MTDPS4B
MCID: MTC055
MIFTS: 53

Mitochondrial Dna Depletion Syndrome 4b (MTDPS4B)

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 4b

MalaCards integrated aliases for Mitochondrial Dna Depletion Syndrome 4b:

Name: Mitochondrial Dna Depletion Syndrome 4b 57 12 72 13 15 70
Mitochondrial Neurogastrointestinal Encephalopathy Syndrome 12 25 20 43 6 70
Thymidine Phosphorylase Deficiency 25 20 43
Mngie Syndrome 25 20 43
Polyneuropathy, Ophthalmoplegia, Leukoencephalopathy, and Intestinal Pseudo-Obstruction 20 43
Mitochondrial Neurogastrointestinal Encephalopathy Disease 25 43
Mitochondrial Dna Depletion Syndrome 4b, Mngie Type 29 6
Myoneurogastrointestinal Encephalopathy Syndrome 20 43
Oculogastrointestinal Muscular Dystrophy 20 43
Mtdps4b 57 72
Mngie 20 54
Ogimd 20 43
Polip 20 43
Mitochondrial Myopathy with Sensorimotor Polyneuropathy, Ophthalmoplegia, and Pseudo-Obstruction 43
Mitochondrial Neurogastrointestinal Encephalopathy Syndrome, Polg-Related 57
Mitochondrial Neurogastrointestinal Encephalopathy Syndrome Polg-Related 72
Visceral Myopathy Familial External Ophthalmoplegia 70
Mitochondrial Dna Depletion Syndrome 4b Mngie Type 72
Mitochondrial Dna Depletion Syndrome, Type 4b 39
Mngie, Polg-Related 57
Mngie Polg-Related 72
Mngie Disease 43
Mepop 43

Characteristics:

OMIM®:

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

Miscellaneous:
variable severity
progressive disorder
onset in infancy or late childhood
some phenotypic overlap with alpers syndrome (mtdps4a, )


HPO:

31
mitochondrial dna depletion syndrome 4b:
Inheritance autosomal recessive inheritance
Onset and clinical course variable expressivity infantile onset progressive


Classifications:



Summaries for Mitochondrial Dna Depletion Syndrome 4b

GARD : 20 Mitochondrial neurogastrointestinal encephalopathy (MNGIE) syndrome is a condition that mainly affects the digestive system and nervous system. Signs and symptoms most often begin by age 20 and worsen with time. Almost all people with MNGIE have gastrointestinal dysmotility, in which the muscles and nerves of the digestive system do not move food through the digestive tract efficiently and result in early satiety, nausea, dysphagia, gastroesophageal reflux, vomiting after eating (postprandial emesis), episodic abdominal pain and/or distention, and diarrhea. Affected people may also have cachexia, dropped eyelids or weakness of other muscles of the eyes, peripheral neuropathy (manifesting as tingling, numbness, and pain (paresthesias) symmetric weakness, that mainly affect the lower extremities) and hearing loss. Leukoencephalopathy, which is the deterioration of a type of brain tissue known as white matter, is a hallmark of MNGIE; however it does not usually cause symptoms in people with this disorder. MNGIE is caused by variations ( mutations ) in the TYMP gene, important for allowing adequate levels of thymidine in the mitochondria. Inheritance is autosomal recessive. Diagnosis is confirmed by detecting the TYMP gene variations or the increased levels of thymidine and deoxyuridine in blood. Treatment depends on the problems that present, and may include management of the swallowing difficulties and airway protection; specific medication for neuropathic symptoms and for nausea and vomiting. Other treatment may include nutritional support, antibiotics for intestinal bacterial overgrowth, special education and and physical therapy. It is recommended to avoid medication that interfere with mitochondrial function, such as valproate, phenytoin, chloramphenicol, linezolid, aminoglycosides, and tetracycline.

MalaCards based summary : Mitochondrial Dna Depletion Syndrome 4b, also known as mitochondrial neurogastrointestinal encephalopathy syndrome, is related to mitochondrial dna depletion syndrome 8a and mitochondrial neurogastrointestinal encephalomyopathy, and has symptoms including ataxia, vomiting and abdominal pain. An important gene associated with Mitochondrial Dna Depletion Syndrome 4b is POLG (DNA Polymerase Gamma, Catalytic Subunit), and among its related pathways/superpathways are Metabolism of nucleotides and Mitochondrial Gene Expression. Affiliated tissues include eye, bone marrow and skeletal muscle, and related phenotypes are hearing impairment and global developmental delay

Disease Ontology : 12 A mitochondrial DNA depletion syndrome that is characterized by chronic gastrointestinal dysmotility and pseudoobstruction, cachexia, progressive external ophthalmoplegia, axonal sensory ataxic neuropathy, and muscle weakness, and has material basis in autosomal recessive inheritance of compound heterozygous mutation in the mitochondrial DNA polymerase gamma gene on chromosome 15q26.

