TSC2 (tuberous sclerosis 2)

2001-11-01 Aristotelis Astrinidis , Elizabeth Petri Henske Affiliation

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

Identity

HGNC

TSC2

LOCATION

16p13.3

LOCUSID

7249

ALIAS

LAM,PPP1R160,TSC4

FUSION GENES

Show Gene Fusions

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

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.

Entity name

Sporadic lymphangioleiomyomatosis (LAM)

Disease

Lung disease affecting almost exclusively women, characterized by diffuse bilateral proliferation of abnormal smooth muscle cells in the lungs

Bibliography

Pubmed ID	Last Year	Title	Authors
7849708	1994	9q34 loss of heterozygosity in a tuberous sclerosis astrocytoma suggests a growth suppressor-like activity also for the TSC1 gene.	Carbonara C et al
10823953	2000	Mutations in the tuberous sclerosis complex gene TSC2 are a cause of sporadic pulmonary lymphangioleiomyomatosis.	Carsillo T et al
8269512	1993	Identification and characterization of the tuberous sclerosis gene on chromosome 16.
8162074	1994	Loss of heterozygosity on chromosome 16p13.3 in hamartomas from tuberous sclerosis patients.	Green AJ et al
9685410	1998	Tuberous sclerosis gene 2 product modulates transcription mediated by steroid hormone receptor family members.	Henry KW et al
7547639	1995	Loss 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
10052455	1999	gigas, a Drosophila homolog of tuberous sclerosis gene product-2, regulates the cell cycle.	Ito N et al
11438694	2001	A 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
10491404	1999	Tsc2(+/-) mice develop tumors in multiple sites that express gelsolin and are influenced by genetic background.	Onda H et al
9809973	1998	Hamartin, the product of the tuberous sclerosis 1 (TSC1) gene, interacts with tuberin and appears to be localized to cytoplasmic vesicles.	Plank TL et al
9361010	1997	Role 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
7608212	1995	Identification of tuberin, the tuberous sclerosis-2 product. Tuberin possesses specific Rap1GAP activity.	Wienecke R et al
9045618	1997	The tuberous sclerosis 2 gene product, tuberin, functions as a Rab5 GTPase activating protein (GAP) in modulating endocytosis.	Xiao GH et al
9580671	1998	Interaction 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 ID	Transcript ID	Uniprot
ENSG00000103197	ENST00000219476	P49815
ENSG00000103197	ENST00000350773	P49815
ENSG00000103197	ENST00000382538	P49815
ENSG00000103197	ENST00000401874	P49815
ENSG00000103197	ENST00000401874	X5D7Q2
ENSG00000103197	ENST00000432909	C9JX95
ENSG00000103197	ENST00000439117	Q5HYF7
ENSG00000103197	ENST00000439673	P49815
ENSG00000103197	ENST00000471143	I3L134
ENSG00000103197	ENST00000483020	I3L3B1
ENSG00000103197	ENST00000568454	H3BMQ0
ENSG00000103197	ENST00000568566	H3BQY7
ENSG00000103197	ENST00000569110	H3BQK4
ENSG00000103197	ENST00000642206	A0A2R8Y692
ENSG00000103197	ENST00000642365	A0A2R8Y6C9
ENSG00000103197	ENST00000642561	A0A2R8YDZ2
ENSG00000103197	ENST00000642797	X5D2U8
ENSG00000103197	ENST00000642936	P49815
ENSG00000103197	ENST00000643088	A0A2R8Y5F1
ENSG00000103197	ENST00000643298	A0A2R8Y5B2
ENSG00000103197	ENST00000643745	A0A2R8YGE6
ENSG00000103197	ENST00000643946	A0A2R8Y7C8
ENSG00000103197	ENST00000644043	P49815
ENSG00000103197	ENST00000644135	A0A2R8YEJ8
ENSG00000103197	ENST00000644329	A0A2R8Y7X5
ENSG00000103197	ENST00000644335	A0A2R8YGU4
ENSG00000103197	ENST00000644399	A0A2R8YDR3
ENSG00000103197	ENST00000644417	A0A2R8YCR8
ENSG00000103197	ENST00000645186	A0A2R8Y670
ENSG00000103197	ENST00000646388	A0A2R8YGD6
ENSG00000103197	ENST00000646464	A0A2R8YHA2

Expression (GTEx)

