COXPD3
MCID: CMB014
MIFTS: 37

Combined Oxidative Phosphorylation Deficiency 3 (COXPD3)

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

Aliases & Classifications for Combined Oxidative Phosphorylation Deficiency 3

MalaCards integrated aliases for Combined Oxidative Phosphorylation Deficiency 3:

Name: Combined Oxidative Phosphorylation Deficiency 3 57 12 73 29 13 6 44 15 71
Coxpd3 57 12 73
Fatal Mitochondrial Disease Due to Combined Oxidative Phosphorylation Defect Type 3 12 58
Encephalomyopathy, Respiratory Failure, and Lactic Acidosis 57 12
Concentric Cardiomyopathy, Hypotonia, and Lactic Acidosis 57 12
Fatal Mitochondrial Disease Due to Coxpd3 12 58
Encephalomyopathy with Respiratory Failure and Lactic Acidosis 6
Encephalomyopathy Respiratory Failure and Lactic Acidosis 73
Concentric Cardiomyopathy Hypotonia and Lactic Acidosis 73
Combined Oxidative Phosphorylation Deficiency, Type 3 39

Characteristics:

Orphanet epidemiological data:

58
fatal mitochondrial disease due to combined oxidative phosphorylation defect type 3
Inheritance: Autosomal recessive; Prevalence: <1/1000000 (Worldwide); Age of onset: Infancy,Neonatal; Age of death: early childhood;

OMIM®:

57 (Updated 05-Mar-2021)
Inheritance:
autosomal recessive

Miscellaneous:
highly variable phenotype


HPO:

31
combined oxidative phosphorylation deficiency 3:
Inheritance autosomal recessive inheritance
Onset and clinical course death in childhood


Classifications:

Orphanet: 58  
Inborn errors of metabolism


Summaries for Combined Oxidative Phosphorylation Deficiency 3

UniProtKB/Swiss-Prot : 73 Combined oxidative phosphorylation deficiency 3: A mitochondrial disease resulting in severe metabolic acidosis with encephalomyopathy or with hypertrophic cardiomyopathy. Patients show a severe defect in mitochondrial translation leading to a failure to assemble adequate amounts of three of the oxidative phosphorylation complexes.

MalaCards based summary : Combined Oxidative Phosphorylation Deficiency 3, also known as coxpd3, is related to nephrotic syndrome, type 21 and myoclonic epilepsy associated with ragged-red fibers, and has symptoms including seizures, ataxia and tremor. An important gene associated with Combined Oxidative Phosphorylation Deficiency 3 is TSFM (Ts Translation Elongation Factor, Mitochondrial), and among its related pathways/superpathways are Organelle biogenesis and maintenance and Mitochondrial translation. Affiliated tissues include brain, and related phenotypes are dilated cardiomyopathy and ataxia

Disease Ontology : 12 A combined oxidative phosphorylation deficiency that has material basis in homozygous or compound heterozygous mutation in TSFM on chromosome 12q14.1.

More information from OMIM: 610505 PS609060

Related Diseases for Combined Oxidative Phosphorylation Deficiency 3

Diseases related to Combined Oxidative Phosphorylation Deficiency 3 via text searches within MalaCards or GeneCards Suite gene sharing:

# Related Disease Score Top Affiliating Genes
1 nephrotic syndrome, type 21 10.0 TSFM AVIL
2 myoclonic epilepsy associated with ragged-red fibers 9.8 TSFM CYC1
3 combined oxidative phosphorylation deficiency 9.6 TUFM TSFM GFM1
4 combined oxidative phosphorylation deficiency 4 9.6 TUFM TSFM GFM1
5 combined oxidative phosphorylation deficiency 1 9.6 TUFM TSFM GFM1
6 leigh syndrome 9.4 TUFM TSFM GFM1

Graphical network of the top 20 diseases related to Combined Oxidative Phosphorylation Deficiency 3:



Diseases related to Combined Oxidative Phosphorylation Deficiency 3

Symptoms & Phenotypes for Combined Oxidative Phosphorylation Deficiency 3

Human phenotypes related to Combined Oxidative Phosphorylation Deficiency 3:

31 (show all 31)
# Description HPO Frequency HPO Source Accession
1 dilated cardiomyopathy 31 occasional (7.5%) HP:0001644
2 ataxia 31 HP:0001251
3 tremor 31 HP:0001337
4 muscle weakness 31 HP:0001324
5 respiratory insufficiency 31 HP:0002093
6 global developmental delay 31 HP:0001263
7 hepatomegaly 31 HP:0002240
8 visual impairment 31 HP:0000505
9 optic atrophy 31 HP:0000648
10 neonatal hypotonia 31 HP:0001319
11 feeding difficulties in infancy 31 HP:0008872
12 cognitive impairment 31 HP:0100543
13 intrauterine growth retardation 31 HP:0001511
14 elevated serum creatine kinase 31 HP:0003236
15 patent ductus arteriosus 31 HP:0001643
16 ventriculomegaly 31 HP:0002119
17 increased serum lactate 31 HP:0002151
18 decreased fetal movement 31 HP:0001558
19 dystonia 31 HP:0001332
20 respiratory failure 31 HP:0002878
21 decreased activity of mitochondrial complex i 31 HP:0011923
22 optic neuropathy 31 HP:0001138
23 encephalopathy 31 HP:0001298
24 lactic acidosis 31 HP:0003128
25 generalized hypotonia 31 HP:0001290
26 patent foramen ovale 31 HP:0001655
27 rhabdomyolysis 31 HP:0003201
28 decreased activity of mitochondrial complex iii 31 HP:0011924
29 concentric hypertrophic cardiomyopathy 31 HP:0005157
30 decreased activity of mitochondrial complex iv 31 HP:0008347
31 seizure 31 HP:0001250

Symptoms via clinical synopsis from OMIM®:

57 (Updated 05-Mar-2021)
Neurologic Central Nervous System:
seizures
ataxia
tremor
global developmental delay
cognitive impairment
more
Head And Neck Eyes:
visual impairment
optic atrophy
optic neuropathy

Laboratory Abnormalities:
increased serum lactate
increased serum creatine kinase
increased serum ketones
increased serum ammonia
decreased activity of mitochondrial respiratory complexes i, iii, and iv

Metabolic Features:
lactic acidosis

Cardiovascular Vascular:
patent ductus arteriosus (in some patients)

Prenatal Manifestations Movement:
decreased fetal movements

Neurologic Peripheral Nervous System:
axonal sensorimotor neuropathy (in some patients)

Muscle Soft Tissue:
muscle weakness
rhabdomyolysis
hypotonia
ragged red fibers seen on muscle biopsy
cox-deficient fibers

Growth Other:
intrauterine growth retardation

Respiratory:
respiratory failure

Abdomen Gastrointestinal:
poor feeding

Abdomen Liver:
hepatomegaly (in some patients)

Cardiovascular Heart:
patent foramen ovale (in some patients)
dilated cardiomyopathy (in some patients)
concentric hypertrophic cardiomyopathy (in some patients)

Clinical features from OMIM®:

610505 (Updated 05-Mar-2021)

UMLS symptoms related to Combined Oxidative Phosphorylation Deficiency 3:


seizures, ataxia, tremor, muscle weakness

Drugs & Therapeutics for Combined Oxidative Phosphorylation Deficiency 3

Search Clinical Trials , NIH Clinical Center for Combined Oxidative Phosphorylation Deficiency 3

Cochrane evidence based reviews: combined oxidative phosphorylation deficiency 3

Genetic Tests for Combined Oxidative Phosphorylation Deficiency 3

Genetic tests related to Combined Oxidative Phosphorylation Deficiency 3:

# Genetic test Affiliating Genes
1 Combined Oxidative Phosphorylation Deficiency 3 29 TSFM

Anatomical Context for Combined Oxidative Phosphorylation Deficiency 3

MalaCards organs/tissues related to Combined Oxidative Phosphorylation Deficiency 3:

40
Brain

Publications for Combined Oxidative Phosphorylation Deficiency 3

Articles related to Combined Oxidative Phosphorylation Deficiency 3:

# Title Authors PMID Year
1
Mitochondrial EFTs defects in juvenile-onset Leigh disease, ataxia, neuropathy, and optic atrophy. 57 6
25037205 2014
2
Genomic analysis of mitochondrial diseases in a consanguineous population reveals novel candidate disease genes. 57 6
22499341 2012
3
Mutation in subdomain G' of mitochondrial elongation factor G1 is associated with combined OXPHOS deficiency in fibroblasts but not in muscle. 57 6
21119709 2011
4
Distinct clinical phenotypes associated with a mutation in the mitochondrial translation elongation factor EFTs. 57 6
17033963 2006

Variations for Combined Oxidative Phosphorylation Deficiency 3

ClinVar genetic disease variations for Combined Oxidative Phosphorylation Deficiency 3:

6 (show top 50) (show all 55)
# Gene Name Type Significance ClinVarId dbSNP ID GRCh37 Pos GRCh38 Pos
1 TSFM NM_005726.6(TSFM):c.934C>T (p.Arg312Trp) SNV Pathogenic 5379 rs121909485 12:58190322-58190322 12:57796539-57796539
2 TSFM NM_005726.6(TSFM):c.57+4A>G SNV Pathogenic 155720 rs587777689 12:58176645-58176645 12:57782862-57782862
3 TSFM NM_005726.6(TSFM):c.856C>T (p.Gln286Ter) SNV Pathogenic 155718 rs201754030 12:58190244-58190244 12:57796461-57796461
4 TSFM NM_005726.6(TSFM):c.944G>A (p.Cys315Tyr) SNV Pathogenic 155719 rs587777688 12:58190332-58190332 12:57796549-57796549
5 TSFM NM_005726.6(TSFM):c.934C>T (p.Arg312Trp) SNV Likely pathogenic 5379 rs121909485 12:58190322-58190322 12:57796539-57796539
6 TSFM NM_005726.6(TSFM):c.760C>T (p.Arg254Cys) SNV Uncertain significance 310018 rs200132571 12:58190148-58190148 12:57796365-57796365
7 TSFM NM_005726.6(TSFM):c.*182T>G SNV Uncertain significance 310022 rs188261377 12:58190548-58190548 12:57796765-57796765
8 TSFM NM_005726.6(TSFM):c.814G>C (p.Asp272His) SNV Uncertain significance 310019 rs138911653 12:58190202-58190202 12:57796419-57796419
9 TSFM NM_005726.6(TSFM):c.*412C>T SNV Uncertain significance 310025 rs184926061 12:58190778-58190778 12:57796995-57796995
10 TSFM NM_005726.6(TSFM):c.361-14A>G SNV Uncertain significance 310011 rs759604491 12:58180809-58180809 12:57787026-57787026
11 TSFM NM_005726.6(TSFM):c.232-8A>G SNV Uncertain significance 310008 rs768661125 12:58179938-58179938 12:57786155-57786155
12 TSFM NM_005726.6(TSFM):c.*895A>G SNV Uncertain significance 310028 rs58949411 12:58191261-58191261 12:57797478-57797478
13 TSFM NM_005726.6(TSFM):c.484-11C>T SNV Uncertain significance 310014 rs752312466 12:58186758-58186758 12:57792975-57792975
14 TSFM NM_005726.6(TSFM):c.*20C>T SNV Uncertain significance 310021 rs886049732 12:58190386-58190386 12:57796603-57796603
15 TSFM NM_005726.6(TSFM):c.688G>T (p.Val230Leu) SNV Uncertain significance 310017 rs151248026 12:58190076-58190076 12:57796293-57796293
16 TSFM NM_005726.6(TSFM):c.*262T>A SNV Uncertain significance 310024 rs758314098 12:58190628-58190628 12:57796845-57796845
17 TSFM NM_005726.6(TSFM):c.*561A>C SNV Uncertain significance 310027 rs886049734 12:58190927-58190927 12:57797144-57797144
18 TSFM NM_005726.6(TSFM):c.375A>G (p.Thr125=) SNV Uncertain significance 310012 rs886049730 12:58180837-58180837 12:57787054-57787054
19 TSFM NM_005726.6(TSFM):c.520G>T (p.Ala174Ser) SNV Uncertain significance 310015 rs886049731 12:58186805-58186805 12:57793022-57793022
20 TSFM NM_005726.6(TSFM):c.*210G>A SNV Uncertain significance 310023 rs112956536 12:58190576-58190576 12:57796793-57796793
