MCID: TBR026
MIFTS: 65

Tuberous Sclerosis 2

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

Aliases & Classifications for Tuberous Sclerosis 2

MalaCards integrated aliases for Tuberous Sclerosis 2:

Name: Tuberous Sclerosis 2 53 71 28 69
Tuberous Sclerosis, Type 2 72 49
Tuberous Sclerosis-2 53 13
Tuberous Sclerosis 71 69
Tsc2 53 71
Tsc2 Angiomyolipomas, Renal, Modifier of 53
Tuberous Sclerosis Complex 71
Ts 71

Characteristics:

OMIM:

53
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:

31
tuberous sclerosis 2:
Onset and clinical course phenotypic variability
Inheritance heterogeneous autosomal dominant inheritance


Classifications:



Summaries for Tuberous Sclerosis 2

OMIM : 53 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 1 and tuberous sclerosis, and has symptoms including hypothyroidism, precocious puberty and intellectual disability. An important gene associated with Tuberous Sclerosis 2 is TSC2 (TSC Complex Subunit 2), and among its related pathways/superpathways are ERK Signaling and TGF-Beta Pathway. 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 Decreased cell migration and Decreased substrate adherent cell growth

UniProtKB/Swiss-Prot : 71 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 : 72 Tuberous sclerosis complex (TSC) is a rare multisystem genetic disease that causes benign tumors to grow... 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 70)
# Related Disease Score Top Affiliating Genes
1 tuberous sclerosis 1 31.7 TSC1 TSC2
2 tuberous sclerosis 30.8 MTOR TSC1 TSC2
3 lymphangioleiomyomatosis 29.9 MTOR TSC1 TSC2
4 gilles de la tourette syndrome 12.0
5 virus-associated trichodysplasia spinulosa 11.6
6 turner syndrome 11.2
7 trichostasis spinulosa 11.1
8 timothy syndrome 11.1
9 temperature sensitivity complementation, cell cycle specific, k12 11.0
10 growth control, y-chromosome influenced 11.0
11 albinism, oculocutaneous, type ib 10.8
12 adult hepatocellular carcinoma 10.4 TSC1 TSC2
13 colorectal cancer 10.3
14 subependymal glioma 10.3 MTOR TSC1 TSC2
15 kidney angiomyolipoma 10.3 MTOR TSC1 TSC2
16 benign ependymoma 10.3 MTOR TSC1 TSC2
17 focal cortical dysplasia, type ii 10.3 MTOR TSC1 TSC2
18 kidney benign neoplasm 10.3 MTOR TSC1 TSC2
19 subependymal giant cell astrocytoma 10.3 MTOR TSC1 TSC2
20 angiomyolipoma 10.2 MTOR TSC1 TSC2
21 mixed cell adenoma 10.2 IGF1 IRS1
22 multilocular clear cell renal cell carcinoma 10.2 TSC1 TSC2
23 focal epilepsy 10.1 MTOR TSC1 TSC2
24 gastric cancer 10.1
25 sporotrichosis 10.0 CALM1 IFNG
26 lung cancer 10.0
27 autosomal dominant polycystic kidney disease 10.0 IGF1 MTOR TSC1 TSC2
28 small cell cancer of the lung 9.9
29 squamous cell carcinoma 9.9
30 adenocarcinoma 9.9
31 kidney cancer 9.9 IFNG MTOR TSC1 TSC2
32 pancreatic cancer 9.8
33 hepatitis 9.8
34 esophagitis 9.8
35 pancreatitis 9.8
36 renal cell carcinoma, nonpapillary 9.8 IFNG MTOR TSC1 TSC2
37 neurofibromatosis, type iv, of riccardi 9.7
38 cerebritis 9.7
39 ganglioglioma 9.7
40 kidney disease 9.7
41 polycystic kidney disease 9.7
42 febrile seizures 9.7
43 blood group, i system 9.7
44 esophageal cancer 9.7
45 glioma susceptibility 1 9.7
46 popliteal pterygium syndrome, lethal type 9.7
47 premature ovarian failure 1 9.7
48 ovarian cancer 1 9.7
49 human immunodeficiency virus type 1 9.7
50 mutagen sensitivity 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:

53
Neurologic Central Nervous System:
seizures
infantile spasms
subependymal nodules
hamartomatous lesions of the brain
cortical tubers
more
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

