment
PMID: 35812432
Disease Associationsβ“˜21
DDOST-congenital disorder of glycosylationOpen Targets
0.74Strong
neurodegenerative diseaseOpen Targets
0.54Moderate
dengue diseaseOpen Targets
0.50Moderate
congenital disorder of glycosylationOpen Targets
0.42Moderate
COVID-19Open Targets
0.37Weak
lysosomal storage diseaseOpen Targets
0.37Weak
ocular hypertensionOpen Targets
0.33Weak
Intellectual disabilityOpen Targets
0.12Weak
leprosyOpen Targets
0.11Weak
hepatocellular carcinomaOpen Targets
0.09Suggestive
cervical cancerOpen Targets
0.07Suggestive
Alzheimer diseaseOpen Targets
0.06Suggestive
neoplasmOpen Targets
0.06Suggestive
hemoglobin D diseaseOpen Targets
0.05Suggestive
dominant beta-thalassemiaOpen Targets
0.05Suggestive
infectionOpen Targets
0.05Suggestive
Hemoglobin C - beta-thalassemiaOpen Targets
0.05Suggestive
hemoglobin C-beta-thalassemia syndromeOpen Targets
0.05Suggestive
hemoglobin H diseaseOpen Targets
0.05Suggestive
hereditary persistence of fetal hemoglobin-sickle cell disease syndromeOpen Targets
0.05Suggestive
Congenital disorder of glycosylation 1RUniProt
Pathogenic Variants3
NM_005216.5(DDOST):c.645G>C (p.Gln215His)Pathogenic
Congenital disorder of glycosylation type Ir
β˜…β˜…β˜†β˜†2024β†’ Residue 215
NM_005216.5(DDOST):c.1214_1235del (p.Ile405fs)Pathogenic
Congenital disorder of glycosylation type Ir|not provided
β˜…β˜†β˜†β˜†2014β†’ Residue 405
NM_005216.5(DDOST):c.599G>A (p.Gly200Asp)Pathogenic
Congenital disorder of glycosylation type Ir|not provided
β˜…β˜†β˜†β˜†2014β†’ Residue 200
View on ClinVar β†—
Related Genes
CANXProtein interaction100%EMC1Protein interaction100%SEC61GProtein interaction100%SEC61A1Protein interaction100%SEC61A2Protein interaction100%SSR2Protein interaction100%
Tissue Expression6 tissues
Bone Marrow
100%
Heart
88%
Ovary
83%
Lung
76%
Liver
69%
Brain
37%
Gene Interaction Network
Click a node to explore
DDOSTCANXEMC1SEC61GSEC61A1SEC61A2SSR2
PROTEIN STRUCTURE
Preparing viewer…
PDB6S7O Β· 3.50 Γ… Β· EM
View on RCSB β†—
Constraintβ“˜
LOEUFβ“˜
0.75LoF Tolerant
pLIβ“˜
0.00Tolerant
Observed/Expected LoF0.53 [0.38–0.75]
RankingsWhere DDOST stands among ~20K protein-coding genes
  • #1,893of 20,598
    Most Researched218 Β· top 10%
  • #3,929of 5,498
    Most Pathogenic Variants3
  • #5,894of 17,882
    Most Constrained (LOEUF)0.75
Genes detectedDDOST
Sources retrieved25 papers
Response timeβ€”
πŸ“„ Sources
25β–Ό
1
N-glycosylation Modification of CTSD Affects Liver Metastases in Colorectal Cancer.
PMID: 39716927
Adv Sci (Weinh) Β· 2025
1.00
2
Induction of oxidative- and endoplasmic-reticulum-stress dependent apoptosis in pancreatic cancer cell lines by DDOST knockdown.
PMID: 39223141
Sci Rep Β· 2024
0.90
3
Sex- and age-dependent genetics of longevity in a heterogeneous mouse population.
PMID: 36173858
Science Β· 2022
0.80
4
Upregulation of ribosome complexes at the blood-brain barrier in Alzheimer's disease patients.
PMID: 35766008
J Cereb Blood Flow Metab Β· 2022
0.70
5
Macrophage-derived exosome miR-146a-5p modulates PNKP/DDOST/JAGN1 complex to regulate NETs formation in atherosclerosis.
PMID: 41109654
Cell Signal Β· 2025
0.68