| H01368 | |
| H number | H01368 |
| Name | Cytochrome c oxidase (COX) deficiency; Mitochondrial complex IV deficiency (MT-C4D) |
| Description | Cytochrome c oxidase (COX) deficiency is a mitochondrial disease that is caused by the lack of the COX. Cytochrome c oxidase (COX) is the terminal enzyme of the mitochondrial respiratory chain (complex IV). Since COX is encoded by nuclear and mitochondrial genes, COX deficiency can be inherited in either an autosomal recessive or a maternal pattern. Patients can present with a number of different clinical phenotypes, including Leigh syndrome, Fatal infantile cardioencephalomyopathy, and Leber hereditary optic neuropathy. |
| Category | Inherited metabolic disorder, Mitochondrial disease |
| Network | nt06529(H01368) Thermogenesis |
| Gene | (MC4DN1) SURF1 [HSA:6834] [KO:K14998] (MC4DN2) SCO2 [HSA:9997] [KO:K23755] (MC4DN3) COX10 [HSA:1352] [KO:K02257] (MC4DN4) SCO1 [HSA:6341] [KO:K07152] (MC4DN5) LRPPRC [HSA:10128] [KO:K17964] (MC4DN6) COX15 [HSA:1355] [KO:K02259] (MC4DN7) COX6B1 [HSA:1340] [KO:K02267] (MC4DN8) TACO1 [HSA:51204] [KO:K18189] (MC4DN9) COA5 [HSA:493753] [KO:K18178] (MC4DN10) COX14 [HSA:84987] [KO:K18181] (MC4DN11) COX20 [HSA:116228] [KO:K18184] (MC4DN12) PET100 [HSA:100131801] [KO:K18186] (MC4DN13) COA6 [HSA:388753] [KO:K18179] (MC4DN14) COA3 [HSA:28958] [KO:K18175] (MC4DN15) COX8A [HSA:1351] [KO:K02273] (MC4DN16) COX4I1 [HSA:1327] [KO:K02263] (MC4DN17) COA8 [HSA:84334] [KO:K23506] (MC4DN18) COX6A2 [HSA:1339] [KO:K02266] (MC4DN19) PET117 [HSA:100303755] [KO:K18188] (MC4DN20) COX5A [HSA:9377] [KO:K02264] (MC4DN21) NDUFA4 [HSA:4697] [KO:K03948] (MC4DN22) COX16 [HSA:51241] [KO:K18182] (MC4DN23) COX11 [HSA:1353] [KO:K02258] (COXPD44) FASTKD2 [HSA:22868] [KO:K18190] (MT-C4D) COX1 [HSA:4512] [KO:K02256] (MT-C4D) COX2 [HSA:4513] [KO:K02261] (MT-C4D) COX3 [HSA:4514] [KO:K02262] |
| Pathogen | - |
| Env factor | - |
| Carcinogen | - |
| Drug | - |
| Comment | - |
| Other DBs | ICD-11: 5C53.2Y ICD-10: G71.3 MeSH: D030401 OMIM: 604377 619046 619048 220110 220111 615119 619051 619052 616500 619053 619054 619055 616501 619058 619059 619060 619061 619062 619063 619064 619065 618855 619355 620275 |
| Reference | PMID:11579424 AUTHORS Shoubridge EA TITLE Cytochrome c oxidase deficiency. JOURNAL Am J Med Genet 106:46-52 (2001) DOI:10.1002/ajmg.1378 PMID:9843204 (SURF1) AUTHORS Zhu Z, Yao J, Johns T, Fu K, De Bie I, Macmillan C, Cuthbert AP, Newbold RF, Wang J, Chevrette M, Brown GK, Brown RM, Shoubridge EA TITLE SURF1, encoding a factor involved in the biogenesis of cytochrome c oxidase, is mutated in Leigh syndrome. JOURNAL Nat Genet 20:337-43 (1998) DOI:10.1038/3804 PMID:10545952 (SCO2) AUTHORS Papadopoulou LC, Sue CM, Davidson MM, Tanji K, Nishino I, Sadlock JE, Krishna S, Walker W, Selby J, Glerum DM, Coster RV, Lyon G, Scalais E, Lebel R, Kaplan P, Shanske S, De Vivo DC, Bonilla E, Hirano M, DiMauro S, Schon EA TITLE Fatal infantile cardioencephalomyopathy with COX deficiency and mutations in SCO2, a COX assembly gene. JOURNAL Nat Genet 23:333-7 (1999) DOI:10.1038/15513 PMID:10767350 (COX10) AUTHORS