Endocrine Features:
hypothyroidism
precocious puberty

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:

31 (show all 26)
# Description HPO Frequency HPO Source Accession
1 hypothyroidism 31 HP:0000821
2 precocious puberty 31 HP:0000826
3 intellectual disability 31 very rare (1%) HP:0001249
4 cerebral calcification 31 HP:0002514
5 subcutaneous nodule 31 HP:0001482
6 autism 31 HP:0000717
7 attention deficit hyperactivity disorder 31 HP:0007018
8 specific learning disability 31 HP:0001328
9 wolff-parkinson-white syndrome 31 HP:0001716
10 renal cell carcinoma 31 HP:0005584
11 astrocytoma 31 HP:0009592
12 infantile spasms 31 HP:0012469
13 adenoma sebaceum 31 HP:0009720
14 renal cyst 31 HP:0000107
15 shagreen patch 31 HP:0009721
16 cafe-au-lait spot 31 HP:0000957
17 gingival fibromatosis 31 HP:0000169
18 renal angiomyolipoma 31 HP:0006772
19 subependymal nodules 31 HP:0009716
20 achromatic retinal patches 31 HP:0009727
21 cardiac rhabdomyoma 31 HP:0009729
22 ependymoma 31 HP:0002888
23 cortical tubers 31 HP:0009717
24 chordoma 31 HP:0010762
25 optic nerve glioma 31 HP:0009734
26 subungual fibromas 31 HP:0009724

UMLS symptoms related to Tuberous Sclerosis 2:


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

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

25
# Description GenomeRNAi Source Accession Score Top Affiliating Genes
1 Decreased cell migration GR00055-A-1 9.73 DAPK1 MAP2K2 MAPK14 MAPKAPK2 MTOR TSC1
2 Decreased substrate adherent cell growth GR00193-A-2 9.63 DAPK1 MAPK14 MAPKAPK2 MTOR
3 Decreased substrate adherent cell growth GR00193-A-3 9.63 DAPK1 MAPKAPK2
4 Decreased viability with paclitaxel GR00179-A-1 9.35 IGF1 MTOR
5 Decreased viability with paclitaxel GR00179-A-2 9.35 IGF1 MTOR
6 Decreased viability with paclitaxel GR00179-A-3 9.35 MTOR
7 Increased cell viability after pRB stimulation GR00230-A-1 8.92 MAPKAPK2 DAPK1 MAP2K2 MAPK14

MGI Mouse Phenotypes related to Tuberous Sclerosis 2:

43 (show all 12)
# Description MGI Source Accession Score Top Affiliating Genes
1 cardiovascular system MP:0005385 10.24 IFNG IGF1 IRS1 MAP2K2 MAPK14 MAPKAPK2
2 cellular MP:0005384 10.22 TSC1 TSC2 DAPK1 IFNG IGF1 IRS1
3 behavior/neurological MP:0005386 10.21 DAPK1 IFNG KCNA2 MAP2K2 MAPK14 MTOR
4 homeostasis/metabolism MP:0005376 10.18 DAPK1 IFNG IGF1 IRS1 MAP2K2 MAPK14
5 endocrine/exocrine gland MP:0005379 10.11 IFNG IGF1 IRS1 MAP2K2 MAPK14 MTOR
6 mortality/aging MP:0010768 10.11 IFNG IGF1 IRS1 KCNA2 MAP2K2 MAPK14
7 hematopoietic system MP:0005397 10.09 IFNG IGF1 IRS1 MAPK14 MAPKAPK2 MTOR
8 muscle MP:0005369 9.92 IFNG IGF1 IRS1 MAPK14 MAPKAPK2 MTOR
9 nervous system MP:0003631 9.85 MTOR NR1H2 TSC1 TSC2 DAPK1 IFNG
10 neoplasm MP:0002006 9.8 IFNG IGF1 MAP2K2 MAPK14 MAPKAPK2 TSC1
11 normal MP:0002873 9.56 IFNG IGF1 MAP2K2 MAPK14 MAPKAPK2 MTOR
12 skeleton MP:0005390 9.28 NR1H2 TSC1 IFNG IGF1 IRS1 MAP2K2

