COG5
protein-codingcomponent of oligomeric golgi complex 5, the group of Components of oligomeric golgi complex
Gene summary
The protein encoded by this gene is one of eight proteins (Cog1-8) which form a Golgi-localized complex (COG) required for normal Golgi morphology and function. The encoded protein is organized with conserved oligomeric Golgi complex components 6, 7 and 8 into a sub-complex referred to as lobe B. Alternative splicing results in multiple transcript variants. Mutations in this gene result in congenital disorder of glycosylation type 2I.[provided by RefSeq, Jan 2011]
- GOLTC1
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~362.9 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
Inheritance Pattern: AR
Disease ID:MONDO:0013325
Submitter: Laboratory for Molecular Medicine
This gene-disease relationship has undergone rapid assessment. Classifications are based on preliminary review of gene-disease validity during analysis of genomic sequencing results.
Inheritance Pattern: AR
Disease ID:MONDO:0013325
Submitter: Orphanet
Inheritance Pattern: AR
Disease ID:MONDO:0013325
Submitter: ClinGen
COG5 was first reported in relation to autosomal recessive congenital disorder of glycosylation, type IIi in 2009 (Praesold-Burda et al., PMID:19690088). To date, 13 COG5 mutations have been reported in relation to 10 cases (Wang et al., PMID:32174980). Common symptoms among the reported cases include neurological, morphological, and hepatic abnormalities. Defects in the COG5 protein are mainly associated with abnormalities of the brain, liver, bladder, and auditory and visual systems (Yin et al., PMID:31572517). Most of the COG5 mutations are located in exons, while one mutation is a homozygous intronic substitution that leads to COG5 exon skipping. Due to the COG5 protein being highly conserved among numerous species, the full-length protein is important for its function (Yin et al., PMID:31572517). More evidence is available in the literature, but the maximum score for genetic evidence (12pts) has been reached. The gene-disease relationship is also supported by experimental evidence in the form of biochemical function in COG5 proteins (Wang et al., PMID:32174980) and Brefeldin A (BFA) treatment (Praesold-Burda et al., PMID:19690088). Additional experimental evidence highlights interactions between COG5 and other COG proteins (Ungar et al., PMID:11980916). In summary, there is definitive evidence supporting the relationship between COG5 and autosomal recessive congenital disorder of glycosylation (CDG). This has been repeatedly demonstrated in both research and clinical diagnostic settings and has been upheld over time. This classification was approved by the ClinGen Congenital Disorders of Glycosylation GCEP on August 7, 2024 (SOP Version 10).
Inheritance Pattern: AR
Disease ID:MONDO:0013325
Submitter: Labcorp Genetics (formerly Invitae)
Inheritance Pattern: AR
Disease ID:MONDO:0013325
Submitter: G2P
Clinical Genomic Database (CGD)
Manifestation: Audiologic/Otolaryngologic; Biochemical; Hematologic; Neurologic; Ophthalmologic
Intervention: Hematologic
Rationale: Awareness of coagulopathies may be beneficial in terms of medical management, especially in situations such as surgery
Comments: Hepatic-metabolized agents should be avoided
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to COG5 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_006348.5. Only rare variants are included.
We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.
Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 6 | 177 | 2 | 185 | ||
| missense | 2 | 2 | 333 | 12 | 2 | 351 |
| nonsense | 21 | 3 | 1 | 1 | 26 | |
| start loss | 1 | 3 | 4 | |||
| frameshift | 14 | 7 | 3 | 24 | ||
| splice donor/acceptor (+/-2bp) | 16 | 8 | 24 | |||
| Total | 37 | 29 | 354 | 190 | 4 | 614 |
Highest pathogenic variant AF is 0.000046477675
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_006339.4 | 22 | MANE Select | |
| Ensembl | ENSP00000297135.4 | 22 | MANE Select | |
| RefSeq | NP_001154992.2 | 21 | Standard | |
| RefSeq | NP_001366440.1 | 21 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Vesicle-mediated transport
- Membrane Trafficking
- Post-translational protein modification
- Metabolism of proteins
- Transport to the Golgi and subsequent modification
Biological Process
- endoplasmic reticulum to Golgi vesicle-mediated transport
- intra-Golgi vesicle-mediated transport
- protein transport
Molecular Function
- molecular_function
- protein binding
Cellular Component
- Golgi membrane
- nucleoplasm
- Golgi apparatus
- cytosol
- membrane
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000297135
- Coding exons
- 22
- Length
- 362960
- Individuals with no LoFs
- 125645
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 103
- Defined
- 125748
- p
- 0.000410
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | -0.483 | 492 | 463 | 1.06 | 0.0000231 | 5568 |
| Missense (PolyPhen) | 104 | 118.25 | 0.87953 | 1447 | ||
| Synonymous | -2.00 | 192 | 160 | 1.20 | 0.00000786 | 1691 |
| Loss of Function | 1.75 | 37 | 50.4 | 0.734 | 0.00000258 | 585 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00056 | 0.00055 | rare |
| Latino/Admixed American | 0.00055 | 0.00055 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.00087 | 0.00087 | rare |
| Finnish | 0.000093 | 0.000092 | rare |
| European (Non-Finnish) | 0.00036 | 0.00036 | rare |
| South Asian | 0.00046 | 0.00046 | rare |
| Other | 0.00033 | 0.00033 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Required for normal Golgi function. {ECO:0000250}.;
- Disease
- DISEASE: Congenital disorder of glycosylation 2I (CDG2I) [MIM:613612]: 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. Congenital disorder of glycosylation type 2I is characterized by mild neurological impairments. {ECO:0000269|PubMed:19690088}. Note=The disease is caused by mutations affecting the gene represented in this entry.;
Recessive Scores
- pRec
- 0.100
Intolerance Scores
- LoFtool
- 0.980
- RVIS EVS
- -0.02
- RVIS percentile EVS
- 52.32
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- E
- Indispensability pred.
- E
- Indispensability score
- 0.754
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |