MAN1B1-congenital disorder of glycosylation

Summary

MAN1B1-congenital disorder of glycosylation (MONDO:0018349) is a disease caused by MAN1B1 (GenCC Definitive), with 1 cohort gene.

At a glance

• Prevalence: <1 / 1 000 000 (Worldwide) [Orphanet-validated]
• Causal gene: MAN1B1 (GenCC Definitive)
• Cohort genes: 1
• ClinVar variants: 1
• Phenotypes (HPO): 53

Clinical features

Epidemiology

Prevalence records

2 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Cases/families		25	Worldwide	Validated
Point prevalence	<1 / 1 000 000		Worldwide	Validated

Signs & symptoms

Clinical features (HPO)

53 HPO clinical features (Orphanet curated; top 50 by frequency):

HPO ID	Term	Frequency
HP:0001249	Intellectual disability	Very frequent (80-99%)
HP:0001263	Global developmental delay	Very frequent (80-99%)
HP:0001999	Abnormal facial shape	Very frequent (80-99%)
HP:0008947	Floppy infant	Very frequent (80-99%)
HP:0000316	Hypertelorism	Frequent (30-79%)
HP:0000369	Low-set ears	Frequent (30-79%)
HP:0000400	Macrotia	Frequent (30-79%)
HP:0000494	Downslanted palpebral fissures	Frequent (30-79%)
HP:0001256	Intellectual disability, mild	Frequent (30-79%)
HP:0001956	Truncal obesity	Frequent (30-79%)
HP:0002465	Poor speech	Frequent (30-79%)
HP:0012301	Type II transferrin isoform profile	Frequent (30-79%)
HP:0012443	Abnormality of brain morphology	Frequent (30-79%)
HP:0000219	Thin upper lip vermilion	Occasional (5-29%)
HP:0000268	Dolichocephaly	Occasional (5-29%)
HP:0000272	Malar flattening	Occasional (5-29%)
HP:0000307	Pointed chin	Occasional (5-29%)
HP:0000319	Smooth philtrum	Occasional (5-29%)
HP:0000322	Short philtrum	Occasional (5-29%)
HP:0000331	Short chin	Occasional (5-29%)
HP:0000431	Wide nasal bridge	Occasional (5-29%)
HP:0000445	Wide nose	Occasional (5-29%)
HP:0000448	Prominent nose	Occasional (5-29%)
HP:0000470	Short neck	Occasional (5-29%)
HP:0000540	Hypermetropia	Occasional (5-29%)
HP:0000708	Atypical behavior	Occasional (5-29%)
HP:0000717	Autism	Occasional (5-29%)
HP:0000768	Pectus carinatum	Occasional (5-29%)
HP:0000973	Cutis laxa	Occasional (5-29%)
HP:0001250	Seizure	Occasional (5-29%)
HP:0001321	Cerebellar hypoplasia	Occasional (5-29%)
HP:0001382	Joint hypermobility	Occasional (5-29%)
HP:0002007	Frontal bossing	Occasional (5-29%)
HP:0002136	Broad-based gait	Occasional (5-29%)
HP:0002342	Intellectual disability, moderate	Occasional (5-29%)
HP:0002591	Polyphagia	Occasional (5-29%)
HP:0003186	Inverted nipples	Occasional (5-29%)
HP:0004523	Long eyebrows	Occasional (5-29%)
HP:0010801	Underdeveloped nasolabial fold	Occasional (5-29%)
HP:0010814	Abnormal position of hair whorl	Occasional (5-29%)
HP:0010864	Intellectual disability, severe	Occasional (5-29%)
HP:0045075	Sparse eyebrow	Occasional (5-29%)
HP:0000276	Long face	Very rare (<1-4%)
HP:0000286	Epicanthus	Very rare (<1-4%)
HP:0000527	Long eyelashes	Very rare (<1-4%)
HP:0002322	Resting tremor	Very rare (<1-4%)
HP:0004209	Clinodactyly of the 5th finger	Very rare (<1-4%)
HP:0004691	2-3 toe syndactyly	Very rare (<1-4%)
HP:0005469	Flat occiput	Very rare (<1-4%)
HP:0007165	Periventricular heterotopia	Very rare (<1-4%)

Identifiers

Disease identifiers

Field	Value
Canonical name	MAN1B1-congenital disorder of glycosylation
Mondo ID	MONDO:0018349
Orphanet	397941
SNOMED CT	733450008
UMLS	C4518783
MedGen	1375785
GARD	0012417
Is cancer (heuristic)	no

