COG8

component of oligomeric golgi complex 8, the group of Components of oligomeric golgi complex

Basic information

Region (hg38): 16:69320139-69339583

Links

ENSG00000213380 ∙ NCBI:84342 ∙ OMIM:606979 ∙ HGNC:18623 ∙ Uniprot:Q96MW5 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• COG8-congenital disorder of glycosylation (Strong), mode of inheritance: AR
• COG8-congenital disorder of glycosylation (Moderate), mode of inheritance: AR
• COG8-congenital disorder of glycosylation (Strong), mode of inheritance: AR
• COG8-congenital disorder of glycosylation (Definitive), mode of inheritance: AR
• COG8-congenital disorder of glycosylation (Supportive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Congenital disorder of glycosylation, type IIh	AR	Hematologic	Awareness of coagulopathies may be beneficial in terms of medical management, especially in situations such as surgery	Biochemical; Hematologic; Neurologic	17220172; 17331980; 20301507; 30690882
Hepatic-metabolized agents should be avoided

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the COG8 gene.

• COG8-congenital disorder of glycosylation (125 variants)
• not provided (56 variants)
• Inborn genetic diseases (41 variants)
• not specified (24 variants)
• COG8-related condition (4 variants)
• Congenital disorder of glycosylation (3 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the COG8 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			7	39	1	47
missense			63	9		72
nonsense		3	1			4
start loss						0
frameshift	2	3	1			6
inframe indel			1			1
splice donor/acceptor (+/-2bp)		2				2
splice region			3	3		6
non coding			24	13	14	51
Total	2	8	97	61	15

Highest pathogenic variant AF is 0.0000854

Variants in COG8

This is a list of pathogenic ClinVar variants found in the COG8 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
16-69320171-G-A			Benign (Mar 01, 2022)
16-69320226-C-T			Uncertain significance (Jun 08, 2021)
16-69320231-T-C			Likely benign (Apr 01, 2022)
16-69320237-TGAGA-T			Uncertain significance (Dec 02, 2016)
16-69320292-G-A		not specified	Uncertain significance (Oct 12, 2023)
16-69320768-A-G		Cerebellar hypoplasia-intellectual disability-congenital microcephaly-dystonia-anemia-growth retardation syndrome	Pathogenic (Jun 01, 2020)
16-69320768-A-T		Syndromic congenital hemolytic and dyserythropoietic anemia • Cerebellar hypoplasia-intellectual disability-congenital microcephaly-dystonia-anemia-growth retardation syndrome	Pathogenic (Jun 01, 2020)
16-69321100-C-T			Uncertain significance (Jun 11, 2022)
16-69321110-G-A		Inborn genetic diseases	Likely benign (Feb 07, 2023)
16-69321142-A-G			Uncertain significance (Sep 09, 2022)
16-69321143-C-T		Cerebellar hypoplasia-intellectual disability-congenital microcephaly-dystonia-anemia-growth retardation syndrome	Uncertain significance (Mar 01, 2023)
16-69321159-C-T			Benign (Oct 01, 2022)
16-69321196-G-A			Uncertain significance (Jan 22, 2023)
16-69321254-C-T		Inborn genetic diseases	Uncertain significance (Apr 08, 2022)
16-69321269-A-T			Uncertain significance (Dec 03, 2022)
16-69322570-C-A		Inborn genetic diseases	Likely benign (Apr 07, 2023)
16-69322595-G-A			Uncertain significance (Aug 26, 2020)
16-69322597-T-C		VPS4A-related disorder • Inborn genetic diseases	Likely benign (Jan 23, 2024)
16-69322642-T-C		Inborn genetic diseases	Uncertain significance (Sep 19, 2022)
16-69322648-T-G		Inborn genetic diseases	Uncertain significance (Mar 12, 2024)
16-69322681-T-C		Inborn genetic diseases	Uncertain significance (Jan 10, 2023)
16-69324221-G-T			Uncertain significance (Mar 31, 2023)
16-69324227-T-C		Cerebellar hypoplasia-intellectual disability-congenital microcephaly-dystonia-anemia-growth retardation syndrome	Uncertain significance (Apr 20, 2023)
16-69324256-G-C			Uncertain significance (May 14, 2023)
16-69324303-G-C			Uncertain significance (Nov 06, 2021)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
COG8	protein_coding	protein_coding	ENST00000306875	5	19528

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
2.97e-9	0.504	125661	0	86	125747	0.000342

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.0937	375	370	1.01	0.0000214	3934
Missense in Polyphen		108	100.17	1.0782		1101
Synonymous	-1.35	181	159	1.14	0.00000882	1325
Loss of Function	1.09	16	21.4	0.746	0.00000110	219

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00145	0.00141
Ashkenazi Jewish	0.00	0.00
East Asian	0.000218	0.000217
Finnish	0.0000462	0.0000462
European (Non-Finnish)	0.000285	0.000264
Middle Eastern	0.000218	0.000217
South Asian	0.000426	0.000425
Other	0.000660	0.000652

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Required for normal Golgi function. {ECO:0000250}.
• Disease: DISEASE: Congenital disorder of glycosylation 2H (CDG2H) [MIM:611182]: CDGs are a family of severe inherited diseases caused by a defect in protein N-glycosylation. They are characterized by under-glycosylated serum proteins. These multisystem disorders present with a wide variety of clinical features, such as disorders of the nervous system development, psychomotor retardation, dysmorphic features, hypotonia, coagulation disorders, and immunodeficiency. The broad spectrum of features reflects the critical role of N-glycoproteins during embryonic development, differentiation, and maintenance of cell functions. {ECO:0000269|PubMed:17331980}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Vesicle-mediated transport;Membrane Trafficking;Post-translational protein modification;Metabolism of proteins;Transport to the Golgi and subsequent modification;Asparagine N-linked glycosylation;Intra-Golgi traffic;COPI-mediated anterograde transport;ER to Golgi Anterograde Transport;Retrograde transport at the Trans-Golgi-Network;Intra-Golgi and retrograde Golgi-to-ER traffic (Consensus)

Recessive Scores

• pRec: 0.110

Intolerance Scores

• loftool: 0.723
• rvis_EVS: -0.22
• rvis_percentile_EVS: 37.54

Haploinsufficiency Scores

• pHI: 0.284
• hipred: N
• hipred_score: 0.162
• ghis: 0.538

Essentials

• essential_gene_CRISPR: E
• essential_gene_CRISPR2: E
• essential_gene_gene_trap: E
• gene_indispensability_pred: E
• gene_indispensability_score: 0.917

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Cog8

Gene ontology

• Biological process: endoplasmic reticulum to Golgi vesicle-mediated transport;intra-Golgi vesicle-mediated transport;protein transport
• Cellular component: Golgi membrane;Golgi apparatus;membrane;Golgi transport complex;trans-Golgi network membrane
• Molecular function: protein binding