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 57 12 72 29 6 15 70
Coxpd20 57 12 58 72
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®:

57 (Updated 05-Apr-2021)
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® 57 615917
OMIM Phenotypic Series 57 PS609060
MeSH 44 D028361
ICD10 via Orphanet 33 E88.8
Orphanet 58 ORPHA420728
UMLS 70 C4014660

Summaries for Combined Oxidative Phosphorylation Deficiency 20

UniProtKB/Swiss-Prot : 72 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. Related phenotypes are ptosis and ataxia

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 22)
# Related Disease Score Top Affiliating Genes
1 combined oxidative phosphorylation deficiency 2 10.3 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 pontocerebellar hypoplasia, type 6 10.0 RARS2 KARS1
5 charcot-marie-tooth disease, axonal, type 2u 10.0 KARS1 GARS1
6 developmental and epileptic encephalopathy 29 9.9 RARS2 KARS1 GARS1
7 charcot-marie-tooth disease, recessive intermediate b 9.9 YARS2 KARS1 GARS1
8 charcot-marie-tooth disease, axonal, type 2n 9.9 YARS2 KARS1 GARS1
9 charcot-marie-tooth disease intermediate type 9.9 YARS2 KARS1 GARS1
10 combined oxidative phosphorylation deficiency 12 9.9 YARS2 VARS2 VARS1 RARS2
11 charcot-marie-tooth disease, dominant intermediate c 9.9 YARS2 KARS1 GARS1
12 autosomal dominant distal hereditary motor neuronopathy 9.9 YARS2 KARS1 GARS1
13 charcot-marie-tooth disease, axonal, type 2d 9.9 YARS2 KARS1 GARS1
14 pituitary adenoma 1, multiple types 9.9 VARS2 IGFBP3
15 neuronopathy, distal hereditary motor, type va 9.9 YARS2 KARS1 GARS1
16 cohen syndrome 9.9 VPS13B KARS1 AGBL5
17 angelman syndrome due to imprinting defect in 15q11-q13 9.8 UBE3A SNRPN
18 congenital nervous system abnormality 9.7 VPS13B UBE3A RARS2
19 mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes 9.6 YARS2 RARS2 GARS1
20 perrault syndrome 9.5 YARS2 VARS2 VARS1 RARS2 KARS1 GARS1
21 microcephaly 9.2 VPS13B VARS2 VARS1 UBE3A RARS2 KARS1
22 disease of mental health 8.4 VPS13B UBE3A SNRPN SMAD9 KARS1 IGFBP3

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 ptosis 31 occasional (7.5%) HP:0000508
2 ataxia 31 occasional (7.5%) HP:0001251
3 global developmental delay 31 occasional (7.5%) HP:0001263
4 abnormal facial shape 31 occasional (7.5%) HP:0001999
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®:

57 (Updated 05-Apr-2021)
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 (Updated 05-Apr-2021)

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:

46
# Description MGI Source Accession Score Top Affiliating Genes
1 behavior/neurological MP:0005386 9.65 ALDH3A2 GARS1 IGFBP3 KARS1 MRTFA RARS2
2 mortality/aging MP:0010768 9.32 AGBL5 GARS1 KARS1 MRTFA RARS2 SMAD9

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

Publications for Combined Oxidative Phosphorylation Deficiency 20

Articles related to Combined Oxidative Phosphorylation Deficiency 20:

# Title Authors PMID Year
1
VARS2-linked mitochondrial encephalopathy: two case reports enlarging the clinical phenotype. 6 57
31064326 2019
2
Clinical, biochemical, and genetic features associated with VARS2-related mitochondrial disease. 57 6
29314548 2018
3
Neonatal encephalocardiomyopathy caused by mutations in VARS2. 6 57
27502409 2017
4
VARS2 and TARS2 mutations in patients with mitochondrial encephalomyopathies. 6 57
24827421 2014
5
Use of whole-exome sequencing to determine the genetic basis of multiple mitochondrial respiratory chain complex deficiencies. 57 6
25058219 2014
6
The combination of whole-exome sequencing and clinical analysis allows better diagnosis of rare syndromic retinal dystrophies. 61
30925032 2019
7
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 38)
# Gene Name Type Significance ClinVarId dbSNP ID Position
1 VARS2 NM_020442.6(VARS2):c.1456G>T (p.Glu486Ter) SNV Pathogenic 933233 GRCh37: 6:30888503-30888503
GRCh38: 6:30920726-30920726
2 VARS2 NM_020442.6(VARS2):c.2149G>A (p.Ala717Thr) SNV Pathogenic 933235 GRCh37: 6:30890717-30890717
GRCh38: 6:30922940-30922940
3 VARS2 NM_020442.6(VARS2):c.1060G>A (p.Asp354Asn) SNV Pathogenic 933236 GRCh37: 6:30886678-30886678
GRCh38: 6:30918901-30918901
4 VARS2 NM_020442.6(VARS2):c.2758T>C (p.Tyr920His) SNV Pathogenic 997679 GRCh37: 6:30893135-30893135
GRCh38: 6:30925358-30925358
5 VARS2 NM_020442.5(VARS2):c.1045G>A (p.Ala349Thr) SNV Pathogenic 141424 rs587777583 GRCh37: 6:30886663-30886663
GRCh38: 6:30918886-30918886
6 VARS2 NM_020442.5(VARS2):c.1787C>A (p.Ala596Asp) SNV Pathogenic 141426 rs587777584 GRCh37: 6:30889753-30889753
GRCh38: 6:30921976-30921976
7 VARS2 NM_001167734.1(VARS2):c.1100C>T (p.Thr367Ile) SNV Pathogenic 141427 rs587777585 GRCh37: 6:30886628-30886628
GRCh38: 6:30918851-30918851
8 VARS2 NM_020442.6(VARS2):c.2038-1G>A SNV Pathogenic 1032680 GRCh37: 6:30890482-30890482
GRCh38: 6:30922705-30922705
9 VARS2 NM_020442.6(VARS2):c.2467-2A>G SNV Pathogenic 933237 GRCh37: 6:30892129-30892129
GRCh38: 6:30924352-30924352
10 VARS2 NM_020442.6(VARS2):c.1270_1271insA (p.Ser424fs) Insertion Pathogenic 1029201 GRCh37: 6:30887970-30887971
GRCh38: 6:30920193-30920194
11 VARS2 NM_020442.6(VARS2):c.3004C>T (p.Arg1002Ter) SNV Pathogenic 1032684 GRCh37: 6:30893699-30893699
GRCh38: 6:30925922-30925922
12 VARS2 NM_020442.6(VARS2):c.2869_2876dup (p.Leu961fs) Duplication Likely pathogenic 1029203 GRCh37: 6:30893396-30893397
GRCh38: 6:30925619-30925620
13 VARS2 NM_020442.6(VARS2):c.511C>T (p.Arg171Trp) SNV Likely pathogenic 488636 rs139515727 GRCh37: 6:30883762-30883762
GRCh38: 6:30915985-30915985
14 VARS2 NM_020442.5(VARS2):c.1463_1465del (p.Gly488del) Deletion Likely pathogenic 488638 rs1554268077 GRCh37: 6:30888508-30888510
GRCh38: 6:30920731-30920733
15 VARS2 NM_020442.5(VARS2):c.1400G>C (p.Arg467Pro) SNV Likely pathogenic 488637 rs775439829 GRCh37: 6:30888447-30888447
GRCh38: 6:30920670-30920670
16 VARS2 NM_020442.5(VARS2):c.1834_1835del (p.Leu612fs) Deletion Likely pathogenic 802194 rs777028011 GRCh37: 6:30889920-30889921
GRCh38: 6:30922143-30922144
17 VARS2 NM_020442.6(VARS2):c.1168G>A SNV Conflicting interpretations of pathogenicity 522814 rs202201763 GRCh37: 6:30887868-30887868
GRCh38: 6:30920091-30920091
18 VARS2 NM_020442.6(VARS2):c.1400G>A (p.Arg467His) SNV Uncertain significance 933234 GRCh37: 6:30888447-30888447
GRCh38: 6:30920670-30920670
19 VARS2 NM_020442.5(VARS2):c.1691C>T (p.Ala564Val) SNV Uncertain significance 809891 rs143408155 GRCh37: 6:30889424-30889424
GRCh38: 6:30921647-30921647
20 VARS2 NM_020442.6(VARS2):c.1637A>T (p.Glu546Val) SNV Uncertain significance 915300 GRCh37: 6:30889370-30889370
GRCh38: 6:30921593-30921593
21 VARS2 NM_001167734.1(VARS2):c.1076-14A>G SNV Uncertain significance 522815 rs1297230026 GRCh37: 6:30886590-30886590
GRCh38: 6:30918813-30918813
22 VARS2 NM_001167734.1(VARS2):c.3110A>G (p.Gln1037Arg) SNV Uncertain significance 638479 rs773482888 GRCh37: 6:30893715-30893715
GRCh38: 6:30925938-30925938
23 VARS2 NM_001167734.1(VARS2):c.194A>G (p.His65Arg) SNV Uncertain significance 638480 rs199534441 GRCh37: 6:30882717-30882717
GRCh38: 6:30914940-30914940
24 VARS2 NM_020442.6(VARS2):c.3005G>A (p.Arg1002Gln) SNV Uncertain significance 1029204 GRCh37: 6:30893700-30893700
GRCh38: 6:30925923-30925923
25 VARS2 NM_020442.6(VARS2):c.275A>G (p.Glu92Gly) SNV Uncertain significance 1029205 GRCh37: 6:30883006-30883006
GRCh38: 6:30915229-30915229
26 VARS2 NM_020442.6(VARS2):c.631C>T (p.Arg211Trp) SNV Uncertain significance 1029206 GRCh37: 6:30883986-30883986
GRCh38: 6:30916209-30916209
27 VARS2 NM_020442.6(VARS2):c.1954C>T (p.Arg652Trp) SNV Uncertain significance 1032679 GRCh37: 6:30890248-30890248
GRCh38: 6:30922471-30922471
28 VARS2 NM_020442.6(VARS2):c.142C>G (p.Gln48Glu) SNV Uncertain significance 1032681 GRCh37: 6:30882755-30882755
GRCh38: 6:30914978-30914978
29 VARS2 NM_001167734.1(VARS2):c.2641C>T (p.Arg881Cys) SNV Uncertain significance 445608 rs138855624 GRCh37: 6:30892215-30892215
GRCh38: 6:30924438-30924438
30 VARS2 NM_020442.6(VARS2):c.2624C>T (p.Pro875Leu) SNV Uncertain significance 1032682 GRCh37: 6:30892288-30892288
GRCh38: 6:30924511-30924511
31 VARS2 NM_020442.6(VARS2):c.2684G>A (p.Arg895His) SNV Uncertain significance 1032683 GRCh37: 6:30893061-30893061
GRCh38: 6:30925284-30925284
32 VARS2 NM_020442.6(VARS2):c.3092T>G (p.Leu1031Arg) SNV Uncertain significance 1032685 GRCh37: 6:30893887-30893887
GRCh38: 6:30926110-30926110
33 VARS2 NM_020442.6(VARS2):c.736T>C (p.Cys246Arg) SNV Uncertain significance 1032686 GRCh37: 6:30884719-30884719
GRCh38: 6:30916942-30916942
34 VARS2 NM_020442.6(VARS2):c.2501G>A (p.Arg834His) SNV Uncertain significance 1029202 GRCh37: 6:30892165-30892165
GRCh38: 6:30924388-30924388
35 VARS2 NM_001167734.1(VARS2):c.1435T>C (p.Trp479Arg) SNV Benign 380154 rs2249464 GRCh37: 6:30888161-30888161
GRCh38: 6:30920384-30920384
36 VARS2 NM_001167734.1(VARS2):c.2128G>T (p.Val710Leu) SNV Benign 380157 rs2074506 GRCh37: 6:30890483-30890483
GRCh38: 6:30922706-30922706
37 VARS2 NM_001167734.1(VARS2):c.2840G>A (p.Arg947Gln) SNV Benign 380161 rs9394021 GRCh37: 6:30893127-30893127
GRCh38: 6:30925350-30925350
38 VARS2 NM_001167734.1(VARS2):c.1940C>T (p.Thr647Met) SNV not provided 373702 rs367837827 GRCh37: 6:30889936-30889936
GRCh38: 6:30922159-30922159

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

72
# 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 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
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-Apr-2021)
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 Tocris
70 UMLS
71 UMLS via Orphanet
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