MedlinePlus Genetics : 43 Mitochondrial neurogastrointestinal encephalopathy (MNGIE) disease is a condition that affects several parts of the body, particularly the digestive system and nervous system. The major features of MNGIE disease can appear anytime from infancy to adulthood, but signs and symptoms most often begin by age 20. The medical problems associated with this disorder worsen with time.Abnormalities of the digestive system are among the most common and severe features of MNGIE disease. Almost all affected people have a condition known as gastrointestinal dysmotility, in which the muscles and nerves of the digestive system do not move food through the digestive tract efficiently. The resulting digestive problems include feelings of fullness (satiety) after eating only a small amount, trouble swallowing (dysphagia), nausea and vomiting after eating, episodes of abdominal pain, diarrhea, and intestinal blockage. These gastrointestinal problems lead to extreme weight loss and reduced muscle mass (cachexia).MNGIE disease is also characterized by abnormalities of the nervous system, although these tend to be milder than the gastrointestinal problems. Affected individuals experience tingling, numbness, and weakness in their limbs (peripheral neuropathy), particularly in the hands and feet. Additional neurological signs and symptoms can include droopy eyelids (ptosis), weakness of the muscles that control eye movement (ophthalmoplegia), and hearing loss. Leukoencephalopathy, which is the deterioration of a type of brain tissue known as white matter, is a hallmark of MNGIE disease. These changes in the brain can be seen with magnetic resonance imaging (MRI), though they usually do not cause symptoms in people with this disorder.

OMIM® : 57 Mitochondrial DNA depletion syndrome-4B is an autosomal recessive progressive multisystem disorder clinically characterized by chronic gastrointestinal dysmotility and pseudoobstruction, cachexia, progressive external ophthalmoplegia (PEO), axonal sensory ataxic neuropathy, and muscle weakness (van Goethem et al., 2003). For a discussion of genetic heterogeneity of autosomal recessive mtDNA depletion syndromes, see MTDPS1 (603041). (613662) (Updated 05-Apr-2021)

UniProtKB/Swiss-Prot : 72 Mitochondrial DNA depletion syndrome 4B: An autosomal recessive progressive multisystem disorder due to mitochondrial dysfunction. It is clinically characterized by chronic gastrointestinal dysmotility and pseudo-obstruction, cachexia, progressive external ophthalmoplegia, axonal sensory ataxic neuropathy, and muscle weakness.

GeneReviews: NBK1179

Related Diseases for Mitochondrial Dna Depletion Syndrome 4b

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 4b via text searches within MalaCards or GeneCards Suite gene sharing:

(show top 50) (show all 102)
# Related Disease Score Top Affiliating Genes
1 mitochondrial dna depletion syndrome 8a 32.2 TEFM RRM2B
2 mitochondrial neurogastrointestinal encephalomyopathy 31.9 TYMP SCO2 RRM2B POLG EDAR
3 mitochondrial dna depletion syndrome 1 31.7 TYMP TEFM SCO2 POLG MPV17 FANCI
4 dysphagia 30.5 TWNK POLG
5 progressive external ophthalmoplegia with mitochondrial dna deletions, autosomal recessive 1 30.4 POLG FANCI
6 neuropathy 30.3 TYMP TWNK SLC25A4 POLG MPV17
7 ptosis 30.3 TYMP TWNK RRM2B POLG
8 polg-related disorders 30.2 TWNK POLG
9 axonal neuropathy 30.1 TWNK SLC25A4 RRM2B POLG
10 mitochondrial encephalomyopathy 29.2 TWNK SUCLG1 POLG MT-TT DGUOK
11 kearns-sayre syndrome 28.8 TYMP TWNK SUCLG1 SSBP1 SLC25A4 SCO2
12 mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes 28.8 TYMP TWNK TMEM70 POLG MT-TT MT-TM
13 myopathy 28.6 TYMP TWNK TMEM70 SLC25A4 RRM2B POLG2
14 chronic progressive external ophthalmoplegia 28.6 TYMP TWNK SUCLG1 SSBP1 SLC25A4 RRM2B
15 lactic acidosis 28.6 SUCLG1 SLC25A4 SCO2 RRM2B POLG2 POLG
16 mitochondrial metabolism disease 28.6 TWNK SUCLG1 SLC25A4 SCO2 RRM2B POLG2
17 3-methylglutaconic aciduria, type iii 28.5 TYMP TWNK TMEM70 SUCLG1 SLC25A4 SCO2
18 mitochondrial disorders 28.4 TYMP TWNK SLC25A4 SCO2 RRM2B POLG2
19 mitochondrial myopathy 28.4 TYMP TWNK SLC25A4 RRM2B POLG2 POLG
20 mitochondrial dna depletion syndrome 4a 27.8 TYMP TWNK SUCLG1 SSBP1 SLC25A4 RRM2B
21 visceral myopathy, familial, with external ophthalmoplegia 11.3
22 central nervous system origin vertigo 10.3 SLC25A4 POLG
23 mitochondrial dna depletion syndrome 12a 10.3 SLC25A4 POLG
24 myotonic cataract 10.3 TWNK POLG
25 ataxia neuropathy spectrum 10.3 TWNK POLG
26 cardioencephalomyopathy 10.3 TYMP SCO2
27 peripheral nervous system disease 10.3
28 encephalopathy 10.3
29 mitochondrial complex iii deficiency, nuclear type 2 10.2 TWNK POLG
30 mitochondrial dna depletion syndrome 12b 10.2 SLC25A4 POLG
31 camptocormism 10.2 RRM2B POLG
32 visual cortex disease 10.2 POLG2 POLG
33 neuropathy, ataxia, and retinitis pigmentosa 10.2 TWNK SCO2 POLG
34 mitochondrial myopathy, episodic, with or without optic atrophy and reversible leukoencephalopathy 10.2 SLC25A4 MT-TM
35 visual pathway disease 10.2 POLG2 POLG
36 3-methylglutaconic aciduria with deafness, encephalopathy, and leigh-like syndrome 10.2 TMEM70 POLG MPV17
37 motor peripheral neuropathy 10.1 POLG MPV17 DGUOK
38 mitochondrial dna depletion syndrome 11 10.1 TEFM MPV17
39 gastroesophageal reflux 10.1
40 krabbe disease 10.1
41 metachromatic leukodystrophy 10.1
42 aspiration pneumonia 10.1
43 crohn's colitis 10.1
44 leukodystrophy 10.1
45 crohn's disease 10.1
46 overgrowth syndrome 10.1
47 mitochondrial dna depletion syndrome 2 10.1 TEFM SCO2 DGUOK
48 acute liver failure 10.1 POLG2 POLG
49 myoclonic epilepsy associated with ragged-red fibers 10.1 TWNK TMEM70 SCO2 POLG
50 encephalopathy, ethylmalonic 10.1 TMEM70 MPV17

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



Diseases related to Mitochondrial Dna Depletion Syndrome 4b

Symptoms & Phenotypes for Mitochondrial Dna Depletion Syndrome 4b

Human phenotypes related to Mitochondrial Dna Depletion Syndrome 4b:

31 (show all 18)
# Description HPO Frequency HPO Source Accession
1 hearing impairment 31 occasional (7.5%) HP:0000365
2 global developmental delay 31 occasional (7.5%) HP:0001263
3 abnormality of the cerebral white matter 31 occasional (7.5%) HP:0002500
4 seizure 31 occasional (7.5%) HP:0001250
5 ataxia 31 HP:0001251
6 constipation 31 HP:0002019
7 malabsorption 31 HP:0002024
8 progressive external ophthalmoplegia 31 HP:0000590
9 abdominal pain 31 HP:0002027
10 slender build 31 HP:0001533
11 cachexia 31 HP:0004326
12 mitochondrial myopathy 31 HP:0003737
13 generalized muscle weakness 31 HP:0003324
14 generalized hypotonia 31 HP:0001290
15 abdominal distention 31 HP:0003270
16 gastrointestinal dysmotility 31 HP:0002579
17 malnutrition 31 HP:0004395
18 sensory ataxic neuropathy 31 HP:0003434

Symptoms via clinical synopsis from OMIM®:

57 (Updated 05-Apr-2021)
Neurologic Central Nervous System:
ataxia
developmental delay (in some)
seizures (in some)
white matter abnormalities (in some)

Muscle Soft Tissue:
mitochondrial myopathy
hypotonia
muscle weakness, diffuse
ragged red fibers seen on muscle biopsy
multiple mitochondrial dna (mtdna) deletions seen on muscle biopsy
more
Growth Other:
thin body habitus
marked cachexia

Growth Weight:
weight loss, progressive

Abdomen Liver:
some patients may have hepatic dysfunction

Abdomen Gastrointestinal:
malabsorption
abdominal pain
abdominal distention
gastrointestinal dysmotility
constipation, chronic
more
Neurologic Peripheral Nervous System:
sensory ataxic neuropathy

Head And Neck Eyes:
external ophthalmoplegia, progressive (peo)

Head And Neck Ears:
hearing loss (1 patient)

Clinical features from OMIM®:

613662 (Updated 05-Apr-2021)