21 TSFM NM_005726.6(TSFM):c.*461T>C SNV Uncertain significance 310026 rs886049733 12:58190827-58190827 12:57797044-57797044
22 TSFM NM_005726.6(TSFM):c.644C>T (p.Ser215Phe) SNV Uncertain significance 418526 rs376562033 12:58190032-58190032 12:57796249-57796249
23 TSFM NM_005726.6(TSFM):c.787A>T (p.Met263Leu) SNV Uncertain significance 882314 12:58190175-58190175 12:57796392-57796392
24 TSFM NM_005726.6(TSFM):c.797T>A (p.Leu266His) SNV Uncertain significance 559172 rs146777264 12:58190185-58190185 12:57796402-57796402
25 TSFM NM_005726.6(TSFM):c.*98A>G SNV Uncertain significance 882315 12:58190464-58190464 12:57796681-57796681
26 TSFM NM_005726.6(TSFM):c.*176T>C SNV Uncertain significance 882581 12:58190542-58190542 12:57796759-57796759
27 TSFM NM_005726.6(TSFM):c.*291T>C SNV Uncertain significance 882582 12:58190657-58190657 12:57796874-57796874
28 TSFM NM_005726.6(TSFM):c.*381C>T SNV Uncertain significance 882583 12:58190747-58190747 12:57796964-57796964
29 TSFM NM_005726.6(TSFM):c.48G>A (p.Gly16=) SNV Uncertain significance 883314 12:58176632-58176632 12:57782849-57782849
30 TSFM NM_005726.6(TSFM):c.140A>G (p.Lys47Arg) SNV Uncertain significance 883315 12:58176975-58176975 12:57783192-57783192
31 TSFM NM_005726.6(TSFM):c.322G>A (p.Gly108Arg) SNV Uncertain significance 883316 12:58180036-58180036 12:57786253-57786253
32 TSFM NM_005726.6(TSFM):c.*491G>A SNV Uncertain significance 883367 12:58190857-58190857 12:57797074-57797074
33 TSFM NM_005726.6(TSFM):c.*554A>G SNV Uncertain significance 883368 12:58190920-58190920 12:57797137-57797137
34 TSFM NM_005726.6(TSFM):c.*558C>T SNV Uncertain significance 883369 12:58190924-58190924 12:57797141-57797141
35 TSFM NM_005726.6(TSFM):c.*656A>G SNV Uncertain significance 883370 12:58191022-58191022 12:57797239-57797239
36 TSFM NM_005726.6(TSFM):c.*866T>G SNV Uncertain significance 883371 12:58191232-58191232 12:57797449-57797449
37 TSFM NM_005726.6(TSFM):c.361-12T>G SNV Uncertain significance 137763 rs368313488 12:58180811-58180811 12:57787028-57787028
38 TSFM NM_005726.6(TSFM):c.12G>T (p.Leu4=) SNV Uncertain significance 705419 rs773572404 12:58176596-58176596 12:57782813-57782813
39 TSFM NM_005726.6(TSFM):c.484-10G>A SNV Uncertain significance 706660 rs374795252 12:58186759-58186759 12:57792976-57792976
40 TSFM NM_005726.6(TSFM):c.69T>A (p.Leu23=) SNV Uncertain significance 310007 rs147317818 12:58176904-58176904 12:57783121-57783121
41 TSFM NM_005726.6(TSFM):c.408G>A (p.Leu136=) SNV Uncertain significance 310013 rs144109380 12:58180870-58180870 12:57787087-57787087
42 TSFM NM_005726.6(TSFM):c.539G>C (p.Gly180Ala) SNV Uncertain significance 310016 rs138534976 12:58186824-58186824 12:57793041-57793041
43 TSFM NM_005726.6(TSFM):c.816C>T (p.Asp272=) SNV Uncertain significance 310020 rs183575246 12:58190204-58190204 12:57796421-57796421
44 TSFM NM_005726.6(TSFM):c.24C>T (p.Arg8=) SNV Uncertain significance 137764 rs138461986 12:58176608-58176608 12:57782825-57782825
45 TSFM NM_005726.6(TSFM):c.271T>G (p.Trp91Gly) SNV Likely benign 310010 rs542571914 12:58179985-58179985 12:57786202-57786202
46 TSFM NM_005726.6(TSFM):c.885C>T (p.Thr295=) SNV Likely benign 725434 rs750718644 12:58190273-58190273 12:57796490-57796490
47 TSFM NM_005726.6(TSFM):c.53A>T (p.Tyr18Phe) SNV Likely benign 989550 12:58176637-58176637 12:57782854-57782854
48 TSFM NM_005726.6(TSFM):c.726G>A (p.Thr242=) SNV Likely benign 740261 rs140461538 12:58190114-58190114 12:57796331-57796331
49 TSFM NM_005726.6(TSFM):c.30T>C (p.Phe10=) SNV Benign 310006 rs10747783 12:58176614-58176614 12:57782831-57782831
50 TSFM NM_005726.6(TSFM):c.*997G>C SNV Benign 310030 rs114214463 12:58191363-58191363 12:57797580-57797580

