congenital disorder of glycosylation, type IIq

Summary

congenital disorder of glycosylation, type IIq (MONDO:0054559) is a disease caused by COG2 (GenCC Strong), with 2 cohort genes.

At a glance

• Prevalence: <1 / 1 000 000 (Worldwide) [Orphanet-validated]
• Causal gene: COG2 (GenCC Strong)
• Cohort genes: 2
• ClinVar variants: 145
• Phenotypes (HPO): 13

Clinical features

Epidemiology

Prevalence records

2 prevalence record(s), Orphanet:

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

Signs & symptoms

Clinical features (HPO)

13 HPO clinical features (Orphanet curated; top 13 by frequency):

HPO ID	Term	Frequency
HP:0001249	Intellectual disability	Frequent (30-79%)
HP:0001410	Decreased liver function	Frequent (30-79%)
HP:0001999	Abnormal facial shape	Frequent (30-79%)
HP:0002079	Hypoplasia of the corpus callosum	Frequent (30-79%)
HP:0002361	Psychomotor deterioration	Frequent (30-79%)
HP:0002506	Diffuse cerebral atrophy	Frequent (30-79%)
HP:0002510	Spastic tetraplegia	Frequent (30-79%)
HP:0003256	Abnormality of the coagulation cascade	Frequent (30-79%)
HP:0005484	Secondary microcephaly	Frequent (30-79%)
HP:0010818	Generalized tonic seizure	Frequent (30-79%)
HP:0010837	Decreased circulating ceruloplasmin concentration	Frequent (30-79%)
HP:0011967	Decreased circulating copper concentration	Frequent (30-79%)
HP:0012506	Small pituitary gland	Frequent (30-79%)

Identifiers

Disease identifiers

Field	Value
Canonical name	congenital disorder of glycosylation, type IIq
Mondo ID	MONDO:0054559
OMIM	617395
Orphanet	435934
DOID	DOID:0070269
UMLS	C4479353
MedGen	1390458
GARD	0017720
Is cancer (heuristic)	no

Also known as: CDG Iiq · CDG2Q · COG2-CDG · COG2-related congenital disorder of glycosylation

Data availability: 145 ClinVar variants · 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 › congenital disorder of glycosylation type II › congenital disorder of glycosylation, type IIq

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 2v, congenital disorder of glycosylation, type IIw, 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

145 retrieved; paginated sample, class counts are floors:

74 likely benign, 46 uncertain significance, 8 benign, 7 pathogenic, 4 conflicting classifications of pathogenicity, 3 benign/likely benign, 2 no classifications from unflagged records, 1 likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
2425124	NC_000001.10:g.(?230203028)(231413288_?)del	CAPN9	Pathogenic	criteria provided, single submitter
1970272	NM_007357.3(COG2):c.260del (p.Gln87fs)	COG2	Pathogenic	criteria provided, single submitter
3251550	NC_000001.10:g.(230814799_230819319)_(230820983_230822680)del	COG2	Pathogenic	criteria provided, single submitter
3727680	NM_007357.3(COG2):c.523delinsCAGGCCCATACAGGTGCAATGGTTTTCTGGAGCACCTGTATGCTC (p.Thr175fs)	COG2	Pathogenic	criteria provided, single submitter
4689533	NC_000001.10:g.(?230778226)(230829729_?)del	COG2	Pathogenic	criteria provided, single submitter
4753913	NM_007357.3(COG2):c.1509del (p.Lys503fs)	COG2	Pathogenic	criteria provided, single submitter
568944	NM_007357.3(COG2):c.436dup (p.Ile146fs)	COG2	Pathogenic	criteria provided, single submitter
996958	NM_007357.3(COG2):c.1855C>T (p.Gln619Ter)	COG2	Likely pathogenic	criteria provided, single submitter
1399803	NM_007357.3(COG2):c.1565A>G (p.Lys522Arg)	COG2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
579951	NM_007357.3(COG2):c.2026G>A (p.Ala676Thr)	COG2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
714955	NM_007357.3(COG2):c.402A>G (p.Ile134Met)	COG2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
718942	NM_007357.3(COG2):c.218A>G (p.Asn73Ser)	COG2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1009715	NM_007357.3(COG2):c.1601T>A (p.Ile534Asn)	COG2	Uncertain significance	criteria provided, multiple submitters, no conflicts
1011775	NM_007357.3(COG2):c.1015G>C (p.Ala339Pro)	COG2	Uncertain significance	criteria provided, multiple submitters, no conflicts
1017465	NM_007357.3(COG2):c.1284G>T (p.Arg428Ser)	COG2	Uncertain significance	criteria provided, single submitter
1021470	NM_007357.3(COG2):c.1765G>C (p.Val589Leu)	COG2	Uncertain significance	criteria provided, single submitter
1030210	NM_007357.3(COG2):c.116G>A (p.Arg39Gln)	COG2	Uncertain significance	criteria provided, multiple submitters, no conflicts
1030211	NM_007357.3(COG2):c.1529G>T (p.Arg510Leu)	COG2	Uncertain significance	criteria provided, multiple submitters, no conflicts
1040914	NM_007357.3(COG2):c.1358G>A (p.Arg453Gln)	COG2	Uncertain significance	criteria provided, single submitter
1350078	NM_007357.3(COG2):c.1067G>A (p.Arg356Gln)	COG2	Uncertain significance	criteria provided, multiple submitters, no conflicts
1352034	NM_007357.3(COG2):c.412C>T (p.Arg138Trp)	COG2	Uncertain significance	criteria provided, single submitter
1362595	NM_007357.3(COG2):c.722G>A (p.Arg241Gln)	COG2	Uncertain significance	criteria provided, multiple submitters, no conflicts
1386352	NM_007357.3(COG2):c.504A>C (p.Gln168His)	COG2	Uncertain significance	criteria provided, multiple submitters, no conflicts
1413898	NM_007357.3(COG2):c.115C>T (p.Arg39Trp)	COG2	Uncertain significance	criteria provided, multiple submitters, no conflicts
1417869	NM_007357.3(COG2):c.860G>A (p.Cys287Tyr)	COG2	Uncertain significance	criteria provided, single submitter
1420836	NM_007357.3(COG2):c.1133A>G (p.Lys378Arg)	COG2	Uncertain significance	criteria provided, single submitter
1464722	NM_007357.3(COG2):c.109A>G (p.Arg37Gly)	COG2	Uncertain significance	criteria provided, single submitter
1470130	NM_007357.3(COG2):c.151C>T (p.Leu51Phe)	COG2	Uncertain significance	criteria provided, single submitter
1946848	NM_007357.3(COG2):c.482G>A (p.Ser161Asn)	COG2	Uncertain significance	criteria provided, single submitter
1959196	NM_007357.3(COG2):c.1301T>C (p.Met434Thr)	COG2	Uncertain significance	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 2 · 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
COG2	Strong	Autosomal recessive	congenital disorder of glycosylation, type IIq	2

