Mitochondrial Dna Depletion Syndrome 7 (MTDPS7)

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

Aliases & Classifications for Mitochondrial Dna Depletion Syndrome 7

MalaCards integrated aliases for Mitochondrial Dna Depletion Syndrome 7:

Name: Mitochondrial Dna Depletion Syndrome 7 57 12 72 13 15
Infantile Onset Spinocerebellar Ataxia 12 20 29 6 44 70
Ohaha Syndrome 57 12 20 43 58 72
Iosca 57 20 43 58 72
Infantile-Onset Spinocerebellar Ataxia 25 43 58
Ophthalmoplegia-Hypotonia-Ataxia-Hypoacusis-Athetosis Syndrome 20 58
Ophthalmoplegia, Hypotonia, Ataxia, Hypacusis, and Athetosis 20 43
Spinocerebellar Ataxia Infantile with Sensory Neuropathy 20 72
Spinocerebellar Ataxia 8 72 70
Mtdps7 57 72
Ophthalmoplegia, Hypotonia, Ataxia, Hypoacusis, and Athetosis 57
Ophthalmoplegia - Hypotonia - Ataxia - Hypoacusis - Athetosis 20
Mitochondrial Dna Depletion Syndrome, Hepatocerebrorenal Form 58
Spinocerebellar Ataxia, Infantile, with Sensory Neuropathy 57
Mitochondrial Dna Depletion Syndrome 7 Hepatocerebral Type 72
Ophthalmoplegia Hypotonia Ataxia Hypoacusis and Athetosis 72
Spinocerebellar Ataxia 8, Formerly; Sca8, Formerly 57
Mtdna Depletion Syndrome, Hepatocerebrorenal Form 58
Spinocerebellar Ataxia, Infantile-Onset; Iosca 57
Mitochondrial Dna Depletion Syndrome , Type 7 39
Iosca, Mitochondrial Dna Depletion Syndrome 7 25
Pure Spinocerebellar Ataxia Japanese Type 72
Spinocerebellar Ataxia, Infantile-Onset 57
Spinocerebellar Ataxia Infantile-Onset 72
Spinocerebellar Ataxia 8, Formerly 57
Sca4 Pure Japanese Type 72
Sca8, Formerly 57
Sca8 72


Orphanet epidemiological data:

infantile-onset spinocerebellar ataxia
Inheritance: Autosomal recessive; Prevalence: <1/1000000 (Worldwide); Age of onset: Infancy; Age of death: adolescent,early childhood,infantile,late childhood,young Adult;
mitochondrial dna depletion syndrome, hepatocerebrorenal form
Inheritance: Autosomal recessive; Prevalence: <1/1000000 (Worldwide); Age of onset: Infancy,Neonatal;


57 (Updated 05-Apr-2021)
autosomal recessive

progressive disorder
onset 6 to 18 months
some features occur in adolescence, including migraine, seizures, and psychiatric disorders
severe epilepsy may lead to early death
carrier frequency in finland is 1 in 230


mitochondrial dna depletion syndrome 7:
Inheritance autosomal recessive inheritance
Onset and clinical course progressive


Orphanet: 58  
Rare neurological diseases
Rare hepatic diseases
Rare renal diseases
Inborn errors of metabolism

Summaries for Mitochondrial Dna Depletion Syndrome 7

GARD : 20 The following summary is from Orphanet, a European reference portal for information on rare diseases and orphan drugs. Orpha Number: 1186 Definition Infantile-onset spinocerebellar ataxia (IOSCA) is a hereditary neurological disorder with early and severe involvement of both the peripheral and central nervous systems. It has only been described in Finnish families. Epidemiology So far, 24 cases have been reported. In Finland, IOSCA has a population carrier frequency of more than 1:230. Clinical description IOSCA is characterized by very early ataxia, athetosis and reduced tendon reflexes (between 9 and 18 months of age). Ophthalmoplegia and sensorineural hearing loss are diagnosed in childhood. Other features, such as optic atrophy and sensory neuropathy with progressive loss of myelinated fibers in the sural nerve, appear later in the disease course. Hypogonadism may occur in females. Some patients show intellectual deficit. Epilepsy is a late manifestation and seizures may be life-threatening. Etiology IOSCA is caused by mutations in the C10orf2 gene (10q24) encoding the mitochondrial helicase Twinkle. The c.1523A>G (p.Y508C) causative mutation has been postulated to be a founder mutation. Twenty-one of the reported patients were homozygous for this mutation, and three were compound heterozygotes : c.952G>A/c.1523A>G (two patients) and c.1523A>G/c.1287C>T (one patient). The mutations lead to mtDNA depletion in the brain and the liver, but not in the muscle. Diagnostic methods The diagnosis is based on clinical and pathological findings. Studies of sural nerve biopsies reveal an early and rapidly progressive axonal neuropathy. Neuroimaging studies revealing cerebellar atrophy and genetic testing for the c.1523A>G mutation may also help to confirm the diagnosis. Differential diagnosis Differential diagnoses include early-onset cerebellar ataxias with sensory axonal neuropathy and epileptic encephalopathy, mitochondrial disorders with axonal neuropathy (such as Friedreich ataxia), progressive external ophthalmoplegia (PEO), juvenile- or adult-onset mitochondrial recessive ataxia syndrome (MIRAS), and POLG -related disorders (see theseterms). Antenatal diagnosis Prenatal testing may be available for families in which the disease-causing mutations have already been identified. Genetic counseling IOSCA is inherited in an autosomal recessive manner. Genetic counseling is an important clinical tool for preventing new cases, especially for couples with an affected first child: the risk of having an affected child in further pregnancies is 25%. Management and treatment IOSCA patients are often managed by a multidisciplinary team, involving a pediatrician, neurologist, psychiatrist, orthopedic surgeon, physical and occupational therapists, genetic counselor, and social worker. Treatment is symptomatic and may include: (1) hearing aids, speech therapy and sign language for deafness; (2) physical therapy, orthotic devices and orthopedic surgery for sensory axonal neuropathy; (3) walking aids, a wheelchair, physiotherapy and occupational therapy for ataxia; (4) antiepileptic drugs for seizures and (5) antipsychotics and antidepressants for psychiatric symptoms. Prognosis Prognosis is unfavorable. Patients are wheelchair-bound by adolescence. Early death is common due to severe seizures. The clinical course seems to be more rapid and severe (with death during infancy) in c.952G>A/ c.1523A>G compound heterozygotes.

MalaCards based summary : Mitochondrial Dna Depletion Syndrome 7, also known as infantile onset spinocerebellar ataxia, is related to dysphagia and axonal neuropathy, and has symptoms including ataxia, tremor and muscle weakness. An important gene associated with Mitochondrial Dna Depletion Syndrome 7 is TWNK (Twinkle MtDNA Helicase), and among its related pathways/superpathways are Spinocerebellar ataxia and Mitochondrial Gene Expression. Affiliated tissues include eye, liver and cerebellum, and related phenotypes are ataxia and hearing impairment

Disease Ontology : 12 A mitochondrial DNA depletion syndrome that is characterized by progressive ataxia, hypotonia, hyporeflexia, athetosis and sensory impairment and has material basis in autosomal recessive homozygous or compound heterozygous mutation in the C10ORF2 gene, which encodes the twinkle and twinky proteins, on chromosome 10q24.

MedlinePlus Genetics : 43 Infantile-onset spinocerebellar ataxia (IOSCA) is a progressive disorder that affects the nervous system. Babies with IOSCA develop normally during the first year of life. During early childhood, however, they begin experiencing difficulty coordinating movements (ataxia); very weak muscle tone (hypotonia); involuntary writhing movements of the limbs (athetosis); and decreased reflexes. By their teenage years affected individuals require wheelchair assistance.People with IOSCA often develop problems with the autonomic nervous system, which controls involuntary body functions. As a result, they may experience excessive sweating, difficulty controlling urination, and severe constipation.IOSCA also leads to vision and hearing problems that begin by about age 7. Children with this disorder develop weakness in the muscles that control eye movement (ophthalmoplegia). In their teenage years they experience degeneration of the nerves that carry information from the eyes to the brain (optic atrophy), which can result in vision loss. Hearing loss caused by nerve damage (sensorineural hearing loss) typically occurs during childhood and progresses to profound deafness.Individuals with IOSCA may have recurrent seizures (epilepsy). These seizures can lead to severe brain dysfunction (encephalopathy).Most people with IOSCA survive into adulthood. However, a few individuals with IOSCA have an especially severe form of the disorder involving liver damage and encephalopathy that develops during early childhood. These children do not generally live past age 5.

OMIM® : 57 Mitochondrial DNA depletion syndrome-7 is an autosomal recessive severe neurodegenerative disorder characterized primarily by hypotonia, ataxia, ophthalmoplegia, hearing loss, seizures, and sensory axonal neuropathy. Although originally classified as a form of spinocerebellar ataxia (see, e.g., SCA1, 164400) (Koskinen et al., 1994), it has been reclassified as a mitochondrial DNA depletion syndrome (Hakonen et al., 2008) based on the finding of mtDNA depletion in the brain and liver of affected individuals. For a discussion of genetic heterogeneity of autosomal recessive mtDNA depletion syndromes, see MTDPS1 (603041). (271245) (Updated 05-Apr-2021)

UniProtKB/Swiss-Prot : 72 Mitochondrial DNA depletion syndrome 7: A severe disease associated with mitochondrial dysfunction. Some patients are affected by progressive atrophy of the cerebellum, brain stem, the spinal cord, and sensory axonal neuropathy. Clinical features include hypotonia, athetosis, ataxia, ophthalmoplegia, sensorineural hearing deficit, sensory axonal neuropathy, epileptic encephalopathy and female hypogonadism. In some individuals liver dysfunction and multi-organ failure is present.

