COG4

Chr 16ARAD

component of oligomeric golgi complex 4

Also known as: CDG2J, COD1, SWILS

NCBI Gene: 25839ENSG00000103051UniProt: Q9H9E3

The protein encoded by this gene is a component of an oligomeric protein complex involved in the structure and function of the Golgi apparatus. Defects in this gene may be a cause of congenital disorder of glycosylation type IIj. Two transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, Aug 2010]

Primary Disease Associations & Inheritance

Congenital disorder of glycosylation, type IIjMIM #613489
AR
Saul-Wilson syndromeMIM #618150
AD
502
ClinVar variants
58
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— COG4
🧬
Gene-Disease Validity (ClinGen)
COG4-congenital disorder of glycosylation · ARModerate

Moderate evidence — consider for supplementary testing

2 total gene-disease associations curated

⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
58 Pathogenic / Likely Pathogenic· 274 VUS of 502 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.
0.71LOEUF
pLI 0.000
Z-score 3.05
OE 0.49 (0.35–0.71)
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.
-0.28Z-score
OE missense 1.04 (0.96–1.12)
454 obs / 437.4 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.0.49 (0.35–0.71)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.1.04 (0.96–1.12)
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.1.10
0≤1.21.6
LoF obs/exp: 21 / 42.4Missense obs/exp: 454 / 437.4Syn Z: -1.01

ClinVar Variant Classifications

502 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic41
Likely Pathogenic17
VUS274
Likely Benign108
Benign49
Conflicting13
41
Pathogenic
17
Likely Pathogenic
274
VUS
108
Likely Benign
49
Benign
13
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
8
3
30
0
41
Likely Pathogenic
6
6
5
0
17
VUS
3
230
36
5
274
Likely Benign
0
6
53
49
108
Benign
0
1
44
4
49
Conflicting
—13
Total1724616858502

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

View in ClinVar →

Protein Context — Lollipop Plot

COG4 · protein map & ClinVar variants

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

Gene2Phenotype Curations

COG4-related Saul Wilson syndrome

strong
ADGain Of FunctionAltered Gene Product Structure
Dev. DisordersSkeletal
G2P ↗

COG4-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 IIj

MIM #613489

Molecular basis of disorder known

Autosomal recessive

Saul-Wilson syndrome

MIM #618150

Molecular basis of disorder known

Autosomal dominant
📖
GeneReview available — COG4
Authoritative clinical overview · NCBI Bookshelf · Recommended first read
Open GeneReview ↗
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Expanding the genotypes and phenotypes for 19 rare diseases by exome sequencing performed in pediatric intensive care unit.
Liu J et al.·Hum Mutat
2021
Congenital Disorders of Glycosylation in Portugal-Two Decades of Experience.
Quelhas D et al.·J Pediatr
2021
The Undiagnosed Diseases Network (UDN) Solves Ocular Syndromic Diagnostic Dilemmas.
Tinker RJ et al.·Am J Ophthalmol
2025Case report
Defining the clinical phenotype of Saul-Wilson syndrome.
Ferreira CR et al.·Genet Med
2020
Deep learning-based assessment of missense variants in the COG4 gene presented with bilateral congenital cataract.
Xiao B et al.·BMJ Open Ophthalmol
2025
Biallelic missense variants in COG3 cause a congenital disorder of glycosylation with impairment of retrograde vesicular trafficking.
Duan R et al.·J Inherit Metab Dis
2023
Normal transferrin patterns in congenital disorders of glycosylation with Golgi homeostasis disruption: apolipoprotein C-III at the rescue!
Raynor A et al.·Clin Chim Acta
2021
A Mendelian Randomization-Based Causal Investigation on Bacterial Infection-Related Genes and Neurodegenerative Diseases.
Liu G et al.·Stud Health Technol Inform
2023
Genome-Wide Association Studies of 3 Distinct Recovery Phenotypes in Mild Ischemic Stroke.
Aldridge CM et al.·Neurology
2024
The utility of next-generation sequencing technologies in diagnosis of Mendelian mitochondrial diseases and reflections on clinical spectrum.
Kose M et al.·J Pediatr Endocrinol Metab
2021
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