COG8-congenital disorder of glycosylation

Summary

COG8-congenital disorder of glycosylation (MONDO:0012635) is a disease caused by COG8 (GenCC Strong), with 2 cohort genes.

At a glance

• Prevalence: <1 / 1 000 000 (Worldwide) [Orphanet-validated]
• Causal gene: COG8 (GenCC Strong)
• Cohort genes: 2
• ClinVar variants: 157
• Phenotypes (HPO): 24

Clinical features

Epidemiology

Prevalence records

2 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Cases/families		2	Worldwide	Validated
Point prevalence	<1 / 1 000 000		Worldwide	Validated

Signs & symptoms

Clinical features (HPO)

24 HPO clinical features (Orphanet curated; top 24 by frequency):

HPO ID	Term	Frequency
HP:0001249	Intellectual disability	Frequent (30-79%)
HP:0001250	Seizure	Frequent (30-79%)
HP:0001251	Ataxia	Frequent (30-79%)
HP:0001508	Failure to thrive	Frequent (30-79%)
HP:0002243	Protein-losing enteropathy	Frequent (30-79%)
HP:0002376	Developmental regression	Frequent (30-79%)
HP:0002421	Poor head control	Frequent (30-79%)
HP:0002465	Poor speech	Frequent (30-79%)
HP:0003202	Skeletal muscle atrophy	Frequent (30-79%)
HP:0007267	Chronic axonal neuropathy	Frequent (30-79%)
HP:0008947	Floppy infant	Frequent (30-79%)
HP:0011344	Severe global developmental delay	Frequent (30-79%)
HP:0012537	Food intolerance	Frequent (30-79%)
HP:0000253	Progressive microcephaly	Occasional (5-29%)
HP:0001137	Alternating esotropia	Occasional (5-29%)
HP:0001272	Cerebellar atrophy	Occasional (5-29%)
HP:0001336	Myoclonus	Occasional (5-29%)
HP:0001943	Hypoglycemia	Occasional (5-29%)
HP:0002119	Ventriculomegaly	Occasional (5-29%)
HP:0002910	Elevated circulating hepatic transaminase concentration	Occasional (5-29%)
HP:0006846	Acute encephalopathy	Occasional (5-29%)
HP:0007366	Atrophy/Degeneration affecting the brainstem	Occasional (5-29%)
HP:0007420	Spontaneous hematomas	Occasional (5-29%)
HP:0008151	Prolonged prothrombin time	Occasional (5-29%)

Identifiers

Disease identifiers

Field	Value
Canonical name	COG8-congenital disorder of glycosylation
Mondo ID	MONDO:0012635
MeSH	C566987
OMIM	611182
Orphanet	95428
DOID	DOID:0070260
SNOMED CT	717774004
UMLS	C1970021
MedGen	409971
GARD	0012411
Is cancer (heuristic)	no

Also known as: carbohydrate deficient glycoprotein syndrome type IIh · CDG syndrome type IIh · CDG-IIh · CDG2H · COG8-CDG · COG8-CDG (CDG-IIh) · COG8-congenital disorder of glycosylation · congenital disorder of glycosylation type 2h · congenital disorder of glycosylation type IIh · congenital disorder of glycosylation, type IIh

Data availability: 157 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 › COG8-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, 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 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

157 retrieved; paginated sample, class counts are floors:

68 uncertain significance, 46 likely benign, 22 conflicting classifications of pathogenicity, 7 benign/likely benign, 5 likely pathogenic, 4 pathogenic, 3 benign, 2 pathogenic/likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
1098271	NM_032382.5(COG8):c.1550_1556del (p.Leu517fs)	COG8	Pathogenic	criteria provided, single submitter
3647	NM_032382.5(COG8):c.1611C>G (p.Tyr537Ter)	COG8	Pathogenic	no assertion criteria provided
3648	NM_032382.5(COG8):c.1413+1G>A	COG8	Pathogenic	no assertion criteria provided
4712261	NM_032382.5(COG8):c.1027del (p.Asp343fs)	COG8	Pathogenic	criteria provided, single submitter
932935	NM_032382.5(COG8):c.1583-1G>A	COG8	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
966979	NM_032382.5(COG8):c.1680_1681del (p.Glu560fs)	COG8	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2504275	NM_032382.5(COG8):c.1396del (p.Glu466fs)	COG8	Likely pathogenic	criteria provided, multiple submitters, no conflicts
3767116	NM_032382.5(COG8):c.317_327dup (p.Ser110fs)	COG8	Likely pathogenic	criteria provided, single submitter
3779115	NM_032382.5(COG8):c.513T>G (p.Tyr171Ter)	COG8	Likely pathogenic	criteria provided, single submitter
659501	NM_032382.5(COG8):c.585+1G>T	COG8	Likely pathogenic	criteria provided, single submitter
3649	NM_032382.5(COG8):c.1687_1688del (p.Phe563fs)	LOC130059304	Likely pathogenic	criteria provided, multiple submitters, no conflicts
1040489	NM_032382.5(COG8):c.1468G>T (p.Gly490Trp)	COG8	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1060995	NM_032382.5(COG8):c.19A>G (p.Ile7Val)	COG8	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1384072	NM_032382.5(COG8):c.1549C>G (p.Leu517Val)	COG8	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1414165	NM_032382.5(COG8):c.416G>A (p.Arg139His)	COG8	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
196567	NM_032382.5(COG8):c.597C>T (p.Asn199=)	COG8	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
196568	NM_032382.5(COG8):c.1017C>T (p.Gly339=)	COG8	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
285872	NM_032382.5(COG8):c.1079G>A (p.Gly360Glu)	COG8	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
286530	NM_032382.5(COG8):c.1006C>T (p.Arg336Trp)	COG8	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
320314	NM_032382.5(COG8):c.903C>G (p.Pro301=)	COG8	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
320317	NM_032382.5(COG8):c.585+8C>T	COG8	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
384763	NM_032382.5(COG8):c.603G>A (p.Val201=)	COG8	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
391032	NM_032382.5(COG8):c.996C>T (p.Thr332=)	COG8	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
468871	NM_032382.5(COG8):c.525G>A (p.Leu175=)	COG8	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
508007	NM_032382.5(COG8):c.1467C>T (p.Ser489=)	COG8	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
703036	NM_032382.5(COG8):c.386T>C (p.Val129Ala)	COG8	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
885271	NM_032382.5(COG8):c.1524G>A (p.Pro508=)	COG8	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
885272	NM_032382.5(COG8):c.1413+12C>G	COG8	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
886168	NM_032382.5(COG8):c.1093G>C (p.Gly365Arg)	COG8	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
886170	NM_032382.5(COG8):c.886G>A (p.Glu296Lys)	COG8	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications

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
COG8	Strong	Autosomal recessive	COG8-congenital disorder of glycosylation	3

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
COG8	Orphanet:95428	COG8-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
COG8	HGNC:18623	ENSG00000213380	Q96MW5	Conserved oligomeric Golgi complex subunit 8	gencc,clinvar
PDF	HGNC:30012	ENSG00000258429	Q9HBH1	Peptide deformylase, mitochondrial	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
COG8	Conserved oligomeric Golgi complex subunit 8	Required for normal Golgi function.
PDF	Peptide deformylase, mitochondrial	Removes the formyl group from the N-terminal Met of newly synthesized proteins.

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
Enzyme (other)	1	6.0×	0.320
Other/Unknown	1	0.9×	0.805

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
COG8	Other/Unknown	no		COG8, Cullin_repeat-like_dom_sf, COG8_Metazoal_Plant
PDF	Enzyme (other)	yes	3.5.1.88	Peptide_deformylase, Peptide_deformylase_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)	2
unknown	0

Top tissues across cohort

Tissue	Cohort genes
kidney epithelium	1
tibialis anterior	1
upper arm skin	1
adult mammalian kidney	1
male germ line stem cell (sensu Vertebrata) in testis	1
primordial germ cell in gonad	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
COG8	236	ubiquitous	marker	upper arm skin, kidney epithelium, tibialis anterior
PDF	131	ubiquitous	yes	male germ line stem cell (sensu Vertebrata) in testis, primordial germ cell in gonad, adult mammalian kidney

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
PDF	1,833
COG8	1,359

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
PDF	Q9HBH1	2

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
COG8	Q96MW5	80.67

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 3. Enrichment computed across 2 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	COG8
Retrograde transport at the Trans-Golgi-Network	1	219.6×	0.007	COG8
COPI-mediated anterograde transport	1	109.8×	0.009	COG8

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
peptidyl-methionine modification	1	2808.7×	0.003	PDF
retrograde transport, vesicle recycling within Golgi	1	936.2×	0.004	COG8
intra-Golgi vesicle-mediated transport	1	263.3×	0.009	COG8
post-translational protein modification	1	210.7×	0.009	PDF
Golgi organization	1	66.9×	0.024	COG8
translation	1	51.4×	0.026	PDF
protein transport	1	21.9×	0.051	COG8
positive regulation of cell population proliferation	1	16.8×	0.059	PDF

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
COG8	0	0
PDF	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
PDF	22	Binding:22
COG8	2	Binding:2

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
PDF	3.5.1.88	peptide deformylase

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	PDF
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	1	COG8

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)
COG8	2	—
PDF	22	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.