MCID: TBR026
MIFTS: 65

Tuberous Sclerosis 2

Categories: Genetic diseases, Rare diseases, Nephrological diseases, Neuronal diseases, Eye diseases, Skin diseases, Fetal diseases

Aliases & Classifications for Tuberous Sclerosis 2

MalaCards integrated aliases for Tuberous Sclerosis 2:

Name: Tuberous Sclerosis 2 57 75 29 6 73
Tuberous Sclerosis, Type 2 76 53 40
Tsc2 Angiomyolipomas, Renal, Modifier of 57 6
Tuberous Sclerosis-2 57 13
Tuberous Sclerosis 75 73
Tsc2 57 75
Tuberous Sclerosis Complex 75
Ts 75

Characteristics:

OMIM:

57
Inheritance:
autosomal dominant

Miscellaneous:
majority of cases are sporadic
highly variable phenotype
genetic heterogeneity (see )
one-third of cases are familial
prevalence of 1 in 6,000 to 1 in 10,000
many studies have reported that the phenotype of tuberous sclerosis-2 (tsc2) is more severe than that of tuberous sclerosis-1 (e.g., lower iq, more seizures, more macules, cust-like cortical tubers)
frequent new mutations (~60%) and/or gonadal mosaicism in tsc2


HPO:

32
tuberous sclerosis 2:
Onset and clinical course phenotypic variability
Inheritance heterogeneous autosomal dominant inheritance


Classifications:



Summaries for Tuberous Sclerosis 2

OMIM : 57 Tuberous sclerosis complex (TSC) is an autosomal dominant multisystem disorder characterized by hamartomas in multiple organ systems, including the brain, skin, heart, kidneys, and lung. These changes can result in epilepsy, learning difficulties, behavioral problems, and renal failure, among other complications (reviews by Crino et al., 2006 and Curatolo et al., 2008). For a general phenotypic description and a discussion of genetic heterogeneity of tuberous sclerosis, see tuberous sclerosis-1 (191100), caused by mutation in the TSC1 gene (605284) on chromosome 9q34. Approximately 10 to 30% of cases of tuberous sclerosis are due to mutations in the TSC1 gene: the frequency of cases due to mutations in the TSC2 gene is consistently higher. TSC2 mutations are associated with more severe disease (Crino et al., 2006) (see GENOTYPE/PHENOTYPE CORRELATIONS section). (613254)

MalaCards based summary : Tuberous Sclerosis 2, also known as tuberous sclerosis, type 2, is related to tuberous sclerosis and lymphangioleiomyomatosis, and has symptoms including back pain, headache and pain. An important gene associated with Tuberous Sclerosis 2 is TSC2 (TSC Complex Subunit 2), and among its related pathways/superpathways are TGF-Beta Pathway and Akt Signaling. The drugs Everolimus and Miconazole have been mentioned in the context of this disorder. Affiliated tissues include brain, kidney and heart, and related phenotypes are hypothyroidism and precocious puberty

UniProtKB/Swiss-Prot : 75 Tuberous sclerosis 2: An autosomal dominant multi-system disorder that affects especially the brain, kidneys, heart, and skin. It is characterized by hamartomas (benign overgrowths predominantly of a cell or tissue type that occurs normally in the organ) and hamartias (developmental abnormalities of tissue combination). Clinical manifestations include epilepsy, learning difficulties, behavioral problems, and skin lesions. Seizures can be intractable and premature death can occur from a variety of disease-associated causes.

Wikipedia : 76 Tuberous sclerosis complex (TSC), or epiloia (acronym of \"epilepsy, low intelligence, adenoma... more...

Related Diseases for Tuberous Sclerosis 2

Diseases in the Tuberous Sclerosis family:

Tuberous Sclerosis 1 Tuberous Sclerosis 2

Diseases related to Tuberous Sclerosis 2 via text searches within MalaCards or GeneCards Suite gene sharing:

(show top 50) (show all 74)
# Related Disease Score Top Affiliating Genes
1 tuberous sclerosis 30.4 MTOR NTHL1 PKD1 TSC1 TSC2
2 lymphangioleiomyomatosis 29.8 MTOR TSC1 TSC2
3 gilles de la tourette syndrome 12.0
4 turner syndrome 11.8
5 virus-associated trichodysplasia spinulosa 11.6
6 tuberous sclerosis 1 11.1
7 timothy syndrome 11.1
8 trichostasis spinulosa 11.1
9 temperature sensitivity complementation, cell cycle specific, k12 11.0
10 albinism, oculocutaneous, type ib 10.9
11 polycystic kidney disease, infantile severe, with tuberous sclerosis 10.8 PKD1 TSC2
12 familial adenomatous polyposis 3 10.7 NTHL1 TSC2
13 adult hepatocellular carcinoma 10.6 TSC1 TSC2
14 mixed cell adenoma 10.5 IGF1 IRS1
15 polycystic liver disease 1 with or without kidney cysts 10.4 PKD1 TSC1 TSC2
16 subependymal glioma 10.3 MTOR TSC1 TSC2
17 kidney angiomyolipoma 10.3 MTOR TSC1 TSC2
18 colorectal cancer 10.3
19 benign ependymoma 10.3 MTOR TSC1 TSC2
20 hepatic angiomyolipoma 10.3 MTOR TSC2
21 kidney benign neoplasm 10.3 MTOR TSC1 TSC2
22 subependymal giant cell astrocytoma 10.3 MTOR TSC1 TSC2
23 focal cortical dysplasia, type ii 10.3 MTOR TSC1 TSC2
24 angiomyolipoma 10.3 MTOR TSC1 TSC2
25 gastric cancer 10.1
26 polycystic kidney disease 1 with or without polycystic liver disease 10.1 MTOR PKD1 TSC1 TSC2
27 multilocular clear cell renal cell carcinoma 10.1 TSC1 TSC2
28 endometrial adenocarcinoma 10.0
29 lung cancer 10.0
30 focal epilepsy 9.9 MTOR TSC1 TSC2
31 small cell cancer of the lung 9.9
32 esophagitis 9.9
33 squamous cell carcinoma 9.9
34 adenocarcinoma 9.9
35 sporotrichosis 9.9 CALM1 IFNG
36 breast cancer 9.8
37 esophageal cancer 9.8
38 pancreatic cancer 9.8
39 hepatitis 9.8
40 pancreatitis 9.8
41 autosomal dominant polycystic kidney disease 9.8 IGF1 MTOR PKD1 TSC1 TSC2
42 neurofibromatosis, type ii 9.7
43 neurofibromatosis, type i 9.7
44 neurofibromatosis, type iv, of riccardi 9.7
45 cerebritis 9.7
46 ganglioglioma 9.7
47 kidney disease 9.7
48 polycystic kidney disease 9.7
49 febrile seizures 9.7
50 glioma susceptibility 1 9.7