UniProtKB/Swiss-Prot genetic disease variations for Combined Oxidative Phosphorylation Deficiency 3:

73
# Symbol AA change Variation ID SNP ID
1 TSFM p.Arg312Trp VAR_068973 rs121909485
2 TSFM p.Cys240Ser VAR_077697 rs750799705

Expression for Combined Oxidative Phosphorylation Deficiency 3

Search GEO for disease gene expression data for Combined Oxidative Phosphorylation Deficiency 3.

Pathways for Combined Oxidative Phosphorylation Deficiency 3

Pathways related to Combined Oxidative Phosphorylation Deficiency 3 according to GeneCards Suite gene sharing:

# Super pathways Score Top Affiliating Genes
1
Show member pathways
11.86 TUFM TSFM GFM1
2
Show member pathways
11.36 TUFM TSFM GFM1

GO Terms for Combined Oxidative Phosphorylation Deficiency 3

Cellular components related to Combined Oxidative Phosphorylation Deficiency 3 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 mitochondrion GO:0005739 9.1 TUFM TSFM TOMM34 SLC25A28 GFM1 CYC1

Biological processes related to Combined Oxidative Phosphorylation Deficiency 3 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 translation GO:0006412 9.33 TUFM TSFM GFM1
2 mitochondrial translational elongation GO:0070125 9.13 TUFM TSFM GFM1
3 translational elongation GO:0006414 8.8 TUFM TSFM GFM1

Molecular functions related to Combined Oxidative Phosphorylation Deficiency 3 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 heat shock protein binding GO:0031072 8.96 TOMM34 METTL18
2 translation elongation factor activity GO:0003746 8.8 TUFM TSFM GFM1

Sources for Combined Oxidative Phosphorylation Deficiency 3

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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