COXPD23
MCID: CMB054
MIFTS: 31

Combined Oxidative Phosphorylation Deficiency 23 (COXPD23)

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

Aliases & Classifications for Combined Oxidative Phosphorylation Deficiency 23

MalaCards integrated aliases for Combined Oxidative Phosphorylation Deficiency 23:

Name: Combined Oxidative Phosphorylation Deficiency 23 57 12 72 29 6 15 70
Coxpd23 57 12 58 72
Combined Oxidative Phosphorylation Defect Type 23 58 17
Oxidative Phosphorylation Deficiency, Combined, Type 23 39

Characteristics:

Orphanet epidemiological data:

58
combined oxidative phosphorylation defect type 23
Inheritance: Autosomal recessive; Prevalence: <1/1000000 (Worldwide); Age of onset: Childhood,Infancy,Neonatal; Age of death: infantile;

OMIM®:

57 (Updated 20-May-2021)
Inheritance:
autosomal recessive

Miscellaneous:
variable severity
onset in early childhood


HPO:

31
combined oxidative phosphorylation deficiency 23:
Inheritance autosomal recessive inheritance
Onset and clinical course variable expressivity


Classifications:

Orphanet: 58  
Rare neurological diseases
Inborn errors of metabolism


Summaries for Combined Oxidative Phosphorylation Deficiency 23

OMIM® : 57 Combined oxidative phosphorylation deficiency-23 is an autosomal recessive disorder characterized by early childhood onset of hypertrophic cardiomyopathy and/or neurologic symptoms, including hypotonia and delayed psychomotor development. Laboratory investigations are consistent with a defect in mitochondrial function resulting in lactic acidosis, impaired activities of respiratory complexes I and IV, and defective translation of mitochondrial proteins. Brain imaging shows abnormal lesions in the basal ganglia, thalamus, and brainstem. The severity of the disorder is variable, ranging from death in early infancy to survival into the second decade (summary by Kopajtich et al., 2014). For a discussion of genetic heterogeneity of combined oxidative phosphorylation deficiency, see COXPD1 (609060). (616198) (Updated 20-May-2021)

MalaCards based summary : Combined Oxidative Phosphorylation Deficiency 23, also known as coxpd23, is related to proprotein convertase 1/3 deficiency. An important gene associated with Combined Oxidative Phosphorylation Deficiency 23 is GTPBP3 (GTP Binding Protein 3, Mitochondrial). Affiliated tissues include thalamus, heart and skeletal muscle, and related phenotypes are hypertrophic cardiomyopathy and lactic acidosis

Disease Ontology : 12 A combined oxidative phosphorylation deficiency characterized by early childhood onset of hypertrophic cardiomyopathy and/or neurologic symptoms, including hypotonia and delayed psychomotor development that has material basis in homozygous or compound heterozygous mutation in GTPBP3 on chromosome 19p13.11.

UniProtKB/Swiss-Prot : 72 Combined oxidative phosphorylation deficiency 23: An autosomal recessive mitochondrial disorder characterized by hypertrophic cardiomyopathy and/or neurologic symptoms with onset in early childhood. Disease features include hypertrophic cardiomyopathy, hypotonia, delayed psychomotor development, lactic acidosis, impaired activities of respiratory complexes I and IV, and defective translation of mitochondrial proteins. Disease severity is variable, ranging from death in early infancy to survival into the second decade of life.

Related Diseases for Combined Oxidative Phosphorylation Deficiency 23

Diseases related to Combined Oxidative Phosphorylation Deficiency 23 via text searches within MalaCards or GeneCards Suite gene sharing:

# Related Disease Score Top Affiliating Genes
1 proprotein convertase 1/3 deficiency 9.2 TPP2 PEX26 GTPBP3 ATP13A4

Symptoms & Phenotypes for Combined Oxidative Phosphorylation Deficiency 23

Human phenotypes related to Combined Oxidative Phosphorylation Deficiency 23:

58 31 (show all 34)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 hypertrophic cardiomyopathy 58 31 hallmark (90%) Very frequent (99-80%) HP:0001639
2 lactic acidosis 58 31 hallmark (90%) Very frequent (99-80%) HP:0003128
3 global developmental delay 58 31 frequent (33%) Occasional (29-5%) HP:0001263
4 infantile muscular hypotonia 58 31 frequent (33%) Frequent (79-30%) HP:0008947
5 failure to thrive 58 31 occasional (7.5%) Occasional (29-5%) HP:0001508
6 visual impairment 58 31 occasional (7.5%) Occasional (29-5%) HP:0000505
7 feeding difficulties in infancy 58 31 occasional (7.5%) Occasional (29-5%) HP:0008872
8 cognitive impairment 58 31 occasional (7.5%) Occasional (29-5%) HP:0100543
9 intellectual disability, mild 58 31 occasional (7.5%) Occasional (29-5%) HP:0001256
10 congestive heart failure 58 31 occasional (7.5%) Occasional (29-5%) HP:0001635
11 easy fatigability 58 31 occasional (7.5%) Occasional (29-5%) HP:0003388
12 left ventricular hypertrophy 58 31 occasional (7.5%) Occasional (29-5%) HP:0001712
13 respiratory failure 58 31 occasional (7.5%) Occasional (29-5%) HP:0002878
14 decreased activity of mitochondrial complex i 58 31 occasional (7.5%) Occasional (29-5%) HP:0011923
15 leukodystrophy 58 31 occasional (7.5%) Occasional (29-5%) HP:0002415
16 cyanosis 58 31 occasional (7.5%) Occasional (29-5%) HP:0000961
17 stridor 58 31 occasional (7.5%) Occasional (29-5%) HP:0010307
18 abnormal thalamic mri signal intensity 58 31 occasional (7.5%) Occasional (29-5%) HP:0012696
19 wolff-parkinson-white syndrome 58 31 occasional (7.5%) Occasional (29-5%) HP:0001716
20 paroxysmal dyspnea 58 31 occasional (7.5%) Occasional (29-5%) HP:0012763
21 abnormal basal ganglia mri signal intensity 58 31 occasional (7.5%) Occasional (29-5%) HP:0012751
22 abnormal brainstem mri signal intensity 58 31 occasional (7.5%) Occasional (29-5%) HP:0012747
23 right ventricular hypertrophy 58 31 occasional (7.5%) Occasional (29-5%) HP:0001667
24 decreased activity of mitochondrial complex iv 58 31 occasional (7.5%) Occasional (29-5%) HP:0008347
25 severely reduced ejection fraction 58 31 occasional (7.5%) Occasional (29-5%) HP:0012666
26 seizure 31 occasional (7.5%) HP:0001250
27 seizures 58 Occasional (29-5%)
28 intrauterine growth retardation 31 HP:0001511
29 arrhythmia 31 HP:0011675
30 increased serum lactate 31 HP:0002151
31 abnormality of the nervous system 58 Frequent (79-30%)
32 feeding difficulties 31 HP:0011968
33 cardiomyopathy 31 HP:0001638
34 generalized hypotonia 31 HP:0001290

Symptoms via clinical synopsis from OMIM®:

57 (Updated 20-May-2021)
Growth Other:
intrauterine growth retardation

Laboratory Abnormalities:
increased serum lactate

Muscle Soft Tissue:
hypotonia
decreased activity of mitochondrial complexes i and iv seen on skeletal muscle biopsy

Abdomen Gastrointestinal:
feeding problems

Cardiovascular Heart:
arrhythmia
cardiomyopathy
cardiac failures

Metabolic Features:
lactic acidosis

Neurologic Central Nervous System:
seizures (in some patients)
delayed psychomotor development, variable
t2-weighted hyperintense lesions in the thalamus, basal ganglia, and brainstem

Head And Neck Eyes:
visual impairment (in some patients)

Clinical features from OMIM®:

616198 (Updated 20-May-2021)

MGI Mouse Phenotypes related to Combined Oxidative Phosphorylation Deficiency 23:

46
# Description MGI Source Accession Score Top Affiliating Genes
1 mortality/aging MP:0010768 9.1 ATP6V0A4 F13A1 GTPBP3 MMACHC PEX26 TPP2

Drugs & Therapeutics for Combined Oxidative Phosphorylation Deficiency 23

Search Clinical Trials , NIH Clinical Center for Combined Oxidative Phosphorylation Deficiency 23

Genetic Tests for Combined Oxidative Phosphorylation Deficiency 23

Genetic tests related to Combined Oxidative Phosphorylation Deficiency 23:

# Genetic test Affiliating Genes
1 Combined Oxidative Phosphorylation Deficiency 23 29 GTPBP3

Anatomical Context for Combined Oxidative Phosphorylation Deficiency 23

MalaCards organs/tissues related to Combined Oxidative Phosphorylation Deficiency 23:

40
Thalamus, Heart, Skeletal Muscle

Publications for Combined Oxidative Phosphorylation Deficiency 23

Articles related to Combined Oxidative Phosphorylation Deficiency 23:

# Title Authors PMID Year
1
Mutations in GTPBP3 cause a mitochondrial translation defect associated with hypertrophic cardiomyopathy, lactic acidosis, and encephalopathy. 6 57
25434004 2014

Variations for Combined Oxidative Phosphorylation Deficiency 23

ClinVar genetic disease variations for Combined Oxidative Phosphorylation Deficiency 23:

6 (show all 18)
# Gene Name Type Significance ClinVarId dbSNP ID Position
1 GTPBP3 NM_032620.4(GTPBP3):c.1375G>A (p.Glu459Lys) SNV Pathogenic 180615 rs886037734 GRCh37: 19:17452408-17452408
GRCh38: 19:17341599-17341599
2 GTPBP3 NM_032620.4(GTPBP3):c.476A>T (p.Glu159Val) SNV Pathogenic 180616 rs730880255 GRCh37: 19:17449435-17449435
GRCh38: 19:17338626-17338626
3 GTPBP3 NM_032620.4(GTPBP3):c.1009G>C (p.Asp337His) SNV Pathogenic 180618 rs886037735 GRCh37: 19:17451887-17451887
GRCh38: 19:17341078-17341078
4 GTPBP3 NM_032620.4(GTPBP3):c.1291dup (p.Arg431fs) Duplication Pathogenic 180614 rs869320746 GRCh37: 19:17452321-17452322
GRCh38: 19:17341512-17341513
5 GTPBP3 NM_032620.4(GTPBP3):c.32_33delinsGTG (p.Gln11fs) Indel Pathogenic 180619 rs886037736 GRCh37: 19:17448452-17448453
GRCh38: 19:17337643-17337644
6 GTPBP3 NM_032620.4(GTPBP3):c.643G>T (p.Glu215Ter) SNV Pathogenic 488527 rs1555726849 GRCh37: 19:17449814-17449814
GRCh38: 19:17339005-17339005
7 GTPBP3 NM_032620.4(GTPBP3):c.1112T>C (p.Leu371Pro) SNV Likely pathogenic 488528 rs770871640 GRCh37: 19:17451990-17451990
GRCh38: 19:17341181-17341181
8 GTPBP3 NM_032620.4(GTPBP3):c.440C>T (p.Ala147Val) SNV Likely pathogenic 488525 rs774708853 GRCh37: 19:17449399-17449399
GRCh38: 19:17338590-17338590
9 GTPBP3 NM_032620.4(GTPBP3):c.517C>T (p.Arg173Trp) SNV Likely pathogenic 488526 rs1274363168 GRCh37: 19:17449476-17449476
GRCh38: 19:17338667-17338667
10 GTPBP3 NM_032620.4(GTPBP3):c.1439T>A (p.Ile480Asn) SNV Likely pathogenic 800909 rs558425417 GRCh37: 19:17452472-17452472
GRCh38: 19:17341663-17341663
11 GTPBP3 NM_032620.4(GTPBP3):c.964G>C (p.Ala322Pro) SNV Uncertain significance 180617 rs372174278 GRCh37: 19:17450398-17450398
GRCh38: 19:17339589-17339589
12 GTPBP3 NM_032620.4(GTPBP3):c.673G>A (p.Glu225Lys) SNV Uncertain significance 931027 GRCh37: 19:17449940-17449940
GRCh38: 19:17339131-17339131
13 GTPBP3 NM_032620.4(GTPBP3):c.392G>C (p.Ser131Thr) SNV Uncertain significance 931581 GRCh37: 19:17449351-17449351
GRCh38: 19:17338542-17338542
14 GTPBP3 NM_032620.4(GTPBP3):c.215C>T (p.Pro72Leu) SNV Uncertain significance 693995 rs542667981 GRCh37: 19:17448978-17448978
GRCh38: 19:17338169-17338169
15 GTPBP3 NM_032620.4(GTPBP3):c.188G>A (p.Arg63Gln) SNV Uncertain significance 1031119 GRCh37: 19:17448951-17448951
GRCh38: 19:17338142-17338142
16 GTPBP3 NM_032620.4(GTPBP3):c.1409G>A (p.Arg470Gln) SNV Uncertain significance 1031608 GRCh37: 19:17452442-17452442
GRCh38: 19:17341633-17341633
17 GTPBP3 NM_032620.4(GTPBP3):c.1175C>G (p.Pro392Arg) SNV Benign 693994 rs149578279 GRCh37: 19:17452053-17452053
GRCh38: 19:17341244-17341244
18 GTPBP3 NM_032620.4(GTPBP3):c.424G>A (p.Glu142Lys) SNV not provided 973076 GRCh37: 19:17449383-17449383
GRCh38: 19:17338574-17338574

UniProtKB/Swiss-Prot genetic disease variations for Combined Oxidative Phosphorylation Deficiency 23:

72
# Symbol AA change Variation ID SNP ID
1 GTPBP3 p.Glu142Lys VAR_073299
2 GTPBP3 p.Glu159Val VAR_073300 rs730880255
3 GTPBP3 p.Ala162Pro VAR_073301
4 GTPBP3 p.Ala222Gly VAR_073302 rs373370177
5 GTPBP3 p.Pro257His VAR_073304
6 GTPBP3 p.Asp337His VAR_073307 rs886037735
7 GTPBP3 p.Glu459Lys VAR_073308 rs886037734

Expression for Combined Oxidative Phosphorylation Deficiency 23

Search GEO for disease gene expression data for Combined Oxidative Phosphorylation Deficiency 23.

Pathways for Combined Oxidative Phosphorylation Deficiency 23

GO Terms for Combined Oxidative Phosphorylation Deficiency 23

Molecular functions related to Combined Oxidative Phosphorylation Deficiency 23 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 ATPase binding GO:0051117 8.62 PEX26 ATP6V0A4

Sources for Combined Oxidative Phosphorylation Deficiency 23

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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