COG5

Chr 7AR

component of oligomeric golgi complex 5

NCBI Gene: 10466ENSG00000164597UniProt: Q9UP83

Required for normal Golgi function

Primary Disease Associations & Inheritance

Congenital disorder of glycosylation, type IIiMIM #613612
AR
574
ClinVar variants
51
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— COG5
🧬
Gene-Disease Validity (ClinGen)
COG5-congenital disorder of glycosylation · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
51 Pathogenic / Likely Pathogenic· 275 VUS of 574 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.96LOEUF
pLI 0.000
Z-score 1.75
OE 0.73 (0.56–0.96)
Tolerant

Typical tolerance to LoF variation

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
-0.48Z-score
OE missense 1.06 (0.99–1.15)
492 obs / 462.7 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.73 (0.56–0.96)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.1.06 (0.99–1.15)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.20
0≤1.21.6
LoF obs/exp: 37 / 50.4Missense obs/exp: 492 / 462.7Syn Z: -2.00

ClinVar Variant Classifications

574 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic34
Likely Pathogenic17
VUS275
Likely Benign219
Benign26
Conflicting3
34
Pathogenic
17
Likely Pathogenic
275
VUS
219
Likely Benign
26
Benign
3
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
9
0
25
0
34
Likely Pathogenic
12
0
5
0
17
VUS
5
231
33
6
275
Likely Benign
0
0
116
103
219
Benign
0
0
26
0
26
Conflicting
—3
Total26231205109574

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

COG5 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Gene2Phenotype Curations

COG5-related congenital disorder of glycosylation

strong
ARLoss Of FunctionAbsent Gene Product
Dev. Disorders
G2P ↗

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Congenital disorder of glycosylation, type IIi

MIM #613612

Molecular basis of disorder known

Autosomal recessive
📖
GeneReview available — COG5
Authoritative clinical overview · NCBI Bookshelf · Recommended first read
Open GeneReview ↗
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Characterization of a missense variant in COG5 in a Tunisian patient with COG5-CDG syndrome and insights into the effect of non-synonymous variants on COG5 protein.
Khabou B et al.·J Hum Genet
2024Case report
Fetal glycosylation defect due to ALG3 and COG5 variants detected via amniocentesis: Complex glycosylation defect with embryonic lethal phenotype.
Ferrer A et al.·Mol Genet Metab
2020
MALDI-MS profiling of serum O-glycosylation and N-glycosylation in COG5-CDG.
Palmigiano A et al.·J Mass Spectrom
2017
COG5 variants lead to complex early onset retinal degeneration, upregulation of PERK and DNA damage.
Tabbarah S et al.·Sci Rep
2020Case report
COG5-CDG: expanding the clinical spectrum.
Rymen D et al.·Orphanet J Rare Dis
2012Case report
Clinical and genetic characterization of congenital disorders of glycosylation in 20 Chinese patients.
Zhao P et al.·Orphanet J Rare Dis
2025Cohort
Biomarker candidates for progression and clinical management of COVID-19 associated pneumonia at time of admission.
Calvet J et al.·Sci Rep
2022
Role of the conserved oligomeric Golgi (COG) complex in protein glycosylation.
Smith RD et al.·Carbohydr Res
2008Review
Deficiency in COG5 causes a moderate form of congenital disorders of glycosylation.
Paesold-Burda P et al.·Hum Mol Genet
2009Case report
Hypothesis: lobe A (COG1-4)-CDG causes a more severe phenotype than lobe B (COG5-8)-CDG.
Haijes HA et al.·J Med Genet
2018
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools