MCID: CMB008
MIFTS: 34

Combined Oxidative Phosphorylation Deficiency

Categories: Cardiovascular diseases, Liver diseases, Metabolic diseases, Rare diseases

Aliases & Classifications for Combined Oxidative Phosphorylation Deficiency

MalaCards integrated aliases for Combined Oxidative Phosphorylation Deficiency:

Name: Combined Oxidative Phosphorylation Deficiency 12 20 36 29 6 15 39

Classifications:



External Ids:

Disease Ontology 12 DOID:0060286
KEGG 36 H00891

Summaries for Combined Oxidative Phosphorylation Deficiency

GARD : 20 Combined oxidative phosphorylation deficiency is a disease that affects many parts of the body. Onset occurs at or soon after birth in most cases, and features can include growth retardation, small head (microcephaly), increased muscle tone, floppiness of the trunk and head, brain disease (encephalopathy), enlarged heart muscle (cardiomyopathy), and liver dysfunction. There are many subtypes, caused by many different gene mutations. It is inherited in an autosomal recessive pattern. Treatment is supportive.

MalaCards based summary : Combined Oxidative Phosphorylation Deficiency is related to combined oxidative phosphorylation deficiency 4 and combined oxidative phosphorylation deficiency 3. An important gene associated with Combined Oxidative Phosphorylation Deficiency is GFM1 (G Elongation Factor Mitochondrial 1), and among its related pathways/superpathways are Organelle biogenesis and maintenance and Mitochondrial translation. Related phenotype is mortality/aging.

Disease Ontology : 12 A mitochondrial metabolism disease that is characterized by growth retardation, microcephaly, hypertonia, encephalopathy, cardiomyopathy and liver dysfunction.

KEGG : 36 Combined oxidative phosphorylation deficiency (COXPD) is a group of multisystem disorders with variable manifestations resulting from a defect in the mitochondrial oxidative phosphorylation system. It has been reported that the mutations in the ribosomal protein gene (MRPS) cause severe antenatal-onset infantile disease. The patients with COXPD caused by mutations in mitochondrial translation elongation factor genes (GFM1, GFM2, TUFM, TSFM and C12orf65) have also been reported.

Related Diseases for Combined Oxidative Phosphorylation Deficiency

Diseases related to Combined Oxidative Phosphorylation Deficiency via text searches within MalaCards or GeneCards Suite gene sharing:

(show top 50) (show all 82)
# Related Disease Score Top Affiliating Genes
1 combined oxidative phosphorylation deficiency 4 33.2 TUFM TSFM GFM1
2 combined oxidative phosphorylation deficiency 3 33.2 TUFM TSFM GFM1
3 combined oxidative phosphorylation deficiency 12 33.2 VARS2 FARS2 EARS2 AARS2