Graphical network of the top 20 diseases related to Tuberous Sclerosis 2:



Diseases related to Tuberous Sclerosis 2

Symptoms & Phenotypes for Tuberous Sclerosis 2

Symptoms via clinical synopsis from OMIM:

57
Endocrine Features:
hypothyroidism
precocious puberty

Neurologic Behavioral Psychiatric Manifestations:
autism
hyperactivity
attention deficit disorder

Head And Neck Eyes:
achromatic retinal patches
retinal astrocytoma
optic gliomas

Neoplasia:
ependymoma
renal carcinoma
myocardial rhabdomyoma
multiple bilateral renal angiomyolipoma
giant cell astrocytoma
more
Head And Neck Mouth:
pitted dental enamel
gingival fibroma

Skeletal:
cystic areas of bone rarefaction, esp. phalanges

Neurologic Central Nervous System:
seizures
infantile spasms
subependymal nodules
hamartomatous lesions of the brain
cortical tubers
more
Skin Nails Hair Skin:
shagreen patch
subcutaneous nodules
cafe-au-lait spots
facial angiofibroma (adenoma sebaceum)
white ash leaf-shaped macules
more
Cardiovascular Heart:
cardiac rhabdomyoma
wolf-parkinson-white syndrome

Genitourinary Kidneys:
renal cysts
tumors of the kidney (may progress to malignancy in less than 2%)

Respiratory Lung:
lymphangiomyomatosis, rare

Laboratory Abnormalities:
increased frequency of premature centromere disjunction (pcd) in cultured fibroblasts, esp. chromosome 3
allelic loss on 16p13.3 in angiomyolipoma, cardiac rhabdomyoma, cortical tuber, and giant cell astrocytoma


Clinical features from OMIM:

613254

Human phenotypes related to Tuberous Sclerosis 2:

32 (show all 27)
# Description HPO Frequency HPO Source Accession
1 hypothyroidism 32 HP:0000821
2 precocious puberty 32 HP:0000826
3 intellectual disability 32 very rare (1%) HP:0001249
4 seizures 32 HP:0001250
5 cerebral calcification 32 HP:0002514
6 subcutaneous nodule 32 HP:0001482
7 autism 32 HP:0000717
8 attention deficit hyperactivity disorder 32 HP:0007018
9 specific learning disability 32 HP:0001328
10 wolff-parkinson-white syndrome 32 HP:0001716
11 renal cell carcinoma 32 HP:0005584
12 astrocytoma 32 HP:0009592
13 infantile spasms 32 HP:0012469
14 adenoma sebaceum 32 HP:0009720
15 renal cyst 32 HP:0000107
16 shagreen patch 32 HP:0009721
17 cafe-au-lait spot 32 HP:0000957
18 gingival fibromatosis 32 HP:0000169
19 renal angiomyolipoma 32 HP:0006772
20 subependymal nodules 32 HP:0009716
21 achromatic retinal patches 32 HP:0009727
22 cardiac rhabdomyoma 32 HP:0009729
23 ependymoma 32 HP:0002888
24 cortical tubers 32 HP:0009717
25 chordoma 32 HP:0010762
26 optic nerve glioma 32 HP:0009734
27 subungual fibromas 32 HP:0009724

UMLS symptoms related to Tuberous Sclerosis 2:


back pain, headache, pain, sciatica, seizures, syncope, tremor, chronic pain, vertigo/dizziness, sleeplessness

GenomeRNAi Phenotypes related to Tuberous Sclerosis 2 according to GeneCards Suite gene sharing:

26 (show all 15)
# Description GenomeRNAi Source Accession Score Top Affiliating Genes
1 Decreased viability GR00055-A-2 10.16 DAPK1 MAPKAPK2 MTOR PKD1
2 Decreased viability GR00221-A-1 10.16 DAPK1 MTOR
3 Decreased viability GR00221-A-3 10.16 MAPKAPK2
4 Decreased viability GR00221-A-4 10.16 DAPK1 MTOR
5 Decreased viability GR00342-S-1 10.16 DAPK1 MTOR
6 Decreased viability GR00342-S-2 10.16 MTOR
7 Decreased viability GR00402-S-2 10.16 DAPK1 MAPKAPK2 MTOR PKD1
8 Decreased cell migration GR00055-A-1 9.91 DAPK1 MAP2K2 MAPK14 MAPKAPK2 MTOR PKD1
9 Decreased substrate adherent cell growth GR00193-A-2 9.8 DAPK1 MAPK14 MAPKAPK2 MTOR
10 Decreased substrate adherent cell growth GR00193-A-3 9.8 DAPK1 MAPKAPK2
11 Decreased viability with paclitaxel GR00179-A-1 9.55 MTOR IGF1
12 Decreased viability with paclitaxel GR00179-A-2 9.55 IGF1 MTOR
13 Decreased viability with paclitaxel GR00179-A-3 9.55 MTOR
14 Increased cell migration GR00055-A-3 9.26 MTOR PKD1 DAPK1 MAPK14
15 Increased cell viability after pRB stimulation GR00230-A-1 8.92 DAPK1 MAP2K2 MAPK14 MAPKAPK2

MGI Mouse Phenotypes related to Tuberous Sclerosis 2:

46 (show all 17)
# Description MGI Source Accession Score Top Affiliating Genes
1 cardiovascular system MP:0005385 10.37 TSC1 TSC2 IFNG IGF1 IRS1 MAP2K2
2 homeostasis/metabolism MP:0005376 10.37 DAPK1 IFNG IGF1 IRS1 MAP2K2 MAPK14
3 cellular MP:0005384 10.36 IRS1 MAP2K2 MAPK14 MAPKAPK2 MTOR NR1H2
4 behavior/neurological MP:0005386 10.31 DAPK1 IFNG KCNA2 MAP2K2 MAPK14 MTOR
5 hematopoietic system MP:0005397 10.25 IFNG IGF1 IRS1 MAPK14 MAPKAPK2 MTOR
6 mortality/aging MP:0010768 10.25 PKD1 SERPINC1 TSC1 TSC2 IFNG IGF1
7 endocrine/exocrine gland MP:0005379 10.22 IFNG IGF1 IRS1 MAP2K2 MAPK14 MTOR
8 embryo MP:0005380 10.14 MAPKAPK2 MTOR PKD1 SERPINC1 TSC1 TSC2
9 nervous system MP:0003631 10.1 SERPINC1 TSC1 TSC2 DAPK1 IFNG IGF1
10 integument MP:0010771 10.08 IFNG IGF1 MAP2K2 MAPK14 NR1H2 PKD1
11 liver/biliary system MP:0005370 10.06 IFNG IRS1 MAPK14 NR1H2 PKD1 SERPINC1
12 muscle MP:0005369 10.06 IFNG IGF1 IRS1 MAPK14 MAPKAPK2 MTOR
13 neoplasm MP:0002006 10.02 IFNG IGF1 MAP2K2 MAPK14 MAPKAPK2 NTHL1
14 normal MP:0002873 9.91 IFNG IGF1 MAP2K2 MAPK14 MAPKAPK2 MTOR
15 renal/urinary system MP:0005367 9.76 SERPINC1 TSC1 TSC2 DAPK1 IFNG IGF1
16 respiratory system MP:0005388 9.5 IFNG IGF1 KCNA2 MAPK14 MTOR PKD1
17 skeleton MP:0005390 9.32 IFNG IGF1 IRS1 MAP2K2 MAPK14 MAPKAPK2

Drugs & Therapeutics for Tuberous Sclerosis 2

Drugs for Tuberous Sclerosis 2 (from DrugBank, HMDB, Dgidb, PharmGKB, IUPHAR, NovoSeek, BitterDB):

(show top 50) (show all 58)
# Name Status Phase Clinical Trials Cas Number PubChem Id
1
Everolimus Approved Phase 2, Phase 3,Phase 3,Phase 1 159351-69-6 6442177
2
Miconazole Approved, Investigational, Vet_approved Phase 2, Phase 3,Phase 3,Phase 1 22916-47-8 4189
3
Sirolimus Approved, Investigational Phase 2, Phase 3,Phase 3,Phase 1 53123-88-9 5284616 6436030 46835353
4 Anti-Bacterial Agents Phase 2, Phase 3,Phase 3,Phase 1
5 Antibiotics, Antitubercular Phase 2, Phase 3,Phase 3,Phase 1
6 Antifungal Agents Phase 2, Phase 3,Phase 3,Phase 1
7 Anti-Infective Agents Phase 2, Phase 3,Phase 3,Phase 1
8 Immunosuppressive Agents Phase 2, Phase 3,Phase 3,Phase 1
9
Gemcitabine Approved Phase 2 95058-81-4 60750
10
Metformin Approved Phase 2 657-24-9 14219 4091
11
Celecoxib Approved, Investigational Phase 2 169590-42-5 2662
12
Menthol Approved Phase 2 2216-51-5 16666
13
Olaparib Approved Phase 2 763113-22-0 23725625
14
Adenosine Approved, Investigational Phase 2 58-61-7 60961
15
Crizotinib Approved Phase 2 877399-52-5 11626560 10366136 10366137 10366138 10366139 10366140 10366141
16
Dabrafenib Approved, Investigational Phase 2 1195765-45-7 44462760 44516822
17
Dasatinib Approved, Investigational Phase 2 302962-49-8 3062316
18
Epinephrine Approved, Vet_approved Phase 2 51-43-4 5816
19
nivolumab Approved Phase 2 946414-94-4
20
Osimertinib Approved Phase 2 1421373-65-0 71496458
21
Palbociclib Approved, Investigational Phase 2 571190-30-2 11431660 5005498 5330286
22
Pertuzumab Approved Phase 2 145040-37-5, 380610-27-5 2540
23
Racepinephrine Approved Phase 2 329-65-7 838
24
Sunitinib Approved, Investigational Phase 2 341031-54-7, 557795-19-4 5329102
25
Trametinib Approved Phase 2 871700-17-3 11707110
26
Trastuzumab Approved, Investigational Phase 2 180288-69-1 9903
27
Sorafenib Approved, Investigational Phase 2 284461-73-0 216239 406563
28
Axitinib Approved, Investigational Phase 2 319460-85-0 6450551
29
Lapatinib Approved March 2007, Investigational Phase 2 231277-92-2, 388082-78-8 208908 9941095
30 Antimetabolites Phase 2
31 Antimetabolites, Antineoplastic Phase 2
32 Antiviral Agents Phase 2
33
Erlotinib Hydrochloride Phase 2 183319-69-9 176871
34 Hypoglycemic Agents Phase 2
35 Protein Kinase Inhibitors Phase 2
36 Analgesics Phase 2
37 Analgesics, Non-Narcotic Phase 2
38 Anti-Inflammatory Agents Phase 2
39 Anti-Inflammatory Agents, Non-Steroidal Phase 2
40 Antirheumatic Agents Phase 2
41 Cyclooxygenase 2 Inhibitors Phase 2
42 Cyclooxygenase Inhibitors Phase 2
43 Peripheral Nervous System Agents Phase 2
44 Poly(ADP-ribose) Polymerase Inhibitors Phase 2
45 Ado-trastuzumab emtansine Phase 2
46 Angiogenesis Inhibitors Phase 2
47 Angiogenesis Modulating Agents Phase 2
48 Antibodies Phase 2
49 Antibodies, Monoclonal Phase 2
50 Antimitotic Agents Phase 2

Interventional clinical trials:

(show all 16)
# Name Status NCT ID Phase Drugs
1 Efficacy of RAD001/Everolimus in Autism and NeuroPsychological Deficits in Children With Tuberous Sclerosis Complex Unknown status NCT01730209 Phase 2, Phase 3 Everolimus;Placebo
2 Efficacy and Safety of RAD001 in Patients Aged 18 and Over With Angiomyolipoma Associated With Either Tuberous Sclerosis Complex (TSC) or Sporadic Lymphangioleiomyomatosis (LAM) Completed NCT00790400 Phase 3 Everolimus (RAD001);Everolimus Placebo
3 Everolimus in Patients With Advanced Solid Malignancies With TSC1, TSC2, NF1, NF2, or STK11 Mutations Completed NCT02352844 Phase 2 Everolimus
4 Metformin Combined With Chemotherapy for Pancreatic Cancer Completed NCT01210911 Phase 2 gemcitabine;erlotinib;metformin;placebo
5 Everolimus for Treatment of Disfiguring Cutaneous Lesions in Neurofibromatosis1 CRAD001CUS232T Completed NCT02332902 Phase 2 Everolimus
6 Everolimus for Cancer With TSC1 or TSC2 Mutation Recruiting NCT02201212 Phase 2 Everolimus
7 Sapanisertib in Treating Patients With Locally Advanced or Metastatic Bladder Cancer With TSC1 and/or TSC2 Mutations Recruiting NCT03047213 Phase 2 Sapanisertib
8 COLA: A Pilot Clinical Trial of COX-2 Inhibition in LAM and TSC Recruiting NCT02484664 Phase 2 Celecoxib
9 PI3K/mTOR Inhibitor LY3023414 in Treating Patients With Relapsed or Refractory Advanced Solid Tumors, Non-Hodgkin Lymphoma, or Histiocytic Disorders With TSC or PI3K/MTOR Mutations (A Pediatric MATCH Treatment Trial) Recruiting NCT03213678 Phase 2 PI3K/mTOR Inhibitor LY3023414
10 Targeted Therapy Directed by Genetic Testing in Treating Pediatric Patients With Relapsed or Refractory Advanced Solid Tumors, Non-Hodgkin Lymphomas, or Histiocytic Disorders (The Pediatric MATCH Screening Trial) Recruiting NCT03155620 Phase 2 Ensartinib;Erdafitinib;Larotrectinib;Olaparib;Palbociclib;PI3K/mTOR Inhibitor LY3023414;Selumetinib Sulfate;Tazemetostat;Vemurafenib
11 Targeted Therapy Directed by Genetic Testing in Treating Patients With Advanced Refractory Solid Tumors, Lymphomas, or Multiple Myeloma (The MATCH Screening Trial) Recruiting NCT02465060 Phase 2 Adavosertib;Afatinib;Binimetinib;Capivasertib;Crizotinib;Dabrafenib;Dasatinib;Defactinib;FGFR Inhibitor AZD4547;Larotrectinib;Osimertinib;Palbociclib;PI3K-beta Inhibitor GSK2636771;Sapanisertib;Sunitinib Malate;Taselisib;Trametinib;Vismodegib
12 Adapting Treatment to the Tumor Molecular Alterations for Patients With Advanced Solid Tumors: My Own Specific Treatment Recruiting NCT02029001 Phase 2 Nilotinib (400 mg BID);Everolimus (10 mg QD);Sorafenib (400 mg BID);Lapatinib (1500 mg QD);Pazopanib (800 mg QD)
13 Canadian Profiling and Targeted Agent Utilization Trial (CAPTUR) Recruiting NCT03297606 Phase 2 Olaparib;Dasatinib;Nivolumab plus Ipilimumab;Afatinib;Axitinib;Bosutinib;Crizotinib;Palbociclib;Sunitinib;Temsirolimus;Erlotinib;Trastuzumab plus Pertuzumab;Vemurafenib plus Cobimetinib;Vismodegib
14 A Phase I Study of BKM120 and Everolimus in Advanced Solid Malignancies Completed NCT01470209 Phase 1 BKM120;Everolimus
15 Genetic Heterogeneity and Genotype-phenotype Correlation of Children and Adults With Tuberous Sclerosis Complex Recruiting NCT02654340
16 Characterization of Patients With Tuberous Sclerosis Complex, Lymphangioleiomyomatosis and Angiomyolipoma Recruiting NCT02325505

Search NIH Clinical Center for Tuberous Sclerosis 2

Genetic Tests for Tuberous Sclerosis 2

Genetic tests related to Tuberous Sclerosis 2:

# Genetic test Affiliating Genes
1 Tuberous Sclerosis 2 29 IFNG TSC2

Anatomical Context for Tuberous Sclerosis 2

MalaCards organs/tissues related to Tuberous Sclerosis 2:

41
Brain, Kidney, Heart, Skin, Lung, Eye, Liver

Publications for Tuberous Sclerosis 2

Articles related to Tuberous Sclerosis 2:

(show all 22)
# Title Authors Year
1
Novel Inflammatory Neuropathology in Immature Brain: (1) Fetal Tuberous Sclerosis, (2) Febrile Seizures, (3) I+-B-crystallin, and (4) Role of Astrocytes. ( 29103422 )
2017
2
AMP-activated protein kinase inhibits IGF-I signaling and protein synthesis in vascular smooth muscle cells via stimulation of insulin receptor substrate 1 S794 and tuberous sclerosis 2 S1345 phosphorylation. ( 20363874 )
2010
3
The G1556S-type tuberin variant suppresses tumor formation in tuberous sclerosis 2 mutant (Eker) rats despite its deficiency in mTOR inhibition. ( 18695678 )
2008
4
The p38 and MK2 kinase cascade phosphorylates tuberin, the tuberous sclerosis 2 gene product, and enhances its interaction with 14-3-3. ( 12582162 )
2003
5
Polycystic kidney disease as a result of loss of the tuberous sclerosis 2 tumor suppressor gene during development. ( 12547704 )
2003
6
Aberrant splicing in several human tumors in the tumor suppressor genes neurofibromatosis type 1, neurofibromatosis type 2, and tuberous sclerosis 2. ( 11888927 )
2002
7
A calmodulin binding site in the tuberous sclerosis 2 gene product is essential for regulation of transcription events and is altered by mutations linked to tuberous sclerosis and lymphangioleiomyomatosis. ( 11811958 )
2002
8
The tuberous sclerosis 2 gene product can localize to nuclei in a phosphorylation-dependent manner. ( 11703097 )
2001
9
Genetic variants of the tuberous sclerosis 2 tumour suppressor gene in mouse t haplotypes. ( 10584558 )
1999
10
Mutation and polymorphism analysis in the tuberous sclerosis 2 (TSC2) gene. ( 10732801 )
1998
11
Loss of function of the tuberous sclerosis 2 tumor suppressor gene results in embryonic lethality characterized by disrupted neuroepithelial growth and development. ( 9861021 )
1998
12
Novel intragenic polymorphisms in the tuberous sclerosis 2 (TSC2) gene. Mutations in brief no. 184. Online. ( 10660335 )
1998
13
An EcoRV polymorphism in exon 40 of the tuberous sclerosis 2 (TSC2) gene. ( 9076719 )
1997
14
Identification of a leader exon and a core promoter for the rat tuberous sclerosis 2 (Tsc2) gene and structural comparison with the human homolog. ( 9250859 )
1997
15
The tuberous sclerosis 2 gene product, tuberin, functions as a Rab5 GTPase activating protein (GAP) in modulating endocytosis. ( 9045618 )
1997
16
A novel splice site associated polymorphism in the tuberous sclerosis 2 (TSC2) gene may predispose to the development of sporadic gangliogliomas. ( 9210877 )
1997
17
Expression of the tuberous sclerosis 2 gene product, tuberin, in adult and developing nervous system tissues. ( 9173918 )
1996
18
Localization of tuberous sclerosis 2 mRNA and its protein product tuberin in normal human brain and in cerebral lesions of patients with tuberous sclerosis. ( 8944308 )
1996
19
Comparative analysis and genomic structure of the tuberous sclerosis 2 (TSC2) gene in human and pufferfish. ( 8789450 )
1996
20
Alternative splicing of the tuberous sclerosis 2 (TSC2) gene in human and mouse tissues. ( 7558029 )
1995
21
The tuberous sclerosis 2 gene is expressed at high levels in the cerebellum and developing spinal cord. ( 8562486 )
1995
22
Predisposition to renal carcinoma in the Eker rat is determined by germ-line mutation of the tuberous sclerosis 2 (TSC2) gene. ( 7972075 )
1994

