MCID: MTC097
MIFTS: 51

Mitochondrial Complex Iv Deficiency

Categories: Genetic diseases, Rare diseases, Metabolic diseases, Cardiovascular diseases

Aliases & Classifications for Mitochondrial Complex Iv Deficiency

MalaCards integrated aliases for Mitochondrial Complex Iv Deficiency:

Name: Mitochondrial Complex Iv Deficiency 54 12 50 24 24 25 71
Cytochrome C Oxidase Deficiency 50 24 25 71 13 52
Cytochrome-C Oxidase Deficiency 25 29 42 69
Cox Deficiency 50 24 25 71
Complex 4 Mitochondrial Respiratory Chain Deficiency 50 71
Cytochrome-C Oxidase Deficiency Disease 12 14
Complex Iv Deficiency 50 25
Lethal Neonatal Cardiomyopathy Hypertrophic Due to Cytochrome C Oxidase Deficiency 71
Isolated Mitochondrial Respiratory Chain Complex Iv Deficiency 56
Deficiency of Mitochondrial Respiratory Chain Complex4 50
Mitochondrial Respiratory Chain Complex Iv Deficiency 24
Complex Iv Mitochondrial Respiratory Chain Deficiency 71
Isolated Cytochrome C Oxidase Deficiency 56
Isolated Cox Deficiency 56
Mt-C4d 71

Characteristics:

Orphanet epidemiological data:

56
isolated cytochrome c oxidase deficiency
Inheritance: Autosomal recessive,Mitochondrial inheritance;

OMIM:

54
Inheritance:
autosomal recessive
mitochondrial

Miscellaneous:
marked clinical heterogeneity
symptom onset ranges from infancy to adulthood
death may occur in infancy
genetic heterogeneity (may be caused by mutation in nuclear-encoded or mitochondrial-encoded genes)
subset of patients have leigh syndrome
subset of patients have french-canadian leigh syndrome


HPO:

32
mitochondrial complex iv deficiency:
Inheritance heterogeneous autosomal recessive inheritance mitochondrial inheritance


Classifications:

Orphanet: 56  
Inborn errors of metabolism


Summaries for Mitochondrial Complex Iv Deficiency

NIH Rare Diseases : 50 cytochrome c oxidase deficiency (cox deficiency) is a condition that can affect several parts of the body including the skeletal muscles, heart, brain and liver. there are four types of cox deficiency differentiated by symptoms and age of onset: benign infantile mitochondrial type, french-canadian type, infantile mitochondrial myopathy type, and leigh syndrome. the range and severity of signs and symptoms can vary widely among affected individuals (even within the same subtype and same family) and depend on the form of the condition present. features in mildly affected individuals may include muscle weakness and hypotonia; in more severely affected individuals, brain dysfunction; heart problems; an enlarged liver; lactic acidosis; and/or a specific group of features known as leigh syndrome may also be present. cox deficiency is caused by mutations in any of at least 14 genes; the inheritance pattern depends on the gene involved. the condition is frequently fatal in childhood, but mildly affected individuals may survive into adolescence or adulthood. last updated: 5/19/2016

MalaCards based summary : Mitochondrial Complex Iv Deficiency, also known as cytochrome c oxidase deficiency, is related to cardioencephalomyopathy, fatal infantile, due to cytochrome c oxidase deficiency 1 and cardioencephalomyopathy, fatal infantile, due to cytochrome c oxidase deficiency 2, and has symptoms including failure to thrive, optic atrophy and ataxia. An important gene associated with Mitochondrial Complex Iv Deficiency is COX6B1 (Cytochrome C Oxidase Subunit 6B1), and among its related pathways/superpathways are Metabolism and Gene Expression. The drugs Micronutrients and Trace Elements have been mentioned in the context of this disorder. Affiliated tissues include liver, heart and brain.

UniProtKB/Swiss-Prot : 71 Mitochondrial complex IV deficiency: 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.

Genetics Home Reference : 25 Cytochrome c oxidase deficiency is a genetic condition that can affect several parts of the body, including the muscles used for movement (skeletal muscles), the heart, the brain, or the liver. Signs and symptoms of cytochrome c oxidase deficiency usually begin before age 2 but can appear later in mildly affected individuals.

