COX4I1 (cytochrome c oxidase subunit 4I1)

Gene

• Entrez ID: 1327
• Gene name: Cytochrome c oxidase subunit 4I1
• Gene symbol: COX4I1
• Synonyms (NCBI Gene): COX IV-1, COX4, COX4-1, COXIV, COXIV-1, MC4DN16
• Chromosome: 16
• Chromosome location: 16q24.1
• Summary: Cytochrome c oxidase (COX) is the terminal enzyme of the mitochondrial respiratory chain. It is a multi-subunit enzyme complex that couples the transfer of electrons from cytochrome c to molecular oxygen and contributes to a proton electrochemical gradien

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT049222	hsa-miR-92a-3p	CLASH	23622248
MIRT905277	hsa-miR-1271	CLIP-seq
MIRT905278	hsa-miR-145	CLIP-seq
MIRT905279	hsa-miR-182	CLIP-seq
MIRT905280	hsa-miR-1972	CLIP-seq
MIRT905281	hsa-miR-3121-3p	CLIP-seq
MIRT905282	hsa-miR-3180-5p	CLIP-seq
MIRT905283	hsa-miR-338-3p	CLIP-seq
MIRT905284	hsa-miR-3622b-5p	CLIP-seq
MIRT905285	hsa-miR-3665	CLIP-seq
MIRT905286	hsa-miR-4274	CLIP-seq
MIRT905287	hsa-miR-4519	CLIP-seq
MIRT905288	hsa-miR-452	CLIP-seq
MIRT905289	hsa-miR-4524	CLIP-seq
MIRT905290	hsa-miR-4642	CLIP-seq
MIRT905291	hsa-miR-4653-3p	CLIP-seq
MIRT905292	hsa-miR-4676-3p	CLIP-seq
MIRT905293	hsa-miR-4712-5p	CLIP-seq
MIRT905294	hsa-miR-4729	CLIP-seq
MIRT905295	hsa-miR-4755-3p	CLIP-seq
MIRT905296	hsa-miR-542-3p	CLIP-seq
MIRT905297	hsa-miR-548g	CLIP-seq
MIRT905298	hsa-miR-582-3p	CLIP-seq
MIRT905299	hsa-miR-764	CLIP-seq
MIRT905300	hsa-miR-770-5p	CLIP-seq
MIRT905301	hsa-miR-96	CLIP-seq
MIRT905277	hsa-miR-1271	CLIP-seq
MIRT905278	hsa-miR-145	CLIP-seq
MIRT905279	hsa-miR-182	CLIP-seq
MIRT905281	hsa-miR-3121-3p	CLIP-seq
MIRT905282	hsa-miR-3180-5p	CLIP-seq
MIRT905284	hsa-miR-3622b-5p	CLIP-seq
MIRT905285	hsa-miR-3665	CLIP-seq
MIRT905286	hsa-miR-4274	CLIP-seq
MIRT905287	hsa-miR-4519	CLIP-seq
MIRT905288	hsa-miR-452	CLIP-seq
MIRT905289	hsa-miR-4524	CLIP-seq
MIRT905290	hsa-miR-4642	CLIP-seq
MIRT905291	hsa-miR-4653-3p	CLIP-seq
MIRT905292	hsa-miR-4676-3p	CLIP-seq
MIRT905293	hsa-miR-4712-5p	CLIP-seq
MIRT905294	hsa-miR-4729	CLIP-seq
MIRT905295	hsa-miR-4755-3p	CLIP-seq
MIRT905296	hsa-miR-542-3p	CLIP-seq
MIRT905297	hsa-miR-548g	CLIP-seq
MIRT905298	hsa-miR-582-3p	CLIP-seq
MIRT905299	hsa-miR-764	CLIP-seq
MIRT905300	hsa-miR-770-5p	CLIP-seq
MIRT905301	hsa-miR-96	CLIP-seq
MIRT905277	hsa-miR-1271	CLIP-seq
MIRT905278	hsa-miR-145	CLIP-seq
MIRT905279	hsa-miR-182	CLIP-seq
MIRT905281	hsa-miR-3121-3p	CLIP-seq
MIRT905282	hsa-miR-3180-5p	CLIP-seq
MIRT905284	hsa-miR-3622b-5p	CLIP-seq
MIRT905286	hsa-miR-4274	CLIP-seq
MIRT905287	hsa-miR-4519	CLIP-seq
MIRT905288	hsa-miR-452	CLIP-seq
MIRT905289	hsa-miR-4524	CLIP-seq
MIRT905290	hsa-miR-4642	CLIP-seq
MIRT905291	hsa-miR-4653-3p	CLIP-seq
MIRT905292	hsa-miR-4676-3p	CLIP-seq
MIRT905293	hsa-miR-4712-5p	CLIP-seq
MIRT905294	hsa-miR-4729	CLIP-seq
MIRT905296	hsa-miR-542-3p	CLIP-seq
MIRT905297	hsa-miR-548g	CLIP-seq
MIRT905298	hsa-miR-582-3p	CLIP-seq
MIRT905300	hsa-miR-770-5p	CLIP-seq
MIRT905301	hsa-miR-96	CLIP-seq
MIRT905286	hsa-miR-4274	CLIP-seq
MIRT905287	hsa-miR-4519	CLIP-seq
MIRT905289	hsa-miR-4524	CLIP-seq
MIRT905294	hsa-miR-4729	CLIP-seq

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0004129	Function	Cytochrome-c oxidase activity	TAS	2157630
GO:0005515	Function	Protein binding	IPI	23260140, 25416956, 26321642, 26759378, 28514442, 31515488, 32814053, 33961781
GO:0005654	Component	Nucleoplasm	IDA
GO:0005739	Component	Mitochondrion	HDA	20833797
GO:0005739	Component	Mitochondrion	HTP	34800366
GO:0005739	Component	Mitochondrion	IDA	15565177, 26746385
GO:0005739	Component	Mitochondrion	IEA
GO:0005743	Component	Mitochondrial inner membrane	IEA
GO:0005743	Component	Mitochondrial inner membrane	ISS
GO:0005743	Component	Mitochondrial inner membrane	TAS
GO:0005758	Component	Mitochondrial intermembrane space	IEA
GO:0005758	Component	Mitochondrial intermembrane space	TAS
GO:0005829	Component	Cytosol	IEA
GO:0006091	Process	Generation of precursor metabolites and energy	TAS	2157630
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	IEA
GO:0006123	Process	Mitochondrial electron transport, cytochrome c to oxygen	NAS	30030519
GO:0007584	Process	Response to nutrient	IEA
GO:0016020	Component	Membrane	HDA	19946888
GO:0016020	Component	Membrane	IEA
GO:0031966	Component	Mitochondrial membrane	IDA	30030519
GO:0031966	Component	Mitochondrial membrane	IEA
GO:0045277	Component	Respiratory chain complex IV	IBA
GO:0045277	Component	Respiratory chain complex IV	IEA
GO:0045277	Component	Respiratory chain complex IV	IMP	19393246
GO:0045333	Process	Cellular respiration	NAS	30030519
GO:1902600	Process	Proton transmembrane transport	IEA

Other IDs

• MIM: 123864
• HGNC: 2265
• e!Ensembl: ENSG00000131143

Protein

• UniProt ID: P13073
• Protein name: Cytochrome c oxidase subunit 4 isoform 1, mitochondrial (Cytochrome c oxidase polypeptide IV) (Cytochrome c oxidase subunit IV isoform 1) (COX IV-1)
• 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
• PDB: 5Z62
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF02936	COX4	30 → 168	Cytochrome c oxidase subunit IV	Family

• Tissue specificity: TISSUE SPECIFICITY: Ubiquitous.
• Sequence:

  MLATRVFSLVGKRAISTSVCVRAHESVVKSEDFSLPAYMDRRDHPLPEVAHVKHLSASQK
  ALKEKEKASWSSLSMDEKVELYRIKFKESFAEMNRGSNEWKTVVGGAMFFIGFTALVIMW
  QKHYVYGPLPQSFDKEWVAKQTKRMLDMKVNPIQGLASKWDYEKNEWKK

• Sequence length: 169

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

Reactome:

TP53 Regulates Metabolic Genes
Respiratory electron transport

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)

Causal
Phenotype Name	Clinical Significance	dbSNP ID	RCV Accession	Evidence Score
Mitochondrial complex IV deficiency, nuclear type 1	Pathogenic	rs1906146144	RCV001034697	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Mitochondrial complex IV deficiency, nuclear type 16	Pathogenic	rs1906247824	RCV001034698	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)

Unknown / Other Associations
Phenotype Name	Clinical Significance	Source	Evidence Score
COX4I1-related disorder	Likely benign; Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
CYTOCHROME-C OXIDASE DEFICIENCY DISEASE	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
LEIGH SYNDROME	—	ClinGen, GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
LEPROSY	—	GWAS catalog	★★☆☆☆ 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

Associations from Text Mining
Disease Name	Disease (Merged)	Source	PMID	Relationship Type	Evidence Score
Adrenocortical Carcinoma	Adrenocortical carcinoma	Pubtator	33776902	Associate	★☆☆☆☆ Found in Text Mining only
Anemia	Anemia	Pubtator	29886046	Associate	★☆☆☆☆ Found in Text Mining only
Asthenozoospermia	Asthenozoospermia	Pubtator	31268247	Associate	★☆☆☆☆ Found in Text Mining only
Atrial Fibrillation	Atrial fibrillation	Pubtator	38149324	Associate	★☆☆☆☆ Found in Text Mining only
Atrophy	Atrophy	Pubtator	40095452	Associate	★☆☆☆☆ Found in Text Mining only
Bone Marrow Failure Disorders	Bone marrow failure syndromes	Pubtator	35456968	Associate	★☆☆☆☆ Found in Text Mining only
Brain Diseases	Brain disease	Pubtator	31290619	Associate	★☆☆☆☆ Found in Text Mining only
Breast Carcinoma	Breast Carcinoma	BEFREE	25270118		★☆☆☆☆ Found in Text Mining only
Cardiomyopathy, Familial Idiopathic	Cardiomyopathy	BEFREE	30223867		★☆☆☆☆ Found in Text Mining only
Congenital Abnormalities	Congenital abnormalities	Pubtator	28766551, 31290619	Associate	★☆☆☆☆ Found in Text Mining only
Coronary Artery Disease	Coronary artery disease	Pubtator	31979197	Inhibit	★☆☆☆☆ Found in Text Mining only
Cytochrome c Oxidase Deficiency	Cytochrome c oxidase deficiency	Pubtator	29396562, 35456968	Associate	★☆☆☆☆ Found in Text Mining only
Cytochrome-c Oxidase Deficiency	Cytochrome-C Oxidase Deficiency	BEFREE	20812865		★☆☆☆☆ Found in Text Mining only
Depressive disorder	Mental Depression	BEFREE	25869607		★☆☆☆☆ Found in Text Mining only
Developmental regression	Developmental regression	BEFREE	31290619		★☆☆☆☆ Found in Text Mining only
Diabetes Mellitus, Non-Insulin-Dependent	Diabetes Mellitus	BEFREE	25869607, 28730835		★☆☆☆☆ Found in Text Mining only
Dwarfism	Dwarfism	BEFREE	28766551, 31290619		★☆☆☆☆ Found in Text Mining only
Dysmorphic features	Dysmorphic Features	BEFREE	28766551		★☆☆☆☆ Found in Text Mining only
Epilepsy	Epilepsy	Pubtator	40095452	Associate	★☆☆☆☆ Found in Text Mining only
Fanconi Anemia	Fanconi Anemia	BEFREE	28766551, 29886046, 31290619		★☆☆☆☆ Found in Text Mining only
Fanconi Anemia	Fanconi anemia	Pubtator	28766551, 29396562, 29886046, 31290619, 35456968, 40095452	Associate	★☆☆☆☆ Found in Text Mining only
FANCONI ANEMIA, COMPLEMENTATION GROUP A (disorder)	Anemia	BEFREE	28766551, 29886046, 31290619		★☆☆☆☆ Found in Text Mining only
Glioma	Glioma	BEFREE	28455961		★☆☆☆☆ Found in Text Mining only
Growth Disorders	Growth disorder	Pubtator	28766551, 31290619, 35456968, 40095452	Associate	★☆☆☆☆ Found in Text Mining only
Hyperglycemia	Hyperglycemia	BEFREE	31184310		★☆☆☆☆ Found in Text Mining only
Hypertensive disease	Hypertension	BEFREE	31679456		★☆☆☆☆ Found in Text Mining only
Hypoxia	Hypoxia	Pubtator	37927240	Stimulate	★☆☆☆☆ Found in Text Mining only
Intellectual Disability	Intellectual developmental disorder	Pubtator	31290619, 40095452	Associate	★☆☆☆☆ Found in Text Mining only
Isolated cytochrome C oxidase deficiency	Isolated Cytochrome C Oxidase Deficiency	Orphanet			★☆☆☆☆ Found in Text Mining only
Leigh Disease	Leigh Syndrome	BEFREE	31290619		★☆☆☆☆ Found in Text Mining only
Leigh Disease	Leigh syndrome	Pubtator	31290619	Associate	★☆☆☆☆ Found in Text Mining only
Leprosy	Leprosy	GWASCAT_DG	25642632		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Lung Diseases Interstitial	Lung disease	Pubtator	30940853	Associate	★☆☆☆☆ Found in Text Mining only
Malignant neoplasm of breast	Breast Cancer	BEFREE	25270118		★☆☆☆☆ Found in Text Mining only
Mental Depression	Mental Depression	BEFREE	25869607		★☆☆☆☆ Found in Text Mining only
Metabolic Syndrome X	Metabolic Syndrome	BEFREE	25869607		★☆☆☆☆ Found in Text Mining only
Microcephaly	Microcephaly	Pubtator	40095452	Associate	★☆☆☆☆ Found in Text Mining only
Mitochondrial Diseases	Mitochondrial disease	Pubtator	18332166, 25844556, 28766551, 29396562, 33578848	Associate	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Mitochondrial Diseases	Mitochondrial Diseases	GENOMICS_ENGLAND_DG			★★☆☆☆ 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
Nervous System Diseases	Nervous system disease	Pubtator	40095452	Associate	★☆☆☆☆ Found in Text Mining only
Obesity	Obesity	BEFREE	20200320, 25869607		★☆☆☆☆ Found in Text Mining only
Obesity	Obesity	Pubtator	28730835	Associate	★☆☆☆☆ Found in Text Mining only
Ovarian Neoplasms	Ovarian neoplasm	Pubtator	36012230	Associate	★☆☆☆☆ Found in Text Mining only
Seizures	Seizures	Pubtator	31290619, 40095452	Associate	★☆☆☆☆ Found in Text Mining only