congenital disorder of glycosylation, type ICC

Summary

congenital disorder of glycosylation, type ICC (MONDO:0026729) is a disease with 1 cohort gene.

At a glance

• Cohort genes: 1
• ClinVar variants: 11

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	congenital disorder of glycosylation, type ICC
Mondo ID	MONDO:0026729
OMIM	301031
DOID	DOID:0111839
UMLS	C5231393
MedGen	1684742
GARD	0025484
Is cancer (heuristic)	no

Also known as: CDG1CC · congenital disorder of glycosylation, type Icc, X-linked recessive

Data availability: 11 ClinVar variants.

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 › congenital disorder of glycosylation, type ICC

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, STT3B-congenital disorder of glycosylation, developmental and epileptic encephalopathy, 50, congenital disorder of glycosylation, type IAA, 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

11 retrieved; paginated sample, class counts are floors:

4 uncertain significance, 3 conflicting classifications of pathogenicity, 2 pathogenic, 1 likely pathogenic, 1 benign/likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
625836	NM_001367916.1(MAGT1):c.972A>C (p.Lys324Asn)	MAGT1	Pathogenic	criteria provided, single submitter
625837	NM_001367916.1(MAGT1):c.895C>T (p.Arg299Ter)	MAGT1	Pathogenic	criteria provided, multiple submitters, no conflicts
4849474	NM_032121.5(MAGT1):c.44_45insGG (p.Leu16fs)	MAGT1	Likely pathogenic	criteria provided, single submitter
2782795	NM_001367916.1(MAGT1):c.49G>A (p.Ala17Thr)	LOC130068460	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
996948	NM_001367916.1(MAGT1):c.-3A>G	LOC130068460	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
2765352	NM_001367916.1(MAGT1):c.628A>G (p.Met210Val)	MAGT1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1369602	NM_001367916.1(MAGT1):c.-20T>C	LOC130068460	Uncertain significance	criteria provided, multiple submitters, no conflicts
1802597	NM_001367916.1(MAGT1):c.752C>T (p.Thr251Met)	MAGT1	Uncertain significance	criteria provided, single submitter
2582378	NM_001367916.1(MAGT1):c.297C>G (p.Ile99Met)	MAGT1	Uncertain significance	criteria provided, multiple submitters, no conflicts
3598434	NM_001367916.1(MAGT1):c.826+16A>C	MAGT1	Uncertain significance	criteria provided, single submitter
96213	NM_001367916.1(MAGT1):c.932T>G (p.Val311Gly)	MAGT1	Benign/Likely benign	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

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

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
MAGT1	Orphanet:317476	XMEN

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
MAGT1	HGNC:28880	ENSG00000102158	Q9H0U3	Dolichyl-diphosphooligosaccharide–protein glycosyltransferase subunit MAGT1	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
MAGT1	Dolichyl-diphosphooligosaccharide–protein glycosyltransferase subunit MAGT1	Accessory component of the STT3B-containing form of the N-oligosaccharyl transferase (OST) complex which catalyzes the transfer of a high mannose oligosaccharide from a lipid-linked oligosaccharide donor to an asparagine residue within an…

Protein-family classification

Druggable: 0 · Difficult: 0 · Unknown: 1 · Druggable fraction: 0.0

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
Other/Unknown	1	1.8×	0.558

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
MAGT1	Other/Unknown	no		MAGT1/OST3/OST6, Thioredoxin-like_sf

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
corpus epididymis	1
esophagus squamous epithelium	1
palpebral conjunctiva	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
MAGT1	282	ubiquitous	marker	palpebral conjunctiva, corpus epididymis, esophagus squamous epithelium

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
MAGT1	1,824

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
MAGT1	Q9H0U3	1

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 18. 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×	0.014	MAGT1
Miscellaneous transport and binding events	1	439.2×	0.014	MAGT1
Translation of Structural Proteins	1	407.9×	0.014	MAGT1
Late SARS-CoV-2 Infection Events	1	292.8×	0.014	MAGT1
Maturation of spike protein	1	265.6×	0.014	MAGT1
Maturation of DENV proteins	1	211.5×	0.014	MAGT1
SARS-CoV-2 Infection	1	80.4×	0.032	MAGT1
Asparagine N-linked glycosylation	1	60.1×	0.036	MAGT1
SARS-CoV Infections	1	55.4×	0.036	MAGT1
Viral Infection Pathways	1	30.8×	0.056	MAGT1
Innate Immune System	1	25.5×	0.056	MAGT1
Transport of small molecules	1	25.1×	0.056	MAGT1
Infectious disease	1	24.8×	0.056	MAGT1
Neutrophil degranulation	1	23.1×	0.056	MAGT1
Post-translational protein modification	1	19.2×	0.063	MAGT1
Disease	1	13.1×	0.081	MAGT1
Immune System	1	13.0×	0.081	MAGT1
Metabolism of proteins	1	12.4×	0.081	MAGT1

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
magnesium ion transmembrane transport	1	4213.0×	0.001	MAGT1
magnesium ion transport	1	1203.7×	0.002	MAGT1
obsolete protein N-linked glycosylation via asparagine	1	674.1×	0.003	MAGT1
cognition	1	285.6×	0.005	MAGT1
protein N-linked glycosylation	1	263.3×	0.005	MAGT1
transmembrane transport	1	168.5×	0.006	MAGT1

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
MAGT1	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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

Symbol	Assays	Type breakdown
MAGT1	1	Binding:1

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	0
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	1	MAGT1

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)
MAGT1	1	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.