MT-CO3

mitochondrially encoded cytochrome c oxidase III, the group of Mitochondrial complex IV: cytochrome c oxidase subunits|Mitochondrially encoded protein coding genes

Basic information

Region (hg38): M:9207-9990

Previous symbols: [ "MTCO3" ]

Links

ENSG00000198938 ∙ NCBI:4514 ∙ OMIM:516050 ∙ HGNC:7422 ∙ Uniprot:P00414 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• Leber hereditary optic neuropathy (Supportive), mode of inheritance: Mitochondrial
• hereditary recurrent myoglobinuria (Supportive), mode of inheritance: AD
• cytochrome-c oxidase deficiency disease (Supportive), mode of inheritance: AR
• Leigh syndrome (Limited), mode of inheritance: Mitochondrial
• mitochondrial disease (Definitive), mode of inheritance: Mitochondrial

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Myoglobinuria, recurrent	Maternal	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Biochemical; Musculoskeletal; Neurologic; Ophthalmologic; Renal	8240356; 8630495; 10788526; 11063732

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the MT-CO3 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the MT-CO3 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous						0
missense						0
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding						0
Total	0	0	0	0	0

Variants in MT-CO3

This is a list of pathogenic ClinVar variants found in the MT-CO3 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
M-9210-A-G		Leigh syndrome	Benign (Oct 17, 2019)
M-9211-C-T		Leigh syndrome	Benign (Oct 17, 2019)
M-9214-A-G		Leigh syndrome	Likely benign (Oct 17, 2019)
M-9217-A-G		Leigh syndrome	Uncertain significance (Oct 17, 2019)
M-9219-T-G		Leigh syndrome	Uncertain significance (Oct 17, 2019)
M-9234-A-G		Leigh syndrome	Likely benign (Oct 17, 2019)
M-9237-G-A		Epilepsy;Mitochondrial encephalopathy;Developmental delay • Leber optic atrophy	Pathogenic (May 04, 2022)
M-9247-G-A		Leigh syndrome	Uncertain significance (Oct 17, 2019)
M-9247-G-C		Juvenile myopathy, encephalopathy, lactic acidosis AND stroke	Uncertain significance (Dec 01, 2021)
M-9261-A-G		Leigh syndrome	Uncertain significance (Oct 17, 2019)
M-9265-G-A		Leigh syndrome	Uncertain significance (Oct 17, 2019)
M-9267-G-A		Leigh syndrome	Uncertain significance (Oct 17, 2019)
M-9270-C-T		Leigh syndrome	Likely benign (Oct 17, 2019)
M-9273-T-TATC		Tetralogy of Fallot	Pathogenic (-)
M-9276-G-A		Leigh syndrome	Likely benign (Oct 17, 2019)
M-9281-C-T			Uncertain significance (Oct 09, 2015)
M-9285-A-G		Leigh syndrome	Likely benign (Oct 17, 2019)
M-9286-T-C		Leigh syndrome	Likely benign (Oct 17, 2019)
M-9288-A-G		Leigh syndrome	Benign (Oct 17, 2019)
M-9294-G-A		Leigh syndrome	Uncertain significance (Oct 17, 2019)
M-9300-G-A		Leigh syndrome	Benign (Oct 17, 2019)
M-9301-C-T		Leigh syndrome	Likely benign (Oct 17, 2019)
M-9304-T-C		Leigh syndrome	Uncertain significance (Oct 17, 2019)
M-9309-T-C		Leigh syndrome	Uncertain significance (Oct 17, 2019)
M-9311-T-TGCA		Abnormal aortic valve physiology	Likely pathogenic (-)

GnomAD

Source: gnomAD

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Subunits I, II and III form the functional core of the enzyme complex.
• Disease: DISEASE: Leber hereditary optic neuropathy (LHON) [MIM:535000]: A maternally inherited disease resulting in acute or subacute loss of central vision, due to optic nerve dysfunction. Cardiac conduction defects and neurological defects have also been described in some patients. LHON results from primary mitochondrial DNA mutations affecting the respiratory chain complexes. {ECO:0000269|PubMed:8240356}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Mitochondrial complex IV deficiency (MT-C4D) [MIM:220110]: A disorder of the mitochondrial respiratory chain with heterogeneous clinical manifestations, ranging from isolated myopathy to severe multisystem disease affecting several tissues and organs. Features include hypertrophic cardiomyopathy, hepatomegaly and liver dysfunction, hypotonia, muscle weakness, exercise intolerance, developmental delay, delayed motor development and mental retardation. Some affected individuals manifest a fatal hypertrophic cardiomyopathy resulting in neonatal death. A subset of patients manifest Leigh syndrome. {ECO:0000269|PubMed:8630495}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Recurrent myoglobinuria mitochondrial (RM-MT) [MIM:550500]: Recurrent myoglobinuria is characterized by recurrent attacks of rhabdomyolysis (necrosis or disintegration of skeletal muscle) associated with muscle pain and weakness, and followed by excretion of myoglobin in the urine. {ECO:0000269|PubMed:8630495}. Note=The gene represented in this entry may be involved in disease pathogenesis.
• Pathway: Cardiac muscle contraction - Homo sapiens (human);Non-alcoholic fatty liver disease (NAFLD) - Homo sapiens (human);Alzheimer,s disease - Homo sapiens (human);Huntington,s disease - Homo sapiens (human);Thermogenesis - Homo sapiens (human);Oxidative phosphorylation - Homo sapiens (human);Parkinson,s disease - Homo sapiens (human);Electron Transport Chain;Gene expression (Transcription);mechanism of acetaminophen activity and toxicity;Generic Transcription Pathway;RNA Polymerase II Transcription;Respiratory electron transport;The citric acid (TCA) cycle and respiratory electron transport;Metabolism;TP53 Regulates Metabolic Genes;Transcriptional Regulation by TP53;Respiratory electron transport, ATP synthesis by chemiosmotic coupling, and heat production by uncoupling proteins. (Consensus)

Haploinsufficiency Scores

• pHI: 0.230
• ghis: 0.394

Essentials

• gene_indispensability_pred: N
• gene_indispensability_score: 0.114

Mouse Genome Informatics

• Gene name: mt-Co3

Gene ontology

• Biological process: mitochondrial electron transport, cytochrome c to oxygen;respiratory chain complex IV assembly;aerobic respiration;proton transmembrane transport
• Cellular component: mitochondrion;mitochondrial inner membrane;integral component of membrane;respiratory chain complex IV
• Molecular function: cytochrome-c oxidase activity;protein binding;electron transfer activity;oxidoreduction-driven active transmembrane transporter activity