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27 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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STT3A
STT3 oligosaccharyltransferase complex catalytic subunit A
Chromosome 11 · 11q24.2
NCBI Gene: 3703Ensembl: ENSG00000134910.15HGNC: HGNC:6172UniProt: P46977
170PubMed Papers
22Diseases
0Drugs
6Pathogenic Variants
FUNCTIONAL ROLE
Hub Gene
RESEARCH IMPACT
Trending
CLINICAL
OMIM Disease Gene
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
membraneoligosaccharyltransferase complexoligosaccharyltransferase complex Aprotein N-linked glycosylationcongenital disorder of glycosylation, type Iw, autosomal dominantSTT3A-congenital disorder of glycosylationdengue diseaseCOVID-19
✦AI Summary

STT3A is the catalytic subunit of the oligosaccharyltransferase complex (OST-A) that catalyzes the initial transfer of a defined glycan (Glc₃Man₉GlcNAc₂) from dolichol-pyrophosphate to asparagine residues within Asn-X-Ser/Thr motifs in nascent polypeptide chains during cotranslational protein N-glycosylation 1. STT3A contains the active site and substrate-binding pockets and associates with the Sec61 translocon complex at the endoplasmic reticulum membrane 2. While STT3A-containing OST-A complexes mediate cotranslational N-glycosylation of most sites, STT3A also prevents hyperglycosylation by restricting glycosylation of facultative sites before protein folding is complete, working alongside chaperones like HSP90B1 1. Beyond housekeeping functions, STT3A activity is regulated by specificity factors controlling cell surface receptor signaling and tissue development 1. Notably, STT3A mediates N-glycosylation of PD-L1, a key immune checkpoint ligand, through recruitment by signaling molecules, thereby promoting tumor immune evasion in multiple cancer contexts 3456. The catalytic site represents a druggable target, with inhibitors like NGI-1 showing promise for therapeutic development 7. Mutations in STT3A cause congenital disorders of glycosylation type 1W, demonstrating its essential role in human health 8.

Sources cited
1
STT3A catalyzes cotranslational N-glycosylation and prevents hyperglycosylation through regulation by ER chaperones and specificity factors
PMID: 39509507
2
Cryo-EM structure of OST-A shows STT3A contains active site and binds to other OST-A subunits including DC2
PMID: 31831667
3
STT3A catalytic site is druggable; NGI-1 inhibitor binds the active site and traps donor substrate
PMID: 38670073
4
STT3A recruits to PD-L1 to enhance N-glycosylation and stability in tumor immune evasion
PMID: 36376293
5
STT3A mediates PD-L1 N-glycosylation in cervical cancer; aberrant glycosylation leads to ER accumulation and degradation
PMID: 37658376
6
JAK1 phosphorylation of PD-L1 recruits STT3A to catalyze PD-L1 glycosylation and maintain stability
PMID: 31305264
7
GMPS enhances interaction between PD-L1 and STT3A, promoting PD-L1 glycosylation and tumor immune evasion in HCC
PMID: 39690246
8
STT3A deletion impairs protein expression and N-glycosylation broadly; mutations cause congenital disorder of glycosylation type 1W
PMID: 36139350
Disease Associationsⓘ22
congenital disorder of glycosylation, type Iw, autosomal dominantOpen Targets
0.75Strong
STT3A-congenital disorder of glycosylationOpen Targets
0.74Strong
dengue diseaseOpen Targets
0.51Moderate
COVID-19Open Targets
0.37Weak
