COXPD27
MCID: CMB071
MIFTS: 28

Combined Oxidative Phosphorylation Deficiency 27 (COXPD27)

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

Aliases & Classifications for Combined Oxidative Phosphorylation Deficiency 27

MalaCards integrated aliases for Combined Oxidative Phosphorylation Deficiency 27:

Name: Combined Oxidative Phosphorylation Deficiency 27 57 12 72 29 6
Coxpd27 57 12 58 72
Combined Oxidative Phosphorylation Defect Type 27 58 17

Characteristics:

OMIM®:

57 (Updated 05-Apr-2021)
Inheritance:
autosomal recessive

Miscellaneous:
two unrelated families have been reported (last curated december 2015)
family a has 2 sibs born of consanguineous turkish parents with a milder phenotype with onset in childhood
patient b is 1 child born of unrelated scandinavian parents with a more severe phenotype with onset in the neonatal period


HPO:

31
combined oxidative phosphorylation deficiency 27:
Inheritance autosomal recessive inheritance


Classifications:

Orphanet: 58  
Rare neurological diseases
Inborn errors of metabolism


Summaries for Combined Oxidative Phosphorylation Deficiency 27

UniProtKB/Swiss-Prot : 72 Combined oxidative phosphorylation deficiency 27: An autosomal recessive mitochondrial disorder characterized by multiple mitochondrial respiratory-chain-complex deficiencies causing neurological regression, progressive cognitive decline, complex movement disorder, epileptic encephalopathy, progressive spastic tetraparesis, and progressive impairment of vision and hearing.

MalaCards based summary : Combined Oxidative Phosphorylation Deficiency 27, is also known as coxpd27. An important gene associated with Combined Oxidative Phosphorylation Deficiency 27 is CARS2 (Cysteinyl-TRNA Synthetase 2, Mitochondrial). Affiliated tissues include eye, and related phenotypes are intellectual disability and developmental regression

Disease Ontology : 12 A combined oxidative phosphorylation deficiency that has material basis in homozygous or compound heterozygous mutation in CARS2 on chromosome 13q34.

More information from OMIM: 616672 PS609060

Related Diseases for Combined Oxidative Phosphorylation Deficiency 27

Symptoms & Phenotypes for Combined Oxidative Phosphorylation Deficiency 27

Human phenotypes related to Combined Oxidative Phosphorylation Deficiency 27:

58 31 (show all 44)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 intellectual disability 58 31 frequent (33%) Frequent (79-30%) HP:0001249
2 developmental regression 58 31 frequent (33%) Frequent (79-30%) HP:0002376
3 hearing impairment 58 31 frequent (33%) Frequent (79-30%) HP:0000365
4 global developmental delay 58 31 frequent (33%) Frequent (79-30%) HP:0001263
5 progressive visual loss 58 31 frequent (33%) Frequent (79-30%) HP:0000529
6 ragged-red muscle fibers 58 31 frequent (33%) Frequent (79-30%) HP:0003200
7 increased serum lactate 58 31 occasional (7.5%) Frequent (79-30%) HP:0002151
8 decreased activity of mitochondrial complex i 58 31 frequent (33%) Frequent (79-30%) HP:0011923
9 status epilepticus 58 31 frequent (33%) Frequent (79-30%) HP:0002133
10 tetraparesis 58 31 frequent (33%) Frequent (79-30%) HP:0002273
11 epileptic encephalopathy 58 31 frequent (33%) Frequent (79-30%) HP:0200134
12 diffuse cerebral atrophy 58 31 frequent (33%) Frequent (79-30%) HP:0002506
13 multifocal seizures 58 31 frequent (33%) Frequent (79-30%) HP:0031165
14 decreased activity of mitochondrial complex iii 58 31 frequent (33%) Frequent (79-30%) HP:0011924
15 decreased activity of mitochondrial complex iv 58 31 frequent (33%) Frequent (79-30%) HP:0008347
16 generalized myoclonic seizure 31 frequent (33%) HP:0002123
17 dysphagia 58 31 occasional (7.5%) Occasional (29-5%) HP:0002015
18 absent speech 58 31 occasional (7.5%) Occasional (29-5%) HP:0001344
19 hypoplasia of the corpus callosum 58 31 occasional (7.5%) Occasional (29-5%) HP:0002079
20 autistic behavior 58 31 occasional (7.5%) Occasional (29-5%) HP:0000729
21 nonimmune hydrops fetalis 58 31 occasional (7.5%) Occasional (29-5%) HP:0001790
22 pain 58 31 occasional (7.5%) Occasional (29-5%) HP:0012531
23 diffuse cerebellar atrophy 58 31 occasional (7.5%) Occasional (29-5%) HP:0100275
24 upper limb postural tremor 58 31 occasional (7.5%) Occasional (29-5%) HP:0007351
25 hypoplastic hippocampus 58 31 occasional (7.5%) Occasional (29-5%) HP:0025517
26 nasogastric tube feeding 58 31 occasional (7.5%) Occasional (29-5%) HP:0040288
27 eeg with periodic lateralized epileptiform discharges 58 31 occasional (7.5%) Occasional (29-5%) HP:0010853
28 failure to thrive 31 HP:0001508
29 chorea 31 HP:0002072
30 visual impairment 31 HP:0000505
31 myoclonus 31 HP:0001336
32 generalized myoclonic seizures 58 Frequent (79-30%)
33 areflexia 31 HP:0001284
34 involuntary movements 58 Occasional (29-5%)
35 dystonia 31 HP:0001332
36 severe muscular hypotonia 31 HP:0006829
37 cerebellar hypoplasia 31 HP:0001321
38 feeding difficulties 31 HP:0011968
39 cerebral atrophy 31 HP:0002059
40 postnatal microcephaly 31 HP:0005484
41 abnormality of the cerebral white matter 58 Frequent (79-30%)
42 multifocal epileptiform discharges 31 HP:0010841
43 opisthotonus 31 HP:0002179
44 microvesicular hepatic steatosis 31 HP:0001414

Symptoms via clinical synopsis from OMIM®:

57 (Updated 05-Apr-2021)
Neurologic Central Nervous System:
cerebral atrophy
myoclonic epilepsy
white matter abnormalities
delayed psychomotor development (patient b)
cerebellar hypoplasia (patient b)
more
Growth Other:
failure to thrive (patient b)

Head And Neck Ears:
hearing impairment, progressive (family a)

Abdomen Liver:
combined mitochondrial respiratory chain deficiency (patient b)
microvesicular steatosis (patient b)

Muscle Soft Tissue:
hypotonia, severe (patient b)
lack of antigravity movements (patient b)
decreased mitochondrial respiratory chain enzyme activity (patient b)

Laboratory Abnormalities:
increased serum lactate (in some patients)

Head And Neck Head:
microcephaly, postnatal (patient b)

Head And Neck Eyes:
visual impairment, progressive (family a)
oculogyric crises (patient b)
no purposeful eye movements (patient b)

Abdomen Gastrointestinal:
feeding difficulties (patient b)

Neurologic Peripheral Nervous System:
areflexia (patient b)

Clinical features from OMIM®:

616672 (Updated 05-Apr-2021)

Drugs & Therapeutics for Combined Oxidative Phosphorylation Deficiency 27

Search Clinical Trials , NIH Clinical Center for Combined Oxidative Phosphorylation Deficiency 27

Genetic Tests for Combined Oxidative Phosphorylation Deficiency 27

Genetic tests related to Combined Oxidative Phosphorylation Deficiency 27:

# Genetic test Affiliating Genes
1 Combined Oxidative Phosphorylation Deficiency 27 29 CARS2

Anatomical Context for Combined Oxidative Phosphorylation Deficiency 27

MalaCards organs/tissues related to Combined Oxidative Phosphorylation Deficiency 27:

40
Eye

Publications for Combined Oxidative Phosphorylation Deficiency 27

Articles related to Combined Oxidative Phosphorylation Deficiency 27:

# Title Authors PMID Year
1
Mutations in the mitochondrial cysteinyl-tRNA synthase gene, CARS2, lead to a severe epileptic encephalopathy and complex movement disorder. 6 57
25787132 2015
2
A homozygous splice-site mutation in CARS2 is associated with progressive myoclonic epilepsy. 57 6
25361775 2014

Variations for Combined Oxidative Phosphorylation Deficiency 27

ClinVar genetic disease variations for Combined Oxidative Phosphorylation Deficiency 27:

6 (show top 50) (show all 246)
# Gene Name Type Significance ClinVarId dbSNP ID Position
1 CARS2 NM_024537.4(CARS2):c.752C>T (p.Pro251Leu) SNV Pathogenic 218178 rs557671802 GRCh37: 13:111329354-111329354
GRCh38: 13:110677007-110677007
2 CARS2 NM_024537.4(CARS2):c.649_651del (p.Glu217del) Deletion Pathogenic 218177 rs753472937 GRCh37: 13:111335402-111335404
GRCh38: 13:110683055-110683057
3 CARS2 NM_024537.4(CARS2):c.1360dup (p.Ile454fs) Duplication Pathogenic 521824 rs1555342802 GRCh37: 13:111296787-111296788
GRCh38: 13:110644440-110644441
4 CARS2 NM_024537.4(CARS2):c.655G>A (p.Ala219Thr) SNV Pathogenic 180135 rs727505361 GRCh37: 13:111335398-111335398
GRCh38: 13:110683051-110683051
5 CARS2 NM_024537.4(CARS2):c.225-2A>G SNV Pathogenic 1031375 GRCh37: 13:111357920-111357920
GRCh38: 13:110705573-110705573
6 CARS2 NM_024537.4(CARS2):c.239dup (p.Thr81fs) Duplication Pathogenic 1030849 GRCh37: 13:111357903-111357904
GRCh38: 13:110705556-110705557
7 CARS2 NM_024537.4(CARS2):c.1426G>T (p.Gly476Ter) SNV Likely pathogenic 972919 GRCh37: 13:111294859-111294859
GRCh38: 13:110642512-110642512
8 CARS2 NM_024537.4(CARS2):c.1632C>A (p.Ser544Arg) SNV Conflicting interpretations of pathogenicity 475624 rs141184379 GRCh37: 13:111293947-111293947
GRCh38: 13:110641600-110641600
9 CARS2 NM_024537.4(CARS2):c.302G>A (p.Arg101Gln) SNV Conflicting interpretations of pathogenicity 475628 rs112070421 GRCh37: 13:111353876-111353876
GRCh38: 13:110701529-110701529
10 CARS2 NM_024537.4(CARS2):c.1683dup (p.Ser562fs) Duplication Conflicting interpretations of pathogenicity 475625 rs575601185 GRCh37: 13:111293895-111293896
GRCh38: 13:110641548-110641549
11 CARS2 NM_024537.4(CARS2):c.1448T>G (p.Leu483Trp) SNV Conflicting interpretations of pathogenicity 770085 rs766266851 GRCh37: 13:111294837-111294837
GRCh38: 13:110642490-110642490
12 CARS2 NM_024537.4(CARS2):c.1377G>C (p.Gln459His) SNV Uncertain significance 1030848 GRCh37: 13:111296771-111296771
GRCh38: 13:110644424-110644424
13 CARS2 NM_024537.4(CARS2):c.9G>T (p.Arg3Ser) SNV Uncertain significance 1030850 GRCh37: 13:111358432-111358432
GRCh38: 13:110706085-110706085
14 CARS2 NM_024537.4(CARS2):c.1684_1685insA (p.Ser562fs) Insertion Uncertain significance 1031374 GRCh37: 13:111293894-111293895
GRCh38: 13:110641547-110641548
15 CARS2 NM_024537.4(CARS2):c.851_852delinsGG (p.Glu284Gly) Indel Uncertain significance 644921 rs1594296703 GRCh37: 13:111319754-111319755
GRCh38: 13:110667407-110667408
16 CARS2 NM_024537.4(CARS2):c.101C>G (p.Ala34Gly) SNV Uncertain significance 475611 rs567317952 GRCh37: 13:111358340-111358340
GRCh38: 13:110705993-110705993
17 CARS2 NM_024537.4(CARS2):c.1141A>G (p.Met381Val) SNV Uncertain significance 521236 rs148857540 GRCh37: 13:111299500-111299500
GRCh38: 13:110647153-110647153
18 CARS2 NM_024537.4(CARS2):c.1135G>A (p.Ala379Thr) SNV Uncertain significance 521237 rs748825203 GRCh37: 13:111299506-111299506
GRCh38: 13:110647159-110647159
19 CARS2 NM_024537.4(CARS2):c.1540C>T (p.Gln514Ter) SNV Uncertain significance 1034681 GRCh37: 13:111294745-111294745
GRCh38: 13:110642398-110642398
20 CARS2 NM_024537.4(CARS2):c.2T>C (p.Met1Thr) SNV Uncertain significance 265071 rs774110184 GRCh37: 13:111358439-111358439
GRCh38: 13:110706092-110706092
21 CARS2 NC_000013.10:g.(?_111293884)_(111319830_?)dup Duplication Uncertain significance 1037860 GRCh37: 13:111293884-111319830
GRCh38:
22 CARS2 NM_024537.4(CARS2):c.922C>G (p.His308Asp) SNV Uncertain significance 1038057 GRCh37: 13:111315863-111315863
GRCh38: 13:110663516-110663516
23 CARS2 NM_024537.4(CARS2):c.943GAA[1] (p.Glu316del) Microsatellite Uncertain significance 1038346 GRCh37: 13:111315837-111315839
GRCh38: 13:110663490-110663492
24 CARS2 NM_024537.4(CARS2):c.527T>C (p.Ile176Thr) SNV Uncertain significance 1040214 GRCh37: 13:111340112-111340112
GRCh38: 13:110687765-110687765
25 CARS2 NM_024537.4(CARS2):c.1417T>G (p.Tyr473Asp) SNV Uncertain significance 1040635 GRCh37: 13:111294868-111294868
GRCh38: 13:110642521-110642521
26 CARS2 NM_024537.4(CARS2):c.281A>G (p.Tyr94Cys) SNV Uncertain significance 1040693 GRCh37: 13:111353897-111353897
GRCh38: 13:110701550-110701550
27 CARS2 NM_024537.4(CARS2):c.535A>C (p.Ile179Leu) SNV Uncertain significance 1040925 GRCh37: 13:111340104-111340104
GRCh38: 13:110687757-110687757
28 CARS2 NM_024537.4(CARS2):c.126G>C (p.Trp42Cys) SNV Uncertain significance 1043837 GRCh37: 13:111358315-111358315
GRCh38: 13:110705968-110705968
29 CARS2 NM_024537.4(CARS2):c.1528G>A (p.Asp510Asn) SNV Uncertain significance 1044151 GRCh37: 13:111294757-111294757
GRCh38: 13:110642410-110642410
30 CARS2 NM_024537.4(CARS2):c.1693T>G (p.Ter565Gly) SNV Uncertain significance 1044498 GRCh37: 13:111293886-111293886
GRCh38: 13:110641539-110641539
31 CARS2 NM_024537.4(CARS2):c.574A>G (p.Asn192Asp) SNV Uncertain significance 475632 rs150286306 GRCh37: 13:111335479-111335479
GRCh38: 13:110683132-110683132
32 CARS2 NM_024537.4(CARS2):c.244G>A (p.Val82Ile) SNV Uncertain significance 542307 rs117788141 GRCh37: 13:111357899-111357899
GRCh38: 13:110705552-110705552
33 CARS2 NM_024537.4(CARS2):c.466G>T (p.Val156Phe) SNV Uncertain significance 542308 rs148098469 GRCh37: 13:111340173-111340173
GRCh38: 13:110687826-110687826
34 CARS2 NM_024537.4(CARS2):c.1177G>A (p.Ala393Thr) SNV Uncertain significance 569829 rs868498923 GRCh37: 13:111299464-111299464
GRCh38: 13:110647117-110647117
35 CARS2 NM_024537.4(CARS2):c.671G>A (p.Arg224His) SNV Uncertain significance 639615 rs199589765 GRCh37: 13:111329435-111329435
GRCh38: 13:110677088-110677088
36 CARS2 NM_024537.4(CARS2):c.1579G>A (p.Asp527Asn) SNV Uncertain significance 643586 rs150780076 GRCh37: 13:111294706-111294706
GRCh38: 13:110642359-110642359
37 CARS2 NM_024537.4(CARS2):c.1075G>A (p.Ala359Thr) SNV Uncertain significance 650817 rs570568500 GRCh37: 13:111299566-111299566
GRCh38: 13:110647219-110647219
38 CARS2 NM_024537.4(CARS2):c.1133G>A (p.Arg378His) SNV Uncertain significance 835739 GRCh37: 13:111299508-111299508
GRCh38: 13:110647161-110647161
39 CARS2 NM_024537.4(CARS2):c.634C>T (p.Pro212Ser) SNV Uncertain significance 837383 GRCh37: 13:111335419-111335419
GRCh38: 13:110683072-110683072
40 CARS2 NM_024537.4(CARS2):c.499G>A (p.Glu167Lys) SNV Uncertain significance 843421 GRCh37: 13:111340140-111340140
GRCh38: 13:110687793-110687793
41 CARS2 NM_024537.4(CARS2):c.1523C>T (p.Thr508Met) SNV Uncertain significance 845685 GRCh37: 13:111294762-111294762
GRCh38: 13:110642415-110642415
42 CARS2 NM_024537.4(CARS2):c.376A>G (p.Ile126Val) SNV Uncertain significance 849127 GRCh37: 13:111353802-111353802
GRCh38: 13:110701455-110701455
43 CARS2 NM_024537.4(CARS2):c.373A>G (p.Ile125Val) SNV Uncertain significance 857042 GRCh37: 13:111353805-111353805
GRCh38: 13:110701458-110701458
44 CARS2 NM_024537.4(CARS2):c.1438G>C (p.Glu480Gln) SNV Uncertain significance 857208 GRCh37: 13:111294847-111294847
GRCh38: 13:110642500-110642500
45 CARS2 NM_024537.4(CARS2):c.601G>A (p.Gly201Arg) SNV Uncertain significance 864312 GRCh37: 13:111335452-111335452
GRCh38: 13:110683105-110683105
46 CARS2 NM_024537.4(CARS2):c.1592G>A (p.Arg531Gln) SNV Uncertain significance 933621 GRCh37: 13:111294693-111294693
GRCh38: 13:110642346-110642346
47 CARS2 NM_024537.4(CARS2):c.1430A>G (p.Asp477Gly) SNV Uncertain significance 934649 GRCh37: 13:111294855-111294855
GRCh38: 13:110642508-110642508
48 CARS2 NM_024537.4(CARS2):c.545G>A (p.Arg182His) SNV Uncertain significance 936704 GRCh37: 13:111340094-111340094
GRCh38: 13:110687747-110687747
49 CARS2 NM_024537.4(CARS2):c.666C>A (p.Asp222Glu) SNV Uncertain significance 938663 GRCh37: 13:111329440-111329440
GRCh38: 13:110677093-110677093
50 CARS2 NM_024537.4(CARS2):c.269A>G (p.His90Arg) SNV Uncertain significance 943806 GRCh37: 13:111357874-111357874
GRCh38: 13:110705527-110705527

UniProtKB/Swiss-Prot genetic disease variations for Combined Oxidative Phosphorylation Deficiency 27:

72
# Symbol AA change Variation ID SNP ID
1 CARS2 p.Pro251Leu VAR_075669 rs557671802

Expression for Combined Oxidative Phosphorylation Deficiency 27

Search GEO for disease gene expression data for Combined Oxidative Phosphorylation Deficiency 27.

Pathways for Combined Oxidative Phosphorylation Deficiency 27

GO Terms for Combined Oxidative Phosphorylation Deficiency 27

Sources for Combined Oxidative Phosphorylation Deficiency 27

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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