Cytochrome c oxidase (COX), the terminal enzyme of the mitochondrial respiratory chain, catalyzes the electron transfer from reduced cytochrome c to oxygen. It is a heteromeric complex consisting of 3 catalytic subunits encoded by mitochondrial genes and multiple structural subunits encoded by nuclear genes. The mitochondrially-encoded subunits function in the electron transfer... See more...

Aliases for COX6A1 Gene

Aliases for COX6A1 Gene

  • Cytochrome C Oxidase Subunit 6A1 2 3 5
  • Cytochrome C Oxidase Subunit 6A1, Mitochondrial 3 4
  • Cytochrome C Oxidase Subunit VIa Polypeptide 1 2 3
  • Cytochrome C Oxidase Polypeptide VIa-Liver 3 4
  • Cytochrome C Oxidase Subunit VIA-Liver 3 4
  • COX VIa-L 3 4
  • COX6AL 3 4
  • Cytochrome C Oxidase Subunit VIa Homolog 3
  • CMTRID 3
  • COX6A 3

External Ids for COX6A1 Gene

Previous HGNC Symbols for COX6A1 Gene

  • COX6A

Previous GeneCards Identifiers for COX6A1 Gene

  • GC12P119748
  • GC12P120402
  • GC12P120658
  • GC12P119287
  • GC12P119338
  • GC12P120875
  • GC12P117884

Summaries for COX6A1 Gene

Entrez Gene Summary for COX6A1 Gene

  • Cytochrome c oxidase (COX), the terminal enzyme of the mitochondrial respiratory chain, catalyzes the electron transfer from reduced cytochrome c to oxygen. It is a heteromeric complex consisting of 3 catalytic subunits encoded by mitochondrial genes and multiple structural subunits encoded by nuclear genes. The mitochondrially-encoded subunits function in the electron transfer and the nuclear-encoded subunits may function in the regulation and assembly of the complex. This nuclear gene encodes polypeptide 1 (liver isoform) of subunit VIa, and polypeptide 1 is found in all non-muscle tissues. Polypeptide 2 (heart/muscle isoform) of subunit VIa is encoded by a different gene, and is present only in striated muscles. These two polypeptides share 66% amino acid sequence identity. It has been reported that there may be several pseudogenes on chromosomes 1, 6, 7q21, 7q31-32 and 12. However, only one pseudogene (COX6A1P) on chromosome 1p31.1 has been documented. [provided by RefSeq, Jul 2008]

GeneCards Summary for COX6A1 Gene

COX6A1 (Cytochrome C Oxidase Subunit 6A1) is a Protein Coding gene. Diseases associated with COX6A1 include Charcot-Marie-Tooth Disease, Recessive Intermediate D and Charcot-Marie-Tooth Disease. Among its related pathways are Respiratory electron transport, ATP synthesis by chemiosmotic coupling, and heat production by uncoupling proteins. and Gene Expression. Gene Ontology (GO) annotations related to this gene include cytochrome-c oxidase activity. An important paralog of this gene is COX6A2.

UniProtKB/Swiss-Prot Summary for COX6A1 Gene

  • This protein is one of the nuclear-coded polypeptide chains of cytochrome c oxidase, the terminal oxidase in mitochondrial electron transport.

Gene Wiki entry for COX6A1 Gene

Additional gene information for COX6A1 Gene

No data available for CIViC Summary , Tocris Summary , PharmGKB "VIP" Summary , Rfam classification and piRNA Summary for COX6A1 Gene

Genomics for COX6A1 Gene

GeneHancer (GH) Regulatory Elements for COX6A1 Gene

Promoters and enhancers for COX6A1 Gene
GeneHancer (GH) Identifier GH Type GH
Score
GH Sources Gene Association Score Total Score TSS distance (kb) Number of Genes Away Size (kb) Transcription Factor
Binding Sites
Gene Targets
GH12J120437 Promoter/Enhancer 2 EPDnew Ensembl ENCODE CraniofacialAtlas 500.7 +0.6 610 3 ZBTB40 ZNF217 CTCF NRF1 POLR2G SP1 PHF8 ZFX POLR2A ZBTB11 COX6A1 ENSG00000111780 RF00004-033 COQ5 GATC RNF10
GH12J120494 Promoter/Enhancer 2 EPDnew Ensembl ENCODE CraniofacialAtlas 10.9 +58.5 58477 3.5 RXRA SIN3A NRF1 TCF12 POLR2G SP1 GTF2E2 PHF8 FOS ZFX DYNLL1 SRSF9 NRAV NONHSAG012519.2 COQ5 GATC RPL29P24 RPL31P52 GCN1 RNF10
GH12J120549 Enhancer 1.1 Ensembl ENCODE 14.9 +113.3 113310 3.2 FOXK2 NCOR1 KDM6A TCF7 SKI TEAD1 ZBTB26 TBX3 ZSCAN9 KMT2B COQ5 GATC COX6A1 RPL29P24 NRAV DYNLL1 SRSF9 TRIAP1 RPL31P52 ENSG00000111780
GH12J120388 Promoter/Enhancer 1.4 Ensembl ENCODE CraniofacialAtlas dbSUPER 10.9 -48.7 -48687 1.6 USF1 ZNF639 ZBTB5 TOE1 HINFP GATAD2B HDAC2 POLR2A RAD51 WT1 ENSG00000256695 MSI1 SIRT4 PLA2G1B COX6A1 ENSG00000111780 RNU6-1088P RPS27P25
GH12J120487 Enhancer 1.2 FANTOM5 Ensembl ENCODE 10.9 +50.3 50311 2.4 AFF1 TOE1 CTBP1 ATF2 TAF9B HDAC3 NCOR1 TRIM25 ZNF282 NFIC GATC COQ5 RPL31P52 TRIAP1 ENSG00000111780 COX6A1 SIRT4 NRAV DYNLL1
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around COX6A1 on UCSC Golden Path with GeneCards custom track

Cistromic (ChIP-Seq) regulation report from SPP (The Signaling Pathways Project) for COX6A1

Top Transcription factor binding sites by QIAGEN in the COX6A1 gene promoter:
  • AML1a
  • c-Myc
  • E47
  • Max
  • MIF-1
  • Olf-1
  • p53
  • Pbx1a
  • RFX1
  • Tal-1beta

Genomic Locations for COX6A1 Gene

Genomic Locations for COX6A1 Gene
chr12:120,438,090-120,440,742
(GRCh38/hg38)
Size:
2,653 bases
Orientation:
Plus strand
chr12:120,875,893-120,878,545
(GRCh37/hg19)
Size:
2,653 bases
Orientation:
Plus strand

Genomic View for COX6A1 Gene

Genes around COX6A1 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
COX6A1 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for COX6A1 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for COX6A1 Gene

Proteins for COX6A1 Gene

  • Protein details for COX6A1 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    P12074-CX6A1_HUMAN
    Recommended name:
    Cytochrome c oxidase subunit 6A1, mitochondrial
    Protein Accession:
    P12074
    Secondary Accessions:
    • B2R500
    • O43714
    • Q32Q37

    Protein attributes for COX6A1 Gene

    Size:
    109 amino acids
    Molecular mass:
    12155 Da
    Quaternary structure:
    No Data Available
    SequenceCaution:
    • Sequence=CAA33392.1; Type=Frameshift; Evidence={ECO:0000305};

    Three dimensional structures from OCA and Proteopedia for COX6A1 Gene

neXtProt entry for COX6A1 Gene

Post-translational modifications for COX6A1 Gene

  • Ubiquitination at Lys82
  • Modification sites at PhosphoSitePlus

Other Protein References for COX6A1 Gene

ENSEMBL proteins:
REFSEQ proteins:

No data available for DME Specific Peptides for COX6A1 Gene

Domains & Families for COX6A1 Gene

Gene Families for COX6A1 Gene

HGNC:
Human Protein Atlas (HPA):
  • Disease related genes
  • Predicted membrane proteins

Protein Domains for COX6A1 Gene

Blocks:
  • Cytochrome c oxidase, subunit VIa
InterPro:
ProtoNet:

Suggested Antigen Peptide Sequences for COX6A1 Gene

GenScript: Design optimal peptide antigens:
  • Cytochrome c oxidase subunit VIA-liver (CX6A1_HUMAN)

Graphical View of Domain Structure for InterPro Entry

P12074

UniProtKB/Swiss-Prot:

CX6A1_HUMAN :
  • Belongs to the cytochrome c oxidase subunit 6A family.
Family:
  • Belongs to the cytochrome c oxidase subunit 6A family.
genes like me logo Genes that share domains with COX6A1: view

Function for COX6A1 Gene

Molecular function for COX6A1 Gene

UniProtKB/Swiss-Prot Function:
This protein is one of the nuclear-coded polypeptide chains of cytochrome c oxidase, the terminal oxidase in mitochondrial electron transport.
GENATLAS Biochemistry:
cytochrome c oxidase,subunit VIa,polypeptide 1,liver specific,97.5kDa,component of the complex IV,terminal enzyme complex for electron transfert,oxidative phosphorylation (OXPHOS),inner mitochondrial membrane

Phenotypes From GWAS Catalog for COX6A1 Gene

Gene Ontology (GO) - Molecular Function for COX6A1 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0004129 contributes_to cytochrome-c oxidase activity IBA 21873635
GO:0030234 enzyme regulator activity IBA 21873635
genes like me logo Genes that share ontologies with COX6A1: view
genes like me logo Genes that share phenotypes with COX6A1: view

Human Phenotype Ontology for COX6A1 Gene

HPO Id HPO Name Alternative Ids Definition Synonyms

Animal Models for COX6A1 Gene

MGI Knock Outs for COX6A1:
  • Cox6a1 Cox6a1<tm1(KOMP)Wtsi>

Animal Model Products

CRISPR Products

Inhibitory RNA Products

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for COX6A1

Clone Products

No data available for Enzyme Numbers (IUBMB) , Transcription Factor Targets and HOMER Transcription for COX6A1 Gene

Localization for COX6A1 Gene

Subcellular locations from UniProtKB/Swiss-Prot for COX6A1 Gene

Mitochondrion inner membrane.

Subcellular locations from

COMPARTMENTS
Extracellular space Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi Apparatus Nucleus Mitochondrion 0 1 2 3 4 5 Confidence
COMPARTMENTS Subcellular localization image for COX6A1 gene
Compartment Confidence
mitochondrion 5
nucleus 2
plasma membrane 1
extracellular 1
cytoskeleton 1
endoplasmic reticulum 1
endosome 1
cytosol 1
lysosome 1
golgi apparatus 1
peroxisome 0

Subcellular locations from the

Human Protein Atlas (HPA)

Gene Ontology (GO) - Cellular Components for COX6A1 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005739 mitochondrion IEA,IDA --
GO:0005743 mitochondrial inner membrane TAS --
GO:0005751 mitochondrial respiratory chain complex IV IBA 21873635
GO:0016020 membrane IEA --
GO:0016021 integral component of membrane IEA --
genes like me logo Genes that share ontologies with COX6A1: view

Pathways & Interactions for COX6A1 Gene

genes like me logo Genes that share pathways with COX6A1: view

Gene Ontology (GO) - Biological Process for COX6A1 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0006091 generation of precursor metabolites and energy TAS 2549515
GO:0006123 mitochondrial electron transport, cytochrome c to oxygen IBA,TAS --
GO:0009060 aerobic respiration IBA 21873635
GO:0022900 electron transport chain IEA --
GO:0050790 regulation of catalytic activity IEA --
genes like me logo Genes that share ontologies with COX6A1: view

No data available for SIGNOR curated interactions for COX6A1 Gene

Drugs & Compounds for COX6A1 Gene

(2) Drugs for COX6A1 Gene - From: HMDB

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
Oxygen Approved, Vet_approved Pharma 0
Water Approved Pharma 0
genes like me logo Genes that share compounds with COX6A1: view

Transcripts for COX6A1 Gene

mRNA/cDNA for COX6A1 Gene

1 REFSEQ mRNAs :
8 NCBI additional mRNA sequence :
3 Ensembl transcripts including schematic representations, and UCSC links to gene/alias where relevant :

CRISPR Products

Inhibitory RNA Products

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for COX6A1

Clone Products

Alternative Splicing Database (ASD) splice patterns (SP) for COX6A1 Gene

No ASD Table

Relevant External Links for COX6A1 Gene

GeneLoc Exon Structure for
COX6A1

Expression for COX6A1 Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and SAGE for COX6A1 Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

Protein differential expression in normal tissues from HIPED for COX6A1 Gene

This gene is overexpressed in CD8 Tcells (9.8) and Fetal Liver (9.0).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB, MaxQB, and MOPED for COX6A1 Gene



Protein tissue co-expression partners for COX6A1 Gene

Transcriptomic regulation report from SPP (The Signaling Pathways Project) for COX6A1

SOURCE GeneReport for Unigene cluster for COX6A1 Gene:

Hs.369624

Evidence on tissue expression from TISSUES for COX6A1 Gene

  • Nervous system(4.8)
  • Liver(4.7)
  • Stomach(3)
  • Eye(2.9)
  • Heart(2.9)
  • Kidney(2.7)
  • Intestine(2.6)
  • Lung(2.6)
  • Spleen(2.5)
  • Muscle(2.4)
  • Thyroid gland(2.1)

