eRAM
encyclopedia of Rare Disease Annotation for Precision Medicine
| mitochondrial complex iv deficiency | ||||
| Disease ID | 1424 |
|---|---|
| Disease | mitochondrial complex iv deficiency |
| Definition | A very rare inherited metabolic disorder characterized by deficiency of the enzyme cytochrome-C oxidase. It may be manifested as an isolated myopathy or a systemic disorder. Signs and symptoms include myotonia, dysfunction of the heart, kidney, and brain, and lactic acidosis. |
| Synonym | c cytochrome deficiency oxidase complex iv deficiencies complex iv deficiency cox - cytochrome c oxidase deficiency cox deficiencies cox deficiency cytochrome c oxidase defic cytochrome c oxidase deficiency cytochrome c oxidase deficiency (disorder) cytochrome oxidase defic cytochrome oxidase deficiencies cytochrome oxidase deficiency cytochrome-c oxidase deficiencies cytochrome-c oxidase deficiency cytochrome-c oxidase deficiency (disorder) cytochrome-c oxidase deficiency [disease/finding] defic cytochrome oxidase c deficiencies, complex iv deficiencies, cox deficiencies, cytochrome oxidase deficiencies, cytochrome-c oxidase deficiency of cytochrome a3 deficiency of cytochrome a3 deficiency of cytochrome a>3< deficiency of cytochrome aa3 deficiency of cytochrome aa3 deficiency of cytochrome aa>3< deficiency of cytochrome oxidase deficiency of cytochrome-c oxidase deficiency of cytochrome-c oxidase (disorder) deficiency, complex iv deficiency, cox deficiency, cytochrome c oxidase deficiency, cytochrome oxidase deficiency, cytochrome-c oxidase oxidase deficiencies, cytochrome oxidase deficiencies, cytochrome-c oxidase deficiency, cytochrome oxidase deficiency, cytochrome-c |
| OMIM | |
| DOID | |
| UMLS | C0268237 |
| MeSH | |
| SNOMED-CT | |
| Comorbidity | UMLS | Disease | Sentences' Count(Total Sentences:9) C0162666 | mitochondrial encephalomyopathy | 3 C0751651 | mitochondrial disease | 2 C0023264 | leigh syndrome | 2 C0442874 | neuropathy | 1 C0270612 | leukoencephalopathy | 1 C0751651 | mitochondrial diseases | 1 C0026848 | myopathy | 1 C0162670 | mitochondrial myopathy | 1 C0020255 | hydrocephalus | 1 |
| Curated Gene | Entrez_id | Symbol | Resource(Total Genes:12) 9997 | SCO2 | CTD_human 6834 | SURF1 | CLINVAR 22868 | FASTKD2 | CLINVAR;CTD_human 84987 | COX14 | CLINVAR;ORPHANET 1352 | COX10 | CLINVAR;ORPHANET;UNIPROT 6341 | SCO1 | CLINVAR;UNIPROT 84334 | APOPT1 | CLINVAR 116228 | COX20 | ORPHANET 51204 | TACO1 | CTD_human 28958 | COA3 | ORPHANET 1340 | COX6B1 | CTD_human;ORPHANET;UNIPROT 100131801 | PET100 | CLINVAR |
| Inferring Gene | (Waiting for update.) |
| Text Mined Gene | (Waiting for update.) |
| Locus | (Waiting for update.) |
| Disease ID | 1424 |
|---|---|
| Disease | mitochondrial complex iv deficiency |
| Integrated Phenotype | HPO | Name(Total Integrated Phenotypes:31) HP:0003109 | Hyperphosphaturia HP:0002240 | Enlarged liver HP:0003688 | Decreased skeletal muscle cytochrome c oxidase activity HP:0002098 | Respiratory distress HP:0000093 | Proteinuria HP:0002490 | Increased CSF lactate HP:0000648 | Optic-nerve degeneration HP:0000508 | Drooping upper eyelid HP:0001251 | Ataxia HP:0000124 | Renal tubular defect HP:0000580 | Pigmentary retinopathy HP:0001639 | Hypertrophic cardiomyopathy HP:0001270 | Motor retardation HP:0001903 | Anemia HP:0001249 | Mental retardation HP:0002747 | Respiratory distress due to muscle weakness HP:0001252 | Hypotonia HP:0001250 | Seizures HP:0006565 | Increased hepatocellular lipid droplets HP:0001263 | Developmental retardation HP:0002875 | Exertional dyspnea HP:0003128 | Lactic acidosis HP:0001410 | Decreased liver function HP:0003355 | Aminoaciduria HP:0012240 | Increased intramyocellular lipid droplets HP:0001508 | Weight faltering HP:0003546 | Exercise intolerance HP:0003076 | Glucosuria HP:0000407 | sensorineural hearing loss HP:0001994 | 'de toni-fanconi-debre' syndrome HP:0002151 | Increased serum lactate |
