COG6

component of oligomeric golgi complex 6, the group of Components of oligomeric golgi complex

Basic information

Region (hg38): 13:39655627-39791666

Links

ENSG00000133103 ∙ NCBI:57511 ∙ OMIM:606977 ∙ HGNC:18621 ∙ Uniprot:Q9Y2V7 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• COG6-congenital disorder of glycosylation (Strong), mode of inheritance: AR
• COG6-congenital disorder of glycosylation (Strong), mode of inheritance: AR
• hypohidrosis-enamel hypoplasia-palmoplantar keratoderma-intellectual disability syndrome (Supportive), mode of inheritance: AR
• COG6-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 IIl	AR	Allergy/Immunology/Infectious; Hematologic	The condition can include recurrent infections as well as other multi-systemic manifestations, and awareness may allow preventive measures as well as early and aggressive treatment of infections; A described individual presented with neurological manifestations as well as vitamin K deficiency and intracranial bleeding; Awareness of coagulopathies may be beneficial in terms of medical management, especially in situations such as surgery	Allergy/Immunology/Infectious; Biochemical; Craniofacial; Dental; Dermatologic; Gastrointestinal; Hematologic; Neurologic	20605848; 23606727
Hepatic-metabolized agents should be avoided

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the COG6 gene.

• COG6-congenital_disorder_of_glycosylation (171 variants)
• Hypohidrosis-enamel_hypoplasia-palmoplantar_keratoderma-intellectual_disability_syndrome (125 variants)
• Inborn_genetic_diseases (104 variants)
• not_provided (59 variants)
• COG6-related_disorder (24 variants)
• not_specified (23 variants)
• Hypohidrosis (1 variants)
• Intellectual_disability (1 variants)
• Autosomal_dominant_intellectual_disability-craniofacial_anomalies-cardiac_defects_syndrome (1 variants)
• See_cases (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the COG6 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000020751.3. Only rare variants are included in the table.

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.

Effect	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous		1	10	45	1	57
missense	1	2	146	10	1	160
nonsense	5	4	1			10
start loss		1				1
frameshift	4	5	2			11
splice donor/acceptor (+/-2bp)	1	7	6			14
Total	11	20	165	55	2

Highest pathogenic variant AF is 0.00002377535

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
COG6	protein_coding	protein_coding	ENST00000455146	19	136039

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
6.36e-16	0.336	125663	0	85	125748	0.000338

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.184	371	361	1.03	0.0000187	4277
Missense in Polyphen		120	116.42	1.0308		1371
Synonymous	0.538	121	129	0.940	0.00000656	1264
Loss of Function	1.46	29	38.8	0.748	0.00000195	469

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000693	0.000692
Ashkenazi Jewish	0.000298	0.000298
East Asian	0.000381	0.000381
Finnish	0.0000464	0.0000462
European (Non-Finnish)	0.000336	0.000334
Middle Eastern	0.000381	0.000381
South Asian	0.000559	0.000555
Other	0.000490	0.000489

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Required for normal Golgi function. {ECO:0000250}.
• Disease: DISEASE: Congenital disorder of glycosylation 2L (CDG2L) [MIM:614576]: 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 CDG2L include neonatal intractable focal seizures, vomiting, loss of consciousness, intracranial bleeding due to vitamin K deficiency, and death in infancy. {ECO:0000269|PubMed:20605848}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Shaheen syndrome (SHNS) [MIM:615328]: An autosomal recessive form of syndromic mental retardation. Affected individuals show severe intellectual disability, hypohidrosis, dental enamel hypoplasia, and hyperkeratosis of the palms and soles. Some may develop mild microcephaly. {ECO:0000269|PubMed:23606727}. 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: 0.105

Intolerance Scores

• loftool: 0.969
• rvis_EVS: 0.62
• rvis_percentile_EVS: 83.53

Haploinsufficiency Scores

• pHI: 0.178
• hipred: N
• hipred_score: 0.454
• ghis: 0.562

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: K
• gene_indispensability_pred: E
• gene_indispensability_score: 0.747

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	High	High	High
Primary Immunodeficiency	High	High	High
Cancer	High	High	High

Mouse Genome Informatics

• Gene name: Cog6
• Phenotype: nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); skeleton phenotype; immune system phenotype; liver/biliary system phenotype; embryo phenotype; cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); hematopoietic system phenotype; normal phenotype

Gene ontology

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