Phenotype-based relationships between genes and organs from Gene ORGANizer for COX6A1 Gene

Germ Layers:
  • ectoderm
  • mesoderm
Systems:
  • nervous
  • skeletal muscle
  • skeleton
Regions:
Head and neck:
  • brain
  • head
Limb:
  • foot
  • lower limb
  • shin
General:
  • peripheral nerve
  • peripheral nervous system
  • spinal cord
genes like me logo Genes that share expression patterns with COX6A1: view

No data available for mRNA differential expression in normal tissues and mRNA Expression by UniProt/SwissProt for COX6A1 Gene

Orthologs for COX6A1 Gene

This gene was present in the common ancestor of animals and fungi.

Orthologs for COX6A1 Gene

Organism Taxonomy Gene Similarity Type Details
chimpanzee
(Pan troglodytes)
Mammalia COX6A1 31
  • 100 (a)
OneToOne
LOC100616508 30
  • 99.69 (n)
dog
(Canis familiaris)
Mammalia LOC477508 30
  • 87.04 (n)
-- 31
  • 70 (a)
ManyToMany
-- 31
  • 69 (a)
ManyToMany
-- 31
  • 38 (a)
ManyToMany
rat
(Rattus norvegicus)
Mammalia Cox6a1 30
  • 84.26 (n)
cow
(Bos Taurus)
Mammalia COX6A1 31
  • 84 (a)
ManyToMany
-- 31
  • 83 (a)
ManyToMany
mouse
(Mus musculus)
Mammalia Cox6a1 17 31 30
  • 82.41 (n)
oppossum
(Monodelphis domestica)
Mammalia -- 31
  • 62 (a)
OneToMany
chicken
(Gallus gallus)
Aves COX6A1 31 30
  • 69.5 (n)
OneToMany
lizard
(Anolis carolinensis)
Reptilia -- 31
  • 64 (a)
OneToMany
tropical clawed frog
(Silurana tropicalis)
Amphibia cox6a1 30
  • 62.26 (n)
zebrafish
(Danio rerio)
Actinopterygii cox6a1 31 30
  • 60.9 (n)
OneToMany
African malaria mosquito
(Anopheles gambiae)
Insecta AgaP_AGAP000851 30
  • 61.33 (n)
fruit fly
(Drosophila melanogaster)
Insecta levy 31 30
  • 56.73 (n)
ManyToMany
CG30093 31
  • 43 (a)
ManyToMany
CG14077 31
  • 14 (a)
ManyToMany
worm
(Caenorhabditis elegans)
Secernentea tag-174 31
  • 26 (a)
OneToMany
baker's yeast
(Saccharomyces cerevisiae)
Saccharomycetes COX13 33
Species where no ortholog for COX6A1 was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Ashbya gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African clawed frog (Xenopus laevis)
  • Alicante grape (Vitis vinifera)
  • alpha proteobacteria (Wolbachia pipientis)
  • amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • barley (Hordeum vulgare)
  • beta proteobacteria (Neisseria meningitidis)
  • bread mold (Neurospora crassa)
  • Chromalveolata (Phytophthora infestans)
  • common water flea (Daphnia pulex)
  • corn (Zea mays)
  • E. coli (Escherichia coli)
  • filamentous fungi (Aspergillus nidulans)
  • Firmicute bacteria (Streptococcus pneumoniae)
  • fission yeast (Schizosaccharomyces pombe)
  • green algae (Chlamydomonas reinhardtii)
  • honey bee (Apis mellifera)
  • K. lactis yeast (Kluyveromyces lactis)
  • loblloly pine (Pinus taeda)
  • malaria parasite (Plasmodium falciparum)
  • medicago trunc (Medicago Truncatula)
  • moss (Physcomitrella patens)
  • orangutan (Pongo pygmaeus)
  • pig (Sus scrofa)
  • platypus (Ornithorhynchus anatinus)
  • rainbow trout (Oncorhynchus mykiss)
  • rice (Oryza sativa)
  • rice blast fungus (Magnaporthe grisea)
  • schistosome parasite (Schistosoma mansoni)
  • sea anemone (Nematostella vectensis)
  • sea squirt (Ciona intestinalis)
  • sea squirt (Ciona savignyi)
  • sea urchin (Strongylocentrotus purpuratus)
  • sorghum (Sorghum bicolor)
  • soybean (Glycine max)
  • stem rust fungus (Puccinia graminis)
  • sugarcane (Saccharum officinarum)
  • thale cress (Arabidopsis thaliana)
  • tomato (Lycopersicon esculentum)
  • toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • wheat (Triticum aestivum)

