Human Gene TSC1 (uc004cca.2)
  Description: Homo sapiens tuberous sclerosis 1 (TSC1), transcript variant 1, mRNA.
RefSeq Summary (NM_000368): This gene is a tumor suppressor gene that encodes the growth inhibitory protein hamartin. The encoded protein interacts with and stabilizes the GTPase activating protein tuberin. This hamartin-tuberin complex negatively regulates mammalian target of rapamycin complex 1 (mTORC1) signalling which is a major regulator of anabolic cell growth. This protein also functions as a co-chaperone for Hsp90 that inhibits its ATPase activity. This protein functions as a facilitator of Hsp90-mediated folding of kinase and non-kinase clients, including Tsc2 and thereby preventing their ubiquitination and proteasomal degradation. Mutations in this gene have been associated with tuberous sclerosis. [provided by RefSeq, Apr 2018].
Transcript (Including UTRs)
   Position: hg19 chr9:135,766,735-135,820,020 Size: 53,286 Total Exon Count: 23 Strand: -
Coding Region
   Position: hg19 chr9:135,771,622-135,804,259 Size: 32,638 Coding Exon Count: 21 

Page IndexSequence and LinksUniProtKB CommentsPrimersGenetic AssociationsMalaCards
CTDGene AllelesRNA-Seq ExpressionMicroarray ExpressionRNA StructureProtein Structure
Other SpeciesGO AnnotationsmRNA DescriptionsPathwaysOther NamesGeneReviews
Model InformationMethods
Data last updated at UCSC: 2013-06-14

-  Sequence and Links to Tools and Databases
 
Genomic Sequence (chr9:135,766,735-135,820,020)mRNA (may differ from genome)Protein (1164 aa)
Gene SorterGenome BrowserOther Species FASTAVisiGeneGene interactionsTable Schema
AlphaFoldBioGPSEnsemblEntrez GeneExonPrimerGeneCards
GeneNetworkH-INVHGNCHPRDHuman Cortex Gene ExpressionLynx
MalacardsMGIneXtProtOMIMPubMedReactome
TreefamUniProtKBWikipediaBioGrid CRISPR DB

-  Comments and Description Text from UniProtKB
  ID: TSC1_HUMAN
DESCRIPTION: RecName: Full=Hamartin; AltName: Full=Tuberous sclerosis 1 protein;
FUNCTION: In complex with TSC2, inhibits the nutrient-mediated or growth factor-stimulated phosphorylation of S6K1 and EIF4EBP1 by negatively regulating mTORC1 signaling. Seems not to be required for TSC2 GAP activity towards RHEB. Implicated as a tumor suppressor. Involved in microtubule-mediated protein transport, but this seems to be due to unregulated mTOR signaling.
SUBUNIT: Interacts with TSC2, leading to stabilize TSC2. In the absence of TSC2, TSC1 self-aggregates. Interacts with DOCK7. Interacts with FBXW5 and TBC1D7.
INTERACTION: O14920:IKBKB; NbExp=3; IntAct=EBI-1047085, EBI-81266; Q16539:MAPK14; NbExp=2; IntAct=EBI-1047085, EBI-73946; Q00994:NGFRAP1; NbExp=5; IntAct=EBI-1047085, EBI-741753; P49815:TSC2; NbExp=7; IntAct=EBI-1047085, EBI-396587;
SUBCELLULAR LOCATION: Cytoplasm. Membrane; Peripheral membrane protein. Note=At steady state found in association with membranes.
TISSUE SPECIFICITY: Highly expressed in skeletal muscle, followed by heart, brain, placenta, pancreas, lung, liver and kidney. Also expressed in embryonic kidney cells.
DOMAIN: The C-terminal putative coiled-coil domain is necessary for interaction with TSC2.
PTM: Phosphorylation at Ser-505 does not affect interaction with TSC2. Phosphorylated upon DNA damage, probably by ATM or ATR.
DISEASE: Defects in TSC1 are the cause of tuberous sclerosis type 1 (TSC1) [MIM:191100]. It is an autosomal dominant multi-system disorder that affects especially the brain, kidneys, heart, and skin. TS1C 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 symptoms can range from benign hypopigmented macules of the skin to profound mental retardation with intractable seizures to premature death from a variety of disease-associated causes.
DISEASE: Defects in TSC1 may be a cause of focal cortical dysplasia of Taylor balloon cell type (FCDBC) [MIM:607341]. FCDBC is a subtype of cortical displasias linked to chronic intractable epilepsy. Cortical dysplasias display a broad spectrum of structural changes, which appear to result from changes in proliferation, migration, differentiation, and apoptosis of neuronal precursors and neurons during cortical development.
WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and Haematology; URL="http://atlasgeneticsoncology.org/Genes/TSC1ID183.html";
WEB RESOURCE: Name=GeneReviews; URL="http://www.ncbi.nlm.nih.gov/sites/GeneTests/lab/gene/TSC1";
WEB RESOURCE: Name=Tuberous sclerosis database Tuberous sclerosis 1 (TSC1); Note=Leiden Open Variation Database (LOVD); URL="http://www.LOVD.nl/TSC1";

