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    COX18 cytochrome c oxidase assembly factor COX18 [ Homo sapiens (human) ]

    Gene ID: 285521, updated on 27-Nov-2024

    Summary

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    Official Symbol
    COX18provided by HGNC
    Official Full Name
    cytochrome c oxidase assembly factor COX18provided by HGNC
    Primary source
    HGNC:HGNC:26801
    See related
    Ensembl:ENSG00000163626 MIM:610428; AllianceGenome:HGNC:26801
    Gene type
    protein coding
    RefSeq status
    REVIEWED
    Organism
    Homo sapiens
    Lineage
    Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
    Also known as
    OXA1L2; COX18HS
    Summary
    This gene encodes a cytochrome c oxidase assembly protein. The encoded protein is essential for integral membrane protein insertion into the mitochondrial inner membrane. It is also required for cytochrome c oxidase assembly and activity. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2014]
    Expression
    Ubiquitous expression in kidney (RPKM 3.3), adrenal (RPKM 2.9) and 25 other tissues See more
    Orthologs
    mouse all
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    Genomic context

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    See COX18 in Genome Data Viewer
    Location:
    4q13.3
    Exon count:
    6
    Annotation release Status Assembly Chr Location
    RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 4 NC_000004.12 (73052362..73069759, complement)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 4 NC_060928.1 (76395977..76413374, complement)
    RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 4 NC_000004.11 (73918079..73935476, complement)

    Chromosome 4 - NC_000004.12Genomic Context describing neighboring genes Neighboring gene uncharacterized LOC105377273 Neighboring gene uncharacterized LOC107986286 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr4:73877285-73878180 Neighboring gene Sharpr-MPRA regulatory region 13076 Neighboring gene RNA, U6atac small nuclear 5, pseudogene Neighboring gene ATAC-STARR-seq lymphoblastoid active region 21608 Neighboring gene H3K27ac hESC enhancer GRCh37_chr4:73934752-73935267 Neighboring gene H3K27ac hESC enhancer GRCh37_chr4:73935268-73935784 Neighboring gene uncharacterized LOC112268467 Neighboring gene ankyrin repeat domain 17 Neighboring gene high mobility group AT-hook 1 pseudogene 2

    Genomic regions, transcripts, and products

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    Go to nucleotide: Graphics FASTA GenBank

    Expression

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    • Project title: HPA RNA-seq normal tissues
    • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
    • BioProject: PRJEB4337
    • Publication: PMID 24309898
    • Analysis date: Wed Apr 4 07:08:55 2018

    Bibliography

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    Related articles in PubMed

    1. Mutation analysis of COX18 in 29 patients with isolated cytochrome c oxidase deficiency. Sacconi S, et al. J Hum Genet, 2009 Jul. PMID 19373256
    2. A biallelic variant in COX18 cause isolated Complex IV deficiency associated with neonatal encephalo-cardio-myopathy and axonal sensory neuropathy. Ronchi D, et al. Eur J Hum Genet, 2023 Dec. PMID 37468577, Free PMC Article
    3. hCOX18 and hCOX19: two human genes involved in cytochrome c oxidase assembly. Sacconi S, et al. Biochem Biophys Res Commun, 2005 Nov 25. PMID 16212937
    4. The COX18 gene, involved in mitochondrial biogenesis, is functionally conserved and tightly regulated in humans and fission yeast. Gaisne M, et al. FEMS Yeast Res, 2006 Sep. PMID 16911509
    5. Human mitochondrial cytochrome c oxidase assembly factor COX18 acts transiently as a membrane insertase within the subunit 2 maturation module. Bourens M, et al. J Biol Chem, 2017 May 12. PMID 28330871, Free PMC Article

    See all (22) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. A biallelic variant in COX18 cause isolated Complex IV deficiency associated with neonatal encephalo-cardio-myopathy and axonal sensory neuropathy.
      Title: A biallelic variant in COX18 cause isolated Complex IV deficiency associated with neonatal encephalo-cardio-myopathy and axonal sensory neuropathy.
    2. COX20 stabilizes COX2 during insertion of its N-proximal transmembrane domain, and subsequently, COX18 transiently interacts with COX2 to promote translocation across the inner membrane of the COX2 C-tail that contains the apo-CuA site. The release of COX18 from this complex coincides with the binding of the SCO1-SCO2-COA6 copper metallation module to COX2-COX20 to finalize COX2 biogenesis.
      Title: Human mitochondrial cytochrome c oxidase assembly factor COX18 acts transiently as a membrane insertase within the subunit 2 maturation module.
    3. Observational study of gene-disease association. (HuGE Navigator)
      Title: Genetic variants in nuclear-encoded mitochondrial genes influence AIDS progression.
    4. Observational study of gene-disease association and gene-gene interaction. (HuGE Navigator)
      Title: MicroRNA-related genetic variations as predictors for risk of second primary tumor and/or recurrence in patients with early-stage head and neck cancer.
    5. Clinical trial of gene-disease association and gene-environment interaction. (HuGE Navigator)
      Title: Personalized smoking cessation: interactions between nicotine dose, dependence and quit-success genotype score.
    6. Observational study and genome-wide association study of gene-disease association. (HuGE Navigator)
      Title: Genome-wide pleiotropy of osteoporosis-related phenotypes: the Framingham Study.
    7. COX18 mutations may be very rare or associated with other phenotypes than isolated COX deficiency in infancy.
      Title: Mutation analysis of COX18 in 29 patients with isolated cytochrome c oxidase deficiency.
    8. Both hCox18p and hCox19p present significant amino acid identity with the corresponding yeast polypeptides and reveal highly conserved functional domains.
      Title: hCOX18 and hCOX19: two human genes involved in cytochrome c oxidase assembly.
    Submit: New GeneRIF Correction

    Phenotypes

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    Find tests for this gene in the NIH Genetic Testing Registry (GTR)

    Review eQTL and phenotype association data in this region using PheGenI

    EBI GWAS Catalog

    Description
    A meta-analysis of 87,040 individuals identifies 23 new susceptibility loci for prostate cancer.
    EBI GWAS Catalog
    Genome-wide association scan for survival on dialysis in African-Americans with type 2 diabetes.
    EBI GWAS Catalog
    Identification of 23 new prostate cancer susceptibility loci using the iCOGS custom genotyping array.
    EBI GWAS Catalog

    Variation

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    See variants in ClinVar

    See studies and variants in dbVar

    See Variation Viewer (GRCh37.p13)

    See Variation Viewer (GRCh38)

    HIV-1 interactions

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    Replication interactions

    Interaction Pubs
    Knockdown of COX18 cytochrome c oxidase assembly homolog (S. cerevisiae) by siRNA enhances the early stages of HIV-1 replication in HeLa-CD4 cells infected with viral pseudotypes HIV89.6R and HIV8.2N PubMed

    Go to the HIV-1, Human Interaction Database

    Pathways from PubChem

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    Interactions

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    Products Interactant Other Gene Complex Source Pubs Description

    General gene information

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    Markers

    Homology

    Clone Names

    • FLJ38991, MGC126733

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    enables membrane insertase activity EXP
    Inferred from Experiment
    more info
    		 PubMed 
    enables membrane insertase activity IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    enables membrane insertase activity IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables membrane insertase activity IGI
    Inferred from Genetic Interaction
    more info
    		 PubMed 
    enables protein binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    Process Evidence Code Pubs
    involved_in mitochondrial cytochrome c oxidase assembly IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in mitochondrial cytochrome c oxidase assembly IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in mitochondrial cytochrome c oxidase assembly TAS
    Traceable Author Statement
    more info
    		  
    involved_in protein insertion into mitochondrial inner membrane from matrix IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in protein insertion into mitochondrial inner membrane from matrix IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in protein insertion into mitochondrial membrane IGI
    Inferred from Genetic Interaction
    more info
    		 PubMed 
    involved_in respiratory chain complex IV assembly IGI
    Inferred from Genetic Interaction
    more info
    		 PubMed 
    Component Evidence Code Pubs
    is_active_in mitochondrial inner membrane IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    located_in mitochondrial inner membrane IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    located_in mitochondrial inner membrane TAS
    Traceable Author Statement
    more info
    		  
    located_in mitochondrion HTP PubMed 

    General protein information

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    Preferred Names
    cytochrome c oxidase assembly protein COX18, mitochondrial
    Names
    COX18, cytochrome c oxidase assembly factor
    cytochrome c oxidase assembly homolog 18
    cytochrome c oxidase assembly protein 18
    mitochondrial inner membrane protein COX18

    NCBI Reference Sequences (RefSeq)

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    RefSeqs maintained independently of Annotated Genomes

    These reference sequences exist independently of genome builds. Explain

    These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

    mRNA and Protein(s)

    1. NM_001297732.2 → NP_001284661.1  cytochrome c oxidase assembly protein COX18, mitochondrial isoform 1

      See identical proteins and their annotated locations for NP_001284661.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (1) represents the longest transcript and encodes isoform 1.
      Source sequence(s)
      AC095053, BC143642, DA385228
      Consensus CDS
      CCDS75139.1
      UniProtKB/TrEMBL
      B7ZL88
      Related
      ENSP00000425261.3, ENST00000507544.3
      Conserved Domains (1) summary
      cl00489
      Location:71 → 300
      60KD_IMP; 60Kd inner membrane protein

    2. NM_001297733.2 → NP_001284662.1  cytochrome c oxidase assembly protein COX18, mitochondrial isoform 3

      See identical proteins and their annotated locations for NP_001284662.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (3) differs in its 5' UTR, uses a downstream start codon, and uses an alternate splice site in the central coding region, compared to variant 1. The encoded isoform (3) is shorter, compared to isoform 1.
      Source sequence(s)
      AC095053, AM055751, DA674605
      UniProtKB/Swiss-Prot
      Q8N8Q8
      Conserved Domains (1) summary
      cl00489
      Location:7 → 148
      60KD_IMP; 60Kd inner membrane protein

    3. NM_001300729.1 → NP_001287658.1  cytochrome c oxidase assembly protein COX18, mitochondrial isoform 4

      Status: REVIEWED

      Description
      Transcript Variant: This variant (4) lacks an exon in the central coding region, which results in the use of an alternate start codon and a frameshift, compared to variant 1. The encoded isoform (4) has a longer and distinct N-terminus, compared to isoform 1.
      Source sequence(s)
      AC095053, AM055752, DA674605
      UniProtKB/Swiss-Prot
      Q8N8Q8
      Conserved Domains (1) summary
      cl00489
      Location:153 → 302
      60KD_IMP; 60Kd inner membrane protein

    4. NM_173827.4 → NP_776188.1  cytochrome c oxidase assembly protein COX18, mitochondrial isoform 2

      See identical proteins and their annotated locations for NP_776188.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (2) uses an alternate splice site in the central coding region, but maintains the reading frame, compared to variant 1. The encoded isoform (2) is shorter, compared to isoform 1.
      Source sequence(s)
      AC095053, AK096310, BC101684, DA385228
      Consensus CDS
      CCDS3554.1
      UniProtKB/Swiss-Prot
      Q2PB66, Q2PB67, Q2PB68, Q49B97, Q6IPP9, Q8N8Q8
      Related
      ENSP00000295890.4, ENST00000295890.8
      Conserved Domains (1) summary
      cl00489
      Location:71 → 299
      60KD_IMP; 60Kd inner membrane protein

    RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2024_08

    The following sections contain reference sequences that belong to a specific genome build. Explain

    Reference GRCh38.p14 Primary Assembly

    Genomic

    1. NC_000004.12 Reference GRCh38.p14 Primary Assembly

      Range
      73052362..73069759 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_017008045.3 → XP_016863534.1  cytochrome c oxidase assembly protein COX18, mitochondrial isoform X2

    2. XM_005265680.6 → XP_005265737.1  cytochrome c oxidase assembly protein COX18, mitochondrial isoform X1

      See identical proteins and their annotated locations for XP_005265737.1

      Conserved Domains (1) summary
      cl00489
      Location:71 → 277
      60KD_IMP; 60Kd inner membrane protein

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060928.1 Alternate T2T-CHM13v2.0

      Range
      76395977..76413374 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_054349734.1 → XP_054205709.1  cytochrome c oxidase assembly protein COX18, mitochondrial isoform X2

    2. XM_054349733.1 → XP_054205708.1  cytochrome c oxidase assembly protein COX18, mitochondrial isoform X1

    Suppressed Reference Sequence(s)

    The following Reference Sequences have been suppressed. Explain

    1. NM_001033760.1: Suppressed sequence

      Description
      NM_001033760.1: This RefSeq was permanently suppressed because it is a nonsense-mediated mRNA decay (NMD) candidate.
    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    Q8N8Q8.1 GenPept UniProtKB/Swiss-Prot:Q8N8Q8

    Gene LinkOut

    The following LinkOut resources are supplied by external providers. These providers are responsible for maintaining the links.

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