COG1

component of oligomeric golgi complex 1, the group of Components of oligomeric golgi complex

Basic information

Region (hg38): 17:73193054-73208507

Previous symbols: [ "LDLB" ]

Links

ENSG00000166685 ∙ NCBI:9382 ∙ OMIM:606973 ∙ HGNC:6545 ∙ Uniprot:Q8WTW3 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• COG1-congenital disorder of glycosylation (Strong), mode of inheritance: AR
• COG1-congenital disorder of glycosylation (Strong), mode of inheritance: AR
• COG1-congenital disorder of glycosylation (Definitive), mode of inheritance: AR
• COG1-congenital disorder of glycosylation (Supportive), mode of inheritance: AR
• COG1-congenital disorder of glycosylation (Moderate), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Congenital disorder of glycosylation, type IIg	AR	Hematologic	Awareness of coagulopathies may be beneficial in terms of medical management, especially in situations such as surgery	Biochemical; Cardiovascular; Gastrointestinal; Musculoskeletal; Neurologic	16537452; 19008299
The condition can include cardiac manifestations as well as other multi-system manifestations; Hepatic-metabolized agents should be avoided

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the COG1 gene.

• COG1 congenital disorder of glycosylation (309 variants)
• not provided (72 variants)
• Inborn genetic diseases (50 variants)
• not specified (13 variants)
• Congenital disorder of glycosylation (2 variants)
• Nephrotic syndrome (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the COG1 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			4	61	4	69
missense			185	8	3	196
nonsense	1	2	4			7
start loss			1			1
frameshift	1	2	3	1		7
inframe indel			4			4
splice donor/acceptor (+/-2bp)			1			1
splice region	1		8	4		13
non coding			4	27	22	53
Total	2	4	206	97	29

Highest pathogenic variant AF is 0.0000723

Variants in COG1

This is a list of pathogenic ClinVar variants found in the COG1 region.

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

Position	Type	Phenotype	Significance	ClinVar
17-73193070-A-G		COG1 congenital disorder of glycosylation	Uncertain significance (May 21, 2022)
17-73193073-G-A		Inborn genetic diseases	Uncertain significance (May 23, 2023)
17-73193078-C-T		COG1 congenital disorder of glycosylation	Likely benign (Nov 03, 2023)
17-73193080-C-G		Inborn genetic diseases	Uncertain significance (Aug 30, 2021)
17-73193089-C-T		COG1 congenital disorder of glycosylation	Conflicting classifications of pathogenicity (Oct 13, 2023)
17-73193094-G-A		Inborn genetic diseases	Uncertain significance (Jan 30, 2024)
17-73193095-C-T		COG1 congenital disorder of glycosylation	Uncertain significance (Jan 13, 2018)
17-73193103-C-T		COG1 congenital disorder of glycosylation	Conflicting classifications of pathogenicity (Nov 10, 2023)
17-73193112-C-A		Inborn genetic diseases	Uncertain significance (Nov 21, 2023)
17-73193116-G-T		COG1 congenital disorder of glycosylation	Uncertain significance (Jul 12, 2022)
17-73193119-A-C		Inborn genetic diseases	Uncertain significance (Feb 26, 2024)
17-73193126-G-T			Likely benign (Aug 02, 2018)
17-73193127-G-C		COG1 congenital disorder of glycosylation	Benign/Likely benign (Jan 31, 2024)
17-73193148-G-T		COG1 congenital disorder of glycosylation	Uncertain significance (Sep 19, 2022)
17-73193154-G-A		COG1 congenital disorder of glycosylation	Uncertain significance (Mar 01, 2022)
17-73193156-G-C		COG1 congenital disorder of glycosylation	Uncertain significance (Jan 13, 2018)
17-73193165-G-A		COG1 congenital disorder of glycosylation	Likely benign (Mar 08, 2023)
17-73193174-C-G		COG1 congenital disorder of glycosylation	Likely benign (Feb 24, 2022)
17-73193186-C-T		COG1 congenital disorder of glycosylation	Likely benign (Dec 02, 2023)
17-73193194-A-C		COG1 congenital disorder of glycosylation	Uncertain significance (Dec 28, 2021)
17-73193195-G-A		COG1 congenital disorder of glycosylation	Likely benign (Jun 27, 2022)
17-73193217-C-T		COG1 congenital disorder of glycosylation	Pathogenic (Jul 21, 2023)
17-73193222-G-A		COG1 congenital disorder of glycosylation	Uncertain significance (Nov 22, 2021)
17-73193232-C-T		COG1 congenital disorder of glycosylation	Uncertain significance (Mar 28, 2022)
17-73193233-G-C		COG1 congenital disorder of glycosylation	Uncertain significance (Dec 16, 2021)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
COG1	protein_coding	protein_coding	ENST00000299886	14	15518

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
4.94e-8	1.00	125685	0	63	125748	0.000251

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.181	537	525	1.02	0.0000306	6357
Missense in Polyphen		130	146.93	0.88476		1804
Synonymous	-0.444	226	218	1.04	0.0000131	1987
Loss of Function	3.43	20	44.8	0.447	0.00000250	495

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00121	0.00121
Ashkenazi Jewish	0.00	0.00
East Asian	0.000326	0.000326
Finnish	0.0000462	0.0000462
European (Non-Finnish)	0.000220	0.000220
Middle Eastern	0.000326	0.000326
South Asian	0.000163	0.000163
Other	0.000163	0.000163

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Required for normal Golgi function. {ECO:0000250}.
• Disease: DISEASE: Congenital disorder of glycosylation 2G (CDG2G) [MIM:611209]: A multisystem disorder caused by a defect in glycoprotein biosynthesis and characterized by under-glycosylated serum glycoproteins. Congenital disorders of glycosylation result in a wide variety of clinical features, such as defects in 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. Clinical features of CDG2G include failure to thrive, generalized hypotonia, growth retardation and mild psychomotor retardation. CDG2G is biochemically characterized by a defect in O-glycosylation as well as N-glycosylation. {ECO:0000269|PubMed:16537452}. 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: 0.134

Intolerance Scores

• loftool: 0.559
• rvis_EVS: 0.03
• rvis_percentile_EVS: 55.84

Haploinsufficiency Scores

• pHI: 0.164
• hipred: N
• hipred_score: 0.426
• ghis: 0.537

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: S
• essential_gene_gene_trap: E
• gene_indispensability_pred: E
• gene_indispensability_score: 0.933

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Cog1

Gene ontology

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