COX4I2 (cytochrome c oxidase subunit 4I2)

Gene

• Entrez ID: 84701
• Gene name: Cytochrome c oxidase subunit 4I2
• Gene symbol: COX4I2
• Synonyms (NCBI Gene): COX4, COX4-2, COX4B, COX4L2, COXIV-2, dJ857M17.2
• Chromosome: 20
• Chromosome location: 20q11.21
• Summary: 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

SNPs

SNP ID	Visualize variation	Clinical significance	Consequence
rs119455950	G>A,T	Uncertain-significance, pathogenic	Stop gained, coding sequence variant, missense variant

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0005739	Component	Mitochondrion	HTP	34800366
GO:0005739	Component	Mitochondrion	IEA
GO:0005743	Component	Mitochondrial inner membrane	IEA
GO:0005743	Component	Mitochondrial inner membrane	TAS
GO:0005758	Component	Mitochondrial intermembrane space	IEA
GO:0005758	Component	Mitochondrial intermembrane space	TAS
GO:0006091	Process	Generation of precursor metabolites and energy	NAS	11311561
GO:0006119	Process	Oxidative phosphorylation	IEA
GO:0006123	Process	Mitochondrial electron transport, cytochrome c to oxygen	IBA
GO:0006123	Process	Mitochondrial electron transport, cytochrome c to oxygen	IDA	11311561
GO:0006123	Process	Mitochondrial electron transport, cytochrome c to oxygen	IEA
GO:0016020	Component	Membrane	IEA
GO:0031966	Component	Mitochondrial membrane	IEA
GO:0045277	Component	Respiratory chain complex IV	IBA
GO:0045277	Component	Respiratory chain complex IV	IC	11311561
GO:0045277	Component	Respiratory chain complex IV	IEA
GO:0045333	Process	Cellular respiration	NAS	11911854

Other IDs

• MIM: 607976
• HGNC: 16232
• e!Ensembl: ENSG00000131055

Protein

• UniProt ID: Q96KJ9
• Protein name: Cytochrome c oxidase subunit 4 isoform 2, mitochondrial (Cytochrome c oxidase subunit IV isoform 2) (COX IV-2)
• Protein function: Component of the cytochrome c oxidase, the last enzyme in the mitochondrial electron transport chain which drives oxidative phosphorylation. The respiratory chain contains 3 multisubunit complexes succinate dehydrogenase (complex II, CII), ubiqu
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF02936	COX4	33 → 170	Cytochrome c oxidase subunit IV	Family

• Tissue specificity: TISSUE SPECIFICITY: Highly expressed in lung.
• Sequence:

  MLPRAAWSLVLRKGGGGRRGMHSSEGTTRGGGKMSPYTNCYAQRYYPMPEEPFCTELNAE
  EQALKEKEKGSWTQLTHAEKVALYRLQFNETFAEMNRRSNEWKTVMGCVFFFIGFAALVI
  WWQRVYVFPPKPITLTDERKAQQLQRMLDMKVNPVQGLASRWDYEKKQWKK

• Sequence length: 171

Pathways

KEGG:

Oxidative phosphorylation
Metabolic pathways
Cardiac muscle contraction
Thermogenesis
Non-alcoholic fatty liver disease
Alzheimer disease
Parkinson disease
Amyotrophic lateral sclerosis
Huntington disease
Prion disease
Pathways of neurodegeneration - multiple diseases
Chemical carcinogenesis - reactive oxygen species
Diabetic cardiomyopathy

Associated diseases

Evidence Score:

• ★☆☆☆☆  Gene-disease association found in Text Mining only
• ★★☆☆☆  Found in Text Mining and Unknown/Other Associations
• ★★★☆☆  Reported in Unknown/Other Associations across ≥2 Sources
• ★★★★☆  ClinVar: Pathogenic/Likely Pathogenic (<5 Variants)
• ★★★★★  ClinVar: Pathogenic/Likely Pathogenic (≥5 Variants)

Unknown / Other Associations
Phenotype Name	Clinical Significance	Source	Evidence Score
ALZHEIMER DISEASE	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
COX4I2-related disorder	Likely benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
MITOCHONDRIAL DISEASE	—	ClinGen, GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
MITOCHONDRIAL DISEASES	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Pancreatic insufficiency-anemia-hyperostosis syndrome	Conflicting classifications of pathogenicity; Uncertain significance; Benign; Likely benign	ClinVar ClinVar, GenCC, Orphanet ClinVar, GenCC, Orphanet	★★★☆☆ Reported in Unknown/Other Associations (≥2 sources)