GeneReviews: NBK3795

Related Diseases for Mitochondrial Dna Depletion Syndrome 7

Diseases in the Mitochondrial Dna Depletion Syndrome 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 16 Mitochondrial Dna Depletion Syndrome 17
Mitochondrial Dna Depletion Syndrome 18 Mitochondrial Dna Depletion Syndrome 19
Mitochondrial Dna Depletion Syndrome 12a Mitochondrial Dna Depletion Syndrome 12b
Mitochondrial Dna Deletion Syndromes Multiple Mitochondrial Dna Deletion Syndrome

Diseases related to Mitochondrial Dna Depletion Syndrome 7 via text searches within MalaCards or GeneCards Suite gene sharing:

(show top 50) (show all 126)
# Related Disease Score Top Affiliating Genes
1 dysphagia 30.1 TWNK POLG
2 axonal neuropathy 30.1 TWNK SLC25A4 RRM2B POLG
3 peripheral nervous system disease 29.8 TWNK POLG FXN APTX
4 autosomal dominant progressive external ophthalmoplegia 29.7 TWNK SLC25A4 RRM2B POLG2 POLG DNA2
5 neuropathy 29.7 TWNK SLC25A4 POLG MPV17 APTX
6 myopathy 29.5 TWNK SLC25A4 RRM2B POLG2 POLG DNA2
7 dentatorubral-pallidoluysian atrophy 29.4 TWNK SPTBN2 POLG FXN APTX
8 hereditary ataxia 29.4 TWNK SPTBN2 FXN APTX
9 autosomal dominant cerebellar ataxia 29.4 TWNK SPTBN2 POLG FXN APTX
10 chronic progressive external ophthalmoplegia 28.2 TWNK SUCLG1 SUCLA2 SSBP1 SLC25A4 RRM2B
11 3-methylglutaconic aciduria, type iii 27.9 TWNK SUCLG1 SUCLA2 SLC25A4 POLG2 POLG
12 kearns-sayre syndrome 27.1 TWNK SUCLG1 SUCLA2 SSBP1 SLC25A4 RRM2B
13 spinocerebellar ataxia 8 11.8
14 spinocerebellar ataxia, autosomal recessive 8 11.7
15 spinocerebellar ataxia 31 11.4
16 spinocerebellar ataxia, autosomal recessive 14 11.3
17 anemia, sideroblastic, and spinocerebellar ataxia 11.2
18 spinocerebellar ataxia 12 11.0
19 polg-related disorders 10.3 TWNK POLG
20 myotonic cataract 10.3 TWNK POLG
21 ataxia neuropathy spectrum 10.3 TWNK POLG
22 spinocerebellar ataxia 5 10.3
23 branchiootic syndrome 1 10.3
24 status epilepticus 10.3
25 parkinsonism 10.3
26 camptocormism 10.3 RRM2B POLG
27 mitochondrial neurogastrointestinal encephalomyopathy 10.3 RRM2B POLG
28 central nervous system origin vertigo 10.3 SLC25A4 POLG
29 mitochondrial dna depletion syndrome 12a 10.3 SLC25A4 POLG
30 visual cortex disease 10.2 POLG2 POLG
31 visual pathway disease 10.2 POLG2 POLG
32 spinocerebellar ataxia 2 10.2
33 alacrima, achalasia, and mental retardation syndrome 10.2
34 mitochondrial dna depletion syndrome 12b 10.2 SLC25A4 POLG
35 neuropathy, ataxia, and retinitis pigmentosa 10.2 TWNK POLG
36 machado-joseph disease 10.2
37 ataxia and polyneuropathy, adult-onset 10.2
38 acute liver failure 10.2 POLG2 POLG
39 coenzyme q10 deficiency disease 10.2 POLG APTX
40 mitochondrial dna depletion syndrome 8a 10.2 RRM2B MGME1
41 parkinson disease, late-onset 10.2
42 infantile cerebellar-retinal degeneration 10.2 SUCLG1 SUCLA2
43 spinocerebellar ataxia 20 10.2 SPTBN2 POLG
44 mitochondrial dna depletion syndrome, encephalomyopathic form 10.1 SUCLG1 SUCLA2 RRM2B
45 mitochondrial dna depletion syndrome 11 10.1 MPV17 MGME1
46 friedreich ataxia 10.1
47 3-methylglutaconic aciduria with deafness, encephalopathy, and leigh-like syndrome 10.1 SUCLA2 POLG MPV17
48 spinocerebellar ataxia 29 10.1
49 seizures, benign familial neonatal, 1 10.1
50 spinocerebellar ataxia 1 10.1

Graphical network of the top 20 diseases related to Mitochondrial Dna Depletion Syndrome 7:

Diseases related to Mitochondrial Dna Depletion Syndrome 7

Symptoms & Phenotypes for Mitochondrial Dna Depletion Syndrome 7

Human phenotypes related to Mitochondrial Dna Depletion Syndrome 7:

58 31 (show all 31)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 ataxia 58 31 hallmark (90%) Very frequent (99-80%) HP:0001251
2 hearing impairment 58 31 hallmark (90%) Very frequent (99-80%) HP:0000365
3 optic atrophy 58 31 hallmark (90%) Very frequent (99-80%) HP:0000648
4 reduced tendon reflexes 58 31 hallmark (90%) Very frequent (99-80%) HP:0001315
5 ophthalmoplegia 58 31 hallmark (90%) Very frequent (99-80%) HP:0000602
6 abnormality of the autonomic nervous system 58 31 hallmark (90%) Very frequent (99-80%) HP:0002270
7 elevated hepatic transaminase 31 occasional (7.5%) HP:0002910
8 intellectual disability 31 HP:0001249
9 nystagmus 31 HP:0000639
10 muscle weakness 31 HP:0001324
11 abnormality of movement 58 Very frequent (99-80%)
12 specific learning disability 31 HP:0001328
13 cerebral cortical atrophy 31 HP:0002120
14 areflexia 31 HP:0001284
15 migraine 31 HP:0002076
16 psychosis 31 HP:0000709
17 poor eye contact 31 HP:0000817
18 encephalopathy 31 HP:0001298
19 clumsiness 31 HP:0002312
20 cerebellar atrophy 31 HP:0001272
21 status epilepticus 31 HP:0002133
22 hypergonadotropic hypogonadism 31 HP:0000815
23 athetosis 31 HP:0002305
24 loss of ability to walk 31 HP:0006957
25 generalized hypotonia 31 HP:0001290
26 excessive daytime somnolence 31 HP:0001262
27 atrophy/degeneration affecting the brainstem 31 HP:0007366
28 epileptic encephalopathy 31 HP:0200134
29 sensory axonal neuropathy 31 HP:0003390
30 epilepsia partialis continua 31 HP:0012847
31 hypotonia 31 HP:0001252

Symptoms via clinical synopsis from OMIM®:

57 (Updated 05-Apr-2021)
Head And Neck Eyes:
optic atrophy
poor eye contact
abnormal eye movements

Muscle Soft Tissue:
muscle weakness
decreased complex i activity (rare)

Neurologic Peripheral Nervous System:
sensory axonal neuropathy
loss of deep tendon reflexes

Abdomen Liver:
mitochondrial dna depletion

Endocrine Features:
hypergonadotrophic hypogonadism (in females in adolescence)

Neurologic Central Nervous System:
cerebellar atrophy
status epilepticus
Neurologic Behavioral Psychiatric Manifestations:
mood disorders
uncontrolled rage

Head And Neck Ears:
loss of vestibular caloric response

Genitourinary Internal Genitalia Female:
hypergonadotrophic hypogonadism (in females in adolescence)

Laboratory Abnormalities:
abnormal liver enzymes (rare)

Clinical features from OMIM®:

271245 (Updated 05-Apr-2021)

UMLS symptoms related to Mitochondrial Dna Depletion Syndrome 7:

ataxia; tremor; muscle weakness; ophthalmoplegia; clumsiness; athetosis; muscle spasticity; abnormal pyramidal signs

MGI Mouse Phenotypes related to Mitochondrial Dna Depletion Syndrome 7:

# Description MGI Source Accession Score Top Affiliating Genes
1 cellular MP:0005384 9.73 APTX DGUOK DNA2 FXN MGME1 MPV17
2 adipose tissue MP:0005375 9.63 APTX DGUOK MGME1 MPV17 POLG RRM2B
3 skeleton MP:0005390 9.23 APTX MGME1 MPV17 POLG RRM2B SLC25A4

Drugs & Therapeutics for Mitochondrial Dna Depletion Syndrome 7

Search Clinical Trials , NIH Clinical Center for Mitochondrial Dna Depletion Syndrome 7

Cochrane evidence based reviews: infantile onset spinocerebellar ataxia

Genetic Tests for Mitochondrial Dna Depletion Syndrome 7

Genetic tests related to Mitochondrial Dna Depletion Syndrome 7:

# Genetic test Affiliating Genes
1 Infantile Onset Spinocerebellar Ataxia 29 TWNK

Anatomical Context for Mitochondrial Dna Depletion Syndrome 7

MalaCards organs/tissues related to Mitochondrial Dna Depletion Syndrome 7:

Eye, Liver, Cerebellum, Spinal Cord, Brain

Publications for Mitochondrial Dna Depletion Syndrome 7

Articles related to Mitochondrial Dna Depletion Syndrome 7:

(show all 32)
# Title Authors PMID Year
Twinkle helicase (PEO1) gene mutation causes mitochondrial DNA depletion. 6 57 25
17722119 2007
Recessive Twinkle mutations in early onset encephalopathy with mtDNA depletion. 6 25 57
17921179 2007
Infantile onset spinocerebellar ataxia is caused by recessive mutations in mitochondrial proteins Twinkle and Twinky. 57 6 25
16135556 2005
Infantile onset spinocerebellar ataxia caused by compound heterozygosity for Twinkle mutations and modeling of Twinkle mutations causing recessive disease. 25 6
27551684 2016
Recessive twinkle mutations cause severe epileptic encephalopathy. 57 25
19304794 2009
Infantile-onset spinocerebellar ataxia and mitochondrial recessive ataxia syndrome are associated with neuronal complex I defect and mtDNA depletion. 57 25
18775955 2008
Infantile onset spinocerebellar ataxia with sensory neuropathy: a new inherited disease. 57 25
8133312 1994
cDNA cloning, expression profile and genomic structure of a novel human transcript on chromosome 10q24, and its analyses as a candidate gene for infantile onset spinocerebellar ataxia. 57
12459258 2002
Toward cloning of a novel ataxia gene: refined assignment and physical map of the IOSCA locus (SCA8) on 10q24. 57
9027505 1997
Random search for shared chromosomal regions in four affected individuals: the assignment of a new hereditary ataxia locus. 57
7726163 1995
Recessive C10orf2 mutations in a family with infantile-onset spinocerebellar ataxia, sensorimotor polyneuropathy, and myopathy. 25
24816431 2014
Exome sequencing reveals a homozygous mutation in TWINKLE as the cause of multisystemic failure including renal tubulopathy in three siblings. 25
23375728 2013
Novel Autosomal Recessive c10orf2 Mutations Causing Infantile-Onset Spinocerebellar Ataxia. 25
22928142 2012
Human mitochondrial RNA polymerase primes lagging-strand DNA synthesis in vitro. 25
18685103 2008
Physiological and biochemical defects in carboxyl-terminal mutants of mitochondrial DNA helicase. 25
18593709 2008
Structure-function defects of the TWINKLE linker region in progressive external ophthalmoplegia. 25
18279890 2008
The N-terminal domain of TWINKLE contributes to single-stranded DNA binding and DNA helicase activities. 25
18039713 2008
Twinkle, the mitochondrial replicative DNA helicase, is widespread in the eukaryotic radiation and may also be the mitochondrial DNA primase in most eukaryotes. 25
16612544 2006
Twinkle helicase is essential for mtDNA maintenance and regulates mtDNA copy number. 25
15509589 2004
Reconstitution of a minimal mtDNA replisome in vitro. 25
15167897 2004
TWINKLE Has 5' -> 3' DNA helicase activity and is specifically stimulated by mitochondrial single-stranded DNA-binding protein. 25
12975372 2003
Human mitochondrial DNA deletions associated with mutations in the gene encoding Twinkle, a phage T7 gene 4-like protein localized in mitochondria. 25
11431692 2001
Infantile onset spinocerebellar ataxia with sensory neuropathy (IOSCA): neuropathological features. 25
9879682 1998
Primary hypogonadism in females with infantile onset spinocerebellar ataxia. 25
8552218 1995
Infantile-onset spinocerebellar ataxia: MR and CT findings. 25
7484627 1995
Sensory neuropathy in infantile onset spinocerebellar ataxia (IOSCA). 25
8159181 1994
Multiple deletions of mitochondrial DNA in several tissues of a patient with severe retarded depression and familial progressive external ophthalmoplegia. 25
1634620 1992
An autosomal dominant disorder with multiple deletions of mitochondrial DNA starting at the D-loop region. 25
2725645 1989
Middle-age-onset cerebellar ataxia caused by a homozygous TWNK variant: a case report. 61
32234020 2020
Homozygous Mutation in TWNK Cases Ataxia, Sensorineural Hearing Loss and Optic Nerve Atrophy. 61
31823625 2019
Mutations in Twinkle primase-helicase cause Perrault syndrome with neurologic features. 61
25355836 2014
Bovine TWINKLE and mitochondrial ribosomal protein L43 genes are regulated by an evolutionary conserved bidirectional promoter. 61
24361965 2014

Variations for Mitochondrial Dna Depletion Syndrome 7

ClinVar genetic disease variations for Mitochondrial Dna Depletion Syndrome 7:

6 (show top 50) (show all 88)
# Gene Name Type Significance ClinVarId dbSNP ID Position
1 TWNK NM_021830.5(TWNK):c.49del (p.Leu17fs) Deletion Pathogenic 694436 rs779142717 GRCh37: 10:102748013-102748013
GRCh38: 10:100988256-100988256
2 TWNK NM_021830.5(TWNK):c.1287C>T (p.Ala429=) SNV Pathogenic 21673 rs80356541 GRCh37: 10:102749444-102749444
GRCh38: 10:100989687-100989687
3 TWNK NM_021830.5(TWNK):c.952G>A (p.Ala318Thr) SNV Pathogenic 4630 rs80356542 GRCh37: 10:102748919-102748919
GRCh38: 10:100989162-100989162
4 TWNK NM_021830.5(TWNK):c.333del (p.Leu112fs) Deletion Pathogenic 225837 rs886037832 GRCh37: 10:102748298-102748298
GRCh38: 10:100988541-100988541
5 TWNK NM_021830.5(TWNK):c.1523A>G (p.Tyr508Cys) SNV Pathogenic 4627 rs80356540 GRCh37: 10:102750231-102750231
GRCh38: 10:100990474-100990474
6 TWNK NM_021830.5(TWNK):c.1370C>T (p.Thr457Ile) SNV Pathogenic 4626 rs80356544 GRCh37: 10:102749527-102749527
GRCh38: 10:100989770-100989770
7 TWNK NM_021830.5(TWNK):c.904C>T (p.Arg302Trp) SNV Likely pathogenic 225838 rs374997012 GRCh37: 10:102748871-102748871
GRCh38: 10:100989114-100989114
8 TWNK NM_021830.5(TWNK):c.247C>T (p.Pro83Ser) SNV Likely pathogenic 56728 rs386834147 GRCh37: 10:102748214-102748214
GRCh38: 10:100988457-100988457
9 TWNK NM_021830.5(TWNK):c.1387C>T (p.Arg463Trp) SNV Likely pathogenic 56727 rs386834146 GRCh37: 10:102749544-102749544
GRCh38: 10:100989787-100989787
10 TWNK NM_021830.5(TWNK):c.1441C>G (p.Leu481Val) SNV Likely pathogenic 638300 rs1590020571 GRCh37: 10:102749598-102749598
GRCh38: 10:100989841-100989841
11 TWNK NM_021830.5(TWNK):c.1199G>T (p.Arg400Leu) SNV Likely pathogenic 694431 rs781016340 GRCh37: 10:102749166-102749166
GRCh38: 10:100989409-100989409
12 TWNK NM_021830.5(TWNK):c.1628G>A (p.Arg543Gln) SNV Likely pathogenic 694432 rs753386843 GRCh37: 10:102750661-102750661
GRCh38: 10:100990904-100990904
13 TWNK NM_021830.5(TWNK):c.1314C>G (p.Asn438Lys) SNV Likely pathogenic 694434 rs1366090807 GRCh37: 10:102749471-102749471
GRCh38: 10:100989714-100989714
14 TWNK NM_021830.5(TWNK):c.1366C>G (p.Leu456Val) SNV Likely pathogenic 56726 rs386834145 GRCh37: 10:102749523-102749523
GRCh38: 10:100989766-100989766
15 TWNK NM_021830.5(TWNK):c.1196A>G (p.Asn399Ser) SNV Conflicting interpretations of pathogenicity 214185 rs863223921 GRCh37: 10:102749163-102749163
GRCh38: 10:100989406-100989406
16 TWNK NM_021830.5(TWNK):c.639C>T (p.Gly213=) SNV Uncertain significance 136587 rs11542130 GRCh37: 10:102748606-102748606
GRCh38: 10:100988849-100988849
17 TWNK NM_021830.5(TWNK):c.1735-14C>A SNV Uncertain significance 136594 rs201795189 GRCh37: 10:102752933-102752933
GRCh38: 10:100993176-100993176
18 TWNK NM_021830.5(TWNK):c.1609T>C (p.Tyr537His) SNV Uncertain significance 383137 rs144001072 GRCh37: 10:102750642-102750642
GRCh38: 10:100990885-100990885
19 TWNK NM_021830.5(TWNK):c.56G>A (p.Gly19Glu) SNV Uncertain significance 426493 rs767175342 GRCh37: 10:102748023-102748023
GRCh38: 10:100988266-100988266
20 TWNK NM_021830.5(TWNK):c.241C>G (p.Leu81Val) SNV Uncertain significance 279715 rs145068570 GRCh37: 10:102748208-102748208
GRCh38: 10:100988451-100988451
21 TWNK NM_021830.5(TWNK):c.1244-14C>T SNV Uncertain significance 507889 rs758757135 GRCh37: 10:102749387-102749387
GRCh38: 10:100989630-100989630
22 TWNK NM_021830.5(TWNK):c.1853C>T (p.Pro618Leu) SNV Uncertain significance 298504 rs886046632 GRCh37: 10:102753065-102753065
GRCh38: 10:100993308-100993308
23 TWNK NM_021830.5(TWNK):c.-470G>A SNV Uncertain significance 298488 rs886046626 GRCh37: 10:102747498-102747498
GRCh38: 10:100987741-100987741
24 TWNK NM_021830.5(TWNK):c.*574C>T SNV Uncertain significance 298515 rs886046636 GRCh37: 10:102753841-102753841
