COXPD4
MCID: CMB015
MIFTS: 36

Combined Oxidative Phosphorylation Deficiency 4 (COXPD4)

Categories: Genetic diseases, Metabolic diseases, Rare diseases

Aliases & Classifications for Combined Oxidative Phosphorylation Deficiency 4

MalaCards integrated aliases for Combined Oxidative Phosphorylation Deficiency 4:

Name: Combined Oxidative Phosphorylation Deficiency 4 57 12 72 29 13 6 44 15 70
Coxpd4 57 12 58 72
Combined Oxidative Phosphorylation Deficiency, Type 4 39
Combined Oxidative Phosphorylation Defect Type 4 58

Characteristics:

Orphanet epidemiological data:

58
combined oxidative phosphorylation defect type 4
Inheritance: Autosomal recessive; Prevalence: <1/1000000 (Worldwide); Age of onset: Neonatal; Age of death: early childhood;

OMIM®:

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

Miscellaneous:
onset in infancy
death in infancy may occur


HPO:

31
combined oxidative phosphorylation deficiency 4:
Onset and clinical course death in infancy infantile onset
Inheritance autosomal recessive inheritance


Classifications:

Orphanet: 58  
Inborn errors of metabolism


External Ids:

Disease Ontology 12 DOID:0111494
OMIM® 57 610678
OMIM Phenotypic Series 57 PS609060
ICD10 via Orphanet 33 E88.8
UMLS via Orphanet 71 C1857682
Orphanet 58 ORPHA254925
MedGen 41 C1857682
UMLS 70 C1857682

Summaries for Combined Oxidative Phosphorylation Deficiency 4

UniProtKB/Swiss-Prot : 72 Combined oxidative phosphorylation deficiency 4: A mitochondrial disease resulting in neonatal lactic acidosis, rapidly progressive encephalopathy, severely decreased mitochondrial protein synthesis, and combined deficiency of mtDNA-related mitochondrial respiratory chain complexes.

MalaCards based summary : Combined Oxidative Phosphorylation Deficiency 4, also known as coxpd4, is related to combined oxidative phosphorylation deficiency and lactic acidosis. An important gene associated with Combined Oxidative Phosphorylation Deficiency 4 is TUFM (Tu Translation Elongation Factor, Mitochondrial), and among its related pathways/superpathways is Mitochondrial translation. Affiliated tissues include brain, and related phenotypes are nystagmus and developmental regression

Disease Ontology : 12 A combined oxidative phosphorylation deficiency that has material basis in homozygous or compound heterozygous mutation in TUFM on chromosome 16p11.2.

More information from OMIM: 610678 PS609060

Related Diseases for Combined Oxidative Phosphorylation Deficiency 4

Graphical network of the top 20 diseases related to Combined Oxidative Phosphorylation Deficiency 4:



Diseases related to Combined Oxidative Phosphorylation Deficiency 4

Symptoms & Phenotypes for Combined Oxidative Phosphorylation Deficiency 4

Human phenotypes related to Combined Oxidative Phosphorylation Deficiency 4:

31 (show all 15)
# Description HPO Frequency HPO Source Accession
1 nystagmus 31 HP:0000639
2 developmental regression 31 HP:0002376
3 hepatomegaly 31 HP:0002240
4 microcephaly 31 HP:0000252
5 neonatal hypotonia 31 HP:0001319
6 intrauterine growth retardation 31 HP:0001511
7 increased serum lactate 31 HP:0002151
8 hyperammonemia 31 HP:0001987
9 polymicrogyria 31 HP:0002126
10 respiratory failure 31 HP:0002878
11 encephalopathy 31 HP:0001298
12 leukodystrophy 31 HP:0002415
13 lactic acidosis 31 HP:0003128
14 metabolic acidosis 31 HP:0001942
15 opisthotonus 31 HP:0002179

Symptoms via clinical synopsis from OMIM®:

57 (Updated 20-May-2021)
Neurologic Central Nervous System:
developmental regression
leigh syndrome
encephalopathy (patient a)
hypertonia (patient a)
spasticity (patient a)
more
Laboratory Abnormalities:
increased serum lactate
hyperammonemia

Metabolic Features:
lactic acidosis

Head And Neck Head:
microcephaly (patient a)

Growth Other:
intrauterine growth retardation

Respiratory:
respiratory failure

Muscle Soft Tissue:
hypotonia, neonatal

Head And Neck Eyes:
nystagmus (patient a)

Clinical features from OMIM®:

610678 (Updated 20-May-2021)

Drugs & Therapeutics for Combined Oxidative Phosphorylation Deficiency 4

Search Clinical Trials , NIH Clinical Center for Combined Oxidative Phosphorylation Deficiency 4

Cochrane evidence based reviews: combined oxidative phosphorylation deficiency 4

Genetic Tests for Combined Oxidative Phosphorylation Deficiency 4

Genetic tests related to Combined Oxidative Phosphorylation Deficiency 4:

# Genetic test Affiliating Genes
1 Combined Oxidative Phosphorylation Deficiency 4 29 TUFM

Anatomical Context for Combined Oxidative Phosphorylation Deficiency 4

MalaCards organs/tissues related to Combined Oxidative Phosphorylation Deficiency 4:

40
Brain

Publications for Combined Oxidative Phosphorylation Deficiency 4

Articles related to Combined Oxidative Phosphorylation Deficiency 4:

# Title Authors PMID Year
1
A Comprehensive Genomic Analysis Reveals the Genetic Landscape of Mitochondrial Respiratory Chain Complex Deficiencies. 6 57
26741492 2016
2
Infantile encephalopathy and defective mitochondrial DNA translation in patients with mutations of mitochondrial elongation factors EFG1 and EFTu. 6 57
17160893 2007
3
A novel TUFM homozygous variant in a child with mitochondrial cardiomyopathy expands the phenotype of combined oxidative phosphorylation deficiency 4. 61
30903008 2019
4
The NLR protein, NLRX1, and its partner, TUFM, reduce type I interferon, and enhance autophagy. 61
23321557 2013

Variations for Combined Oxidative Phosphorylation Deficiency 4

ClinVar genetic disease variations for Combined Oxidative Phosphorylation Deficiency 4:

6 (show top 50) (show all 59)
# Gene Name Type Significance ClinVarId dbSNP ID Position
1 TUFM NM_003321.5(TUFM):c.440T>A (p.Leu147His) SNV Pathogenic 372182 rs1057518742 GRCh37: 16:28856351-28856351
GRCh38: 16:28845030-28845030
2 TUFM NM_003321.5(TUFM):c.162del (p.Thr53_Tyr54insTer) Deletion Pathogenic 372183 rs1057518743 GRCh37: 16:28857318-28857318
GRCh38: 16:28845997-28845997
3 TUFM NM_003321.5(TUFM):c.1016G>A (p.Arg339Gln) SNV Pathogenic 7275 rs121434452 GRCh37: 16:28855329-28855329
GRCh38: 16:28844008-28844008
4 TUFM NM_003321.5(TUFM):c.989G>C (p.Arg330Pro) SNV Likely pathogenic 488629 rs924099073 GRCh37: 16:28855356-28855356
GRCh38: 16:28844035-28844035
5 TUFM NM_003321.5(TUFM):c.684+8C>T SNV Uncertain significance 318750 rs117782882 GRCh37: 16:28856011-28856011
GRCh38: 16:28844690-28844690
6 TUFM NM_003321.5(TUFM):c.622G>A (p.Glu208Lys) SNV Uncertain significance 215311 rs143189885 GRCh37: 16:28856081-28856081
GRCh38: 16:28844760-28844760
7 TUFM NM_003321.5(TUFM):c.519+15G>A SNV Uncertain significance 318753 rs758912548 GRCh37: 16:28856257-28856257
GRCh38: 16:28844936-28844936
8 TUFM NM_003321.5(TUFM):c.759C>T (p.Pro253=) SNV Uncertain significance 318749 rs185379779 GRCh37: 16:28855798-28855798
GRCh38: 16:28844477-28844477
9 TUFM NM_003321.5(TUFM):c.*149G>C SNV Uncertain significance 318739 rs886051876 GRCh37: 16:28854147-28854147
GRCh38: 16:28842826-28842826
10 TUFM NM_003321.5(TUFM):c.558T>C (p.Ala186=) SNV Uncertain significance 379527 rs141728293 GRCh37: 16:28856145-28856145
GRCh38: 16:28844824-28844824
11 TUFM NM_003321.5(TUFM):c.35C>G (p.Ala12Gly) SNV Uncertain significance 215318 rs559685074 GRCh37: 16:28857556-28857556
GRCh38: 16:28846235-28846235
12 TUFM NM_003321.5(TUFM):c.6C>T (p.Thr2=) SNV Uncertain significance 425103 rs751421456 GRCh37: 16:28857585-28857585
GRCh38: 16:28846264-28846264
13 TUFM NM_003321.5(TUFM):c.562G>A (p.Ala188Thr) SNV Uncertain significance 1028594 GRCh37: 16:28856141-28856141
GRCh38: 16:28844820-28844820
14 TUFM NM_003321.5(TUFM):c.100C>G (p.Leu34Val) SNV Uncertain significance 1031324 GRCh37: 16:28857380-28857380
GRCh38: 16:28846059-28846059
15 TUFM NM_003321.5(TUFM):c.1348A>G (p.Lys450Glu) SNV Uncertain significance 215314 rs199674838 GRCh37: 16:28854316-28854316
GRCh38: 16:28842995-28842995
16 TUFM NM_003321.5(TUFM):c.922+8A>G SNV Uncertain significance 516840 rs760803572 GRCh37: 16:28855543-28855543
GRCh38: 16:28844222-28844222
17 TUFM NM_003321.5(TUFM):c.825C>G (p.Gly275=) SNV Uncertain significance 884916 GRCh37: 16:28855648-28855648
GRCh38: 16:28844327-28844327
18 TUFM NM_003321.5(TUFM):c.810C>T (p.Ser270=) SNV Uncertain significance 884917 GRCh37: 16:28855747-28855747
GRCh38: 16:28844426-28844426
19 TUFM NM_003321.5(TUFM):c.800C>T (p.Ala267Val) SNV Uncertain significance 884918 GRCh37: 16:28855757-28855757
GRCh38: 16:28844436-28844436
20 TUFM NM_003321.5(TUFM):c.-61C>T SNV Uncertain significance 884984 GRCh37: 16:28857651-28857651
GRCh38: 16:28846330-28846330
21 TUFM NM_003321.5(TUFM):c.619A>C (p.Thr207Pro) SNV Uncertain significance 885837 GRCh37: 16:28856084-28856084
GRCh38: 16:28844763-28844763
22 TUFM NM_003321.5(TUFM):c.595G>C (p.Glu199Gln) SNV Uncertain significance 885838 GRCh37: 16:28856108-28856108
GRCh38: 16:28844787-28844787
23 TUFM NM_003321.5(TUFM):c.581T>C (p.Met194Thr) SNV Uncertain significance 885839 GRCh37: 16:28856122-28856122
GRCh38: 16:28844801-28844801
24 TUFM NM_003321.5(TUFM):c.*433T>C SNV Uncertain significance 886766 GRCh37: 16:28853863-28853863
GRCh38: 16:28842542-28842542
25 TUFM NM_003321.5(TUFM):c.*270C>T SNV Uncertain significance 886767 GRCh37: 16:28854026-28854026
GRCh38: 16:28842705-28842705
26 TUFM NM_003321.5(TUFM):c.519+14G>C SNV Uncertain significance 886834 GRCh37: 16:28856258-28856258
GRCh38: 16:28844937-28844937
27 TUFM NM_003321.5(TUFM):c.470A>G (p.Asn157Ser) SNV Uncertain significance 886835 GRCh37: 16:28856321-28856321
GRCh38: 16:28845000-28845000
28 TUFM NM_003321.5(TUFM):c.*229G>A SNV Uncertain significance 888045 GRCh37: 16:28854067-28854067
GRCh38: 16:28842746-28842746
29 TUFM NM_003321.5(TUFM):c.*60T>G SNV Uncertain significance 888046 GRCh37: 16:28854236-28854236
GRCh38: 16:28842915-28842915
30 TUFM NM_003321.5(TUFM):c.166C>G (p.Arg56Gly) SNV Uncertain significance 888109 GRCh37: 16:28857314-28857314
GRCh38: 16:28845993-28845993
31 TUFM NM_003321.5(TUFM):c.12G>T (p.Met4Ile) SNV Uncertain significance 888110 GRCh37: 16:28857579-28857579
GRCh38: 16:28846258-28846258
32 TUFM NM_003321.5(TUFM):c.1120G>A (p.Val374Met) SNV Uncertain significance 215309 rs114590091 GRCh37: 16:28855131-28855131
GRCh38: 16:28843810-28843810
33 TUFM NM_003321.5(TUFM):c.248-13T>G SNV Uncertain significance 318755 rs775737562 GRCh37: 16:28856814-28856814
GRCh38: 16:28845493-28845493
34 TUFM NM_003321.5(TUFM):c.-37C>T SNV Uncertain significance 318757 rs886051877 GRCh37: 16:28857627-28857627
GRCh38: 16:28846306-28846306
35 TUFM NM_003321.5(TUFM):c.*445G>A SNV Uncertain significance 318734 rs542944452 GRCh37: 16:28853851-28853851
GRCh38: 16:28842530-28842530
36 TUFM NM_003321.5(TUFM):c.*110A>G SNV Uncertain significance 318740 rs753564296 GRCh37: 16:28854186-28854186
GRCh38: 16:28842865-28842865
37 TUFM NM_003321.5(TUFM):c.*349G>A SNV Uncertain significance 318737 rs749982691 GRCh37: 16:28853947-28853947
GRCh38: 16:28842626-28842626
38 TUFM NM_003321.5(TUFM):c.923-9C>A SNV Uncertain significance 318745 rs763468042 GRCh37: 16:28855431-28855431
GRCh38: 16:28844110-28844110
39 TUFM NM_003321.5(TUFM):c.760G>A (p.Ala254Thr) SNV Uncertain significance 318748 rs138917503 GRCh37: 16:28855797-28855797
GRCh38: 16:28844476-28844476
40 TUFM NM_003321.5(TUFM):c.*561A>T SNV Uncertain significance 318732 rs184878749 GRCh37: 16:28853735-28853735
GRCh38: 16:28842414-28842414
41 TUFM NM_003321.5(TUFM):c.*398G>A SNV Uncertain significance 318735 rs560701501 GRCh37: 16:28853898-28853898
GRCh38: 16:28842577-28842577
42 TUFM NM_003321.5(TUFM):c.*37G>A SNV Uncertain significance 318741 rs375508343 GRCh37: 16:28854259-28854259
GRCh38: 16:28842938-28842938
43 TUFM NM_003321.5(TUFM):c.-44G>T SNV Uncertain significance 318758 rs781545296 GRCh37: 16:28857634-28857634
GRCh38: 16:28846313-28846313
44 TUFM NM_003321.5(TUFM):c.894T>C (p.His298=) SNV Uncertain significance 318746 rs780273573 GRCh37: 16:28855579-28855579
GRCh38: 16:28844258-28844258
45 TUFM NM_003321.5(TUFM):c.1A>G (p.Met1Val) SNV Uncertain significance 318756 rs759426337 GRCh37: 16:28857590-28857590
GRCh38: 16:28846269-28846269
46 TUFM NM_003321.5(TUFM):c.*370T>G SNV Uncertain significance 318736 rs567224368 GRCh37: 16:28853926-28853926
GRCh38: 16:28842605-28842605
47 TUFM NM_003321.5(TUFM):c.*517G>C SNV Uncertain significance 318733 rs886051875 GRCh37: 16:28853779-28853779
GRCh38: 16:28842458-28842458
48 TUFM NM_003321.5(TUFM):c.427G>A (p.Gly143Ser) SNV Uncertain significance 318754 rs34283928 GRCh37: 16:28856364-28856364
GRCh38: 16:28845043-28845043
49 TUFM NM_003321.5(TUFM):c.568C>T (p.Gln190Ter) SNV Uncertain significance 318751 rs764968635 GRCh37: 16:28856135-28856135
GRCh38: 16:28844814-28844814
50 TUFM NM_003321.5(TUFM):c.975C>T (p.Leu325=) SNV Uncertain significance 318744 rs757569717 GRCh37: 16:28855370-28855370
GRCh38: 16:28844049-28844049

UniProtKB/Swiss-Prot genetic disease variations for Combined Oxidative Phosphorylation Deficiency 4:

72
# Symbol AA change Variation ID SNP ID
1 TUFM p.Arg336Gln VAR_031902

Expression for Combined Oxidative Phosphorylation Deficiency 4

Search GEO for disease gene expression data for Combined Oxidative Phosphorylation Deficiency 4.

Pathways for Combined Oxidative Phosphorylation Deficiency 4

Pathways related to Combined Oxidative Phosphorylation Deficiency 4 according to GeneCards Suite gene sharing:

# Super pathways Score Top Affiliating Genes
1
Show member pathways
11.36 TUFM TSFM GFM1

GO Terms for Combined Oxidative Phosphorylation Deficiency 4

Cellular components related to Combined Oxidative Phosphorylation Deficiency 4 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 mitochondrion GO:0005739 9.23 UQCC3 TUFM TTC19 TSFM NLRX1 MAVS
2 mitochondrial matrix GO:0005759 9.13 TSFM LYRM7 GFM1

Biological processes related to Combined Oxidative Phosphorylation Deficiency 4 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 translation GO:0006412 9.56 TUFM TSFM GFM1 FARSA
2 mitochondrial translational elongation GO:0070125 9.33 TUFM TSFM GFM1
3 negative regulation of type I interferon production GO:0032480 9.32 NLRX1 MAVS
4 translational elongation GO:0006414 9.13 TUFM TSFM GFM1
5 mitochondrial respiratory chain complex III assembly GO:0034551 8.8 UQCC3 TTC19 LYRM7

Molecular functions related to Combined Oxidative Phosphorylation Deficiency 4 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 translation elongation factor activity GO:0003746 8.8 TUFM TSFM GFM1

Sources for Combined Oxidative Phosphorylation Deficiency 4

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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