COXPD12
MCID: CMB026
MIFTS: 47

Combined Oxidative Phosphorylation Deficiency 12 (COXPD12)

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

Aliases & Classifications for Combined Oxidative Phosphorylation Deficiency 12

MalaCards integrated aliases for Combined Oxidative Phosphorylation Deficiency 12:

Name: Combined Oxidative Phosphorylation Deficiency 12 57 12 20 43 72 29 13 6 15 70
Coxpd12 57 12 20 43 58 72
Ltbl 57 12 20 43 58 72
Leukoencephalopathy with Thalamus and Brainstem Involvement and High Lactate 57 12 20 43 72
Leukoencephalopathy-Thalamus and Brainstem Anomalies-High Lactate Syndrome 12 20 58
Combined Oxidative Phosphorylation Defect Type 12 20 58
Leukoencephalopathy with Thalamus and Brainstem Involvement and High Lactate; Ltbl 57
Combined Oxidative Phosphorylation Deficiency, Type 12 39

Characteristics:

Orphanet epidemiological data:

58
leukoencephalopathy-thalamus and brainstem anomalies-high lactate syndrome
Prevalence: <1/1000000 (Worldwide); Age of onset: Infancy,Neonatal;

OMIM®:

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

Miscellaneous:
onset in first year of life
two main phenotypes, severe and mild
mild cases show clinical, biochemical, and mri improvement after the second year of life


HPO:

31
combined oxidative phosphorylation deficiency 12:
Inheritance autosomal recessive inheritance
Onset and clinical course infantile onset


Classifications:

Orphanet: 58  
Rare neurological diseases
Inborn errors of metabolism


Summaries for Combined Oxidative Phosphorylation Deficiency 12

MedlinePlus Genetics : 43 Leukoencephalopathy with thalamus and brainstem involvement and high lactate (LTBL) is a disorder that affects the brain. LTBL is one of a group of genetic disorders called leukodystrophies, which feature abnormalities of the nervous system's white matter. White matter consists of nerve fibers covered by a fatty substance, called myelin, that insulates nerve fibers and promotes the rapid transmission of nerve impulses.LTBL is characterized by distinct changes in the brain, which can be seen using magnetic resonance imaging (MRI). These abnormalities typically involve white matter in regions of the brain known as the cerebrum and cerebellum. Abnormalities can also be seen in other regions of the brain, including the brainstem, which is the part that connects to the spinal cord. Affected brain regions include the thalamus, midbrain, pons, and medulla oblongata. Thinning of the tissue that connects the left and right halves of the brain (the corpus callosum) also occurs in people with LTBL. In addition, most affected individuals have a high level of a substance called lactate in the brain and elsewhere in the body.The severity of the condition varies. Mildly affected individuals usually develop signs and symptoms after the age of 6 months. Loss of mental and movement abilities (psychomotor regression), muscle stiffness (spasticity), and extreme irritability are common, and some people with mild LTBL develop seizures. However, after age 2, the signs and symptoms of the condition improve: affected children regain some psychomotor abilities, seizures are reduced or disappear, MRI results become more normal, and lactate levels drop.Severely affected individuals have features that begin soon after birth. These infants typically have delayed development of mental and movement abilities (psychomotor delay), weak muscle tone (hypotonia), involuntary muscle tensing (dystonia), muscle spasticity, and seizures. Some have extremely high levels of lactate (lactic acidosis), which can cause serious breathing problems and an abnormal heartbeat. Liver failure occurs in some severely affected infants. In severe cases, the signs and symptoms do not improve and can be life-threatening. In some people with LTBL, the features fall between mild and severe.

MalaCards based summary : Combined Oxidative Phosphorylation Deficiency 12, also known as coxpd12, is related to encephalopathy and hypotonia, and has symptoms including seizures and ophthalmoplegia. An important gene associated with Combined Oxidative Phosphorylation Deficiency 12 is EARS2 (Glutamyl-TRNA Synthetase 2, Mitochondrial), and among its related pathways/superpathways are Gene Expression and tRNA Aminoacylation. Affiliated tissues include brain, thalamus and cerebellum, and related phenotypes are hepatomegaly and cleft palate

Disease Ontology : 12 A combined oxidative phosphorylation deficiency characterized by infantile onset of hypotonia and delayed psychomotor development or developmental regression that has material basis in homozygous or compound heterozygous mutation in EARS2 on chromosome 16p12.2.

GARD : 20 Leukoencephalopathy with thalamus and brainstem involvement and high lactate (LTBL) is a rare disorder that affects the brain. It is part of a group of disorders known as leukodystrophies. Leukodystrophies are diseases that affect the white matter of the brain. The white matter contains nerve fibers ( axons ), surrounded by a type of sheath or covering called myelin (a fatty, white colored substance) that allows the transmission of impulses or communication among brain cells (neurons). LTBL is characterized by changes in specific parts of the brain including the cerebellum, thalamus and brainstem. These changes can be seen by brain imaging exams ( MRI ). High levels of lactate in the blood and in the cerebral spinal fluid are also seen. There are basically two forms of the disease based on severity of symptoms and age of onset: A mild disease, with onset around 6 months of age, characterized by the loss of acquired skills (psychomotor regression), muscle stiffness ( spasticity ), irritability and seizures. These symptoms often improve during the toddler years. A severe disease with symptoms that start in newborns and include brain and liver problems. Symptoms generally do not improve with age. LTBL is caused by changes ( mutations ) in the EARS2 gene. Mutations in this gene decrease the amount of a specific mitochondrial enzyme needed for proper mitochondrial function ( mitochondria are cell structures that convert the energy from food into a form that cells can use), and therefore, LTBL is also considered a type of mitochondrial disorder. It is inherited in an autosomal recessive pattern. There is still no cure for this disease. Treatment is typically supportive based on presenting symptoms.

OMIM® : 57 COXPD12 is an autosomal recessive mitochondrial neurologic disorder characterized by onset in infancy of hypotonia and delayed psychomotor development, or early developmental regression, associated with T2-weighted hyperintensities in the deep cerebral white matter, brainstem, and cerebellar white matter. Serum lactate is increased due to a defect in mitochondrial respiration. There are 2 main phenotypic groups: those with a milder disease course and some recovery of skills after age 2 years, and those with a severe disease course resulting in marked disability (summary by Steenweg et al., 2012). For a discussion of genetic heterogeneity of combined oxidative phosphorylation deficiency, see COXPD1 (609060). (614924) (Updated 05-Apr-2021)

UniProtKB/Swiss-Prot : 72 Combined oxidative phosphorylation deficiency 12: An autosomal recessive, mitochondrial, neurologic disorder characterized by onset in infancy of hypotonia and delayed psychomotor development, or early developmental regression, associated with T2- weighted hyperintensities in the deep cerebral white matter, brainstem, and cerebellar white matter. Serum lactate is increased due to a defect in mitochondrial respiration. There are 2 main phenotypic groups: those with a milder disease course and some recovery of skills after age 2 years, and those with a severe disease course resulting in marked disability.

Related Diseases for Combined Oxidative Phosphorylation Deficiency 12

Diseases related to Combined Oxidative Phosphorylation Deficiency 12 via text searches within MalaCards or GeneCards Suite gene sharing:

(show all 36)
# Related Disease Score Top Affiliating Genes
1 encephalopathy 10.5
2 hypotonia 10.5
3 metabolic acidosis 10.4
4 spasticity 10.4
5 deafness, autosomal recessive 89 10.1 RARS2 EPRS1
6 deafness, autosomal recessive 94 10.1 FARS2 EARS2
7 pontocerebellar hypoplasia 10.1 RARS2 EPRS1 DARS2
8 combined oxidative phosphorylation deficiency 2 10.1 VARS2 VARS1
9 neurodevelopmental disorder with microcephaly, seizures, and cortical atrophy 10.0 VARS2 VARS1
10 antisynthetase syndrome 10.0 TARS2 EPRS1
11 mitochondrial dna depletion syndrome 5 10.0 RARS2 DARS2
12 myopathy, lactic acidosis, and sideroblastic anemia 10.0 YARS2 AARS2
13 lactic acidosis 9.9
14 myopathy, lactic acidosis, and sideroblastic anemia 2 9.9 YARS2 TARS2
15 46 xx gonadal dysgenesis 9.9 EPRS1 DARS2
16 myopathy, lactic acidosis, and sideroblastic anemia 1 9.9 YARS2 AARS2
17 charcot-marie-tooth disease, axonal, type 2u 9.9 EPRS1 AARS1
18 leukodystrophy 9.9 EPRS1 EARS2 DARS2 AARS2
19 mitochondrial encephalomyopathy 9.7 TARS2 FARS2 EPRS1 AARS2
20 developmental and epileptic encephalopathy 29 9.7 RARS2 MARS2 AARS1
21 mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes 9.7 YARS2 RARS2 EPRS1 DARS2
22 charcot-marie-tooth disease intermediate type 9.6 YARS2 AARS1
23 infantile liver failure syndrome 9.6 RARS2 MARS2 EPRS1 AARS1
24 autosomal dominant distal hereditary motor neuronopathy 9.6 YARS2 EPRS1 AARS1
25 pontocerebellar hypoplasia, type 6 9.6 RARS2 MARS2 DARS2 AARS1
26 combined oxidative phosphorylation deficiency 20 9.6 YARS2 VARS2 VARS1 RARS2
27 charcot-marie-tooth disease, recessive intermediate b 9.6 YARS2 AARS2 AARS1
28 robinow syndrome, autosomal recessive 1 9.5 RARS2 EPRS1 DARS1 AARS1
29 charcot-marie-tooth disease, dominant intermediate c 9.5 YARS2 EPRS1 DARS2 AARS1
30 charcot-marie-tooth disease, axonal, type 2n 9.5 YARS2 EPRS1 AARS2 AARS1
31 charcot-marie-tooth disease, axonal, type 2d 9.5 YARS2 EPRS1 DARS2 AARS1
32 combined oxidative phosphorylation deficiency 9.4 VARS2 TARS2 MARS2 FARS2 EARS2 AARS2
33 charcot-marie-tooth disease 9.3 YARS2 MARS2 EPRS1 AARS2 AARS1
34 mitochondrial dna depletion syndrome 4a 9.1 YARS2 RARS2 FARS2 EARS2 DARS2 AARS1
35 neuronopathy, distal hereditary motor, type va 8.8 YARS2 FARS2 EPRS1 DARS2 DARS1 AARS2
36 perrault syndrome 7.9 YARS2 VARS2 VARS1 TARS2 RARS2 MARS2

Graphical network of the top 20 diseases related to Combined Oxidative Phosphorylation Deficiency 12:



Diseases related to Combined Oxidative Phosphorylation Deficiency 12

Symptoms & Phenotypes for Combined Oxidative Phosphorylation Deficiency 12

Human phenotypes related to Combined Oxidative Phosphorylation Deficiency 12:

31 (show all 25)
# Description HPO Frequency HPO Source Accession
1 hepatomegaly 31 occasional (7.5%) HP:0002240
2 cleft palate 31 occasional (7.5%) HP:0000175
3 cholestasis 31 occasional (7.5%) HP:0001396
4 macrovesicular hepatic steatosis 31 occasional (7.5%) HP:0001403
5 failure to thrive 31 HP:0001508
6 ptosis 31 HP:0000508
7 developmental regression 31 HP:0002376
8 global developmental delay 31 HP:0001263
9 visual impairment 31 HP:0000505
10 neonatal hypotonia 31 HP:0001319
11 absent speech 31 HP:0001344
12 ragged-red muscle fibers 31 HP:0003200
13 ophthalmoplegia 31 HP:0000602
14 increased serum lactate 31 HP:0002151
15 dystonia 31 HP:0001332
16 hypoplasia of the corpus callosum 31 HP:0002079
17 decreased activity of mitochondrial complex i 31 HP:0011923
18 leukoencephalopathy 31 HP:0002352
19 lactic acidosis 31 HP:0003128
20 spastic tetraparesis 31 HP:0001285
21 bradykinesia 31 HP:0002067
22 dysplastic corpus callosum 31 HP:0006989
23 decreased activity of mitochondrial complex iii 31 HP:0011924
24 decreased activity of mitochondrial complex iv 31 HP:0008347
25 seizure 31 HP:0001250

Symptoms via clinical synopsis from OMIM®:

57 (Updated 05-Apr-2021)
Neurologic Central Nervous System:
seizures
dysplastic corpus callosum
thinning of the corpus callosum
delayed psychomotor development (in severe cases)
psychomotor regression (in milder cases)
more
Head And Neck Eyes:
ptosis
visual impairment
ophthalmoplegia

Metabolic Features:
lactic acidosis

Abdomen Liver:
cholestasis (1 patient)
hepatomegaly (1 patient)
macrovesicular steatosis (1 patient)
fibrosis, mild (1 patient)

Cardiovascular Heart:
interventricular septal hypertrophy (1 patient)

Growth Other:
failure to thrive

Laboratory Abnormalities:
increased serum lactate
abnormal liver enzymes, intermittent (1 patient)
increased alpha-fetoprotein (1 patient)

Muscle Soft Tissue:
hypotonia, neonatal
ragged-red fibers
muscle biopsy shows cytochrome c oxidase-negative fibers
decreased activities of mitochondrial complexes i, iii, and iv
impaired mitochondrial respiration

Head And Neck Mouth:
cleft palate (1 patient)

Clinical features from OMIM®:

614924 (Updated 05-Apr-2021)

UMLS symptoms related to Combined Oxidative Phosphorylation Deficiency 12:


seizures; ophthalmoplegia

MGI Mouse Phenotypes related to Combined Oxidative Phosphorylation Deficiency 12:

46
# Description MGI Source Accession Score Top Affiliating Genes
1 mortality/aging MP:0010768 9.36 AARS1 AARS2 DARS1 DARS2 EARS2 EPRS1

Drugs & Therapeutics for Combined Oxidative Phosphorylation Deficiency 12

Search Clinical Trials , NIH Clinical Center for Combined Oxidative Phosphorylation Deficiency 12

Genetic Tests for Combined Oxidative Phosphorylation Deficiency 12

Genetic tests related to Combined Oxidative Phosphorylation Deficiency 12:

# Genetic test Affiliating Genes
1 Combined Oxidative Phosphorylation Deficiency 12 29 EARS2

Anatomical Context for Combined Oxidative Phosphorylation Deficiency 12

MalaCards organs/tissues related to Combined Oxidative Phosphorylation Deficiency 12:

40
Brain, Thalamus, Cerebellum, Spinal Cord, Pons, Medulla Oblongata, Liver

Publications for Combined Oxidative Phosphorylation Deficiency 12

Articles related to Combined Oxidative Phosphorylation Deficiency 12:

(show all 16)
# Title Authors PMID Year
1
Leukoencephalopathy with thalamus and brainstem involvement and high lactate 'LTBL' caused by EARS2 mutations. 20 57 6 61
22492562 2012
2
Multisystem fatal infantile disease caused by a novel homozygous EARS2 mutation. 6 57
23008233 2013
3
EARS2 mutations cause fatal neonatal lactic acidosis, recurrent hypoglycemia and agenesis of corpus callosum. 6
26780086 2016
4
Mitochondrial syndromes with leukoencephalopathies. 20
22422207 2012
5
Identification of a Novel Variant in EARS2 Associated with a Severe Clinical Phenotype Expands the Clinical Spectrum of LTBL. 61
32887222 2020
6
The impact of bile leakage on long-term prognosis in primary liver cancers after hepatectomy: A propensity-score-matched study. 61
31611103 2020
7
An update on clinical, pathological, diagnostic, and therapeutic perspectives of childhood leukodystrophies. 61
31829048 2020
8
Functionally pathogenic EARS2 variants in vitro may not manifest a phenotype in vivo. 61
28748214 2017
9
Severe Metabolic Acidosis and Hepatopathy due to Leukoencephalopathy with Thalamus and Brainstem Involvement and High Lactate. 61
27875839 2017
10
Lethal Neonatal LTBL Associated with Biallelic EARS2 Variants: Case Report and Review of the Reported Neuroradiological Features. 61
27571996 2017
11
A compound heterozygous EARS2 mutation associated with mild leukoencephalopathy with thalamus and brainstem involvement and high lactate (LTBL). 61
27117034 2016
12
Early-Onset Mild Type Leukoencephalopathy Caused by a Homozygous EARS2 Mutation. 61
26893310 2016
13
Leukoencephalopathy with thalamus and brainstem involvement and high lactate caused by novel mutations in the EARS2 gene in two siblings. 61
27206875 2016
14
Absent Thalami Caused by a Homozygous EARS2 Mutation: Expanding Disease Spectrum of LTBL. 61
26619324 2016
15
Expanding the Clinical and Magnetic Resonance Spectrum of Leukoencephalopathy with Thalamus and Brainstem Involvement and High Lactate (LTBL) in a Patient Harboring a Novel EARS2 Mutation. 61
25854774 2015
16
[Retrospective analysis of 54 patients with high risk aggressive T-cell non-Hodgkin lymphomas]. 61
18072627 2007

Variations for Combined Oxidative Phosphorylation Deficiency 12

ClinVar genetic disease variations for Combined Oxidative Phosphorylation Deficiency 12:

6 (show top 50) (show all 101)
# Gene Name Type Significance ClinVarId dbSNP ID Position
1 EARS2 NM_001083614.2(EARS2):c.502A>G (p.Arg168Gly) SNV Pathogenic 39788 rs397514591 GRCh37: 16:23546665-23546665
GRCh38: 16:23535344-23535344
2 EARS2 NM_001083614.2(EARS2):c.610G>A (p.Gly204Ser) SNV Pathogenic 39790 rs397514592 GRCh37: 16:23546557-23546557
GRCh38: 16:23535236-23535236
3 EARS2 NM_001083614.2(EARS2):c.286G>A (p.Glu96Lys) SNV Pathogenic 39791 rs397514593 GRCh37: 16:23563479-23563479
GRCh38: 16:23552158-23552158
4 EARS2 NM_001083614.2(EARS2):c.500G>A (p.Cys167Tyr) SNV Pathogenic 39792 rs397514594 GRCh37: 16:23546667-23546667
GRCh38: 16:23535346-23535346
5 EARS2 NM_001083614.2(EARS2):c.193A>G (p.Lys65Glu) SNV Pathogenic 39793 rs397514595 GRCh37: 16:23563572-23563572
GRCh38: 16:23552251-23552251
6 EARS2 NM_001083614.2(EARS2):c.684C>A (p.Tyr228Ter) SNV Pathogenic 803228 rs1445826036 GRCh37: 16:23546483-23546483
GRCh38: 16:23535162-23535162
7 EARS2 NM_001083614.2(EARS2):c.1283del (p.Pro428fs) Deletion Pathogenic 973189 GRCh37: 16:23540892-23540892
GRCh38: 16:23529571-23529571
8 EARS2 NM_001083614.2(EARS2):c.322C>T (p.Arg108Trp) SNV Pathogenic 39787 rs376103091 GRCh37: 16:23555998-23555998
GRCh38: 16:23544677-23544677
9 EARS2 NM_001083614.2(EARS2):c.320G>A (p.Arg107His) SNV Pathogenic 449533 rs1021330566 GRCh37: 16:23556000-23556000
GRCh38: 16:23544679-23544679
10 EARS2 NM_001083614.2(EARS2):c.1294C>T (p.Arg432Ter) SNV Pathogenic 1033281 GRCh37: 16:23540881-23540881
GRCh38: 16:23529560-23529560
11 EARS2 NM_001083614.2(EARS2):c.291G>A (p.Trp97Ter) SNV Pathogenic 1033676 GRCh37: 16:23563474-23563474
GRCh38: 16:23552153-23552153
12 EARS2 NM_001083614.2(EARS2):c.328G>A (p.Gly110Ser) SNV Pathogenic/Likely pathogenic 39789 rs201842633 GRCh37: 16:23555992-23555992
GRCh38: 16:23544671-23544671
13 EARS2 NM_001083614.2(EARS2):c.1547G>A (p.Arg516Gln) SNV Likely pathogenic 265109 rs201727231 GRCh37: 16:23535717-23535717
GRCh38: 16:23524396-23524396
14 EARS2 NM_001083614.2(EARS2):c.319C>T (p.Arg107Cys) SNV Likely pathogenic 973188 GRCh37: 16:23556001-23556001
GRCh38: 16:23544680-23544680
15 EARS2 NM_001083614.2(EARS2):c.745G>C (p.Glu249Gln) SNV Uncertain significance 1033677 GRCh37: 16:23546422-23546422
GRCh38: 16:23535101-23535101
16 EARS2 NM_001083614.2(EARS2):c.263C>A (p.Ala88Glu) SNV Uncertain significance 318556 rs201929423 GRCh37: 16:23563502-23563502
GRCh38: 16:23552181-23552181
17 EARS2 NM_001083614.2(EARS2):c.1352G>T (p.Gly451Val) SNV Uncertain significance 318544 rs201181229 GRCh37: 16:23540823-23540823
GRCh38: 16:23529502-23529502
18 EARS2 NM_001083614.2(EARS2):c.1045G>A (p.Glu349Lys) SNV Uncertain significance 425101 rs187662524 GRCh37: 16:23544000-23544000
GRCh38: 16:23532679-23532679
19 EARS2 NM_001083614.2(EARS2):c.1351G>A (p.Gly451Arg) SNV Uncertain significance 1030114 GRCh37: 16:23540824-23540824
GRCh38: 16:23529503-23529503
20 EARS2 NM_001083614.2(EARS2):c.43T>C (p.Ser15Pro) SNV Uncertain significance 1030115 GRCh37: 16:23568622-23568622
GRCh38: 16:23557301-23557301
21 EARS2 NM_001083614.2(EARS2):c.913G>A (p.Asp305Asn) SNV Uncertain significance 1030116 GRCh37: 16:23546254-23546254
GRCh38: 16:23534933-23534933
22 EARS2 NM_001083614.2(EARS2):c.667G>A (p.Asp223Asn) SNV Uncertain significance 318552 rs746087016 GRCh37: 16:23546500-23546500
GRCh38: 16:23535179-23535179
23 EARS2 NM_001308211.1(EARS2):c.-19G>A SNV Uncertain significance 318557 rs377067442 GRCh37: 16:23568683-23568683
GRCh38: 16:23557362-23557362
24 EARS2 NM_001083614.2(EARS2):c.*180A>G SNV Uncertain significance 885122 GRCh37: 16:23535512-23535512
GRCh38: 16:23524191-23524191
25 EARS2 NM_001083614.2(EARS2):c.994A>C (p.Thr332Pro) SNV Uncertain significance 888297 GRCh37: 16:23544051-23544051
GRCh38: 16:23532730-23532730
26 EARS2 NM_001083614.2(EARS2):c.1243G>A (p.Asp415Asn) SNV Uncertain significance 803227 rs763888954 GRCh37: 16:23540932-23540932
GRCh38: 16:23529611-23529611
27 EARS2 NM_001083614.2(EARS2):c.*155A>G SNV Uncertain significance 318537 rs886051830 GRCh37: 16:23535537-23535537
GRCh38: 16:23524216-23524216
28 EARS2 NM_001083614.2(EARS2):c.209G>T (p.Ser70Ile) SNV Uncertain significance 559206 rs201941745 GRCh37: 16:23563556-23563556
GRCh38: 16:23552235-23552235
29 EARS2 NM_001083614.2(EARS2):c.1234C>T (p.Arg412Cys) SNV Uncertain significance 870561 GRCh37: 16:23540941-23540941
GRCh38: 16:23529620-23529620
30 EARS2 NM_001083614.2(EARS2):c.*1904A>G SNV Uncertain significance 885046 GRCh37: 16:23533788-23533788
GRCh38: 16:23522467-23522467
31 EARS2 NM_001083614.2(EARS2):c.*1902A>C SNV Uncertain significance 885047 GRCh37: 16:23533790-23533790
GRCh38: 16:23522469-23522469
32 EARS2 NM_001083614.2(EARS2):c.*637A>G SNV Uncertain significance 885120 GRCh37: 16:23535055-23535055
GRCh38: 16:23523734-23523734
33 EARS2 NM_001083614.2(EARS2):c.873C>T (p.Asp291=) SNV Uncertain significance 885191 GRCh37: 16:23546294-23546294
GRCh38: 16:23534973-23534973
34 EARS2 NM_001083614.2(EARS2):c.851A>G (p.Lys284Arg) SNV Uncertain significance 885192 GRCh37: 16:23546316-23546316
GRCh38: 16:23534995-23534995
35 EARS2 NM_001083614.2(EARS2):c.*1647C>T SNV Uncertain significance 885965 GRCh37: 16:23534045-23534045
GRCh38: 16:23522724-23522724
36 EARS2 NM_001083614.2(EARS2):c.1491A>G (p.Gln497=) SNV Uncertain significance 886035 GRCh37: 16:23535773-23535773
GRCh38: 16:23524452-23524452
37 EARS2 NM_001083614.2(EARS2):c.403G>A (p.Gly135Arg) SNV Uncertain significance 886093 GRCh37: 16:23555917-23555917
GRCh38: 16:23544596-23544596
38 EARS2 NM_001083614.2(EARS2):c.263C>T (p.Ala88Val) SNV Uncertain significance 886094 GRCh37: 16:23563502-23563502
GRCh38: 16:23552181-23552181
39 EARS2 NM_001083614.2(EARS2):c.*1082T>C SNV Uncertain significance 886968 GRCh37: 16:23534610-23534610
GRCh38: 16:23523289-23523289
40 EARS2 NM_001083614.2(EARS2):c.1193A>G (p.Tyr398Cys) SNV Uncertain significance 887028 GRCh37: 16:23541093-23541093
GRCh38: 16:23529772-23529772
41 EARS2 NM_001083614.2(EARS2):c.197A>T (p.Lys66Met) SNV Uncertain significance 887095 GRCh37: 16:23563568-23563568
GRCh38: 16:23552247-23552247
42 EARS2 NM_001083614.2(EARS2):c.102G>T (p.Gly34=) SNV Uncertain significance 887096 GRCh37: 16:23568563-23568563
GRCh38: 16:23557242-23557242
43 EARS2 NM_001083614.2(EARS2):c.*1027G>A SNV Uncertain significance 888230 GRCh37: 16:23534665-23534665
GRCh38: 16:23523344-23523344
44 EARS2 NM_001083614.2(EARS2):c.*966G>C SNV Uncertain significance 888231 GRCh37: 16:23534726-23534726
GRCh38: 16:23523405-23523405
45 EARS2 NM_001083614.2(EARS2):c.*936T>C SNV Uncertain significance 888232 GRCh37: 16:23534756-23534756
GRCh38: 16:23523435-23523435
46 EARS2 NM_001083614.2(EARS2):c.*824G>A SNV Uncertain significance 888233 GRCh37: 16:23534868-23534868
GRCh38: 16:23523547-23523547
47 EARS2 NM_001083614.2(EARS2):c.949G>T (p.Gly317Cys) SNV Uncertain significance 318550 rs746838793 GRCh37: 16:23546218-23546218
GRCh38: 16:23534897-23534897
48 EARS2 NM_001083614.2(EARS2):c.790C>G (p.Leu264Val) SNV Uncertain significance 522736 rs1555503379 GRCh37: 16:23546377-23546377
GRCh38: 16:23535056-23535056
49 EARS2 NM_001083614.2(EARS2):c.1489-14C>T SNV Uncertain significance 318540 rs369770210 GRCh37: 16:23535789-23535789
GRCh38: 16:23524468-23524468
50 EARS2 NM_001083614.2(EARS2):c.*1408A>G SNV Uncertain significance 318520 rs571312854 GRCh37: 16:23534284-23534284
GRCh38: 16:23522963-23522963

UniProtKB/Swiss-Prot genetic disease variations for Combined Oxidative Phosphorylation Deficiency 12:

72 (show all 14)
# Symbol AA change Variation ID SNP ID
1 EARS2 p.Arg55His VAR_069235 rs770862902
2 EARS2 p.Lys65Glu VAR_069236 rs397514595
3 EARS2 p.Glu96Lys VAR_069237 rs397514593
4 EARS2 p.Arg107His VAR_069238 rs102133056
5 EARS2 p.Arg108Trp VAR_069239 rs376103091
6 EARS2 p.Gly110Ser VAR_069240 rs201842633
7 EARS2 p.Cys167Tyr VAR_069241 rs397514594
8 EARS2 p.Arg168Gly VAR_069242 rs397514591
9 EARS2 p.Gly204Ser VAR_069243 rs397514592
10 EARS2 p.Gly224Ser VAR_069244 rs141129877
11 EARS2 p.Gly317Cys VAR_069245 rs746838793
12 EARS2 p.Arg516Gln VAR_069247 rs201727231
13 EARS2 p.Arg107Cys VAR_076183 rs135568545
14 EARS2 p.Arg489Gln VAR_076184 rs757965573

Expression for Combined Oxidative Phosphorylation Deficiency 12

Search GEO for disease gene expression data for Combined Oxidative Phosphorylation Deficiency 12.

Pathways for Combined Oxidative Phosphorylation Deficiency 12

Pathways related to Combined Oxidative Phosphorylation Deficiency 12 according to GeneCards Suite gene sharing:

# Super pathways Score Top Affiliating Genes
1
Show member pathways
13.2 YARS2 VARS2 VARS1 TARS2 RARS2 MARS2
2
Show member pathways
11.68 YARS2 VARS2 VARS1 TARS2 RARS2 MARS2
3 11.29 VARS1 MARS2 EPRS1

GO Terms for Combined Oxidative Phosphorylation Deficiency 12

Cellular components related to Combined Oxidative Phosphorylation Deficiency 12 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 mitochondrial matrix GO:0005759 9.5 YARS2 TARS2 RARS2 MARS2 FARS2 EARS2
2 mitochondrion GO:0005739 9.32 YARS2 VARS2 TARS2 RARS2 MARS2 FARS2
3 aminoacyl-tRNA synthetase multienzyme complex GO:0017101 9.16 EPRS1 DARS1

Biological processes related to Combined Oxidative Phosphorylation Deficiency 12 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 tRNA aminoacylation GO:0043039 9.76 YARS2 TARS2 FARS2 EPRS1 EARS2 DARS2
2 tRNA aminoacylation for protein translation GO:0006418 9.73 YARS2 VARS2 VARS1 TARS2 RARS2 MARS2
3 aminoacyl-tRNA metabolism involved in translational fidelity GO:0106074 9.65 VARS2 VARS1 TARS2 AARS2 AARS1
4 translation GO:0006412 9.44 YARS2 VARS2 VARS1 TARS2 RARS2 MARS2
5 tRNA modification GO:0006400 9.43 AARS2 AARS1
6 alanyl-tRNA aminoacylation GO:0006419 9.4 AARS2 AARS1
7 valyl-tRNA aminoacylation GO:0006438 9.37 VARS2 VARS1
8 glutamyl-tRNA aminoacylation GO:0006424 9.32 EPRS1 EARS2

Molecular functions related to Combined Oxidative Phosphorylation Deficiency 12 according to GeneCards Suite gene sharing:

(show all 13)
# Name GO ID Score Top Affiliating Genes
1 nucleotide binding GO:0000166 10.07 YARS2 VARS2 VARS1 TARS2 RARS2 MARS2
2 RNA binding GO:0003723 10.04 YARS2 RARS2 EPRS1 EARS2 DARS1 AARS2
3 ATP binding GO:0005524 9.97 YARS2 VARS2 VARS1 TARS2 RARS2 MARS2
4 tRNA binding GO:0000049 9.85 YARS2 FARS2 EARS2 DARS2 AARS2 AARS1
5 protein homodimerization activity GO:0042803 9.83 YARS2 TARS2 EPRS1 DARS2
6 ligase activity GO:0016874 9.77 YARS2 VARS2 VARS1 TARS2 RARS2 MARS2
7 aminoacyl-tRNA editing activity GO:0002161 9.72 VARS2 VARS1 TARS2 AARS2 AARS1
8 amino acid binding GO:0016597 9.51 AARS2 AARS1
9 alanine-tRNA ligase activity GO:0004813 9.48 AARS2 AARS1
10 valine-tRNA ligase activity GO:0004832 9.46 VARS2 VARS1
11 aminoacyl-tRNA ligase activity GO:0004812 9.44 YARS2 VARS2 VARS1 TARS2 RARS2 MARS2
12 glutamate-tRNA ligase activity GO:0004818 9.43 EPRS1 EARS2
13 aspartate-tRNA ligase activity GO:0004815 9.4 DARS2 DARS1

Sources for Combined Oxidative Phosphorylation Deficiency 12

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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