Congenital disorder of glycosylation, type 2v

Summary

Congenital disorder of glycosylation, type 2v (MONDO:0030423) is a disease caused by EDEM3 (GenCC Strong), with 1 cohort gene.

At a glance

• Causal gene: EDEM3 (GenCC Strong)
• Cohort genes: 1
• ClinVar variants: 18

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	congenital disorder of glycosylation, type 2v
Mondo ID	MONDO:0030423
OMIM	619493
Orphanet	695783
DOID	DOID:0051050
UMLS	C5561971
MedGen	1794181
GARD	0025557
Is cancer (heuristic)	no

Also known as: CDG2V

Data availability: 18 ClinVar variants · 3 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 › congenital disorder of glycosylation, type 2v

Related subtypes (25): MGAT2-congenital disorder of glycosylation, leukocyte adhesion deficiency type II, SLC35A2-congenital disorder of glycosylation, SLC35A1-congenital disorder of glycosylation, MOGS-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 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

18 retrieved; paginated sample, class counts are floors:

11 pathogenic, 4 uncertain significance, 2 likely pathogenic, 1 benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
1210133	NM_025191.4(EDEM3):c.1859del (p.Ile620fs)	EDEM3	Pathogenic	no assertion criteria provided
1210134	NM_025191.4(EDEM3):c.2001dup (p.Ala668fs)	EDEM3	Pathogenic	no assertion criteria provided
1210135	NM_025191.4(EDEM3):c.1369del (p.Arg457fs)	EDEM3	Pathogenic	no assertion criteria provided
1210136	NM_025191.4(EDEM3):c.940A>T (p.Arg314Ter)	EDEM3	Pathogenic	no assertion criteria provided
1210137	NM_025191.4(EDEM3):c.853+1G>T	EDEM3	Pathogenic	no assertion criteria provided
1210138	NM_025191.4(EDEM3):c.1407T>A (p.Tyr469Ter)	EDEM3	Pathogenic	no assertion criteria provided
1210139	NM_025191.4(EDEM3):c.1382_1385del (p.Phe461fs)	EDEM3	Pathogenic	no assertion criteria provided
1210140	NM_025191.4(EDEM3):c.182A>G (p.Asp61Gly)	EDEM3	Pathogenic	no assertion criteria provided
1210141	NM_025191.4(EDEM3):c.1366G>A (p.Asp456Asn)	EDEM3	Pathogenic	no assertion criteria provided
3382610	NM_025191.4(EDEM3):c.848del (p.Arg283fs)	EDEM3	Pathogenic	criteria provided, single submitter
4845475	NM_025191.4(EDEM3):c.1998del (p.Pro667fs)	EDEM3	Pathogenic	criteria provided, single submitter
1803729	NM_025191.4(EDEM3):c.1090del (p.Asp364fs)	EDEM3	Likely pathogenic	criteria provided, single submitter
3767979	NM_025191.4(EDEM3):c.793C>T (p.Arg265Ter)	EDEM3	Likely pathogenic	criteria provided, single submitter
2582423	NM_025191.4(EDEM3):c.295G>A (p.Ala99Thr)	EDEM3	Uncertain significance	criteria provided, single submitter
2582512	NM_025191.4(EDEM3):c.1692-28A>T	EDEM3	Uncertain significance	criteria provided, single submitter
3382958	NM_025191.4(EDEM3):c.1661A>T (p.Asp554Val)	EDEM3	Uncertain significance	criteria provided, multiple submitters, no conflicts
3382959	NM_025191.4(EDEM3):c.286G>A (p.Val96Ile)	EDEM3	Uncertain significance	criteria provided, single submitter
3068615	NM_025191.4(EDEM3):c.2236C>T (p.Pro746Ser)	EDEM3	Benign	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 3 · 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
EDEM3	Strong	Autosomal recessive	congenital disorder of glycosylation, type 2v	3

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
EDEM3	Orphanet:695783	EDEM3-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
EDEM3	HGNC:16787	ENSG00000116406	Q9BZQ6	ER degradation-enhancing alpha-mannosidase-like protein 3	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
EDEM3	ER degradation-enhancing alpha-mannosidase-like protein 3	Involved in endoplasmic reticulum-associated degradation (ERAD).

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)
EDEM3	Other/Unknown	no		Glyco_hydro_47, PA_domain, 6hp_glycosidase-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
jejunal mucosa	1
mucosa of sigmoid colon	1
pylorus	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
EDEM3	280	ubiquitous	marker	pylorus, mucosa of sigmoid colon, jejunal mucosa

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
EDEM3	1,252

Structural data

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

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
EDEM3	Q9BZQ6	78.50

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 1. 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
ER Quality Control Compartment (ERQC)	1	543.8×	0.002	EDEM3

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
ubiquitin-dependent glycoprotein ERAD pathway	1	8426.0×	6e-04	EDEM3
endoplasmic reticulum mannose trimming	1	1203.7×	0.002	EDEM3
endoplasmic reticulum unfolded protein response	1	295.6×	0.006	EDEM3
ERAD pathway	1	181.2×	0.007	EDEM3
carbohydrate metabolic process	1	135.9×	0.007	EDEM3

Therapeutics

Drug target analysis

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

Druggability breadth: 0 of 1 evidence-associated genes (0%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
EDEM3	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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	EDEM3

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)
EDEM3	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.