| Text Mined Phenotype | HPO | Name | Sentences' Count(Total Phenotypes:10) HP:0003546 | Exercise intolerance | 2 HP:0000238 | Nonsyndromal hydrocephalus | 1 HP:0003287 | Abnormality of mitochondrial metabolism | 1 HP:0001250 | Seizures | 1 HP:0001941 | acidemia | 1 HP:0003198 | Myopathic changes | 1 HP:0003715 | Myofibrillar changes | 1 HP:0002180 | Neurodegeneration | 1 HP:0002352 | Leukoencephalopathy | 1 HP:0003737 | Mitochondrial myopathy | 1 |
| Disease ID | 1424 |
|---|---|
| Disease | mitochondrial complex iv deficiency |
| Manually Symptom | (Waiting for update.) |
| Text Mined Symptom | UMLS | Name | Sentences' Count(Total Symptoms:5) |
Manually Genotype(Total Text Mining Genotypes:0) |
|---|
| (Waiting for update.) |
Text Mining Genotype(Total Genotypes:0) | |
|---|---|
| (Waiting for update.) | |
All Snps(Total Genotypes:30) | |||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| snpId | pubmedId | geneId | geneSymbol | diseaseId | sourceId | sentence | score | Year | geneSymbol_dbSNP | CHROMOSOME | POS | REF | ALT |
| rs104894555 | NA | 1352 | COX10 | umls:C0268237 | CLINVAR | NA | 0.441085767 | NA | COX10 | 17 | 14102205 | C | A |
| rs104894556 | NA | 1352 | COX10 | umls:C0268237 | CLINVAR | NA | 0.441085767 | NA | COX10 | 17 | 14159926 | C | T |
| rs104894556 | 12928484 | 1352 | COX10 | umls:C0268237 | UNIPROT | Mutations in COX10 result in a defect in mitochondrial heme A biosynthesis and account for multiple, early-onset clinical phenotypes associated with isolated COX deficiency. | 0.441085767 | 2003 | COX10 | 17 | 14159926 | C | T |
| rs104894557 | 24100867 | 1352 | COX10 | umls:C0268237 | BeFree | Whole-exome sequencing detected 1 known pathogenic and 1 novel COX10 mutation: c.1007A>T; p.Asp336Val, previously associated with fatal infantile COX deficiency, and c.1015C>T; p.Arg339Trp. | 0.441085767 | 2014 | COX10 | 17 | 14206888 | A | G,T |
| rs104894560 | NA | 1352 | COX10 | umls:C0268237 | CLINVAR | NA | 0.441085767 | NA | COX10 | 17 | 14102230 | C | A |
| rs104894630 | NA | 6341 | SCO1 | umls:C0268237 | CLINVAR | NA | 0.241085767 | NA | SCO1 | 17 | 10692805 | G | A |
| rs118203917 | NA | 22868 | FASTKD2 | umls:C0268237 | CLINVAR | NA | 0.240271442 | NA | FASTKD2 | 2 | 206774264 | C | T |
| rs121912438 | 18334481 | 9973 | CCS | umls:C0268237 | BeFree | In contrast, CCS/G93A SOD1 mouse spinal cord showed no reduction in levels of selected subunits from complexes I, II, III, or V. Heme A analyses of spinal cord further support the existence of cytochrome c oxidase deficiency in CCS/G93A SOD1 mice. | 0.000271442 | 2008 | SOD1 | 21 | 31667299 | G | C |
| rs121912438 | 18334481 | 6647 | SOD1 | umls:C0268237 | BeFree | Isolated cytochrome c oxidase deficiency in G93A SOD1 mice overexpressing CCS protein. | 0.000271442 | 2008 | SOD1 | 21 | 31667299 | G | C |
| rs199474657 | NA | 4567 | TRNL1 | umls:C0268237 | CLINVAR | NA | 0.12 | NA | NA | MT | 3243 | A | G |
| rs199474825 | NA | 4513 | COX2 | umls:C0268237 | CLINVAR | NA | 0.241085767 | NA | COX2 | MT | 7587 | T | C |
| rs199474827 | NA | 4513 | COX2 | umls:C0268237 | CLINVAR | NA | 0.241085767 | NA | COX2 | MT | 7671 | T | A |
| rs199474828 | NA | 4513 | COX2 | umls:C0268237 | CLINVAR | NA | 0.241085767 | NA | COX2 | MT | 8042 | AT | - |
| rs199474829 | NA | 4513 | COX2 | umls:C0268237 | CLINVAR | NA | 0.241085767 | NA | COX2 | MT | 7896 | G | A |
| rs199476128 | NA | 4512 | COX1 | umls:C0268237 | CLINVAR | NA | 0.241085767 | NA | COX1 | MT | 6480 | G | A |
| rs199476132 | NA | 4570 | TRNN | umls:C0268237 | CLINVAR | NA | 0.12 | NA | NA | MT | 5728 | T | C |
| rs267606612 | NA | 4514 | COX3 | umls:C0268237 | CLINVAR | NA | 0.12 | NA | COX3 | MT | 9487 | TCGCAGGATTTTTCT | - |