GRCh38: 10:100994084-100994084
25 TWNK NM_021830.5(TWNK):c.-622C>T SNV Uncertain significance 877083 GRCh37: 10:102747346-102747346
GRCh38: 10:100987589-100987589
26 TWNK NM_021830.5(TWNK):c.-418C>T SNV Uncertain significance 877145 GRCh37: 10:102747550-102747550
GRCh38: 10:100987793-100987793
27 TWNK NM_021830.5(TWNK):c.-304G>A SNV Uncertain significance 877146 GRCh37: 10:102747664-102747664
GRCh38: 10:100987907-100987907
28 TWNK NM_021830.5(TWNK):c.1070G>C (p.Arg357Pro) SNV Uncertain significance 632124 rs758026634 GRCh37: 10:102749037-102749037
GRCh38: 10:100989280-100989280
29 TWNK NM_021830.5(TWNK):c.1572C>T (p.His524=) SNV Uncertain significance 877318 GRCh37: 10:102750280-102750280
GRCh38: 10:100990523-100990523
30 TWNK NM_021830.5(TWNK):c.1826G>T (p.Arg609Leu) SNV Uncertain significance 877377 GRCh37: 10:102753038-102753038
GRCh38: 10:100993281-100993281
31 TWNK NM_021830.5(TWNK):c.*248G>A SNV Uncertain significance 877431 GRCh37: 10:102753515-102753515
GRCh38: 10:100993758-100993758
32 TWNK NM_021830.5(TWNK):c.-592C>T SNV Uncertain significance 878124 GRCh37: 10:102747376-102747376
GRCh38: 10:100987619-100987619
33 TWNK NM_021830.5(TWNK):c.596G>A (p.Arg199Gln) SNV Uncertain significance 878242 GRCh37: 10:102748563-102748563
GRCh38: 10:100988806-100988806
34 TWNK NM_021830.5(TWNK):c.1906G>A (p.Ala636Thr) SNV Uncertain significance 878400 GRCh37: 10:102753118-102753118
GRCh38: 10:100993361-100993361
35 TWNK NM_021830.5(TWNK):c.1953G>A (p.Lys651=) SNV Uncertain significance 878401 GRCh37: 10:102753165-102753165
GRCh38: 10:100993408-100993408
36 TWNK NM_021830.5(TWNK):c.*341G>A SNV Uncertain significance 878455 GRCh37: 10:102753608-102753608
GRCh38: 10:100993851-100993851
37 TWNK NM_021830.5(TWNK):c.*346A>C SNV Uncertain significance 878456 GRCh37: 10:102753613-102753613
GRCh38: 10:100993856-100993856
38 TWNK NM_021830.5(TWNK):c.*552G>C SNV Uncertain significance 878511 GRCh37: 10:102753819-102753819
GRCh38: 10:100994062-100994062
39 TWNK NM_021830.5(TWNK):c.*769G>A SNV Uncertain significance 878551 GRCh37: 10:102754036-102754036
GRCh38: 10:100994279-100994279
40 TWNK NM_021830.5(TWNK):c.672T>C (p.Ala224=) SNV Uncertain significance 878844 GRCh37: 10:102748639-102748639
GRCh38: 10:100988882-100988882
41 TWNK NM_021830.5(TWNK):c.1597G>A (p.Ala533Thr) SNV Uncertain significance 878940 GRCh37: 10:102750630-102750630
GRCh38: 10:100990873-100990873
42 TWNK NM_021830.5(TWNK):c.*561C>T SNV Uncertain significance 879092 GRCh37: 10:102753828-102753828
GRCh38: 10:100994071-100994071
43 TWNK NM_021830.5(TWNK):c.-584G>C SNV Uncertain significance 879588 GRCh37: 10:102747384-102747384
GRCh38: 10:100987627-100987627
44 TWNK NM_021830.5(TWNK):c.913G>A (p.Val305Ile) SNV Uncertain significance 880052 GRCh37: 10:102748880-102748880
GRCh38: 10:100989123-100989123
45 TWNK NM_021830.5(TWNK):c.*453G>A SNV Uncertain significance 880257 GRCh37: 10:102753720-102753720
GRCh38: 10:100993963-100993963
46 TWNK NM_021830.5(TWNK):c.1101C>T (p.Ile367=) SNV Uncertain significance 298501 rs200798080 GRCh37: 10:102749068-102749068
GRCh38: 10:100989311-100989311
47 TWNK NM_021830.5(TWNK):c.*709C>G SNV Uncertain significance 298517 rs41291470 GRCh37: 10:102753976-102753976
GRCh38: 10:100994219-100994219
48 TWNK NM_021830.5(TWNK):c.1975G>A (p.Ala659Thr) SNV Uncertain significance 214178 rs370814108 GRCh37: 10:102753187-102753187
GRCh38: 10:100993430-100993430
49 TWNK NM_021830.5(TWNK):c.492C>T (p.Leu164=) SNV Uncertain significance 298498 rs775463083 GRCh37: 10:102748459-102748459
GRCh38: 10:100988702-100988702
50 TWNK NM_021830.5(TWNK):c.*763T>C SNV Uncertain significance 298519 rs886046639 GRCh37: 10:102754030-102754030
GRCh38: 10:100994273-100994273

