Alternative titles; symbols
HGNC Approved Gene Symbol: COG8
SNOMEDCT: 717774004;
Cytogenetic location: 16q22.1 Genomic coordinates (GRCh38) : 16:69,326,428-69,339,564 (from NCBI)
| Location | Phenotype |
Phenotype MIM number |
Inheritance |
Phenotype mapping key |
|---|---|---|---|---|
| 16q22.1 | Congenital disorder of glycosylation, type IIh | 611182 | 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 COG8 (Ungar et al., 2002).
By database searching for sequences homologous to the yeast dependent on Ric1 (Dor1) protein, Whyte and Munro (2001) identified cDNAs encoding COG8. They subsequently identified other members of the COG complex. The deduced 613-amino acid COG8 protein contains an N-terminal coiled-coil region and is homologous to the yeast protein, which associates with Sec34 (COG3; 606975). The coiled-coil regions are found in all members of the COG complex and may be involved in holding the complex together or in binding other proteins involved in vesicle docking and fusion.
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 (LDLB; 606973) colocalizes with COG7 (606978), as well as with COG3 and COG5 (606821), with a Golgi marker in a perinuclear distribution. Immunoprecipitation analysis showed that all COG subunits interact with COG2 (LDLC; 606974). 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 (2020) mapped the COG8 gene to chromosome 16q22.1 based on an alignment of the COG8 sequence (GenBank BC121022) with the genomic sequence (GRCh38).
In a patient with congenital disorder of glycosylation type II (CDG2H; 611182), Foulquier et al. (2007) identified a homozygous nonsense mutation in the COG8 gene (Y537X; 606979.0001).
In a patient with CDG2H, Kranz et al. (2007) identified compound heterozygous mutations in the COG8 gene: a splice donor mutation in intron 3 (606979.0002) and a dinucleotide deletion in exon 5 (606979.0003).
Arora et al. (2019) identified a homozygous splice site mutation in the COG8 gene (606979.0004) in a patient with CDG2H. The mutation, which was identified by whole-exome sequencing and confirmed by Sanger sequencing, segregated with the disorder in the family.
Foulquier et al. (2007) described a Spanish girl with a novel congenital disorder of glycosylation (CDG2H; 611182) who was homozygous for a C-to-G transversion at position 1611 in the COG8 gene, which resulted in a tyr537-to-ter amino acid substitution (Y537X). Cotransfection experiments revealed impaired interaction of the truncated COG8 protein with COG1 (606973). Biochemical consequences of the defect were corrected in vitro in the patient's fibroblasts by transfection with full-length COG8 transcript.
Kranz et al. (2007) reported a male patient with a novel congenital disorder of glycosylation (CDG2H; 611182) who was compound heterozygous for mutations in the COG8 gene: a splice donor mutation in intron 3 (IVS3+1G-A) and a dinucleotide deletion in exon 5 (c.1687_1688delTT; 606979.0003). Biochemical consequences of the defect were corrected in vitro in the patient's fibroblasts by transfection with full-length COG8 transcript.
For discussion of the 2-bp deletion (c.1687_1688delTT) in the COG8 gene that was found in compound heterozygous state in a patient with congenital disorder of glycosylation type IIh (CDG2H; 611182) by Kranz et al. (2007), see 606979.0002.
In a patient with a prenatal presentation of congenital disorder of glycosylation type IIH (CDG2H; 611182), Arora et al. (2019) identified a homozygous c.1583-1G-A mutation in the acceptor splice site of intron 4 (IVS4-1G-A) of the COG8 gene. The mutation, which was identified by whole-exome sequencing and confirmed by Sanger sequencing, was present in heterozygous state in the parents. The mutation was predicted to generate a new splice acceptor site, resulting in a change in reading frame and a truncated protein 12 amino acids downstream. Functional studies were not performed.
Arora, V., Puri, R. D., Bhai, P., Sharma, N., Bijarnia-Mahay, S., Dimri, N., Bijal, A., Saxena, R., Verma, I. The first case of antenatal presentation in COG8-congenital disorder of glycosylation with a novel splice site mutation and an extended phenotype. Am. J. Med. Genet. 179A: 480-485, 2019. [PubMed: 30690882] [Full Text: https://doi.org/10.1002/ajmg.a.61030]
Foulquier, F., Ungar, D., Reynders, E., Zeevaert, R., Mills, P., Garcia-Silva, M. T., Briones, P., Winchester, B., Morelle, W., Krieger, M., Annaert, W., Matthijs, G. A new inborn error of glycosylation due to a Cog8 deficiency reveals a critical role for the Cog1-Cog8 interaction in COG complex formation. Hum. Molec. Genet. 16: 717-730, 2007. [PubMed: 17220172] [Full Text: https://doi.org/10.1093/hmg/ddl476]
Kranz, C., Ng, B. G., Sun, L., Sharma, V., Eklund, E. A., Miura, Y., Ungar, D., Lupashin, V., Winkel, R. D., Cipollo, J. F., Costello, C. E., Loh, E., Hong, W., Freeze, H. H. COG8 deficiency causes new congenital disorder of glycosylation type IIh. Hum. Molec. Genet. 16: 731-741, 2007. [PubMed: 17331980] [Full Text: https://doi.org/10.1093/hmg/ddm028]
Stumpf, A. M. Personal Communication. Baltimore, Md. 07/08/2020.
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]
Whyte, J. R. C., Munro, S. The Sec34/35 Golgi transport complex is related to the exocyst, defining a family of complexes involved in multiple steps of membrane traffic. Dev. Cell 1: 527-537, 2001. [PubMed: 11703943] [Full Text: https://doi.org/10.1016/s1534-5807(01)00063-6]