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 1 159351-69-6 6442177
2
Miconazole Approved, Investigational, Vet_approved Phase 2, Phase 3, Phase 1 22916-47-8 4189
3
Sirolimus Approved, Investigational Phase 2, Phase 3, Phase 1 53123-88-9 46835353 6436030 5284616
4 Anti-Bacterial Agents Phase 2, Phase 3, Phase 1
5 Antibiotics, Antitubercular Phase 2, Phase 3, Phase 1
6 Antifungal Agents Phase 2, Phase 3, Phase 1
7 Anti-Infective Agents Phase 2, Phase 3, Phase 1
8 Immunosuppressive Agents Phase 2, Phase 3, Phase 1
9
Gemcitabine Approved Phase 2 95058-81-4 60750
10
Metformin Approved Phase 2 657-24-9 4091 14219
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 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 5330286 11431660 5005498
22
Pertuzumab Approved Phase 2 380610-27-5, 145040-37-5 2540
23 Racepinephrine Approved Phase 2 329-65-7
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 15)

# 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 Metformin Combined With Chemotherapy for Pancreatic Cancer Completed NCT01210911 Phase 2 gemcitabine;erlotinib;metformin;placebo
4 Everolimus for Cancer With TSC1 or TSC2 Mutation Recruiting NCT02201212 Phase 2 Everolimus
5 Sapanisertib in Treating Patients With Locally Advanced or Metastatic Bladder Cancer With TSC1 and/or TSC2 Mutations Recruiting NCT03047213 Phase 2 Sapanisertib
6 COLA: A Pilot Clinical Trial of COX-2 Inhibition in LAM and TSC Recruiting NCT02484664 Phase 2 Celecoxib
7 Pediatric MATCH: 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 Recruiting NCT03213678 Phase 2 PI3K/mTOR Inhibitor LY3023414
8 Pediatric MATCH: Targeted Therapy Directed by Genetic Testing in Treating Pediatric Patients With Relapsed or Refractory Advanced Solid Tumors, Non-Hodgkin Lymphomas, or Histiocytic Disorders Recruiting NCT03155620 Phase 2 Ensartinib;Erdafitinib;Larotrectinib;Olaparib;PI3K/mTOR Inhibitor LY3023414;Selumetinib Sulfate;Tazemetostat;Vemurafenib
9 NCI-MATCH: Targeted Therapy Directed by Genetic Testing in Treating Patients With Advanced Refractory Solid Tumors, Lymphomas, or Multiple Myeloma 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
10 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)
11 Everolimus in Patients With Advanced Solid Malignancies With TSC1, TSC2, NF1, NF2, or STK11 Mutations Active, not recruiting NCT02352844 Phase 2 Everolimus
12 Canadian Profiling and Targeted Agent Utilization Trial (CAPTUR) Not yet recruiting NCT03297606 Phase 2 Olaparib;Dasatinib;Nivolumab plus Ipilimumab;Afatinib;Axitinib;Bosutinib;Crizotinib;Palbociclib;Sunitinib;Temsirolimus;Erlotinib;Trastuzumab plus Pertuzumab;Vemurafenib plus Cobimetinib;Vismodegib
13 A Phase I Study of BKM120 and Everolimus in Advanced Solid Malignancies Active, not recruiting NCT01470209 Phase 1 BKM120;Everolimus
14 Genetic Heterogeneity and Genotype-phenotype Correlation of Children and Adults With Tuberous Sclerosis Complex Recruiting NCT02654340
15 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 28 IFNG TSC2

Anatomical Context for Tuberous Sclerosis 2

MalaCards organs/tissues related to Tuberous Sclerosis 2:

38
Brain, Kidney, Heart, Skin, Lung, Eye, Liver

Publications for Tuberous Sclerosis 2

Articles related to Tuberous Sclerosis 2:

(show all 21)
# 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
Polycystic kidney disease as a result of loss of the tuberous sclerosis 2 tumor suppressor gene during development. ( 12547704 )
2003
5
The p38 and MK2 kinase cascade phosphorylates tuberin, the tuberous sclerosis 2 gene product, and enhances its interaction with 14-3-3. ( 12582162 )
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
Novel intragenic polymorphisms in the tuberous sclerosis 2 (TSC2) gene. Mutations in brief no. 184. Online. ( 10660335 )
1998
12
Loss of function of the tuberous sclerosis 2 tumor suppressor gene results in embryonic lethality characterized by disrupted neuroepithelial growth and development. ( 9861021 )
1998
13
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
14
The tuberous sclerosis 2 gene product, tuberin, functions as a Rab5 GTPase activating protein (GAP) in modulating endocytosis. ( 9045618 )
1997
15
An EcoRV polymorphism in exon 40 of the tuberous sclerosis 2 (TSC2) gene. ( 9076719 )
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
Comparative analysis and genomic structure of the tuberous sclerosis 2 (TSC2) gene in human and pufferfish. ( 8789450 )
1996
18
Expression of the tuberous sclerosis 2 gene product, tuberin, in adult and developing nervous system tissues. ( 9173918 )
1996
19
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
20
The tuberous sclerosis 2 gene is expressed at high levels in the cerebellum and developing spinal cord. ( 8562486 )
1995
21
Alternative splicing of the tuberous sclerosis 2 (TSC2) gene in human and mouse tissues. ( 7558029 )
1995

Variations for Tuberous Sclerosis 2

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

71 (show top 50) (show all 52)
# 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.Arg1329His VAR_008029 rs45517323
27 TSC2 p.Pro1709Leu VAR_008030 rs45517393
28 TSC2 p.Arg1743Gln VAR_008031 rs45507199
29 TSC2 p.His1773Pro VAR_008032 rs45517418
30 TSC2 p.Glu1783Gln VAR_008033
31 TSC2 p.Lys258Asn VAR_009417 rs137854875
32 TSC2 p.Arg261Pro VAR_009418 rs45502703
33 TSC2 p.Gly294Glu VAR_009422 rs45487497
34 TSC2 p.Leu361Pro VAR_009426 rs45517147
35 TSC2 p.Asn525Ser VAR_009432 rs45457694
36 TSC2 p.Lys599Met VAR_009435 rs45517202
37 TSC2 p.Ala614Asp VAR_009436 rs45454398
38 TSC2 p.Cys696Tyr VAR_009439 rs45486196
39 TSC2 p.Leu717Arg VAR_009440 rs45517214
40 TSC2 p.Met895Val VAR_009442 rs45470695
41 TSC2 p.Pro1497Arg VAR_009445 rs45497997
42 TSC2 p.Ser1498Asn VAR_009446 rs137854879
43 TSC2 p.His1620Tyr VAR_009448 rs45446901
44 TSC2 p.Asn1643Lys VAR_009449 rs45517381
45 TSC2 p.Asn1651Ser VAR_009450 rs45517382
46 TSC2 p.Pro1675Leu VAR_009451 rs45483392
47 TSC2 p.Asn1681Lys VAR_009452 rs45476793
48 TSC2 p.Ser1704Thr VAR_009453 rs45474691
49 TSC2 p.Arg1743Pro VAR_009454 rs45507199
50 TSC2 p.Leu1744Pro VAR_009455 rs45517413

ClinVar genetic disease variations for Tuberous Sclerosis 2:

6 (show top 50) (show all 253)
# 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.5024C> T (p.Pro1675Leu) single nucleotide variant Pathogenic rs45483392 GRCh37 Chromosome 16, 2137898: 2137898
4 TSC2 NM_000548.4(TSC2): c.34A> T (p.Lys12Ter) single nucleotide variant Pathogenic rs45512692 GRCh37 Chromosome 16, 2098650: 2098650
5 TSC2 NM_000548.4(TSC2): c.2056_2059dupTACT (p.Ser687Leufs) duplication Pathogenic rs137854337 GRCh37 Chromosome 16, 2121894: 2121897
6 TSC2 NM_000548.4(TSC2): c.1513C> T (p.Arg505Ter) single nucleotide variant Pathogenic rs45517179 GRCh37 Chromosome 16, 2114342: 2114342
7 TSC2 NM_000548.4(TSC2): c.1832G> A (p.Arg611Gln) single nucleotide variant Pathogenic rs28934872 GRCh37 Chromosome 16, 2120572: 2120572
8 TSC2 NM_000548.4(TSC2): c.2150T> G (p.Leu717Arg) single nucleotide variant Pathogenic rs45517214 GRCh37 Chromosome 16, 2122294: 2122294
9 TSC2 NM_000548.4(TSC2): c.1432C> T (p.Gln478Ter) single nucleotide variant Pathogenic rs121964862 GRCh37 Chromosome 16, 2113043: 2113043
10 TSC2 NM_000548.4(TSC2): c.1096G> T (p.Glu366Ter) single nucleotide variant Pathogenic rs45517148 GRCh37 Chromosome 16, 2110791: 2110791
11 TSC2 NM_000548.4(TSC2): c.5238_5255del18 (p.His1746_Arg1751del) deletion Pathogenic rs137854218 GRCh37 Chromosome 16, 2138305: 2138322
12 TSC2 NM_000548.4(TSC2): c.2714G> A (p.Arg905Gln) single nucleotide variant Pathogenic rs45517259 GRCh37 Chromosome 16, 2126143: 2126143
13 TSC2 NM_000548.4(TSC2): c.2713C> T (p.Arg905Trp) single nucleotide variant Pathogenic rs45517258 GRCh37 Chromosome 16, 2126142: 2126142
14 TSC2 NM_000548.4(TSC2): c.2713C> G (p.Arg905Gly) single nucleotide variant Pathogenic rs45517258 GRCh37 Chromosome 16, 2126142: 2126142
15 TSC2 NM_000548.4(TSC2): c.2355+2_2355+5delTAGG deletion Pathogenic rs137854250 GRCh37 Chromosome 16, 2122986: 2122989
16 TSC2 NM_000548.4(TSC2): c.1322G> A (p.Trp441Ter) single nucleotide variant Pathogenic rs45515894 GRCh37 Chromosome 16, 2112562: 2112562
17 TSC1 NM_000368.4(TSC1): c.1152delA (p.Gly385Glufs) deletion Pathogenic rs118203501 GRCh37 Chromosome 9, 135786069: 135786069
18 TSC1 NM_000368.4(TSC1): c.1257delC (p.Arg420Glyfs) deletion Pathogenic rs118203506 GRCh37 Chromosome 9, 135785964: 135785964
19 TSC1 NM_000368.4(TSC1): c.1431_1434delAGAA (p.Glu478Lysfs) deletion Pathogenic rs118203527 GRCh37 Chromosome 9, 135782122: 135782125
20 TSC1 NM_000368.4(TSC1): c.1498C> T (p.Arg500Ter) single nucleotide variant Pathogenic rs118203537 GRCh37 Chromosome 9, 135781467: 135781467
21 TSC1 NM_000368.4(TSC1): c.1525C> T (p.Arg509Ter) single nucleotide variant Pathogenic rs118203542 GRCh37 Chromosome 9, 135781440: 135781440
22 TSC1 NM_000368.4(TSC1): c.1580_1581delAG (p.Gln527Argfs) deletion Pathogenic rs118203550 GRCh37 Chromosome 9, 135781384: 135781385
23 TSC1 NM_000368.4(TSC1): c.1697delC (p.Pro566Leufs) deletion Pathogenic rs118203563 GRCh37 Chromosome 9, 135781268: 135781268
24 TSC1 NM_000368.4(TSC1): c.1708_1709delAG (p.Arg570Glyfs) deletion Pathogenic rs118203564 GRCh37 Chromosome 9, 135781256: 135781257
25 TSC1 NM_000368.4(TSC1): c.1959dupA (p.Gln654Thrfs) duplication Pathogenic rs118203603 GRCh37 Chromosome 9, 135781006: 135781006
26 TSC1 NM_000368.4(TSC1): c.1963C> T (p.Gln655Ter) single nucleotide variant Pathogenic rs118203606 GRCh37 Chromosome 9, 135781002: 135781002
