COG7-congenital disorder of glycosylation

Summary

COG7-congenital disorder of glycosylation (MONDO:0012118) is a disease caused by COG7 (GenCC Definitive), with 3 cohort genes.

At a glance

• Prevalence: <1 / 1 000 000 (Worldwide) [Orphanet-validated]
• Causal gene: COG7 (GenCC Definitive)
• Cohort genes: 3
• ClinVar variants: 512
• Phenotypes (HPO): 33

Clinical features

Epidemiology

Prevalence records

2 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Cases/families		8	Worldwide	Validated
Point prevalence	<1 / 1 000 000		Worldwide	Validated

Signs & symptoms

Clinical features (HPO)

33 HPO clinical features (Orphanet curated; top 33 by frequency):

HPO ID	Term	Frequency
HP:0001252	Hypotonia	Very frequent (80-99%)
HP:0001508	Failure to thrive	Very frequent (80-99%)
HP:0001954	Recurrent fever	Very frequent (80-99%)
HP:0002719	Recurrent infections	Very frequent (80-99%)
HP:0002910	Elevated circulating hepatic transaminase concentration	Very frequent (80-99%)
HP:0008897	Postnatal growth retardation	Very frequent (80-99%)
HP:0011968	Feeding difficulties	Very frequent (80-99%)
HP:0012301	Type II transferrin isoform profile	Very frequent (80-99%)
HP:0012444	Brain atrophy	Very frequent (80-99%)
HP:0000077	Abnormality of the kidney	Frequent (30-79%)
HP:0000253	Progressive microcephaly	Frequent (30-79%)
HP:0000952	Jaundice	Frequent (30-79%)
HP:0001167	Abnormality of finger	Frequent (30-79%)
HP:0001250	Seizure	Frequent (30-79%)
HP:0001265	Hyporeflexia	Frequent (30-79%)
HP:0001284	Areflexia	Frequent (30-79%)
HP:0001518	Small for gestational age	Frequent (30-79%)
HP:0001627	Abnormal heart morphology	Frequent (30-79%)
HP:0001999	Abnormal facial shape	Frequent (30-79%)
HP:0002014	Diarrhea	Frequent (30-79%)
HP:0002240	Hepatomegaly	Frequent (30-79%)
HP:0003236	Elevated circulating creatine kinase concentration	Frequent (30-79%)
HP:0007392	Excessive wrinkled skin	Frequent (30-79%)
HP:0011451	Congenital microcephaly	Frequent (30-79%)
HP:0000160	Narrow mouth	Occasional (5-29%)
HP:0000278	Retrognathia	Occasional (5-29%)
HP:0000347	Micrognathia	Occasional (5-29%)
HP:0000470	Short neck	Occasional (5-29%)
HP:0001181	Adducted thumb	Occasional (5-29%)
HP:0001272	Cerebellar atrophy	Occasional (5-29%)
HP:0001433	Hepatosplenomegaly	Occasional (5-29%)
HP:0012157	Subcortical cerebral atrophy	Occasional (5-29%)
HP:0100807	Long fingers	Occasional (5-29%)

Identifiers

Disease identifiers

Field	Value
Canonical name	COG7-congenital disorder of glycosylation
Mondo ID	MONDO:0012118
MeSH	C535754
OMIM	608779
Orphanet	79333
DOID	DOID:0070257
SNOMED CT	717773005
UMLS	C2931010
MedGen	419311
GARD	0009842
Is cancer (heuristic)	no

Also known as: carbohydrate deficient glycoprotein syndrome type IIe · CDG 2E · CDG syndrome type IIe · CDG-IIe · CDG2E · COG7-CDG · COG7-CDG (CDG-IIe) · COG7-congenital disorder of glycosylation · congenital disorder of glycosylation type 2e · congenital disorder of glycosylation type IIe · congenital disorder of glycosylation, type IIe

Data availability: 512 ClinVar variants · 4 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 › COG7-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, 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 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

512 retrieved; paginated sample, class counts are floors:

248 likely benign, 178 uncertain significance, 37 conflicting classifications of pathogenicity, 17 pathogenic, 11 benign/likely benign, 10 benign, 8 likely pathogenic, 3 pathogenic/likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
1333	NM_025114.4(CEP290):c.5668G>T (p.Gly1890Ter)	CEP290	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1184979	NM_153603.4(COG7):c.1817C>A (p.Ala606Asp)	COG7	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
196587	NM_153603.4(COG7):c.323dup (p.Leu108fs)	COG7	Pathogenic	criteria provided, multiple submitters, no conflicts
2004610	NM_153603.4(COG7):c.1375del (p.Gln459fs)	COG7	Pathogenic	criteria provided, single submitter
2113880	NM_153603.4(COG7):c.698del (p.Leu232_Leu233insTer)	COG7	Pathogenic	criteria provided, single submitter
2120057	NM_153603.4(COG7):c.1255dup (p.Cys419fs)	COG7	Pathogenic	criteria provided, single submitter
2505114	NM_153603.4(COG7):c.1330C>T (p.Arg444Ter)	COG7	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2773270	NM_153603.4(COG7):c.1784T>A (p.Leu595Ter)	COG7	Pathogenic	criteria provided, single submitter
2775952	NM_153603.4(COG7):c.1498dup (p.Tyr500fs)	COG7	Pathogenic	criteria provided, single submitter
2813995	NM_153603.4(COG7):c.1808G>A (p.Trp603Ter)	COG7	Pathogenic	criteria provided, single submitter
3243501	NC_000016.9:g.(?23417377)(23417603_?)del	COG7	Pathogenic	criteria provided, single submitter
3615091	NM_153603.4(COG7):c.1702C>T (p.Arg568Ter)	COG7	Pathogenic	criteria provided, single submitter
3650	NM_153603.4(COG7):c.169+4A>C	COG7	Pathogenic	criteria provided, single submitter
3656005	NM_153603.4(COG7):c.343_344insTCCCTCTCCCTCTCCCGTCTCCCTCTCCCTCTCCCGTCTCCCGCTCCCTCTCCCGGCTCCCGCTCCCGCTCCCGGGGCCCTCTCCCGCGCGCGGCNNNNNNNNNNAAAAAAAAAAAAAAAAAAAAAGAAATTGACCAAGTGA (p.Lys115delinsIleProLeuProLeuProSerProSerProSerProValSerArgSerLeuSerArgLeuProLeuProLeuProGlyProSerProAlaArgGlyXaaXaaXaaXaaLysLysLysLysLysLysArgAsnTer)	COG7	Pathogenic	criteria provided, single submitter
3671796	NM_153603.4(COG7):c.79G>T (p.Glu27Ter)	COG7	Pathogenic	criteria provided, single submitter
4715337	NM_153603.4(COG7):c.669C>A (p.Tyr223Ter)	COG7	Pathogenic	criteria provided, single submitter
4730928	NM_153603.4(COG7):c.1673C>A (p.Ser558Ter)	COG7	Pathogenic	criteria provided, single submitter
4803547	NM_153603.4(COG7):c.1999C>T (p.Gln667Ter)	COG7	Pathogenic	criteria provided, single submitter
548708	NM_153603.4(COG7):c.1476-1G>T	COG7	Pathogenic	criteria provided, single submitter
1334892	NM_153603.4(COG7):c.1A>G (p.Met1Val)	LOC130058658	Pathogenic	criteria provided, single submitter
1184980	NM_153603.4(COG7):c.1046A>G (p.Asp349Gly)	COG7	Likely pathogenic	criteria provided, single submitter
1676422	NM_153603.4(COG7):c.318+1G>A	COG7	Likely pathogenic	criteria provided, multiple submitters, no conflicts
1986961	NM_153603.4(COG7):c.687+1G>A	COG7	Likely pathogenic	criteria provided, single submitter
2020320	NM_153603.4(COG7):c.1410-2A>T	COG7	Likely pathogenic	criteria provided, single submitter
2813996	NM_153603.4(COG7):c.848T>G (p.Leu283Arg)	COG7	Likely pathogenic	criteria provided, single submitter
3615150	NM_153603.4(COG7):c.1887+1G>A	COG7	Likely pathogenic	criteria provided, single submitter
4692143	NM_153603.4(COG7):c.1009+1G>A	COG7	Likely pathogenic	criteria provided, single submitter
548709	NM_153603.4(COG7):c.2T>C (p.Met1Thr)	LOC130058658	Likely pathogenic	criteria provided, single submitter
1380654	NM_153603.4(COG7):c.1293G>A (p.Lys431=)	COG7	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
194800	NM_153603.4(COG7):c.2283C>T (p.Thr761=)	COG7	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 4 · Orphanet: 9 · 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
COG7	Definitive	Autosomal recessive	COG7-congenital disorder of glycosylation	4

