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GeneE
10 sources retrieved Β· Most recent: April 2026 Β· Index updated 15 days ago
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COG4
component of oligomeric golgi complex 4
Chromosome 16 Β· 16q22.1
NCBI Gene: 25839Ensembl: ENSG00000103051.21HGNC: HGNC:18620UniProt: A0A0A0MS45
59PubMed Papers
22Diseases
0Drugs
33Pathogenic Variants
FUNCTIONAL ROLE
Transporter
CLINICAL
OMIM Disease Gene
DATA QUALITY
βœ“ Experimental GO Evidenceβœ“ Swiss-Prot Reviewed
COG complexretrograde transport, vesicle recycling within Golgiretrograde vesicle-mediated transport, Golgi to endoplasmic reticulumGolgi organizationmicrocephalic osteodysplastic dysplasia, Saul-Wilson typeCOG4-congenital disorder of glycosylationgenetic disorderneurodegenerative disease
✦AI Summary

COG4 is a component of the conserved oligomeric Golgi (COG) complex, an octameric protein complex essential for normal Golgi function and intra-Golgi trafficking of glycosylation enzymes 1. COG4 plays critical roles in SNARE-pin assembly and Golgi-to-ER retrograde transport through interaction with SCFD1 2. The protein's C-terminal domain stabilizes the complex via a salt bridge network centered at Arg729, which is essential for proper glycosylation of cell surface proteins despite not being required for COG complex incorporation 3. COG4 mutations cause two distinct disease entities. Biallelic mutations cause congenital disorder of glycosylation type 2J (CDG-2J), characterized by neurological, skeletal, and hepatic abnormalities 1. The recurrent heterozygous COG4 p.Gly516Arg substitution causes Saul-Wilson syndrome, a primordial dwarfism with spondyloepimetaphyseal dysplasia, microcephaly, facial dysmorphism, and skeletal abnormalities 4. This mutation disrupts vesicular trafficking equilibrium, causing decreased Golgi volume and selective impairment of proteoglycan secretion, particularly affecting chondrogenic proteins like MMP13 and IGFBP7 5. Growth hormone therapy does not improve stature in affected individuals 6. Ocular manifestations including cataracts, retinitis pigmentosa, and nystagmus have been reported 7.

Sources cited
1
COG4 required for normal Golgi function and plays role in SNARE-pin assembly and Golgi-to-ER retrograde transport via SCFD1 interaction
PMID: 19536132
2
COG4 is component of octameric COG complex that orchestrates intra-Golgi trafficking of glycosylation enzymes; over 100 individuals with 31 different COG mutations identified with neurological, skeletal, and hepatic abnormalities
PMID: 34603392
3
COG4 C-terminal domain with Arg729 at center of salt bridge network is essential for proper glycosylation of cell surface proteins; COG4 mutation p.R729W causes CDG
PMID: 19651599
4
Heterozygous COG4 p.G516R substitution causes Saul-Wilson syndrome with primordial dwarfism and skeletal dysplasia; mutation disrupts vesicular trafficking and alters proteoglycan glycosylation including decorin
PMID: 30290151
5
COG4 p.G516R mutation selectively affects secretion of chondrogenic proteins including MMP13 and IGFBP7 in chondrocyte-like cells and impairs chondrogenesis
PMID: 36393834
6
Saul-Wilson syndrome characterized by microcephalic primordial dwarfism, spondyloepimetaphyseal dysplasia, and multiple skeletal abnormalities; growth hormone therapy ineffective
PMID: 32652690
7
De novo COG4 variant causes ocular phenotype including cataract, retinitis pigmentosa, and nystagmus
PMID: 40780579
8
Novel COG4 SNV identified in pediatric intensive care patient with rare genetic disease
PMID: 34298581
Disease Associationsβ“˜22
microcephalic osteodysplastic dysplasia, Saul-Wilson typeOpen Targets
0.80Strong
COG4-congenital disorder of glycosylationOpen Targets
0.80Strong
genetic disorderOpen Targets
0.42Moderate
neurodegenerative diseaseOpen Targets
0.38Weak
congenital disorder of glycosylationOpen Targets
0.37Weak
Delayed gross motor developmentOpen Targets
0.34Weak
joint diseaseOpen Targets
0.26Weak
attention deficit hyperactivity disorderOpen Targets
0.09Suggestive
attention deficit-hyperactivity disorder 8Open Targets
0.07Suggestive
hereditary attention deficit-hyperactivity disorderOpen Targets
0.07Suggestive
intellectual disability, autosomal recessive 59Open Targets
0.07Suggestive
movement disorderOpen Targets
0.07Suggestive
schizophrenia 15Open Targets
0.07Suggestive
Gorham-Stout diseaseOpen Targets
0.07Suggestive
Phelan-McDermid syndromeOpen Targets
0.05Suggestive
autismOpen Targets