UMLS symptoms related to Mitochondrial Dna Depletion Syndrome 4b:


ataxia; vomiting; abdominal pain; generalized muscle weakness; intermittent diarrhea; chronic constipation; diffuse abdominal pain

MGI Mouse Phenotypes related to Mitochondrial Dna Depletion Syndrome 4b:

46
# Description MGI Source Accession Score Top Affiliating Genes
1 cellular MP:0005384 9.97 DGUOK EDAR GHR MPV17 POLG POLG2
2 cardiovascular system MP:0005385 9.96 DGUOK EDAR GHR MPV17 POLG RRM2B
3 mortality/aging MP:0010768 9.8 DGUOK EDAR FANCI GHR MPV17 POLG
4 muscle MP:0005369 9.23 GHR MPV17 POLG RRM2B SCO2 SLC25A4

Drugs & Therapeutics for Mitochondrial Dna Depletion Syndrome 4b

Interventional clinical trials:


# Name Status NCT ID Phase Drugs
1 The Safety, Tolerability, Pharmacodynamics, and Efficacy of Erythrocyte Encapsulated Thymidine Phosphorylase (EE-TP) in Patients With MNGIE Not yet recruiting NCT03866954 Phase 2
2 MNGIE (Mitochondrial Neurogastrointestinal Encephalomyopathy) AHSCT (Allogeneic Hematopoietic Stem Cell Transplant) Safety Study Recruiting NCT02427178 Phase 1
3 The Rare Disease Clinical Research Network Natural History Study of MNGIE Unknown status NCT01694953

Search NIH Clinical Center for Mitochondrial Dna Depletion Syndrome 4b

Genetic Tests for Mitochondrial Dna Depletion Syndrome 4b

Genetic tests related to Mitochondrial Dna Depletion Syndrome 4b:

# Genetic test Affiliating Genes
1 Mitochondrial Dna Depletion Syndrome 4b, Mngie Type 29 POLG

Anatomical Context for Mitochondrial Dna Depletion Syndrome 4b

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

40
Eye, Bone Marrow, Skeletal Muscle, Small Intestine, Endothelial

Publications for Mitochondrial Dna Depletion Syndrome 4b

Articles related to Mitochondrial Dna Depletion Syndrome 4b:

(show top 50) (show all 93)
# Title Authors PMID Year
1
Multiple mtDNA deletions with features of MNGIE. 6 57 25
12297582 2002
2
Novel POLG mutations in progressive external ophthalmoplegia mimicking mitochondrial neurogastrointestinal encephalomyopathy. 54 6 57
12825077 2003
3
A novel POLG gene mutation in 4 children with Alpers-like hepatocerebral syndromes. 6 57
20142534 2010
4
Fatal congenital myopathy and gastrointestinal pseudo-obstruction due to POLG1 mutations. 57 6
19307547 2009
5
Mitochondrial neurogastrointestinal encephalomyopathy: an autosomal recessive disorder due to thymidine phosphorylase mutations. 25 54 6
10852545 2000
6
Four novel thymidine phosphorylase gene mutations in mitochondrial neurogastrointestinal encephalomyopathy syndrome (MNGIE) patients. 54 6
12529715 2003
7
Purification and functional characterization of human mitochondrial DNA polymerase gamma harboring disease mutations. 6
20176107 2010
8
Late-onset MNGIE without peripheral neuropathy due to incomplete loss of thymidine phosphorylase activity. 54 25
19853446 2009
9
Assessment of stability, toxicity and immunogenicity of new polymeric nanoreactors for use in enzyme replacement therapy of MNGIE. 54 25
19371766 2009
10
R964C mutation of DNA polymerase gamma imparts increased stavudine toxicity by decreasing nucleoside analog discrimination and impairing polymerase activity. 6
19364868 2009
11
Carrier erythrocyte entrapped thymidine phosphorylase therapy for MNGIE. 54 25
18725595 2008
12
Thymidine and deoxyuridine accumulate in tissues of patients with mitochondrial neurogastrointestinal encephalomyopathy (MNGIE). 25 54
17612528 2007
13
Abundance of the POLG disease mutations in Europe, Australia, New Zealand, and the United States explained by single ancient European founders. 6
17426723 2007
14
Novel mutation of human DNA polymerase gamma associated with mitochondrial toxicity induced by anti-HIV treatment. 6
17436221 2007
15
Cognitive dysfunction and hypogonadotrophic hypogonadism in a Brazilian patient with mitochondrial neurogastrointestinal encephalomyopathy and a novel ECGF1 mutation. 25 54
17437622 2007
16
Allogeneic stem cell transplantation corrects biochemical derangements in MNGIE. 25 54
16971696 2006
17
Infusion of platelets transiently reduces nucleoside overload in MNGIE. 25 54
16971699 2006
18
POLG mutations in Alpers syndrome. 6
16177225 2005
19
Late-onset MNGIE due to partial loss of thymidine phosphorylase activity. 25 54
16178026 2005
20
POLG mutations and Alpers syndrome. 6
15929042 2005
21
Sequence analysis of familial PEO shows additional mutations associated with the 752C-->T and 3527C-->T changes in the POLG1 gene. 6
15349879 2004
22
MNGIE with lack of skeletal muscle involvement and a novel TP splice site mutation. 25 54
14757860 2004
23
Mitochondrial neurogastrointestinal encephalomyopathy (MNGIE): a disease of two genomes. 25 54
14720311 2004
24
Definitive diagnosis of mitochondrial neurogastrointestinal encephalomyopathy by biochemical assays. 54 25
14633909 2004
25
Deoxyribonucleotide pool imbalance stimulates deletions in HeLa cell mitochondrial DNA. 54 25
13679382 2003
26
Clinical and genetic heterogeneity in progressive external ophthalmoplegia due to mutations in polymerase gamma. 6
12975295 2003
27
Digenic progressive external ophthalmoplegia in a sporadic patient: recessive mutations in POLG and C10orf2/Twinkle. 6
12872260 2003
28
Site-specific somatic mitochondrial DNA point mutations in patients with thymidine phosphorylase deficiency. 25 54
12813027 2003
29
Elevated plasma deoxyuridine in patients with thymidine phosphorylase deficiency. 54 25
12646159 2003
30
Deoxyuridine accumulation in urine in thymidine phosphorylase deficiency (MNGIE). 25 54
12638947 2002
31
Mutations of mitochondrial DNA polymerase gammaA are a frequent cause of autosomal dominant or recessive progressive external ophthalmoplegia. 6
12210792 2002
32
Altered thymidine metabolism due to defects of thymidine phosphorylase. 54 25
11733540 2002
33
Thymidine phosphorylase gene mutations in MNGIE, a human mitochondrial disorder. 25 54
9924029 1999
34
Mitochondrial neurogastrointestinal encephalomyopathy: diagnosis by rectal biopsy. 25 61
9737248 1998
35
Allogeneic haematopoietic stem cell transplantation for mitochondrial neurogastrointestinal encephalomyopathy. 25
26264513 2015
36
Mitochondrial Neurogastrointestinal Encephalomyopathy Treated with Stem Cell Transplantation: A Case Report and Review of Literature. 25
25585305 2015
37
Deoxynucleoside stress exacerbates the phenotype of a mouse model of mitochondrial neurogastrointestinal encephalopathy. 25
24727567 2014
38
Loss-of-function mutations in MGME1 impair mtDNA replication and cause multisystemic mitochondrial disease. 25
23313956 2013
39
MNGIE Syndrome: Liver Cirrhosis Should Be Ruled Out Prior to Bone Marrow Transplantation. 25
23430799 2013
40
Human mitochondrial DNA: roles of inherited and somatic mutations. 25
23154810 2012
41
A novel finding in MNGIE (mitochondrial neurogastrointestinal encephalomyopathy): hypergonadotropic hypogonadism. 25
22908072 2012
42
Clinical and genetic spectrum of mitochondrial neurogastrointestinal encephalomyopathy. 25
21933806 2011
43
Absence of the interstitial cell of Cajal network in mitochondrial neurogastrointestinal encephalomyopathy. 25
19368660 2009
44
Unbalanced deoxynucleotide pools cause mitochondrial DNA instability in thymidine phosphorylase-deficient mice. 25
19028666 2009
45
Gastrointestinal dysmotility in mitochondrial neurogastrointestinal encephalomyopathy is caused by mitochondrial DNA depletion. 25
18787099 2008
46
Allogeneic stem cell transplantation corrects biochemical derangements in MNGIE. 25
17515557 2007
47
Treatment of mitochondrial neurogastrointestinal encephalomyopathy with dialysis. 25
17353390 2007
48
Abdominal pain related to mitochondrial neurogastrointestinal encephalomyopathy syndrome may benefit from splanchnic nerve blockade. 25
16972839 2006
49
MPV17 encodes an inner mitochondrial membrane protein and is mutated in infantile hepatic mitochondrial DNA depletion. 25
16582910 2006
50
Mitochondrial neurogastrointestinal encephalomyopathy: evidence of mitochondrial DNA depletion in the small intestine. 25
16530527 2006