Evolution for COX6A1 Gene

ENSEMBL:
Gene Tree for COX6A1 (if available)
TreeFam:
Gene Tree for COX6A1 (if available)
Aminode:
Evolutionary constrained regions (ECRs) for COX6A1: view image

Paralogs for COX6A1 Gene

Paralogs for COX6A1 Gene

(2) SIMAP similar genes for COX6A1 Gene using alignment to 2 proteins:

  • CX6A1_HUMAN
  • H6SG15_HUMAN
genes like me logo Genes that share paralogs with COX6A1: view

Variants for COX6A1 Gene

Sequence variations, with clinical significance, from ClinVar and Humsavar, with links to dbSNP for COX6A1 Gene

SNP ID Clinical significance and condition Chr 12 pos Variation AA Info Type
669703 Benign: not provided 120,438,673(+) T/A INTRON_VARIANT
676114 Benign: not provided 120,438,262(+) A/C INTRON_VARIANT
676664 Likely Benign: not provided 120,437,972(+) T/C
676665 Likely Benign: not provided 120,438,079(+) G/A
682112 Likely Benign: not provided 120,438,241(+) G/A INTRON_VARIANT

Additional dbSNP identifiers (rs#s) for COX6A1 Gene

Structural Variations from Database of Genomic Variants (DGV) for COX6A1 Gene

Variant ID Type Subtype PubMed ID
esv3630923 CNV gain 21293372
nsv509482 CNV insertion 20534489

Variation tolerance for COX6A1 Gene

Residual Variation Intolerance Score: 51.2% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 0.36; 7.87% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for COX6A1 Gene

Human Gene Mutation Database (HGMD)
COX6A1
SNPedia medical, phenotypic, and genealogical associations of SNPs for
COX6A1

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for COX6A1 Gene

Disorders for COX6A1 Gene

MalaCards: The human disease database

(10) MalaCards diseases for COX6A1 Gene - From: OMIM, ClinVar, GTR, Orphanet, DISEASES, and GeneCards

- elite association - COSMIC cancer census association via MalaCards

UniProtKB/Swiss-Prot

CX6A1_HUMAN
  • Charcot-Marie-Tooth disease, recessive, intermediate type, D (CMTRID) [MIM:616039]: A form of Charcot-Marie-Tooth disease, a disorder of the peripheral nervous system, characterized by progressive weakness and atrophy, initially of the peroneal muscles and later of the distal muscles of the arms. Recessive intermediate forms of Charcot-Marie-Tooth disease are characterized by clinical and pathologic features intermediate between demyelinating and axonal peripheral neuropathies, and motor median nerve conduction velocities ranging from 25 to 45 m/sec. {ECO:0000269 PubMed:25152455}. Note=The disease is caused by mutations affecting the gene represented in this entry.

Additional Disease Information for COX6A1

Genetic Association Database
(GAD)
Human Genome Epidemiology Navigator
(HuGE)
ATLAS of Genetics and Cytogenetics in Oncology and Haematology
genes like me logo Genes that share disorders with COX6A1: view

No data available for Genatlas for COX6A1 Gene

Publications for COX6A1 Gene

  1. A mutation of COX6A1 causes a recessive axonal or mixed form of Charcot-Marie-Tooth disease. (PMID: 25152455) Tamiya G … Hayasaka K (American journal of human genetics 2014) 3 4 54
  2. Genetic variants in nuclear-encoded mitochondrial genes influence AIDS progression. (PMID: 20877624) Hendrickson SL … O'Brien SJ (PloS one 2010) 3 41 54
  3. Identification of cytochrome c oxidase subunit 6A1 as a suppressor of Bax-induced cell death by yeast-based functional screening. (PMID: 18549809) Eun SY … Seo HG (Biochemical and biophysical research communications 2008) 3 23 54
  4. The finished DNA sequence of human chromosome 12. (PMID: 16541075) Scherer SE … Baylor College of Medicine Human Genome Sequencing Center Sequence Production Team (Nature 2006) 3 4 54
  5. The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). (PMID: 15489334) Gerhard DS … MGC Project Team (Genome research 2004) 3 4 54

Products for COX6A1 Gene

Sources for COX6A1 Gene