Second degree atrioventricular blockOpen Targets
0.27Weak
actinic keratosisOpen Targets
0.24Weak
mouth neoplasmOpen Targets
0.22Weak
genetic disorderOpen Targets
0.19Weak
microcephalyOpen Targets
0.11Weak
neoplasmOpen Targets
0.08Suggestive
neurodegenerative diseaseOpen Targets
0.07Suggestive
hepatocellular carcinomaOpen Targets
0.07Suggestive
lung adenocarcinomaOpen Targets
0.06Suggestive
nasopharyngeal carcinomaOpen Targets
0.03Suggestive
follicular thyroid adenomaOpen Targets
0.03Suggestive
infectionOpen Targets
0.03Suggestive
follicular thyroid carcinomaOpen Targets
0.03Suggestive
breast cancerOpen Targets
0.03Suggestive
Zika virus infectious diseaseOpen Targets
0.02Suggestive
Flavivirus InfectionsOpen Targets
0.02Suggestive
Congenital disorder of glycosylation 1W, autosomal dominantUniProt
Congenital disorder of glycosylation 1W, autosomal recessiveUniProt
Pathogenic Variants6
NM_152713.5(STT3A):c.1213C>T (p.Arg405Cys)Pathogenic
Congenital disorder of glycosylation, type Iw, autosomal dominant|not provided
★★☆☆2025→ Residue 405
NM_152713.5(STT3A):c.1214G>A (p.Arg405His)Pathogenic
Congenital disorder of glycosylation, type Iw, autosomal dominant|STT3A-congenital disorder of glycosylation
★★☆☆2022→ Residue 405
NM_152713.5(STT3A):c.1877T>C (p.Val626Ala)Likely pathogenic
STT3A-congenital disorder of glycosylation|not provided
★☆☆☆2024→ Residue 626
NM_152713.5(STT3A):c.479G>A (p.Arg160Gln)Likely pathogenic
Congenital disorder of glycosylation, type Iw, autosomal dominant
★☆☆☆2022→ Residue 160
NM_152713.5(STT3A):c.1213C>A (p.Arg405Ser)Likely pathogenic
Congenital disorder of glycosylation, type Iw, autosomal dominant
★☆☆☆2022→ Residue 405
NM_152713.5(STT3A):c.251T>C (p.Ile84Thr)Likely pathogenic
Congenital disorder of glycosylation, type Iw, autosomal dominant
★☆☆☆→ Residue 84
View on ClinVar ↗
Related Genes
RPL12Protein interaction100%RPL27Protein interaction100%RPLP0Protein interaction100%RPL32Protein interaction100%RPL31Protein interaction100%RPL28Protein interaction100%
Tissue Expression6 tissues
Ovary
100%
Heart
91%
Liver
90%
Brain
84%
Lung
80%
Bone Marrow
58%
Gene Interaction Network
Click a node to explore
STT3ARPL12RPL27RPLP0RPL32RPL31RPL28
PROTEIN STRUCTURE
Preparing viewer…
PDB6S7O · 3.50 Å · EM
View on RCSB ↗
Constraintⓘ
LOEUFⓘ
0.51Moderately Constrained
pLIⓘ
0.90Intolerant
Observed/Expected LoF0.38 [0.28–0.51]
RankingsWhere STT3A stands among ~20K protein-coding genes
  • #2,610of 20,598
    Most Researched170 · top quartile
  • #3,321of 5,498
    Most Pathogenic Variants6
  • #3,104of 17,882
    Most Constrained (LOEUF)0.51 · top quartile
Genes detectedSTT3A
Sources retrieved27 papers
Response time—
📄 Sources
27▼
1
Regulated N-glycosylation controls chaperone function and receptor trafficking.
PMID: 39509507
Science · 2024
1.00
2
Positive selection CRISPR screens reveal a druggable pocket in an oligosaccharyltransferase required for inflammatory signaling to NF-κB.
PMID: 38670073
Cell · 2024
0.90
3
Shared host genetic landscape of respiratory viral infection.
PMID: 40372436
Proc Natl Acad Sci U S A · 2025
0.80
4
Promoting anti-tumor immunity by targeting TMUB1 to modulate PD-L1 polyubiquitination and glycosylation.
PMID: 36376293
Nat Commun · 2022
0.80
5
FAT4 overexpression promotes antitumor immunity by regulating the β-catenin/STT3/PD-L1 axis in cervical cancer.
PMID: 37658376
J Exp Clin Cancer Res · 2023
0.70