COG4: Component of Oligomeric Golgi Complex 4
A key regulator of Golgi structure and function, implicated in congenital disorders of glycosylation and cancer.
Gene Information Card
| Symbol | COG4 |
|---|---|
| Full Name | Component of Oligomeric Golgi Complex 4 |
| Gene Type | Protein coding |
| Chromosomal Location | 16q22.1 |
| NCBI Gene ID | 25839 ncbi.nlm.nih.gov/gene/25839 |
| Ensembl ID | ENSG00000103089 |
| UniProt ID | Q9H9E3 |
| OMIM ID | 606976 |
| HGNC ID | 18620 |
| Aliases | COD1, CDG2J, CGI-62, SEC34, GOLGIN-4 |
Description
COG4 encodes a subunit of the conserved oligomeric Golgi (COG) complex, which is essential for tethering and fusion of transport vesicles within the Golgi apparatus. The COG complex is composed of eight subunits (COG1-8) organized into two lobes (A and B). COG4 is part of lobe A and is critical for maintaining Golgi structure, protein glycosylation, and intracellular trafficking. Mutations in COG4 cause congenital disorder of glycosylation type IIj (CDG IIj), and somatic alterations are observed in various cancers.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Congenital disorder of glycosylation type IIj (CDG IIj) | Loss-of-function mutations in COG4 disrupt Golgi trafficking and glycosylation, leading to multisystem developmental abnormalities. | ClinVar, OMIM #606976 |
| Colorectal cancer | Somatic missense mutations and copy number alterations in COG4 are reported, potentially affecting Golgi-mediated protein sorting and cell adhesion. | COSMIC, NCBI Gene |
| Breast cancer | COG4 overexpression and mutations are associated with altered glycosylation and tumor progression. | COSMIC |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 10.2 | Medium |
| Liver | 8.5 | Medium |
| Kidney | 7.1 | Medium |
| Heart | 6.3 | Low |
| Lung | 5.8 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HeLa | 12.4 | Cervical cancer cell line; high expression |
| HEK293 | 11.0 | Embryonic kidney; moderate expression |
| HCT116 | 9.8 | Colorectal carcinoma; moderate expression |
| MCF7 | 7.5 | Breast cancer; low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1690C>T (p.Arg564Trp) | Missense | <0.01% | Reported in CDG IIj; disrupts COG complex assembly (ClinVar) |
| c.1A>G (p.Met1Val) | Missense | <0.01% | Start codon loss; likely loss-of-function (ClinVar) |
| c.1183G>A (p.Glu395Lys) | Missense | 0.02% | Somatic in colorectal cancer; functional impact unknown (COSMIC) |
| c.2032C>T (p.Arg678Cys) | Missense | 0.01% | Somatic in breast cancer; potential gain-of-function (COSMIC) |
Mutation functional classification
Loss of Function (LOF)
Missense mutations (e.g., p.Arg564Trp) and start-loss variants impair COG4 stability or COG complex assembly, leading to defective Golgi trafficking and glycosylation.
Gain of Function (GOF)
Somatic mutations (e.g., p.Arg678Cys) may enhance COG4 activity or alter substrate specificity, potentially promoting cancer cell proliferation.
Dominant Negative (DN)
Heterozygous missense mutations in CDG IIj are thought to exert dominant-negative effects by incorporating mutant COG4 into the COG complex and disrupting its function.
View complete mutation data：
Gene Ontology (GO)
| • Golgi organization (GO:0007030) | • Intra-Golgi vesicle-mediated transport (GO:0006891) |
| • Protein glycosylation (GO:0006486) | • COG complex (GO:0017119) |
| • Golgi membrane (GO:0000139) |
Pathways
• COG complex-mediated vesicle tethering (Reactome: R-HSA-6811442)
• Golgi-to-ER retrograde transport (Reactome: R-HSA-6811434)
• N-glycan biosynthesis (KEGG: hsa00510)
Protein Summary
COG4 is a 785-amino-acid protein (UniProt Q9H9E3) localized to the Golgi membrane. It functions as a scaffold within the COG complex lobe A, interacting with COG1, COG2, COG3, and COG8. The protein contains coiled-coil domains that mediate tethering of COPI vesicles. Defects in COG4 lead to mislocalization of Golgi enzymes and abnormal glycosylation. In cancer, altered COG4 expression correlates with poor prognosis.
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