STT3A

Chr 11ADAR

STT3 oligosaccharyltransferase complex catalytic subunit A

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

NCBI Gene: 3703ENSG00000134910UniProt: P46977

The protein encoded by this gene is a catalytic subunit of the N-oligosaccharyltransferase (OST) complex, which functions in the endoplasmic reticulum to transfer glycan chains to asparagine residues of target proteins. A separate complex containing a similar catalytic subunit with an overlapping function also exists. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Aug 2015]

Primary Disease Associations & Inheritance

Congenital disorder of glycosylation, type Iw, autosomal dominantMIM #619714
AD
Congenital disorder of glycosylation, type Iw, autosomal recessiveMIM #615596
AR
321
ClinVar variants
67
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— STT3A
🧬
Gene-Disease Validity (ClinGen)
STT3A-congenital disorder of glycosylation · ARModerate

Moderate evidence — consider for supplementary testing

2 total gene-disease associations curated

⚡
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.31) despite low pLI — interpret in context.
📋
ClinVar Variants
67 Pathogenic / Likely Pathogenic· 109 VUS of 321 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Missense constrained — critical functional residues
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
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?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
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?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.31 (0.20–0.49)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.50 (0.44–0.56)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.0.85
0≤1.21.6
LoF obs/exp: 13 / 42.3Missense obs/exp: 205 / 411.7Syn Z: 1.42

ClinVar Variant Classifications

321 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic59
Likely Pathogenic8
VUS109
Likely Benign82
Benign62
Conflicting1
59
Pathogenic
8
Likely Pathogenic
109
VUS
82
Likely Benign
62
Benign
1
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
59
0
59
Likely Pathogenic
0
6
2
0
8
VUS
2
93
12
2
109
Likely Benign
0
0
46
36
82
Benign
0
0
56
6
62
Conflicting
—1
Total29917544321

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.

Gene2Phenotype Curations

STT3A-related type I congenital disorder of glycosylation with neuromusculoskeletal disease

strong
ADUndeterminedAltered Gene Product Structure
Dev. Disorders
G2P ↗

STT3A-related congenital disorder of glycosylation

limited
ARUndeterminedAltered Gene Product Structure
Dev. Disorders
G2P ↗
missense variantinframe deletioninframe insertion

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Congenital disorder of glycosylation, type Iw, autosomal dominant

MIM #619714

Molecular basis of disorder known

Autosomal dominant

Congenital disorder of glycosylation, type Iw, autosomal recessive

MIM #615596

Molecular basis of disorder known

Autosomal recessive
📖
GeneReview available — STT3A
Authoritative clinical overview · NCBI Bookshelf · Recommended first read
Open GeneReview ↗
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Promoting anti-tumor immunity by targeting TMUB1 to modulate PD-L1 polyubiquitination and glycosylation.
Shi C et al.·Nat Commun
2022
Pharmacological suppression of HHLA2 glycosylation restores anti-tumor immunity in colorectal cancer.
Zhang D et al.·Cancer Lett
2024
Heterozygous pathogenic STT3A variation leads to dominant congenital glycosylation disorders and functional validation in zebrafish.
Meng L et al.·Orphanet J Rare Dis
2025Functional
Factor VIII and vWF deficiency in STT3A-CDG.
Chang IJ et al.·J Inherit Metab Dis
2019Case report
STT3B promotes porcine epidemic diarrhea virus replication by regulating N-glycosylation of PEDV S protein.
Zhu H et al.·J Virol
2025
Phenotypic Heterogeneity in a Congenital Disorder of Glycosylation Caused by Mutations in STT3A.
Ghosh A et al.·J Child Neurol
2017
DC2 and KCP2 mediate the interaction between the oligosaccharyltransferase and the ER translocon.
Shrimal S et al.·J Cell Biol
2017
STT3A, C1orf24, TFF3: putative markers for characterization of follicular thyroid neoplasms from fine-needle aspirates.
Patel MR et al.·Laryngoscope
2011
Molecular mechanisms of missense mutations that generate ectopic N-glycosylation sites in coagulation factor VIII.
Wei W et al.·Biochem J
2018Functional
Targeting conserved N-glycosylation blocks SARS-CoV-2 variant infection in vitro.
Huang HC et al.·EBioMedicine
2021
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools