COXPD20
MCID: CMB052
MIFTS: 38

Combined Oxidative Phosphorylation Deficiency 20 (COXPD20)

Categories: Genetic diseases, Metabolic diseases, Neuronal diseases, Rare diseases

Aliases & Classifications for Combined Oxidative Phosphorylation Deficiency 20

MalaCards integrated aliases for Combined Oxidative Phosphorylation Deficiency 20:

Name: Combined Oxidative Phosphorylation Deficiency 20 56 12 73 29 6 15 71
Coxpd20 56 12 58 73
Oxidative Phosphorylation Deficiency, Combined, Type 20 39
Combined Oxidative Phosphorylation Defect Type 20 58

Characteristics:

Orphanet epidemiological data:

58
combined oxidative phosphorylation defect type 20
Inheritance: Autosomal recessive; Prevalence: <1/1000000 (Worldwide); Age of onset: Infancy;

OMIM:

56
Inheritance:
autosomal recessive

Miscellaneous:
onset in infancy
variable features
two unrelated patients have been reported (last curated july 2014)


HPO:

31
combined oxidative phosphorylation deficiency 20:
Inheritance autosomal recessive inheritance
Onset and clinical course infantile onset


Classifications:

Orphanet: 58  
Rare neurological diseases
Inborn errors of metabolism


External Ids:

Disease Ontology 12 DOID:0111478
OMIM 56 615917
OMIM Phenotypic Series 56 PS609060
MeSH 43 D028361
ICD10 via Orphanet 33 E88.8
Orphanet 58 ORPHA420728
UMLS 71 C4014660

Summaries for Combined Oxidative Phosphorylation Deficiency 20

UniProtKB/Swiss-Prot : 73 Combined oxidative phosphorylation deficiency 20: A disorder due to mitochondrial respiratory chain complex defects. Clinical features are variable and include muscle weakness with hypotonia, central neurological disease with progressive external ophthalmoplegia, ptosis and ataxia, delayed psychomotor development, cardiomyopathy, abnormal liver function, facial dysmorphism, microcephaly and epilepsy.

MalaCards based summary : Combined Oxidative Phosphorylation Deficiency 20, also known as coxpd20, is related to combined oxidative phosphorylation deficiency 2 and neurodevelopmental disorder with microcephaly, seizures, and cortical atrophy. An important gene associated with Combined Oxidative Phosphorylation Deficiency 20 is VARS2 (Valyl-TRNA Synthetase 2, Mitochondrial), and among its related pathways/superpathways are Gene Expression and tRNA Aminoacylation. Affiliated tissues include liver, and related phenotypes are global developmental delay and abnormal facial shape

Disease Ontology : 12 A combined oxidative phosphorylation deficiency that has material basis in homozygous or compound heterozygous mutation in VARS2 on chromosome 6p21.33.

More information from OMIM: 615917 PS609060

Related Diseases for Combined Oxidative Phosphorylation Deficiency 20

Diseases related to Combined Oxidative Phosphorylation Deficiency 20 via text searches within MalaCards or GeneCards Suite gene sharing:

(show all 20)
# Related Disease Score Top Affiliating Genes
1 combined oxidative phosphorylation deficiency 2 10.4 VARS2 VARS1
2 neurodevelopmental disorder with microcephaly, seizures, and cortical atrophy 10.2 VARS2 VARS1
3 deafness, autosomal recessive 89 10.0 RARS2 KARS1
4 charcot-marie-tooth disease, axonal, type 2u 9.9 KARS1 GARS1
5 pontocerebellar hypoplasia, type 6 9.9 RARS2 KARS1 GARS1
6 charcot-marie-tooth disease, recessive intermediate b 9.9 YARS2 KARS1 GARS1
7 charcot-marie-tooth disease, axonal, type 2n 9.9 YARS2 KARS1 GARS1
8 combined oxidative phosphorylation deficiency 12 9.8 YARS2 VARS2 VARS1 RARS2
9 epileptic encephalopathy, early infantile, 29 9.8 RARS2 KARS1 GARS1
10 charcot-marie-tooth disease intermediate type 9.8 YARS2 KARS1 GARS1
11 charcot-marie-tooth disease, dominant intermediate c 9.8 YARS2 KARS1 GARS1
12 charcot-marie-tooth disease, axonal, type 2d 9.8 YARS2 KARS1 GARS1
13 autosomal dominant distal hereditary motor neuronopathy 9.8 YARS2 KARS1 GARS1
14 robinow syndrome, autosomal recessive 1 9.7 RARS2 KARS1
15 mitochondrial metabolism disease 9.7 YARS2 VARS2 VARS1 RARS2
16 angelman syndrome due to imprinting defect in 15q11-q13 9.7 UBE3A SNRPN
17 neuronopathy, distal hereditary motor, type va 9.6 YARS2 RARS2 KARS1 GARS1
18 mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes 9.6 YARS2 RARS2 GARS1
19 perrault syndrome 9.3 YARS2 VARS2 VARS1 RARS2 KARS1 GARS1
20 microcephaly 9.1 VPS13B VARS2 VARS1 UBE3A KARS1

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



Diseases related to Combined Oxidative Phosphorylation Deficiency 20

Symptoms & Phenotypes for Combined Oxidative Phosphorylation Deficiency 20

Human phenotypes related to Combined Oxidative Phosphorylation Deficiency 20:

31 (show all 8)
# Description HPO Frequency HPO Source Accession
1 global developmental delay 31 occasional (7.5%) HP:0001263
2 abnormal facial shape 31 occasional (7.5%) HP:0001999
3 ataxia 31 occasional (7.5%) HP:0001251
4 ptosis 31 occasional (7.5%) HP:0000508
5 progressive external ophthalmoplegia 31 occasional (7.5%) HP:0000590
6 seizure 31 occasional (7.5%) HP:0001250
7 microcephaly 31 HP:0000252
8 generalized hypotonia 31 HP:0001290

Symptoms via clinical synopsis from OMIM:

56
Muscle Soft Tissue:
hypotonia
mitochondrial complex i deficiency
muscle biopsy may show deficiency of multiple mitochondrial respiratory complexes

Head And Neck Head:
microcephaly (1 patient)

Head And Neck Eyes:
ptosis (1 patient)
progressive external ophthalmoplegia (1 patient)

Neurologic Central Nervous System:
seizures (1 patient)
delayed psychomotor development (1 patient)
ataxia (1 patient)
white matter abnormalities in the periventricular regions (1 patient)

Head And Neck Face:
facial dysmorphism (1 patient)

Clinical features from OMIM:

615917

GenomeRNAi Phenotypes related to Combined Oxidative Phosphorylation Deficiency 20 according to GeneCards Suite gene sharing:

26
# Description GenomeRNAi Source Accession Score Top Affiliating Genes
1 Reduced mammosphere formation GR00396-S 9.1 GARS1 IGFBP3 KARS1 VARS1 VARS2 YARS2

MGI Mouse Phenotypes related to Combined Oxidative Phosphorylation Deficiency 20:

45
# Description MGI Source Accession Score Top Affiliating Genes
1 behavior/neurological MP:0005386 9.65 ALDH3A2 GARS1 IGFBP3 KARS1 MRTFA RARS2
2 growth/size/body region MP:0005378 9.28 GARS1 IGFBP3 KARS1 MRTFA SMAD9 SNRPN

Drugs & Therapeutics for Combined Oxidative Phosphorylation Deficiency 20

Search Clinical Trials , NIH Clinical Center for Combined Oxidative Phosphorylation Deficiency 20

Genetic Tests for Combined Oxidative Phosphorylation Deficiency 20

Genetic tests related to Combined Oxidative Phosphorylation Deficiency 20:

# Genetic test Affiliating Genes
1 Combined Oxidative Phosphorylation Deficiency 20 29 VARS2

Anatomical Context for Combined Oxidative Phosphorylation Deficiency 20

MalaCards organs/tissues related to Combined Oxidative Phosphorylation Deficiency 20:

40
Liver

Publications for Combined Oxidative Phosphorylation Deficiency 20

Articles related to Combined Oxidative Phosphorylation Deficiency 20:

# Title Authors PMID Year
1
VARS2 and TARS2 mutations in patients with mitochondrial encephalomyopathies. 56 6
24827421 2014
2
Use of whole-exome sequencing to determine the genetic basis of multiple mitochondrial respiratory chain complex deficiencies. 6 56
25058219 2014
3
The combination of whole-exome sequencing and clinical analysis allows better diagnosis of rare syndromic retinal dystrophies. 61
30925032 2019
4
Mitochondrial Encephalopathy: First Portuguese Report of a VARS2 Causative Variant. 61
29478218 2018

Variations for Combined Oxidative Phosphorylation Deficiency 20

ClinVar genetic disease variations for Combined Oxidative Phosphorylation Deficiency 20:

6 (show all 16) ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎
# Gene Name Type Significance ClinVarId dbSNP ID GRCh37 Pos GRCh38 Pos
1 VARS2 NM_020442.5(VARS2):c.1045G>A (p.Ala349Thr)SNV Pathogenic 141424 rs587777583 6:30886663-30886663 6:30918886-30918886
2 VARS2 NM_020442.5(VARS2):c.1787C>A (p.Ala596Asp)SNV Pathogenic 141426 rs587777584 6:30889753-30889753 6:30921976-30921976
3 VARS2 NM_001167734.1(VARS2):c.1100C>T (p.Thr367Ile)SNV Pathogenic 141427 rs587777585 6:30886628-30886628 6:30918851-30918851
4 VARS2 NM_001167734.1(VARS2):c.601C>T (p.Arg201Trp)SNV Likely pathogenic 488636 rs139515727 6:30883762-30883762 6:30915985-30915985
5 VARS2 NM_020442.5(VARS2):c.1400G>C (p.Arg467Pro)SNV Likely pathogenic 488637 rs775439829 6:30888447-30888447 6:30920670-30920670
6 VARS2 NM_020442.5(VARS2):c.1463_1465del (p.Gly488del)deletion Likely pathogenic 488638 rs1554268077 6:30888508-30888510 6:30920731-30920733
7 VARS2 NM_020442.5(VARS2):c.1834_1835del (p.Leu612fs)deletion Likely pathogenic 802194 6:30889920-30889921 6:30922143-30922144
8 VARS2 NM_001167734.1(VARS2):c.1258G>A (p.Ala420Thr)SNV Conflicting interpretations of pathogenicity 522814 rs202201763 6:30887868-30887868 6:30920091-30920091
9 VARS2 NM_001167734.1(VARS2):c.194A>G (p.His65Arg)SNV Uncertain significance 638480 6:30882717-30882717 6:30914940-30914940
10 VARS2 NM_001167734.1(VARS2):c.3110A>G (p.Gln1037Arg)SNV Uncertain significance 638479 6:30893715-30893715 6:30925938-30925938
11 VARS2 NM_020442.6(VARS2):c.1637A>T (p.Glu546Val)SNV Uncertain significance 915300 6:30889370-30889370 6:30921593-30921593
12 VARS2 NM_001167734.1(VARS2):c.1076-14A>GSNV Uncertain significance 522815 rs1297230026 6:30886590-30886590 6:30918813-30918813
13 VARS2 NM_001167734.1(VARS2):c.1940C>T (p.Thr647Met)SNV Uncertain significance 373702 rs367837827 6:30889936-30889936 6:30922159-30922159
14 VARS2 NM_001167734.1(VARS2):c.2840G>A (p.Arg947Gln)SNV Benign 380161 rs9394021 6:30893127-30893127 6:30925350-30925350
15 VARS2 NM_001167734.1(VARS2):c.2128G>T (p.Val710Leu)SNV Benign 380157 rs2074506 6:30890483-30890483 6:30922706-30922706
16 VARS2 NM_001167734.1(VARS2):c.1435T>C (p.Trp479Arg)SNV Benign 380154 rs2249464 6:30888161-30888161 6:30920384-30920384

UniProtKB/Swiss-Prot genetic disease variations for Combined Oxidative Phosphorylation Deficiency 20:

73
# Symbol AA change Variation ID SNP ID
1 VARS2 p.Thr337Ile VAR_071850 rs587777585
2 VARS2 p.Ala349Thr VAR_071851 rs587777583
3 VARS2 p.Ala596Asp VAR_071852 rs587777584

Expression for Combined Oxidative Phosphorylation Deficiency 20

Search GEO for disease gene expression data for Combined Oxidative Phosphorylation Deficiency 20.

Pathways for Combined Oxidative Phosphorylation Deficiency 20

Pathways related to Combined Oxidative Phosphorylation Deficiency 20 according to GeneCards Suite gene sharing:

# Super pathways Score Top Affiliating Genes
1
Show member pathways
12.99 YARS2 VARS2 VARS1 SNRPN RARS2 KARS1
2
Show member pathways
11.34 YARS2 VARS2 VARS1 RARS2 KARS1 GARS1

GO Terms for Combined Oxidative Phosphorylation Deficiency 20

Cellular components related to Combined Oxidative Phosphorylation Deficiency 20 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 cytosol GO:0005829 9.61 YARS2 VARS2 VARS1 UBE3A SMAD9 MRTFA
2 mitochondrial matrix GO:0005759 8.92 YARS2 RARS2 KARS1 GARS1

Biological processes related to Combined Oxidative Phosphorylation Deficiency 20 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 translation GO:0006412 9.43 YARS2 VARS2 VARS1 RARS2 KARS1 GARS1
2 aminoacyl-tRNA metabolism involved in translational fidelity GO:0106074 9.32 VARS2 VARS1
3 diadenosine tetraphosphate biosynthetic process GO:0015966 9.26 KARS1 GARS1
4 valyl-tRNA aminoacylation GO:0006438 9.16 VARS2 VARS1
5 tRNA aminoacylation for protein translation GO:0006418 9.1 YARS2 VARS2 VARS1 RARS2 KARS1 GARS1

Molecular functions related to Combined Oxidative Phosphorylation Deficiency 20 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 nucleotide binding GO:0000166 9.85 YARS2 VARS2 VARS1 RARS2 KARS1 GARS1
2 ATP binding GO:0005524 9.8 YARS2 VARS2 VARS1 RARS2 KARS1 GARS1
3 ligase activity GO:0016874 9.5 YARS2 VARS2 VARS1 UBE3A RARS2 KARS1
4 aminoacyl-tRNA editing activity GO:0002161 9.26 VARS2 VARS1
5 valine-tRNA ligase activity GO:0004832 9.16 VARS2 VARS1
6 aminoacyl-tRNA ligase activity GO:0004812 9.1 YARS2 VARS2 VARS1 RARS2 KARS1 GARS1

Sources for Combined Oxidative Phosphorylation Deficiency 20

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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