Valnot I, von Kleist-Retzow JC, Barrientos A, Gorbatyuk M, Taanman JW, Mehaye B, Rustin P, Tzagoloff A, Munnich A, Rotig A TITLE A mutation in the human heme A:farnesyltransferase gene (COX10 ) causes cytochrome c oxidase deficiency. JOURNAL Hum Mol Genet 9:1245-9 (2000) DOI:10.1093/hmg/9.8.1245 PMID:11013136 (SCO1) AUTHORS Valnot I, Osmond S, Gigarel N, Mehaye B, Amiel J, Cormier-Daire V, Munnich A, Bonnefont JP, Rustin P, Rotig A TITLE Mutations of the SCO1 gene in mitochondrial cytochrome c oxidase deficiency with neonatal-onset hepatic failure and encephalopathy. JOURNAL Am J Hum Genet 67:1104-9 (2000) DOI:10.1016/S0002-9297(07)62940-1 PMID:12529507 (LRPPRC) AUTHORS Mootha VK, Lepage P, Miller K, Bunkenborg J, Reich M, Hjerrild M, Delmonte T, Villeneuve A, Sladek R, Xu F, Mitchell GA, Morin C, Mann M, Hudson TJ, Robinson B, Rioux JD, Lander ES TITLE Identification of a gene causing human cytochrome c oxidase deficiency by integrative genomics. JOURNAL Proc Natl Acad Sci U S A 100:605-10 (2003) DOI:10.1073/pnas.242716699 PMID:21412973 (COX15) AUTHORS Alfadhel M, Lillquist YP, Waters PJ, Sinclair G, Struys E, McFadden D, Hendson G, Hyams L, Shoffner J, Vallance HD TITLE Infantile cardioencephalopathy due to a COX15 gene defect: report and review. JOURNAL Am J Med Genet A 155A:840-4 (2011) DOI:10.1002/ajmg.a.33881 PMID:18499082 (COX6B1) AUTHORS Massa V, Fernandez-Vizarra E, Alshahwan S, Bakhsh E, Goffrini P, Ferrero I, Mereghetti P, D'Adamo P, Gasparini P, Zeviani M TITLE Severe infantile encephalomyopathy caused by a mutation in COX6B1, a nucleus-encoded subunit of cytochrome c oxidase. JOURNAL Am J Hum Genet 82:1281-9 (2008) DOI:10.1016/j.ajhg.2008.05.002 PMID:19503089 (TACO1) AUTHORS Weraarpachai W, Antonicka H, Sasarman F, Seeger J, Schrank B, Kolesar JE, Lochmuller H, Chevrette M, Kaufman BA, Horvath R, Shoubridge EA TITLE Mutation in TACO1, encoding a translational activator of COX I, results in cytochrome c oxidase deficiency and late-onset Leigh syndrome. JOURNAL Nat Genet 41:833-7 (2009) DOI:10.1038/ng.390 PMID:21457908 (COA5) AUTHORS Huigsloot M, Nijtmans LG, Szklarczyk R, Baars MJ, van den Brand MA, Hendriksfranssen MG, van den Heuvel LP, Smeitink JA, Huynen MA, Rodenburg RJ TITLE A mutation in C2orf64 causes impaired cytochrome c oxidase assembly and mitochondrial cardiomyopathy. JOURNAL Am J Hum Genet 88:488-93 (2011) DOI:10.1016/j.ajhg.2011.03.002 PMID:22243966 (COX14) AUTHORS Weraarpachai W, Sasarman F, Nishimura T, Antonicka H, Aure K, Rotig A, Lombes A, Shoubridge EA TITLE Mutations in C12orf62, a factor that couples COX I synthesis with cytochrome c oxidase assembly, cause fatal neonatal lactic acidosis. JOURNAL Am J Hum Genet 90:142-51 (2012) DOI:10.1016/j.ajhg.2011.11.027 PMID:23125284 (COX20) AUTHORS Szklarczyk R, Wanschers BF, Nijtmans LG, Rodenburg RJ, Zschocke J, Dikow N, van den Brand MA, Hendriks-Franssen MG, Gilissen C, Veltman JA, Nooteboom M, Koopman WJ, Willems PH, Smeitink JA, Huynen MA, van den Heuvel LP TITLE A mutation in the FAM36A gene, the human ortholog of COX20, impairs cytochrome c oxidase assembly