Variations for Mitochondrial Dna Depletion Syndrome 4b

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

6 (show top 50) (show all 106)
# Gene Name Type Significance ClinVarId dbSNP ID Position
1 POLG NM_002693.2(POLG):c.2591A>G (p.Asn864Ser) SNV Pathogenic 13506 rs121918050 GRCh37: 15:89864974-89864974
GRCh38: 15:89321743-89321743
2 POLG NM_002693.2(POLG):c.679C>T (p.Arg227Trp) SNV Pathogenic 13515 rs121918056 GRCh37: 15:89873488-89873488
GRCh38: 15:89330257-89330257
3 POLG NM_002693.2(POLG):c.2740A>C (p.Thr914Pro) SNV Pathogenic 279961 rs139590686 GRCh37: 15:89864238-89864238
GRCh38: 15:89321007-89321007
4 POLG NM_001126131.2(POLG):c.752C>T (p.Thr251Ile) SNV Pathogenic 13503 rs113994094 GRCh37: 15:89873415-89873415
GRCh38: 15:89330184-89330184
5 POLG NM_001126131.2(POLG):c.752C>T (p.Thr251Ile) SNV Pathogenic 13503 rs113994094 GRCh37: 15:89873415-89873415
GRCh38: 15:89330184-89330184
6 POLG NM_001126131.2(POLG):c.2542G>A (p.Gly848Ser) SNV Pathogenic 13502 rs113994098 GRCh37: 15:89865023-89865023
GRCh38: 15:89321792-89321792
7 POLG NM_001126131.2(POLG):c.1760C>T (p.Pro587Leu) SNV Pathogenic 13505 rs113994096 GRCh37: 15:89868870-89868870
GRCh38: 15:89325639-89325639
8 EDAR NM_022336.4(EDAR):c.266G>A (p.Arg89His) SNV Pathogenic 5849 rs121908450 GRCh37: 2:109545744-109545744
GRCh38: 2:108929288-108929288
9 POLG NM_001126131.2(POLG):c.1760C>T (p.Pro587Leu) SNV Pathogenic 13505 rs113994096 GRCh37: 15:89868870-89868870
GRCh38: 15:89325639-89325639
10 POLG NM_001126131.2(POLG):c.2542G>A (p.Gly848Ser) SNV Pathogenic 13502 rs113994098 GRCh37: 15:89865023-89865023
GRCh38: 15:89321792-89321792
11 POLG NM_001126131.2(POLG):c.3218C>T (p.Pro1073Leu) SNV Pathogenic 13516 rs267606959 GRCh37: 15:89862217-89862217
GRCh38: 15:89318986-89318986
12 POLG NM_002693.3(POLG):c.1399G>A (p.Ala467Thr) SNV Pathogenic 13496 rs113994095 GRCh37: 15:89870432-89870432
GRCh38: 15:89327201-89327201
13 POLG NM_001126131.2(POLG):c.911T>G (p.Leu304Arg) SNV Pathogenic 13497 rs121918044 GRCh37: 15:89872286-89872286
GRCh38: 15:89329055-89329055
14 POLG NM_002693.3(POLG):c.2243G>C SNV Pathogenic 13507 rs113994097 GRCh37: 15:89866657-89866657
GRCh38: 15:89323426-89323426
15 POLG NM_002693.3(POLG):c.1399G>A (p.Ala467Thr) SNV Pathogenic 13496 rs113994095 GRCh37: 15:89870432-89870432
GRCh38: 15:89327201-89327201
16 POLG NM_001126131.2(POLG):c.2542G>A (p.Gly848Ser) SNV Pathogenic 13502 rs113994098 GRCh37: 15:89865023-89865023
GRCh38: 15:89321792-89321792
17 POLG NM_002693.3(POLG):c.1399G>A (p.Ala467Thr) SNV Pathogenic 13496 rs113994095 GRCh37: 15:89870432-89870432
GRCh38: 15:89327201-89327201
18 POLG NM_002693.3(POLG):c.2209G>C (p.Gly737Arg) SNV Pathogenic 13513 rs121918054 GRCh37: 15:89866691-89866691
GRCh38: 15:89323460-89323460
19 POLG NM_002693.2(POLG):c.2554C>T (p.Arg852Cys) SNV Pathogenic 206528 rs144500145 GRCh37: 15:89865011-89865011
GRCh38: 15:89321780-89321780
20 TYMP NM_001953.5(TYMP):c.866A>C (p.Glu289Ala) SNV Pathogenic 16653 rs121913036 GRCh37: 22:50965067-50965067
GRCh38: 22:50526638-50526638
21 TYMP NM_001953.5(TYMP):c.215-1G>C SNV Pathogenic 16662 rs767245071 GRCh37: 22:50967768-50967768
GRCh38: 22:50529339-50529339
22 SCO2 , TYMP NM_001953.5(TYMP):c.1160-1G>A SNV Pathogenic 223064 rs797044455 GRCh37: 22:50964571-50964571
GRCh38: 22:50526142-50526142
23 POLG NM_001126131.2(POLG):c.2890C>T (p.Arg964Cys) SNV Pathogenic/Likely pathogenic 206537 rs201477273 GRCh37: 15:89864088-89864088
GRCh38: 15:89320857-89320857
24 POLG NM_002693.3(POLG):c.3282del (p.Ser1095fs) Deletion Likely pathogenic 813494 rs1596350117 GRCh37: 15:89861972-89861972
GRCh38: 15:89318741-89318741
25 POLG NM_002693.3(POLG):c.502G>C (p.Ala168Pro) SNV Likely pathogenic 972918 GRCh37: 15:89876484-89876484
GRCh38: 15:89333253-89333253
