Alternative titles; symbols
HGNC Approved Gene Symbol: COG1
SNOMEDCT: 718750004;
Cytogenetic location: 17q25.1 Genomic coordinates (GRCh38) : 17:73,193,055-73,208,507 (from NCBI)
| Location | Phenotype |
Phenotype MIM number |
Inheritance |
Phenotype mapping key |
|---|---|---|---|---|
| 17q25.1 | Congenital disorder of glycosylation, type IIg | 611209 | Autosomal recessive | 3 |
Multiprotein complexes are key determinants of Golgi apparatus structure and its capacity for intracellular transport and glycoprotein modification. Several complexes have been identified, including the Golgi transport complex (GTC), the LDLC complex, which is involved in glycosylation reactions, and the SEC34 complex, which is involved in vesicular transport. These 3 complexes are identical and have been termed the conserved oligomeric Golgi (COG) complex, which includes COG1 (Ungar et al., 2002).
Using an expression cloning strategy, Chatterton et al. (1999) obtained a mouse cDNA encoding Ldlb. By EST database searching, they obtained the human homolog. The deduced 980-amino acid cytoplasmic human protein is 82% identical to the mouse sequence. Expression of the mouse gene in ldlB Chinese hamster ovary (CHO) cells corrected their LDLR (606945) deficiency, which includes N- and O-glycosylation defects. Chatterton et al. (1999) found that a cytosolic complex containing Ldlc (606974) requires Ldlb for Golgi association.
By searching for cDNAs with the potential to encode large proteins expressed in brain, Nagase et al. (2000) identified a partial cDNA encoding LDLB, which they termed KIAA1381. RT-PCR analysis detected ubiquitous expression that was highest in liver, testis, and ovary. Within brain, expression was highest in amygdala, subthalamic nucleus, thalamus, and cerebellum.
By SDS-PAGE analysis of bovine brain cytosol, Ungar et al. (2002) identified the 8 subunits of the COG complex. Immunofluorescence microscopy demonstrated that COG1 colocalizes with COG7 (606978), as well as with COG3 (606975) and COG5 (606821), with a Golgi marker in a perinuclear distribution. Immunoprecipitation analysis showed that all COG subunits interact with COG2 (LDLC). Immunoblot analysis confirmed that COG1 is not expressed in ldlB CHO cell mutants and that its absence does not alter the levels of COPB (600959), which is also involved in secretion. Ungar et al. (2002) concluded that the COG complex is critical for the structure and function of the Golgi apparatus and can influence intracellular membrane trafficking.
Stumpf (2025) mapped the COG1 gene to chromosome 17q25.1 based on an alignment of the COG1 sequence (GenBank BC021985) with the genomic sequence (GRCh38).
In a patient with congenital disorder of glycosylation type IIg (CDG2G; 611209), Foulquier et al. (2006) identified a homozygous mutation in the COG1 gene (606973.0001).
In 2 patients with a CDG2G, which the authors designated cerebrocostomandibular-like syndrome (611209), Zeevaert et al. (2009) identified a homozygous splice site mutation in the COG1 gene (606973.0002).
In a patient with congenital disorder of glycosylation type IIg (CDG2G; 611209), Foulquier et al. (2006) identified a homozygous 1-bp insertion (2659insC) in the COG1 gene, resulting in premature termination of the protein with a loss of 80 amino acids. Cellular studies showed that the mutation destabilized several other COG subunits and altered their subcellular localization and the overall integrity of the COG complex. Both parents were heterozygous for the mutation.
In 2 patients with congenital disorder of glycosylation type IIg (CDG2G; 611209), Zeevaert et al. (2009) identified a homozygous G-to-A transition in intron 6 of the COG1 gene (1070+5G-A), resulting in the skipping of exon 6, a frameshift, and a prematurely terminated protein of 321 amino acids. RT-PCR analysis showed 3% of normal transcript in 1 patient compared with controls, suggesting that the mutation is a leaky mutation. Zeevaert et al. (2009) noted that the phenotype in these patients was similar to cerebrocostomandibular syndrome and they designated the disorder cerebrocostomandibular-like syndrome.
Chatterton, J. E., Hirsch, D., Schwartz, J. J., Bickel, P. E., Rosenberg, R. D., Lodish, H. F., Krieger, M. Expression cloning of LDLB, a gene essential for normal Golgi function and assembly of the ldlCp complex. Proc. Nat. Acad. Sci. 96: 915-920, 1999. [PubMed: 9927668] [Full Text: https://doi.org/10.1073/pnas.96.3.915]
Foulquier, F., Vasile, E., Schollen, E., Callewaert, N., Raemaekers, T., Quelhas, D., Jaeken, J., Mills, P., Winchester, B., Krieger, M., Annaert, W., Matthijs, G. Conserved oligomeric Golgi complex subunit 1 deficiency reveals a previously uncharacterized congenital disorder of glycosylation type II. Proc. Nat. Acad. Sci. 103: 3764-3769, 2006. [PubMed: 16537452] [Full Text: https://doi.org/10.1073/pnas.0507685103]
Nagase, T., Kikuno, R., Ishikawa, K., Hirosawa, M., Ohara, O. Prediction of the coding sequences of unidentified human genes. XVI. The complete sequences of 150 new cDNA clones from brain which code for large proteins in vitro. DNA Res. 7: 65-73, 2000. [PubMed: 10718198] [Full Text: https://doi.org/10.1093/dnares/7.1.65]
Stumpf, A. M. Personal Communication. Baltimore, Md. 2/12/2025.
Ungar, D., Oka, T., Brittle, E. E., Vasile, E., Lupashin, V. V., Chatterton, J. E., Heuser, J. E., Krieger, M., Waters, M. G. Characterization of a mammalian Golgi-localized protein complex, COG, that is required for normal Golgi morphology and function. J. Cell Biol. 157: 405-415, 2002. [PubMed: 11980916] [Full Text: https://doi.org/10.1083/jcb.200202016]
Zeevaert, R., Foulquier, F., Dimitrov, B., Reynders, E., Van Damme-Lombaerts, R., Simeonov, E., Annaert, W., Matthijs, G., Jaeken, J. Cerebrocostomandibular-like syndrome and a mutation in the conserved oligomeric Golgi complex, subunit 1. Hum. Molec. Genet. 18: 517-524, 2009. [PubMed: 19008299] [Full Text: https://doi.org/10.1093/hmg/ddn379]