COXPD10
MCID: CMB025
MIFTS: 38

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 57 12 72 29 13 6 15 70
Coxpd10 57 12 58 72
Mitochondrial Hypertrophic Cardiomyopathy with Lactic Acidosis Due to Mto1 Deficiency 12 58
Cardiomyopathy, Infantile Hypertrophic Mitochondrial, and Lactic Acidosis 57
Infantile Hypertrophic Mitochondrial Cardiomyopathy and Lactic Acidosis 12
Cardiomyopathy Infantile Hypertrophic Mitochondrial and Lactic Acidosis 72
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®:

57 (Updated 20-May-2021)
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 (in some patients)
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® : 57 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) (Updated 20-May-2021)

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 spasticity and optic atrophy

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 : 72 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 spasticity 31 occasional (7.5%) HP:0001257
2 optic atrophy 31 occasional (7.5%) HP:0000648
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 failure to thrive 31 HP:0001508
7 global developmental delay 31 HP:0001263
8 cognitive impairment 31 HP:0100543
9 hypoglycemia 31 HP:0001943
10 hypertrophic cardiomyopathy 31 HP:0001639
11 arrhythmia 31 HP:0011675
12 increased serum lactate 31 HP:0002151
13 lactic acidosis 31 HP:0003128
14 feeding difficulties 31 HP:0011968
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®:

57 (Updated 20-May-2021)
Neurologic Central Nervous System:
global developmental delay
cognitive impairment
poor speech
seizures (in some patients)
delayed psychomotor development
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 (Updated 20-May-2021)

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
The genotypic and phenotypic spectrum of MTO1 deficiency. 57 6 61
29331171 2018
2
MTO1 mutations are associated with hypertrophic cardiomyopathy and lactic acidosis and cause respiratory chain deficiency in humans and yeast. 57 6
23929671 2013
3
Mutations of the mitochondrial-tRNA modifier MTO1 cause hypertrophic cardiomyopathy and lactic acidosis. 6 57
22608499 2012
4
Genetic defects in mtDNA-encoded protein translation cause pediatric, mitochondrial cardiomyopathy with early-onset brain disease. 6
29440775 2018
5
The homozygous R504C mutation in MTO1 gene is responsible for ONCE syndrome. 6
27256614 2017
6
Optic neuropathy, cardiomyopathy, cognitive disability in patients with a homozygous mutation in the nuclear MTO1 and a mitochondrial MT-TF variant. 6
26061759 2015
7
Use of whole-exome sequencing to determine the genetic basis of multiple mitochondrial respiratory chain complex deficiencies. 6
25058219 2014

Variations for Combined Oxidative Phosphorylation Deficiency 10

ClinVar genetic disease variations for Combined Oxidative Phosphorylation Deficiency 10:

6 (show top 50) (show all 100)
# Gene Name Type Significance ClinVarId dbSNP ID Position
1 MTO1 NM_012123.4(MTO1):c.1232C>T (p.Thr411Ile) SNV Pathogenic 89038 rs398122419 GRCh37: 6:74190500-74190500
GRCh38: 6:73480777-73480777
2 MTO1 NM_012123.4(MTO1):c.97del (p.Arg33fs) Deletion Pathogenic 638475 rs1582666067 GRCh37: 6:74171671-74171671
GRCh38: 6:73461948-73461948
3 MTO1 NM_012123.4(MTO1):c.1324C>T (p.Arg442Ter) SNV Pathogenic 445467 rs200583827 GRCh37: 6:74191826-74191826
GRCh38: 6:73482103-73482103
4 MTO1 NM_012123.4(MTO1):c.1822del (p.Leu608fs) Deletion Pathogenic 574880 rs1561954433 GRCh37: 6:74207524-74207524
GRCh38: 6:73497801-73497801
5 MTO1 NM_012123.4(MTO1):c.1858dup (p.Arg620fs) Duplication Pathogenic 35495 rs397518449 GRCh37: 6:74207559-74207560
GRCh38: 6:73497836-73497837
6 MTO1 NM_012123.4(MTO1):c.1282G>A (p.Ala428Thr) SNV Pathogenic 35496 rs143747297 GRCh37: 6:74191784-74191784
GRCh38: 6:73482061-73482061
7 MTO1 NM_012123.4(MTO1):c.1430G>A (p.Arg477His) SNV Pathogenic/Likely pathogenic 89037 rs201544686 GRCh37: 6:74191932-74191932
GRCh38: 6:73482209-73482209
8 MTO1 NM_012123.4(MTO1):c.1201C>T (p.Arg401Ter) SNV Pathogenic/Likely pathogenic 840849 GRCh37: 6:74190469-74190469
GRCh38: 6:73480746-73480746
9 MTO1 NM_012123.4(MTO1):c.417+2T>C SNV Likely pathogenic 834420 GRCh37: 6:74176133-74176133
GRCh38: 6:73466410-73466410
10 MTO1 NM_012123.4(MTO1):c.1390C>T (p.Arg464Cys) SNV Likely pathogenic 937542 GRCh37: 6:74191892-74191892
GRCh38: 6:73482169-73482169
11 MTO1 NM_012123.4(MTO1):c.153_174del (p.Thr53fs) Deletion Likely pathogenic 931370 GRCh37: 6:74171728-74171749
GRCh38: 6:73462005-73462026
12 MTO1 NM_012123.4(MTO1):c.963A>C (p.Lys321Asn) SNV Likely pathogenic 488551 rs1554148965 GRCh37: 6:74189683-74189683
GRCh38: 6:73479960-73479960
13 MTO1 NM_012123.4(MTO1):c.1261-5T>G SNV Likely pathogenic 488552 rs1275100093 GRCh37: 6:74191758-74191758
GRCh38: 6:73482035-73482035
14 MTO1 NM_012123.4(MTO1):c.1429C>T (p.Arg477Cys) SNV Likely pathogenic 488553 rs1033653237 GRCh37: 6:74191931-74191931
GRCh38: 6:73482208-73482208
15 MTO1 NM_012123.4(MTO1):c.344del (p.Asn115fs) Deletion Likely pathogenic 996114 GRCh37: 6:74176056-74176056
GRCh38: 6:73466333-73466333
16 MTO1 NM_012123.4(MTO1):c.1450C>T (p.Arg484Trp) SNV Conflicting interpretations of pathogenicity 408272 rs748152539 GRCh37: 6:74191952-74191952
GRCh38: 6:73482229-73482229
17 MTO1 NM_012123.4(MTO1):c.1325G>A (p.Arg442Gln) SNV Conflicting interpretations of pathogenicity 807632 rs765548847 GRCh37: 6:74191827-74191827
GRCh38: 6:73482104-73482104
18 MTO1 NM_012123.4(MTO1):c.938G>A (p.Arg313Gln) SNV Conflicting interpretations of pathogenicity 488550 rs371179032 GRCh37: 6:74189567-74189567
GRCh38: 6:73479844-73479844
19 MTO1 NM_012123.4(MTO1):c.1391G>T (p.Arg464Leu) SNV Uncertain significance 70512 rs141970072 GRCh37: 6:74191893-74191893
GRCh38: 6:73482170-73482170
20 MTO1 NM_012123.4(MTO1):c.1393A>G (p.Met465Val) SNV Uncertain significance 1027765 GRCh37: 6:74191895-74191895
GRCh38: 6:73482172-73482172
21 MTO1 NM_012123.4(MTO1):c.79A>T (p.Ser27Cys) SNV Uncertain significance 1027766 GRCh37: 6:74171656-74171656
GRCh38: 6:73461933-73461933
22 MTO1 NM_012123.4(MTO1):c.82G>A (p.Asp28Asn) SNV Uncertain significance 1031741 GRCh37: 6:74171659-74171659
GRCh38: 6:73461936-73461936
23 MTO1 NM_012123.4(MTO1):c.552A>G (p.Val184=) SNV Uncertain significance 1039509 GRCh37: 6:74183104-74183104
GRCh38: 6:73473381-73473381
24 MTO1 NM_012123.4(MTO1):c.386T>C (p.Ile129Thr) SNV Uncertain significance 1041724 GRCh37: 6:74176100-74176100
GRCh38: 6:73466377-73466377
25 MTO1 NM_012123.4(MTO1):c.868A>G (p.Arg290Gly) SNV Uncertain significance 851199 GRCh37: 6:74189497-74189497
GRCh38: 6:73479774-73479774
26 MTO1 NM_012123.4(MTO1):c.1292G>A (p.Arg431Gln) SNV Uncertain significance 852190 GRCh37: 6:74191794-74191794
GRCh38: 6:73482071-73482071
27 MTO1 NM_012123.4(MTO1):c.94C>T (p.Pro32Ser) SNV Uncertain significance 935389 GRCh37: 6:74171671-74171671
GRCh38: 6:73461948-73461948
28 MTO1 NM_012123.4(MTO1):c.1340T>C (p.Ile447Thr) SNV Uncertain significance 941436 GRCh37: 6:74191842-74191842
GRCh38: 6:73482119-73482119
29 MTO1 NM_012123.4(MTO1):c.2006C>T (p.Ser669Leu) SNV Uncertain significance 958454 GRCh37: 6:74210385-74210385
GRCh38: 6:73500662-73500662
30 MTO1 NM_012123.4(MTO1):c.1222A>G (p.Ile408Val) SNV Uncertain significance 240846 rs149407452 GRCh37: 6:74190490-74190490
GRCh38: 6:73480767-73480767
31 MTO1 NM_012123.4(MTO1):c.1391G>A (p.Arg464His) SNV Uncertain significance 835604 GRCh37: 6:74191893-74191893
GRCh38: 6:73482170-73482170
32 MTO1 NM_012123.4(MTO1):c.476T>C (p.Ile159Thr) SNV Uncertain significance 845336 GRCh37: 6:74176270-74176270
GRCh38: 6:73466547-73466547
33 MTO1 NM_012123.4(MTO1):c.535+5G>A SNV Uncertain significance 846664 GRCh37: 6:74176334-74176334
GRCh38: 6:73466611-73466611
34 MTO1 NM_012123.4(MTO1):c.1609A>G (p.Ile537Val) SNV Uncertain significance 850387 GRCh37: 6:74192315-74192315
GRCh38: 6:73482592-73482592
35 MTO1 NM_012123.4(MTO1):c.1013G>A (p.Gly338Glu) SNV Uncertain significance 855717 GRCh37: 6:74189733-74189733
GRCh38: 6:73480010-73480010
36 MTO1 NM_012123.4(MTO1):c.1100G>T (p.Gly367Val) SNV Uncertain significance 943984 GRCh37: 6:74189820-74189820
GRCh38: 6:73480097-73480097
37 MTO1 NM_012123.4(MTO1):c.1312T>C (p.Phe438Leu) SNV Uncertain significance 945404 GRCh37: 6:74191814-74191814
GRCh38: 6:73482091-73482091
38 MTO1 NM_012123.4(MTO1):c.1172C>G (p.Thr391Ser) SNV Uncertain significance 958933 GRCh37: 6:74190440-74190440
GRCh38: 6:73480717-73480717
39 MTO1 NM_012123.4(MTO1):c.260G>A (p.Gly87Glu) SNV Uncertain significance 970039 GRCh37: 6:74175974-74175974
GRCh38: 6:73466251-73466251
40 MTO1 NM_012123.4(MTO1):c.1687A>G (p.Lys563Glu) SNV Uncertain significance 1051937 GRCh37: 6:74202006-74202006
GRCh38: 6:73492283-73492283
41 MTO1 NM_012123.4(MTO1):c.736G>C (p.Glu246Gln) SNV Uncertain significance 1052249 GRCh37: 6:74183288-74183288
GRCh38: 6:73473565-73473565
42 MTO1 NM_012123.4(MTO1):c.108C>G (p.His36Gln) SNV Uncertain significance 1057655 GRCh37: 6:74171685-74171685
GRCh38: 6:73461962-73461962
43 MTO1 NM_012123.4(MTO1):c.806A>G (p.Asn269Ser) SNV Uncertain significance 1060685 GRCh37: 6:74183358-74183358
GRCh38: 6:73473635-73473635
44 MTO1 NM_012123.4(MTO1):c.1790A>C (p.Gln597Pro) SNV Uncertain significance 1061859 GRCh37: 6:74207492-74207492
GRCh38: 6:73497769-73497769
45 MTO1 NM_012123.4(MTO1):c.1055C>T (p.Thr352Met) SNV Uncertain significance 996115 GRCh37: 6:74189775-74189775
GRCh38: 6:73480052-73480052
46 MTO1 NM_012123.4(MTO1):c.1339A>G (p.Ile447Val) SNV Uncertain significance 577330 rs747475822 GRCh37: 6:74191841-74191841
GRCh38: 6:73482118-73482118
47 MTO1 NM_012123.4(MTO1):c.1725T>G (p.Cys575Trp) SNV Uncertain significance 837793 GRCh37: 6:74202044-74202044
GRCh38: 6:73492321-73492321
48 MTO1 NM_012123.4(MTO1):c.521G>A (p.Ser174Asn) SNV Uncertain significance 1003326 GRCh37: 6:74176315-74176315
GRCh38: 6:73466592-73466592
49 MTO1 NM_012123.4(MTO1):c.83A>C (p.Asp28Ala) SNV Uncertain significance 1009341 GRCh37: 6:74171660-74171660
GRCh38: 6:73461937-73461937
50 MTO1 NM_012123.4(MTO1):c.1996C>T (p.Arg666Ter) SNV Uncertain significance 547882 rs200217371 GRCh37: 6:74210375-74210375
GRCh38: 6:73500652-73500652

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

72
# 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 MTO1 GTPBP3
2
Show member pathways
11.39 TRMU TRMT5 TRIT1 MTO1 GTPBP3

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 MTO1 MRPS34 MRPL44

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 9.37 MRPS34 MRPL44
2 mitochondrial translational elongation GO:0070125 9.32 MRPS34 MRPL44
3 tRNA modification GO:0006400 9.26 TRIT1 GTPBP3
4 tRNA wobble uridine modification GO:0002098 9.16 MTO1 GTPBP3
5 tRNA methylation GO:0030488 9.13 TRMT5 MTO1 GTPBP3
6 tRNA processing GO:0008033 9.02 TRMU TRMT5 TRIT1 MTO1 GTPBP3

Sources for Combined Oxidative Phosphorylation Deficiency 10

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 20-May-2021)
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 Tocris
70 UMLS
71 UMLS via Orphanet
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