and is associated with ataxia and muscle hypotonia. JOURNAL Hum Mol Genet 22:656-67 (2013) DOI:10.1093/hmg/dds473 PMID:24462369 (PET100) AUTHORS Lim SC, Smith KR, Stroud DA, Compton AG, Tucker EJ, Dasvarma A, Gandolfo LC, Marum JE, McKenzie M, Peters HL, Mowat D, Procopis PG, Wilcken B, Christodoulou J, Brown GK, Ryan MT, Bahlo M, Thorburn DR TITLE A founder mutation in PET100 causes isolated complex IV deficiency in Lebanese individuals with Leigh syndrome. JOURNAL Am J Hum Genet 94:209-22 (2014) DOI:10.1016/j.ajhg.2013.12.015 PMID:25339201 (COA6) AUTHORS Baertling F, A M van den Brand M, Hertecant JL, Al-Shamsi A, P van den Heuvel L, Distelmaier F, Mayatepek E, Smeitink JA, Nijtmans LG, Rodenburg RJ TITLE Mutations in COA6 cause cytochrome c oxidase deficiency and neonatal hypertrophic cardiomyopathy. JOURNAL Hum Mutat 36:34-8 (2015) DOI:10.1002/humu.22715 PMID:25604084 (COA3) AUTHORS Ostergaard E, Weraarpachai W, Ravn K, Born AP, Jonson L, Duno M, Wibrand F, Shoubridge EA, Vissing J TITLE Mutations in COA3 cause isolated complex IV deficiency associated with neuropathy, exercise intolerance, obesity, and short stature. JOURNAL J Med Genet 52:203-7 (2015) DOI:10.1136/jmedgenet-2014-102914 PMID:26685157 (COX8A) AUTHORS Hallmann K, Kudin AP, Zsurka G, Kornblum C, Reimann J, Stuve B, Waltz S, Hattingen E, Thiele H, Nurnberg P, Rub C, Voos W, Kopatz J, Neumann H, Kunz WS TITLE Loss of the smallest subunit of cytochrome c oxidase, COX8A, causes Leigh-like syndrome and epilepsy. JOURNAL Brain 139:338-45 (2016) DOI:10.1093/brain/awv357 PMID:28766551 (COX4I1) AUTHORS Abu-Libdeh B, Douiev L, Amro S, Shahrour M, Ta-Shma A, Miller C, Elpeleg O, Saada A TITLE Mutation in the COX4I1 gene is associated with short stature, poor weight gain and increased chromosomal breaks, simulating Fanconi anemia. JOURNAL Eur J Hum Genet 25:1142-1146 (2017) DOI:10.1038/ejhg.2017.112 PMID:25175347 (COA8) AUTHORS Melchionda L, Haack TB, Hardy S, Abbink TE, Fernandez-Vizarra E, Lamantea E, Marchet S, Morandi L, Moggio M, Carrozzo R, Torraco A, Diodato D, Strom TM, Meitinger T, Tekturk P, Yapici Z, Al-Murshedi F, Stevens R, Rodenburg RJ, Lamperti C, Ardissone A, Moroni I, Uziel G, Prokisch H, Taylor RW, Bertini E, van der Knaap MS, Ghezzi D, Zeviani M TITLE Mutations in APOPT1, encoding a mitochondrial protein, cause cavitating leukoencephalopathy with cytochrome c oxidase deficiency. JOURNAL Am J Hum Genet 95:315-25 (2014) DOI:10.1016/j.ajhg.2014.08.003 PMID:31155743 (COX6A2) AUTHORS Inoue M, Uchino S, Iida A, Noguchi S, Hayashi S, Takahashi T, Fujii K, Komaki H, Takeshita E, Nonaka I, Okada Y, Yoshizawa T, Van Lommel L, Schuit F, Goto YI, Mimaki M, Nishino I TITLE COX6A2 variants cause a muscle-specific cytochrome c oxidase deficiency. JOURNAL Ann Neurol 86:193-202 (2019) DOI:10.1002/ana.25517 PMID:28386624 (PET117) AUTHORS Renkema GH, Visser G, Baertling F, Wintjes LT, Wolters VM, van Montfrans J, de Kort GAP, Nikkels PGJ, van Hasselt PM, van der Crabben SN, Rodenburg RJT TITLE Mutated PET117 causes complex IV deficiency and is associated with neurodevelopmental regression