100

150

Adipose - Subcutaneous

Adipose - Visceral

Adrenal Gland

Artery - Aorta

Artery - Tibial

Bladder

Brain - Amygdala

Brain - Anterior cingulate cortex

Brain - Caudate

Brain - Cerebellar Hemisphere

Brain - Cerebellum

Brain - Cortex

Brain - Frontal Cortex

Brain - Hippocampus

Brain - Hypothalamus

Brain - Nucleus accumbens

Brain - Putamen

Brain - Spinal cord

Brain - Substantia nigra

Breast - Mammary Tissue

Cells - Cultured fibroblasts

Cells - EBV - transformed lymphocytes

Cervix - Ectocervix

Cervix - Endocervix

Colon - Sigmoid

Colon - Transverse

Esophagus - Gastroesophageal Junction

Esophagus - Mucosa

Esophagus - Muscularis

Fallopian Tube

Heart - Atrial Appendage

Heart - Left Ventricle

Kidney - Cortex

Kidney - Medulla

Liver

Lung

Minor Salivary Gland

Muscle - Skeletal

Nerve - Tibial

Ovary

Pancreas

Pituitary

Prostate

Skin - Not Sun Exposed

Skin - Sun Exposed

Small Intestine - Terminal Ileum

Spleen

Stomach

Testis

Thyroid

Uterus

Vagina

Whole Blood

Pathways

Pathway	Source	External ID
p53 signaling pathway	KEGG	ko04115
Autophagy - animal	KEGG	ko04140
mTOR signaling pathway	KEGG	ko04150
Insulin signaling pathway	KEGG	ko04910
p53 signaling pathway	KEGG	hsa04115
Autophagy - animal	KEGG	hsa04140
mTOR signaling pathway	KEGG	hsa04150
Insulin signaling pathway	KEGG	hsa04910
PI3K-Akt signaling pathway	KEGG	hsa04151
PI3K-Akt signaling pathway	KEGG	ko04151
Thyroid hormone signaling pathway	KEGG	hsa04919
AMPK signaling pathway	KEGG	hsa04152
AMPK signaling pathway	KEGG	ko04152
Choline metabolism in cancer	KEGG	hsa05231
Choline metabolism in cancer	KEGG	ko05231
Disease	REACTOME	R-HSA-1643685
Diseases of signal transduction	REACTOME	R-HSA-5663202
PI3K/AKT Signaling in Cancer	REACTOME	R-HSA-2219528
Constitutive Signaling by AKT1 E17K in Cancer	REACTOME	R-HSA-5674400
Immune System	REACTOME	R-HSA-168256
Adaptive Immune System	REACTOME	R-HSA-1280218
Signaling by the B Cell Receptor (BCR)	REACTOME	R-HSA-983705
Downstream signaling events of B Cell Receptor (BCR)	REACTOME	R-HSA-1168372
PIP3 activates AKT signaling	REACTOME	R-HSA-1257604
AKT phosphorylates targets in the cytosol	REACTOME	R-HSA-198323
Innate Immune System	REACTOME	R-HSA-168249
DAP12 interactions	REACTOME	R-HSA-2172127
DAP12 signaling	REACTOME	R-HSA-2424491
Fc epsilon receptor (FCERI) signaling	REACTOME	R-HSA-2454202
Role of LAT2/NTAL/LAB on calcium mobilization	REACTOME	R-HSA-2730905
Signal Transduction	REACTOME	R-HSA-162582
Signaling by EGFR	REACTOME	R-HSA-177929
GAB1 signalosome	REACTOME	R-HSA-180292
Signaling by Insulin receptor	REACTOME	R-HSA-74752
Insulin receptor signalling cascade	REACTOME	R-HSA-74751
IRS-mediated signalling	REACTOME	R-HSA-112399
PI3K Cascade	REACTOME	R-HSA-109704
PKB-mediated events	REACTOME	R-HSA-109703
mTOR signalling	REACTOME	R-HSA-165159
Inhibition of TSC complex formation by PKB	REACTOME	R-HSA-165181
Energy dependent regulation of mTOR by LKB1-AMPK	REACTOME	R-HSA-380972
Signalling by NGF	REACTOME	R-HSA-166520
NGF signalling via TRKA from the plasma membrane	REACTOME	R-HSA-187037
PI3K/AKT activation	REACTOME	R-HSA-198203
Signaling by PDGF	REACTOME	R-HSA-186797
Downstream signal transduction	REACTOME	R-HSA-186763
Signaling by SCF-KIT	REACTOME	R-HSA-1433557
Signaling by Type 1 Insulin-like Growth Factor 1 Receptor (IGF1R)	REACTOME	R-HSA-2404192
IGF1R signaling cascade	REACTOME	R-HSA-2428924
IRS-related events triggered by IGF1R	REACTOME	R-HSA-2428928
Gene Expression	REACTOME	R-HSA-74160
Generic Transcription Pathway	REACTOME	R-HSA-212436
Transcriptional Regulation by TP53	REACTOME	R-HSA-3700989
TP53 Regulates Metabolic Genes	REACTOME	R-HSA-5628897
Vesicle-mediated transport	REACTOME	R-HSA-5653656
Membrane Trafficking	REACTOME	R-HSA-199991
Cellular responses to stress	REACTOME	R-HSA-2262752
Macroautophagy	REACTOME	R-HSA-1632852
Phospholipase D signaling pathway	KEGG	ko04072
Phospholipase D signaling pathway	KEGG	hsa04072
Longevity regulating pathway	KEGG	hsa04211
TBC/RABGAPs	REACTOME	R-HSA-8854214

Protein levels (Protein atlas)

Not detected

Low

Medium

High

PharmGKB

Entity ID	Name	Type	Evidence	Association	PK	PD	PMIDs
PA37034	TSC1	Gene	DataAnnotation	associated
PA445965	Tuberous Sclerosis	Disease	DataAnnotation, Literature, MultilinkAnnotation	associated			23788249

References

Pubmed ID	Year	Title	Citations
12172553	2002	TSC2 is phosphorylated and inhibited by Akt and suppresses mTOR signalling.	1005
12869586	2003	Rheb GTPase is a direct target of TSC2 GAP activity and regulates mTOR signaling.	654
21252315	2011	DAXX/ATRX, MEN1, and mTOR pathway genes are frequently altered in pancreatic neuroendocrine tumors.	498
15851026	2005	Phosphorylation and functional inactivation of TSC2 by Erk implications for tuberous sclerosis and cancer pathogenesis.	474
12820960	2003	Insulin activation of Rheb, a mediator of mTOR/S6K/4E-BP signaling, is inhibited by TSC1 and 2.	349
18848473	2008	The TSC-mTOR signaling pathway regulates the innate inflammatory response.	252
12271141	2002	Tuberous sclerosis complex-1 and -2 gene products function together to inhibit mammalian target of rapamycin (mTOR)-mediated downstream signaling.	243
20160076	2010	ATM signals to TSC2 in the cytoplasm to regulate mTORC1 in response to ROS.	240
22795129	2012	TBC1D7 is a third subunit of the TSC1-TSC2 complex upstream of mTORC1.	204
18342602	2008	Loss 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-(tuberous-sclerosis-2)