4 combined oxidative phosphorylation deficiency 14 33.1 LYRM4 FARS2
5 combined oxidative phosphorylation deficiency 2 32.9 VARS2 MRPS16
6 combined oxidative phosphorylation deficiency 1 32.8 VARS2 TUFM TSFM NARS2 MRPS22 GFM1
7 mitochondrial dna depletion syndrome 4a 32.1 NARS2 FARS2 EARS2
8 lactic acidosis 29.3 TUFM TSFM RMND1 MTO1 LYRM4 FARS2
9 combined oxidative phosphorylation deficiency 16 12.0
10 combined oxidative phosphorylation deficiency 6 12.0
11 combined oxidative phosphorylation deficiency 8 12.0
12 combined oxidative phosphorylation deficiency 10 12.0
13 combined oxidative phosphorylation deficiency 11 12.0
14 combined oxidative phosphorylation deficiency 17 12.0
15 combined oxidative phosphorylation deficiency 18 12.0
16 combined oxidative phosphorylation deficiency 23 12.0
17 combined oxidative phosphorylation deficiency 13 12.0
18 combined oxidative phosphorylation deficiency 15 12.0
19 combined oxidative phosphorylation deficiency 5 12.0
20 combined oxidative phosphorylation deficiency 7 12.0
21 combined oxidative phosphorylation deficiency 9 12.0
22 combined oxidative phosphorylation deficiency 33 11.9
23 combined oxidative phosphorylation deficiency 24 11.9
24 combined oxidative phosphorylation deficiency 32 11.9
25 combined oxidative phosphorylation deficiency 19 11.9
26 combined oxidative phosphorylation deficiency 21 11.9
27 combined oxidative phosphorylation deficiency 35 11.9
28 combined oxidative phosphorylation deficiency 28 11.9
29 combined oxidative phosphorylation deficiency 31 11.9
30 combined oxidative phosphorylation deficiency 37 11.9
31 combined oxidative phosphorylation deficiency 39 11.9
32 combined oxidative phosphorylation deficiency 40 11.9
33 combined oxidative phosphorylation deficiency 42 11.9
34 combined oxidative phosphorylation deficiency 34 11.9
35 combined oxidative phosphorylation deficiency 20 11.9
36 combined oxidative phosphorylation deficiency 22 11.9
37 combined oxidative phosphorylation deficiency 30 11.9
38 combined oxidative phosphorylation deficiency 44 11.9
39 combined oxidative phosphorylation deficiency 45 11.9
40 combined oxidative phosphorylation deficiency 25 11.9
41 combined oxidative phosphorylation deficiency 26 11.9
42 combined oxidative phosphorylation deficiency 27 11.9
43 combined oxidative phosphorylation deficiency 29 11.9
44 combined oxidative phosphorylation deficiency 36 11.9
45 combined oxidative phosphorylation deficiency 38 11.9
46 combined oxidative phosphorylation deficiency 41 11.9
47 combined oxidative phosphorylation deficiency 43 11.9
48 combined oxidative phosphorylation deficiency 46 11.9
49 combined oxidative phosphorylation deficiency 47 11.9
50 combined oxidative phosphorylation deficiency 48 11.7