and medulla oblongata lesions. JOURNAL Hum Genet 136:759-769 (2017) DOI:10.1007/s00439-017-1794-7 PMID:28247525 (COX5A) AUTHORS Baertling F, Al-Murshedi F, Sanchez-Caballero L, Al-Senaidi K, Joshi NP, Venselaar H, van den Brand MA, Nijtmans LG, Rodenburg RJ TITLE Mutation in mitochondrial complex IV subunit COX5A causes pulmonary arterial hypertension, lactic acidemia, and failure to thrive. JOURNAL Hum Mutat 38:692-703 (2017) DOI:10.1002/humu.23210 PMID:23746447 (NDUFA4) AUTHORS Pitceathly RD, Rahman S, Wedatilake Y, Polke JM, Cirak S, Foley AR, Sailer A, Hurles ME, Stalker J, Hargreaves I, Woodward CE, Sweeney MG, Muntoni F, Houlden H, Taanman JW, Hanna MG TITLE NDUFA4 mutations underlie dysfunction of a cytochrome c oxidase subunit linked to human neurological disease. JOURNAL Cell Rep 3:1795-805 (2013) DOI:10.1016/j.celrep.2013.05.005 PMID:33169484 (COX16) AUTHORS Wintjes LTM, Kava M, van den Brandt FA, van den Brand MAM, Lapina O, Bliksrud YT, Kulseth MA, Amundsen SS, Selberg TR, Ybema-Antoine M, Tutakhel OAZ, Greed L, Thorburn DR, Tangeraas T, Balasubramaniam S, Rodenburg RJT TITLE A novel variant in COX16 causes cytochrome c oxidase deficiency, severe fatal neonatal lactic acidosis, encephalopathy, cardiomyopathy, and liver dysfunction. JOURNAL Hum Mutat 42:135-141 (2021) DOI:10.1002/humu.24137 PMID:36030551 (COX11) AUTHORS Rius R, Bennett NK, Bhattacharya K, Riley LG, Yuksel Z, Formosa LE, Compton AG, Dale RC, Cowley MJ, Gayevskiy V, Al Tala SM, Almehery AA, Ryan MT, Thorburn DR, Nakamura K, Christodoulou J TITLE Biallelic pathogenic variants in COX11 are associated with an infantile-onset mitochondrial encephalopathy. JOURNAL Hum Mutat 43:1970-1978 (2022) DOI:10.1002/humu.24453 PMID:18771761 (FASTKD2) AUTHORS Ghezzi D, Saada A, D'Adamo P, Fernandez-Vizarra E, Gasparini P, Tiranti V, Elpeleg O, Zeviani M TITLE FASTKD2 nonsense mutation in an infantile mitochondrial encephalomyopathy associated with cytochrome c oxidase deficiency. JOURNAL Am J Hum Genet 83:415-23 (2008) DOI:10.1016/j.ajhg.2008.08.009 PMID:10441567 (COX1) AUTHORS Bruno C, Martinuzzi A, Tang Y, Andreu AL, Pallotti F, Bonilla E, Shanske S, Fu J, Sue CM, Angelini C, DiMauro S, Manfredi G TITLE A stop-codon mutation in the human mtDNA cytochrome c oxidase I gene disrupts the functional structure of complex IV. JOURNAL Am J Hum Genet 65:611-20 (1999) DOI:10.1086/302546 PMID:10205264 (COX2) AUTHORS Clark KM, Taylor RW, Johnson MA, Chinnery PF, Chrzanowska-Lightowlers ZM, Andrews RM, Nelson IP, Wood NW, Lamont PJ, Hanna MG, Lightowlers RN, Turnbull DM TITLE An mtDNA mutation in the initiation codon of the cytochrome C oxidase subunit II gene results in lower levels of the protein and a mitochondrial encephalomyopathy. JOURNAL Am J Hum Genet 64:1330-9 (1999) DOI:10.1086/302361 PMID:8630495 (COX3) AUTHORS Keightley JA, Hoffbuhr KC, Burton MD, Salas VM, Johnston WS, Penn AM, Buist NR, Kennaway NG TITLE A microdeletion in cytochrome c oxidase (COX) subunit III associated with COX deficiency and recurrent myoglobinuria. JOURNAL Nat Genet 12:410-6 (1996) DOI:10.1038/ng0496-410 |