MTDPS4A
MCID: MTC056
MIFTS: 54

Mitochondrial Dna Depletion Syndrome 4a (MTDPS4A)

Categories: Bone diseases, Cardiovascular diseases, Ear diseases, Eye diseases, Gastrointestinal diseases, Genetic diseases, Liver diseases, Metabolic diseases, Muscle diseases, Nephrological diseases, Neuronal diseases, Rare diseases

Aliases & Classifications for Mitochondrial Dna Depletion Syndrome 4a

MalaCards integrated aliases for Mitochondrial Dna Depletion Syndrome 4a:

Name: Mitochondrial Dna Depletion Syndrome 4a 57 12 12 75 13
Alpers Syndrome 57 12 53 25 59 75 37 55 15 73
Alpers-Huttenlocher Syndrome 57 12 53 25 59 75
Alpers Progressive Infantile Poliodystrophy 57 12 53 25 75
Progressive Sclerosing Poliodystrophy 12 25 54 29 6
Alpers Diffuse Degeneration of Cerebral Gray Matter with Hepatic Cirrhosis 57 53 25 75
Alpers Disease 76 53 25
Pndc 57 53 75
Neuronal Degeneration of Childhood with Liver Disease, Progressive 57 53
Diffuse Cerebral Sclerosis of Schilder 25 73
Mtdps4a 57 75
Neuronal Degeneration of Childhood with Liver Disease, Progressive; Pndc 57
Progressive Neuronal Degeneration of Childhood with Liver Disease 59
Neuronal Degeneration of Childhood with Liver Disease Progressive 75
Mitochondrial Dna Depletion Syndrome 4a Alpers Type 75
Alpers Progressive Sclerosing Poliodystrophy 59
Alpers' Disease or Gray-Matter Degeneration 12
Diffuse Cerebral Degeneration in Infancy 53
Poliodystrophia Cerebri Progressiva 53
Progressive Cerebral Poliodystrophy 53
Infantile Poliodystrophy 53
Alper's Syndrome 12
Alpers' Disease 54
Ahs 75

Characteristics:

Orphanet epidemiological data:

59
alpers-huttenlocher syndrome
Inheritance: Autosomal recessive; Prevalence: 1-9/1000000 (Europe); Age of onset: Adolescent,Adult,Childhood,Infancy; Age of death: adolescent,adult,late childhood,young Adult;

OMIM:

57
Inheritance:
autosomal recessive

Miscellaneous:
rapidly progressive
onset in infancy after normal birth and neonatal period
death usually by age 3 years
later onset (late childhood to young adult) has been reported
increased sensitivity to valproic acid toxicity


HPO:

32
mitochondrial dna depletion syndrome 4a:
Onset and clinical course rapidly progressive infantile onset
Inheritance autosomal recessive inheritance


Classifications:



Summaries for Mitochondrial Dna Depletion Syndrome 4a

NINDS : 54 Alpers' disease is a progressive, neurodevelopmental, mitochondrial DNA depletion syndrome characterized by three co-occurring clinical symptoms: psychomotor regression (dementia); seizures; and liver disease.  It is an autosomal recessive disease caused by mutation in the gene for the mitochondrial DNA polymerase POLG.  The disease occurs in about one in 100,000 persons.  Most individuals with Alpers' disease do not show symptoms at birth and develop normally for weeks to years before the onset of symptoms.  Diagnosis is established by testing for the POLG gene.  Symptoms typically occur months before tissue samples show the mitochondrial DNA depletion, so that these depletion studies cannot be used for early diagnosis.  About 80 percent of individuals with Alpers' disease develop symptoms in the first two years of life, and 20 percent develop symptoms between ages 2 and 25.  The first symptoms of the disorder are usually nonspecific and may include hypoglycemia secondary to underlying liver disease, failure to thrive, infection-associated encephalopathy, spasticity, myoclonus (involuntary jerking of a muscle or group of muscles), seizures, or liver failure.  An increased protein level is seen in cerebrospinal fluid analysis.  Cortical blindness (loss of vision due to damage to the area of the cortex that controls vision) develops in about 25 percent of cases. Gastrointestinal dysfunction and cardiomyopathy may occur.  Dementia is typically episodic and often associated with an infection that occurs while another disease is in process.  Seizures may be difficult to control and unrelenting seizures can cause developmental regression as well.  "Alpers-like" disorders  without liver disease are genetically different and have a different clinical course.  Fewer than one-third of individuals with the "Alpers-like" phenotype without liver disease have POLG mutations.

MalaCards based summary : Mitochondrial Dna Depletion Syndrome 4a, also known as alpers syndrome, is related to ah amyloidosis and tumefactive multiple sclerosis, and has symptoms including convulsions, ataxia and vomiting. An important gene associated with Mitochondrial Dna Depletion Syndrome 4a is POLG (DNA Polymerase Gamma, Catalytic Subunit), and among its related pathways/superpathways is tRNA Aminoacylation. Affiliated tissues include liver, brain and cortex, and related phenotypes are ataxia and muscular hypotonia

Disease Ontology : 12 A cerebral degeneration that results in progressive degeneration of grey matter in the cerebrum and has symptom convulsions.

Genetics Home Reference : 25 Alpers-Huttenlocher syndrome is one of the most severe of a group of conditions called the POLG-related disorders. The conditions in this group feature a range of similar signs and symptoms involving muscle-, nerve-, and brain-related functions. Alpers-Huttenlocher syndrome typically becomes apparent in children between ages 2 and 4. People with this condition usually have three characteristic features: recurrent seizures that do not improve with treatment (intractable epilepsy), loss of mental and movement abilities (psychomotor regression), and liver disease.

NIH Rare Diseases : 53 Alpers syndrome is a progressive neurologic disorder that begins during childhood and is complicated in many instances by serious liver disease. Symptoms include increased muscle tone with exaggerated reflexes (spasticity), seizures, and loss of cognitive ability (dementia).   Most often Alpers syndrome is caused by mutations in the POLG gene.

OMIM : 57 Mitochondrial DNA depletion syndrome-4A, also known as Alpers syndrome, is an autosomal recessive disorder characterized by a clinical triad of psychomotor retardation, intractable epilepsy, and liver failure in infants and young children. Pathologic findings include neuronal loss in the cerebral gray matter with reactive astrocytosis and liver cirrhosis. The disorder is progressive and often leads to death from hepatic failure or status epilepticus before age 3 years (review by Milone and Massie, 2010). Some affected individuals may show mild intermittent 3-methylglutaconic aciduria and defects in mitochondrial oxidative phosphorylation (Wortmann et al., 2009). For a discussion of genetic heterogeneity of autosomal recessive mtDNA depletion syndromes, see MTDPS1 (603041). Neuropathologic changes characteristic of Alpers syndrome, namely laminar cortical necrosis, may also be seen in some patients with combined oxidative phosphorylation deficiency-14 (COXPD14; 614946), caused by mutation in the FARS2 gene (611592), and COXPD24 (616239), caused by mutation in the NARS2 gene (612803). (203700)

UniProtKB/Swiss-Prot : 75 Mitochondrial DNA depletion syndrome 4A: An autosomal recessive hepatocerebral syndrome due to mitochondrial dysfunction. The typical course of the disease includes severe developmental delay, intractable seizures, liver failure, and death in childhood. Refractory seizures, cortical blindness, progressive liver dysfunction, and acute liver failure after exposure to valproic acid are considered diagnostic features. The neuropathological hallmarks are neuronal loss, spongiform degeneration, and astrocytosis of the visual cortex. Liver biopsy results show steatosis, often progressing to cirrhosis.

Wikipedia : 76 Mitochondrial DNA depletion syndrome (MDS or MDDS) is any of a group of autosomal recessive disorders... more...

Related Diseases for Mitochondrial Dna Depletion Syndrome 4a

Diseases in the Mitochondrial Dna Deletion Syndromes family:

Mitochondrial Dna Depletion Syndrome 4a Mitochondrial Dna Depletion Syndrome 9
Mitochondrial Dna Depletion Syndrome 3 Mitochondrial Dna Depletion Syndrome 6
Mitochondrial Dna Depletion Syndrome 7 Mitochondrial Dna Depletion Syndrome 1
Mitochondrial Dna Depletion Syndrome 2 Mitochondrial Dna Depletion Syndrome 5
Mitochondrial Dna Depletion Syndrome 8a Mitochondrial Dna Depletion Syndrome 4b
Mitochondrial Dna Depletion Syndrome 11 Mitochondrial Dna Depletion Syndrome 12b , Autosomal Recessive
Mitochondrial Dna Depletion Syndrome 13 Mitochondrial Dna Depletion Syndrome 14
Mitochondrial Dna Depletion Syndrome 15 Mitochondrial Dna Depletion Syndrome 12a , Autosomal Dominant
Mitochondrial Dna Depletion Syndrome 12a Mitochondrial Dna Depletion Syndrome 12b
Mitochondrial Dna Depletion Syndrome Rrm2b-Related Mitochondrial Dna Depletion Syndrome

Diseases related to Mitochondrial Dna Depletion Syndrome 4a via text searches within MalaCards or GeneCards Suite gene sharing:

(show top 50) (show all 120)
# Related Disease Score Top Affiliating Genes
1 ah amyloidosis 12.2
2 tumefactive multiple sclerosis 11.9
3 myelinoclastic diffuse sclerosis 11.8
4 adrenoleukodystrophy 11.6
5 sudanophilic cerebral sclerosis 11.5
6 pelizaeus-merzbacher disease 11.5
7 balo concentric sclerosis 11.5
8 hypotrichosis 7 11.3
9 hemophilia 11.3
10 combined oxidative phosphorylation deficiency 24 11.2
11 atrial standstill 1 11.2
12 combined oxidative phosphorylation deficiency 14 11.1
13 hemochromatosis, type 1 11.1
14 aplastic anemia 11.1
15 hemolytic anemia 11.1
16 primary ciliary dyskinesia 11.1
17 atrial fibrillation 11.1
18 long qt syndrome 11.1
19 adrenal hyperplasia, congenital, due to 3-beta-hydroxysteroid dehydrogenase 2 deficiency 11.0
20 adrenal hyperplasia, congenital, due to 21-hydroxylase deficiency 11.0
21 adrenal hyperplasia, congenital, due to steroid 11-beta-hydroxylase deficiency 11.0
22 adrenal hyperplasia, congenital, due to 17-alpha-hydroxylase deficiency 11.0
23 pulmonary fibrosis, idiopathic 10.9
24 polycythemia vera 10.9
25 abdominal obesity-metabolic syndrome 1 10.9
26 bronchopulmonary dysplasia 10.9
27 thrombocytopenia 10.9
28 sleep apnea 10.9
29 thrombotic thrombocytopenic purpura 10.9
30 thrombocytopenia due to platelet alloimmunization 10.9
31 pneumonia 10.9
32 lymphopenia 10.9
33 alien hand syndrome 10.9
34 mitochondrial encephalomyopathy 10.4
35 hypotonia 10.4
36 amyloidosis 10.2
37 alcoholic hepatitis 10.2
38 mitochondrial dna depletion syndrome 4b 10.1 EDAR POLG
39 breast cancer 10.1
40 ataxia neuropathy spectrum 10.1 POLG TWNK
41 maternally-inherited progressive external ophthalmoplegia 10.1 POLG TWNK
42 prostate cancer 10.0
43 hemophilia a 10.0
44 heart disease 10.0
45 acquired hemophilia 10.0
46 acquired hemophilia a 10.0
47 headache 10.0
48 mitochondrial neurogastrointestinal encephalopathy disease 10.0 POLG TYMP
49 sensory ataxic neuropathy, dysarthria, and ophthalmoparesis 10.0 POLG TWNK
50 mitochondrial dna depletion syndrome 3 10.0 DGUOK TWNK

Graphical network of the top 20 diseases related to Mitochondrial Dna Depletion Syndrome 4a:



Diseases related to Mitochondrial Dna Depletion Syndrome 4a

Symptoms & Phenotypes for Mitochondrial Dna Depletion Syndrome 4a

Symptoms via clinical synopsis from OMIM:

57
Neurologic Central Nervous System:
ataxia
hypertonia
myoclonus
status epilepticus
paralysis
more
Abdomen Liver:
hepatomegaly
micronodular cirrhosis
liver failure
biopsy shows microvesicular steatosis
hepatocyte dropout
more
Laboratory Abnormalities:
increased serum lactate
increased csf protein
elevated liver function tests
decreased dna polymerase-gamma (polg, ) activity
intermittent 3-methylglutaconic aciduria
more
Head And Neck Eyes:
loss of vision
visual disturbances
cortical blindness
abnormal visual evoked potential (vep)

Growth Other:
failure to thrive

Abdomen Gastrointestinal:
vomiting

Muscle Soft Tissue:
hypotonia
decreased mitochondrial respiratory chain complex activity
mitochondrial dna depletion


Clinical features from OMIM:

203700

Symptoms:

12
  • convulsions

Human phenotypes related to Mitochondrial Dna Depletion Syndrome 4a:

59 32 (show all 46)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 ataxia 59 32 frequent (33%) Frequent (79-30%) HP:0001251
2 muscular hypotonia 59 32 frequent (33%) Frequent (79-30%) HP:0001252
3 developmental regression 59 32 frequent (33%) Frequent (79-30%) HP:0002376
4 global developmental delay 59 32 frequent (33%) Frequent (79-30%) HP:0001263
5 microcephaly 59 32 frequent (33%) Frequent (79-30%) HP:0000252
6 blindness 59 32 occasional (7.5%) Occasional (29-5%) HP:0000618
7 myoclonus 59 32 frequent (33%) Frequent (79-30%) HP:0001336
8 generalized tonic-clonic seizures 59 32 frequent (33%) Frequent (79-30%) HP:0002069
9 coma 59 32 frequent (33%) Frequent (79-30%) HP:0001259
10 areflexia 59 32 frequent (33%) Frequent (79-30%) HP:0001284
11 choreoathetosis 59 32 frequent (33%) Frequent (79-30%) HP:0001266
12 progressive spasticity 59 32 frequent (33%) Frequent (79-30%) HP:0002191
13 spastic paraparesis 59 32 frequent (33%) Frequent (79-30%) HP:0002313
14 spasticity 59 Frequent (79-30%)
15 failure to thrive 32 HP:0001508
16 hepatomegaly 32 HP:0002240
17 abnormality of visual evoked potentials 32 HP:0000649
18 hypertonia 32 HP:0001276
19 vomiting 32 HP:0002013
20 abnormality of the eye 59 Frequent (79-30%)
21 abnormality of vision 59 Frequent (79-30%)
22 abnormality of movement 59 Frequent (79-30%)
23 increased serum lactate 32 HP:0002151
24 status epilepticus 32 HP:0002133
25 visual loss 32 HP:0000572
26 paralysis 32 HP:0003470
27 dementia 32 HP:0000726
28 hepatic failure 32 HP:0001399
29 focal seizures 59 Frequent (79-30%)
30 cerebellar atrophy 32 HP:0001272
31 astrocytosis 32 HP:0002446
32 generalized hypotonia 32 HP:0001290
33 paraparesis 59 Frequent (79-30%)
34 increased csf protein 32 HP:0002922
35 neuronal loss in central nervous system 32 HP:0002529
36 gliosis 32 HP:0002171
37 microvesicular hepatic steatosis 32 HP:0001414
38 3-methylglutaconic aciduria 32 HP:0003535
39 micronodular cirrhosis 32 HP:0001413
40 ethylmalonic aciduria 32 HP:0003219
41 bile duct proliferation 32 HP:0001408
42 epilepsia partialis continua 32 HP:0012847
43 cerebral cortical neurodegeneration 32 HP:0006964
44 cerebral visual impairment 32 HP:0100704
45 focal-onset seizure 32 frequent (33%) HP:0007359
46 elevated hepatic transaminase 32 HP:0002910

UMLS symptoms related to Mitochondrial Dna Depletion Syndrome 4a:


ataxia, vomiting, myoclonus, visual disturbance, unspecified visual loss

Drugs & Therapeutics for Mitochondrial Dna Depletion Syndrome 4a

Search Clinical Trials , NIH Clinical Center for Mitochondrial Dna Depletion Syndrome 4a

Genetic Tests for Mitochondrial Dna Depletion Syndrome 4a

Genetic tests related to Mitochondrial Dna Depletion Syndrome 4a:

# Genetic test Affiliating Genes
1 Progressive Sclerosing Poliodystrophy 29 POLG

Anatomical Context for Mitochondrial Dna Depletion Syndrome 4a

MalaCards organs/tissues related to Mitochondrial Dna Depletion Syndrome 4a:

41
Liver, Brain, Cortex, Testes, Eye, Bone, Heart

Publications for Mitochondrial Dna Depletion Syndrome 4a

Articles related to Mitochondrial Dna Depletion Syndrome 4a:

(show all 37)
# Title Authors Year
1
Dissecting the neuronal vulnerability underpinning Alpers' syndrome: a clinical and neuropathological study. ( 30021052 )
2018
2
Specific EEG markers in POLG1 Alpers' syndrome. ( 30103161 )
2018
3
Whole exome sequencing reveals mutations in NARS2 and PARS2, encoding the mitochondrial asparaginyl-tRNA synthetase and prolyl-tRNA synthetase, in patients with Alpers syndrome. ( 25629079 )
2015
4
Valproic acid-induced hepatotoxicity in alpers syndrome is associated with mitochondrial permeability transition pore opening-dependent apoptotic sensitivity in an induced pluripotent stem cell model. ( 25605636 )
2015
5
Abnormalities in Glycogen Metabolism in a Patient with Alpers' Syndrome Presenting with Hypoglycemia. ( 24272679 )
2013
6
Alpers syndrome: an unusual etiology of failure to thrive. ( 22849523 )
2012
7
Alpers syndrome: the natural history of a case highlighting neuroimaging, neuropathology, and fat metabolism. ( 22114215 )
2012
8
Polymerase gamma deficiency (POLG): clinical course in a child with a two stage evolution from infantile myocerebrohepatopathy spectrum to an Alpers syndrome and neuropathological findings of Leigh's encephalopathy. ( 22342071 )
2012
9
Complete Deletion of a POLG1 Allele in a Patient with Alpers Syndrome. ( 23430898 )
2012
10
Phenotypic and genotypic variability in Alpers syndrome. ( 22237560 )
2012
11
POLG exon 22 skipping induced by different mechanisms in two unrelated cases of Alpers syndrome. ( 20691285 )
2011
12
Application of oligonucleotide array CGH in the detection of a large intragenic deletion in POLG associated with Alpers Syndrome. ( 20708716 )
2011
13
Gender variability in presentation with Alpers' syndrome: a report of eight patients from the UAE. ( 21305355 )
2011
14
Alpers syndrome with mutations in POLG: clinical and investigative features. ( 22000311 )
2011
15
Molecular and biochemical characterisation of a novel mutation in POLG associated with Alpers syndrome. ( 21235791 )
2011
16
Alpers syndrome presenting with anatomopathological features of fulminant autoimmune hepatitis. ( 20582478 )
2010
17
Juvenile-onset Alpers syndrome: interpreting MRI findings. ( 20385895 )
2010
18
Proof of progression over time: finally fulminant brain, muscle, and liver affection in Alpers syndrome associated with the A467T POLG1 mutation. ( 18783964 )
2009
19
De novo mutation in POLG leads to haplotype insufficiency and Alpers syndrome. ( 19501198 )
2009
20
Alpers syndrome with prominent white matter changes. ( 17923349 )
2008
21
Rapidly progressive neurological deterioration in a child with Alpers syndrome exhibiting a previously unremarkable brain MRI. ( 18991199 )
2008
22
Homozygous W748S mutation in the POLG1 gene in patients with juvenile-onset Alpers syndrome and status epilepticus. ( 18294203 )
2008
23
Molecular diagnosis of Alpers syndrome. ( 16545482 )
2006
24
Alpers syndrome: progressive neuronal degeneration of children with liver disease. ( 17109792 )
2006
25
Mono-allelic POLG expression resulting from nonsense-mediated decay and alternative splicing in a patient with Alpers syndrome. ( 16181814 )
2005
26
POLG mutations associated with Alpers syndrome and mitochondrial DNA depletion. ( 16130100 )
2005
27
POLG mutations and Alpers syndrome. ( 15929042 )
2005
28
POLG mutations in Alpers syndrome. ( 16177225 )
2005
29
POLG mutations associated with Alpers' syndrome and mitochondrial DNA depletion. ( 15122711 )
2004
30
Is variant Creutzfeldt-Jakob disease in young children misdiagnosed as Alpers' syndrome? An analysis of a national surveillance study. ( 15146014 )
2004
31
Mitochondrial DNA depletion in Alpers syndrome. ( 15328560 )
2004
32
Respiratory chain deficiency in Alpers syndrome. ( 11521212 )
2001
33
Mitochondrial DNA polymerase gamma deficiency and mtDNA depletion in a child with Alpers' syndrome. ( 9894877 )
1999
34
[Neurophysiological study in Alpers syndrome]. ( 9533210 )
1998
35
Brain MR imaging findings in two patients with Alpers' syndrome. ( 8959359 )
1996
36
Alpers' syndrome presenting with seizures and multiple stroke-like episodes in a 17-year-old male. ( 8605737 )
1995
37
Progressive neuronal degeneration of childhood (Alpers syndrome) with hepatic cirrhosis. ( 8444257 )
1993

Variations for Mitochondrial Dna Depletion Syndrome 4a

UniProtKB/Swiss-Prot genetic disease variations for Mitochondrial Dna Depletion Syndrome 4a:

75 (show all 16)
# Symbol AA change Variation ID SNP ID
1 POLG p.Ala467Thr VAR_012155 rs113994095
2 POLG p.Thr251Ile VAR_023664 rs113994094
3 POLG p.Pro587Leu VAR_023671 rs113994096
4 POLG p.Gly848Ser VAR_023675 rs113994098
5 POLG p.Arg232Gly VAR_058870
6 POLG p.Leu244Pro VAR_058872
7 POLG p.Ala767Asp VAR_058886
8 POLG p.Gln879His VAR_058890
9 POLG p.Thr885Ser VAR_058891
10 POLG p.Thr914Pro VAR_058892 rs139590686
11 POLG p.Ala957Pro VAR_058893
12 POLG p.Arg1096His VAR_058894 rs368435864
13 POLG p.His1110Tyr VAR_058895
14 POLG p.His1134Arg VAR_058896
15 POLG p.Lys1191Asn VAR_058898 rs108530774
16 POLG p.Glu1136Lys VAR_065092 rs56047213

ClinVar genetic disease variations for Mitochondrial Dna Depletion Syndrome 4a:

6 (show top 50) (show all 497)
# Gene Variation Type Significance SNP ID Assembly Location
1 EDAR NM_022336.3(EDAR): c.266G> A (p.Arg89His) single nucleotide variant Pathogenic rs121908450 GRCh37 Chromosome 2, 109545744: 109545744
2 EDAR NM_022336.3(EDAR): c.266G> A (p.Arg89His) single nucleotide variant Pathogenic rs121908450 GRCh38 Chromosome 2, 108929288: 108929288
3 POLG NM_002693.2(POLG): c.1399G> A (p.Ala467Thr) single nucleotide variant Pathogenic/Likely pathogenic rs113994095 GRCh37 Chromosome 15, 89870432: 89870432
4 POLG NM_002693.2(POLG): c.1399G> A (p.Ala467Thr) single nucleotide variant Pathogenic/Likely pathogenic rs113994095 GRCh38 Chromosome 15, 89327201: 89327201
5 POLG NM_002693.2(POLG): c.911T> G (p.Leu304Arg) single nucleotide variant Pathogenic/Likely pathogenic rs121918044 GRCh37 Chromosome 15, 89872286: 89872286
6 POLG NM_002693.2(POLG): c.911T> G (p.Leu304Arg) single nucleotide variant Pathogenic/Likely pathogenic rs121918044 GRCh38 Chromosome 15, 89329055: 89329055
7 POLG NM_002693.2(POLG): c.3151G> C (p.Gly1051Arg) single nucleotide variant Conflicting interpretations of pathogenicity rs121918049 GRCh37 Chromosome 15, 89862284: 89862284
8 POLG NM_002693.2(POLG): c.3151G> C (p.Gly1051Arg) single nucleotide variant Conflicting interpretations of pathogenicity rs121918049 GRCh38 Chromosome 15, 89319053: 89319053
9 POLG NM_002693.2(POLG): c.2542G> A (p.Gly848Ser) single nucleotide variant Pathogenic rs113994098 GRCh37 Chromosome 15, 89865023: 89865023
10 POLG NM_002693.2(POLG): c.2542G> A (p.Gly848Ser) single nucleotide variant Pathogenic rs113994098 GRCh38 Chromosome 15, 89321792: 89321792
11 POLG NM_002693.2(POLG): c.752C> T (p.Thr251Ile) single nucleotide variant Conflicting interpretations of pathogenicity rs113994094 GRCh37 Chromosome 15, 89873415: 89873415
12 POLG NM_002693.2(POLG): c.752C> T (p.Thr251Ile) single nucleotide variant Conflicting interpretations of pathogenicity rs113994094 GRCh38 Chromosome 15, 89330184: 89330184
13 POLG NM_002693.2(POLG): c.2617G> T (p.Glu873Ter) single nucleotide variant Pathogenic rs121918047 GRCh37 Chromosome 15, 89864473: 89864473
14 POLG NM_002693.2(POLG): c.2617G> T (p.Glu873Ter) single nucleotide variant Pathogenic rs121918047 GRCh38 Chromosome 15, 89321242: 89321242
15 POLG NM_002693.2(POLG): c.1760C> T (p.Pro587Leu) single nucleotide variant Conflicting interpretations of pathogenicity rs113994096 GRCh37 Chromosome 15, 89868870: 89868870
16 POLG NM_002693.2(POLG): c.1760C> T (p.Pro587Leu) single nucleotide variant Conflicting interpretations of pathogenicity rs113994096 GRCh38 Chromosome 15, 89325639: 89325639
17 POLG NM_002693.2(POLG): c.2243G> C (p.Trp748Ser) single nucleotide variant Conflicting interpretations of pathogenicity rs113994097 GRCh37 Chromosome 15, 89866657: 89866657
18 POLG NM_002693.2(POLG): c.2243G> C (p.Trp748Ser) single nucleotide variant Conflicting interpretations of pathogenicity rs113994097 GRCh38 Chromosome 15, 89323426: 89323426
19 POLG NM_002693.2(POLG): c.2492A> G (p.Tyr831Cys) single nucleotide variant Conflicting interpretations of pathogenicity rs41549716 GRCh37 Chromosome 15, 89865073: 89865073
20 POLG NM_002693.2(POLG): c.2492A> G (p.Tyr831Cys) single nucleotide variant Conflicting interpretations of pathogenicity rs41549716 GRCh38 Chromosome 15, 89321842: 89321842
21 POLG NM_002693.2(POLG): c.1491G> C (p.Gln497His) single nucleotide variant Uncertain significance rs121918052 GRCh37 Chromosome 15, 89870237: 89870237
22 POLG NM_002693.2(POLG): c.1491G> C (p.Gln497His) single nucleotide variant Uncertain significance rs121918052 GRCh38 Chromosome 15, 89327006: 89327006
23 POLG NM_002693.2: c.3057G> A single nucleotide variant Pathogenic
24 POLG NM_002693.2(POLG): c.2557C> T (p.Arg853Trp) single nucleotide variant Uncertain significance rs121918053 GRCh37 Chromosome 15, 89865008: 89865008