Graphical network of the top 20 diseases related to Combined Oxidative Phosphorylation Deficiency:



Diseases related to Combined Oxidative Phosphorylation Deficiency

Symptoms & Phenotypes for Combined Oxidative Phosphorylation Deficiency

MGI Mouse Phenotypes related to Combined Oxidative Phosphorylation Deficiency:

46
# Description MGI Source Accession Score Top Affiliating Genes
1 mortality/aging MP:0010768 9.5 AARS2 AIFM1 CARS2 EARS2 ELAC2 FARS2

Drugs & Therapeutics for Combined Oxidative Phosphorylation Deficiency

Search Clinical Trials , NIH Clinical Center for Combined Oxidative Phosphorylation Deficiency

Genetic Tests for Combined Oxidative Phosphorylation Deficiency

Genetic tests related to Combined Oxidative Phosphorylation Deficiency:

# Genetic test Affiliating Genes
1 Combined Oxidative Phosphorylation Deficiency 29

Anatomical Context for Combined Oxidative Phosphorylation Deficiency

Publications for Combined Oxidative Phosphorylation Deficiency

Articles related to Combined Oxidative Phosphorylation Deficiency:

(show all 30)
# Title Authors PMID Year
1
Activation of a cryptic splice site in the mitochondrial elongation factor GFM1 causes combined OXPHOS deficiency. 6
28216230 2017
2
The first Korean cases of combined oxidative phosphorylation deficiency 35 with two novel TRIT1 mutations in two siblings confirmed by clinical and molecular investigation. 61
32948376 2021
3
Novel Biallelic NSUN3 Variants Cause Early-Onset Mitochondrial Encephalomyopathy and Seizures. 61
32488845 2020
4
Novel compound heterozygous TARS2 variants in a Chinese family with mitochondrial encephalomyopathy: a case report. 61
33153448 2020
5
[Analysis of GFM1 gene mutations in a family with combined oxidative phosphorylation deficiency 1]. 61
33210482 2020
6
Two Novel Pathogenic Variants Confirm RMND1 Causative Role in Perrault Syndrome with Renal Involvement. 61
32911714 2020
7
Generation of two induced pluripotent stem cell lines (XACHi0010-A, XACHi0011-A) from a Chinese family with combined oxidative phosphorylation deficiency carrying homozygous and heterozygous C1QBP-L275F mutation. 61
32707487 2020
8
Early Onset of Combined Oxidative Phosphorylation Deficiency in Two Chinese Brothers Caused by a Homozygous (Leu275Phe) Mutation in the C1QBP Gene. 61
33344382 2020
9
A patient with juvenile-onset refractory status epilepticus caused by two novel compound heterozygous mutations in FARS2 gene. 61
31329004 2019
10
[Clinical and genetic characteristics of 62 children with mitochondrial epilepsy]. 61
31665838 2019
11
The combination of whole-exome sequencing and clinical analysis allows better diagnosis of rare syndromic retinal dystrophies. 61
30925032 2019
12
A novel TUFM homozygous variant in a child with mitochondrial cardiomyopathy expands the phenotype of combined oxidative phosphorylation deficiency 4. 61
30903008 2019
13
Implications of the mitochondrial interactome of mammalian thioredoxin 2 for normal cellular function and disease. 61
31018154 2019
14
Is PNPT1-related hearing loss ever non-syndromic? Whole exome sequencing of adult siblings expands the natural history of PNPT1-related disorders. 61
30244537 2018
15
Expanding the Phenotype of the Founder South Asian Mutation in the Nuclear Encoding Mitochondrial RMND1 Gene. 61
29071585 2018
16
Mitochondrial Encephalopathy: First Portuguese Report of a VARS2 Causative Variant. 61
29478218 2018
17
The genotypic and phenotypic spectrum of MTO1 deficiency. 61
29331171 2018
18
Retinopathy and optic atrophy: Expanding the phenotypic spectrum of pathogenic variants in the AARS2 gene. 61
28820624 2018
19
The First Korean case of combined oxidative phosphorylation deficiency-17 diagnosed by clinical and molecular investigation. 61
29302266 2017
20
Rapid Targeted Genomics in Critically Ill Newborns. 61
28939701 2017
21
Mitochondrial iron-sulfur cluster biogenesis from molecular understanding to clinical disease. 61
28064324 2017
22
COXPD9 an Evolving Multisystem Disease; Congenital Lactic Acidosis, Sensorineural Hearing Loss, Hypertrophic Cardiomyopathy, Cirrhosis and Interstitial Nephritis. 61
27815843 2017
23
The homozygous R504C mutation in MTO1 gene is responsible for ONCE syndrome. 61
27256614 2017
24
Clinical findings in a patient with FARS2 mutations and early-infantile-encephalopathy with epilepsy. 61
27549011 2016
25
A novel AIFM1 mutation expands the phenotype to an infantile motor neuron disease. 61
26173962 2016
26
Methionyl-tRNA Formyltransferase (MTFMT) Deficiency Mimicking Acquired Demyelinating Disease. 61
26060307 2016
27
Mutations in FARS2 and non-fatal mitochondrial dysfunction in two siblings. 61
25851414 2015
28
Biochemical characterization of pathogenic mutations in human mitochondrial methionyl-tRNA formyltransferase. 61
25288793 2014
29
Optic atrophy and a Leigh-like syndrome due to mutations in the c12orf65 gene: report of a novel mutation and review of the literature. 61
24284555 2014
30
Mutant mitochondrial elongation factor G1 and combined oxidative phosphorylation deficiency. 61
15537906 2004

Variations for Combined Oxidative Phosphorylation Deficiency

ClinVar genetic disease variations for Combined Oxidative Phosphorylation Deficiency:

6 (show top 50) (show all 117)
# Gene Name Type Significance ClinVarId dbSNP ID GRCh37 Pos GRCh38 Pos
1 GFM1 NM_024996.5(GFM1):c.689+908G>A SNV Likely pathogenic 509754 rs751069628 3:158367854-158367854 3:158650065-158650065
2 GFM1 NM_024996.5(GFM1):c.748C>T (p.Arg250Trp) SNV Likely pathogenic 30598 rs139430866 3:158369943-158369943 3:158652154-158652154
3 MTRFR NM_152269.5(MTRFR):c.*14del Deletion Uncertain significance 307498 rs886049040 12:123741592-123741592 12:123257045-123257045
4 RAB33A NM_004208.4(AIFM1):c.1643C>T (p.Pro548Leu) SNV Uncertain significance 411665 rs750418813 X:129264072-129264072 X:130130097-130130097
5 RAB33A NM_004208.4(AIFM1):c.952G>A (p.Ala318Thr) SNV Uncertain significance 594797 rs773680831 X:129272583-129272583 X:130138608-130138608
6 RAB33A NM_004208.4(AIFM1):c.452G>A (p.Arg151Gln) SNV Uncertain significance 214082 rs752742151 X:129281749-129281749 X:130147774-130147774
7 AARS2 NM_020745.4(AARS2):c.1534G>C (p.Asp512His) SNV Uncertain significance 357070 rs146512155 6:44272836-44272836 6:44305099-44305099
8 TUFM NM_003321.4(TUFM):c.-81G>C SNV Uncertain significance 318761 rs573249163 16:28857671-28857671 16:28846350-28846350
9 TUFM NM_003321.4(TUFM):c.-128G>C SNV Uncertain significance 318762 rs555362028 16:28857718-28857718 16:28846397-28846397
10 COPB2 NM_020191.4(MRPS22):c.987+15del Deletion Uncertain significance 343491 rs372892045 3:139074639-139074639 3:139355797-139355797
11 RAB33A NM_004208.4(AIFM1):c.1047C>T (p.Ser349=) SNV Uncertain significance 214080 rs781350745 X:129271081-129271081 X:130137106-130137106
12 RAB33A NM_004208.4(AIFM1):c.1597G>A (p.Glu533Lys) SNV Uncertain significance 372555 rs1057517852 X:129264118-129264118 X:130130143-130130143
13 MTRFR NM_152269.5(MTRFR):c.*702_*705CAGT[1] Microsatellite Uncertain significance 307511 rs886049046 12:123742280-123742283 12:123257733-123257736
14 RAB33A NM_004208.4(AIFM1):c.1627A>G (p.Ile543Val) SNV Uncertain significance 916843 X:129264088-129264088 X:130130113-130130113
15 DNAJC9-AS1 NM_016065.4(MRPS16):c.-85_-84GT[1] Microsatellite Uncertain significance 300726 rs886047201 10:75012322-75012323 10:73252564-73252565
16 DNAJC9-AS1 NM_016065.4(MRPS16):c.-120_-118del Deletion Uncertain significance 300729 rs574159820 10:75012358-75012360 10:73252600-73252602
17 DNAJC9-AS1 NM_016065.4(MRPS16):c.*450del Deletion Uncertain significance 300712 rs886047196 10:75010160-75010160 10:73250402-73250402
18 DNAJC9-AS1 NM_016065.4(MRPS16):c.275-5T>G SNV Uncertain significance 300717 rs763591161 10:75010754-75010754 10:73250996-73250996
19 MRPS22 NM_020191.3(MRPS22):c.799T>C (p.Tyr267His) SNV Uncertain significance 343490 rs762299963 3:139071555-139071555 3:139352713-139352713
20 DNAJC9-AS1 NM_016065.4(MRPS16):c.*1503A>G SNV Uncertain significance 300690 rs2018198 10:75009107-75009107 10:73249349-73249349
21 DNAJC9-AS1 NM_016065.4(MRPS16):c.*854_*856del Deletion Uncertain significance 300699 rs886047188 10:75009754-75009756 10:73249996-73249998
22 DNAJC9-AS1 NM_016065.4(MRPS16):c.*1291_*1293del Deletion Uncertain significance 300694 rs767465725 10:75009317-75009319 10:73249559-73249561
23 AARS2 NM_020745.4(AARS2):c.*1284_*1287del Deletion Uncertain significance 357034 rs201274623 6:44266997-44267000 6:44299260-44299263
24 AARS2 NM_020745.4(AARS2):c.*1473del Deletion Uncertain significance 357031 rs766302064 6:44266811-44266811 6:44299074-44299074
25 TUFM NM_003321.5(TUFM):c.1195-3T>C SNV Uncertain significance 318743 rs376169369 16:28854472-28854472 16:28843151-28843151