Associations from Text Mining
Disease Name	Disease (Merged)	Source	PMID	Relationship Type	Evidence Score
Adrenal Gland Pheochromocytoma	Adrenal Gland Pheochromocytoma	BEFREE	31106414		★☆☆☆☆ Found in Text Mining only
Allergic rhinitis (disorder)	Allergic rhinitis	HPO_DG			★☆☆☆☆ Found in Text Mining only
Anemia	Anemia	BEFREE	19268275		★☆☆☆☆ Found in Text Mining only
Anemia	Anemia	Pubtator	19268275	Associate	★☆☆☆☆ Found in Text Mining only
Anemia	Anemia	HPO_DG			★☆☆☆☆ Found in Text Mining only
Anemia of inadequate production	Anemia	HPO_DG			★☆☆☆☆ Found in Text Mining only
Asthma	Asthma	HPO_DG			★☆☆☆☆ Found in Text Mining only
Atrial Fibrillation	Atrial fibrillation	Pubtator	38149324	Associate	★☆☆☆☆ Found in Text Mining only
Cardiomyopathy, Familial Idiopathic	Cardiomyopathy	BEFREE	30223867		★☆☆☆☆ Found in Text Mining only
Cytochrome-c Oxidase Deficiency	Cytochrome-C Oxidase Deficiency	BEFREE	20812865		★☆☆☆☆ Found in Text Mining only
Exocrine pancreatic insufficiency	Exocrine pancreatic insufficiency	BEFREE	19268275		★☆☆☆☆ Found in Text Mining only
Exocrine pancreatic insufficiency	Exocrine pancreatic insufficiency	HPO_DG			★☆☆☆☆ Found in Text Mining only
Exocrine Pancreatic Insufficiency, Dyserythropoietic Anemia, and Calvarial Hyperostosis	Exocrine Pancreatic Insufficiency, Dyserythropoietic Anemia, And Calvarial Hyperostosis	GENOMICS_ENGLAND_DG	19268275, 22592081		★☆☆☆☆ Found in Text Mining only
Exocrine Pancreatic Insufficiency, Dyserythropoietic Anemia, and Calvarial Hyperostosis	Exocrine Pancreatic Insufficiency, Dyserythropoietic Anemia, And Calvarial Hyperostosis	UNIPROT_DG	19268275		★☆☆☆☆ Found in Text Mining only
Exocrine Pancreatic Insufficiency, Dyserythropoietic Anemia, and Calvarial Hyperostosis	Exocrine Pancreatic Insufficiency, Dyserythropoietic Anemia, And Calvarial Hyperostosis	ORPHANET_DG			★☆☆☆☆ Found in Text Mining only
Exocrine Pancreatic Insufficiency, Dyserythropoietic Anemia, and Calvarial Hyperostosis	Exocrine Pancreatic Insufficiency, Dyserythropoietic Anemia, And Calvarial Hyperostosis	CTD_human_DG			★☆☆☆☆ Found in Text Mining only
Global developmental delay	Developmental Delay	HPO_DG			★☆☆☆☆ Found in Text Mining only
Hyperglycemia	Hyperglycemia	BEFREE	31184310		★☆☆☆☆ Found in Text Mining only
Hypoxia	Hypoxia	Pubtator	19268275	Associate	★☆☆☆☆ Found in Text Mining only
Hypoxia	Hypoxia	Pubtator	38149324	Stimulate	★☆☆☆☆ Found in Text Mining only
Malabsorption Syndrome	Malabsorption Syndrome	BEFREE	19268275		★☆☆☆☆ Found in Text Mining only
Malabsorption Syndromes	Malabsorption syndrome	Pubtator	19268275	Associate	★☆☆☆☆ Found in Text Mining only
Malnutrition	Malnutrition	HPO_DG			★☆☆☆☆ Found in Text Mining only
Mitochondrial Diseases	Mitochondrial Diseases	GENOMICS_ENGLAND_DG	22592081		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Mitochondrial Diseases	Mitochondrial disease	Pubtator	38149324	Associate	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Myocardial Ischemia	Myocardial Ischemia	BEFREE	30744415		★☆☆☆☆ Found in Text Mining only
Myopathy	Myopathy	BEFREE	10912924		★☆☆☆☆ Found in Text Mining only
Neoplasms	Neoplasms	BEFREE	29762853		★☆☆☆☆ Found in Text Mining only
Osteopenia	Osteopenia	HPO_DG			★☆☆☆☆ Found in Text Mining only
Pancreatic insufficiency-anemia-hyperostosis syndrome	Pancreatic insufficiency-anemia-hyperostosis syndrome	Orphanet			★★★☆☆ Reported in Unknown/Other Associations (≥2 sources)