COG7

Chr 16AR

component of oligomeric golgi complex 7

NCBI Gene: 91949ENSG00000168434UniProt: P83436

Required for normal Golgi function

Primary Disease Associations & Inheritance

Congenital disorder of glycosylation, type IIeMIM #608779
AR
388
ClinVar variants
25
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— COG7
🧬
Gene-Disease Validity (ClinGen)
COG7-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
25 Pathogenic / Likely Pathogenic· 156 VUS of 388 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.
0.66LOEUF
pLI 0.000
Z-score 3.26
OE 0.45 (0.31–0.66)
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.
0.76Z-score
OE missense 0.90 (0.82–0.98)
382 obs / 426.0 exp
Tolerant

Mild missense constraint

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.0.45 (0.31–0.66)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.90 (0.82–0.98)
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.0.96
0≤1.21.6
LoF obs/exp: 18 / 40.4Missense obs/exp: 382 / 426.0Syn Z: 0.38

ClinVar Variant Classifications

388 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic17
Likely Pathogenic8
VUS156
Likely Benign201
Benign3
Conflicting3
17
Pathogenic
8
Likely Pathogenic
156
VUS
201
Likely Benign
3
Benign
3
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
3
0
14
0
17
Likely Pathogenic
5
1
2
0
8
VUS
1
147
8
0
156
Likely Benign
0
2
92
107
201
Benign
0
0
3
0
3
Conflicting
—3
Total9150119107388

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

View in ClinVar →

Protein Context — Lollipop Plot

COG7 · protein map & ClinVar variants

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

Gene2Phenotype Curations

COG7-related congenital disorder of glycosylation

definitive
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 IIe

MIM #608779

Molecular basis of disorder known

Autosomal recessive
📖
GeneReview available — COG7
Authoritative clinical overview · NCBI Bookshelf · Recommended first read
Open GeneReview ↗
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Metabolic Cardiomyopathies and Cardiac Defects in Inherited Disorders of Carbohydrate Metabolism: A Systematic Review.
Conte F et al.·Int J Mol Sci
2023Review
Metabolic cutis laxa syndromes.
Mohamed M et al.·J Inherit Metab Dis
2011Review
A common mutation in the COG7 gene with a consistent phenotype including microcephaly, adducted thumbs, growth retardation, VSD and episodes of hyperthermia.
Morava E et al.·Eur J Hum Genet
2007Case report
Role of the conserved oligomeric Golgi (COG) complex in protein glycosylation.
Smith RD et al.·Carbohydr Res
2008Review
Molecular and clinical characterization of a Moroccan Cog7 deficient patient.
Ng BG et al.·Mol Genet Metab
2007Case report
A new mutation in COG7 extends the spectrum of COG subunit deficiencies.
Zeevaert R et al.·Eur J Med Genet
2009Case report
Congenital myasthenic syndrome in China: genetic and myopathological characterization.
Zhao Y et al.·Ann Clin Transl Neurol
2021
Clinical and molecular diagnosis of non-phosphomannomutase 2 N-linked congenital disorders of glycosylation in Spain.
Medrano C et al.·Clin Genet
2019
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
Wrinkled skin and fat pads in patients with ALG8-CDG: revisiting skin manifestations in congenital disorders of glycosylation.
Kouwenberg D et al.·Pediatr Dermatol
2014Review
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