STT3B-congenital disorder of glycosylation

Summary

STT3B-congenital disorder of glycosylation (MONDO:0014271) is a disease with 1 cohort gene.

At a glance

• Prevalence: <1 / 1 000 000 (Worldwide) [Orphanet-validated]
• Cohort genes: 1
• ClinVar variants: 108
• Phenotypes (HPO): 17

Clinical features

Epidemiology

Prevalence records

2 prevalence record(s), Orphanet:

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

Signs & symptoms

Clinical features (HPO)

17 HPO clinical features (Orphanet curated; top 17 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:0000078	Abnormality of the genital system	Frequent (30-79%)
HP:0000648	Optic atrophy	Frequent (30-79%)
HP:0001511	Intrauterine growth retardation	Frequent (30-79%)
HP:0001873	Thrombocytopenia	Frequent (30-79%)
HP:0002098	Respiratory distress	Frequent (30-79%)

Identifiers

Disease identifiers

Field	Value
Canonical name	STT3B-congenital disorder of glycosylation
Mondo ID	MONDO:0014271
MeSH	C535751
OMIM	615597
Orphanet	370924
DOID	DOID:0080573
SNOMED CT	733112007
UMLS	C2931007
MedGen	419309
GARD	0017603
Is cancer (heuristic)	no

Also known as: carbohydrate deficient glycoprotein syndrome type IX · CDG syndrome type IX · CDG-Ix · CDG1X · congenital disorder of glycosylation type 1x · congenital disorder of glycosylation type IX · congenital disorder of glycosylation, type IX · STT3B-CDG · STT3B-congenital disorder of glycosylation

Data availability: 108 ClinVar variants · 5 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 › STT3B-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, STT3A-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

108 retrieved; paginated sample, class counts are floors:

53 likely benign, 37 uncertain significance, 9 benign, 5 benign/likely benign, 2 pathogenic, 2 conflicting classifications of pathogenicity

ClinVar	Variant (HGVS)	Gene	Classification	Review
1686968	NM_178862.3(STT3B):c.38C>G (p.Ser13Trp)	LOC129936407	Pathogenic	no assertion criteria provided
102449	NM_178862.3(STT3B):c.1539+20G>T	STT3B	Pathogenic	no assertion criteria provided
2150766	NM_178862.3(STT3B):c.1562C>T (p.Ala521Val)	STT3B	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
585072	NM_178862.3(STT3B):c.895A>G (p.Ile299Val)	STT3B	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1042772	NM_178862.3(STT3B):c.11C>T (p.Pro4Leu)	LOC129936407	Uncertain significance	criteria provided, single submitter
2073887	NM_178862.3(STT3B):c.32A>G (p.His11Arg)	LOC129936407	Uncertain significance	criteria provided, multiple submitters, no conflicts
2827339	NM_178862.3(STT3B):c.13T>C (p.Ser5Pro)	LOC129936407	Uncertain significance	criteria provided, single submitter
4177213	NM_178862.3(STT3B):c.47A>G (p.Asn16Ser)	LOC129936407	Uncertain significance	criteria provided, multiple submitters, no conflicts
4722764	NM_178862.3(STT3B):c.292A>G (p.Ile98Val)	LOC129936409	Uncertain significance	criteria provided, single submitter
1346179	NM_178862.3(STT3B):c.887C>G (p.Thr296Ser)	STT3B	Uncertain significance	criteria provided, single submitter
1354333	NM_178862.3(STT3B):c.307G>T (p.Asp103Tyr)	STT3B	Uncertain significance	criteria provided, single submitter
1392903	NM_178862.3(STT3B):c.1948A>G (p.Arg650Gly)	STT3B	Uncertain significance	criteria provided, single submitter
1393970	NM_178862.3(STT3B):c.490G>A (p.Val164Ile)	STT3B	Uncertain significance	criteria provided, multiple submitters, no conflicts
1970903	NM_178862.3(STT3B):c.976+5G>T	STT3B	Uncertain significance	criteria provided, single submitter
2015567	NM_178862.3(STT3B):c.2071C>T (p.Arg691Trp)	STT3B	Uncertain significance	criteria provided, single submitter
2049333	NM_178862.3(STT3B):c.1073C>T (p.Ser358Leu)	STT3B	Uncertain significance	criteria provided, multiple submitters, no conflicts
2122459	NM_178862.3(STT3B):c.1014G>T (p.Gln338His)	STT3B	Uncertain significance	criteria provided, single submitter
2123911	NM_178862.3(STT3B):c.1837G>A (p.Gly613Arg)	STT3B	Uncertain significance	criteria provided, single submitter
2164557	NM_178862.3(STT3B):c.812A>G (p.Asn271Ser)	STT3B	Uncertain significance	criteria provided, single submitter
2415838	NM_178862.3(STT3B):c.1102G>T (p.Val368Phe)	STT3B	Uncertain significance	criteria provided, single submitter
2523788	NM_178862.3(STT3B):c.2320G>A (p.Ala774Thr)	STT3B	Uncertain significance	criteria provided, multiple submitters, no conflicts
2695561	NM_178862.3(STT3B):c.601G>A (p.Ala201Thr)	STT3B	Uncertain significance	criteria provided, single submitter
2719019	NM_178862.3(STT3B):c.2378A>C (p.Lys793Thr)	STT3B	Uncertain significance	criteria provided, single submitter
2723388	NM_178862.3(STT3B):c.2349C>A (p.His783Gln)	STT3B	Uncertain significance	criteria provided, single submitter
2746656	NM_178862.3(STT3B):c.448G>T (p.Ala150Ser)	STT3B	Uncertain significance	criteria provided, single submitter
2761967	NM_178862.3(STT3B):c.1263T>G (p.Leu421=)	STT3B	Uncertain significance	criteria provided, single submitter
2789047	NM_178862.3(STT3B):c.1612A>G (p.Ile538Val)	STT3B	Uncertain significance	criteria provided, single submitter
2795740	NM_178862.3(STT3B):c.387A>C (p.Arg129Ser)	STT3B	Uncertain significance	criteria provided, single submitter
2913533	NM_178862.3(STT3B):c.778-3T>C	STT3B	Uncertain significance	criteria provided, single submitter
3017234	NM_178862.3(STT3B):c.496A>G (p.Ile166Val)	STT3B	Uncertain significance	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 6 · 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
STT3B	Supportive	Autosomal recessive	STT3B-congenital disorder of glycosylation	6

