STT3A

Chr 11ADAR

STT3 oligosaccharyltransferase complex catalytic subunit A

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

NCBI Gene: 3703 ENSG00000134910 UniProt: P46977 OMIM: 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.

OMIM ResearchSummary from RefSeq, OMIM, UniProt

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]

OMIM ResearchGenerating clinical summary…

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

6 unique Pathogenic / Likely Pathogenic· 107 VUS of 288 total submissions

Explore recent and relevant literature in Research Assistant →

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 OE?0.31 (0.20–0.49)

0≤0.351.4

Missense OE?0.50 (0.44–0.56)

0≤0.61.4

Synonymous OE?0.85

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

This gene — mechanism propensity

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

288 submitted variants in ClinVar

ClinVar

Classification Summary

Likely Pathogenic6

VUS107

Likely Benign83

Benign62

Conflicting1

Likely Pathogenic

107

VUS

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	0	0	0	0	0
Likely Pathogenic	0	6	0	0	6
VUS	3	96	6	2	107
Likely Benign	0	0	47	36	83
Benign	0	0	56	6	62
Conflicting	—				1
Total	3	102	109	44	259

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

View in ClinVar →

63 pathogenic / likely-pathogenic (of 69) ClinVar copy-number / structural variants overlap STT3A — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →