MOGS-congenital disorder of glycosylation

Summary

MOGS-congenital disorder of glycosylation (MONDO:0011629) is a disease caused by MOGS (GenCC Definitive), with 2 cohort genes.

At a glance

• Prevalence: <1 / 1 000 000 (Worldwide) [Orphanet-validated]
• Causal gene: MOGS (GenCC Definitive)
• Cohort genes: 2
• ClinVar variants: 539
• Phenotypes (HPO): 44

Clinical features

Epidemiology

Prevalence records

2 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Cases/families		3	Worldwide	Validated
Point prevalence	<1 / 1 000 000		Worldwide	Validated

Signs & symptoms

Clinical features (HPO)

44 HPO clinical features (Orphanet curated; top 44 by frequency):

HPO ID	Term	Frequency
HP:0000278	Retrognathia	Frequent (30-79%)
HP:0000445	Wide nose	Frequent (30-79%)
HP:0000527	Long eyelashes	Frequent (30-79%)
HP:0001007	Hirsutism	Frequent (30-79%)
HP:0001250	Seizure	Frequent (30-79%)
HP:0001999	Abnormal facial shape	Frequent (30-79%)
HP:0002720	Decreased circulating IgA level	Frequent (30-79%)
HP:0002850	Decreased circulating total IgM	Frequent (30-79%)
HP:0003241	External genital hypoplasia	Frequent (30-79%)
HP:0004313	Decreased circulating antibody level	Frequent (30-79%)
HP:0008947	Floppy infant	Frequent (30-79%)
HP:0012745	Short palpebral fissure	Frequent (30-79%)
HP:0000034	Hydrocele testis	Occasional (5-29%)
HP:0000218	High palate	Occasional (5-29%)
HP:0000269	Prominent occiput	Occasional (5-29%)
HP:0000407	Sensorineural hearing impairment	Occasional (5-29%)
HP:0000648	Optic atrophy	Occasional (5-29%)
HP:0000649	Abnormality of visual evoked potentials	Occasional (5-29%)
HP:0000821	Hypothyroidism	Occasional (5-29%)
HP:0000969	Edema	Occasional (5-29%)
HP:0001332	Dystonia	Occasional (5-29%)
HP:0001433	Hepatosplenomegaly	Occasional (5-29%)
HP:0001561	Polyhydramnios	Occasional (5-29%)
HP:0001596	Alopecia	Occasional (5-29%)
HP:0001631	Atrial septal defect	Occasional (5-29%)
HP:0001640	Cardiomegaly	Occasional (5-29%)
HP:0001712	Left ventricular hypertrophy	Occasional (5-29%)
HP:0001873	Thrombocytopenia	Occasional (5-29%)
HP:0002079	Hypoplasia of the corpus callosum	Occasional (5-29%)
HP:0002098	Respiratory distress	Occasional (5-29%)
HP:0002104	Apnea	Occasional (5-29%)
HP:0002240	Hepatomegaly	Occasional (5-29%)
HP:0002286	Fair hair	Occasional (5-29%)
HP:0002791	Hypoventilation	Occasional (5-29%)
HP:0002943	Thoracic scoliosis	Occasional (5-29%)
HP:0004315	Decreased circulating IgG level	Occasional (5-29%)
HP:0004463	Absent brainstem auditory responses	Occasional (5-29%)
HP:0007430	Generalized edema	Occasional (5-29%)
HP:0010557	Overlapping fingers	Occasional (5-29%)
HP:0012450	Chronic constipation	Occasional (5-29%)
HP:0020110	Bone fracture	Occasional (5-29%)
HP:0031218	Inappropriate antidiuretic hormone secretion	Occasional (5-29%)
HP:0040288	Nasogastric tube feeding	Occasional (5-29%)
HP:0100598	Pulmonary edema	Occasional (5-29%)

Identifiers

Disease identifiers

Field	Value
Canonical name	MOGS-congenital disorder of glycosylation
Mondo ID	MONDO:0011629
MeSH	C565264
OMIM	606056
Orphanet	79330
DOID	DOID:0070254
SNOMED CT	725028009
UMLS	C1853736
MedGen	342954
GARD	0010767
Is cancer (heuristic)	no

Also known as: carbohydrate deficient glycoprotein syndrome type IIb · CDG 2B · CDG syndrome type IIb · CDG-IIb · CDG2B · congenital disorder of glycosylation type 2b · congenital disorder of glycosylation type IIb · congenital disorder of glycosylation, type IIb · GCS1-CDG · glucosidase 1 deficiency · MOGS-CDG · MOGS-CDG (CDG-IIb) · MOGS-congenital disorder of glycosylation

Data availability: 539 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 II › MOGS-congenital disorder of glycosylation

Related subtypes (25): MGAT2-congenital disorder of glycosylation, leukocyte adhesion deficiency type II, SLC35A2-congenital disorder of glycosylation, SLC35A1-congenital disorder of glycosylation, B4GALT1-congenital disorder of glycosylation, COG7-congenital disorder of glycosylation, COG8-congenital disorder of glycosylation, COG1-congenital disorder of glycosylation, COG4-congenital disorder of glycosylation, COG5-congenital disorder of glycosylation, COG6-congenital disorder of glycosylation, TMEM165-congenital disorder of glycosylation, SLC39A8-CDG, CCDC115-CDG, TMEM199-CDG, congenital disorder of glycosylation, type IIr, congenital disorder of glycosylation, type iit, congenital disorder of glycosylation, type 2v, congenital disorder of glycosylation, type IIw, congenital disorder of glycosylation, type IIq, congenital disorder of glycosylation, type IIy, congenital disorder of glycosylation, type IIz, congenital disorder of glycosylation, type IIaa, congenital disorder of glycosylation, type IIbb, congenital disorder of glycosylation, type IIcc

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

539 retrieved; paginated sample, class counts are floors:

268 uncertain significance, 201 likely benign, 25 pathogenic, 15 benign/likely benign, 13 conflicting classifications of pathogenicity, 11 likely pathogenic, 3 pathogenic/likely pathogenic, 3 benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
375688	NM_006302.2(MOGS):c.[329G>A;65C>A]		Pathogenic	no assertion criteria provided
1400487	NM_006302.3(MOGS):c.287G>A (p.Trp96Ter)	LOC129934128	Pathogenic	criteria provided, single submitter
3022833	NM_006302.3(MOGS):c.94_95insTCCG (p.Gly32fs)	LOC129934128	Pathogenic	criteria provided, single submitter
1039350	NM_006302.3(MOGS):c.1483C>T (p.Arg495Ter)	MOGS	Pathogenic	criteria provided, multiple submitters, no conflicts
1071539	NM_006302.3(MOGS):c.882del (p.Glu295fs)	MOGS	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
127098	NM_006302.3(MOGS):c.370C>T (p.Gln124Ter)	MOGS	Pathogenic	criteria provided, multiple submitters, no conflicts
1323285	NM_006302.3(MOGS):c.1385G>A (p.Trp462Ter)	MOGS	Pathogenic	criteria provided, single submitter
1943297	NM_006302.3(MOGS):c.1513C>T (p.Gln505Ter)	MOGS	Pathogenic	criteria provided, single submitter
2022184	NM_006302.3(MOGS):c.1204del (p.Ile402fs)	MOGS	Pathogenic	criteria provided, single submitter
2096379	NM_006302.3(MOGS):c.1142dup (p.Leu383fs)	MOGS	Pathogenic	criteria provided, single submitter
2161830	NM_006302.3(MOGS):c.422del (p.Asp141fs)	MOGS	Pathogenic	criteria provided, single submitter
2203107	NM_006302.3(MOGS):c.832_833del (p.Lys278fs)	MOGS	Pathogenic	criteria provided, single submitter
2703760	NM_006302.3(MOGS):c.551G>A (p.Trp184Ter)	MOGS	Pathogenic	criteria provided, single submitter
2846552	NM_006302.3(MOGS):c.881del (p.Pro294fs)	MOGS	Pathogenic	criteria provided, single submitter
2913879	NM_006302.3(MOGS):c.54dup (p.Ala19fs)	MOGS	Pathogenic	criteria provided, single submitter
2976812	NM_006302.3(MOGS):c.1222del (p.Gln408fs)	MOGS	Pathogenic	criteria provided, single submitter
2982038	NM_006302.3(MOGS):c.1421G>A (p.Trp474Ter)	MOGS	Pathogenic	criteria provided, single submitter
3672613	NM_006302.3(MOGS):c.1250dup (p.Glu418fs)	MOGS	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
3690170	NM_006302.3(MOGS):c.1516C>T (p.Arg506Ter)	MOGS	Pathogenic	criteria provided, single submitter
4717315	NM_006302.3(MOGS):c.1076dup (p.Ala360fs)	MOGS	Pathogenic	criteria provided, single submitter
4729233	NM_006302.3(MOGS):c.634_635del (p.Asp212fs)	MOGS	Pathogenic	criteria provided, single submitter
4797570	NM_006302.3(MOGS):c.451del (p.His151fs)	MOGS	Pathogenic	criteria provided, single submitter
565387	NM_006302.3(MOGS):c.646del (p.Val216fs)	MOGS	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
8193	NM_006302.3(MOGS):c.1457G>C (p.Arg486Thr)	MOGS	Pathogenic	no assertion criteria provided
8194	NM_006302.3(MOGS):c.1954T>C (p.Phe652Leu)	MOGS	Pathogenic	no assertion criteria provided
831030	NC_000002.12:g.(?74461255)(74465267_?)del	MOGS	Pathogenic	criteria provided, single submitter
841487	NM_006302.3(MOGS):c.851G>A (p.Trp284Ter)	MOGS	Pathogenic	criteria provided, single submitter
2425561	NC_000002.11:g.(?72359356)(74779761_?)del	STAMBP	Pathogenic	criteria provided, single submitter
1903342	NM_006302.3(MOGS):c.353-1G>A	MOGS	Likely pathogenic	criteria provided, single submitter
217735	NM_006302.3(MOGS):c.329G>A (p.Arg110His)	MOGS	Likely pathogenic	no assertion criteria provided