0.05Suggestive
Tourette syndromeOpen Targets
0.05Suggestive
osteoporosisOpen Targets
0.05Suggestive
postmenopausal osteoporosisOpen Targets
0.05Suggestive
12q14 microdeletion syndromeOpen Targets
0.05Suggestive
Congenital disorder of glycosylation 2JUniProt
Saul-Wilson syndromeUniProt
Pathogenic Variants33
NM_015386.3(COG4):c.529C>T (p.Arg177Ter)Pathogenic
COG4-congenital disorder of glycosylation|not provided|COG4-Related Disorders
β˜…β˜…β˜†β˜†2026β†’ Residue 177
NM_015386.3(COG4):c.1546G>A (p.Gly516Arg)Pathogenic
not provided|COG4-congenital disorder of glycosylation|Microcephalic osteodysplastic dysplasia, Saul-Wilson type|Inborn genetic diseases
β˜…β˜…β˜†β˜†2025β†’ Residue 516
NM_015386.3(COG4):c.1654_1655del (p.Leu552fs)Pathogenic
not provided|COG4-related disorder
β˜…β˜…β˜†β˜†2025β†’ Residue 552
NM_015386.3(COG4):c.73G>T (p.Gly25Ter)Pathogenic
COG4-congenital disorder of glycosylation|Microcephalic osteodysplastic dysplasia, Saul-Wilson type|not provided
β˜…β˜…β˜†β˜†2025β†’ Residue 25
NM_015386.3(COG4):c.2197C>T (p.Arg733Trp)Pathogenic
COG4-congenital disorder of glycosylation|not provided|See cases
β˜…β˜…β˜†β˜†2024β†’ Residue 733
NM_015386.3(COG4):c.1840G>T (p.Glu614Ter)Pathogenic
Delayed gross motor development|not provided|COG4-congenital disorder of glycosylation;Microcephalic osteodysplastic dysplasia, Saul-Wilson type|COG4-congenital disorder of glycosylation
β˜…β˜…β˜†β˜†2023β†’ Residue 614
NM_015386.3(COG4):c.1828delGPathogenic
COG4-Related Disorders
β˜…β˜†β˜†β˜†2026
NM_015386.3(COG4):c.1122dup (p.Arg375fs)Pathogenic
COG4-congenital disorder of glycosylation
β˜…β˜†β˜†β˜†2026β†’ Residue 375
NM_015386.3(COG4):c.1955G>A (p.Trp652Ter)Pathogenic
COG4-congenital disorder of glycosylation
β˜…β˜†β˜†β˜†2025β†’ Residue 652
NM_015386.3(COG4):c.1434_1435del (p.Ala480fs)Pathogenic
COG4-congenital disorder of glycosylation
β˜…β˜†β˜†β˜†2025β†’ Residue 480
NM_015386.3(COG4):c.599_600del (p.Lys200fs)Pathogenic
COG4-congenital disorder of glycosylation
β˜…β˜†β˜†β˜†2025β†’ Residue 200
NM_015386.3(COG4):c.739-1G>CLikely pathogenic
COG4-congenital disorder of glycosylation
β˜…β˜†β˜†β˜†2025
NM_015386.3(COG4):c.1290C>A (p.Tyr430Ter)Likely pathogenic
COG4-congenital disorder of glycosylation;Microcephalic osteodysplastic dysplasia, Saul-Wilson type
β˜…β˜†β˜†β˜†2024β†’ Residue 430
NM_015386.3(COG4):c.2006C>T (p.Ala669Val)Likely pathogenic
Microcephalic osteodysplastic dysplasia, Saul-Wilson type
β˜…β˜†β˜†β˜†2024β†’ Residue 669
NM_015386.3(COG4):c.1002+1G>TLikely pathogenic
Microcephalic osteodysplastic dysplasia, Saul-Wilson type
β˜…β˜†β˜†β˜†2024
NM_015386.3(COG4):c.15G>A (p.Met5Ile)Likely pathogenic
not provided
β˜…β˜†β˜†β˜†2024β†’ Residue 5
NM_015386.3(COG4):c.1608del (p.Gly537fs)Pathogenic
COG4-congenital disorder of glycosylation
β˜…β˜†β˜†β˜†2023β†’ Residue 537
NM_015386.3(COG4):c.844+1G>APathogenic
not provided
β˜…β˜†β˜†β˜†2023
NM_015386.3(COG4):c.883G>T (p.Glu295Ter)Pathogenic
COG4-congenital disorder of glycosylation
β˜…β˜†β˜†β˜†2022β†’ Residue 295
NM_015386.3(COG4):c.6del (p.Thr3fs)Pathogenic
COG4-congenital disorder of glycosylation
β˜…β˜†β˜†β˜†2022β†’ Residue 3
View on ClinVar β†—
Related Genes
STX6Protein interaction100%YKT6Protein interaction99%VTI1AProtein interaction94%VPS53Protein interaction93%VPS54Protein interaction88%RAB30Protein interaction85%
Tissue Expression6 tissues
Heart
100%
Liver
96%
Brain
81%
Ovary
76%
Lung
76%
Bone Marrow
51%
Gene Interaction Network
Click a node to explore
COG4STX6YKT6VTI1AVPS53VPS54RAB30
PROTEIN STRUCTURE
Preparing viewer…
PDB3HR0 Β· 1.90 Γ… Β· X-ray
View on RCSB β†—
Constraintβ“˜
LOEUFβ“˜
0.81LoF Tolerant
pLIβ“˜
0.00Tolerant
Observed/Expected LoF0.65 [0.53–0.81]
RankingsWhere COG4 stands among ~20K protein-coding genes
  • #7,752of 20,598
    Most Researched59
  • #1,729of 5,498
    Most Pathogenic Variants33
  • #6,717of 17,882
    Most Constrained (LOEUF)0.81
Genes detectedCOG4
Sources retrieved10 papers
Response timeβ€”
πŸ“„ Sources
10β–Ό
1
PMID: 32078278
1.00
2
Expanding the genotypes and phenotypes for 19 rare diseases by exome sequencing performed in pediatric intensive care unit.
PMID: 34298581
Hum Mutat Β· 2021
0.90
3
PMID: 20301507
0.80
4
Structural basis for a human glycosylation disorder caused by mutation of the COG4 gene.
PMID: 19651599
Proc Natl Acad Sci U S A Β· 2009
0.70
5
COG4 mutation in Saul-Wilson syndrome selectively affects secretion of proteins involved in chondrogenesis in chondrocyte-like cells.
PMID: 36393834
Front Cell Dev Biol Β· 2022
0.60