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
STT3B	Orphanet:370924	STT3B-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
STT3B	HGNC:30611	ENSG00000163527	Q8TCJ2	Dolichyl-diphosphooligosaccharide–protein glycosyltransferase subunit STT3B	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
STT3B	Dolichyl-diphosphooligosaccharide–protein glycosyltransferase subunit STT3B	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)
STT3B	Enzyme (other)	yes	2.4.99.18	Oligo_trans_STT3, STT3_N, STT3-PglB_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
cardiac muscle of right atrium	1
ileal mucosa	1
upper arm skin	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
STT3B	263	ubiquitous	marker	ileal mucosa, cardiac muscle of right atrium, upper arm skin

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
STT3B	2,615

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
STT3B	Q8TCJ2	1

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 8. 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
Regulation of MITF-M-dependent genes involved in extracellular matrix, focal adhesion and epithelial-to-mesenchymal transition	1	878.5×	0.008	STT3B
PD-L1(CD274) glycosylation and translocation to plasma membrane	1	519.1×	0.008	STT3B
Maturation of spike protein	1	265.6×	0.009	STT3B
Maturation of DENV proteins	1	211.5×	0.009	STT3B
MITF-M-dependent gene expression	1	181.3×	0.009	STT3B
MITF-M-regulated melanocyte development	1	114.2×	0.012	STT3B
Asparagine N-linked glycosylation	1	60.1×	0.019	STT3B
Developmental Biology	1	14.5×	0.069	STT3B

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
glycoprotein catabolic process	1	1053.2×	0.004	STT3B
obsolete protein N-linked glycosylation via asparagine	1	674.1×	0.004	STT3B
post-translational protein modification	1	421.3×	0.005	STT3B
response to unfolded protein	1	300.9×	0.005	STT3B
protein N-linked glycosylation	1	263.3×	0.005	STT3B
ERAD pathway	1	181.2×	0.006	STT3B

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
STT3B	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
STT3B	2	Binding:2

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
STT3B	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	STT3B
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)
STT3B	2	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.