Variations for Tuberous Sclerosis 2

UniProtKB/Swiss-Prot genetic disease variations for Tuberous Sclerosis 2:

75 (show top 50) (show all 51)
# Symbol AA change Variation ID SNP ID
1 TSC2 p.Leu292Pro VAR_005646 rs45517138
2 TSC2 p.Tyr407Asp VAR_005647 rs45517156
3 TSC2 p.Met449Ile VAR_005648 rs45443091
4 TSC2 p.Arg611Gln VAR_005650 rs28934872
5 TSC2 p.Arg611Trp VAR_005651 rs45469298
6 TSC2 p.Leu826Met VAR_005652 rs45517238
7 TSC2 p.Arg905Gln VAR_005653 rs45517259
8 TSC2 p.Arg905Trp VAR_005654 rs45517258
9 TSC2 p.Asp1084Glu VAR_005655 rs45517286
10 TSC2 p.Arg1200Trp VAR_005656 rs45438205
11 TSC2 p.Pro1227Leu VAR_005657
12 TSC2 p.Arg1240Trp VAR_005658
13 TSC2 p.Asp1295Val VAR_005659
14 TSC2 p.Tyr1549Cys VAR_005661 rs45517355
15 TSC2 p.Asn1643Ile VAR_005663 rs45517380
16 TSC2 p.Tyr1650Cys VAR_005664 rs45501091
17 TSC2 p.Asp1690Tyr VAR_005665 rs137854882
18 TSC2 p.Ala1712Glu VAR_005666
19 TSC2 p.Leu1750Phe VAR_005667 rs45459299
20 TSC2 p.Cys227Tyr VAR_008020 rs45517122
21 TSC2 p.Asn331Lys VAR_008021 rs45517153
22 TSC2 p.Asn486Ile VAR_008022 rs45486599
23 TSC2 p.Pro816Leu VAR_008026 rs45517236
24 TSC2 p.Val1144Met VAR_008027 rs45517294
25 TSC2 p.Pro1315Ser VAR_008028 rs397514916
26 TSC2 p.Pro1709Leu VAR_008030 rs45517393
27 TSC2 p.Arg1743Gln VAR_008031 rs45507199
28 TSC2 p.His1773Pro VAR_008032 rs45517418
29 TSC2 p.Glu1783Gln VAR_008033
30 TSC2 p.Lys258Asn VAR_009417 rs137854875
31 TSC2 p.Arg261Pro VAR_009418 rs45502703
32 TSC2 p.Gly294Glu VAR_009422 rs45487497
33 TSC2 p.Leu361Pro VAR_009426 rs45517147
34 TSC2 p.Asn525Ser VAR_009432 rs45457694
35 TSC2 p.Lys599Met VAR_009435 rs45517202
36 TSC2 p.Ala614Asp VAR_009436 rs45454398
37 TSC2 p.Cys696Tyr VAR_009439 rs45486196
38 TSC2 p.Leu717Arg VAR_009440 rs45517214
39 TSC2 p.Met895Val VAR_009442 rs45470695
40 TSC2 p.Pro1497Arg VAR_009445 rs45497997
41 TSC2 p.Ser1498Asn VAR_009446 rs137854879
42 TSC2 p.His1620Tyr VAR_009448 rs45446901
43 TSC2 p.Asn1643Lys VAR_009449 rs45517381
44 TSC2 p.Asn1651Ser VAR_009450 rs45517382
45 TSC2 p.Pro1675Leu VAR_009451 rs45483392
46 TSC2 p.Asn1681Lys VAR_009452 rs45476793
47 TSC2 p.Ser1704Thr VAR_009453 rs45474691
48 TSC2 p.Arg1743Pro VAR_009454 rs45507199
49 TSC2 p.Leu1744Pro VAR_009455 rs45517413
50 TSC2 p.Ser1653Phe VAR_018603 rs45517383

ClinVar genetic disease variations for Tuberous Sclerosis 2:

6
(show top 50) (show all 3006)
# Gene Variation Type Significance SNP ID Assembly Location
1 TSC2 TSC2, 1-BP DEL, 5110A deletion Pathogenic
2 TSC2 NM_000548.4(TSC2): c.4642delC (p.Leu1548Cysfs) deletion Pathogenic rs137854083 GRCh37 Chromosome 16, 2135303: 2135303
3 TSC2 NM_000548.4(TSC2): c.4642delC (p.Leu1548Cysfs) deletion Pathogenic rs137854083 GRCh38 Chromosome 16, 2085302: 2085302
4 TSC2 NM_000548.4(TSC2): c.5024C> T (p.Pro1675Leu) single nucleotide variant Pathogenic rs45483392 GRCh37 Chromosome 16, 2137898: 2137898
5 TSC2 NM_000548.4(TSC2): c.5024C> T (p.Pro1675Leu) single nucleotide variant Pathogenic rs45483392 GRCh38 Chromosome 16, 2087897: 2087897
6 TSC2 NM_000548.4(TSC2): c.34A> T (p.Lys12Ter) single nucleotide variant Pathogenic rs45512692 GRCh37 Chromosome 16, 2098650: 2098650
7 TSC2 NM_000548.4(TSC2): c.34A> T (p.Lys12Ter) single nucleotide variant Pathogenic rs45512692 GRCh38 Chromosome 16, 2048649: 2048649
8 TSC2 NM_000548.4(TSC2): c.2056_2059dupTACT (p.Ser687Leufs) duplication Pathogenic rs137854337 GRCh37 Chromosome 16, 2121894: 2121897
9 TSC2 NM_000548.4(TSC2): c.2056_2059dupTACT (p.Ser687Leufs) duplication Pathogenic rs137854337 GRCh38 Chromosome 16, 2071893: 2071896
10 TSC2 NM_000548.4(TSC2): c.1513C> T (p.Arg505Ter) single nucleotide variant Pathogenic rs45517179 GRCh37 Chromosome 16, 2114342: 2114342
11 TSC2 NM_000548.4(TSC2): c.1513C> T (p.Arg505Ter) single nucleotide variant Pathogenic rs45517179 GRCh38 Chromosome 16, 2064341: 2064341
12 TSC2 NM_000548.4(TSC2): c.1832G> A (p.Arg611Gln) single nucleotide variant Pathogenic rs28934872 GRCh37 Chromosome 16, 2120572: 2120572
13 TSC2 NM_000548.4(TSC2): c.1832G> A (p.Arg611Gln) single nucleotide variant Pathogenic rs28934872 GRCh38 Chromosome 16, 2070571: 2070571
14 TSC2 NM_000548.4(TSC2): c.2150T> G (p.Leu717Arg) single nucleotide variant Pathogenic rs45517214 GRCh37 Chromosome 16, 2122294: 2122294
15 TSC2 NM_000548.4(TSC2): c.2150T> G (p.Leu717Arg) single nucleotide variant Pathogenic rs45517214 GRCh38 Chromosome 16, 2072293: 2072293
16 TSC2 NM_000548.4(TSC2): c.1432C> T (p.Gln478Ter) single nucleotide variant Pathogenic rs121964862 GRCh37 Chromosome 16, 2113043: 2113043
17 TSC2 NM_000548.4(TSC2): c.1432C> T (p.Gln478Ter) single nucleotide variant Pathogenic rs121964862 GRCh38 Chromosome 16, 2063042: 2063042
18 TSC2 NM_000548.4(TSC2): c.5238_5255del18 (p.His1746_Arg1751del) deletion Pathogenic rs137854218 GRCh37 Chromosome 16, 2138305: 2138322
19 TSC2 NM_000548.4(TSC2): c.5238_5255del18 (p.His1746_Arg1751del) deletion Pathogenic rs137854218 GRCh38 Chromosome 16, 2088304: 2088321
20 TSC2 NM_000548.4(TSC2): c.2714G> A (p.Arg905Gln) single nucleotide variant Pathogenic rs45517259 GRCh37 Chromosome 16, 2126143: 2126143
21 TSC2 NM_000548.4(TSC2): c.2714G> A (p.Arg905Gln) single nucleotide variant Pathogenic rs45517259 GRCh38 Chromosome 16, 2076142: 2076142
22 TSC2 NM_000548.4(TSC2): c.2713C> T (p.Arg905Trp) single nucleotide variant Pathogenic rs45517258 GRCh37 Chromosome 16, 2126142: 2126142
23 TSC2 NM_000548.4(TSC2): c.2713C> T (p.Arg905Trp) single nucleotide variant Pathogenic rs45517258 GRCh38 Chromosome 16, 2076141: 2076141
24 TSC2 NM_000548.4(TSC2): c.2713C> G (p.Arg905Gly) single nucleotide variant Pathogenic rs45517258 GRCh37 Chromosome 16, 2126142: 2126142
25 TSC2 NM_000548.4(TSC2): c.2713C> G (p.Arg905Gly) single nucleotide variant Pathogenic rs45517258 GRCh38 Chromosome 16, 2076141: 2076141
26 TSC2 NM_000548.4(TSC2): c.2355+2_2355+5delTAGG deletion Pathogenic rs137854250 GRCh37 Chromosome 16, 2122986: 2122989
27 TSC2 NM_000548.4(TSC2): c.2355+2_2355+5delTAGG deletion Pathogenic rs137854250 GRCh38 Chromosome 16, 2072985: 2072988
28 TSC2 NM_000548.4(TSC2): c.1322G> A (p.Trp441Ter) single nucleotide variant Pathogenic rs45515894 GRCh37 Chromosome 16, 2112562: 2112562
29 TSC2 NM_000548.4(TSC2): c.1322G> A (p.Trp441Ter) single nucleotide variant Pathogenic rs45515894 GRCh38 Chromosome 16, 2062561: 2062561
30 IFNG NM_000619.2(IFNG): c.115-484_115-457CA[12] NT expansion risk factor rs587776821 GRCh37 Chromosome 12, 68552496: 68552497
31 IFNG NM_000619.2(IFNG): c.115-484_115-457CA[12] NT expansion risk factor rs587776821 GRCh38 Chromosome 12, 68158716: 68158717
32 TSC2 NM_000548.4(TSC2): c.1111C> T (p.Gln371Ter) single nucleotide variant Pathogenic rs45469099 GRCh37 Chromosome 16, 2110806: 2110806
33 TSC2 NM_000548.4(TSC2): c.1111C> T (p.Gln371Ter) single nucleotide variant Pathogenic rs45469099 GRCh38 Chromosome 16, 2060805: 2060805
34 TSC2 NM_000548.4(TSC2): c.133_136delCTGA (p.Leu45Glufs) deletion Pathogenic rs137854360 GRCh37 Chromosome 16, 2098749: 2098752
35 TSC2 NM_000548.4(TSC2): c.133_136delCTGA (p.Leu45Glufs) deletion Pathogenic rs137854360 GRCh38 Chromosome 16, 2048748: 2048751
36 TSC2 NM_000548.4(TSC2): c.1372C> T (p.Arg458Ter) single nucleotide variant Pathogenic rs45517169 GRCh37 Chromosome 16, 2112983: 2112983
37 TSC2 NM_000548.4(TSC2): c.1372C> T (p.Arg458Ter) single nucleotide variant Pathogenic rs45517169 GRCh38 Chromosome 16, 2062982: 2062982
38 TSC2 NM_000548.4(TSC2): c.226-2A> G single nucleotide variant Pathogenic rs45517096 GRCh37 Chromosome 16, 2103341: 2103341
39 TSC2 NM_000548.4(TSC2): c.226-2A> G single nucleotide variant Pathogenic rs45517096 GRCh38 Chromosome 16, 2053340: 2053340
40 TSC2 NM_000548.4(TSC2): c.2356-2A> C single nucleotide variant Pathogenic rs45517229 GRCh37 Chromosome 16, 2124199: 2124199
41 TSC2 NM_000548.4(TSC2): c.2356-2A> C single nucleotide variant Pathogenic rs45517229 GRCh38 Chromosome 16, 2074198: 2074198
42 TSC2 NM_000548.4(TSC2): c.3094C> T (p.Arg1032Ter) single nucleotide variant Pathogenic rs45465195 GRCh37 Chromosome 16, 2129160: 2129160
43 TSC2 NM_000548.4(TSC2): c.3094C> T (p.Arg1032Ter) single nucleotide variant Pathogenic rs45465195 GRCh38 Chromosome 16, 2079159: 2079159
44 TSC2 NM_000548.4(TSC2): c.3095G> C (p.Arg1032Pro) single nucleotide variant Pathogenic/Likely pathogenic rs45491698 GRCh37 Chromosome 16, 2129161: 2129161
45 TSC2 NM_000548.4(TSC2): c.3095G> C (p.Arg1032Pro) single nucleotide variant Pathogenic/Likely pathogenic rs45491698 GRCh38 Chromosome 16, 2079160: 2079160
46 TSC2 NM_000548.4(TSC2): c.3206_3207delTG (p.Val1069Aspfs) deletion Pathogenic rs137854076 GRCh37 Chromosome 16, 2129351: 2129352
47 TSC2 NM_000548.4(TSC2): c.3206_3207delTG (p.Val1069Aspfs) deletion Pathogenic rs137854076 GRCh38 Chromosome 16, 2079350: 2079351
48 TSC2 NM_000548.4(TSC2): c.3310_3311delCA (p.Gln1104Aspfs) deletion Pathogenic rs137854018 GRCh37 Chromosome 16, 2129583: 2129584
49 TSC2 NM_000548.4(TSC2): c.3310_3311delCA (p.Gln1104Aspfs) deletion Pathogenic rs137854018 GRCh38 Chromosome 16, 2079582: 2079583
50 TSC2 NM_000548.4(TSC2): c.3412C> T (p.Arg1138Ter) single nucleotide variant Pathogenic rs45451497 GRCh37 Chromosome 16, 2130180: 2130180

