STT3A-congenital disorder of glycosylation

Summary

STT3A-congenital disorder of glycosylation (MONDO:0014270) is a disease caused by STT3A (GenCC Strong), with 1 cohort gene.

At a glance

• Prevalence: <1 / 1 000 000 (Worldwide) [Orphanet-validated]
• Causal gene: STT3A (GenCC Strong)
• Cohort genes: 1
• ClinVar variants: 14
• Phenotypes (HPO): 13

Clinical features

Epidemiology

Prevalence records

2 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Cases/families		2	Worldwide	Validated
Point prevalence	<1 / 1 000 000		Worldwide	Validated

Signs & symptoms

Clinical features (HPO)

13 HPO clinical features (Orphanet curated; top 13 by frequency):

HPO ID	Term	Frequency
HP:0000252	Microcephaly	Obligate (100%)
HP:0001249	Intellectual disability	Obligate (100%)
HP:0001250	Seizure	Obligate (100%)
HP:0001263	Global developmental delay	Obligate (100%)
HP:0001272	Cerebellar atrophy	Obligate (100%)
HP:0001290	Generalized hypotonia	Obligate (100%)
HP:0001508	Failure to thrive	Obligate (100%)
HP:0011968	Feeding difficulties	Obligate (100%)
HP:0012345	Abnormal glycosylation	Obligate (100%)
HP:0000028	Cryptorchidism	Frequent (30-79%)
HP:0000046	Small scrotum	Frequent (30-79%)
HP:0000054	Micropenis	Frequent (30-79%)
HP:0007772	Impaired smooth pursuit	Frequent (30-79%)

Identifiers

Disease identifiers

Field	Value
Canonical name	STT3A-congenital disorder of glycosylation
Mondo ID	MONDO:0014270
OMIM	615596
Orphanet	370921
DOID	DOID:0080572
SNOMED CT	733111000
UMLS	C5561935
MedGen	1794145
GARD	0017602
Is cancer (heuristic)	no

Also known as: CDG syndrome type Iw · CDG-Iw · CDG1W · congenital disorder of glycosylation type 1w · congenital disorder of glycosylation type Iw · congenital disorder of glycosylation, type Iw · congenital disorder of glycosylation, type Iw, autosomal recessive · STT3A-CDG · STT3A-congenital disorder of glycosylation

Data availability: 14 ClinVar variants · 6 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by etiologic mechanism › disease of genetic or genomic mechanism › hereditary disease › inborn errors of metabolism › congenital disorder of glycosylation › congenital disorder of glycosylation type I › STT3A-congenital disorder of glycosylation

Related subtypes (27): PMM2-congenital disorder of glycosylation, developmental and epileptic encephalopathy, 36, SSR4-congenital disorder of glycosylation, ALG3-congenital disorder of glycosylation, MPI-congenital disorder of glycosylation, ALG6-congenital disorder of glycosylation 1C, ALG12-congenital disorder of glycosylation, ALG2-congenital disorder of glycosylation, DPAGT1-congenital disorder of glycosylation, ALG8-congenital disorder of glycosylation, ALG1-congenital disorder of glycosylation, ALG9-congenital disorder of glycosylation, congenital disorder of glycosylation type 1E, MPDU1-congenital disorder of glycosylation, DK1-congenital disorder of glycosylation, RFT1-congenital disorder of glycosylation, SRD5A3-congenital disorder of glycosylation, DPM3-congenital disorder of glycosylation, ALG11-congenital disorder of glycosylation, DDOST-congenital disorder of glycosylation, PGM1-congenital disorder of glycosylation, congenital muscular dystrophy with intellectual disability and severe epilepsy, STT3B-congenital disorder of glycosylation, developmental and epileptic encephalopathy, 50, congenital disorder of glycosylation, type IAA, congenital disorder of glycosylation, type ICC, SSR3-CDG

Genetics & variants

GWAS landscape

No GWAS associations recorded — common-variant (GWAS) studies don’t cover this disease (typical for Mendelian / rare diseases). See the curated gene cohort and Mendelian overlap below.

Variant details and genetic-evidence tiers

ClinVar germline variants

14 retrieved; paginated sample, class counts are floors:

7 uncertain significance, 3 benign, 1 likely pathogenic, 1 benign/likely benign, 1 pathogenic/likely pathogenic, 1 likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
1334781	NM_152713.5(STT3A):c.1214G>A (p.Arg405His)	STT3A	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
102443	NM_152713.5(STT3A):c.1877T>C (p.Val626Ala)	STT3A	Likely pathogenic	criteria provided, single submitter
1027877	NM_152713.5(STT3A):c.415A>C (p.Lys139Gln)	STT3A	Uncertain significance	criteria provided, single submitter
1299225	NM_152713.5(STT3A):c.1310G>A (p.Arg437His)	STT3A	Uncertain significance	criteria provided, multiple submitters, no conflicts
3065465	NM_152713.5(STT3A):c.544A>G (p.Met182Val)	STT3A	Uncertain significance	criteria provided, single submitter
3450914	NM_152713.5(STT3A):c.440C>G (p.Ala147Gly)	STT3A	Uncertain significance	criteria provided, multiple submitters, no conflicts
4086119	NM_152713.5(STT3A):c.871A>T (p.Asn291Tyr)	STT3A	Uncertain significance	criteria provided, single submitter
4278019	NM_152713.5(STT3A):c.482C>G (p.Ser161Cys)	STT3A	Uncertain significance	criteria provided, single submitter
4529496	NM_152713.5(STT3A):c.1613G>A (p.Arg538Gln)	STT3A	Uncertain significance	criteria provided, single submitter
1287809	NM_152713.5(STT3A):c.1775-8dup	STT3A	Benign/Likely benign	criteria provided, multiple submitters, no conflicts
1292112	NM_152713.5(STT3A):c.961+25C>T	STT3A	Benign	criteria provided, multiple submitters, no conflicts
380015	NM_152713.5(STT3A):c.996G>A (p.Ser332=)	STT3A	Benign	criteria provided, multiple submitters, no conflicts
380031	NM_152713.5(STT3A):c.1117+12C>T	STT3A	Benign	criteria provided, multiple submitters, no conflicts
702848	NM_152713.5(STT3A):c.780+5G>A	STT3A	Likely benign	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 11 · Orphanet: 1 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