27 TSC1 NM_000368.4(TSC1): c.1997+1G> A single nucleotide variant Pathogenic rs118203610 GRCh37 Chromosome 9, 135780967: 135780967
28 TSC1 NM_000368.4(TSC1): c.2023delG (p.Asp675Thrfs) deletion Pathogenic rs118203620 GRCh37 Chromosome 9, 135779816: 135779816
29 TSC1 NM_000368.4(TSC1): c.2074C> T (p.Arg692Ter) single nucleotide variant Pathogenic rs118203631 GRCh37 Chromosome 9, 135779172: 135779172
30 TSC1 NM_000368.4(TSC1): c.211-2A> C single nucleotide variant Pathogenic rs118203352 GRCh37 Chromosome 9, 135801128: 135801128
31 TSC1 NM_000368.4(TSC1): c.2111_2112delAT (p.Tyr704Terfs) deletion Pathogenic rs118203645 GRCh37 Chromosome 9, 135779134: 135779135
32 TSC1 NM_000368.4(TSC1): c.2227C> T (p.Gln743Ter) single nucleotide variant Pathogenic rs118203661 GRCh37 Chromosome 9, 135778156: 135778156
33 TSC1 NM_000368.4(TSC1): c.2283C> A (p.Tyr761Ter) single nucleotide variant Pathogenic rs118203668 GRCh37 Chromosome 9, 135778100: 135778100
34 TSC1 NM_000368.4(TSC1): c.2293C> T (p.Gln765Ter) single nucleotide variant Pathogenic rs118203673 GRCh37 Chromosome 9, 135778090: 135778090
35 TSC1 NM_000368.4(TSC1): c.2341C> T (p.Gln781Ter) single nucleotide variant Pathogenic rs118203680 GRCh37 Chromosome 9, 135778042: 135778042
36 TSC1 NM_000368.4(TSC1): c.2356C> T (p.Arg786Ter) single nucleotide variant Pathogenic rs118203682 GRCh37 Chromosome 9, 135778027: 135778027
37 TSC1 NM_000368.4(TSC1): c.2401G> T (p.Glu801Ter) single nucleotide variant Pathogenic rs118203687 GRCh37 Chromosome 9, 135777077: 135777077
38 TSC1 NM_000368.3(TSC1): c.2509_2512delAACA (p.Asn837Valfs) deletion Pathogenic rs118203707 GRCh37 Chromosome 9, 135776215: 135776218
39 TSC1 NM_000368.4(TSC1): c.2510dupA (p.Asn837Lysfs) duplication Pathogenic rs118203709 GRCh37 Chromosome 9, 135776217: 135776217
40 TSC1 NM_000368.4(TSC1): c.2569delG (p.Glu857Argfs) deletion Pathogenic rs118203712 GRCh37 Chromosome 9, 135776158: 135776158
41 TSC1 NM_000368.4(TSC1): c.2672dupA (p.Asn891Lysfs) duplication Pathogenic rs118203724 GRCh37 Chromosome 9, 135772951: 135772951
42 TSC1 NM_000368.4(TSC1): c.2689C> T (p.Gln897Ter) single nucleotide variant Pathogenic rs118203727 GRCh37 Chromosome 9, 135772934: 135772934
43 TSC1 NM_000368.4(TSC1): c.2692C> T (p.Gln898Ter) single nucleotide variant Pathogenic rs118203728 GRCh37 Chromosome 9, 135772931: 135772931
44 TSC1 NM_000368.4(TSC1): c.271_272delTC (p.Ser91Valfs) deletion Pathogenic rs118203360 GRCh37 Chromosome 9, 135801065: 135801066
45 TSC1 NM_000368.4(TSC1): c.395_406delGCGTCTTGGTGTinsCA (p.Gly132Alafs) indel Pathogenic rs118203380 GRCh37 Chromosome 9, 135798837: 135798848
46 TSC1 NM_000368.4(TSC1): c.445C> T (p.Gln149Ter) single nucleotide variant Pathogenic rs118203384 GRCh37 Chromosome 9, 135798798: 135798798
47 TSC1 NM_000368.4(TSC1): c.491G> A (p.Trp164Ter) single nucleotide variant Pathogenic rs118203387 GRCh37 Chromosome 9, 135798752: 135798752
48 TSC1 NM_000368.4(TSC1): c.664-1G> C single nucleotide variant Pathogenic rs118203423 GRCh37 Chromosome 9, 135796824: 135796824
49 TSC1 NM_000368.4(TSC1): c.682C> T (p.Arg228Ter) single nucleotide variant Pathogenic rs118203427 GRCh37 Chromosome 9, 135796805: 135796805
50 TSC1 NM_000368.4(TSC1): c.733C> T (p.Arg245Ter) single nucleotide variant Pathogenic rs118203434 GRCh37 Chromosome 9, 135796754: 135796754