Expression for Tuberous Sclerosis 2

Search GEO for disease gene expression data for Tuberous Sclerosis 2.

Pathways for Tuberous Sclerosis 2

Pathways related to Tuberous Sclerosis 2 according to GeneCards Suite gene sharing:

(show top 50) (show all 83)
# Super pathways Score Top Affiliating Genes
1
Show member pathways
13.54 IFNG IGF1 IRS1 MAP2K2 MAPK14 MAPKAPK2
2
Show member pathways
13.45 IGF1 IRS1 MAPK14 MAPKAPK2 MTOR TSC1
3
Show member pathways
13.32 CALM1 IGF1 MAP2K2 MAPK14 TSC1 TSC2
4
Show member pathways
13.04 IGF1 IRS1 MAP2K2 MAPK14 MTOR TSC1
5
Show member pathways
13.01 IGF1 IRS1 MAP2K2 MTOR TSC1 TSC2
6
Show member pathways
12.9 IGF1 IRS1 MAP2K2 MTOR TSC2
7 12.88 CALM1 DAPK1 IFNG IGF1 MAP2K2 MTOR
8
Show member pathways
12.85 CALM1 IGF1 IRS1 MAP2K2 MAPK14 MTOR
9
Show member pathways
12.84 IRS1 MAP2K2 MAPK14 MTOR YWHAB
10
Show member pathways
12.83 CALM1 IFNG IRS1 MAP2K2 MAPK14
11
Show member pathways
12.83 IGF1 IRS1 MAP2K2 MAPK14 MTOR
12
Show member pathways
12.8 CALM1 IGF1 IRS1 MAP2K2 MAPK14 MAPKAPK2
13
Show member pathways
12.78 CALM1 IGF1 MAP2K2 MAPK14 RAB5A
14
Show member pathways
12.71 CALM1 IGF1 MAP2K2 MAPK14 MTOR TSC2
15
Show member pathways
12.7 CALM1 IRS1 MAP2K2 MAPK14 MAPKAPK2 MTOR
16
Show member pathways
12.68 CALM1 IGF1 IRS1 MAP2K2 MAPK14 MTOR
17
Show member pathways
12.62 CALM1 IGF1 IRS1 MAP2K2 YWHAB
18
Show member pathways
12.61 CALM1 MAP2K2 MAPK14 MAPKAPK2 MTOR YWHAB
19
Show member pathways
12.56 IRS1 MAP2K2 MAPK14 MTOR TSC1 TSC2
20
Show member pathways
12.52 IGF1 IRS1 MAP2K2 MTOR TSC1 TSC2
21
Show member pathways
12.51 IRS1 MAP2K2 MAPK14 MTOR
22
Show member pathways
12.49 IGF1 IRS1 MTOR TSC1 TSC2
23
Show member pathways
12.47 MAP2K2 MAPK14 MTOR YWHAB
24
Show member pathways
12.47 MAP2K2 MAPK14 MTOR YWHAB
25
Show member pathways
12.46 CALM1 IFNG MAP2K2 MAPK14
26
Show member pathways
12.46 IRS1 MTOR TSC1 TSC2 YWHAB
27
Show member pathways
12.43 MAP2K2 MTOR TSC1 TSC2
28
Show member pathways
12.39 CALM1 IGF1 MAPK14 YWHAB
29
Show member pathways
12.37 CALM1 MAP2K2 MAPK14 MTOR YWHAB
30
Show member pathways
12.36 CALM1 IGF1 IRS1 MAP2K2 MAPK14
31 12.34 IGF1 MAP2K2 MAPK14 MTOR
32 12.28 CALM1 IFNG MAPK14 RAB5A
33
Show member pathways
12.26 CALM1 MAP2K2 MAPK14 MAPKAPK2
34
Show member pathways
12.26 IRS1 MAP2K2 MAPK14 MTOR
35
Show member pathways
12.26 IRS1 MAPK14 MTOR TSC1 TSC2
36 12.24 MAP2K2 MAPK14 MTOR RAB5A
37
Show member pathways
12.22 MAP2K2 MAPK14 MTOR YWHAB
38
Show member pathways
12.21 CALM1 IGF1 MAP2K2 MAPK14 MTOR
39 12.2 MTOR TSC1 TSC2 YWHAB
40 12.2 IRS1 MTOR TSC1 TSC2
41
Show member pathways
12.18 IGF1 IRS1 MTOR TSC1 TSC2
42
Show member pathways
12.18 IFNG IRS1 MAPK14 MAPKAPK2 MTOR TSC1
43
Show member pathways
12.17 IGF1 IRS1 MTOR TSC2
44 12.15 IRS1 MAP2K2 MAPK14 MTOR TSC2
45
Show member pathways
12.14 IGF1 IRS1 MAP2K2 MAPK14
46
Show member pathways
12.11 MAP2K2 MTOR TSC1 TSC2
47
Show member pathways
12.1 IFNG IRS1 MAP2K2 MAPK14 MAPKAPK2
48
Show member pathways
12.07 CALM1 MAP2K2 MTOR TSC2
49
Show member pathways
12.05 CALM1 DAPK1 IFNG IGF1 MAP2K2 MAPK14
50 12.03 MAP2K2 MAPK14 MAPKAPK2 YWHAB

