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
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

Article 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
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

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
cerebral cortex
cerebellum
hippocampus
caudate
thyroid gland
parathyroid gland
adrenal gland
nasopharynx
bronchus
lung
oral mucosa
salivary gland
esophagus
stomach 1
stomach 2
duodenum
small intestine
colon
rectum
liver
gallbladder
pancreas
kidney
urinary bladder
testis
epididymis
seminal vesicle
prostate
vagina
ovary
fallopian tube
endometrium 1
endometrium 2
cervix, uterine
placenta
breast
heart muscle
smooth muscle
skeletal muscle
soft tissue 1
soft tissue 2
adipose tissue
skin 1
skin 2
appendix
spleen
lymph node
tonsil
bone marrow

PharmGKB

Entity IDNameTypeEvidenceAssociationPKPDPMIDs
PA37034TSC1GeneDataAnnotationassociated
PA445965Tuberous SclerosisDiseaseDataAnnotation, Literature, MultilinkAnnotationassociated23788249

References

Pubmed IDYearTitleCitations
377408602024Multi-dimensional Insight into the Coexistence of Pathogenic Genes for ADAR1 and TSC2: Careful Consideration is Essential for Interpretation of ADAR1 Variants.0
379141492024Novel MSH2 and TSC2 variants in a Chinese family with Lynch syndrome and their synergistic impact in urothelial carcinoma.0
382123742024The role of TSC1 and TSC2 proteins in neuronal axons.0
384129452024A large deletion in TSC2 causes tuberous sclerosis complex by dysregulating PI3K/AKT/mTOR signaling pathway.1
377408602024Multi-dimensional Insight into the Coexistence of Pathogenic Genes for ADAR1 and TSC2: Careful Consideration is Essential for Interpretation of ADAR1 Variants.0
379141492024Novel MSH2 and TSC2 variants in a Chinese family with Lynch syndrome and their synergistic impact in urothelial carcinoma.0
382123742024The role of TSC1 and TSC2 proteins in neuronal axons.0
384129452024A large deletion in TSC2 causes tuberous sclerosis complex by dysregulating PI3K/AKT/mTOR signaling pathway.1
365813422023Concurrent Reduced Expression of Contiguous PKD1, TSC2 and NTHL1 Leading to Kidney Diseases and Multiple Diverse Renal Cancers.1
365864332023Knockout of TSC2 in Nav1.8+ neurons predisposes to the onset of normal weight obesity.0
366085752023Tuberin levels during cellular differentiation in brain development.1
367154482023TSC2 regulates tumor susceptibility to TRAIL-mediated T-cell killing by orchestrating mTOR signaling.3
367190212023Refractive Errors, Retinal Findings, and Genotype of Tuberous Sclerosis Complex: A Retrospective Cohort Study.0
368835642023mTOR inhibition overcomes RSK3-mediated resistance to BET inhibitors in small cell lung cancer.6
370881382023Detecting Low-Variant Allele Frequency Mosaic Pathogenic Variants of NF1, TSC2, and AKT3 Genes from Blood in Patients with Neurodevelopmental Disorders.1

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)