OMIM : 54
Complex IV (cytochrome c oxidase; EC 1.9.3.1) is the terminal enzyme of the respiratory chain and consists of 13 polypeptide subunits, 3 of which are encoded by mitochondrial DNA. The 3 mitochondrially encoded proteins in the cytochrome oxidase complex are the actual catalytic subunits that carry out the electron transport function (Saraste, 1983). See 123995 for discussion of some of the nuclear-encoded subunits. Shoubridge (2001) provided a comprehensive review of cytochrome c oxidase deficiency and noted that most isolated COX deficiencies are inherited as autosomal recessive disorders caused by mutations in nuclear-encoded genes; mutations in the mtDNA-encoded COX subunit genes are relatively rare. (220110)

Related Diseases for Mitochondrial Complex Iv Deficiency

Diseases related to Mitochondrial Complex Iv Deficiency via text searches within MalaCards or GeneCards Suite gene sharing:

(show all 34)
id Related Disease Score Top Affiliating Genes
1 cardioencephalomyopathy, fatal infantile, due to cytochrome c oxidase deficiency 1 12.6
2 cardioencephalomyopathy, fatal infantile, due to cytochrome c oxidase deficiency 2 12.5
3 leigh syndrome, french-canadian type 11.7
4 mitochondrial myopathy, infantile, transient 11.5
5 leigh syndrome 11.1
6 cardioencephalomyopathy, fatal infantile, due to cytochrome c oxidase deficiency 4 11.0
7 cardioencephalomyopathy, fatal infantile, due to cytochrome c oxidase deficiency 3 11.0
8 charcot-marie-tooth disease, type 4k 11.0
9 nipah virus disease 10.8 MT-CO1 MT-CO3
10 cerebral folate receptor alpha deficiency 10.8 COX10 MT-CO1
11 familial isolated restrictive cardiomyopathy 10.8 COX5A MT-CO1
12 myosin storage myopathy 10.7 COX5A MT-CO1
13 androgen insensitivity 10.5 COX10 MT-CO1 MT-CO3
14 cardiomyopathy and deafness due to trna lysine gene mutation 10.5 COX5A SCO1 SURF1
15 enchondromatosis dwarfism deafness 10.4 COX6B1 MT-CO3
16 mitochondrial neurogastrointestinal encephalopathy disease 10.4 MT-CO3 MT-TL1
17 lmna-related emery-dreifuss muscular dystrophy, autosomal 10.4 COX8A MT-CO3 SURF1
18 hypokalemic periodic paralysis, type 2 10.4 COX10 SURF1 TACO1
19 congenital pulmonary veins atresia or stenosis 10.4 MT-TL1 MT-TN
20 sparganosis 10.4 MT-CO1 MT-TL1
21 mental retardation with spastic paraplegia 10.3 COX5A MT-CO2 MT-TL1
22 mixed germ cell tumor of central nervous system 10.3 PET100 SURF1 TACO1
23 familial episodic pain syndrome 10.2 MT-CO1 MT-CO2
24 myoclonic epilepsy associated with ragged-red fibers 10.1 FASTKD2 MT-CO1 MT-CO2 MT-CO3 MT-TL1
25 dermatophytosis 10.1 FASTKD2 MT-CO1 MT-CO2 MT-CO3 MT-TL1
26 intestinal pseudo-obstruction 9.9
27 lactic acidosis 9.8
28 fatal infantile lactic acidosis 9.8
29 multiminicore disease 9.8 COX10 COX5A MT-CO2 MT-TL1 SCO1 SURF1
30 hydrocephalus 9.7
31 encephalomyopathy 9.7
32 cardiomyopathy 9.7
33 protoplasmic astrocytoma 9.5 COX10 MT-CO2 MT-TL1 PET100 SCO1 SURF1
34 bjornstad syndrome 8.8 COX10 COX5A COX6B1 MT-CO1 MT-CO2 MT-CO3

Graphical network of the top 20 diseases related to Mitochondrial Complex Iv Deficiency:



Diseases related to Mitochondrial Complex Iv Deficiency

Symptoms & Phenotypes for Mitochondrial Complex Iv Deficiency

Symptoms via clinical synopsis from OMIM:

54

Growth- Other:
failure to thrive

Muscle Soft Tissue:
hypotonia
muscle weakness
exercise intolerance
muscle biopsy shows decrease or absence of cytochrome c oxidase
increased lipid droplets and abnormal mitochondria

Abdomen- Liver:
hepatomegaly
liver dysfunction
liver biopsy shows increased lipid droplets and abnormal mitochondria

Head And Neck- Ears:
hearing loss, sensorineural

Respiratory:
respiratory difficulties
respiratory failure due to muscle weakness
exertional dyspnea

Metabolic Features:
lactic acidosis

Neurologic- Central Nervous System:
hypotonia
delayed motor development
mental retardation
ataxia
developmental delay
more
Head And Neck- Eyes:
optic atrophy
ptosis
pigmentary retinopathy

Laboratory- Abnormalities:
proteinuria
increased csf lactate
increased serum lactate
glucosuria
aminoaciduria
more
Cardiovascular- Heart:
hypertrophic cardiomyopathy

Genitourinary- Kidneys:
'de toni-fanconi-debre' syndrome
renal tubular dysfunction
biopsy shows decreased cytochrome c oxidase

Hematology:
anemia (associated with mutation in the cox10 gene)


Clinical features from OMIM:

220110

Human phenotypes related to Mitochondrial Complex Iv Deficiency:

32 (show all 31)
id Description HPO Frequency HPO Source Accession
1 failure to thrive 32 HP:0001508
2 optic atrophy 32 HP:0000648
3 ataxia 32 HP:0001251
4 hepatomegaly 32 HP:0002240
5 seizures 32 HP:0001250
6 ptosis 32 HP:0000508
7 pigmentary retinopathy 32 HP:0000580
8 anemia 32 HP:0001903
9 proteinuria 32 HP:0000093
10 global developmental delay 32 HP:0001263
11 hypertrophic cardiomyopathy 32 HP:0001639
12 exertional dyspnea 32 HP:0002875
13 renal tubular dysfunction 32 HP:0000124
14 exercise intolerance 32 HP:0003546
15 increased csf lactate 32 HP:0002490
16 lactic acidosis 32 HP:0003128
17 increased serum lactate 32 HP:0002151
18 aminoaciduria 32 HP:0003355
19 hyperphosphaturia 32 HP:0003109
20 respiratory distress 32 HP:0002098
21 intellectual disability 32 HP:0001249
22 motor delay 32 HP:0001270
23 respiratory insufficiency due to muscle weakness 32 HP:0002747
24 muscular hypotonia 32 HP:0001252
25 sensorineural hearing impairment 32 HP:0000407
26 decreased liver function 32 HP:0001410
27 glycosuria 32 HP:0003076
28 renal fanconi syndrome 32 HP:0001994
29 increased intramyocellular lipid droplets 32 HP:0012240
30 increased hepatocellular lipid droplets 32 HP:0006565
31 cytochrome c oxidase-negative muscle fibers 32 HP:0003688

UMLS symptoms related to Mitochondrial Complex Iv Deficiency:


ataxia, dyspnea, seizures, muscle weakness, dyspnea on exertion

Drugs & Therapeutics for Mitochondrial Complex Iv Deficiency

Drugs for Mitochondrial Complex Iv Deficiency (from DrugBank, HMDB, Dgidb, PharmGKB, IUPHAR, NovoSeek, BitterDB):


id Name Status Phase Clinical Trials Cas Number PubChem Id
1 Micronutrients Phase 3
2 Trace Elements Phase 3
3 Ubiquinone Phase 3
4 Vitamins Phase 3
5
Coenzyme Q10 Experimental, Nutraceutical Phase 3 303-98-0 5281915

Interventional clinical trials:


id Name Status NCT ID Phase Drugs
1 Phase III Trial of Coenzyme Q10 in Mitochondrial Disease Completed NCT00432744 Phase 3 CoenzymeQ10;Placebo
2 North American Mitochondrial Disease Consortium Patient Registry and Biorepository (NAMDC) Recruiting NCT01694940
3 DNA QUANTIFICATION TECHNIQUE AS A INTERPRETATION TOOL IN MITOCHONDRIAL DISEASES Not yet recruiting NCT03216252

