TSC2 (tuberous sclerosis 2)

2001-11-01   Aristotelis Astrinidis , Elizabeth Petri Henske 

Fox Chase Cancer Center, 7701 Burholme Ave, Philadelphia PA 19111, USA

Identity

HGNC
LOCATION
16p13.3
LOCUSID
ALIAS
LAM,PPP1R160,TSC4
FUSION GENES

DNA/RNA

Description

41 exons; spans 41kb

Transcription

At least 3 alternate splicings; 5.5kb mRNA complete cds; coding sequence: CDS 19-5442

Proteins

Description

Tuberin; 1807 amino acids; 190 kDaltons

Expression

Expressed in most embryonic and adult tissues

Localisation

Cytoplasmic

Function

Potential GTPase activating protein (GAP) for Rap1a and/or Rab5; Interacts with hamartin ( TSC1 gene product) and Rabaptin-5

Homology

188 residues at the COOH terminus have homology to Rap/Ran GAP

Mutations

Germinal

Large genomic deletions in <10% of cases; point mutations widely dispersed, with no cluster; truncating effect in 2/3 of cases

Somatic

loss-of-heterozygosity in 2/3 of renal angiomyolipomas; Somatic mutations in angiomyolipomas and pulmonary lymphangioleiomyomatosis (LAM) cells from women with sporadic LAM

Implicated in

Entity name
Tuberous Sclerosis Comples (TSC)
Disease
Autosomal dominant disease characterized by seizures, mental retardation, autism, benign tumors of the brain, heart, skin, kidney, and malignant kidney tumors.
Disease
Lung disease affecting almost exclusively women, characterized by diffuse bilateral proliferation of abnormal smooth muscle cells in the lungs

Bibliography

Pubmed IDLast YearTitleAuthors
784970819949q34 loss of heterozygosity in a tuberous sclerosis astrocytoma suggests a growth suppressor-like activity also for the TSC1 gene.Carbonara C et al
108239532000Mutations in the tuberous sclerosis complex gene TSC2 are a cause of sporadic pulmonary lymphangioleiomyomatosis.Carsillo T et al
82695121993Identification and characterization of the tuberous sclerosis gene on chromosome 16.
81620741994Loss of heterozygosity on chromosome 16p13.3 in hamartomas from tuberous sclerosis patients.Green AJ et al
96854101998Tuberous sclerosis gene 2 product modulates transcription mediated by steroid hormone receptor family members.Henry KW et al
75476391995Loss of heterozygosity in the tuberous sclerosis (TSC2) region of chromosome band 16p13 occurs in sporadic as well as TSC-associated renal angiomyolipomas.Henske EP et al
100524551999gigas, a Drosophila homolog of tuberous sclerosis gene product-2, regulates the cell cycle.Ito N et al
114386942001A germ-line Tsc1 mutation causes tumor development and embryonic lethality that are similar, but not identical to, those caused by Tsc2 mutation in mice.Kobayashi T et al
104914041999Tsc2(+/-) mice develop tumors in multiple sites that express gelsolin and are influenced by genetic background.Onda H et al
98099731998Hamartin, the product of the tuberous sclerosis 1 (TSC1) gene, interacts with tuberin and appears to be localized to cytoplasmic vesicles.Plank TL et al
93610101997Role of the tuberous sclerosis gene-2 product in cell cycle control. Loss of the tuberous sclerosis gene-2 induces quiescent cells to enter S phase.Soucek T et al
76082121995Identification of tuberin, the tuberous sclerosis-2 product. Tuberin possesses specific Rap1GAP activity.Wienecke R et al
90456181997The tuberous sclerosis 2 gene product, tuberin, functions as a Rab5 GTPase activating protein (GAP) in modulating endocytosis.Xiao GH et al
95806711998Interaction between hamartin and tuberin, the TSC1 and TSC2 gene products.van Slegtenhorst M et al

Other Information

Locus ID:

NCBI: 7249
MIM: 191092
HGNC: 12363
Ensembl: ENSG00000103197

Variants:

dbSNP: 7249
ClinVar: 7249
TCGA: ENSG00000103197
COSMIC: TSC2

RNA/Proteins

Gene IDTranscript IDUniprot
ENSG00000103197ENST00000219476P49815
ENSG00000103197ENST00000350773P49815
ENSG00000103197ENST00000382538P49815
ENSG00000103197ENST00000401874P49815
ENSG00000103197ENST00000401874X5D7Q2
ENSG00000103197ENST00000432909C9JX95
ENSG00000103197ENST00000439117Q5HYF7
ENSG00000103197ENST00000439673P49815
ENSG00000103197ENST00000471143I3L134
ENSG00000103197ENST00000483020I3L3B1
ENSG00000103197ENST00000568454H3BMQ0
ENSG00000103197ENST00000568566H3BQY7
ENSG00000103197ENST00000569110H3BQK4
ENSG00000103197ENST00000642206A0A2R8Y692
ENSG00000103197ENST00000642365A0A2R8Y6C9
ENSG00000103197ENST00000642561A0A2R8YDZ2
ENSG00000103197ENST00000642797X5D2U8
ENSG00000103197ENST00000642936P49815
ENSG00000103197ENST00000643088A0A2R8Y5F1
ENSG00000103197ENST00000643298A0A2R8Y5B2
ENSG00000103197ENST00000643745A0A2R8YGE6
ENSG00000103197ENST00000643946A0A2R8Y7C8
ENSG00000103197ENST00000644043P49815
ENSG00000103197ENST00000644135A0A2R8YEJ8
ENSG00000103197ENST00000644329A0A2R8Y7X5
ENSG00000103197ENST00000644335A0A2R8YGU4
ENSG00000103197ENST00000644399A0A2R8YDR3
ENSG00000103197ENST00000644417A0A2R8YCR8
ENSG00000103197ENST00000645186A0A2R8Y670
ENSG00000103197ENST00000646388A0A2R8YGD6
ENSG00000103197ENST00000646464A0A2R8YHA2

Expression (GTEx)

