MCID: CMB008
MIFTS: 35

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 52 36 29 6 15 39

Classifications:



External Ids:

Disease Ontology 12 DOID:0060286
KEGG 36 H00891

Summaries for Combined Oxidative Phosphorylation Deficiency

NIH Rare Diseases : 52 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. Affiliated tissues include liver, brain and heart, and 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 (MRPS16 and MRPS22) cause severe antenatal-onset infantile disease. The patients with COXPD caused by mutations in mitochondrial translation elongation factor genes (GFM1, 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 64)
# Related Disease Score Top Affiliating Genes
1 combined oxidative phosphorylation deficiency 4 34.9 TUFM TSFM GFM1
2 combined oxidative phosphorylation deficiency 3 34.8 TUFM TSFM
3 combined oxidative phosphorylation deficiency 2 34.7 VARS2 MRPS16
4 combined oxidative phosphorylation deficiency 12 34.3 VARS2 NARS2 FARS2 EARS2 AARS2
5 combined oxidative phosphorylation deficiency 1 34.0 VARS2 TUFM TSFM NARS2 MRPS22 GFM1
6 lactic acidosis 29.0 TUFM RMND1 MTO1 LYRM4
7 combined oxidative phosphorylation deficiency 8 13.0
8 combined oxidative phosphorylation deficiency 10 13.0
9 combined oxidative phosphorylation deficiency 11 13.0
10 combined oxidative phosphorylation deficiency 16 13.0
11 combined oxidative phosphorylation deficiency 6 12.9
12 combined oxidative phosphorylation deficiency 14 12.9
13 combined oxidative phosphorylation deficiency 15 12.9
14 combined oxidative phosphorylation deficiency 5 12.9
15 combined oxidative phosphorylation deficiency 7 12.9
16 combined oxidative phosphorylation deficiency 9 12.9
17 combined oxidative phosphorylation deficiency 18 12.9
18 combined oxidative phosphorylation deficiency 23 12.9
19 combined oxidative phosphorylation deficiency 13 12.9
20 combined oxidative phosphorylation deficiency 17 12.9
21 combined oxidative phosphorylation deficiency 19 12.9
22 combined oxidative phosphorylation deficiency 24 12.9
23 combined oxidative phosphorylation deficiency 32 12.9
24 combined oxidative phosphorylation deficiency 33 12.9
25 combined oxidative phosphorylation deficiency 34 12.9
26 combined oxidative phosphorylation deficiency 20 12.9
27 combined oxidative phosphorylation deficiency 21 12.9
28 combined oxidative phosphorylation deficiency 22 12.9
29 combined oxidative phosphorylation deficiency 30 12.9
30 combined oxidative phosphorylation deficiency 28 12.9
31 combined oxidative phosphorylation deficiency 31 12.9
32 combined oxidative phosphorylation deficiency 35 12.9
33 combined oxidative phosphorylation deficiency 37 12.9
34 combined oxidative phosphorylation deficiency 39 12.9
35 combined oxidative phosphorylation deficiency 25 12.9
36 combined oxidative phosphorylation deficiency 26 12.9
37 combined oxidative phosphorylation deficiency 27 12.9
38 combined oxidative phosphorylation deficiency 29 12.9
39 combined oxidative phosphorylation deficiency 36 12.9
40 combined oxidative phosphorylation deficiency 38 12.9
41 combined oxidative phosphorylation deficiency 40 12.8
42 combined oxidative phosphorylation deficiency 42 12.8
43 combined oxidative phosphorylation deficiency 44 12.8
44 combined oxidative phosphorylation deficiency 41 12.6
45 combined oxidative phosphorylation deficiency 43 12.6
46 fars2 deficiency 11.4
47 deafness, autosomal recessive 94 10.2 NARS2 FARS2 EARS2
48 2-aminoadipic 2-oxoadipic aciduria 10.2 TSFM PNPT1
49 neuropathy, hereditary motor and sensory, type via, with optic atrophy 10.2 MRPS16 C12orf65
50 cardiomyopathy, infantile hypertrophic 10.1 MTO1 ELAC2

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:

45
# 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

MalaCards organs/tissues related to Combined Oxidative Phosphorylation Deficiency:

40
Liver, Brain, Heart

Publications for Combined Oxidative Phosphorylation Deficiency

Articles related to Combined Oxidative Phosphorylation Deficiency:

(show all 23)
# Title Authors PMID Year
1
Novel Biallelic NSUN3 Variants Cause Early-Onset Mitochondrial Encephalomyopathy and Seizures. 61
32488845 2020
2
A patient with juvenile-onset refractory status epilepticus caused by two novel compound heterozygous mutations in FARS2 gene. 61
31329004 2019
3
[Clinical and genetic characteristics of 62 children with mitochondrial epilepsy]. 61
31665838 2019
4
The combination of whole-exome sequencing and clinical analysis allows better diagnosis of rare syndromic retinal dystrophies. 61
30925032 2019
5
A novel TUFM homozygous variant in a child with mitochondrial cardiomyopathy expands the phenotype of combined oxidative phosphorylation deficiency 4. 61
30903008 2019
6
Implications of the mitochondrial interactome of mammalian thioredoxin 2 for normal cellular function and disease. 61
31018154 2019
7
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
8
Expanding the Phenotype of the Founder South Asian Mutation in the Nuclear Encoding Mitochondrial RMND1 Gene. 61
29071585 2018
9
Mitochondrial Encephalopathy: First Portuguese Report of a VARS2 Causative Variant. 61
29478218 2018
10
The genotypic and phenotypic spectrum of MTO1 deficiency. 61
29331171 2018
11
Retinopathy and optic atrophy: Expanding the phenotypic spectrum of pathogenic variants in the AARS2 gene. 61
28820624 2018
12
The First Korean case of combined oxidative phosphorylation deficiency-17 diagnosed by clinical and molecular investigation. 61
29302266 2017
13
Rapid Targeted Genomics in Critically Ill Newborns. 61
28939701 2017
14
Mitochondrial iron-sulfur cluster biogenesis from molecular understanding to clinical disease. 61
28064324 2017
15
COXPD9 an Evolving Multisystem Disease; Congenital Lactic Acidosis, Sensorineural Hearing Loss, Hypertrophic Cardiomyopathy, Cirrhosis and Interstitial Nephritis. 61
27815843 2017
16
The homozygous R504C mutation in MTO1 gene is responsible for ONCE syndrome. 61
27256614 2017
17
Clinical findings in a patient with FARS2 mutations and early-infantile-encephalopathy with epilepsy. 61
27549011 2016
18
A novel AIFM1 mutation expands the phenotype to an infantile motor neuron disease. 61
26173962 2016
19
Methionyl-tRNA Formyltransferase (MTFMT) Deficiency Mimicking Acquired Demyelinating Disease. 61
26060307 2016
20
Mutations in FARS2 and non-fatal mitochondrial dysfunction in two siblings. 61
25851414 2015
21
Biochemical characterization of pathogenic mutations in human mitochondrial methionyl-tRNA formyltransferase. 61
25288793 2014
22
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
23
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:

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# Gene Name Type Significance ClinVarId dbSNP ID GRCh37 Pos GRCh38 Pos
1 GFM1 NM_024996.5(GFM1):c.748C>T (p.Arg250Trp)SNV Pathogenic/Likely pathogenic 30598 rs139430866 3:158369943-158369943 3:158652154-158652154
2 AIFM1 NM_004208.4(AIFM1):c.340G>A (p.Ala114Thr)SNV Conflicting interpretations of pathogenicity 857026 X:129283453-129283453 X:130149478-130149478
3 MRPS16 NM_016065.4(MRPS16):c.389C>G (p.Thr130Arg)SNV Conflicting interpretations of pathogenicity 214673 rs117510230 10:75010635-75010635 10:73250877-73250877
4 MRPS16 NM_016065.4(MRPS16):c.112C>A (p.His38Asn)SNV Conflicting interpretations of pathogenicity 214670 rs116157972 10:75011683-75011683 10:73251925-73251925
5 AIFM1 NM_004208.4(AIFM1):c.1047C>T (p.Ser349=)SNV Conflicting interpretations of pathogenicity 214080 rs781350745 X:129271081-129271081 X:130137106-130137106
6 AIFM1 NM_004208.4(AIFM1):c.452G>A (p.Arg151Gln)SNV Conflicting interpretations of pathogenicity 214082 rs752742151 X:129281749-129281749 X:130147774-130147774
7 MRPS16 NM_016065.4(MRPS16):c.-8G>CSNV Conflicting interpretations of pathogenicity 138249 rs2271909 10:75012248-75012248 10:73252490-73252490
8 AIFM1 NM_004208.4(AIFM1):c.1388G>T (p.Arg463Ile)SNV Conflicting interpretations of pathogenicity 243069 rs202219398 X:129267348-129267348 X:130133373-130133373
9 MRPS22 NM_020191.4(MRPS22):c.987+15deldeletion Conflicting interpretations of pathogenicity 343491 rs372892045 3:139074639-139074639 3:139355797-139355797
10 AARS2 NM_020745.4(AARS2):c.1534G>C (p.Asp512His)SNV Conflicting interpretations of pathogenicity 357070 rs146512155 6:44272836-44272836 6:44305099-44305099
11 MRPS16 NM_016065.4(MRPS16):c.63T>C (p.Leu21=)SNV Conflicting interpretations of pathogenicity 300721 rs376338190 10:75011732-75011732 10:73251974-73251974
12 MRPS16 NM_016065.4(MRPS16):c.14-12G>ASNV Conflicting interpretations of pathogenicity 300725 rs11594611 10:75011793-75011793 10:73252035-73252035
13 MRPS16 NM_016065.4(MRPS16):c.96C>T (p.Tyr32=)SNV Conflicting interpretations of pathogenicity 300720 rs201106309 10:75011699-75011699 10:73251941-73251941
14 MRPS16 NM_016065.4(MRPS16):c.59G>A (p.Arg20His)SNV Conflicting interpretations of pathogenicity 300722 rs202242186 10:75011736-75011736 10:73251978-73251978
15 MRPS16 NM_016065.4(MRPS16):c.-147C>GSNV Uncertain significance 300731 rs886047202 10:75012387-75012387 10:73252629-73252629
16 C12orf65 NM_152269.5(C12orf65):c.*14deldeletion Uncertain significance 307498 rs886049040 12:123741592-123741592 12:123257045-123257045
17 TUFM NM_003321.5(TUFM):c.1195-3T>CSNV Uncertain significance 318743 rs376169369 16:28854472-28854472 16:28843151-28843151
18 TUFM NM_003321.5(TUFM):c.-57_-55TCT[2]short repeat Uncertain significance 318759 rs147419027 16:28857639-28857641 16:28846318-28846320
19 TSFM NM_005726.6(TSFM):c.233C>T (p.Ala78Val)SNV Uncertain significance 310009 rs886049729 12:58179947-58179947 12:57786164-57786164
20 C12orf65 NM_152269.5(C12orf65):c.*702_*705CAGT[1]short repeat Uncertain significance 307511 rs886049046 12:123742280-123742283 12:123257733-123257736
21 TUFM NM_003321.4(TUFM):c.-81G>CSNV Uncertain significance 318761 rs573249163 16:28857671-28857671 16:28846350-28846350
22 TUFM NM_003321.4(TUFM):c.-128G>CSNV Uncertain significance 318762 rs555362028 16:28857718-28857718 16:28846397-28846397
23 EARS2 NM_001083614.2(EARS2):c.*1902dupduplication Uncertain significance 318512 rs79556186 16:23533789-23533790 16:23522468-23522469
24 EARS2 NM_001083614.2(EARS2):c.*1048deldeletion Uncertain significance 318526 rs750087699 16:23534644-23534644 16:23523323-23523323
25 EARS2 NM_001083614.2(EARS2):c.*535dupduplication Uncertain significance 318531 rs11300207 16:23535156-23535157 16:23523835-23523836