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 89)
# Super pathways Score Top Affiliating Genes
1
Show member pathways
13.83 IGF1 IRS1 MAP2K2 MAPK14 MAPKAPK2 MTOR
2
Show member pathways
13.57 CALM1 IFNG IGF1 IRS1 MAP2K2 MAPK14
3
Show member pathways
13.44 IGF1 IRS1 MAPK14 MAPKAPK2 MTOR TSC1
4
Show member pathways
13.32 CALM1 IGF1 MAP2K2 MAPK14 TSC1 TSC2
5
Show member pathways
13.25 CALM1 IFNG IGF1 IRS1 MAP2K2 MAPK14
6
Show member pathways
13.08 CALM1 IGF1 IRS1 MAP2K2 MTOR TSC1
7
Show member pathways
13.02 IGF1 IRS1 MAP2K2 MAPK14 MTOR TSC1
8
Show member pathways
13 IGF1 IRS1 MAP2K2 MTOR TSC1 TSC2
9
Show member pathways
12.98 MAPK14 MTOR TSC1 TSC2 YWHAB
10 12.88 CALM1 DAPK1 IFNG IGF1 MAP2K2 MTOR
11
Show member pathways
12.85 CALM1 IGF1 IRS1 MAP2K2 MAPK14 MTOR
12
Show member pathways
12.84 IRS1 MAP2K2 MAPK14 MTOR YWHAB
13
Show member pathways
12.77 CALM1 IGF1 MAP2K2 MAPK14 RAB5A
14
Show member pathways
12.72 CALM1 IGF1 IRS1 MAP2K2 MAPK14 MTOR
15
Show member pathways
12.69 CALM1 IGF1 MAP2K2 MAPK14 MTOR TSC2
16
Show member pathways
12.67 CALM1 IRS1 MAP2K2 MAPK14 MAPKAPK2 MTOR
17
Show member pathways
12.63 CALM1 IGF1 MAP2K2 MAPK14 MTOR
18
Show member pathways
12.62 CALM1 IGF1 IRS1 MAP2K2 YWHAB
19
Show member pathways
12.61 CALM1 MAP2K2 MAPK14 MAPKAPK2 MTOR YWHAB
20
Show member pathways
12.6 CALM1 MAP2K2 MAPK14 MAPKAPK2
21
Show member pathways
12.55 IRS1 MAP2K2 MAPK14 MTOR TSC1 TSC2
22
Show member pathways
12.52 IGF1 IRS1 MAP2K2 MTOR TSC1 TSC2
23
Show member pathways
12.51 IRS1 MAP2K2 MAPK14 MTOR
24
Show member pathways
12.48 IGF1 IRS1 MTOR TSC1 TSC2
25
Show member pathways
12.47 MAP2K2 MAPK14 MTOR YWHAB
26
Show member pathways
12.46 CALM1 IFNG MAP2K2 MAPK14
27
Show member pathways
12.46 IRS1 MTOR TSC1 TSC2 YWHAB
28
Show member pathways
12.44 MAP2K2 MTOR TSC1 TSC2
29
Show member pathways
12.39 CALM1 IGF1 MAPK14 YWHAB
30
Show member pathways
12.38 MAP2K2 MAPK14 MTOR YWHAB
31
Show member pathways
12.36 CALM1 IGF1 IRS1 MAP2K2 MAPK14
32
Show member pathways
12.36 CALM1 MAP2K2 MAPK14 MTOR YWHAB
33 12.34 IGF1 MAP2K2 MAPK14 MTOR
34
Show member pathways
12.3 IRS1 MAP2K2 MAPK14 MTOR
35 12.28 CALM1 IFNG MAPK14 RAB5A
36
Show member pathways
12.27 MAP2K2 MTOR TSC1 TSC2 YWHAB
37
Show member pathways
12.25 IRS1 MAPK14 MTOR TSC1 TSC2
38 12.24 MAP2K2 MAPK14 MTOR RAB5A
39
Show member pathways
12.22 MAP2K2 MAPK14 MTOR YWHAB
40
Show member pathways
12.22 CALM1 IGF1 MAP2K2 MAPK14 MTOR
41 12.2 IRS1 MTOR TSC1 TSC2
42
Show member pathways
12.18 IGF1 IRS1 MTOR TSC1 TSC2
43
Show member pathways
12.18 IFNG IRS1 MAPK14 MAPKAPK2 MTOR TSC1
44
Show member pathways
12.17 IGF1 IRS1 MTOR TSC2
45 12.15 IRS1 MAP2K2 MAPK14 MTOR TSC2
46
Show member pathways
12.14 IGF1 IRS1 MAP2K2 MAPK14
47
Show member pathways
12.09 IFNG IRS1 MAP2K2 MAPK14 MAPKAPK2
48
Show member pathways
12.07 CALM1 MAP2K2 MTOR TSC2
49 12.04 MAP2K2 MAPK14 MAPKAPK2 YWHAB
50 12 MAP2K2 MTOR TSC2