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
COG7	Orphanet:79333	COG7-CDG
SCNN1G	Orphanet:171876	Generalized pseudohypoaldosteronism type 1
SCNN1G	Orphanet:526	Liddle syndrome
SCNN1G	Orphanet:60033	Idiopathic bronchiectasis
CEP290	Orphanet:110	Bardet-Biedl syndrome
CEP290	Orphanet:2318	Joubert syndrome with oculorenal defect
CEP290	Orphanet:3156	Senior-Loken syndrome
CEP290	Orphanet:564	Meckel syndrome
CEP290	Orphanet:65	Leber congenital amaurosis

Cohort genes → proteins

3 cohort genes, 3 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	3

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
COG7	HGNC:18622	ENSG00000168434	P83436	Conserved oligomeric Golgi complex subunit 7	gencc,clinvar
SCNN1G	HGNC:10602	ENSG00000166828	P51170	Epithelial sodium channel subunit gamma	clinvar
CEP290	HGNC:29021	ENSG00000198707	O15078	Centrosomal protein of 290 kDa	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
COG7	Conserved oligomeric Golgi complex subunit 7	Required for normal Golgi function.
SCNN1G	Epithelial sodium channel subunit gamma	This is one of the three pore-forming subunits of the heterotrimeric epithelial sodium channel (ENaC), a critical regulator of sodium balance and fluid homeostasis.
CEP290	Centrosomal protein of 290 kDa	Involved in early and late steps in cilia formation.

Protein-family classification

Druggable: 0 · Difficult: 0 · Unknown: 3 · 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	3	1.8×	0.174

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
COG7	Other/Unknown	no		COG7
SCNN1G	Other/Unknown	no		ENaC, ENaC_chordates, ENaC_CS
CEP290	Other/Unknown	no		Cep290, Cep209_CC5

Expression context

Cohort genes with no expression data: 0.

3 cohort genes 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)	3
unknown	0

Top tissues across cohort

Tissue	Cohort genes
right uterine tube	2
adenohypophysis	1
pituitary gland	1
bronchial epithelial cell	1
kidney epithelium	1
renal medulla	1
male germ line stem cell (sensu Vertebrata) in testis	1
ventricular zone	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
COG7	269	ubiquitous	marker	right uterine tube, adenohypophysis, pituitary gland
SCNN1G	133	broad	marker	renal medulla, kidney epithelium, bronchial epithelial cell
CEP290	278	ubiquitous	marker	right uterine tube, male germ line stem cell (sensu Vertebrata) in testis, ventricular zone

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
CEP290	2,778
COG7	1,539
SCNN1G	1,037

Structural data

PDB: 1 · AlphaFold-only: 2 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
SCNN1G	P51170	5

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
COG7	P83436	82.77
CEP290	O15078	60.90