26 EARS2 NM_001083614.2(EARS2):c.558G>A (p.Ala186=)SNV Uncertain significance 318554 rs374363396 16:23546609-23546609 16:23535288-23535288
27 AIFM1 NM_004208.4(AIFM1):c.1597G>A (p.Glu533Lys)SNV Uncertain significance 372555 rs1057517852 X:129264118-129264118 X:130130143-130130143
28 MRPS16 NM_016065.4(MRPS16):c.16A>C (p.Thr6Pro)SNV Uncertain significance 300724 rs141953041 10:75011779-75011779 10:73252021-73252021
29 MRPS16 NM_016065.4(MRPS16):c.275-7C>ASNV Uncertain significance 300718 rs886047199 10:75010756-75010756 10:73250998-73250998
30 MRPS16 NM_016065.4(MRPS16):c.247C>A (p.Leu83Ile)SNV Uncertain significance 300719 rs886047200 10:75011548-75011548 10:73251790-73251790
31 MRPS16 NM_016065.4(MRPS16):c.*1295T>ASNV Uncertain significance 300693 rs778852449 10:75009315-75009315 10:73249557-73249557
32 MRPS16 NM_016065.4(MRPS16):c.*642T>CSNV Uncertain significance 300703 rs145765900 10:75009968-75009968 10:73250210-73250210
33 MRPS16 NM_016065.4(MRPS16):c.*1074A>CSNV Uncertain significance 300696 rs530487067 10:75009536-75009536 10:73249778-73249778
34 MRPS16 NM_016065.4(MRPS16):c.*979C>GSNV Uncertain significance 300697 rs112218454 10:75009631-75009631 10:73249873-73249873
35 MRPS16 NM_016065.4(MRPS16):c.*593A>GSNV Uncertain significance 300706 rs886047193 10:75010017-75010017 10:73250259-73250259
36 MRPS16 NM_016065.4(MRPS16):c.*566A>GSNV Uncertain significance 300707 rs886047194 10:75010044-75010044 10:73250286-73250286
37 MRPS16 NM_016065.4(MRPS16):c.*280C>TSNV Uncertain significance 300713 rs181757719 10:75010330-75010330 10:73250572-73250572
38 MRPS16 NM_016065.4(MRPS16):c.*1391G>ASNV Uncertain significance 300692 rs139703406 10:75009219-75009219 10:73249461-73249461
39 MRPS16 NM_016065.4(MRPS16):c.*1150G>ASNV Uncertain significance 300695 rs79140810 10:75009460-75009460 10:73249702-73249702
40 MRPS16 NM_016065.4(MRPS16):c.*922G>ASNV Uncertain significance 300698 rs561890630 10:75009688-75009688 10:73249930-73249930
41 MRPS16 NM_016065.4(MRPS16):c.-120_-118deldeletion Uncertain significance 300729 rs574159820 10:75012358-75012360 10:73252600-73252602
42 MRPS16 NM_016065.4(MRPS16):c.*742G>TSNV Uncertain significance 300700 rs886047189 10:75009868-75009868 10:73250110-73250110
43 MRPS16 NM_016065.4(MRPS16):c.*741A>TSNV Uncertain significance 300701 rs886047190 10:75009869-75009869 10:73250111-73250111
44 MRPS16 NM_016065.4(MRPS16):c.*502G>ASNV Uncertain significance 300709 rs560241550 10:75010108-75010108 10:73250350-73250350
45 MRPS16 NM_016065.4(MRPS16):c.*472C>TSNV Uncertain significance 300711 rs886047195 10:75010138-75010138 10:73250380-73250380
46 MRPS16 NM_016065.4(MRPS16):c.*450deldeletion Uncertain significance 300712 rs886047196 10:75010160-75010160 10:73250402-73250402
47 MRPS16 NM_016065.4(MRPS16):c.275-5T>GSNV Uncertain significance 300717 rs763591161 10:75010754-75010754 10:73250996-73250996
48 MRPS16 NM_016065.4(MRPS16):c.*1860G>TSNV Uncertain significance 300686 rs886047186 10:75008750-75008750 10:73248992-73248992
49 MRPS16 NM_016065.4(MRPS16):c.*1503A>GSNV Uncertain significance 300690 rs2018198 10:75009107-75009107 10:73249349-73249349
50 MRPS16 NM_016065.4(MRPS16):c.*1291_*1293deldeletion Uncertain significance 300694 rs767465725 10:75009317-75009319 10:73249559-73249561

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 MTFMT
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
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
43 MeSH
44 MESH via Orphanet
45 MGI
48 NCI
49 NCIt
50 NDF-RT
53 NINDS
54 Novoseek
56 OMIM
57 OMIM via Orphanet
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 TGDB
70 Tocris
71 UMLS
72 UMLS via Orphanet
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