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 73 29 13 6 15 71
Coxpd10 57 12 58 73
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 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®:

57 (Updated 05-Mar-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 05-Mar-2021)

MalaCards based summary : Combined Oxidative Phosphorylation Deficiency 10, also known as coxpd10, is related to queensland tick typhus and deafness, autosomal recessive 26. 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 : 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 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 05-Mar-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 05-Mar-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
MTO1 mutations are associated with hypertrophic cardiomyopathy and lactic acidosis and cause respiratory chain deficiency in humans and yeast. 6 57
23929671 2013
2
Mutations of the mitochondrial-tRNA modifier MTO1 cause hypertrophic cardiomyopathy and lactic acidosis. 6 57
22608499 2012
3
The genotypic and phenotypic spectrum of MTO1 deficiency. 57 61
29331171 2018

Variations for Combined Oxidative Phosphorylation Deficiency 10

ClinVar genetic disease variations for Combined Oxidative Phosphorylation Deficiency 10:

6 (show top 50) (show all 82)
# Gene Name Type Significance ClinVarId dbSNP ID GRCh37 Pos GRCh38 Pos
1 MTO1 NM_012123.4(MTO1):c.1232C>T (p.Thr411Ile) SNV Pathogenic 89038 rs398122419 6:74190500-74190500 6:73480777-73480777
2 MTO1 NM_012123.4(MTO1):c.97del (p.Arg33fs) Deletion Pathogenic 638475 rs1582666067 6:74171671-74171671 6:73461948-73461948
3 MTO1 NM_012123.4(MTO1):c.1324C>T (p.Arg442Ter) SNV Pathogenic 445467 rs200583827 6:74191826-74191826 6:73482103-73482103
4 MTO1 NM_012123.4(MTO1):c.1822del (p.Leu608fs) Deletion Pathogenic 574880 rs1561954433 6:74207524-74207524 6:73497801-73497801
5 MTO1 NM_012123.4(MTO1):c.1858dup (p.Arg620fs) Duplication Pathogenic 35495 rs397518449 6:74207559-74207560 6:73497836-73497837
6 MTO1 NM_012123.4(MTO1):c.1282G>A (p.Ala428Thr) SNV 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.1201C>T (p.Arg401Ter) SNV Pathogenic/Likely pathogenic 840849 6:74190469-74190469 6:73480746-73480746
9 MTO1 NM_012123.4(MTO1):c.153_174del (p.Thr53fs) Deletion Likely pathogenic 931370 6:74171728-74171749 6:73462005-73462026
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>G SNV Likely pathogenic 488552 rs1275100093 6:74191758-74191758 6:73482035-73482035
12 MTO1 NM_012123.4(MTO1):c.938G>A (p.Arg313Gln) SNV Likely pathogenic 488550 rs371179032 6:74189567-74189567 6:73479844-73479844
13 MTO1 NM_012123.4(MTO1):c.1429C>T (p.Arg477Cys) SNV Likely pathogenic 488553 rs1033653237 6:74191931-74191931 6:73482208-73482208
14 MTO1 NM_012123.4(MTO1):c.1390C>T (p.Arg464Cys) SNV Likely pathogenic 937542 6:74191892-74191892 6:73482169-73482169
15 MTO1 NM_012123.4(MTO1):c.417+2T>C SNV Likely pathogenic 834420 6:74176133-74176133 6:73466410-73466410
16 MTO1 NM_012123.4(MTO1):c.1450C>T (p.Arg484Trp) SNV Conflicting interpretations of pathogenicity 408272 rs748152539 6:74191952-74191952 6:73482229-73482229
17 MTO1 NM_012123.4(MTO1):c.1325G>A (p.Arg442Gln) SNV Conflicting interpretations of pathogenicity 807632 rs765548847 6:74191827-74191827 6:73482104-73482104
18 MTO1 NM_012123.4(MTO1):c.623A>G (p.His208Arg) SNV Uncertain significance 575110 rs560308812 6:74183175-74183175 6:73473452-73473452
19 MTO1 NM_012123.4(MTO1):c.1340T>C (p.Ile447Thr) SNV Uncertain significance 941436 6:74191842-74191842 6:73482119-73482119
20 MTO1 NM_012123.4(MTO1):c.1100G>T (p.Gly367Val) SNV Uncertain significance 943984 6:74189820-74189820 6:73480097-73480097
21 MTO1 NM_012123.4(MTO1):c.1312T>C (p.Phe438Leu) SNV Uncertain significance 945404 6:74191814-74191814 6:73482091-73482091
22 MTO1 NM_012123.4(MTO1):c.115G>A (p.Val39Met) SNV Uncertain significance 950281 6:74171692-74171692 6:73461969-73461969
23 MTO1 NM_012123.4(MTO1):c.2006C>T (p.Ser669Leu) SNV Uncertain significance 958454 6:74210385-74210385 6:73500662-73500662
24 MTO1 NM_012123.4(MTO1):c.1172C>G (p.Thr391Ser) SNV Uncertain significance 958933 6:74190440-74190440 6:73480717-73480717
25 MTO1 NM_012123.4(MTO1):c.260G>A (p.Gly87Glu) SNV Uncertain significance 970039 6:74175974-74175974 6:73466251-73466251
26 MTO1 NM_012123.4(MTO1):c.994G>A (p.Val332Ile) SNV Uncertain significance 971633 6:74189714-74189714 6:73479991-73479991
27 MTO1 NM_012123.4(MTO1):c.2036A>G (p.Gln679Arg) SNV Uncertain significance 540424 rs1418465267 6:74210415-74210415 6:73500692-73500692
28 MTO1 NM_012123.4(MTO1):c.1934G>A (p.Arg645His) SNV Uncertain significance 567850 rs758448974 6:74210313-74210313 6:73500590-73500590
29 MTO1 NM_012123.4(MTO1):c.1480G>A (p.Gly494Ser) SNV Uncertain significance 569553 rs139449947 6:74192186-74192186 6:73482463-73482463
30 MTO1 NM_012123.4(MTO1):c.1391G>A (p.Arg464His) SNV Uncertain significance 835604 6:74191893-74191893 6:73482170-73482170
31 MTO1 NM_012123.4(MTO1):c.1725T>G (p.Cys575Trp) SNV Uncertain significance 837793 6:74202044-74202044 6:73492321-73492321
32 MTO1 NM_012123.4(MTO1):c.476T>C (p.Ile159Thr) SNV Uncertain significance 845336 6:74176270-74176270 6:73466547-73466547
33 MTO1 NM_012123.4(MTO1):c.535+5G>A SNV Uncertain significance 846664 6:74176334-74176334 6:73466611-73466611
34 MTO1 NM_012123.4(MTO1):c.1609A>G (p.Ile537Val) SNV Uncertain significance 850387 6:74192315-74192315 6:73482592-73482592
35 MTO1 NM_012123.4(MTO1):c.868A>G (p.Arg290Gly) SNV Uncertain significance 851199 6:74189497-74189497 6:73479774-73479774
36 MTO1 NM_012123.4(MTO1):c.1292G>A (p.Arg431Gln) SNV Uncertain significance 852190 6:74191794-74191794 6:73482071-73482071
37 MTO1 NM_012123.4(MTO1):c.1013G>A (p.Gly338Glu) SNV Uncertain significance 855717 6:74189733-74189733 6:73480010-73480010
38 MTO1 NM_012123.4(MTO1):c.1868C>T (p.Ser623Phe) SNV Uncertain significance 859840 6:74207570-74207570 6:73497847-73497847
39 MTO1 NM_012123.4(MTO1):c.203G>A (p.Arg68His) SNV Uncertain significance 863267 6:74171780-74171780 6:73462057-73462057
40 MTO1 NM_012123.4(MTO1):c.1222A>G (p.Ile408Val) SNV Uncertain significance 240846 rs149407452 6:74190490-74190490 6:73480767-73480767
41 MTO1 NM_012123.4(MTO1):c.1717A>T (p.Thr573Ser) SNV Uncertain significance 240848 rs774500449 6:74202036-74202036 6:73492313-73492313
42 MTO1 NM_012123.4(MTO1):c.547A>G (p.Thr183Ala) SNV Uncertain significance 408274 rs779108851 6:74183099-74183099 6:73473376-73473376
43 MTO1 NM_012123.4(MTO1):c.61C>T (p.Pro21Ser) SNV Uncertain significance 408277 rs753873871 6:74171638-74171638 6:73461915-73461915
44 MTO1 NM_012123.4(MTO1):c.70C>T (p.Arg24Trp) SNV Uncertain significance 408275 rs368723563 6:74171647-74171647 6:73461924-73461924
45 MTO1 NM_012123.4(MTO1):c.1291C>T (p.Arg431Trp) SNV Uncertain significance 408273 rs748328322 6:74191793-74191793 6:73482070-73482070
46 MTO1 NM_012123.4(MTO1):c.1194G>T (p.Leu398Phe) SNV Uncertain significance 408276 rs772209676 6:74190462-74190462 6:73480739-73480739
47 MTO1 NM_012123.4(MTO1):c.983G>A (p.Arg328His) SNV Uncertain significance 473197 rs142148270 6:74189703-74189703 6:73479980-73479980
48 MTO1 NM_012123.4(MTO1):c.1129+246G>A SNV Uncertain significance 638476 rs118010902 6:74190095-74190095 6:73480372-73480372
49 MTO1 NM_012123.4(MTO1):c.1510G>A (p.Ala504Thr) SNV Uncertain significance 641163 rs761290955 6:74192216-74192216 6:73482493-73482493
50 MTO1 NM_012123.4(MTO1):c.1906C>T (p.Arg636Cys) SNV Uncertain significance 648030 rs1582701948 6:74207608-74207608 6:73497885-73497885

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 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 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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