GO Terms for Tuberous Sclerosis 2

Cellular components related to Tuberous Sclerosis 2 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 cytoplasm GO:0005737 9.83 CALM1 DAPK1 IGF1 IRS1 MAP2K2 MAPK14
2 TSC1-TSC2 complex GO:0033596 8.62 TSC1 TSC2

Biological processes related to Tuberous Sclerosis 2 according to GeneCards Suite gene sharing:

(show all 23)
# Name GO ID Score Top Affiliating Genes
1 phosphorylation GO:0016310 9.95 CALM1 DAPK1 MAP2K2 MAPK14 MAPKAPK2 MTOR
2 positive regulation of gene expression GO:0010628 9.89 IFNG IGF1 MAPK14 MTOR NR1H2
3 peptidyl-serine phosphorylation GO:0018105 9.73 MAPK14 MAPKAPK2 MTOR PKD1
4 Ras protein signal transduction GO:0007265 9.7 IGF1 MAPK14 MAPKAPK2
5 activation of MAPK activity GO:0000187 9.67 IGF1 MAP2K2 MAPK14 MAPKAPK2
6 positive regulation of protein serine/threonine kinase activity GO:0071902 9.63 CALM1 IFNG MAP2K2
7 3-UTR-mediated mRNA stabilization GO:0070935 9.61 MAPK14 MAPKAPK2
8 positive regulation of insulin receptor signaling pathway GO:0046628 9.61 IGF1 IRS1
9 positive regulation of phosphoprotein phosphatase activity GO:0032516 9.6 CALM1 MTOR
10 positive regulation of myotube differentiation GO:0010831 9.59 MAPK14 MTOR
11 positive regulation of glycogen biosynthetic process GO:0045725 9.58 IGF1 IRS1
12 negative regulation of macroautophagy GO:0016242 9.58 MTOR TSC1
13 positive regulation of glucose import GO:0046326 9.58 IGF1 IRS1 MAPK14
14 positive regulation of cell growth involved in cardiac muscle cell development GO:0061051 9.57 IGF1 MTOR
15 positive regulation of protein import into nucleus, translocation GO:0033160 9.56 IFNG IGF1
16 response to insulin GO:0032868 9.56 IGF1 IRS1 MTOR TSC1
17 anoikis GO:0043276 9.55 MTOR TSC2
18 negative regulation of cell size GO:0045792 9.54 MTOR TSC1
19 p38MAPK cascade GO:0038066 9.51 MAPK14 MAPKAPK2
20 negative regulation of insulin receptor signaling pathway GO:0046627 9.5 IRS1 TSC1 TSC2
21 cell cycle arrest GO:0007050 9.35 IFNG MTOR PKD1 TSC1 TSC2
22 insulin-like growth factor receptor signaling pathway GO:0048009 9.33 IGF1 IRS1 TSC2
23 MAPK cascade GO:0000165 9.1 CALM1 IRS1 MAP2K2 MAPK14 MAPKAPK2 YWHAB

Molecular functions related to Tuberous Sclerosis 2 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 protein kinase activity GO:0004672 9.72 DAPK1 MAP2K2 MAPK14 MAPKAPK2 MTOR
2 protein serine/threonine kinase activity GO:0004674 9.65 DAPK1 MAP2K2 MAPK14 MAPKAPK2 MTOR
3 kinase activity GO:0016301 9.63 CALM1 DAPK1 MAP2K2 MAPK14 MAPKAPK2 MTOR
4 protein binding GO:0005515 9.6 CALM1 DAPK1 IFNG IGF1 IRS1 KCNA2
5 insulin-like growth factor receptor binding GO:0005159 9.4 IGF1 IRS1
6 MAP kinase kinase activity GO:0004708 9.37 MAP2K2 MAPK14
7 protein domain specific binding GO:0019904 9.35 CALM1 MTOR PKD1 RABEP1 YWHAB

Sources for Tuberous Sclerosis 2

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
35 ICD9CM
36 IUPHAR
37 KEGG
38 LifeMap
40 LOVD
42 MedGen
44 MeSH
45 MESH via Orphanet
46 MGI
49 NCI
50 NCIt
51 NDF-RT
54 NINDS
55 Novoseek
57 OMIM
58 OMIM via Orphanet
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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