congenital disorder of glycosylation type 1EE with or without immunodeficiency

disease

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Also known as MAN2B2-CDGMAN2B2-congenital disorder of glycosylation

Summary

congenital disorder of glycosylation type 1EE with or without immunodeficiency (MONDO:0976261) is a disease with 1 cohort gene.

At a glance

Cohort genes: 1
ClinVar variants: 5

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	congenital disorder of glycosylation type 1EE with or without immunodeficiency
Mondo ID	MONDO:0976261
OMIM	621140
Orphanet	695110
UMLS	C6012707
MedGen	1876461
GARD	0028098
Is cancer (heuristic)	no

Also known as: MAN2B2-CDG · MAN2B2-congenital disorder of glycosylation

Data availability: 5 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 › disorder of protein N-glycosylation › congenital disorder of glycosylation type 1EE with or without immunodeficiency

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

5 retrieved; paginated sample, class counts are floors:

2 uncertain significance, 2 pathogenic, 1 likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
3774402	MAN2B2, 3-BP DEL, 440CTC	MAN2B2	Pathogenic	no assertion criteria provided
3774403	NM_015274.3(MAN2B2):c.2368G>A (p.Glu790Lys)	MAN2B2	Pathogenic	no assertion criteria provided
4529497	NM_015274.3(MAN2B2):c.852G>A (p.Trp284Ter)	MAN2B2	Likely pathogenic	criteria provided, multiple submitters, no conflicts
2347975	NM_015274.3(MAN2B2):c.2923C>A (p.Arg975Ser)	MAN2B2	Uncertain significance	criteria provided, multiple submitters, no conflicts
4279787	NM_015274.3(MAN2B2):c.1222C>T (p.Gln408Ter)	MAN2B2	Uncertain significance	criteria provided, single submitter

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
MAN2B2	Orphanet:695110	MAN2B2-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
MAN2B2	HGNC:29623	ENSG00000013288	Q9Y2E5	Epididymis-specific alpha-mannosidase	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
MAN2B2	Epididymis-specific alpha-mannosidase	Specifically cleaves terminal alpha 1,6-linked mannose residues on Man3GlcNAc and Man2GlcNAc core oligosaccharides generated by N-glycan degradation pathways, having little activity, if any, on larger mannose oligosaccharides.

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)
MAN2B2	Other/Unknown	no		Glyco_hydro_38_N, Gal_mutarotase_sf_dom, Glyco_hydro/deAcase_b/a-brl

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
descending thoracic aorta	1
stromal cell of endometrium	1
tendon of biceps brachii	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
MAN2B2	283	ubiquitous	marker	tendon of biceps brachii, stromal cell of endometrium, descending thoracic aorta

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
MAN2B2	1,079

Structural data

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

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
MAN2B2	Q9Y2E5	91.55

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 3. 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
Lysosomal oligosaccharide catabolism	1	2855.0×	0.001	MAN2B2
Metabolism of carbohydrates and carbohydrate derivatives	1	120.2×	0.012	MAN2B2
Metabolism	1	11.6×	0.086	MAN2B2

GO biological processes by enrichment

GO term	Cohort genes	Fold	FDR	Sample cohort genes
mannose metabolic process	1	2106.5×	9e-04	MAN2B2
oligosaccharide catabolic process	1	1532.0×	9e-04	MAN2B2
glycoprotein catabolic process	1	1053.2×	9e-04	MAN2B2

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
MAN2B2	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
MAN2B2	2	Binding:2

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	MAN2B2

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)
MAN2B2	2	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.

Cohort genes: MAN2B2