| rs267606613 | NA | 4514 | COX3 | umls:C0268237 | CLINVAR | NA | 0.12 | NA | COX3 | MT | 9952 | G | A |
| rs267606614 | NA | 4514 | COX3 | umls:C0268237 | CLINVAR | NA | 0.12 | NA | COX3 | MT | 9537 | - | C |
| rs267606615 | NA | 4514 | COX3 | umls:C0268237 | CLINVAR | NA | 0.12 | NA | COX3 | MT | 9379 | G | A |
| rs28679680 | NA | 4512 | COX1 | umls:C0268237 | CLINVAR | NA | 0.241085767 | NA | COX1 | MT | 6930 | G | A |
| rs587776629 | NA | 6341 | SCO1 | umls:C0268237 | CLINVAR | NA | 0.241085767 | NA | SCO1;ADPRM | 17 | 10695741 | TC | - |
| rs587776904 | NA | 84987 | COX14 | umls:C0268237 | CLINVAR | NA | 0.24 | NA | COX14 | 12 | 50120100 | G | A |
| rs587777220 | NA | 6341 | SCO1 | umls:C0268237 | CLINVAR | NA | 0.241085767 | NA | SCO1 | 17 | 10692932 | C | T |
| rs587777784 | NA | 84334 | APOPT1 | umls:C0268237 | CLINVAR | NA | 0.120271442 | NA | APOPT1 | 14 | 103571695 | C | G,T |
| rs587777785 | NA | 84334 | APOPT1 | umls:C0268237 | CLINVAR | NA | 0.120271442 | NA | APOPT1 | 14 | 103571622 | G | A |
| rs587777786 | NA | 84334 | APOPT1 | umls:C0268237 | CLINVAR | NA | 0.120271442 | NA | APOPT1 | 14 | 103571813 | T | C |
| rs587777787 | NA | 84334 | APOPT1 | umls:C0268237 | CLINVAR | NA | 0.120271442 | NA | APOPT1 | 14 | 103574116 | GAA | - |
| rs587777839 | NA | 100131801 | PET100 | umls:C0268237 | CLINVAR | NA | 0.120271442 | NA | XAB2;PET100 | 19 | 7629836 | G | C |
| rs587779779 | NA | 100131801 | PET100 | umls:C0268237 | CLINVAR | NA | 0.120271442 | NA | XAB2;PCP2;PET100 | 19 | 7631476 | C | T |
GWASdb Annotation(Total Genotypes:0) | |
|---|---|
| (Waiting for update.) | |
GWASdb Snp Trait(Total Genotypes:0) | |
|---|---|
| (Waiting for update.) | |
Mapped by lexical matching(Total Items:13) | ||||
|---|---|---|---|---|
| HP ID | HP Name | MP ID | MP Name | Annotation |
| HP:0003128 | Lactic acidosis | MP:0003031 | acidosis | a pathological state characterized by an increase in the hydrogen ion concentration in tissues and blood caused by an decrease in the concentration of alkaline compounds, or by a increase in the concentration of acidic compounds or carbon dioxide to the b |
| HP:0002151 | Increased serum lactate | MP:0013405 | increased circulating lactate level | greater amount of lactate in the blood which is produced from pyruvate by lactate dehydrogenase |
| HP:0002747 | Respiratory insufficiency due to muscle weakness | MP:0000748 | progressive muscle weakness | increasing loss of muscle strength over time |
| HP:0001639 | Hypertrophic cardiomyopathy | MP:0005330 | cardiomyopathy | diseases of the heart (myocardium); may result from many causes |
| HP:0000407 | Sensorineural hearing impairment | MP:0006330 | syndromic hearing impairment | hearing impairment that is usually associated with malformations of the external ear and other inherited signs and symptoms |
| HP:0001263 | Global developmental delay | MP:0002084 | abnormal developmental patterning | abnormal systematic arrangement of the developing body along an axis |
| HP:0000648 | Optic atrophy | MP:0012506 | brain atrophy | acquired diminution of the size of the brain associated with wasting as from death and reabsorbtion of cells, diminished cellular proliferation, decreased cellular volume, pressure, ischemia, malnutrition, reduced function or malfunction, or hormonal chan |
| HP:0001508 | Failure to thrive | MP:0013294 | prenatal lethality prior to heart atrial septation | death prior to the completion of heart atrial septation (Mus: E14.5-15.5) |
| HP:0002098 | Respiratory distress | MP:0001954 | respiratory distress | physical difficulty or inability to breathe; shortness of breath |
| HP:0001252 | Muscular hypotonia | MP:0004144 | hypotonia | decreased muscle tension resulting in limpness of the muscles in the resting state, not to be confused with weakness |