Also known as: carbohydrate deficient glycoprotein syndrome type II due to MAN1B1 deficiency · congenital disorder of glycosylation type 2 due to MAN1B1 deficiency · congenital disorder of glycosylation type II due to MAN1B1 deficiency · intellectual disability-truncal obesity syndrome · MAN1B1-CDG · MAN1B1-congenital disorder of glycosylation

Data availability: 1 ClinVar variant · 2 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 › disorder of protein N-glycosylation › MAN1B1-congenital disorder of glycosylation

Related subtypes (25): PMM2-congenital disorder of glycosylation, MGAT2-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, MOGS-congenital disorder of glycosylation, 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, RFT1-congenital disorder of glycosylation, ALG11-congenital disorder of glycosylation, DDOST-congenital disorder of glycosylation, TMEM165-congenital disorder of glycosylation, PGM1-congenital disorder of glycosylation, autism spectrum disorder - epilepsy - arthrogryposis syndrome, STT3A-congenital disorder of glycosylation, STT3B-congenital disorder of glycosylation, SLC39A8-CDG, congenital disorder of glycosylation type 1EE with or without immunodeficiency, ST3GAL3-congenital disorder of glycosylation

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

1 retrieved; paginated sample, class counts are floors:

1 pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
1254598	NM_016219.5(MAN1B1):c.484C>T (p.Gln162Ter)	MAN1B1	Pathogenic	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 7 · 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
MAN1B1	Definitive	Autosomal recessive	MAN1B1-congenital disorder of glycosylation	7

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
MAN1B1	Orphanet:397941	MAN1B1-CDG
MAN1B1	Orphanet:88616	Autosomal recessive non-syndromic intellectual disability

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
MAN1B1	HGNC:6823	ENSG00000177239	Q9UKM7	Endoplasmic reticulum mannosyl-oligosaccharide 1,2-alpha-mannosidase	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
MAN1B1	Endoplasmic reticulum mannosyl-oligosaccharide 1,2-alpha-mannosidase	Involved in glycoprotein quality control targeting of misfolded glycoproteins for degradation.

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)
MAN1B1	Enzyme (other)	yes	3.2.1.113	Glyco_hydro_47, 6hp_glycosidase-like_sf, Seven-hairpin_glycosidases

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
right uterine tube	1
skin of leg	1
stromal cell of endometrium	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
MAN1B1	268	ubiquitous	marker	stromal cell of endometrium, right uterine tube, skin of leg

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
MAN1B1	1,682

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
MAN1B1	Q9UKM7	6

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
Defective MAN1B1 causes MRT15	1	11420.0×	0.002	MAN1B1
Calnexin/calreticulin cycle	1	713.8×	0.007	MAN1B1
Diseases associated with N-glycosylation of proteins	1	634.4×	0.007	MAN1B1
ER Quality Control Compartment (ERQC)	1	543.8×	0.007	MAN1B1
N-glycan trimming in the ER and Calnexin/Calreticulin cycle	1	423.0×	0.007	MAN1B1
Translation of Structural Proteins	1	407.9×	0.007	MAN1B1
Late SARS-CoV-2 Infection Events	1	292.8×	0.008	MAN1B1
Maturation of spike protein	1	265.6×	0.008	MAN1B1
Diseases of glycosylation	1	131.3×	0.015	MAN1B1
Diseases of metabolism	1	80.4×	0.020	MAN1B1
SARS-CoV-2 Infection	1	80.4×	0.020	MAN1B1
Asparagine N-linked glycosylation	1	60.1×	0.025	MAN1B1
SARS-CoV Infections	1	55.4×	0.025	MAN1B1
Viral Infection Pathways	1	30.8×	0.042	MAN1B1
Infectious disease	1	24.8×	0.048	MAN1B1
Post-translational protein modification	1	19.2×	0.059	MAN1B1
Disease	1	13.1×	0.081	MAN1B1
Metabolism of proteins	1	12.4×	0.081	MAN1B1

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
protein alpha-1,2-demannosylation	1	16852.0×	4e-04	MAN1B1
endoplasmic reticulum mannose trimming	1	1203.7×	0.002	MAN1B1
N-glycan processing	1	732.7×	0.002	MAN1B1
oligosaccharide metabolic process	1	702.2×	0.002	MAN1B1
viral protein processing	1	543.6×	0.002	MAN1B1
ERAD pathway	1	181.2×	0.006	MAN1B1

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
MAN1B1	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
MAN1B1	1	Binding:1

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
MAN1B1	3.2.1.113, 3.2.1.209	mannosyl-oligosaccharide 1,2-alpha-mannosidase, endoplasmic reticulum Man9GlcNAc2 1,2-alpha-mannosidase

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	MAN1B1
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)
MAN1B1	1	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.