COXPD3
MCID: CMB014
MIFTS: 35

Combined Oxidative Phosphorylation Deficiency 3 (COXPD3)

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

Aliases & Classifications for Combined Oxidative Phosphorylation Deficiency 3

MalaCards integrated aliases for Combined Oxidative Phosphorylation Deficiency 3:

Name: Combined Oxidative Phosphorylation Deficiency 3 56 12 73 29 13 6 43 15 71
Coxpd3 56 12 73
Fatal Mitochondrial Disease Due to Combined Oxidative Phosphorylation Defect Type 3 12 58
Encephalomyopathy, Respiratory Failure, and Lactic Acidosis 56 12
Concentric Cardiomyopathy, Hypotonia, and Lactic Acidosis 56 12
Fatal Mitochondrial Disease Due to Coxpd3 12 58
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:

56
Inheritance:
autosomal recessive

Miscellaneous:
highly variable phenotype


HPO:

31
combined oxidative phosphorylation deficiency 3:
Inheritance autosomal recessive inheritance
Clinical modifier 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 combined oxidative phosphorylation deficiency, and has symptoms including seizures, muscle weakness and ataxia. An important gene associated with Combined Oxidative Phosphorylation Deficiency 3 is TSFM (Ts Translation Elongation Factor, Mitochondrial), and among its related pathways/superpathways is Mitochondrial protein import. Affiliated tissues include brain, and related phenotypes are dilated cardiomyopathy and global developmental delay

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 9.9 TSFM AVIL
2 combined oxidative phosphorylation deficiency 9.6 TUFM TSFM
3 combined oxidative phosphorylation deficiency 4 9.5 TUFM TSFM
4 combined oxidative phosphorylation deficiency 1 9.4 TUFM TSFM

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 global developmental delay 31 HP:0001263
3 hepatomegaly 31 HP:0002240
4 visual impairment 31 HP:0000505
5 optic atrophy 31 HP:0000648
6 neonatal hypotonia 31 HP:0001319
7 feeding difficulties in infancy 31 HP:0008872
8 cognitive impairment 31 HP:0100543
9 muscle weakness 31 HP:0001324
10 elevated serum creatine kinase 31 HP:0003236
11 ataxia 31 HP:0001251
12 tremor 31 HP:0001337
13 intrauterine growth retardation 31 HP:0001511
14 respiratory insufficiency 31 HP:0002093
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:

56
Neurologic Central Nervous System:
global developmental delay
seizures
cognitive impairment
ataxia
tremor
more
Muscle Soft Tissue:
muscle weakness
rhabdomyolysis
hypotonia
ragged red fibers seen on muscle biopsy
cox-deficient fibers

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)

Head And Neck Eyes:
visual impairment
optic atrophy
optic neuropathy

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

UMLS symptoms related to Combined Oxidative Phosphorylation Deficiency 3:


seizures, muscle weakness, ataxia, tremor

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. 6 56
25037205 2014
2
Genomic analysis of mitochondrial diseases in a consanguineous population reveals novel candidate disease genes. 56 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. 56 6
21119709 2011
4
Distinct clinical phenotypes associated with a mutation in the mitochondrial translation elongation factor EFTs. 6 56
17033963 2006

Variations for Combined Oxidative Phosphorylation Deficiency 3

ClinVar genetic disease variations for Combined Oxidative Phosphorylation Deficiency 3:

6 (show all 48) ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎
# 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.944G>A (p.Cys315Tyr)SNV Likely pathogenic 155719 rs587777688 12:58190332-58190332 12:57796549-57796549
3 TSFM NM_005726.6(TSFM):c.57+4A>GSNV Conflicting interpretations of pathogenicity 155720 rs587777689 12:58176645-58176645 12:57782862-57782862
4 TSFM NM_005726.6(TSFM):c.361-12T>GSNV Conflicting interpretations of pathogenicity 137763 rs368313488 12:58180811-58180811 12:57787028-57787028
5 TSFM NM_005726.6(TSFM):c.24C>T (p.Arg8=)SNV Conflicting interpretations of pathogenicity 137764 rs138461986 12:58176608-58176608 12:57782825-57782825
6 TSFM NM_005726.6(TSFM):c.856C>T (p.Gln286Ter)SNV Conflicting interpretations of pathogenicity 155718 rs201754030 12:58190244-58190244 12:57796461-57796461
7 TSFM NM_005726.6(TSFM):c.644C>T (p.Ser215Phe)SNV Conflicting interpretations of pathogenicity 418526 rs376562033 12:58190032-58190032 12:57796249-57796249
8 TSFM NM_005726.6(TSFM):c.797T>A (p.Leu266His)SNV Conflicting interpretations of pathogenicity 559172 rs146777264 12:58190185-58190185 12:57796402-57796402
9 TSFM NM_005726.6(TSFM):c.539G>C (p.Gly180Ala)SNV Conflicting interpretations of pathogenicity 310016 rs138534976 12:58186824-58186824 12:57793041-57793041
10 TSFM NM_005726.6(TSFM):c.408G>A (p.Leu136=)SNV Conflicting interpretations of pathogenicity 310013 rs144109380 12:58180870-58180870 12:57787087-57787087
11 TSFM NM_005726.6(TSFM):c.816C>T (p.Asp272=)SNV Conflicting interpretations of pathogenicity 310020 rs183575246 12:58190204-58190204 12:57796421-57796421
12 TSFM NM_005726.6(TSFM):c.69T>A (p.Leu23=)SNV Conflicting interpretations of pathogenicity 310007 rs147317818 12:58176904-58176904 12:57783121-57783121
13 TSFM NM_005726.6(TSFM):c.760C>T (p.Arg254Cys)SNV Conflicting interpretations of pathogenicity 310018 rs200132571 12:58190148-58190148 12:57796365-57796365
14 TSFM NM_005726.6(TSFM):c.814G>C (p.Asp272His)SNV Uncertain significance 310019 rs138911653 12:58190202-58190202 12:57796419-57796419
15 TSFM NM_005726.6(TSFM):c.*412C>TSNV Uncertain significance 310025 rs184926061 12:58190778-58190778 12:57796995-57796995
16 TSFM NM_005726.6(TSFM):c.*561A>CSNV Uncertain significance 310027 rs886049734 12:58190927-58190927 12:57797144-57797144
17 TSFM NM_005726.6(TSFM):c.361-14A>GSNV Uncertain significance 310011 rs759604491 12:58180809-58180809 12:57787026-57787026
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.484-11C>TSNV Uncertain significance 310014 rs752312466 12:58186758-58186758 12:57792975-57792975
20 TSFM NM_005726.6(TSFM):c.520G>T (p.Ala174Ser)SNV Uncertain significance 310015 rs886049731 12:58186805-58186805 12:57793022-57793022
21 TSFM NM_005726.6(TSFM):c.688G>T (p.Val230Leu)SNV Uncertain significance 310017 rs151248026 12:58190076-58190076 12:57796293-57796293
22 TSFM NM_005726.6(TSFM):c.*182T>GSNV Uncertain significance 310022 rs188261377 12:58190548-58190548 12:57796765-57796765
23 TSFM NM_005726.6(TSFM):c.*461T>CSNV Uncertain significance 310026 rs886049733 12:58190827-58190827 12:57797044-57797044
24 TSFM NM_005726.6(TSFM):c.*895A>GSNV Uncertain significance 310028 rs58949411 12:58191261-58191261 12:57797478-57797478
25 TSFM NM_005726.6(TSFM):c.*20C>TSNV Uncertain significance 310021 rs886049732 12:58190386-58190386 12:57796603-57796603
26 TSFM NM_005726.6(TSFM):c.232-8A>GSNV Uncertain significance 310008 rs768661125 12:58179938-58179938 12:57786155-57786155
27 TSFM NM_005726.6(TSFM):c.*210G>ASNV Uncertain significance 310023 rs112956536 12:58190576-58190576 12:57796793-57796793
28 TSFM NM_005726.6(TSFM):c.*262T>ASNV Uncertain significance 310024 rs758314098 12:58190628-58190628 12:57796845-57796845
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.787A>T (p.Met263Leu)SNV Uncertain significance 882314 12:58190175-58190175 12:57796392-57796392
33 TSFM NM_005726.6(TSFM):c.*98A>GSNV Uncertain significance 882315 12:58190464-58190464 12:57796681-57796681
34 TSFM NM_005726.6(TSFM):c.*176T>CSNV Uncertain significance 882581 12:58190542-58190542 12:57796759-57796759
35 TSFM NM_005726.6(TSFM):c.*291T>CSNV Uncertain significance 882582 12:58190657-58190657 12:57796874-57796874
36 TSFM NM_005726.6(TSFM):c.*381C>TSNV Uncertain significance 882583 12:58190747-58190747 12:57796964-57796964
37 TSFM NM_005726.6(TSFM):c.*491G>ASNV Uncertain significance 883367 12:58190857-58190857 12:57797074-57797074
38 TSFM NM_005726.6(TSFM):c.*554A>GSNV Uncertain significance 883368 12:58190920-58190920 12:57797137-57797137
39 TSFM NM_005726.6(TSFM):c.*558C>TSNV Uncertain significance 883369 12:58190924-58190924 12:57797141-57797141
40 TSFM NM_005726.6(TSFM):c.*656A>GSNV Uncertain significance 883370 12:58191022-58191022 12:57797239-57797239
41 TSFM NM_005726.6(TSFM):c.*866T>GSNV Uncertain significance 883371 12:58191232-58191232 12:57797449-57797449
42 TSFM NM_005726.6(TSFM):c.271T>G (p.Trp91Gly)SNV Likely benign 310010 rs542571914 12:58179985-58179985 12:57786202-57786202
43 TSFM NM_005726.6(TSFM):c.754G>A (p.Val252Ile)SNV Benign/Likely benign 137761 rs114694283 12:58190142-58190142 12:57796359-57796359
44 TSFM NM_005726.6(TSFM):c.796C>A (p.Leu266Ile)SNV Benign/Likely benign 235467 rs62000432 12:58190184-58190184 12:57796401-57796401
45 TSFM NM_005726.6(TSFM):c.5C>T (p.Ser2Leu)SNV Benign 703844 12:58176589-58176589 12:57782806-57782806
46 TSFM NM_005726.6(TSFM):c.30T>C (p.Phe10=)SNV Benign 310006 rs10747783 12:58176614-58176614 12:57782831-57782831
47 TSFM NM_005726.6(TSFM):c.*997G>CSNV Benign 310030 rs114214463 12:58191363-58191363 12:57797580-57797580
48 TSFM NM_005726.6(TSFM):c.*958C>GSNV Benign 310029 rs57561819 12:58191324-58191324 12:57797541-57797541

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 10.42 TOMM70 CYC1

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 TOMM70 TOMM34 SLC25A28 CYC1

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

# Name GO ID Score Top Affiliating Genes
1 mitochondrial translational elongation GO:0070125 9.16 TUFM TSFM
2 translational elongation GO:0006414 8.96 TUFM TSFM
3 protein targeting to mitochondrion GO:0006626 8.62 TOMM70 TOMM34

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 8.62 TUFM TSFM

Sources for Combined Oxidative Phosphorylation Deficiency 3

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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