COG4

component of oligomeric golgi complex 4, the group of Components of oligomeric golgi complex

Basic information

Region (hg38): 16:70480567-70523560

Links

ENSG00000103051 ∙ NCBI:25839 ∙ OMIM:606976 ∙ HGNC:18620 ∙ Uniprot:Q9H9E3 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• microcephalic osteodysplastic dysplasia, Saul-Wilson type (Strong), mode of inheritance: AD
• COG4-congenital disorder of glycosylation (Strong), mode of inheritance: AR
• COG4-congenital disorder of glycosylation (Moderate), mode of inheritance: AR
• microcephalic osteodysplastic dysplasia, Saul-Wilson type (Moderate), mode of inheritance: AD
• COG4-congenital disorder of glycosylation (Definitive), mode of inheritance: AR
• microcephalic osteodysplastic dysplasia, Saul-Wilson type (Supportive), mode of inheritance: AR
• COG4-congenital disorder of glycosylation (Supportive), mode of inheritance: AR
• COG4-congenital disorder of glycosylation (Strong), mode of inheritance: AR
• microcephalic osteodysplastic dysplasia, Saul-Wilson type (Strong), mode of inheritance: AD
• COG4-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 IIj	AR	Allergy/Immunology/Infectious; Hematologic	The condition can include recurrent respiratory infections as well as other multi-systemic manifestations, and precautions may be beneficial; Awareness of coagulopathies may be beneficial in terms of medical management, especially in situations such as surgery	Allergy/Immunology/Infectious; Audiologic/Otolaryngologic; Biochemical; Craniofacial; Gastrointestinal; Hematologic; Musculoskeletal; Neurologic; Ophthalmologic	19494034; 30290151
Hepatic-metabolized agents should be avoided

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the COG4 gene.

• COG4-congenital disorder of glycosylation (136 variants)
• not provided (123 variants)
• Inborn genetic diseases (44 variants)
• not specified (37 variants)
• Microcephalic osteodysplastic dysplasia, Saul-Wilson type (7 variants)
• COG4-related condition (5 variants)
• Microcephalic osteodysplastic dysplasia, Saul-Wilson type;COG4-congenital disorder of glycosylation (2 variants)
• COG4-congenital disorder of glycosylation;Microcephalic osteodysplastic dysplasia, Saul-Wilson type (2 variants)
• Global developmental delay (1 variants)
• See cases (1 variants)
• Delayed gross motor development (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the COG4 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			2	33	4	39
missense	1	3	128	9	1	142
nonsense	4	1				5
start loss						0
frameshift	2	2	3			7
inframe indel						0
splice donor/acceptor (+/-2bp)	2	2				4
splice region			5	6	1	12
non coding				37	40	77
Total	9	8	133	79	45

Highest pathogenic variant AF is 0.0000526

Variants in COG4

This is a list of pathogenic ClinVar variants found in the COG4 region.

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

Position	Type	Phenotype	Significance	ClinVar
16-70480925-A-C			Benign (Jun 23, 2018)
16-70481003-C-G		not specified • COG4-related disorder	Likely benign (Feb 24, 2020)
16-70481017-C-T		Inborn genetic diseases	Uncertain significance (Jun 01, 2021)
16-70481022-C-G		COG4-congenital disorder of glycosylation	Uncertain significance (Oct 04, 2022)
16-70481032-T-C			Uncertain significance (Jan 12, 2017)
16-70481037-A-G		COG4-congenital disorder of glycosylation	Likely benign (Dec 31, 2019)
16-70481038-C-T		COG4-congenital disorder of glycosylation	Uncertain significance (Sep 25, 2022)
16-70481048-C-G		COG4-related disorder	Uncertain significance (Jul 28, 2023)
16-70481062-A-C		COG4-congenital disorder of glycosylation	Pathogenic (Mar 01, 2011)
16-70481065-AC-A		COG4-related disorder	Uncertain significance (Jul 22, 2023)
16-70481070-G-C		COG4-congenital disorder of glycosylation	Conflicting classifications of pathogenicity (Jul 12, 2022)
16-70481072-G-A		Inborn genetic diseases	Uncertain significance (Dec 14, 2021)
16-70481080-GCAGGGGTGAGGCGC-G			Uncertain significance (May 23, 2017)
16-70481087-T-C		Inborn genetic diseases • COG4-congenital disorder of glycosylation	Uncertain significance (Aug 22, 2022)
16-70481092-C-T		Inborn genetic diseases	Uncertain significance (May 15, 2023)
16-70481093-G-A		Inborn genetic diseases	Uncertain significance (Aug 16, 2021)
16-70481098-G-A		COG4-congenital disorder of glycosylation	Uncertain significance (Sep 14, 2022)
16-70481102-A-G		not specified • COG4-congenital disorder of glycosylation	Likely benign (Nov 07, 2023)
16-70481112-A-G		COG4-congenital disorder of glycosylation	Likely benign (Jul 26, 2019)
16-70481129-C-T		COG4-congenital disorder of glycosylation	Conflicting classifications of pathogenicity (Oct 29, 2023)
16-70481133-G-T		COG4-congenital disorder of glycosylation • COG4-related disorder	Likely benign (Oct 13, 2023)
16-70481138-C-T		Inborn genetic diseases	Uncertain significance (Oct 04, 2022)
16-70481144-C-T		COG4-congenital disorder of glycosylation	Uncertain significance (Aug 04, 2023)
16-70481160-T-C		not specified • COG4-congenital disorder of glycosylation	Benign (Jan 16, 2024)
16-70481160-T-TA		not specified	Likely benign (Feb 12, 2016)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
COG4	protein_coding	protein_coding	ENST00000323786	19	42998

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
3.97e-9	0.999	125676	0	72	125748	0.000286

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.282	454	437	1.04	0.0000254	5216
Missense in Polyphen		135	152.16	0.88722		1769
Synonymous	-1.01	188	171	1.10	0.00000984	1511
Loss of Function	3.05	21	42.4	0.495	0.00000221	488

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000642	0.000641
Ashkenazi Jewish	0.00	0.00
East Asian	0.000979	0.000979
Finnish	0.000139	0.000139
European (Non-Finnish)	0.000211	0.000211
Middle Eastern	0.000979	0.000979
South Asian	0.000392	0.000392
Other	0.000489	0.000489

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Required for normal Golgi function. Plays a role in SNARE-pin assembly and Golgi-to-ER retrograde transport via its interaction with SCFD1. {ECO:0000269|PubMed:19536132}.
• Disease: DISEASE: Congenital disorder of glycosylation 2J (CDG2J) [MIM:613489]: 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. {ECO:0000269|PubMed:19494034, ECO:0000269|PubMed:19651599}. 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: 0.113

Intolerance Scores

• loftool: 0.827
• rvis_EVS: -1
• rvis_percentile_EVS: 8.54

Haploinsufficiency Scores

• pHI: 0.269
• hipred: N
• hipred_score: 0.426
• ghis: 0.580

Essentials

• essential_gene_CRISPR: E
• essential_gene_CRISPR2: E
• essential_gene_gene_trap: E
• gene_indispensability_pred: E
• gene_indispensability_score: 0.638

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Cog4

Gene ontology

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