Search NIH Clinical Center for Mitochondrial Complex Iv Deficiency

Cochrane evidence based reviews: cytochrome-c oxidase deficiency

Genetic Tests for Mitochondrial Complex Iv Deficiency

Genetic tests related to Mitochondrial Complex Iv Deficiency:

id Genetic test Affiliating Genes
1 Cytochrome-C Oxidase Deficiency 29
2 Mitochondrial Respiratory Chain Complex Iv Deficiency (nuclear Genes) 24 COX10 COX15 COX6B1 FASTKD2 SCO1 SCO2 SURF1 TACO1 COX20 PET100 COA5 COA6 APOPT1 COX14 COA3
3 Mitochondrial Respiratory Chain Complex Iv Deficiency 24
4 Mitochondrial Respiratory Chain Complex Iv Deficiency (mitochondrial Genes) 24 MT-TS1

Anatomical Context for Mitochondrial Complex Iv Deficiency

MalaCards organs/tissues related to Mitochondrial Complex Iv Deficiency:

39
Liver, Heart, Brain, Skeletal Muscle

Publications for Mitochondrial Complex Iv Deficiency

Articles related to Mitochondrial Complex Iv Deficiency:

id Title Authors Year
1
Mitochondrial complex IV deficiency, caused by mutated COX6B1, is associated with encephalomyopathy, hydrocephalus and cardiomyopathy. ( 24781756 )
2014

Variations for Mitochondrial Complex Iv Deficiency

UniProtKB/Swiss-Prot genetic disease variations for Mitochondrial Complex Iv Deficiency:

71 (show all 12)
id Symbol AA change Variation ID SNP ID
1 COX10 p.Thr196Lys VAR_026562 rs104894555
2 COX10 p.Asn204Lys VAR_026563 rs104894560
3 COX10 p.Pro225Leu VAR_026564 rs104894556
4 COX10 p.Asp336Gly VAR_026565 rs104894557
5 COX10 p.Asp336Val VAR_026566 rs104894557
6 COX10 p.Gly288Arg VAR_076181 rs753048807
7 COX10 p.Pro420Leu VAR_076182 rs773079584
8 COX6B1 p.Arg20His VAR_046775 rs121909602
9 MT-CO1 p.Ser142Phe VAR_033055 rs267606883
10 MT-CO1 p.Leu196Ile VAR_033056 rs28461189
11 MT-CO2 p.Met29Lys VAR_035085 rs199474827
12 SCO1 p.Pro174Leu VAR_012109 rs104894630

ClinVar genetic disease variations for Mitochondrial Complex Iv Deficiency:

6 (show all 35)
id Gene Variation Type Significance SNP ID Assembly Location
1 FASTKD2 NM_001136194.1(FASTKD2): c.1294C> T (p.Arg432Ter) single nucleotide variant Pathogenic rs118203917 GRCh37 Chromosome 2, 207638988: 207638988
2 SCO1 NM_004589.3(SCO1): c.363_364delGA (p.Lys122Valfs) deletion Pathogenic rs587776629 GRCh37 Chromosome 17, 10599058: 10599059
3 SCO1 NM_004589.3(SCO1): c.521C> T (p.Pro174Leu) single nucleotide variant Pathogenic rs104894630 GRCh37 Chromosome 17, 10596122: 10596122
4 COX10 NM_001303.3(COX10): c.612C> A (p.Asn204Lys) single nucleotide variant Pathogenic rs104894560 GRCh37 Chromosome 17, 14005547: 14005547
5 COX10 NM_001303.3(COX10): c.587C> A (p.Thr196Lys) single nucleotide variant Pathogenic rs104894555 GRCh37 Chromosome 17, 14005522: 14005522
6 COX10 NM_001303.3(COX10): c.674C> T (p.Pro225Leu) single nucleotide variant Pathogenic rs104894556 GRCh37 Chromosome 17, 14063243: 14063243
7 MT-TL1 m.3243A> G single nucleotide variant Pathogenic rs199474657 GRCh37 Chromosome MT, 3243: 3243
8 MT-TN m.5728T> C single nucleotide variant Pathogenic rs199476132 GRCh37 Chromosome MT, 5728: 5728
9 MT-CO3 m.9487_9501delTCGCAGGATTTTTCT deletion Pathogenic rs267606612 GRCh37 Chromosome MT, 9487: 9501
10 MT-CO3 m.9952G> A single nucleotide variant Pathogenic rs267606613 GRCh37 Chromosome MT, 9952: 9952
11 MT-CO3 m.9537dupC duplication Pathogenic rs267606614 GRCh37 Chromosome MT, 9537: 9537
12 MT-CO3 m.9379G> A single nucleotide variant Pathogenic rs267606615 GRCh37 Chromosome MT, 9379: 9379
13 MT-CO2 m.7587T> C single nucleotide variant Pathogenic rs199474825 GRCh37 Chromosome MT, 7587: 7587
14 MT-CO2 m.7671T> A single nucleotide variant Pathogenic rs199474827 GRCh37 Chromosome MT, 7671: 7671
15 MT-CO2 m.8042_8043delAT deletion Pathogenic rs199474828 GRCh37 Chromosome MT, 8042: 8043
16 MT-CO2 m.7896G> A single nucleotide variant Pathogenic rs199474829 GRCh37 Chromosome MT, 7896: 7896
17 MT-CO1 m.6480G> A single nucleotide variant Pathogenic rs199476128 GRCh37 Chromosome MT, 6480: 6480
18 MT-CO1 m.6930G> A single nucleotide variant Pathogenic rs28679680 GRCh37 Chromosome MT, 6930: 6930
19 SURF1 SURF1, 2-BP DEL, 790AG deletion Pathogenic
20 COX6B1 NM_001863.4(COX6B1): c.59G> A (p.Arg20His) single nucleotide variant Pathogenic rs121909602 GRCh37 Chromosome 19, 36142204: 36142204
21 COX14 NM_001257133.1(COX14): c.57G> A (p.Met19Ile) single nucleotide variant Pathogenic rs587776904 GRCh37 Chromosome 12, 50513883: 50513883
22 COX20 NM_001312871.1(COX20): c.154A> C (p.Thr52Pro) single nucleotide variant Pathogenic rs587777004 GRCh37 Chromosome 1, 245005357: 245005357
23 SCO1 NM_004589.3(SCO1): c.394G> A (p.Gly132Ser) single nucleotide variant Pathogenic rs587777220 GRCh37 Chromosome 17, 10596249: 10596249
24 PET100 NM_001171155.1(PET100): c.3G> C (p.Met1Ile) single nucleotide variant Pathogenic rs587777839 GRCh38 Chromosome 19, 7629836: 7629836
25 PET100 NM_001171155.1(PET100): c.142C> T (p.Gln48Ter) single nucleotide variant Pathogenic rs587779779 GRCh38 Chromosome 19, 7631476: 7631476
26 APOPT1 NM_032374.4(APOPT1): c.235C> T (p.Arg79Ter) single nucleotide variant Pathogenic rs587777784 GRCh38 Chromosome 14, 103571695: 103571695
27 APOPT1 NM_032374.4(APOPT1): c.163-1G> A single nucleotide variant Pathogenic rs587777785 GRCh37 Chromosome 14, 104037959: 104037959
28 APOPT1 NM_032374.4(APOPT1): c.353T> C (p.Phe118Ser) single nucleotide variant Pathogenic rs587777786 GRCh38 Chromosome 14, 103571813: 103571813
29 APOPT1 NM_032374.4(APOPT1): c.370_372delGAA (p.Glu124del) deletion Pathogenic rs587777787 GRCh38 Chromosome 14, 103574116: 103574118
30 COA3 NM_001040431.2(COA3): c.199dupC (p.Leu67Profs) duplication Pathogenic rs757472611 GRCh37 Chromosome 17, 40950501: 40950501
31 COA3 NM_001040431.2(COA3): c.215A> G (p.Tyr72Cys) single nucleotide variant Pathogenic rs139877390 GRCh37 Chromosome 17, 40950185: 40950185
32 COX6B1 NM_001863.4(COX6B1): c.58C> T (p.Arg20Cys) single nucleotide variant Pathogenic rs778740017 GRCh38 Chromosome 19, 35651301: 35651301
33 COX8A NM_004074.2(COX8A): c.115-1G> C single nucleotide variant Pathogenic rs869025575 GRCh38 Chromosome 11, 63976224: 63976224
34 COA7 COA7, TYR137CYS undetermined variant Pathogenic
35 COA7 COA7, IVS2DS, G-T, +1 single nucleotide variant Pathogenic

Expression for Mitochondrial Complex Iv Deficiency

Search GEO for disease gene expression data for Mitochondrial Complex Iv Deficiency.

