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Aliases for TSC2 Gene

Aliases for TSC2 Gene

  • Tuberous Sclerosis 2 2 3 5
  • Tuberous Sclerosis 2 Protein 3 4
  • TSC4 3 4
  • Protein Phosphatase 1, Regulatory Subunit 160 3
  • Regulatory Subunit 160 2
  • Protein Phosphatase 1 2
  • PPP1R160 3
  • LAM 3

External Ids for TSC2 Gene

Previous HGNC Symbols for TSC2 Gene

  • TSC4

Previous GeneCards Identifiers for TSC2 Gene

  • GC16P002115
  • GC16P002038
  • GC16P002037
  • GC16P002097
  • GC16P002070
  • GC16P002072

Summaries for TSC2 Gene

Entrez Gene Summary for TSC2 Gene

  • Mutations in this gene lead to tuberous sclerosis complex. Its gene product is believed to be a tumor suppressor and is able to stimulate specific GTPases. The protein associates with hamartin in a cytosolic complex, possibly acting as a chaperone for hamartin. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Jul 2008]

GeneCards Summary for TSC2 Gene

TSC2 (Tuberous Sclerosis 2) is a Protein Coding gene. Diseases associated with TSC2 include lymphangioleiomyomatosis and tsc2 angiomyolipomas, renal, modifier of. Among its related pathways are Gene Expression and Signaling by GPCR. GO annotations related to this gene include protein homodimerization activity and binding. An important paralog of this gene is RAP1GAP.

UniProtKB/Swiss-Prot for TSC2 Gene

  • In complex with TSC1, this tumor suppressor inhibits the nutrient-mediated or growth factor-stimulated phosphorylation of S6K1 and EIF4EBP1 by negatively regulating mTORC1 signaling. Acts as a GTPase-activating protein (GAP) for the small GTPase RHEB, a direct activator of the protein kinase activity of mTORC1. May also play a role in microtubule-mediated protein transport. Also stimulates the intrinsic GTPase activity of the Ras-related proteins RAP1A and RAB5.

Gene Wiki entry for TSC2 Gene

No data available for Tocris Summary , PharmGKB "VIP" Summary , fRNAdb sequence ontologies and piRNA Summary for TSC2 Gene

Genomics for TSC2 Gene

Regulatory Elements for TSC2 Gene

Promoters for TSC2 Gene
Ensembl Regulatory Elements (ENSRs) TSS Distance (bp) Size (bp) Binding Sites for Transcription Factors within promoters

ENSRs around TSC2 on UCSC Golden Path with GeneCards custom track

Transcription factor binding sites by QIAGEN in the TSC2 gene promoter:

Genomic Location for TSC2 Gene

Chromosome:
16
Start:
2,047,465 bp from pter
End:
2,088,720 bp from pter
Size:
41,256 bases
Orientation:
Plus strand

Genomic View for TSC2 Gene

Genes around TSC2 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
TSC2 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for TSC2 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for TSC2 Gene

Proteins for TSC2 Gene

  • Protein details for TSC2 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    P49815-TSC2_HUMAN
    Recommended name:
    Tuberin
    Protein Accession:
    P49815
    Secondary Accessions:
    • A7E2E2
    • B4DIL8
    • B4DIQ7
    • B4DRN2
    • B7Z2B8
    • C9J378
    • O75275
    • Q4LE71
    • Q8TAZ1

    Protein attributes for TSC2 Gene

    Size:
    1807 amino acids
    Molecular mass:
    200608 Da
    Quaternary structure:
    • Interacts with TSC1 and HERC1; the interaction with TSC1 stabilizes TSC2 and prevents the interaction with HERC1 (PubMed:9580671, PubMed:10585443, PubMed:15963462, PubMed:16464865). May also interact with the adapter molecule RABEP1 (PubMed:9045618). The final complex contains TSC2 and RABEP1 linked to RAB5 (Probable). Interacts with HSPA1 and HSPA8 (PubMed:15963462). Interacts with DAPK1 (PubMed:18974095). Interacts with FBXW5 (PubMed:18381890). Interacts with NAA10 (via C-terminal domain) (PubMed:20145209). Interacts with RRAGA (polyubiquitinated) (PubMed:25936802). Interacts with human cytomegalovirus protein UL38; this interaction inhibits cellular stress response mediated by mTORC1 (PubMed:18407068).
    SequenceCaution:
    • Sequence=BAE06082.1; Type=Erroneous initiation; Evidence={ECO:0000305};

    Alternative splice isoforms for TSC2 Gene

neXtProt entry for TSC2 Gene

Proteomics data for TSC2 Gene at MOPED

Post-translational modifications for TSC2 Gene

  • Phosphorylation at Ser-1387, Ser-1418 or Ser-1420 does not affect interaction with TSC1. Phosphorylation at Ser-939 and Thr-1462 by PKB/AKT1 is induced by growth factor stimulation. Phosphorylation by AMPK activates it and leads to negatively regulates the mTORC1 complex. Phosphorylated at Ser-1798 by RPS6KA1; phosphorylation inhibits TSC2 ability to suppress mTORC1 signaling. Phosphorylated by DAPK1.
  • Ubiquitinated by the DCX(FBXW5) E3 ubiquitin-protein ligase complex, leading to its subsequent degradation. Ubiquitinated by MYCBP2 independently of its phosphorylation status leading to subsequent degradation; association with TSC1 protects from ubiquitination.
  • Ubiquitination at Lys 34, Lys 72, Lys 438, Lys 634, Lys 914, Lys 930, Lys 1251, Lys 1701, and Lys 1739
  • Modification sites at PhosphoSitePlus

Antibody Products

  • Cell Signaling Technology (CST) Antibodies for TSC2 (TSC2)

No data available for DME Specific Peptides for TSC2 Gene

Domains & Families for TSC2 Gene

Gene Families for TSC2 Gene

Protein Domains for TSC2 Gene

Suggested Antigen Peptide Sequences for TSC2 Gene

Graphical View of Domain Structure for InterPro Entry

P49815

UniProtKB/Swiss-Prot:

TSC2_HUMAN :
  • Contains 1 Rap-GAP domain.
Domain:
  • Contains 1 Rap-GAP domain.
genes like me logo Genes that share domains with TSC2: view

Function for TSC2 Gene

Molecular function for TSC2 Gene

UniProtKB/Swiss-Prot Function:
In complex with TSC1, this tumor suppressor inhibits the nutrient-mediated or growth factor-stimulated phosphorylation of S6K1 and EIF4EBP1 by negatively regulating mTORC1 signaling. Acts as a GTPase-activating protein (GAP) for the small GTPase RHEB, a direct activator of the protein kinase activity of mTORC1. May also play a role in microtubule-mediated protein transport. Also stimulates the intrinsic GTPase activity of the Ras-related proteins RAP1A and RAB5.

Gene Ontology (GO) - Molecular Function for TSC2 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005096 GTPase activator activity IEA,IDA 9045618
genes like me logo Genes that share ontologies with TSC2: view
genes like me logo Genes that share phenotypes with TSC2: view

Human Phenotype Ontology for TSC2 Gene

HPO Id HPO Name Alternative Ids Definition Synonyms

Animal Models for TSC2 Gene

MGI Knock Outs for TSC2:

Animal Model Products

miRNA for TSC2 Gene

miRTarBase miRNAs that target TSC2

No data available for Enzyme Numbers (IUBMB) , Transcription Factor Targets and HOMER Transcription for TSC2 Gene

Localization for TSC2 Gene

Subcellular locations from UniProtKB/Swiss-Prot for TSC2 Gene

Cytoplasm. Membrane; Peripheral membrane protein. Note=At steady state found in association with membranes.

