STT3A

Chr 11ADAR

STT3 oligosaccharyltransferase complex catalytic subunit A

Also known as: CDG1WAD, CDG1WAR, ITM1, STT3-A, TMC

NCBI Gene: 3703ENSG00000134910UniProt: P46977OMIM: 601134

The protein is a catalytic subunit of the oligosaccharyl transferase complex that transfers glycan chains to asparagine residues during protein N-glycosylation in the endoplasmic reticulum, a critical step in protein processing. Mutations cause congenital disorder of glycosylation type Iw with both autosomal dominant and autosomal recessive inheritance patterns. The gene is highly constrained against loss-of-function variants (LOEUF 0.488), reflecting its essential role in cellular protein modification.

GeneReviewsOMIMResearchSummary from RefSeq, OMIM, UniProt
DNmechanismAD/ARLOEUF 0.492 OMIM phenotypes
Clinical Summary— STT3A
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Gene-Disease Validity (ClinGen)
STT3A-congenital disorder of glycosylation · ARModerate

Moderate evidence — consider for supplementary testing

2 total gene-disease associations curated

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Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.31) despite low pLI — interpret in context.
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ClinVar Variants
68 unique Pathogenic / Likely Pathogenic· 111 VUS of 355 total submissions
Explore recent and relevant literature in Research Assistant →
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GeneReview available — STT3A
Authoritative clinical overview · Recommended first read
Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Missense constrained — critical functional residues
LoF Constraint
0.49LOEUF
pLI 0.002
Z-score 4.18
OE 0.31 (0.20–0.49)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint
3.62Z-score
OE missense 0.50 (0.44–0.56)
205 obs / 411.7 exp
Constrained

Highly missense-constrained (top ~0.1%)

Observed / Expected Ratios
LoF OE0.31 (0.20–0.49)
0≤0.351.4
Missense OE0.50 (0.44–0.56)
0≤0.61.4
Synonymous OE0.85
0≤1.21.6
LoF obs/exp: 13 / 42.3Missense obs/exp: 205 / 411.7Syn Z: 1.42
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
strongSTT3A-related type I congenital disorder of glycosylation with neuromusculoskeletal diseaseOTHERAD
limitedSTT3A-related congenital disorder of glycosylationOTHERAR
DN
0.75top 25%
GOF
0.6345th %ile
LOF
0.2872th %ile

The highest-scoring mechanism for this gene is dominant-negative.

DNprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

355 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic60
Likely Pathogenic8
VUS111
Likely Benign83
Benign62
Conflicting1
60
Pathogenic
8
Likely Pathogenic
111
VUS
83
Likely Benign
62
Benign
1
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
60
0
60
Likely Pathogenic
0
6
2
0
8
VUS
3
95
11
2
111
Likely Benign
0
0
47
36
83
Benign
0
0
56
6
62
Conflicting
—1
Total310117644325

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

STT3A · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Proteome and Glycoproteome Analyses Reveal the Protein N-Linked Glycosylation Specificity of STT3A and STT3B
Wen P et al.·Cells
2022
Targeting STT3A produces an anti-tumor effect in lung adenocarcinoma by blocking the MAPK and PI3K/AKT signaling pathway
Cheng J et al.·Transl Lung Cancer Res
2022
STT3A-mediated FCN3 N-glycosylation promotes Treg cell activation to drive hepatocellular carcinoma progression via Wnt/beta-catenin
Zhang H et al.·Cell Oncol (Dordr)
2026
Elevation of spermine remodels immunosuppressive microenvironment through driving the modification of PD-L1 in hepatocellular carcinoma
Shi HX et al.·Cell Commun Signal
2022Functional
Active site variants in STT3A cause a dominant type I congenital disorder of glycosylation with neuromusculoskeletal findings.
Wilson MP et al.·Am J Hum Genet
2021
Top 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Top 5 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients