COXPD14
MCID: CMB044
MIFTS: 31

Combined Oxidative Phosphorylation Deficiency 14 (COXPD14)

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

Aliases & Classifications for Combined Oxidative Phosphorylation Deficiency 14

MalaCards integrated aliases for Combined Oxidative Phosphorylation Deficiency 14:

Name: Combined Oxidative Phosphorylation Deficiency 14 57 12 72 29 13 6 15 70
Coxpd14 57 12 58 72
Oxidative Phosphorylation Deficiency, Combined, Type 14 39
Combined Oxidative Phosphorylation Defect Type 14 58

Characteristics:

Orphanet epidemiological data:

58
combined oxidative phosphorylation defect type 14
Prevalence: <1/1000000 (Worldwide); Age of onset: Infancy,Neonatal; Age of death: early childhood,infantile;

OMIM®:

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

Miscellaneous:
variable severity
onset in early infancy
death in infancy (in some patients)


HPO:

31
combined oxidative phosphorylation deficiency 14:
Onset and clinical course death in infancy variable expressivity
Inheritance autosomal recessive inheritance


Classifications:

Orphanet: 58  
Inborn errors of metabolism


Summaries for Combined Oxidative Phosphorylation Deficiency 14

OMIM® : 57 COXPD14 is a severe multisystemic autosomal recessive disorder characterized by neonatal onset of global developmental delay, refractory seizures, and lactic acidosis. Biochemical studies show deficiencies of multiple mitochondrial respiratory enzymes. Neuropathologic studies in 1 patient showed laminar cortical necrosis, characteristic of Alpers syndrome (203700) (summary by Elo et al., 2012). For a discussion of genetic heterogeneity of combined oxidative phosphorylation deficiency, see COXPD1 (609060). (614946) (Updated 05-Apr-2021)

MalaCards based summary : Combined Oxidative Phosphorylation Deficiency 14, also known as coxpd14, is related to mitochondrial dna depletion syndrome 4a and fars2 deficiency, and has symptoms including myoclonus An important gene associated with Combined Oxidative Phosphorylation Deficiency 14 is FARS2 (Phenylalanyl-TRNA Synthetase 2, Mitochondrial). Related phenotypes are hearing impairment and visual impairment

Disease Ontology : 12 A combined oxidative phosphorylation deficiency characterized by neonatal onset of global developmental delay, refractory seizures, and lactic acidosis that has material basis in homozygous or compound heterozygous mutation in FARS2 on chromosome 6p25.1.

UniProtKB/Swiss-Prot : 72 Combined oxidative phosphorylation deficiency 14: A severe multisystemic autosomal recessive disorder characterized by neonatal onset of global developmental delay, refractory seizures, and lactic acidosis. Biochemical studies show deficiencies of multiple mitochondrial respiratory enzymes.

Related Diseases for Combined Oxidative Phosphorylation Deficiency 14

Diseases related to Combined Oxidative Phosphorylation Deficiency 14 via text searches within MalaCards or GeneCards Suite gene sharing:

# Related Disease Score Top Affiliating Genes
1 mitochondrial dna depletion syndrome 4a 11.4
2 fars2 deficiency 11.4

Symptoms & Phenotypes for Combined Oxidative Phosphorylation Deficiency 14

Human phenotypes related to Combined Oxidative Phosphorylation Deficiency 14:

31 (show all 22)
# Description HPO Frequency HPO Source Accession
1 hearing impairment 31 occasional (7.5%) HP:0000365
2 visual impairment 31 occasional (7.5%) HP:0000505
3 aminoaciduria 31 occasional (7.5%) HP:0003355
4 anemia 31 occasional (7.5%) HP:0001903
5 thrombocytopenia 31 occasional (7.5%) HP:0001873
6 eeg abnormality 31 HP:0002353
7 global developmental delay 31 HP:0001263
8 microcephaly 31 HP:0000252
9 myoclonus 31 HP:0001336
10 growth delay 31 HP:0001510
11 ventriculomegaly 31 HP:0002119
12 increased serum lactate 31 HP:0002151
13 profound global developmental delay 31 HP:0012736
14 lactic acidosis 31 HP:0003128
15 feeding difficulties 31 HP:0011968
16 cerebellar atrophy 31 HP:0001272
17 cerebral atrophy 31 HP:0002059
18 generalized hypotonia 31 HP:0001290
19 atrophy/degeneration affecting the brainstem 31 HP:0007366
20 diffuse cerebral atrophy 31 HP:0002506
21 gliosis 31 HP:0002171
22 seizure 31 HP:0001250

Symptoms via clinical synopsis from OMIM®:

57 (Updated 05-Apr-2021)
Head And Neck Head:
microcephaly

Laboratory Abnormalities:
increased serum lactate
aminoaciduria (rare)

Muscle Soft Tissue:
hypotonia
deficiency of mitochondrial respiratory enzymes seen on muscle biopsy

Growth Other:
poor growth

Head And Neck Eyes:
coarse retinal pigmentation (rare)
visual impairment (rare)

Hematology:
anemia (rare)
thrombocytopenia (rare)

Neurologic Central Nervous System:
myoclonus
cerebellar atrophy
cerebral atrophy
enlarged ventricles
seizures, refractory
more
Metabolic Features:
lactic acidosis

Abdomen Gastrointestinal:
poor feeding

Head And Neck Ears:
hearing impairment (rare)

Abdomen Liver:
enlarged hepatocytes (rare)
increased glycogen content (rare)

Clinical features from OMIM®:

614946 (Updated 05-Apr-2021)

UMLS symptoms related to Combined Oxidative Phosphorylation Deficiency 14:


myoclonus

Drugs & Therapeutics for Combined Oxidative Phosphorylation Deficiency 14

Search Clinical Trials , NIH Clinical Center for Combined Oxidative Phosphorylation Deficiency 14

Genetic Tests for Combined Oxidative Phosphorylation Deficiency 14

Genetic tests related to Combined Oxidative Phosphorylation Deficiency 14:

# Genetic test Affiliating Genes
1 Combined Oxidative Phosphorylation Deficiency 14 29 FARS2

Anatomical Context for Combined Oxidative Phosphorylation Deficiency 14

Publications for Combined Oxidative Phosphorylation Deficiency 14

Articles related to Combined Oxidative Phosphorylation Deficiency 14:

(show all 12)
# Title Authors PMID Year
1
New insights into the phenotype of FARS2 deficiency. 57 6
29126765 2017
2
Novel Compound Heterozygous Mutations Expand the Recognized Phenotypes of FARS2-Linked Disease. 57 6
27095821 2016
3
Mutation of the human mitochondrial phenylalanine-tRNA synthetase causes infantile-onset epilepsy and cytochrome c oxidase deficiency. 57 6
24161539 2014
4
Mitochondrial phenylalanyl-tRNA synthetase mutations underlie fatal infantile Alpers encephalopathy. 57 6
22833457 2012
5
Genomic analysis of mitochondrial diseases in a consanguineous population reveals novel candidate disease genes. 6 57
22499341 2012
6
Clinical findings in a patient with FARS2 mutations and early-infantile-encephalopathy with epilepsy. 6 61
27549011 2016
7
Two types of recessive hereditary spastic paraplegia in Roma patients in compound heterozygous state; no ethnically prevalent variant found. 6
32007496 2020
8
FARS2 deficiency; new cases, review of clinical, biochemical, and molecular spectra, and variants interpretation based on structural, functional, and evolutionary significance. 6
30177229 2018
9
FARS2 mutation and epilepsy: Possible link with early-onset epileptic encephalopathy. 6
28043061 2017
10
Targeted sequencing of 351 candidate genes for epileptic encephalopathy in a large cohort of patients. 6
27652284 2016
11
A patient with juvenile-onset refractory status epilepticus caused by two novel compound heterozygous mutations in FARS2 gene. 61
31329004 2019
12
Mutations in FARS2 and non-fatal mitochondrial dysfunction in two siblings. 61
25851414 2015

Variations for Combined Oxidative Phosphorylation Deficiency 14

ClinVar genetic disease variations for Combined Oxidative Phosphorylation Deficiency 14:

6 (show top 50) (show all 183)
# Gene Name Type Significance ClinVarId dbSNP ID Position
1 FARS2 NC_000006.12:g.(?_5545160)_(5545360_?)del Deletion Pathogenic 833172 GRCh37: 6:5545393-5545593
GRCh38:
2 FARS2 NM_006567.5(FARS2):c.261G>A (p.Trp87Ter) SNV Pathogenic 652282 rs1229314240 GRCh37: 6:5369064-5369064
GRCh38: 6:5368831-5368831
3 FARS2 NM_006567.5(FARS2):c.812del (p.Thr271fs) Deletion Pathogenic 654274 rs1429774361 GRCh37: 6:5431313-5431313
GRCh38: 6:5431080-5431080
4 FARS2 NM_006567.5(FARS2):c.886C>T (p.Gln296Ter) SNV Pathogenic 966064 GRCh37: 6:5431387-5431387
GRCh38: 6:5431154-5431154
5 FARS2 NM_006567.5(FARS2):c.1113G>T (p.Leu371Phe) SNV Pathogenic 973745 GRCh37: 6:5613449-5613449
GRCh38: 6:5613216-5613216
6 FARS2 NM_006567.5(FARS2):c.251A>C (p.His84Pro) SNV Pathogenic 973746 GRCh37: 6:5369054-5369054
GRCh38: 6:5368821-5368821
7 FARS2 NM_006567.5(FARS2):c.1269_1276dup (p.Ser426Ter) Duplication Pathogenic 973744 GRCh37: 6:5771574-5771575
GRCh38: 6:5771341-5771342
8 FARS2 NM_006567.5(FARS2):c.801C>G (p.Tyr267Ter) SNV Pathogenic 522083 rs761709212 GRCh37: 6:5431302-5431302
GRCh38: 6:5431069-5431069
9 FARS2 NC_000006.12:g.(?_5368551)_(5369202_?)del Deletion Pathogenic 473306 GRCh37:
GRCh38: 6:5368551-5369202
10 FARS2 NC_000006.12:g.(?_5368551)_(5431192_?)del Deletion Pathogenic 540542 GRCh37: 6:5368784-5431425
GRCh38: 6:5368551-5431192
11 FARS2 GRCh37/hg19 6p25.1(chr6:5545413-5545573) copy number loss Pathogenic 813308 GRCh37: 6:5545413-5545573
GRCh38:
12 FARS2 NM_006567.5(FARS2):c.792del (p.Asp265fs) Deletion Pathogenic 579997 rs761097220 GRCh37: 6:5431293-5431293
GRCh38: 6:5431060-5431060
13 FARS2 NM_006567.5(FARS2):c.431A>G (p.Tyr144Cys) SNV Pathogenic 39824 rs397514610 GRCh37: 6:5369234-5369234
GRCh38: 6:5369001-5369001
14 FARS2 NM_006567.5(FARS2):c.1256G>A (p.Arg419His) SNV Pathogenic 429663 rs202183509 GRCh37: 6:5771562-5771562
GRCh38: 6:5771329-5771329
15 FARS2 NM_006567.5(FARS2):c.1082C>T (p.Pro361Leu) SNV Pathogenic/Likely pathogenic 214335 rs751459058 GRCh37: 6:5613418-5613418
GRCh38: 6:5613185-5613185
16 FARS2 NM_006567.5(FARS2):c.925G>A (p.Gly309Ser) SNV Likely pathogenic 587672 rs746746116 GRCh37: 6:5545433-5545433
GRCh38: 6:5545200-5545200
17 FARS2 NM_006567.5(FARS2):c.192C>G (p.Ser64Arg) SNV Likely pathogenic 488515 rs1554169280 GRCh37: 6:5368995-5368995
GRCh38: 6:5368762-5368762
18 FARS2 NM_006567.5(FARS2):c.1163T>G (p.Ile388Ser) SNV Likely pathogenic 488516 rs1407198979 GRCh37: 6:5613499-5613499
GRCh38: 6:5613266-5613266
19 FARS2 NC_000006.11:g.5262296_5395849del133554 Deletion Likely pathogenic 587674 GRCh37: 6:5262296-5395849
GRCh38: 6:5262063-5395616
20 overlap with 2 genes NC_000006.11:g.5193613_5281294del87682 Deletion Likely pathogenic 587675 GRCh37: 6:5193613-5281294
GRCh38:
21 FARS2 NM_006567.5(FARS2):c.905-1G>A SNV Likely pathogenic 587678 rs1298860043 GRCh37: 6:5545412-5545412
GRCh38: 6:5545179-5545179
22 FARS2 NM_006567.5(FARS2):c.403C>G (p.His135Asp) SNV Likely pathogenic 214339 rs1554169353 GRCh37: 6:5369206-5369206
GRCh38: 6:5368973-5368973
23 FARS2 NM_006567.5(FARS2):c.457A>G (p.Arg153Gly) SNV Likely pathogenic 587670 rs1561990337 GRCh37: 6:5369260-5369260
GRCh38: 6:5369027-5369027
24 FARS2 NM_006567.5(FARS2):c.530T>A (p.Val177Asp) SNV Likely pathogenic 587671 rs1561990552 GRCh37: 6:5369333-5369333
GRCh38: 6:5369100-5369100
25 FARS2 NM_006567.5(FARS2):c.986T>C (p.Ile329Thr) SNV Likely pathogenic 39825 rs397514611 GRCh37: 6:5545494-5545494
GRCh38: 6:5545261-5545261
26 FARS2 NM_006567.5(FARS2):c.1172A>T (p.Asp391Val) SNV Likely pathogenic 39826 rs397514612 GRCh37: 6:5613508-5613508
GRCh38: 6:5613275-5613275
27 FARS2 NM_006567.5(FARS2):c.973G>T (p.Asp325Tyr) SNV Likely pathogenic 253158 rs764427452 GRCh37: 6:5545481-5545481
GRCh38: 6:5545248-5545248
28 FARS2 NM_006567.5(FARS2):c.407C>A (p.Pro136His) SNV Conflicting interpretations of pathogenicity 473309 rs199863563 GRCh37: 6:5369210-5369210
GRCh38: 6:5368977-5368977
29 FARS2 NM_006567.5(FARS2):c.676C>T (p.His226Tyr) SNV Conflicting interpretations of pathogenicity 473314 rs201991648 GRCh37: 6:5404838-5404838
GRCh38: 6:5404605-5404605
30 FARS2 NM_006567.5(FARS2):c.506A>T (p.Asp169Val) SNV Conflicting interpretations of pathogenicity 214338 rs146356199 GRCh37: 6:5369309-5369309
GRCh38: 6:5369076-5369076
31 FARS2 NM_006567.5(FARS2):c.667C>T (p.Arg223Cys) SNV Conflicting interpretations of pathogenicity 214330 rs202060864 GRCh37: 6:5404829-5404829
GRCh38: 6:5404596-5404596
32 FARS2 NM_006567.5(FARS2):c.467C>T (p.Thr156Met) SNV Conflicting interpretations of pathogenicity 587677 rs146988468 GRCh37: 6:5369270-5369270
GRCh38: 6:5369037-5369037
33 FARS2 NM_006567.5(FARS2):c.253C>G (p.Pro85Ala) SNV Conflicting interpretations of pathogenicity 587669 rs770035560 GRCh37: 6:5369056-5369056
GRCh38: 6:5368823-5368823
34 FARS2 NM_006567.5(FARS2):c.629A>G (p.Lys210Arg) SNV Uncertain significance 850224 GRCh37: 6:5404791-5404791
GRCh38: 6:5404558-5404558
35 FARS2 NM_006567.5(FARS2):c.202C>T (p.Arg68Trp) SNV Uncertain significance 851799 GRCh37: 6:5369005-5369005
GRCh38: 6:5368772-5368772
36 FARS2 NM_006567.5(FARS2):c.786A>G (p.Arg262=) SNV Uncertain significance 935464 GRCh37: 6:5431287-5431287
GRCh38: 6:5431054-5431054
37 FARS2 NM_006567.5(FARS2):c.1012C>A (p.Arg338Ser) SNV Uncertain significance 940097 GRCh37: 6:5545520-5545520
GRCh38: 6:5545287-5545287
38 FARS2 NM_006567.5(FARS2):c.410G>C (p.Ser137Thr) SNV Uncertain significance 949385 GRCh37: 6:5369213-5369213
GRCh38: 6:5368980-5368980
39 FARS2 NM_006567.5(FARS2):c.673G>A (p.Ala225Thr) SNV Uncertain significance 952062 GRCh37: 6:5404835-5404835
GRCh38: 6:5404602-5404602
40 FARS2 NM_006567.5(FARS2):c.625A>G (p.Ile209Val) SNV Uncertain significance 956703 GRCh37: 6:5404787-5404787
GRCh38: 6:5404554-5404554
41 FARS2 NM_006567.5(FARS2):c.1217A>G (p.Lys406Arg) SNV Uncertain significance 959450 GRCh37: 6:5613553-5613553
GRCh38: 6:5613320-5613320
42 FARS2 NM_006567.5(FARS2):c.755C>G (p.Ala252Gly) SNV Uncertain significance 1015556 GRCh37: 6:5404917-5404917
GRCh38: 6:5404684-5404684
43 FARS2 NM_006567.5(FARS2):c.1210C>T (p.His404Tyr) SNV Uncertain significance 1016873 GRCh37: 6:5613546-5613546
GRCh38: 6:5613313-5613313
44 FARS2 NM_006567.5(FARS2):c.80A>G (p.His27Arg) SNV Uncertain significance 1018888 GRCh37: 6:5368883-5368883
GRCh38: 6:5368650-5368650
45 FARS2 NM_006567.5(FARS2):c.586G>T (p.Ala196Ser) SNV Uncertain significance 1019925 GRCh37: 6:5369389-5369389
GRCh38: 6:5369156-5369156
46 FARS2 NM_006567.5(FARS2):c.183C>G (p.Asp61Glu) SNV Uncertain significance 1021309 GRCh37: 6:5368986-5368986
GRCh38: 6:5368753-5368753
47 FARS2 NM_006567.5(FARS2):c.630G>C (p.Lys210Asn) SNV Uncertain significance 1023378 GRCh37: 6:5404792-5404792
GRCh38: 6:5404559-5404559
48 FARS2 NM_006567.5(FARS2):c.920G>A (p.Arg307Gln) SNV Uncertain significance 1023848 GRCh37: 6:5545428-5545428
GRCh38: 6:5545195-5545195
49 FARS2 NC_000006.11:g.(?_5431254)_(5431425_?)del Deletion Uncertain significance 1024826 GRCh37: 6:5431254-5431425
GRCh38:
50 FARS2 NM_006567.5(FARS2):c.550G>A (p.Asp184Asn) SNV Uncertain significance 214340 rs554931092 GRCh37: 6:5369353-5369353
GRCh38: 6:5369120-5369120

UniProtKB/Swiss-Prot genetic disease variations for Combined Oxidative Phosphorylation Deficiency 14:

72
# Symbol AA change Variation ID SNP ID
1 FARS2 p.Tyr144Cys VAR_069487 rs397514610
2 FARS2 p.Ile329Thr VAR_069488 rs397514611
3 FARS2 p.Asp391Val VAR_069489 rs397514612

Expression for Combined Oxidative Phosphorylation Deficiency 14

Search GEO for disease gene expression data for Combined Oxidative Phosphorylation Deficiency 14.

Pathways for Combined Oxidative Phosphorylation Deficiency 14

GO Terms for Combined Oxidative Phosphorylation Deficiency 14

Sources for Combined Oxidative Phosphorylation Deficiency 14

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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