| HP:0001410 | Decreased liver function | MP:0010398 | decreased liver glycogen level | less than the normal concentration of a readily converted carbohydrate reserve in liver |
| HP:0003688 | Decreased activity of cytochrome C oxidase in muscle tissue | MP:0005584 | abnormal enzyme/coenzyme activity | altered ability of any enzyme or their cofactors, to act as catalysts to induce chemical changes in other substances |
| HP:0002490 | Increased CSF lactate | MP:0013405 | increased circulating lactate level | greater amount of lactate in the blood which is produced from pyruvate by lactate dehydrogenase |
Mapped by homologous gene(Total Items:31) | ||||
|---|---|---|---|---|
| HP ID | HP Name | MP ID | MP Name | Annotation |
| HP:0001252 | Muscular hypotonia | MP:3000003 | abnormal Ebner's gland morphology | any structural anomaly of the serous salivary glands which reside adjacent to the moats surrounding the circumvallate and foliate papillae just anterior to the posterior third of the tongue, anterior to the terminal sulcus; these exocrine glands secrete l |
| HP:0001410 | Decreased liver function | MP:0020137 | decreased bone mineralization | decrease in the rate at which minerals are deposited into bone |
| HP:0000508 | Ptosis | MP:0020321 | increased vascular endothelial cell apoptosis | increase in the timing or the number of vascular endothelial cells undergoing programmed cell death |
| HP:0002098 | Respiratory distress | MP:0014198 | absent pituitary infundibular stalk | absence of the apical portion of the tubular structure extending from the hypothalamus to the posterior lobe of the pituitary gland |
| HP:0001250 | Seizures | MP:3000003 | abnormal Ebner's gland morphology | any structural anomaly of the serous salivary glands which reside adjacent to the moats surrounding the circumvallate and foliate papillae just anterior to the posterior third of the tongue, anterior to the terminal sulcus; these exocrine glands secrete l |
| HP:0003109 | Hyperphosphaturia | MP:0013774 | decreased KLRG1-positive T-helper cell number | reduction in the number of CD4-positive alpha-beta T-helper cells expressing KLRG1, a marker associated with activation |
| HP:0003688 | Decreased activity of cytochrome C oxidase in muscle tissue | MP:0013659 | abnormal erythroid lineage cell morphology | any structural anomaly of an immature or mature cell in the lineage leading to and including erythrocytes |
| HP:0002240 | Hepatomegaly | MP:0020329 | decreased capillary density | reduction in the number of capillaries in a given cross-sectional area of a tissue |
| HP:0006565 | Increased hepatocellular lipid droplets | MP:0013405 | increased circulating lactate level | greater amount of lactate in the blood which is produced from pyruvate by lactate dehydrogenase |
| HP:0001903 | Anemia | MP:0020316 | decreased vascular endothelial cell proliferation | decrease in the expansion rate of any vascular endothelial cell population by cell division |
| HP:0000407 | Sensorineural hearing impairment | MP:3000003 | abnormal Ebner's gland morphology | any structural anomaly of the serous salivary glands which reside adjacent to the moats surrounding the circumvallate and foliate papillae just anterior to the posterior third of the tongue, anterior to the terminal sulcus; these exocrine glands secrete l |
| HP:0001508 | Failure to thrive | MP:0020234 | decreased basal metabolism | decrease in heat production of an organism at the lowest level of cell chemistry in an inactive, awake, and fasting state |
| HP:0000093 | Proteinuria | MP:0020216 | decreased circulating complement protein level | less than normal levels of the serum proteins that act sequentially to allow for the direct killing of microbes, the disposal of immune complexes, and the regulation of other immune processes |