-  Primer design for this transcript
 

Primer3Plus can design qPCR Primers that straddle exon-exon-junctions, which amplify only cDNA, not genomic DNA.
Click here to load the transcript sequence and exon structure into Primer3Plus

Exonprimer can design one pair of Sanger sequencing primers around every exon, located in non-genic sequence.
Click here to open Exonprimer with this transcript

To design primers for a non-coding sequence, zoom to a region of interest and select from the drop-down menu: View > In External Tools > Primer3


-  Genetic Association Studies of Complex Diseases and Disorders
  Genetic Association Database (archive): TSC1
CDC HuGE Published Literature: TSC1
Positive Disease Associations: Hip , psoriasis
Related Studies:
  1. Hip
    Douglas P Kiel et al. BMC medical genetics 2007, Genome-wide association with bone mass and geometry in the Framingham Heart Study., BMC medical genetics. [PubMed 17903296]
    The FHS 100K SNP project offers an unbiased genome-wide strategy to identify new candidate loci and to replicate previously suggested candidate genes for osteoporosis.
  2. Hip
    Douglas P Kiel et al. BMC medical genetics 2007, Genome-wide association with bone mass and geometry in the Framingham Heart Study., BMC medical genetics. [PubMed 17903296]
    The FHS 100K SNP project offers an unbiased genome-wide strategy to identify new candidate loci and to replicate previously suggested candidate genes for osteoporosis.
  3. psoriasis
    Nair ,et al. 2009, Genome-wide scan reveals association of psoriasis with IL-23 and NF-kappaB pathways, Nature genetics 2009 41- 2 : 199-204. [PubMed 19169254]
           more ... click here to view the complete list

-  MalaCards Disease Associations
  MalaCards Gene Search: TSC1
Diseases sorted by gene-association score: tuberous sclerosis-1* (1714), focal cortical dysplasia, type ii, somatic* (937), lymphangioleiomyomatosis* (924), tuberous sclerosis* (352), congenital heart defects, hamartomas of tongue, and polysyndactyly* (298), arthrogryposis, renal dysfunction, and cholestasis 1* (283), urinary bladder cancer* (235), tsc2 angiomyolipomas, renal, modifier of* (231), bladder cancer, somatic* (183), visual epilepsy* (111), tsc1-related lymphangioleiomyomatosis* (100), seizure disorder* (97), angiomyolipoma (25), lung disease (21), kidney angiomyolipoma (19), subependymal giant cell astrocytoma (14), peutz-jeghers syndrome (13), subependymal glioma (10), corneal fleck dystrophy (9), multilocular clear cell renal cell carcinoma (9), autosomal dominant polycystic kidney disease (9), pneumothorax (8), benign ependymoma (8), epileptic encephalopathy, childhood-onset (7), ganglioglioma (6), lissencephaly with cerebellar hypoplasia (6), kidney benign neoplasm (5), stromal dystrophy (5), polycystic liver disease 1 (5), aortic disease (4), megalencephaly (4), cowden disease (4), kidney cancer (3), renal cell carcinoma (2), focal epilepsy (2), autism spectrum disorder (2), autistic disorder (2), retinitis pigmentosa (0)
* = Manually curated disease association

-  Comparative Toxicogenomics Database (CTD)
  The following chemicals interact with this gene           more ... click here to view the complete list

+  Common Gene Haplotype Alleles
  Press "+" in the title bar above to open this section.

-  RNA-Seq Expression Data from GTEx (53 Tissues, 570 Donors)
  Highest median expression: 24.10 RPKM in Brain - Cerebellum
Total median expression: 474.77 RPKM



View in GTEx track of Genome Browser    View at GTEx portal     View GTEx Body Map

+  Microarray Expression Data
  Press "+" in the title bar above to open this section.

-  mRNA Secondary Structure of 3' and 5' UTRs
 
RegionFold EnergyBasesEnergy/Base
Display As
5' UTR -81.30234-0.347 Picture PostScript Text
3' UTR -1649.734887-0.338 Picture PostScript Text

The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.

-  Protein Domain and Structure Information
  InterPro Domains: Graphical view of domain structure
IPR007483 - Hamartin

Pfam Domains:
PF04388 - Hamartin protein

ModBase Predicted Comparative 3D Structure on Q92574
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-  Orthologous Genes in Other Species
  Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
MouseRatZebrafishD. melanogasterC. elegansS. cerevisiae
No orthologGenome BrowserGenome BrowserNo orthologNo orthologNo ortholog
 Gene Details    
 Gene Sorter    
 RGDEnsembl   
 Protein SequenceProtein Sequence   
 AlignmentAlignment   

-  Gene Ontology (GO) Annotations with Structured Vocabulary
  Molecular Function:
GO:0005515 protein binding
GO:0030544 Hsp70 protein binding
GO:0032794 GTPase activating protein binding
GO:0042030 ATPase inhibitor activity
GO:0047485 protein N-terminus binding
GO:0051087 chaperone binding
GO:0051879 Hsp90 protein binding

Biological Process:
GO:0001822 kidney development
GO:0001843 neural tube closure
GO:0001952 regulation of cell-matrix adhesion
GO:0002250 adaptive immune response
GO:0006407 rRNA export from nucleus
GO:0006417 regulation of translation
GO:0006813 potassium ion transport
GO:0007160 cell-matrix adhesion
GO:0007399 nervous system development
GO:0008285 negative regulation of cell proliferation
GO:0008344 adult locomotory behavior
GO:0010977 negative regulation of neuron projection development
GO:0016239 positive regulation of macroautophagy
GO:0016242 negative regulation of macroautophagy
GO:0017148 negative regulation of translation
GO:0021766 hippocampus development
GO:0021987 cerebral cortex development
GO:0030030 cell projection organization
GO:0032007 negative regulation of TOR signaling
GO:0032780 negative regulation of ATPase activity
GO:0032868 response to insulin
GO:0034260 negative regulation of GTPase activity
GO:0042552 myelination
GO:0043379 memory T cell differentiation
GO:0043666 regulation of phosphoprotein phosphatase activity
GO:0045792 negative regulation of cell size
GO:0045859 regulation of protein kinase activity
GO:0046323 glucose import
GO:0046627 negative regulation of insulin receptor signaling pathway
GO:0050808 synapse organization
GO:0050821 protein stabilization
GO:0051291 protein heterooligomerization
GO:0051492 regulation of stress fiber assembly
GO:0051496 positive regulation of stress fiber assembly
GO:0051726 regulation of cell cycle
GO:0051893 regulation of focal adhesion assembly
GO:0051894 positive regulation of focal adhesion assembly
GO:0055007 cardiac muscle cell differentiation
GO:0090630 activation of GTPase activity
GO:0090650 cellular response to oxygen-glucose deprivation
GO:1901214 regulation of neuron death
GO:1903204 negative regulation of oxidative stress-induced neuron death

Cellular Component:
GO:0005634 nucleus
GO:0005737 cytoplasm
GO:0005811 lipid particle
GO:0005829 cytosol
GO:0005856 cytoskeleton
GO:0005886 plasma membrane
GO:0005938 cell cortex
GO:0016020 membrane
GO:0030027 lamellipodium
GO:0030426 growth cone
GO:0032991 macromolecular complex
GO:0033596 TSC1-TSC2 complex
GO:0042995 cell projection
GO:0043231 intracellular membrane-bounded organelle
GO:0048471 perinuclear region of cytoplasm
GO:0005884 actin filament


-  Descriptions from all associated GenBank mRNAs
  AF013168 - Homo sapiens hamartin (TSC1) mRNA, complete cds.
AK299654 - Homo sapiens cDNA FLJ50639 complete cds, highly similar to Hamartin.
AK303030 - Homo sapiens cDNA FLJ50429 complete cds, highly similar to Hamartin.
BC167824 - Synthetic construct Homo sapiens clone IMAGE:100068214, MGC:195831 tuberous sclerosis 1 (TSC1) mRNA, encodes complete protein.
KJ534953 - Homo sapiens clone TSC1_iso-A_fetal-F11 tuberous sclerosis 1 isoform A (TSC1) mRNA, partial cds, alternatively spliced.
AK308412 - Homo sapiens cDNA, FLJ98360.
KM516092 - Homo sapiens TSC1-PDGFEB fusion protein (TSC1-PDGFRB fusion) mRNA, partial cds.
LC224281 - Homo sapiens TSC1 mRNA for hamartin, complete cds, isolate: TSC1-2.
BC108668 - Homo sapiens tuberous sclerosis 1, mRNA (cDNA clone IMAGE:6173298), partial cds.
AK297326 - Homo sapiens cDNA FLJ50416 complete cds, highly similar to Hamartin.
AB190910 - Homo sapiens TSC1 mRNA for tumor suppressor, complete cds.
BC070032 - Homo sapiens tuberous sclerosis 1, mRNA (cDNA clone IMAGE:5273541), complete cds.
BC047772 - Homo sapiens tuberous sclerosis 1, mRNA (cDNA clone IMAGE:5785462), complete cds.
BC121000 - Homo sapiens tuberous sclerosis 1, mRNA (cDNA clone IMAGE:40116542), complete cds.
HQ257966 - Synthetic construct Homo sapiens clone IMAGE:100072275 Unknown protein gene, encodes complete protein.
KJ904579 - Synthetic construct Homo sapiens clone ccsbBroadEn_13973 TSC1 gene, encodes complete protein.
D87683 - Homo sapiens mRNA for KIAA0243 gene, partial cds.
JD314482 - Sequence 295506 from Patent EP1572962.
JD515624 - Sequence 496648 from Patent EP1572962.
JD534705 - Sequence 515729 from Patent EP1572962.
JD380203 - Sequence 361227 from Patent EP1572962.
JD510618 - Sequence 491642 from Patent EP1572962.
JD472042 - Sequence 453066 from Patent EP1572962.
JD089879 - Sequence 70903 from Patent EP1572962.
JD297288 - Sequence 278312 from Patent EP1572962.
JD044585 - Sequence 25609 from Patent EP1572962.
JD499131 - Sequence 480155 from Patent EP1572962.
JD530002 - Sequence 511026 from Patent EP1572962.
JD375143 - Sequence 356167 from Patent EP1572962.
JD223103 - Sequence 204127 from Patent EP1572962.
JD079761 - Sequence 60785 from Patent EP1572962.
JD299510 - Sequence 280534 from Patent EP1572962.
JD532040 - Sequence 513064 from Patent EP1572962.
JD068526 - Sequence 49550 from Patent EP1572962.
JD515765 - Sequence 496789 from Patent EP1572962.
JD431322 - Sequence 412346 from Patent EP1572962.
JD280741 - Sequence 261765 from Patent EP1572962.
JD305633 - Sequence 286657 from Patent EP1572962.
JD286122 - Sequence 267146 from Patent EP1572962.
JD299426 - Sequence 280450 from Patent EP1572962.
JD155638 - Sequence 136662 from Patent EP1572962.
JD082375 - Sequence 63399 from Patent EP1572962.
JD133782 - Sequence 114806 from Patent EP1572962.
JD150304 - Sequence 131328 from Patent EP1572962.
JD297990 - Sequence 279014 from Patent EP1572962.
JD133599 - Sequence 114623 from Patent EP1572962.
JD130616 - Sequence 111640 from Patent EP1572962.
JD104975 - Sequence 85999 from Patent EP1572962.
JD223633 - Sequence 204657 from Patent EP1572962.
JD220733 - Sequence 201757 from Patent EP1572962.
JD291072 - Sequence 272096 from Patent EP1572962.
JD160968 - Sequence 141992 from Patent EP1572962.
JD328795 - Sequence 309819 from Patent EP1572962.
JD427321 - Sequence 408345 from Patent EP1572962.
JD427600 - Sequence 408624 from Patent EP1572962.
JD312312 - Sequence 293336 from Patent EP1572962.
JD171929 - Sequence 152953 from Patent EP1572962.
JD369108 - Sequence 350132 from Patent EP1572962.
JD552267 - Sequence 533291 from Patent EP1572962.
JD525269 - Sequence 506293 from Patent EP1572962.
JD110917 - Sequence 91941 from Patent EP1572962.
JD312416 - Sequence 293440 from Patent EP1572962.
JD059789 - Sequence 40813 from Patent EP1572962.
JD520154 - Sequence 501178 from Patent EP1572962.
JD435629 - Sequence 416653 from Patent EP1572962.
JD205145 - Sequence 186169 from Patent EP1572962.
JD214628 - Sequence 195652 from Patent EP1572962.
JD549942 - Sequence 530966 from Patent EP1572962.
JD495375 - Sequence 476399 from Patent EP1572962.
JD548902 - Sequence 529926 from Patent EP1572962.
JD092999 - Sequence 74023 from Patent EP1572962.
JD245005 - Sequence 226029 from Patent EP1572962.
JD147337 - Sequence 128361 from Patent EP1572962.
JD093634 - Sequence 74658 from Patent EP1572962.
JD279904 - Sequence 260928 from Patent EP1572962.
JD295959 - Sequence 276983 from Patent EP1572962.
JD551600 - Sequence 532624 from Patent EP1572962.
JD402298 - Sequence 383322 from Patent EP1572962.
JD307576 - Sequence 288600 from Patent EP1572962.
JD102507 - Sequence 83531 from Patent EP1572962.
JD265341 - Sequence 246365 from Patent EP1572962.
JD559976 - Sequence 541000 from Patent EP1572962.
JD260463 - Sequence 241487 from Patent EP1572962.
JD373731 - Sequence 354755 from Patent EP1572962.
JD297962 - Sequence 278986 from Patent EP1572962.
LP986446 - Sequence 84 from Patent EP3201339.
MA014106 - JP 2017536338-A/84: TARGETED AUGMENTATION OF NUCLEAR GENE OUTPUT.
LP986444 - Sequence 82 from Patent EP3201339.
MA014104 - JP 2017536338-A/82: TARGETED AUGMENTATION OF NUCLEAR GENE OUTPUT.
LP986442 - Sequence 80 from Patent EP3201339.
MA014102 - JP 2017536338-A/80: TARGETED AUGMENTATION OF NUCLEAR GENE OUTPUT.
LC224280 - Homo sapiens TSC1 mRNA for hamartin, complete cds, isolate: TSC1-1.
LP986441 - Sequence 79 from Patent EP3201339.
MA014101 - JP 2017536338-A/79: TARGETED AUGMENTATION OF NUCLEAR GENE OUTPUT.
LP986439 - Sequence 77 from Patent EP3201339.
MA014099 - JP 2017536338-A/77: TARGETED AUGMENTATION OF NUCLEAR GENE OUTPUT.
JD462606 - Sequence 443630 from Patent EP1572962.

-  Biochemical and Signaling Pathways
  KEGG - Kyoto Encyclopedia of Genes and Genomes
hsa04150 - mTOR signaling pathway
hsa04910 - Insulin signaling pathway

BioCarta from NCI Cancer Genome Anatomy Project
h_mTORPathway - mTOR Signaling Pathway

Reactome (by CSHL, EBI, and GO)

Protein Q92574 (Reactome details) participates in the following event(s):

R-HSA-165179 Formation of TSC1:TSC2 complex
R-HSA-165182 Phosphorylation of complexed TSC2 by PKB
R-HSA-380927 p-AMPK phosphorylates TSC1:TSC2
R-HSA-8854302 TBC1D7 binds the TSC1-TSC2 complex
R-HSA-5628897 TP53 Regulates Metabolic Genes
R-HSA-165181 Inhibition of TSC complex formation by PKB
R-HSA-380972 Energy dependent regulation of mTOR by LKB1-AMPK
R-HSA-3700989 Transcriptional Regulation by TP53
R-HSA-8854214 TBC/RABGAPs
R-HSA-165159 mTOR signalling
R-HSA-212436 Generic Transcription Pathway
R-HSA-9007101 Rab regulation of trafficking
R-HSA-162582 Signal Transduction
R-HSA-73857 RNA Polymerase II Transcription
R-HSA-199991 Membrane Trafficking
R-HSA-74160 Gene expression (Transcription)
R-HSA-5653656 Vesicle-mediated transport

-  Other Names for This Gene
  Alternate Gene Symbols: B7Z897, KIAA0243, NM_000368, NP_000359, Q5VVN5, Q92574, TSC, TSC1_HUMAN
UCSC ID: uc004cca.2
RefSeq Accession: NM_000368
Protein: Q92574 (aka TSC1_HUMAN)
CCDS: CCDS6956.1, CCDS55350.1

-  GeneReviews for This Gene
  GeneReviews article(s) related to gene TSC1:
tuberous-sclerosis (Tuberous Sclerosis Complex)

-  Gene Model Information
 
category: coding nonsense-mediated-decay: no RNA accession: NM_000368.4
exon count: 23CDS single in 3' UTR: no RNA size: 8626
ORF size: 3495CDS single in intron: no Alignment % ID: 100.00
txCdsPredict score: 7079.00frame shift in genome: no % Coverage: 99.88
has start codon: yes stop codon in genome: no # of Alignments: 1
has end codon: yes retained intron: no # AT/AC introns 0
selenocysteine: no end bleed into intron: 0# strange splices: 0
Click here for a detailed description of the fields of the table above.

-  Methods, Credits, and Use Restrictions
  Click here for details on how this gene model was made and data restrictions if any.