COG6-congenital disorder of glycosylation

Summary

COG6-congenital disorder of glycosylation (MONDO:0013810) is a disease caused by COG6 (GenCC Strong), with 1 cohort gene.

At a glance

• Prevalence: <1 / 1 000 000 (Worldwide) [Orphanet-validated]
• Causal gene: COG6 (GenCC Strong)
• Cohort genes: 1
• ClinVar variants: 225

Clinical features

Epidemiology

Prevalence records

2 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Cases/families		10	Worldwide	Validated
Point prevalence	<1 / 1 000 000		Worldwide	Validated

Identifiers

Disease identifiers

Field	Value
Canonical name	COG6-congenital disorder of glycosylation
Mondo ID	MONDO:0013810
OMIM	614576
Orphanet	464443
DOID	DOID:0070264
UMLS	C3553230
MedGen	766144
GARD	0010944
Is cancer (heuristic)	no

Also known as: CDG syndrome type IIL · CDG-IIL · CDG2L · CDGIIl · COG6-CDG · COG6-CDG (CDG-IIL) · COG6-congenital disorder of glycosylation · congenital disorder of glycosylation type 2l · congenital disorder of glycosylation type IIL · congenital disorder of glycosylation, type IIL

Data availability: 225 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 › COG6-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, 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, 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

225 retrieved; paginated sample, class counts are floors:

104 uncertain significance, 60 likely benign, 16 benign, 14 conflicting classifications of pathogenicity, 13 pathogenic, 7 likely pathogenic, 7 benign/likely benign, 3 pathogenic/likely pathogenic, 1 not provided

ClinVar	Variant (HGVS)	Gene	Classification	Review
1253806	NM_020751.3(COG6):c.548dup (p.Lys184fs)	COG6	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1454276	NM_020751.3(COG6):c.252del (p.Ala85fs)	COG6	Pathogenic	criteria provided, single submitter
183333	NM_020751.3(COG6):c.1167-24A>G	COG6	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2203823	NM_020751.3(COG6):c.651_654del (p.Leu217fs)	COG6	Pathogenic	criteria provided, multiple submitters, no conflicts
2498080	NM_020751.3(COG6):c.1672C>T (p.Gln558Ter)	COG6	Pathogenic	criteria provided, single submitter
2498081	NM_020751.3(COG6):c.153+392A>G	COG6	Pathogenic	criteria provided, single submitter
2576959	NM_020751.3(COG6):c.1884T>G (p.Tyr628Ter)	COG6	Pathogenic	no assertion criteria provided
30628	NM_020751.3(COG6):c.1646G>T (p.Gly549Val)	COG6	Pathogenic	criteria provided, single submitter
432111	NM_020751.3(COG6):c.1535T>G (p.Leu512Ter)	COG6	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
4783322	NM_020751.3(COG6):c.1078C>T (p.Arg360Ter)	COG6	Pathogenic	criteria provided, single submitter
4791614	NM_020751.3(COG6):c.686G>A (p.Trp229Ter)	COG6	Pathogenic	criteria provided, single submitter
4845389	NM_020751.3(COG6):c.1009+1G>T	COG6	Pathogenic	criteria provided, single submitter
487578	NM_020751.3(COG6):c.388C>T (p.Gln130Ter)	COG6	Pathogenic	criteria provided, single submitter
493007	NM_020751.3(COG6):c.511C>T (p.Arg171Ter)	COG6	Pathogenic	criteria provided, multiple submitters, no conflicts
493010	NM_020751.3(COG6):c.1239dup (p.Phe414fs)	COG6	Pathogenic	no assertion criteria provided
816813	NM_020751.3(COG6):c.726del (p.Cys242fs)	COG6	Pathogenic	no assertion criteria provided
1346002	NM_020751.3(COG6):c.1585-2A>G	COG6	Likely pathogenic	criteria provided, single submitter
2136197	NM_020751.3(COG6):c.298-1G>A	COG6	Likely pathogenic	criteria provided, multiple submitters, no conflicts
3065602	NM_020751.3(COG6):c.1826+2T>C	COG6	Likely pathogenic	criteria provided, single submitter
3779114	NM_020751.3(COG6):c.182C>G (p.Ser61Ter)	COG6	Likely pathogenic	criteria provided, single submitter
493009	NM_020751.3(COG6):c.785A>G (p.Tyr262Cys)	COG6	Likely pathogenic	criteria provided, single submitter
802961	NM_020751.3(COG6):c.154-2A>G	COG6	Likely pathogenic	criteria provided, single submitter
830067	NM_020751.3(COG6):c.540G>A (p.Glu180=)	COG6	Likely pathogenic	criteria provided, single submitter
194778	NM_020751.3(COG6):c.1693-12T>C	COG6	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
312133	NM_020751.3(COG6):c.320A>T (p.Asp107Val)	COG6	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
312137	NM_020751.3(COG6):c.729C>T (p.Asp243=)	COG6	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
312141	NM_020751.3(COG6):c.1075-12A>C	COG6	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
312148	NM_020751.3(COG6):c.1759C>T (p.Arg587Cys)	COG6	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
312150	NM_020751.3(COG6):c.1947G>A (p.Pro649=)	COG6	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
3147123	NM_020751.3(COG6):c.245A>G (p.Lys82Arg)	COG6	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 3 · 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
COG6	Strong	Autosomal recessive	COG6-congenital disorder of glycosylation	3

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
COG6	Orphanet:363523	Hypohidrosis-enamel hypoplasia-palmoplantar keratoderma-intellectual disability syndrome
COG6	Orphanet:464443	COG6-CGD

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
COG6	HGNC:18621	ENSG00000133103	Q9Y2V7	Conserved oligomeric Golgi complex subunit 6	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
COG6	Conserved oligomeric Golgi complex subunit 6	Required for normal Golgi function.

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)
COG6	Other/Unknown	no		COG6, COG6_N, COG6_C

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
calcaneal tendon	1
secondary oocyte	1
tibia	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
COG6	254	ubiquitous	marker	secondary oocyte, tibia, calcaneal tendon

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
COG6	2,336

Structural data

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

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
COG6	Q9Y2V7	86.62

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
Intra-Golgi traffic	1	259.6×	0.007	COG6
Retrograde transport at the Trans-Golgi-Network	1	219.6×	0.007	COG6
COPI-mediated anterograde transport	1	109.8×	0.009	COG6

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
retrograde transport, vesicle recycling within Golgi	1	1872.4×	0.002	COG6
intra-Golgi vesicle-mediated transport	1	526.6×	0.004	COG6
Golgi organization	1	133.8×	0.010	COG6
protein transport	1	43.9×	0.023	COG6

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
COG6	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
COG6	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	COG6

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)
COG6	2	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.