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COG5
component of oligomeric golgi complex 5
The COG5 gene provides instructions for a protein that is part of the conserved oligomeric Golgi (COG) complex, which plays a vital role in the Golgi apparatus's function, particularly in protein modification. The COG5 gene encodes a protein that forms part of the conserved oligomeric Golgi (COG) complex.
COG5 is located on the long (q) arm of chromosome 7, at band 7q22.3. Arm ratio per GRCh38 - banding schematic.
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Overview
The COG5 gene, also known as component of oligomeric Golgi complex 5, provides the genetic blueprint for a protein that is integral to the conserved oligomeric Golgi (COG) complex. This complex is a multiprotein structure found within the Golgi apparatus, a key organelle in human cells responsible for processing and packaging proteins and lipids.
Disruptions in COG5 function can impact the Golgi apparatus's ability to carry out its roles, particularly in the modification of proteins. These modifications are critical for the proper function of numerous proteins throughout the body.
What the gene does
The protein encoded by the COG5 gene is a subunit of the conserved oligomeric Golgi (COG) complex. This complex is primarily involved in the Golgi apparatus, a cellular organelle where proteins undergo essential modifications, such as glycosylation. Glycosylation involves attaching sugar molecules (oligosaccharides) to proteins and fats, which expands their functional diversity.
The COG complex facilitates the transport of proteins within the Golgi apparatus. Specifically, it participates in retrograde transport, a process where proteins move backward through the Golgi. This retrograde movement is vital for recycling Golgi proteins and ensuring they are correctly positioned within the organelle, which is crucial for efficient glycosylation. The COG complex helps control the attachment, or tethering, of vesicles - small sac-like structures that carry proteins - to the Golgi membrane, enabling them to release their contents into the Golgi apparatus.
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Chromosome location
The COG5 gene is situated on the long arm of chromosome 7, at position 7q22.3. This specific location indicates its physical address within the human genome.
Protein structure
The COG5 protein consists of 860 amino acids. A specific region, encompassing amino acids 1-33, has been identified as Disordered (Region). This indicates a segment that lacks a fixed three-dimensional structure and can adopt various conformations, which is often important for protein-protein interactions.
Key variants
Variants within the COG5 gene can lead to alterations in the structure or function of the COG5 protein. These changes may impact the protein's ability to participate effectively in the conserved oligomeric Golgi (COG) complex, thereby affecting its roles in protein modification and transport within the Golgi apparatus. Different types of genetic changes can occur, ranging from single base pair substitutions to larger deletions or insertions, all potentially influencing protein function.
Sample of pathogenic variants
10 pathogenic / likely-pathogenic variants from ClinVar, ranked by review status (expert-panel-reviewed first). This is a sample; recurrent founder variants in a specific population may not appear here - see the full ClinVar listing via the link above.
| Variant (HGVS) | Protein change | Classification | Evidence | Associated condition |
|---|---|---|---|---|
c.1248T>G | p.Tyr416Ter | Pathogenic | ★★☆☆ | Inborn genetic diseases |
c.1381C>T | p.Arg461Ter | Pathogenic/Likely pathogenic | ★★☆☆ | COG5-congenital disorder of glycosylation |
c.1415dup | p.Gly474fs | Pathogenic | ★★☆☆ | COG5-congenital disorder of glycosylation |
c.2068C>T | p.Arg690Ter | Pathogenic/Likely pathogenic | ★★☆☆ | COG5-congenital disorder of glycosylation |
c.2122C>T | p.Arg708Ter | Pathogenic/Likely pathogenic | ★★☆☆ | COG5-congenital disorder of glycosylation |
c.2167del | p.Arg723fs | Pathogenic/Likely pathogenic | ★★☆☆ | COG5-congenital disorder of glycosylation |
c.2295+2T>C | - | Pathogenic/Likely pathogenic | ★★☆☆ | COG5-congenital disorder of glycosylation |
c.2T>G | p.Met1Arg | Pathogenic/Likely pathogenic | ★★☆☆ | COG5-congenital disorder of glycosylation |
c.611_613delinsTAGTGGAATT | p.Ala204fs | Pathogenic | ★★☆☆ | Inborn genetic diseases |
c.613C>T | p.Arg205Ter | Pathogenic | ★★☆☆ | COG5-congenital disorder of glycosylation |
Evidence stars indicate ClinVar review status. Individual variant interpretation should always be performed by a qualified clinical laboratory - many variants remain classified as Variants of Uncertain Significance (VUS) pending more research.
Associated conditions
Pathogenic variants in the COG5 gene are associated with inherited conditions primarily affecting metabolic processes. One such condition is COG5-congenital disorder of glycosylation (COG5-CDG). This disorder often presents with developmental delay and intellectual disability, along with various other abnormalities.
No disease links recorded for this gene in our reference set.
Inheritance pattern
Conditions caused by pathogenic COG5 variants typically follow autosomal recessive inheritance.
When both parents are carriers, each child has a 25% chance of being affected, 50% of being a carrier, and 25% of being unaffected.
UK clinical status
The COG5 gene is recognised within several NHS clinical panels in the UK. It holds a 'green' rating for conditions such as Congenital disorders of glycosylation, DDG2P, Foetal anomalies (R21), Hereditary ataxia (adult onset), Intellectual disability, Likely inborn error of metabolism (R98), and Undiagnosed metabolic disorders. A 'green' rating signifies that there is sufficient evidence to support its inclusion on these diagnostic panels.
Sources: NHS GMS PanelApp · Genomics England PanelApp · NHS National Genomic Test Directory
Frequently asked questions
What is the function of the COG5 gene?
The COG5 gene provides instructions for a protein that is a part of the conserved oligomeric Golgi (COG) complex. This complex helps transport and modify proteins within the Golgi apparatus, particularly through a process called glycosylation.
What happens if there are changes in the COG5 gene?
Changes in the COG5 gene can lead to a reduced amount or complete absence of the COG5 protein. This disruption affects protein transport and modification in the Golgi apparatus, which can result in conditions like COG5-congenital disorder of glycosylation (COG5-CDG).
What is COG5-congenital disorder of glycosylation (COG5-CDG)?
COG5-CDG is a genetic condition caused by mutations in the COG5 gene. It often presents with developmental delay and intellectual disability, alongside other physical and metabolic abnormalities, due to impaired protein glycosylation.
References
- Miller VJ, Sharma P, Kudlyk TA. Molecular insights into vesicle tethering at the Golgi by the conserved oligomeric Golgi (COG) complex and the golgin TATA element modulatory factor (TMF). The Journal of biological chemistry. 2013. PMID: 23239882
- Rymen D, Keldermans L, Race V. COG5-CDG: expanding the clinical spectrum. Orphanet journal of rare diseases. 2012. PMID: 23228021
- Fung CW, Matthijs G, Sturiale L. COG5-CDG with a Mild Neurohepatic Presentation. JIMD reports. 2012. PMID: 23430875
- Reynders E, Foulquier F, Annaert W. How Golgi glycosylation meets and needs trafficking: the case of the COG complex. Glycobiology. 2011. PMID: 21112967
- Smith RD, Lupashin VV. Role of the conserved oligomeric Golgi (COG) complex in protein glycosylation. Carbohydrate research. 2008. PMID: 18353293
- Oka T, Vasile E, Penman M. Genetic analysis of the subunit organization and function of the conserved oligomeric golgi (COG) complex: studies of COG5- and COG7-deficient mammalian cells. The Journal of biological chemistry. 2005. PMID: 16051600