| HP:0003355 | Aminoaciduria | MP:0020137 | decreased bone mineralization | decrease in the rate at which minerals are deposited into bone |
| HP:0012240 | Increased intramyocellular lipid droplets | MP:0013405 | increased circulating lactate level | greater amount of lactate in the blood which is produced from pyruvate by lactate dehydrogenase |
| HP:0003076 | Glycosuria | MP:0013504 | increased embryonic tissue cell apoptosis | increase in the timing or the number of cells in embryonic tissue undergoing programmed cell death |
| HP:0000124 | Renal tubular dysfunction | MP:0020137 | decreased bone mineralization | decrease in the rate at which minerals are deposited into bone |
| HP:0003128 | Lactic acidosis | MP:0020214 | susceptible to malignant hyperthermia | increased susceptibility to hyperthermia triggered by exposure to certain drugs used for general anesthesia, specifically the volatile anesthetic agents and the neuromuscular blocking agent, succinylcholine |
| HP:0001639 | Hypertrophic cardiomyopathy | MP:0020329 | decreased capillary density | reduction in the number of capillaries in a given cross-sectional area of a tissue |
| HP:0001263 | Global developmental delay | MP:3000003 | abnormal Ebner's gland morphology | any structural anomaly of the serous salivary glands which reside adjacent to the moats surrounding the circumvallate and foliate papillae just anterior to the posterior third of the tongue, anterior to the terminal sulcus; these exocrine glands secrete l |
| HP:0001249 | Intellectual disability | MP:0020316 | decreased vascular endothelial cell proliferation | decrease in the expansion rate of any vascular endothelial cell population by cell division |
| HP:0001251 | Ataxia | MP:0020301 | short tongue | decreased length of the mobile mass of muscular tissue and surrounding epithelial tissue occupying the cavity of the mouth and forming part of the floor |
| HP:0002875 | Exertional dyspnea | MP:0013405 | increased circulating lactate level | greater amount of lactate in the blood which is produced from pyruvate by lactate dehydrogenase |
| HP:0002490 | Increased CSF lactate | MP:0013504 | increased embryonic tissue cell apoptosis | increase in the timing or the number of cells in embryonic tissue undergoing programmed cell death |
| HP:0000580 | Pigmentary retinopathy | MP:0020137 | decreased bone mineralization | decrease in the rate at which minerals are deposited into bone |
| HP:0002151 | Increased serum lactate | MP:0013659 | abnormal erythroid lineage cell morphology | any structural anomaly of an immature or mature cell in the lineage leading to and including erythrocytes |
| HP:0001270 | Motor delay | MP:0020316 | decreased vascular endothelial cell proliferation | decrease in the expansion rate of any vascular endothelial cell population by cell division |
| HP:0002747 | Respiratory insufficiency due to muscle weakness | MP:0020220 | decreased tear production | decreased production of the amount of fluid produced in the eye |
| HP:0003546 | Exercise intolerance | MP:0020234 | decreased basal metabolism | decrease in heat production of an organism at the lowest level of cell chemistry in an inactive, awake, and fasting state |
| HP:0001994 | Renal Fanconi syndrome | MP:0013723 | increased circulating tyrosine level | the amount of the amino acid histidine in the blood is more than expected |
| HP:0000648 | Optic atrophy | MP:3000003 | abnormal Ebner's gland morphology | any structural anomaly of the serous salivary glands which reside adjacent to the moats surrounding the circumvallate and foliate papillae just anterior to the posterior third of the tongue, anterior to the terminal sulcus; these exocrine glands secrete l |
| Disease ID | 1424 |
|---|---|
| Disease | mitochondrial complex iv deficiency |
| Case | (Waiting for update.) |