25 POLG NM_002693.2(POLG): c.2557C> T (p.Arg853Trp) single nucleotide variant Uncertain significance rs121918053 GRCh38 Chromosome 15, 89321777: 89321777
26 POLG NM_002693.2(POLG): c.2209G> C (p.Gly737Arg) single nucleotide variant Conflicting interpretations of pathogenicity rs121918054 GRCh37 Chromosome 15, 89866691: 89866691
27 POLG NM_002693.2(POLG): c.2209G> C (p.Gly737Arg) single nucleotide variant Conflicting interpretations of pathogenicity rs121918054 GRCh38 Chromosome 15, 89323460: 89323460
28 POLG NM_002693.2(POLG): c.679C> T (p.Arg227Trp) single nucleotide variant Pathogenic rs121918056 GRCh37 Chromosome 15, 89873488: 89873488
29 POLG NM_002693.2(POLG): c.679C> T (p.Arg227Trp) single nucleotide variant Pathogenic rs121918056 GRCh38 Chromosome 15, 89330257: 89330257
30 POLG NM_002693.2(POLG): c.3218C> T (p.Pro1073Leu) single nucleotide variant Pathogenic rs267606959 GRCh37 Chromosome 15, 89862217: 89862217
31 POLG NM_002693.2(POLG): c.3218C> T (p.Pro1073Leu) single nucleotide variant Pathogenic rs267606959 GRCh38 Chromosome 15, 89318986: 89318986
32 POLG NM_002693.2(POLG): c.1636C> T (p.Arg546Cys) single nucleotide variant Benign/Likely benign rs2307447 GRCh37 Chromosome 15, 89869919: 89869919
33 POLG NM_002693.2(POLG): c.1636C> T (p.Arg546Cys) single nucleotide variant Benign/Likely benign rs2307447 GRCh38 Chromosome 15, 89326688: 89326688
34 POLG NM_002693.2(POLG): c.1984G> A (p.Glu662Lys) single nucleotide variant Benign/Likely benign rs2307450 GRCh37 Chromosome 15, 89867424: 89867424
35 POLG NM_002693.2(POLG): c.1984G> A (p.Glu662Lys) single nucleotide variant Benign/Likely benign rs2307450 GRCh38 Chromosome 15, 89324193: 89324193
36 POLG NM_002693.2(POLG): c.3424C> T (p.Arg1142Trp) single nucleotide variant Uncertain significance rs2307442 GRCh37 Chromosome 15, 89861830: 89861830
37 POLG NM_002693.2(POLG): c.3424C> T (p.Arg1142Trp) single nucleotide variant Uncertain significance rs2307442 GRCh38 Chromosome 15, 89318599: 89318599
38 FANCI; POLG NM_002693.2(POLG): c.3428A> G (p.Glu1143Gly) single nucleotide variant Benign/Likely benign rs2307441 GRCh37 Chromosome 15, 89861826: 89861826
39 FANCI; POLG NM_002693.2(POLG): c.3428A> G (p.Glu1143Gly) single nucleotide variant Benign/Likely benign rs2307441 GRCh38 Chromosome 15, 89318595: 89318595
40 POLG NM_002693.2(POLG): c.3436C> T (p.Arg1146Cys) single nucleotide variant Conflicting interpretations of pathogenicity rs2307440 GRCh37 Chromosome 15, 89861818: 89861818
41 POLG NM_002693.2(POLG): c.3436C> T (p.Arg1146Cys) single nucleotide variant Conflicting interpretations of pathogenicity rs2307440 GRCh38 Chromosome 15, 89318587: 89318587
42 POLG NM_002693.2(POLG): c.578G> A (p.Arg193Gln) single nucleotide variant Conflicting interpretations of pathogenicity rs3176162 GRCh37 Chromosome 15, 89876408: 89876408
43 POLG NM_002693.2(POLG): c.578G> A (p.Arg193Gln) single nucleotide variant Conflicting interpretations of pathogenicity rs3176162 GRCh38 Chromosome 15, 89333177: 89333177
44 POLG NM_002693.2(POLG): c.970C> T (p.Pro324Ser) single nucleotide variant Conflicting interpretations of pathogenicity rs2307437 GRCh37 Chromosome 15, 89872227: 89872227
45 POLG NM_002693.2(POLG): c.970C> T (p.Pro324Ser) single nucleotide variant Conflicting interpretations of pathogenicity rs2307437 GRCh38 Chromosome 15, 89328996: 89328996
46 POLG NM_002693.2(POLG): c.1550G> T (p.Gly517Val) single nucleotide variant Conflicting interpretations of pathogenicity rs61752783 GRCh37 Chromosome 15, 89870178: 89870178
47 POLG NM_002693.2(POLG): c.1550G> T (p.Gly517Val) single nucleotide variant Conflicting interpretations of pathogenicity rs61752783 GRCh38 Chromosome 15, 89326947: 89326947
48 POLG NM_002693.2(POLG): c.128A> G (p.Gln43Arg) single nucleotide variant Benign rs28567406 GRCh37 Chromosome 15, 89876858: 89876858
49 POLG NM_002693.2(POLG): c.128A> G (p.Gln43Arg) single nucleotide variant Benign rs28567406 GRCh38 Chromosome 15, 89333627: 89333627
50 POLG NM_002693.2(POLG): c.2109C> A (p.Ala703=) single nucleotide variant Benign rs2307429 GRCh37 Chromosome 15, 89867094: 89867094