26 POLG NM_002693.3(POLG):c.830A>T (p.His277Leu) SNV Likely pathogenic 206583 rs138929605 GRCh37: 15:89873337-89873337
GRCh38: 15:89330106-89330106
27 POLG NM_002693.2(POLG):c.1402A>G (p.Asn468Asp) SNV Likely pathogenic 206596 rs145843073 GRCh37: 15:89870429-89870429
GRCh38: 15:89327198-89327198
28 POLG NM_002693.3(POLG):c.2209G>C (p.Gly737Arg) SNV Likely pathogenic 13513 rs121918054 GRCh37: 15:89866691-89866691
GRCh38: 15:89323460-89323460
29 POLG NM_002693.3(POLG):c.3286C>T SNV Likely pathogenic 206556 rs201732356 GRCh37: 15:89861968-89861968
GRCh38: 15:89318737-89318737
30 TYMP NM_001953.5(TYMP):c.433G>A (p.Gly145Arg) SNV Likely pathogenic 16655 rs121913037 GRCh37: 22:50967024-50967024
GRCh38: 22:50528595-50528595
31 EDAR NM_022336.4(EDAR):c.265C>T (p.Arg89Cys) SNV Likely pathogenic 562015 rs780424781 GRCh37: 2:109545745-109545745
GRCh38: 2:108929289-108929289
32 POLG NM_002693.2(POLG):c.3098C>T (p.Ala1033Val) SNV Uncertain significance 206470 rs551708243 GRCh37: 15:89862465-89862465
GRCh38: 15:89319234-89319234
33 POLG NM_002693.2(POLG):c.3204C>G (p.Asp1068Glu) SNV Uncertain significance 388649 rs1057523186 GRCh37: 15:89862231-89862231
GRCh38: 15:89319000-89319000
34 POLG NM_002693.2(POLG):c.1402A>G (p.Asn468Asp) SNV Uncertain significance 206596 rs145843073 GRCh37: 15:89870429-89870429
GRCh38: 15:89327198-89327198
35 POLG NM_002693.2(POLG):c.2466C>G (p.Pro822=) SNV Uncertain significance 625997 rs1235161601 GRCh37: 15:89865207-89865207
GRCh38: 15:89321976-89321976
36 POLG NM_002693.2(POLG):c.2468G>A (p.Arg823His) SNV Uncertain significance 448102 rs751172552 GRCh37: 15:89865205-89865205
GRCh38: 15:89321974-89321974
37 SCO2 , TYMP NM_001953.5(TYMP):c.1295G>A (p.Arg432His) SNV Uncertain significance 713848 rs551975117 GRCh37: 22:50964435-50964435
GRCh38: 22:50526006-50526006
38 SCO2 , TYMP NM_001953.5(TYMP):c.1266G>A (p.Glu422=) SNV Uncertain significance 669173 rs932099850 GRCh37: 22:50964464-50964464
GRCh38: 22:50526035-50526035
39 SCO2 , TYMP NM_001953.5(TYMP):c.1209G>A (p.Glu403=) SNV Uncertain significance 990769 GRCh37: 22:50964521-50964521
GRCh38: 22:50526092-50526092
40 SCO2 , TYMP NM_001953.5(TYMP):c.1217C>A (p.Ala406Asp) SNV Uncertain significance 990768 GRCh37: 22:50964513-50964513
GRCh38: 22:50526084-50526084
41 SCO2 , TYMP NM_001953.5(TYMP):c.1225A>G (p.Ser409Gly) SNV Uncertain significance 990767 GRCh37: 22:50964505-50964505
GRCh38: 22:50526076-50526076
42 SCO2 , TYMP NM_001953.5(TYMP):c.1273G>A (p.Val425Ile) SNV Uncertain significance 990766 GRCh37: 22:50964457-50964457
GRCh38: 22:50526028-50526028
43 SCO2 , TYMP NM_001953.5(TYMP):c.1404C>T (p.Ala468=) SNV Uncertain significance 990765 GRCh37: 22:50964244-50964244
GRCh38: 22:50525815-50525815
44 POLG NM_002693.2(POLG):c.862C>T (p.Arg288Cys) SNV Uncertain significance 206586 rs564582352 GRCh37: 15:89872335-89872335
GRCh38: 15:89329104-89329104
45 POLG NM_002693.2(POLG):c.803G>C (p.Gly268Ala) SNV Uncertain significance 196354 rs61752784 GRCh37: 15:89873364-89873364
GRCh38: 15:89330133-89330133
46 POLG NM_002693.2(POLG):c.1174C>G (p.Leu392Val) SNV Uncertain significance 198151 rs145289229 GRCh37: 15:89871763-89871763
GRCh38: 15:89328532-89328532
47 POLG NM_002693.2(POLG):c.2027C>T (p.Ala676Val) SNV Uncertain significance 451086 rs376306906 GRCh37: 15:89867381-89867381
GRCh38: 15:89324150-89324150
48 POLG NM_002693.2(POLG):c.328C>T (p.His110Tyr) SNV Uncertain significance 206619 rs139599587 GRCh37: 15:89876658-89876658
GRCh38: 15:89333427-89333427
49 POLG NM_001126131.2(POLG):c.1550G>T (p.Gly517Val) SNV Uncertain significance 65665 rs61752783 GRCh37: 15:89870178-89870178
GRCh38: 15:89326947-89326947
50 POLG NM_002693.2(POLG):c.1156C>T (p.Arg386Cys) SNV Uncertain significance 206589 rs199759055 GRCh37: 15:89871930-89871930
GRCh38: 15:89328699-89328699

