COXPD10
MCID: CMB025
MIFTS: 37

Combined Oxidative Phosphorylation Deficiency 10 (COXPD10)

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

Aliases & Classifications for Combined Oxidative Phosphorylation Deficiency 10

MalaCards integrated aliases for Combined Oxidative Phosphorylation Deficiency 10:

Name: Combined Oxidative Phosphorylation Deficiency 10 56 12 73 29 13 6 15 71
Coxpd10 56 12 58 73
Mitochondrial Hypertrophic Cardiomyopathy with Lactic Acidosis Due to Mto1 Deficiency 12 58
Cardiomyopathy, Infantile Hypertrophic Mitochondrial, and Lactic Acidosis 56
Infantile Hypertrophic Mitochondrial Cardiomyopathy and Lactic Acidosis 12
Cardiomyopathy Infantile Hypertrophic Mitochondrial and Lactic Acidosis 73
Combined Oxidative Phosphorylation Deficiency, Type 10 39
Combined Oxidative Phosphorylation Defect Type 10 58

Characteristics:

Orphanet epidemiological data:

58
mitochondrial hypertrophic cardiomyopathy with lactic acidosis due to mto1 deficiency
Prevalence: <1/1000000 (Worldwide); Age of onset: Infancy,Neonatal;

OMIM:

56
Inheritance:
autosomal recessive

Miscellaneous:
onset at birth or in first months of life but a few have presented as late as 8 years of age
sudden infantile death may occur
some favorable outcome has been seen with treatment with dichloroacetate (dca) or ketogenic diet


HPO:

31
combined oxidative phosphorylation deficiency 10:
Inheritance autosomal recessive inheritance
Onset and clinical course congenital onset


Classifications:

Orphanet: 58  
Inborn errors of metabolism


Summaries for Combined Oxidative Phosphorylation Deficiency 10

OMIM : 56 COXPD10 is an autosomal recessive disorder resulting in variable defects of mitochondrial oxidative respiration. Affected individuals present in infancy with hypertrophic cardiomyopathy and lactic acidosis. The severity is variable, but can be fatal in the most severe cases (summary by Ghezzi et al., 2012). For a discussion of genetic heterogeneity of combined oxidative phosphorylation deficiency, see COXPD1 (609060). (614702)

MalaCards based summary : Combined Oxidative Phosphorylation Deficiency 10, also known as coxpd10, is related to queensland tick typhus and combined oxidative phosphorylation deficiency. An important gene associated with Combined Oxidative Phosphorylation Deficiency 10 is MTO1 (Mitochondrial TRNA Translation Optimization 1), and among its related pathways/superpathways are Gene Expression and tRNA processing. Affiliated tissues include brain, and related phenotypes are optic atrophy and spasticity

Disease Ontology : 12 A combined oxidative phosphorylation deficiency characterized by hypertrophic cardiomyopathy and lactic acidosis that has material basis in homozygous or compound heterozygous mutation in MTO1 on chromosome 6q13.

UniProtKB/Swiss-Prot : 73 Combined oxidative phosphorylation deficiency 10: An autosomal recessive disorder resulting in variable defects of mitochondrial oxidative respiration. Affected individuals present in infancy with hypertrophic cardiomyopathy and lactic acidosis. The severity is variable, but can be fatal in the most severe cases.

Related Diseases for Combined Oxidative Phosphorylation Deficiency 10

Graphical network of the top 20 diseases related to Combined Oxidative Phosphorylation Deficiency 10:



Diseases related to Combined Oxidative Phosphorylation Deficiency 10

Symptoms & Phenotypes for Combined Oxidative Phosphorylation Deficiency 10

Human phenotypes related to Combined Oxidative Phosphorylation Deficiency 10:

31 (show all 18)
# Description HPO Frequency HPO Source Accession
1 optic atrophy 31 occasional (7.5%) HP:0000648
2 spasticity 31 occasional (7.5%) HP:0001257
3 dystonia 31 occasional (7.5%) HP:0001332
4 hyperalaninemia 31 occasional (7.5%) HP:0003348
5 seizure 31 occasional (7.5%) HP:0001250
6 global developmental delay 31 HP:0001263
7 cognitive impairment 31 HP:0100543
8 failure to thrive 31 HP:0001508
9 hypertrophic cardiomyopathy 31 HP:0001639
10 arrhythmia 31 HP:0011675
11 hypoglycemia 31 HP:0001943
12 feeding difficulties 31 HP:0011968
13 increased serum lactate 31 HP:0002151
14 lactic acidosis 31 HP:0003128
15 metabolic acidosis 31 HP:0001942
16 small for gestational age 31 HP:0001518
17 generalized hypotonia 31 HP:0001290
18 poor speech 31 HP:0002465

Symptoms via clinical synopsis from OMIM:

56
Neurologic Central Nervous System:
global developmental delay
cognitive impairment
poor speech
delayed psychomotor development
ataxia (in some patients) seizures (in some patients)
more
Laboratory Abnormalities:
increased serum lactate
increased serum alanine (in many patients)
elevated urinary lactate

Head And Neck Eyes:
optic atrophy (in some patients)
lack of ocular fixation (1 patient)

Cardiovascular Heart:
arrhythmias
cardiomyopathy, hypertrophic (in many patients)

Abdomen Gastrointestinal:
poor feeding (in some patients)

Metabolic Features:
hypoglycemia
lactic acidosis
metabolic acidosis

Muscle Soft Tissue:
hypotonia
variable deficiencies of mitochondrial respiratory chain complexes i, iii, and iv

Growth Weight:
low birth weight

Growth Other:
failure to thrive (in some patients)

Clinical features from OMIM:

614702

Drugs & Therapeutics for Combined Oxidative Phosphorylation Deficiency 10

Search Clinical Trials , NIH Clinical Center for Combined Oxidative Phosphorylation Deficiency 10

Genetic Tests for Combined Oxidative Phosphorylation Deficiency 10

Genetic tests related to Combined Oxidative Phosphorylation Deficiency 10:

# Genetic test Affiliating Genes
1 Combined Oxidative Phosphorylation Deficiency 10 29 MTO1

Anatomical Context for Combined Oxidative Phosphorylation Deficiency 10

MalaCards organs/tissues related to Combined Oxidative Phosphorylation Deficiency 10:

40
Brain

Publications for Combined Oxidative Phosphorylation Deficiency 10

Articles related to Combined Oxidative Phosphorylation Deficiency 10:

# Title Authors PMID Year
1
MTO1 mutations are associated with hypertrophic cardiomyopathy and lactic acidosis and cause respiratory chain deficiency in humans and yeast. 56 6
23929671 2013
2
Mutations of the mitochondrial-tRNA modifier MTO1 cause hypertrophic cardiomyopathy and lactic acidosis. 6 56
22608499 2012
3
The genotypic and phenotypic spectrum of MTO1 deficiency. 56 61
29331171 2018

Variations for Combined Oxidative Phosphorylation Deficiency 10

ClinVar genetic disease variations for Combined Oxidative Phosphorylation Deficiency 10:

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# Gene Name Type Significance ClinVarId dbSNP ID GRCh37 Pos GRCh38 Pos
1 MTO1 NM_012123.4(MTO1):c.97del (p.Arg33fs)deletion Pathogenic 638475 6:74171671-74171671 6:73461948-73461948
2 MTO1 NM_012123.4(MTO1):c.1822del (p.Leu608fs)deletion Pathogenic 574880 rs1561954433 6:74207524-74207524 6:73497801-73497801
3 MTO1 NM_012123.4(MTO1):c.1201C>T (p.Arg401Ter)SNV Pathogenic 840849 6:74190469-74190469 6:73480746-73480746
4 MTO1 NM_012123.4(MTO1):c.1858dup (p.Arg620fs)duplication Pathogenic 35495 rs397518449 6:74207559-74207560 6:73497836-73497837
5 MTO1 NM_012123.4(MTO1):c.1232C>T (p.Thr411Ile)SNV Pathogenic 89038 rs398122419 6:74190500-74190500 6:73480777-73480777
6 MTO1 NM_012123.4(MTO1):c.1282G>A (p.Ala428Thr)SNV Pathogenic/Likely pathogenic 35496 rs143747297 6:74191784-74191784 6:73482061-73482061
7 MTO1 NM_012123.4(MTO1):c.1430G>A (p.Arg477His)SNV Pathogenic/Likely pathogenic 89037 rs201544686 6:74191932-74191932 6:73482209-73482209
8 MTO1 NM_012123.4(MTO1):c.417+2T>CSNV Likely pathogenic 834420 6:74176133-74176133 6:73466410-73466410
9 MTO1 NM_012123.4(MTO1):c.938G>A (p.Arg313Gln)SNV Likely pathogenic 488550 rs371179032 6:74189567-74189567 6:73479844-73479844
10 MTO1 NM_012123.4(MTO1):c.963A>C (p.Lys321Asn)SNV Likely pathogenic 488551 rs1554148965 6:74189683-74189683 6:73479960-73479960
11 MTO1 NM_012123.4(MTO1):c.1261-5T>GSNV Likely pathogenic 488552 rs1275100093 6:74191758-74191758 6:73482035-73482035
12 MTO1 NM_012123.4(MTO1):c.1429C>T (p.Arg477Cys)SNV Likely pathogenic 488553 rs1033653237 6:74191931-74191931 6:73482208-73482208
13 MTO1 NM_012123.4(MTO1):c.1450C>T (p.Arg484Trp)SNV Conflicting interpretations of pathogenicity 408272 rs748152539 6:74191952-74191952 6:73482229-73482229
14 MTO1 NM_012123.4(MTO1):c.1325G>A (p.Arg442Gln)SNV Conflicting interpretations of pathogenicity 807632 6:74191827-74191827 6:73482104-73482104
15 MTO1 NC_000006.12:g.(?_73461845)_(73462081_?)dupduplication Uncertain significance 833101 6:74171568-74171804
16 MTO1 NM_012123.4(MTO1):c.203G>A (p.Arg68His)SNV Uncertain significance 863267 6:74171780-74171780 6:73462057-73462057
17 MTO1 NM_012123.4(MTO1):c.476T>C (p.Ile159Thr)SNV Uncertain significance 845336 6:74176270-74176270 6:73466547-73466547
18 MTO1 NM_012123.4(MTO1):c.868A>G (p.Arg290Gly)SNV Uncertain significance 851199 6:74189497-74189497 6:73479774-73479774
19 MTO1 NM_012123.4(MTO1):c.1013G>A (p.Gly338Glu)SNV Uncertain significance 855717 6:74189733-74189733 6:73480010-73480010
20 MTO1 NM_012123.4(MTO1):c.1934G>A (p.Arg645His)SNV Uncertain significance 567850 rs758448974 6:74210313-74210313 6:73500590-73500590
21 MTO1 NM_012123.4(MTO1):c.1940C>T (p.Pro647Leu)SNV Uncertain significance 569978 rs151330992 6:74210319-74210319 6:73500596-73500596
22 MTO1 NM_012123.4(MTO1):c.623A>G (p.His208Arg)SNV Uncertain significance 575110 rs560308812 6:74183175-74183175 6:73473452-73473452
23 MTO1 NM_012123.4(MTO1):c.1129+246G>ASNV Uncertain significance 638476 6:74190095-74190095 6:73480372-73480372
24 MTO1 NM_012123.4(MTO1):c.97C>T (p.Arg33Trp)SNV Uncertain significance 648658 6:74171674-74171674 6:73461951-73461951
25 MTO1 NM_012123.4(MTO1):c.496G>A (p.Glu166Lys)SNV Uncertain significance 665725 6:74176290-74176290 6:73466567-73466567
26 MTO1 NM_012123.4(MTO1):c.917A>G (p.Lys306Arg)SNV Uncertain significance 652866 6:74189546-74189546 6:73479823-73479823
27 MTO1 NM_012123.4(MTO1):c.1147G>A (p.Asp383Asn)SNV Uncertain significance 655080 6:74190415-74190415 6:73480692-73480692
28 MTO1 NM_012123.4(MTO1):c.1510G>A (p.Ala504Thr)SNV Uncertain significance 641163 6:74192216-74192216 6:73482493-73482493
29 MTO1 NM_012123.4(MTO1):c.1702C>G (p.Pro568Ala)SNV Uncertain significance 650584 6:74202021-74202021 6:73492298-73492298
30 MTO1 NM_012123.4(MTO1):c.1906C>T (p.Arg636Cys)SNV Uncertain significance 648030 6:74207608-74207608 6:73497885-73497885
31 MTO1 NM_012123.4(MTO1):c.1907G>A (p.Arg636His)SNV Uncertain significance 664297 6:74207609-74207609 6:73497886-73497886
32 MTO1 NC_000006.11:g.(?_74171568)_(74210468_?)dupduplication Uncertain significance 640995 6:74171568-74210468 6:73461845-73500745
33 MTO1 NC_000006.11:g.(?_74171568)_(74202085_?)dupduplication Uncertain significance 641565 6:74171568-74202085 6:73461845-73492362
34 MTO1 NM_012123.4(MTO1):c.61C>T (p.Pro21Ser)SNV Uncertain significance 408277 rs753873871 6:74171638-74171638 6:73461915-73461915
35 MTO1 NM_012123.4(MTO1):c.1194G>T (p.Leu398Phe)SNV Uncertain significance 408276 rs772209676 6:74190462-74190462 6:73480739-73480739
36 MTO1 NM_012123.4(MTO1):c.547A>G (p.Thr183Ala)SNV Uncertain significance 408274 rs779108851 6:74183099-74183099 6:73473376-73473376
37 MTO1 NM_012123.4(MTO1):c.1291C>T (p.Arg431Trp)SNV Uncertain significance 408273 rs748328322 6:74191793-74191793 6:73482070-73482070
38 MTO1 NM_012123.4(MTO1):c.70C>T (p.Arg24Trp)SNV Uncertain significance 408275 rs368723563 6:74171647-74171647 6:73461924-73461924
39 MTO1 NM_012123.4(MTO1):c.2036A>G (p.Gln679Arg)SNV Uncertain significance 540424 rs1418465267 6:74210415-74210415 6:73500692-73500692
40 MTO1 NM_012123.4(MTO1):c.983G>A (p.Arg328His)SNV Uncertain significance 473197 rs142148270 6:74189703-74189703 6:73479980-73479980
41 MTO1 NM_012123.4(MTO1):c.1260+191G>ASNV Uncertain significance 488182 rs1241914180 6:74190719-74190719 6:73480996-73480996
42 MTO1 NM_012123.4(MTO1):c.1260+193C>ASNV Uncertain significance 488183 rs1554149118 6:74190721-74190721 6:73480998-73480998
43 MTO1 NM_012123.4(MTO1):c.535+5G>ASNV Uncertain significance 846664 6:74176334-74176334 6:73466611-73466611
44 MTO1 NM_012123.4(MTO1):c.1996C>T (p.Arg666Ter)SNV Uncertain significance 547882 rs200217371 6:74210375-74210375 6:73500652-73500652
45 MTO1 NM_012123.4(MTO1):c.1339A>G (p.Ile447Val)SNV Uncertain significance 577330 rs747475822 6:74191841-74191841 6:73482118-73482118
46 MTO1 NM_012123.4(MTO1):c.1480G>A (p.Gly494Ser)SNV Uncertain significance 569553 rs139449947 6:74192186-74192186 6:73482463-73482463
47 MTO1 NM_012123.4(MTO1):c.1292G>A (p.Arg431Gln)SNV Uncertain significance 852190 6:74191794-74191794 6:73482071-73482071
48 MTO1 NM_012123.4(MTO1):c.1391G>A (p.Arg464His)SNV Uncertain significance 835604 6:74191893-74191893 6:73482170-73482170
49 MTO1 NM_012123.4(MTO1):c.1609A>G (p.Ile537Val)SNV Uncertain significance 850387 6:74192315-74192315 6:73482592-73482592
50 MTO1 NM_012123.4(MTO1):c.1725T>G (p.Cys575Trp)SNV Uncertain significance 837793 6:74202044-74202044 6:73492321-73492321

UniProtKB/Swiss-Prot genetic disease variations for Combined Oxidative Phosphorylation Deficiency 10:

73
# Symbol AA change Variation ID SNP ID
1 MTO1 p.Ala453Thr VAR_068693 rs143747297

Expression for Combined Oxidative Phosphorylation Deficiency 10

Search GEO for disease gene expression data for Combined Oxidative Phosphorylation Deficiency 10.

Pathways for Combined Oxidative Phosphorylation Deficiency 10

Pathways related to Combined Oxidative Phosphorylation Deficiency 10 according to GeneCards Suite gene sharing:

# Super pathways Score Top Affiliating Genes
1
Show member pathways
12.79 TRMU TRMT5 TRIT1 PUS1 MTO1
2
Show member pathways
11.39 TRMU TRMT5 TRIT1 PUS1 MTO1

GO Terms for Combined Oxidative Phosphorylation Deficiency 10

Cellular components related to Combined Oxidative Phosphorylation Deficiency 10 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 mitochondrion GO:0005739 9.17 TRMU TRMT5 TRIT1 PUS1 MTO1 MRPS34
2 mitochondrial matrix GO:0005759 9.13 TRMT5 TRIT1 PUS1

Biological processes related to Combined Oxidative Phosphorylation Deficiency 10 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 mitochondrial translational termination GO:0070126 9.26 MRPS34 MRPL44
2 mitochondrial translational elongation GO:0070125 9.16 MRPS34 MRPL44
3 tRNA processing GO:0008033 9.02 TRMU TRMT5 TRIT1 PUS1 MTO1
4 tRNA methylation GO:0030488 8.96 TRMT5 MTO1

Molecular functions related to Combined Oxidative Phosphorylation Deficiency 10 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 RNA binding GO:0003723 9.26 TRMU PUS1 MTO1 MRPL44
2 tRNA binding GO:0000049 8.62 TRMU PUS1

Sources for Combined Oxidative Phosphorylation Deficiency 10

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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