GenCC gene–disease validity (cohort genes)

the Disease column is the GenCC-asserted condition — a cohort gene’s strongest validity may be for a related predisposition syndrome.

Gene	Classification	Inheritance	Disease	Records
STT3A	Definitive	Autosomal dominant	congenital disorder of glycosylation, type Iw, autosomal dominant	11

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
STT3A	Orphanet:370921	STT3A-CDG

Cohort genes → proteins

1 cohort genes, 1 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	1

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
STT3A	HGNC:6172	ENSG00000134910	P46977	Dolichyl-diphosphooligosaccharide–protein glycosyltransferase subunit STT3A	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
STT3A	Dolichyl-diphosphooligosaccharide–protein glycosyltransferase subunit STT3A	Catalytic subunit of the oligosaccharyl transferase (OST) complex that catalyzes the initial transfer of a defined glycan (Glc(3)Man(9)GlcNAc(2) in eukaryotes) from the lipid carrier dolichol-pyrophosphate to an asparagine residue within a…

Protein-family classification

Druggable: 1 · Difficult: 0 · Unknown: 0 · Druggable fraction: 1.0

Family distribution

Cohort families vs a genome-wide background (hypergeometric, BH-FDR; fold = observed/expected). Counts kept; sorted by enrichment, so the catch-all Other/Unknown bucket no longer leads.

Family	Genes	Fold	FDR
Enzyme (other)	1	12.0×	0.083

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
STT3A	Enzyme (other)	yes	2.4.99.18	Oligo_trans_STT3, STT3_N, AglB-like_core

Expression context

Cohort genes with no expression data: 0.

1 cohort gene are a single-cell marker in ≥1 SCXA experiment.

Breadth distribution (Bgee present_calls)

Bucket	Genes
narrow (1-5 tissues)	0
moderate (6-20)	0
broad (>20)	1
unknown	0

Top tissues across cohort

Tissue	Cohort genes
body of pancreas	1
islet of Langerhans	1
stromal cell of endometrium	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
STT3A	262	ubiquitous	marker	stromal cell of endometrium, body of pancreas, islet of Langerhans

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
STT3A	2,266

Structural data

PDB: 1 · AlphaFold-only: 0 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
STT3A	P46977	5

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 14. Enrichment computed across 1 evidence-associated genes (1 with Reactome annotation).

Pathways by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
PD-L1(CD274) glycosylation and translocation to plasma membrane	1	519.1×	0.011	STT3A
Translation of Structural Proteins	1	407.9×	0.011	STT3A
Regulation of CDH1 posttranslational processing and trafficking to plasma membrane	1	335.9×	0.011	STT3A
Late SARS-CoV-2 Infection Events	1	292.8×	0.011	STT3A
Maturation of spike protein	1	265.6×	0.011	STT3A
Maturation of DENV proteins	1	211.5×	0.011	STT3A
SARS-CoV-2 Infection	1	80.4×	0.025	STT3A
Asparagine N-linked glycosylation	1	60.1×	0.028	STT3A
SARS-CoV Infections	1	55.4×	0.028	STT3A
Viral Infection Pathways	1	30.8×	0.045	STT3A
Infectious disease	1	24.8×	0.051	STT3A
Post-translational protein modification	1	19.2×	0.061	STT3A
Disease	1	13.1×	0.081	STT3A
Metabolism of proteins	1	12.4×	0.081	STT3A

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
obsolete protein N-linked glycosylation via asparagine	1	674.1×	0.004	STT3A
post-translational protein modification	1	421.3×	0.004	STT3A
protein N-linked glycosylation	1	263.3×	0.004	STT3A

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 1

Druggability breadth: 1 of 1 evidence-associated genes (100%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
STT3A	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

Cohort genes with ChEMBL bioactivity (full, sorted by assay count)

Symbol	Assays	Type breakdown
STT3A	2	Binding:2

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
STT3A	2.4.99.18	dolichyl-diphosphooligosaccharide-protein glycotransferase

Pharmacogenomics

Cohort genes with a PharmGKB record: 1; with CPIC/DPWG dosing guidelines: 0.

No cohort gene has a CPIC/DPWG genotype-guided dosing guideline (PharmGKB).

Chemical tractability of cohort targets

0 approved/phased compounds have measured bioactivity against a cohort gene (and aren’t yet in disease-level trials). This is a research / tractability signal, NOT a therapeutic recommendation — a bioactivity row often reflects off-target or screening binding (e.g. promiscuous kinase inhibitors against a cohort kinase), implying no disease mechanism.

Druggability pyramid

Cohort genes binned by druggability tier (high → low):

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	0
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	1	STT3A
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	0

Undrugged target profiles

1 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).

Symbol	ChEMBL assays	Drugged partners (top 3)
STT3A	2	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.