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
COG2	Orphanet:435934	COG2-CDG

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
COG2	HGNC:6546	ENSG00000135775	Q14746	Conserved oligomeric Golgi complex subunit 2	gencc,clinvar
CAPN9	HGNC:1486	ENSG00000135773	O14815	Calpain-9	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
COG2	Conserved oligomeric Golgi complex subunit 2	Required for normal Golgi morphology and function.
CAPN9	Calpain-9	Calcium-regulated non-lysosomal thiol-protease.

Protein-family classification

Druggable: 1 · Difficult: 0 · Unknown: 1 · Druggable fraction: 0.5

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
Protease	1	18.3×	0.108
Other/Unknown	1	0.9×	0.805

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
COG2	Other/Unknown	no		COG2, COG_su2_N, COG_complex_COG2_C
CAPN9	Protease	yes	3.4.22.B28	Pept_cys_AS, Peptidase_C2_calpain_cat, EF_hand_dom

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)	2
unknown	0

Top tissues across cohort

Tissue	Cohort genes
rectum	2
cerebellar hemisphere	1
right hemisphere of cerebellum	1
C1 segment of cervical spinal cord	1
mucosa of transverse colon	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
COG2	287	ubiquitous	marker	rectum, right hemisphere of cerebellum, cerebellar hemisphere
CAPN9	166	tissue_specific	yes	C1 segment of cervical spinal cord, rectum, mucosa of transverse colon

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
COG2	1,535
CAPN9	1,055

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
CAPN9	O14815	2

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
COG2	Q14746	81.38

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 5. 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
Intra-Golgi traffic	1	129.8×	0.023	COG2
Retrograde transport at the Trans-Golgi-Network	1	109.8×	0.023	COG2
Degradation of the extracellular matrix	1	58.9×	0.023	CAPN9
COPI-mediated anterograde transport	1	54.9×	0.023	COG2
Extracellular matrix organization	1	31.6×	0.031	CAPN9

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
retrograde transport, vesicle recycling within Golgi	1	936.2×	0.006	COG2
digestion	1	312.1×	0.008	CAPN9
intra-Golgi vesicle-mediated transport	1	263.3×	0.008	COG2
Golgi organization	1	66.9×	0.022	COG2
protein transport	1	21.9×	0.054	COG2
proteolysis	1	17.1×	0.058	CAPN9

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
COG2	0	0
CAPN9	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
COG2	1	Binding:1
CAPN9	1	Binding:1

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
CAPN9	3.4.22.B28, 3.4.22.B29	,

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	1	CAPN9
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	1	COG2

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)
COG2	1	—
CAPN9	1	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.