Pathways for Mitochondrial Complex Iv Deficiency

Pathways related to Mitochondrial Complex Iv Deficiency according to GeneCards Suite gene sharing:

id Super pathways Score Top Affiliating Genes
1
Show member pathways
13.84 COX10 COX14 COX20 COX5A COX6B1 COX8A
2
Show member pathways
13.5 COX14 COX20 COX5A COX6B1 COX8A MT-CO1
3
Show member pathways
13.23 COX10 COX14 COX20 COX5A COX6B1 COX8A
4
Show member pathways
12.52 COX14 COX20 COX5A COX6B1 COX8A MT-CO1
5
Show member pathways
11.9 COX10 COX5A COX6B1 COX8A
6 11.52 COX5A COX6B1 COX8A MT-CO1 MT-CO2 MT-CO3
7 11.29 COX14 COX20 COX5A COX6B1 COX8A MT-CO1
8 10.25 COX5A COX8A

GO Terms for Mitochondrial Complex Iv Deficiency

Cellular components related to Mitochondrial Complex Iv Deficiency according to GeneCards Suite gene sharing:

id Name GO ID Score Top Affiliating Genes
1 mitochondrial inner membrane GO:0005743 9.65 COA3 COX10 COX5A COX6B1 COX8A MT-CO1
2 mitochondrion GO:0005739 9.55 APOPT1 COA3 COA7 COX10 COX14 COX20
3 mitochondrial membrane GO:0031966 9.54 COX10 COX14 COX20
4 mitochondrial respiratory chain complex IV GO:0005751 9.46 COX5A COX8A MT-CO1 MT-CO2
5 respiratory chain complex IV GO:0045277 9.43 MT-CO1 MT-CO2 MT-CO3
6 integral component of mitochondrial inner membrane GO:0031305 9.32 COA3 PET100

Biological processes related to Mitochondrial Complex Iv Deficiency according to GeneCards Suite gene sharing:

id Name GO ID Score Top Affiliating Genes
1 hydrogen ion transmembrane transport GO:1902600 9.76 COX10 COX5A COX6B1 COX8A MT-CO1 MT-CO2
2 aerobic respiration GO:0009060 9.62 COX10 COX20 MT-CO1 SURF1
3 respiratory chain complex IV assembly GO:0008535 9.56 COX10 MT-CO3 SCO1 SURF1
4 mitochondrial electron transport, cytochrome c to oxygen GO:0006123 9.5 COX10 COX5A COX6B1 COX8A MT-CO1 MT-CO2
5 cellular respiration GO:0045333 9.4 COX10 FASTKD2
6 oxidative phosphorylation GO:0006119 9.37 MT-CO1 SURF1
7 mitochondrial respiratory chain complex IV assembly GO:0033617 9.17 COA3 COX14 COX20 PET100 PET117 SCO1

Molecular functions related to Mitochondrial Complex Iv Deficiency according to GeneCards Suite gene sharing:

id Name GO ID Score Top Affiliating Genes
1 cytochrome-c oxidase activity GO:0004129 9.02 COX10 COX5A COX6B1 COX8A SURF1

Sources for Mitochondrial Complex Iv Deficiency

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
16 ExPASy
18 FMA
28 GO
29 GTR
30 HGMD
31 HMDB
32 HPO
33 ICD10
34 ICD10 via Orphanet
35 ICD9CM
36 IUPHAR
37 KEGG
38 LifeMap
40 MedGen
42 MeSH
43 MESH via Orphanet
44 MGI
46 NCI
47 NCIt
48 NDF-RT
51 NINDS
52 Novoseek
54 OMIM
55 OMIM via Orphanet
59 PubMed
60 QIAGEN
65 SNOMED-CT via HPO
66 SNOMED-CT via Orphanet
67 TGDB
68 Tocris
69 UMLS
70 UMLS via Orphanet
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