Expression for Mitochondrial Dna Depletion Syndrome 4a

Search GEO for disease gene expression data for Mitochondrial Dna Depletion Syndrome 4a.

Pathways for Mitochondrial Dna Depletion Syndrome 4a

Pathways related to Mitochondrial Dna Depletion Syndrome 4a according to GeneCards Suite gene sharing:

# Super pathways Score Top Affiliating Genes
1
Show member pathways
11.04 DARS2 FARS2 PARS2

GO Terms for Mitochondrial Dna Depletion Syndrome 4a

Cellular components related to Mitochondrial Dna Depletion Syndrome 4a according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 mitochondrion GO:0005739 9.5 DARS2 DGUOK FARS2 PARS2 POLG POLG2
2 mitochondrial nucleoid GO:0042645 9.33 POLG POLG2 TWNK
3 mitochondrial matrix GO:0005759 9.1 DARS2 DGUOK FARS2 PARS2 POLG2 TWNK

Biological processes related to Mitochondrial Dna Depletion Syndrome 4a according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 translation GO:0006412 9.58 DARS2 FARS2 PARS2
2 mitochondrion organization GO:0007005 9.46 POLG2 TWNK
3 cellular response to glucose stimulus GO:0071333 9.43 POLG TWNK
4 DNA replication GO:0006260 9.43 POLG POLG2 TWNK
5 DNA biosynthetic process GO:0071897 9.37 POLG POLG2
6 DNA-dependent DNA replication GO:0006261 9.32 POLG POLG2
7 tRNA aminoacylation GO:0043039 9.16 DARS2 FARS2
8 tRNA aminoacylation for protein translation GO:0006418 9.13 DARS2 FARS2 PARS2
9 mitochondrial DNA replication GO:0006264 8.8 POLG POLG2 TWNK

Molecular functions related to Mitochondrial Dna Depletion Syndrome 4a according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 ATP binding GO:0005524 9.65 DARS2 DGUOK FARS2 PARS2 TWNK
2 protease binding GO:0002020 9.4 POLG TWNK
3 nucleotidyltransferase activity GO:0016779 9.37 POLG POLG2
4 tRNA binding GO:0000049 9.32 DARS2 FARS2
5 DNA-directed DNA polymerase activity GO:0003887 9.16 POLG POLG2
6 ligase activity GO:0016874 9.13 DARS2 FARS2 PARS2
7 aminoacyl-tRNA ligase activity GO:0004812 8.8 DARS2 FARS2 PARS2

Sources for Mitochondrial Dna Depletion Syndrome 4a

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 ExPASy
19 FMA
28 GO
29 GTR
30 HGMD
31 HMDB
32 HPO
33 ICD10
34 ICD10 via Orphanet
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37 KEGG
38 LifeMap
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44 MeSH
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62 PubMed
64 QIAGEN
69 SNOMED-CT via HPO
70 SNOMED-CT via Orphanet
71 TGDB
72 Tocris
73 UMLS
74 UMLS via Orphanet
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