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 6 · Orphanet: 2 · 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
MOGS	Definitive	Autosomal recessive	MOGS-congenital disorder of glycosylation	6

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
MOGS	Orphanet:79330	MOGS-CDG
STAMBP	Orphanet:294016	Microcephaly-capillary malformation syndrome

Cohort genes → proteins

2 cohort genes, 2 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	2

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
MOGS	HGNC:24862	ENSG00000115275	Q13724	Mannosyl-oligosaccharide glucosidase	gencc,clinvar
STAMBP	HGNC:16950	ENSG00000124356	O95630	STAM-binding protein	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
MOGS	Mannosyl-oligosaccharide glucosidase	In the context of N-glycan degradation, cleaves the distal alpha 1,2-linked glucose residue from the Glc(3)Man(9)GlcNAc(2) oligosaccharide precursor in a highly specific manner.
STAMBP	STAM-binding protein	Zinc metalloprotease that specifically cleaves ‘Lys-63’-linked polyubiquitin chains.

Protein-family classification

Druggable: 0 · Difficult: 0 · Unknown: 2 · 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	2	1.8×	0.312

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
MOGS	Other/Unknown	no		Glycoside_hydrolase_63, 6-hairpin_glycosidase_sf, 6hp_glycosidase-like_sf
STAMBP	Other/Unknown	no		JAMM/MPN+_dom, USP8_dimer, MPN

Expression context

Cohort genes with no expression data: 0.

2 cohort genes 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)	2
unknown	0

Top tissues across cohort

Tissue	Cohort genes
body of pancreas	1
body of stomach	1
granulocyte	1
C1 segment of cervical spinal cord	1
corpus callosum	1
spinal cord	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
MOGS	202	ubiquitous	marker	body of pancreas, body of stomach, granulocyte
STAMBP	292	ubiquitous	marker	C1 segment of cervical spinal cord, spinal cord, corpus callosum

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
STAMBP	3,664
MOGS	2,705

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
STAMBP	O95630	5

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
MOGS	Q13724	92.42

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 22. Enrichment computed across 2 evidence-associated genes (2 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 2 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Defective MOGS causes CDG-2b	1	5710.0×	0.004	MOGS
Maturation of spike protein	1	951.7×	0.012	MOGS
Translation of Structural Proteins	1	439.2×	0.014	MOGS
Diseases associated with N-glycosylation of proteins	1	317.2×	0.014	MOGS
N-glycan trimming in the ER and Calnexin/Calreticulin cycle	1	211.5×	0.014	MOGS
Translation of Structural Proteins	1	203.9×	0.014	MOGS
Regulation of CDH1 posttranslational processing and trafficking to plasma membrane	1	167.9×	0.014	MOGS
Metalloprotease DUBs	1	150.3×	0.014	STAMBP
Late SARS-CoV-2 Infection Events	1	146.4×	0.014	MOGS
Post-translational protein modification	2	19.2×	0.014	MOGS, STAMBP
Metabolism of proteins	2	12.4×	0.014	MOGS, STAMBP
Maturation of spike protein	1	132.8×	0.014	MOGS
SARS-CoV-1 Infection	1	71.4×	0.024	MOGS
Diseases of glycosylation	1	65.6×	0.024	MOGS
Deubiquitination	1	62.1×	0.024	STAMBP
Diseases of metabolism	1	40.2×	0.032	MOGS
SARS-CoV-2 Infection	1	40.2×	0.032	MOGS
Asparagine N-linked glycosylation	1	30.1×	0.040	MOGS
SARS-CoV Infections	1	27.7×	0.041	MOGS
Viral Infection Pathways	1	15.4×	0.070	MOGS
Infectious disease	1	12.4×	0.083	MOGS
Disease	1	6.5×	0.147	MOGS

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 2 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
hippocampal neuron apoptotic process	1	1685.2×	0.004	STAMBP
negative regulation of hippocampal neuron apoptotic process	1	1685.2×	0.004	STAMBP
oligosaccharide metabolic process	1	351.1×	0.009	MOGS
negative regulation of Ras protein signal transduction	1	337.0×	0.009	STAMBP
protein K63-linked deubiquitination	1	312.1×	0.009	STAMBP
viral protein processing	1	271.8×	0.009	MOGS
cell surface receptor signaling pathway via JAK-STAT	1	145.3×	0.011	STAMBP
protein N-linked glycosylation	1	131.7×	0.011	MOGS
negative regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction	1	131.7×	0.011	STAMBP
mitotic cytokinesis	1	129.6×	0.011	STAMBP
protein deubiquitination	1	88.7×	0.014	STAMBP
protein folding	1	51.7×	0.022	MOGS
proteolysis	1	17.1×	0.059	STAMBP
positive regulation of cell population proliferation	1	16.8×	0.059	STAMBP

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 2

Druggability breadth: 2 of 2 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
MOGS	0	0
STAMBP	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
MOGS	2	Binding:2
STAMBP	2	Binding:2

Pharmacogenomics

Cohort genes with a PharmGKB record: 2; 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	2	MOGS, STAMBP

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
MOGS	2	—
STAMBP	2	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.