26 TUFM NM_003321.5(TUFM):c.-57_-55TCT[2] Microsatellite Uncertain significance 318759 rs147419027 16:28857639-28857641 16:28846318-28846320
27 MRPS22 NM_020191.4(MRPS22):c.648+19del Deletion Uncertain significance 343487 rs773240427 3:139069180-139069180 3:139350338-139350338
28 EARS2 NM_001083614.2(EARS2):c.*1048del Deletion Uncertain significance 318526 rs750087699 16:23534644-23534644 16:23523323-23523323
29 EARS2 NM_001083614.2(EARS2):c.*1902dup Duplication Uncertain significance 318512 rs79556186 16:23533789-23533790 16:23522468-23522469
30 EARS2 NM_001083614.2(EARS2):c.558G>A (p.Ala186=) SNV Uncertain significance 318554 rs374363396 16:23546609-23546609 16:23535288-23535288
31 GFM1 NM_024996.5(GFM1):c.1384G>T (p.Asp462Tyr) SNV Uncertain significance 343933 rs200244667 3:158383129-158383129 3:158665340-158665340
32 AARS2 NM_020745.4(AARS2):c.*1112dup Duplication Uncertain significance 357037 rs112521684 6:44267171-44267172 6:44299434-44299435
33 DNAJC9-AS1 NM_016065.4(MRPS16):c.*633dup Duplication Uncertain significance 300704 rs555061429 10:75009976-75009977 10:73250218-73250219
34 EARS2 NM_001083614.2(EARS2):c.*535dup Duplication Uncertain significance 318531 rs11300207 16:23535156-23535157 16:23523835-23523836
35 TSFM NM_005726.6(TSFM):c.233C>T (p.Ala78Val) SNV Uncertain significance 310009 rs886049729 12:58179947-58179947 12:57786164-57786164
36 RAB33A NM_004208.4(AIFM1):c.1501A>T (p.Ser501Cys) SNV Uncertain significance 411664 rs769816388 X:129265722-129265722 X:130131747-130131747
37 RAB33A NM_004208.4(AIFM1):c.1481C>T (p.Ala494Val) SNV Uncertain significance 477606 rs1556254400 X:129265742-129265742 X:130131767-130131767
38 RAB33A NM_004208.4(AIFM1):c.1388G>T (p.Arg463Ile) SNV Uncertain significance 243069 rs202219398 X:129267348-129267348 X:130133373-130133373
39 RAB33A NM_004208.4(AIFM1):c.597A>C (p.Lys199Asn) SNV Uncertain significance 477607 rs143670174 X:129281476-129281476 X:130147501-130147501
40 RAB33A NM_004208.4(AIFM1):c.134C>G (p.Pro45Arg) SNV Uncertain significance 214085 rs756361109 X:129290550-129290550 X:130156576-130156576
41 RAB33A NM_004208.4(AIFM1):c.1114G>A (p.Val372Ile) SNV Uncertain significance 543931 rs1056740593 X:129270668-129270668 X:130136693-130136693
42 RAB33A NM_004208.4(AIFM1):c.1081G>A (p.Val361Ile) SNV Uncertain significance 576371 rs1569417347 X:129270701-129270701 X:130136726-130136726
43 RAB33A NM_004208.4(AIFM1):c.170C>G (p.Ser57Cys) SNV Uncertain significance 445310 rs201711375 X:129290514-129290514 X:130156540-130156540
44 RAB33A NM_004208.4(AIFM1):c.341C>T (p.Ala114Val) SNV Uncertain significance 639720 rs138662844 X:129283452-129283452 X:130149477-130149477
45 RAB33A NM_004208.4(AIFM1):c.1075+4G>C SNV Uncertain significance 640384 rs374943447 X:129271049-129271049 X:130137074-130137074
46 RAB33A NM_004208.4(AIFM1):c.1006G>A (p.Glu336Lys) SNV Uncertain significance 641733 rs1603223158 X:129271122-129271122 X:130137147-130137147
47 RAB33A NM_004208.4(AIFM1):c.1693A>G (p.Ile565Val) SNV Uncertain significance 642792 rs1375125488 X:129264022-129264022 X:130130047-130130047
48 RAB33A NM_004208.4(AIFM1):c.238G>A (p.Ala80Thr) SNV Uncertain significance 643584 rs1603230120 X:129290446-129290446 X:130156472-130156472
49 RAB33A NM_004208.4(AIFM1):c.1710C>A (p.Asp570Glu) SNV Uncertain significance 643666 rs1603218828 X:129264005-129264005 X:130130030-130130030
50 RAB33A NM_004208.4(AIFM1):c.1594A>G (p.Ser532Gly) SNV Uncertain significance 646433 rs1603218953 X:129264121-129264121 X:130130146-130130146