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

72
# Symbol AA change Variation ID SNP ID
1 POLG p.Arg227Trp VAR_023663 rs121918056
2 POLG p.Thr251Ile VAR_023664 rs113994094
3 POLG p.Pro587Leu VAR_023671 rs113994096
4 POLG p.Gly848Ser VAR_023675 rs113994098
5 POLG p.Asn864Ser VAR_023676 rs121918050

Expression for Mitochondrial Dna Depletion Syndrome 4b

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

Pathways for Mitochondrial Dna Depletion Syndrome 4b

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

# Super pathways Score Top Affiliating Genes
1
Show member pathways
12.03 UPP2 TYMP RRM2B NT5M DGUOK
2
Show member pathways
11.57 TWNK SSBP1 POLG2
3 10.43 RRM2B POLG
4
Show member pathways
9.7 UPP2 TYMP SCO2

GO Terms for Mitochondrial Dna Depletion Syndrome 4b

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

# Name GO ID Score Top Affiliating Genes
1 mitochondrial matrix GO:0005759 9.56 TWNK TEFM SUCLG1 SSBP1 SCO2 POLG2
2 mitochondrial nucleoid GO:0042645 9.55 TWNK TEFM SSBP1 POLG2 POLG
3 mitochondrion GO:0005739 9.47 TWNK TMEM70 TEFM SUCLG1 SSBP1 SLC25A4
4 integral component of mitochondrial membrane GO:0032592 9.32 TMEM70 SLC25A4
5 gamma DNA polymerase complex GO:0005760 9.26 POLG2 POLG

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

(show all 11)
# Name GO ID Score Top Affiliating Genes
1 mitochondrion organization GO:0007005 9.58 TWNK SSBP1 POLG2
2 DNA-dependent DNA replication GO:0006261 9.49 POLG2 POLG
3 mitochondrion morphogenesis GO:0070584 9.48 SSBP1 POLG2
4 respiratory electron transport chain GO:0022904 9.46 SCO2 POLG2
5 DNA unwinding involved in DNA replication GO:0006268 9.43 TWNK SSBP1
6 pyrimidine nucleoside catabolic process GO:0046135 9.43 UPP2 TYMP NT5M
7 DNA replication GO:0006260 9.43 TWNK SSBP1 RRM2B POLG2 POLG NT5M
8 pyrimidine nucleoside salvage GO:0043097 9.37 UPP2 TYMP
9 mitochondrial genome maintenance GO:0000002 9.33 TYMP SLC25A4 MPV17
10 mitochondrial transcription GO:0006390 9.32 TWNK TEFM
11 mitochondrial DNA replication GO:0006264 9.1 TWNK TEFM SSBP1 RRM2B POLG2 POLG

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

# Name GO ID Score Top Affiliating Genes
1 DNA-directed DNA polymerase activity GO:0003887 9.26 POLG2 POLG
2 DNA polymerase binding GO:0070182 9.16 POLG2 FANCI
3 transferase activity, transferring pentosyl groups GO:0016763 8.96 UPP2 TYMP
4 DNA polymerase processivity factor activity GO:0030337 8.62 TEFM POLG2

Sources for Mitochondrial Dna Depletion Syndrome 4b

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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