0
50
100
150

Pathways

PathwaySourceExternal ID
p53 signaling pathwayKEGGko04115
Autophagy - animalKEGGko04140
mTOR signaling pathwayKEGGko04150
Insulin signaling pathwayKEGGko04910
p53 signaling pathwayKEGGhsa04115
Autophagy - animalKEGGhsa04140
mTOR signaling pathwayKEGGhsa04150
Insulin signaling pathwayKEGGhsa04910
PI3K-Akt signaling pathwayKEGGhsa04151
PI3K-Akt signaling pathwayKEGGko04151
Thyroid hormone signaling pathwayKEGGhsa04919
AMPK signaling pathwayKEGGhsa04152
AMPK signaling pathwayKEGGko04152
Choline metabolism in cancerKEGGhsa05231
Choline metabolism in cancerKEGGko05231
DiseaseREACTOMER-HSA-1643685
Diseases of signal transductionREACTOMER-HSA-5663202
PI3K/AKT Signaling in CancerREACTOMER-HSA-2219528
Constitutive Signaling by AKT1 E17K in CancerREACTOMER-HSA-5674400
Immune SystemREACTOMER-HSA-168256
Adaptive Immune SystemREACTOMER-HSA-1280218
Signaling by the B Cell Receptor (BCR)REACTOMER-HSA-983705
Downstream signaling events of B Cell Receptor (BCR)REACTOMER-HSA-1168372
PIP3 activates AKT signalingREACTOMER-HSA-1257604
AKT phosphorylates targets in the cytosolREACTOMER-HSA-198323
Innate Immune SystemREACTOMER-HSA-168249
DAP12 interactionsREACTOMER-HSA-2172127
DAP12 signalingREACTOMER-HSA-2424491
Fc epsilon receptor (FCERI) signalingREACTOMER-HSA-2454202
Role of LAT2/NTAL/LAB on calcium mobilizationREACTOMER-HSA-2730905
Signal TransductionREACTOMER-HSA-162582
Signaling by EGFRREACTOMER-HSA-177929
GAB1 signalosomeREACTOMER-HSA-180292
Signaling by Insulin receptorREACTOMER-HSA-74752
Insulin receptor signalling cascadeREACTOMER-HSA-74751
IRS-mediated signallingREACTOMER-HSA-112399
PI3K CascadeREACTOMER-HSA-109704
PKB-mediated eventsREACTOMER-HSA-109703
mTOR signallingREACTOMER-HSA-165159
Inhibition of TSC complex formation by PKBREACTOMER-HSA-165181
Energy dependent regulation of mTOR by LKB1-AMPKREACTOMER-HSA-380972
Signalling by NGFREACTOMER-HSA-166520
NGF signalling via TRKA from the plasma membraneREACTOMER-HSA-187037
PI3K/AKT activationREACTOMER-HSA-198203
Signaling by PDGFREACTOMER-HSA-186797
Downstream signal transductionREACTOMER-HSA-186763
Signaling by SCF-KITREACTOMER-HSA-1433557
Signaling by Type 1 Insulin-like Growth Factor 1 Receptor (IGF1R)REACTOMER-HSA-2404192
IGF1R signaling cascadeREACTOMER-HSA-2428924
IRS-related events triggered by IGF1RREACTOMER-HSA-2428928
Gene ExpressionREACTOMER-HSA-74160
Generic Transcription PathwayREACTOMER-HSA-212436
Transcriptional Regulation by TP53REACTOMER-HSA-3700989
TP53 Regulates Metabolic GenesREACTOMER-HSA-5628897
Vesicle-mediated transportREACTOMER-HSA-5653656
Membrane TraffickingREACTOMER-HSA-199991
Cellular responses to stressREACTOMER-HSA-2262752
MacroautophagyREACTOMER-HSA-1632852
Phospholipase D signaling pathwayKEGGko04072
Phospholipase D signaling pathwayKEGGhsa04072
Longevity regulating pathwayKEGGhsa04211
TBC/RABGAPsREACTOMER-HSA-8854214

Protein levels (Protein atlas)

Not detected
Low
Medium
High

PharmGKB

Entity IDNameTypeEvidenceAssociationPKPDPMIDs
PA37034TSC1GeneDataAnnotationassociated
PA445965Tuberous SclerosisDiseaseDataAnnotation, Literature, MultilinkAnnotationassociated23788249

References

Pubmed IDYearTitleCitations
121725532002TSC2 is phosphorylated and inhibited by Akt and suppresses mTOR signalling.1005
128695862003Rheb GTPase is a direct target of TSC2 GAP activity and regulates mTOR signaling.654
212523152011DAXX/ATRX, MEN1, and mTOR pathway genes are frequently altered in pancreatic neuroendocrine tumors.498
158510262005Phosphorylation and functional inactivation of TSC2 by Erk implications for tuberous sclerosis and cancer pathogenesis.474
128209602003Insulin activation of Rheb, a mediator of mTOR/S6K/4E-BP signaling, is inhibited by TSC1 and 2.349
188484732008The TSC-mTOR signaling pathway regulates the innate inflammatory response.252
122711412002Tuberous sclerosis complex-1 and -2 gene products function together to inhibit mammalian target of rapamycin (mTOR)-mediated downstream signaling.243
201600762010ATM signals to TSC2 in the cytoplasm to regulate mTORC1 in response to ROS.240
227951292012TBC1D7 is a third subunit of the TSC1-TSC2 complex upstream of mTORC1.204
183426022008Loss of the tuberous sclerosis complex tumor suppressors triggers the unfolded protein response to regulate insulin signaling and apoptosis.199

Citation

Aristotelis Astrinidis ; Elizabeth Petri Henske

TSC2 (tuberous sclerosis 2)

Atlas Genet Cytogenet Oncol Haematol. 2001-11-01

Online version: http://atlasgeneticsoncology.org/gene/184/tsc2