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 9.77 CALM1 DAPK1 IRS1 MAP2K2 MAPK14 MAPKAPK2
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 protein phosphorylation GO:0006468 9.98 DAPK1 MAP2K2 MAPK14 MAPKAPK2 MTOR
2 phosphorylation GO:0016310 9.91 CALM1 DAPK1 MAP2K2 MAPK14 MAPKAPK2 MTOR
3 positive regulation of gene expression GO:0010628 9.85 IFNG IGF1 MAPK14 MTOR NR1H2
4 movement of cell or subcellular component GO:0006928 9.7 IFNG IGF1 MAPK14
5 Ras protein signal transduction GO:0007265 9.69 IGF1 MAPK14 MAPKAPK2
6 response to insulin GO:0032868 9.67 IRS1 MTOR TSC1
7 cell cycle arrest GO:0007050 9.67 IFNG MTOR TSC1 TSC2
8 mRNA stabilization GO:0048255 9.61 MAPKAPK2 MTOR
9 3-UTR-mediated mRNA stabilization GO:0070935 9.61 MAPK14 MAPKAPK2
10 positive regulation of myotube differentiation GO:0010831 9.6 MAPK14 MTOR
11 positive regulation of glycogen biosynthetic process GO:0045725 9.59 IGF1 IRS1
12 negative regulation of macroautophagy GO:0016242 9.58 MTOR TSC1
13 positive regulation of protein serine/threonine kinase activity GO:0071902 9.58 CALM1 IFNG MAP2K2
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 anoikis GO:0043276 9.55 MTOR TSC2
17 negative regulation of cell size GO:0045792 9.54 MTOR TSC1
18 positive regulation of glucose import GO:0046326 9.5 IGF1 IRS1 MAPK14
19 p38MAPK cascade GO:0038066 9.48 MAPK14 MAPKAPK2
20 activation of MAPK activity GO:0000187 9.46 IGF1 MAP2K2 MAPK14 MAPKAPK2
21 negative regulation of insulin receptor signaling pathway GO:0046627 9.43 IRS1 TSC1 TSC2
22 insulin-like growth factor receptor signaling pathway GO:0048009 9.13 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 9.65 DAPK1 MAP2K2 MAPK14 MAPKAPK2 MTOR
2 protein domain specific binding GO:0019904 9.62 CALM1 MTOR RABEP1 YWHAB
3 protein serine/threonine kinase activity GO:0004674 9.55 DAPK1 MAP2K2 MAPK14 MAPKAPK2 MTOR
4 protein binding GO:0005515 9.53 CALM1 DAPK1 IFNG IGF1 IRS1 KCNA2
5 kinase activity GO:0016301 9.43 CALM1 DAPK1 MAP2K2 MAPK14 MAPKAPK2 MTOR
6 insulin-like growth factor receptor binding GO:0005159 9.4 IGF1 IRS1
7 MAP kinase kinase activity GO:0004708 9.37 MAP2K2 MAPK14

Sources for Tuberous Sclerosis 2

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
16 ExPASy
18 FMA
27 GO
28 GTR
29 HGMD
30 HMDB
31 HPO
32 ICD10
33 ICD10 via Orphanet
34 ICD9CM
35 IUPHAR
36 KEGG
37 LifeMap
39 MedGen
41 MeSH
42 MESH via Orphanet
43 MGI
45 NCI
46 NCIt
47 NDF-RT
50 NINDS
51 Novoseek
53 OMIM
54 OMIM via Orphanet
58 PubMed
60 QIAGEN
65 SNOMED-CT via HPO
66 SNOMED-CT via Orphanet
67 TGDB
68 Tocris
69 UMLS
70 UMLS via Orphanet
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