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 28. Enrichment computed across 3 evidence-associated genes (3 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 3 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Sensory perception of salty taste	1	634.4×	0.044	SCNN1G
Sensory perception of taste	1	112.0×	0.045	SCNN1G
Intra-Golgi traffic	1	86.5×	0.045	COG7
Centrosome maturation	1	84.6×	0.045	CEP290
Retrograde transport at the Trans-Golgi-Network	1	73.2×	0.045	COG7
Loss of Nlp from mitotic centrosomes	1	52.9×	0.045	CEP290
Loss of proteins required for interphase microtubule organization from the centrosome	1	52.9×	0.045	CEP290
AURKA Activation by TPX2	1	50.8×	0.045	CEP290
Stimuli-sensing channels	1	45.3×	0.045	SCNN1G
Recruitment of mitotic centrosome proteins and complexes	1	45.3×	0.045	CEP290
Regulation of PLK1 Activity at G2/M Transition	1	42.3×	0.045	CEP290
Mitotic G2-G2/M phases	1	42.3×	0.045	CEP290
G2/M Transition	1	42.3×	0.045	CEP290
Recruitment of NuMA to mitotic centrosomes	1	38.8×	0.045	CEP290
Anchoring of the basal body to the plasma membrane	1	37.7×	0.045	CEP290
COPI-mediated anterograde transport	1	36.6×	0.045	COG7
Cilium Assembly	1	36.2×	0.045	CEP290
Ion channel transport	1	32.0×	0.046	SCNN1G
Sensory Perception	1	31.7×	0.046	SCNN1G
Mitotic Prometaphase	1	23.1×	0.057	CEP290
Organelle biogenesis and maintenance	1	22.0×	0.057	CEP290
M Phase	1	22.0×	0.057	CEP290
Cell Cycle, Mitotic	1	16.1×	0.074	CEP290
Cell Cycle	1	12.0×	0.094	CEP290
Innate Immune System	1	8.5×	0.123	CEP290
Transport of small molecules	1	8.4×	0.123	SCNN1G
Neutrophil degranulation	1	7.7×	0.129	CEP290
Immune System	1	4.3×	0.214	CEP290

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 3 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
protein localization to organelle	1	2808.7×	0.005	COG7
obsolete ciliary basal body-plasma membrane docking	1	2808.7×	0.005	CEP290
ciliary transition zone assembly	1	1872.4×	0.005	CEP290
sensory perception of salty taste	1	1404.3×	0.005	SCNN1G
pronephros development	1	802.5×	0.005	CEP290
regulation of establishment of protein localization	1	802.5×	0.005	CEP290
cellular response to aldosterone	1	802.5×	0.005	SCNN1G
otic vesicle formation	1	702.2×	0.005	CEP290
cellular response to vasopressin	1	702.2×	0.005	SCNN1G
retrograde transport, vesicle recycling within Golgi	1	624.1×	0.005	COG7
multicellular organismal-level water homeostasis	1	561.7×	0.005	SCNN1G
sensory perception of sour taste	1	561.7×	0.005	SCNN1G
hindbrain development	1	374.5×	0.007	CEP290
sodium ion homeostasis	1	312.1×	0.007	SCNN1G
eye photoreceptor cell development	1	280.9×	0.007	CEP290
protein localization to Golgi apparatus	1	267.5×	0.007	COG7
intracellular sodium ion homeostasis	1	255.3×	0.007	SCNN1G
cellular response to acidic pH	1	244.2×	0.007	SCNN1G
positive regulation of intracellular protein transport	1	224.7×	0.008	CEP290
sodium ion import across plasma membrane	1	208.1×	0.008	SCNN1G
camera-type eye development	1	119.5×	0.013	CEP290
retrograde vesicle-mediated transport, Golgi to endoplasmic reticulum	1	112.3×	0.013	COG7
glycoprotein biosynthetic process	1	112.3×	0.013	COG7
non-motile cilium assembly	1	96.8×	0.014	CEP290
regulation of blood pressure	1	73.9×	0.018	SCNN1G
sodium ion transmembrane transport	1	67.7×	0.019	SCNN1G
kidney development	1	46.8×	0.026	CEP290
Golgi organization	1	44.6×	0.026	COG7
cilium assembly	1	24.5×	0.046	CEP290
protein stabilization	1	22.3×	0.049	COG7

Therapeutics

Drug target analysis

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

Druggability breadth: 2 of 3 evidence-associated genes (67%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
COG7	0	0
SCNN1G	0	0
CEP290	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
SCNN1G	5	Binding:3, ADMET:1, Functional:1
COG7	2	Binding:2

Pharmacogenomics

Cohort genes with a PharmGKB record: 3; 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	3	COG7, SCNN1G, CEP290

Undrugged target profiles

3 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).

Symbol	ChEMBL assays	Drugged partners (top 3)
COG7	2	—
SCNN1G	5	—
CEP290	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.