Subcellular locations from

COMPARTMENTS
Jensen Localization Image for TSC2 Gene COMPARTMENTS Subcellular localization image for TSC2 gene
Compartment Confidence
cytosol 5
golgi apparatus 5
lysosome 5
nucleus 5
vacuole 5
plasma membrane 4
cytoskeleton 2
endoplasmic reticulum 1
endosome 1
mitochondrion 1

Gene Ontology (GO) - Cellular Components for TSC2 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005829 cytosol TAS --
genes like me logo Genes that share ontologies with TSC2: view

Pathways & Interactions for TSC2 Gene

SuperPathways for TSC2 Gene

Superpath Contained pathways
1 Interleukin-3, 5 and GM-CSF signaling
2 PI3K events in ERBB4 signaling
3 Translation Insulin regulation of translation
4 mTOR signalling
5 Immune System
genes like me logo Genes that share pathways with TSC2: view

SIGNOR curated interactions for TSC2 Gene

Activates:
Inactivates:
Is activated by:
Is inactivated by:
Other effect:

Gene Ontology (GO) - Biological Process for TSC2 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0001843 neural tube closure ISS --
GO:0006606 protein import into nucleus ISS --
GO:0007050 cell cycle arrest TAS --
GO:0007173 epidermal growth factor receptor signaling pathway TAS --
GO:0008104 protein localization ISS --
genes like me logo Genes that share ontologies with TSC2: view

Drugs & Compounds for TSC2 Gene

(23) Drugs for TSC2 Gene - From: Novoseek, ClinicalTrials, and PharmGKB

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
Everolimus Approved Pharma mTOR inhibitor, mTOR Inhibitors, Kinase Inhibitors, Mammalian target of rapamycin (mTOR) inhibitors 1797
Miconazole Approved, Investigational Pharma Antagonist, Pore Blocker 3026
Sirolimus Approved, Investigational Pharma Kinase Inhibitors, Mammalian target of rapamycin (mTOR) inhibitors 1797
Anti-Bacterial Agents Pharma 9140
Antibiotics, Antitubercular Pharma 5971

(11) Additional Compounds for TSC2 Gene - From: Novoseek

Name Synonyms Role CAS Number PubChem IDs PubMed IDs
genes like me logo Genes that share compounds with TSC2: view

Transcripts for TSC2 Gene

Unigene Clusters for TSC2 Gene

Tuberous sclerosis 2:
Representative Sequences:

Alternative Splicing Database (ASD) splice patterns (SP) for TSC2 Gene

ExUns: 1 ^ 2 ^ 3 ^ 4 ^ 5a · 5b ^ 6a · 6b ^ 7 ^ 8 ^ 9 ^ 10 ^ 11 ^ 12 ^ 13 ^ 14 ^ 15a · 15b ^ 16a · 16b ^ 17a · 17b · 17c · 17d ^ 18 ^ 19 ^
SP1: - - - - -
SP2:
SP3:
SP4:
SP5:
SP6:
SP7: -
SP8:
SP9:
SP10:
SP11:
SP12: -
SP13:
SP14:
SP15: - -
SP16:
SP17: -
SP18:

ExUns: 20a · 20b ^ 21 ^ 22a · 22b ^ 23a · 23b ^ 24 ^ 25a · 25b · 25c · 25d ^ 26 ^ 27a · 27b ^ 28a · 28b ^ 29a · 29b · 29c ^ 30a · 30b · 30c ^ 31 ^ 32 ^ 33a ·
SP1: - - - -
SP2:
SP3: - - - -
SP4: -
SP5: - - - -
SP6:
SP7:
SP8: - -
SP9: - - -
SP10:
SP11:
SP12:
SP13: -
SP14:
SP15:
SP16:
SP17:
SP18:

ExUns: 33b ^ 34a · 34b ^ 35a · 35b ^ 36 ^ 37a · 37b · 37c ^ 38 ^ 39 ^ 40 ^ 41 ^ 42 ^ 43 ^ 44 ^ 45a · 45b
SP1: - - - -
SP2:
SP3:
SP4:
SP5:
SP6:
SP7:
SP8:
SP9:
SP10: - - -
SP11:
SP12:
SP13:
SP14:
SP15:
SP16: - -
SP17:
SP18:

Relevant External Links for TSC2 Gene

GeneLoc Exon Structure for
TSC2
ECgene alternative splicing isoforms for
TSC2

Expression for TSC2 Gene

mRNA expression in normal human tissues for TSC2 Gene

Protein differential expression in normal tissues from HIPED for TSC2 Gene

This gene is overexpressed in Heart (11.5), Frontal cortex (9.7), and Peripheral blood mononuclear cells (8.4).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB, PaxDb, MOPED, and MaxQB for TSC2 Gene



SOURCE GeneReport for Unigene cluster for TSC2 Gene Hs.90303

mRNA Expression by UniProt/SwissProt for TSC2 Gene

P49815-TSC2_HUMAN
Tissue specificity: Liver, brain, heart, lymphocytes, fibroblasts, biliary epithelium, pancreas, skeletal muscle, kidney, lung and placenta.
genes like me logo Genes that share expression patterns with TSC2: view

Protein tissue co-expression partners for TSC2 Gene

- Elite partner

Primer Products

In Situ Assay Products

No data available for mRNA expression in embryonic tissues and stem cells from LifeMap Discovery and mRNA differential expression in normal tissues for TSC2 Gene

Orthologs for TSC2 Gene

This gene was present in the common ancestor of animals.

Orthologs for TSC2 Gene

Organism Taxonomy Gene Similarity Type Details
cow
(Bos Taurus)
Mammalia TSC2 35
  • 87.47 (n)
  • 91.6 (a)
TSC2 36
  • 91 (a)
OneToOne
dog
(Canis familiaris)
Mammalia TSC2 35
  • 86.77 (n)
  • 91.64 (a)
TSC2 36
  • 91 (a)
OneToOne
mouse
(Mus musculus)
Mammalia Tsc2 35
  • 84.86 (n)
  • 91.65 (a)
Tsc2 16
Tsc2 36
  • 91 (a)
OneToOne
chimpanzee
(Pan troglodytes)
Mammalia TSC2 35
  • 99.04 (n)
  • 99.11 (a)
TSC2 36
  • 99 (a)
OneToOne
rat
(Rattus norvegicus)
Mammalia Tsc2 35
  • 85.16 (n)
  • 91.3 (a)
oppossum
(Monodelphis domestica)
Mammalia -- 36
  • 88 (a)
OneToMany
-- 36
  • 87 (a)
OneToMany
platypus
(Ornithorhynchus anatinus)
Mammalia -- 36
  • 91 (a)
OneToMany
-- 36
  • 82 (a)
OneToMany
-- 36
  • 82 (a)
OneToMany
-- 36
  • 64 (a)
OneToMany
chicken
(Gallus gallus)
Aves TSC2 35
  • 74.88 (n)
  • 82.33 (a)
TSC2 36
  • 81 (a)
OneToOne
lizard
(Anolis carolinensis)
Reptilia TSC2 36
  • 81 (a)
OneToOne
tropical clawed frog
(Silurana tropicalis)
Amphibia Str.18146 35
tsc2 35
  • 68.09 (n)
  • 69.92 (a)
African clawed frog
(Xenopus laevis)
Amphibia Xl.7502 35
zebrafish
(Danio rerio)
Actinopterygii tsc2 35
  • 63.26 (n)
  • 60.21 (a)
tsc2 36
  • 57 (a)
OneToOne
fruit fly
(Drosophila melanogaster)
Insecta gig 37
  • 31 (a)
gig 35
  • 49.52 (n)
  • 37.89 (a)
gig 36
  • 31 (a)
OneToOne
African malaria mosquito
(Anopheles gambiae)
Insecta AgaP_AGAP011123 35
  • 42.47 (n)
  • 26.09 (a)
sea squirt
(Ciona savignyi)
Ascidiacea -- 36
  • 35 (a)
OneToOne
Species with no ortholog for TSC2:
  • A. gosspyii yeast (Ashbya gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • Alicante grape (Vitis vinifera)
  • alpha proteobacteria (Wolbachia pipientis)
  • amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • baker's yeast (Saccharomyces cerevisiae)
  • barley (Hordeum vulgare)
  • beta proteobacteria (Neisseria meningitidis)
  • bread mold (Neurospora crassa)
  • Chromalveolata (Phytophthora infestans)
  • common water flea (Daphnia pulex)
  • corn (Zea mays)
  • E. coli (Escherichia coli)
  • filamentous fungi (Aspergillus nidulans)
  • Firmicute bacteria (Streptococcus pneumoniae)
  • fission yeast (Schizosaccharomyces pombe)
  • green algae (Chlamydomonas reinhardtii)
  • honey bee (Apis mellifera)
  • K. lactis yeast (Kluyveromyces lactis)
  • loblloly pine (Pinus taeda)
  • malaria parasite (Plasmodium falciparum)
  • medicago trunc (Medicago Truncatula)
  • moss (Physcomitrella patens)
  • orangutan (Pongo pygmaeus)
  • pig (Sus scrofa)
  • rainbow trout (Oncorhynchus mykiss)
  • rice (Oryza sativa)
  • rice blast fungus (Magnaporthe grisea)
  • schistosome parasite (Schistosoma mansoni)
  • sea anemone (Nematostella vectensis)
  • sea urchin (Strongylocentrotus purpuratus)
  • sorghum (Sorghum bicolor)
  • soybean (Glycine max)
  • stem rust fungus (Puccinia graminis)
  • sugarcane (Saccharum officinarum)
  • thale cress (Arabidopsis thaliana)
  • tomato (Lycopersicon esculentum)
  • toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • wheat (Triticum aestivum)
  • worm (Caenorhabditis elegans)

Evolution for TSC2 Gene

ENSEMBL:
Gene Tree for TSC2 (if available)
TreeFam:
Gene Tree for TSC2 (if available)

Paralogs for TSC2 Gene

genes like me logo Genes that share paralogs with TSC2: view

Variants for TSC2 Gene

Sequence variations from dbSNP and Humsavar for TSC2 Gene

SNP ID Clin Chr 16 pos Sequence Context AA Info Type
rs45517138 Tuberous sclerosis 2 (TSC2) 2,058,773(+) CCTGC(C/T)GAGAG reference, missense
VAR_005647 Tuberous sclerosis 2 (TSC2)
VAR_005648 Tuberous sclerosis 2 (TSC2)
VAR_005649 -
VAR_005650 Lymphangioleiomyomatosis (LAM)

Structural Variations from Database of Genomic Variants (DGV) for TSC2 Gene

Variant ID Type Subtype PubMed ID
esv2422427 CNV Duplication 17116639
dgv2540n71 CNV Loss 21882294
dgv2544n71 CNV Loss 21882294
dgv2545n71 CNV Loss 21882294
nsv905048 CNV Loss 21882294
dgv2546n71 CNV Loss 21882294
dgv2547n71 CNV Loss 21882294
dgv2548n71 CNV Gain 21882294
dgv2549n71 CNV Loss 21882294
dgv2550n71 CNV Loss 21882294
dgv2552n71 CNV Gain+Loss 21882294
nsv523037 CNV Loss 19592680
nsv471072 CNV Loss 18288195
dgv2555n71 CNV Gain+Loss 21882294
nsv905095 CNV Gain 21882294
nsv905101 CNV Loss 21882294
nsv905102 CNV Loss 21882294
dgv2556n71 CNV Loss 21882294
dgv2557n71 CNV Loss 21882294
nsv827504 CNV Loss 20364138
nsv457349 CNV Loss 19166990
dgv2558n71 CNV Loss 21882294
nsv905113 CNV Loss 21882294
dgv2559n71 CNV Loss 21882294
esv2750376 CNV Deletion 23290073
dgv2560n71 CNV Loss 21882294
dgv2561n71 CNV Loss 21882294
nsv471381 CNV Duplication 19718026
nsv482186 CNV Gain 20164927

Variation tolerance for TSC2 Gene

Residual Variation Intolerance Score: 0.729% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 4.44; 63.99% of all genes are more intolerant (likely to be disease-causing)

Relevant External Links for TSC2 Gene

HapMap Linkage Disequilibrium report
TSC2
Human Gene Mutation Database (HGMD)
TSC2

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for TSC2 Gene

Disorders for TSC2 Gene

MalaCards: The human disease database

(41) MalaCards diseases for TSC2 Gene - From: OMIM, ClinVar, GeneTests, Orphanet, Swiss-Prot, DISEASES, Novoseek, and GeneCards

Disorder Aliases PubMed IDs
lymphangioleiomyomatosis
  • lymphangioleiomyomatosis, somatic
tsc2 angiomyolipomas, renal, modifier of
  • tuberous sclerosis-2
tuberous sclerosis-1
  • tuberous sclerosis
tuberous sclerosis
  • bourneville's disease
chromosome 16p13.3 deletion syndrome
  • 16p13.3 deletion syndrome
- elite association - COSMIC cancer census association via MalaCards
Search TSC2 in MalaCards View complete list of genes associated with diseases

UniProtKB/Swiss-Prot

TSC2_HUMAN
  • Lymphangioleiomyomatosis (LAM) [MIM:606690]: Progressive and often fatal lung disease characterized by a diffuse proliferation of abnormal smooth muscle cells in the lungs. It affects almost exclusively young women and can occur as an isolated disorder or in association with tuberous sclerosis complex. {ECO:0000269 PubMed:10823953}. Note=The disease is caused by mutations affecting the gene represented in this entry.
  • Tuberous sclerosis 2 (TSC2) [MIM:613254]: 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. {ECO:0000269 PubMed:10069705, ECO:0000269 PubMed:10205261, ECO:0000269 PubMed:10533067, ECO:0000269 PubMed:10570911, ECO:0000269 PubMed:10607950, ECO:0000269 PubMed:10732801, ECO:0000269 PubMed:10735580, ECO:0000269 PubMed:15024740, ECO:0000269 PubMed:15595939, ECO:0000269 PubMed:8824881, ECO:0000269 PubMed:9302281, ECO:0000269 PubMed:9463313, ECO:0000269 PubMed:9829910}. Note=The disease is caused by mutations affecting the gene represented in this entry.

Genatlas disease for TSC2 Gene

tuberous sclerosis 2,multisystem disorder characterized by the widespread development of hamartomatous growths noteworthy in eyes,heart,skin and brain,with seizures,behavioral disorder and a renal angiomyolipoma and lymphangiomatosis,with a high risk of mental retardation

Relevant External Links for TSC2

Genetic Association Database (GAD)
TSC2
Human Genome Epidemiology (HuGE) Navigator
TSC2
Atlas of Genetics and Cytogenetics in Oncology and Haematology:
TSC2
genes like me logo Genes that share disorders with TSC2: view

Publications for TSC2 Gene

  1. Alternative splicing of the tuberous sclerosis 2 (TSC2) gene in human and mouse tissues. (PMID: 7558029) Xu L. … Ramesh V. (Genomics 1995) 2 3 4 67
  2. Carboxy terminal tail of polycystin-1 regulates localization of TSC2 to repress mTOR. (PMID: 20169078) Dere R. … Walker C.L. (PLoS ONE 2010) 3 23
  3. Post-transcriptional regulation of chemokine receptor CXCR4 by estrogen in HER2 overexpressing, estrogen receptor-positive breast cancer cells. (PMID: 18807177) Sengupta S. … Katzenellenbogen B.S. (Breast Cancer Res. Treat. 2009) 3 23
  4. Aberrant expression of TSC2 gene in the newly diagnosed acute leukemia. (PMID: 19250671) Xu Z. … Wang J. (Leuk. Res. 2009) 3 23
  5. Three independent mutations in the TSC2 gene in a family with tuberous sclerosis. (PMID: 19259131) Le Caignec C. … David A. (Eur. J. Hum. Genet. 2009) 3 23

Products for TSC2 Gene

Sources for TSC2 Gene

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