Expression for Combined Oxidative Phosphorylation Deficiency

Search GEO for disease gene expression data for Combined Oxidative Phosphorylation Deficiency.

Pathways for Combined Oxidative Phosphorylation Deficiency

Pathways related to Combined Oxidative Phosphorylation Deficiency according to GeneCards Suite gene sharing:

# Super pathways Score Top Affiliating Genes
1
Show member pathways
12.36 TUFM TSFM MTFMT MRPS22 MRPS16 GFM1
2
Show member pathways
11.99 TUFM TSFM MTFMT MRPS22 MRPS16 GFM1
3
Show member pathways
11.41 VARS2 NARS2 MTFMT FARS2 EARS2 CARS2

GO Terms for Combined Oxidative Phosphorylation Deficiency

Cellular components related to Combined Oxidative Phosphorylation Deficiency according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 mitochondrion GO:0005739 9.62 VARS2 TUFM TSFM SLC25A26 RMND1 PNPT1
2 mitochondrial matrix GO:0005759 9.61 TSFM PNPT1 NARS2 LYRM4 GFM1 FARS2
3 mitochondrial inner membrane GO:0005743 9.56 SLC25A26 MRPS22 MRPS16 AIFM1
4 mitochondrial small ribosomal subunit GO:0005763 9.16 MRPS22 MRPS16

Biological processes related to Combined Oxidative Phosphorylation Deficiency according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 mitochondrial translational elongation GO:0070125 9.55 TUFM TSFM MRPS22 MRPS16 GFM1
2 tRNA processing GO:0008033 9.54 MTO1 FARS2 ELAC2
3 translational elongation GO:0006414 9.5 TUFM TSFM GFM1
4 translation GO:0006412 9.44 VARS2 TUFM TSFM RMND1 NARS2 MTRFR
5 tRNA aminoacylation GO:0043039 9.43 FARS2 EARS2 AARS2
6 aminoacyl-tRNA metabolism involved in translational fidelity GO:0106074 9.4 VARS2 AARS2
7 tRNA aminoacylation for protein translation GO:0006418 9.35 VARS2 NARS2 FARS2 EARS2 CARS2

Molecular functions related to Combined Oxidative Phosphorylation Deficiency according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 nucleotide binding GO:0000166 9.97 VARS2 TUFM NARS2 GFM1 FARS2 EARS2
2 RNA binding GO:0003723 9.86 TUFM TSFM PNPT1 MTO1 GFM1 ELAC2
3 tRNA binding GO:0000049 9.5 FARS2 EARS2 AARS2
4 ligase activity GO:0016874 9.43 VARS2 NARS2 FARS2 EARS2 CARS2 AARS2
5 aminoacyl-tRNA editing activity GO:0002161 9.4 VARS2 AARS2
6 translation elongation factor activity GO:0003746 9.33 TUFM TSFM GFM1
7 aminoacyl-tRNA ligase activity GO:0004812 9.1 VARS2 NARS2 FARS2 EARS2 CARS2 AARS2

Sources for Combined Oxidative Phosphorylation Deficiency

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
19 FMA
20 GARD
28 GO
29 GTR
30 HMDB
31 HPO
32 ICD10
33 ICD10 via Orphanet
34 ICD9CM
35 IUPHAR
36 KEGG
37 LifeMap
39 LOVD
41 MedGen
44 MeSH
45 MESH via Orphanet
46 MGI
49 NCI
50 NCIt
51 NDF-RT
53 NINDS
54 Novoseek
56 OMIM via Orphanet
57 OMIM® (Updated 05-Mar-2021)
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 TGDB
70 Tocris
71 UMLS
72 UMLS via Orphanet
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