UniProtKB/Swiss-Prot genetic disease variations for Mitochondrial Dna Depletion Syndrome 7:

# Symbol AA change Variation ID SNP ID
1 TWNK p.Thr457Ile VAR_039045 rs80356544
2 TWNK p.Tyr508Cys VAR_043797 rs80356540
3 TWNK p.Ala318Thr VAR_065104 rs80356542
4 TWNK p.Leu360Gly VAR_065107
5 TWNK p.Leu456Val VAR_067722 rs386834145

Expression for Mitochondrial Dna Depletion Syndrome 7

Search GEO for disease gene expression data for Mitochondrial Dna Depletion Syndrome 7.

Pathways for Mitochondrial Dna Depletion Syndrome 7

GO Terms for Mitochondrial Dna Depletion Syndrome 7

Cellular components related to Mitochondrial Dna Depletion Syndrome 7 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 mitochondrial matrix GO:0005759 9.8 TWNK SUCLG1 SUCLA2 SSBP1 POLG2 FXN
2 mitochondrion GO:0005739 9.47 TWNK SUCLG1 SUCLA2 SSBP1 SLC25A4 RRM2B
3 mitochondrial nucleoid GO:0042645 9.35 TWNK SSBP1 POLG2 POLG DNA2
4 gamma DNA polymerase complex GO:0005760 9.33 POLG2 POLG DNA2

Biological processes related to Mitochondrial Dna Depletion Syndrome 7 according to GeneCards Suite gene sharing:

(show all 11)
# Name GO ID Score Top Affiliating Genes
1 cellular response to DNA damage stimulus GO:0006974 9.83 SLF2 RRM2B MGME1 DNA2 APTX
2 DNA repair GO:0006281 9.73 SLF2 RRM2B POLG2 MGME1 DNA2 APTX
3 nucleic acid phosphodiester bond hydrolysis GO:0090305 9.67 POLG MGME1 DNA2 APTX
4 mitochondrion organization GO:0007005 9.62 TWNK SSBP1 POLG2 FXN
5 DNA-dependent DNA replication GO:0006261 9.49 POLG2 POLG
6 mitochondrion morphogenesis GO:0070584 9.48 SSBP1 POLG2
7 DNA unwinding involved in DNA replication GO:0006268 9.46 TWNK SSBP1
8 DNA replication GO:0006260 9.43 TWNK SSBP1 RRM2B POLG2 POLG DNA2
9 mitochondrial DNA repair GO:0043504 9.4 MGME1 DNA2
10 mitochondrial genome maintenance GO:0000002 9.33 SLC25A4 MPV17 MGME1
11 mitochondrial DNA replication GO:0006264 9.17 TWNK SSBP1 RRM2B POLG2 POLG MGME1

Molecular functions related to Mitochondrial Dna Depletion Syndrome 7 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 single-stranded DNA binding GO:0003697 9.43 TWNK SSBP1 APTX
2 DNA-directed DNA polymerase activity GO:0003887 9.32 POLG2 POLG
3 5'-3' DNA helicase activity GO:0043139 9.16 TWNK DNA2
4 succinate-CoA ligase (GDP-forming) activity GO:0004776 8.96 SUCLG1 SUCLA2
5 succinate-CoA ligase (ADP-forming) activity GO:0004775 8.62 SUCLG1 SUCLA2

Sources for Mitochondrial Dna Depletion Syndrome 7

9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
19 FMA
28 GO
29 GTR
31 HPO
32 ICD10
33 ICD10 via Orphanet
37 LifeMap
41 MedGen
44 MeSH
45 MESH via Orphanet
46 MGI
49 NCI
50 NCIt
54 Novoseek
56 OMIM via Orphanet
57 OMIM® (Updated 05-Apr-2021)
61 PubMed
69 Tocris
71 UMLS via Orphanet
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