TSC1 (Tuberous Sclerosis 1)

2001-11-01   Marjon van Slegtenhorst , Elizabeth Petri Henske 

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

Identity

HGNC
LOCATION
9q34.13
LOCUSID
ALIAS
LAM,TSC
FUSION GENES

DNA/RNA

Description

23 exons, of which 21 are coding; start codon is in exon 3. Different splice variants in the 5UTR

Transcription

1 major detected transcript at 8.6 kb, 2 additional transcripts at 4 and 2.5 kb respectively; open reading frame : 3492 bp

Proteins

Note

called hamartin

Description

1164 amino acids, 130 kDa; C-terminal coiled-coil domain (amino acids 730 to 965)

Expression

housekeeping

Localisation

cytoplasmic localisation

Function

binds to ezrin, member of the ERM (ezrin-moesin-radixin) actin binding proteins

Homology

no strong matches with vertebrate proteins

Mutations

Germinal

germline mutations cause tuberous sclerosis, known as a multiple hamartoma syndrome, autosomal dominant pattern of inheritance. Mutations are inactivating by protein truncation, no missense mutations documented. Some cases of germline mosaicism

Implicated in

Entity name
Tuberous Sclerosis
Note
Classified as one of the phakomatosis, a group of disorders which also includes neurofibromatosis type 1 and neurofibromatosis type 2, von Hippel-Lindau disease and Sturge-Weber syndrome
Disease
Growth of a variety of benign tumors (hamartomas) in multiple organs. Disease is clinically variable. Organs most frequently involved are the heart, skin, brain, lung and kidneys.
Prognosis
  • Lesions in the brain are associated with severe manifestations of TSC. Seizures occur in about 85% of the patients and they often start in the first year of life. About 50% of the children with seizures develop mental retardation. In the second and third decade of life, renal problems are found in the majority of TSC patients. Most characteristic renal abnormalities are cysts and angiomyolipomas. develops occasionally in TSC patients.
  • Life expectancy largely depends on complications caused by the lesions in the brain and the kidneys.
  • Bibliography

    Pubmed IDLast YearTitleAuthors
    112907352001Tuberin phosphorylation regulates its interaction with hamartin. Two proteins involved in tuberous sclerosis.Aicher LD et al
    111753452000The tuberous sclerosis-1 (TSC1) gene product hamartin suppresses cell growth and augments the expression of the TSC2 product tuberin by inhibiting its ubiquitination.Benvenuto G et al
    114448002001Hamartin and tuberin interaction with the G2/M cyclin-dependent kinase CDK1 and its regulatory cyclins A and B.Catania MG et al
    111309852000Genomic organization and comparative analysis of the mouse tuberous sclerosis 1 (Tsc1) locus.Cheadle JP et al
    111126652001Mutational analysis in a cohort of 224 tuberous sclerosis patients indicates increased severity of TSC2, compared with TSC1, disease in multiple organs.Dabora SL et al
    110134392000Mutations of the calcium-sensing receptor (CASR) in familial hypocalciuric hypercalcemia, neonatal severe hyperparathyroidism, and autosomal dominant hypocalcemia.Hendy GN et al
    112665272001Hamartin and tuberin expression in human tissues.Johnson MW et al
    102052611999Comprehensive mutation analysis of TSC1 and TSC2-and phenotypic correlations in 150 families with tuberous sclerosis.Jones AC 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
    108064792000The TSC1 tumour suppressor hamartin regulates cell adhesion through ERM proteins and the GTPase Rho.Lamb RF et al
    109157592000The TSC1 gene product, hamartin, negatively regulates cell proliferation.Miloloza A et al
    105854431999Characterization of the cytosolic tuberin-hamartin complex. Tuberin is a cytosolic chaperone for hamartin.Nellist M et al
    103499941999The expression of hamartin, the product of the TSC1 gene, in normal human tissues and in TSC1- and TSC2-linked angiomyolipomas.Plank TL 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
    113485922001Drosophila Tsc1 functions with Tsc2 to antagonize insulin signaling in regulating cell growth, cell proliferation, and organ size.Potter CJ et al
    113485912001The Drosophila tuberous sclerosis complex gene homologs restrict cell growth and cell proliferation.Tapon N et al
    102273941999Mutational spectrum of the TSC1 gene in a cohort of 225 tuberous sclerosis complex patients: no evidence for genotype-phenotype correlation.van Slegtenhorst M et al

    Other Information

    Locus ID:

    NCBI: 7248
    MIM: 605284
    HGNC: 12362
    Ensembl: ENSG00000165699

    Variants:

    dbSNP: 7248
    ClinVar: 7248
    TCGA: ENSG00000165699
    COSMIC: TSC1

    RNA/Proteins

    Gene IDTranscript IDUniprot
    ENSG00000165699ENST00000298552Q92574
    ENSG00000165699ENST00000298552X5D9D2
    ENSG00000165699ENST00000403810Q86WV8
    ENSG00000165699ENST00000440111Q92574
    ENSG00000165699ENST00000440111X5D9D2
    ENSG00000165699ENST00000475903A0A2R8YGL0
    ENSG00000165699ENST00000490179A0A2R8Y6S8
    ENSG00000165699ENST00000545250Q92574
    ENSG00000165699ENST00000642261A0A2R8Y5U8
    ENSG00000165699ENST00000642344A0A2R8Y5J1
    ENSG00000165699ENST00000642617A0A2R8Y5S3
    ENSG00000165699ENST00000642627A0A2R8YFV7
    ENSG00000165699ENST00000642646Q59IT9
    ENSG00000165699ENST00000642745Q59IT9
    ENSG00000165699ENST00000642811A0A2R8Y419
    ENSG00000165699ENST00000642854A0A2R8Y5Q4
    ENSG00000165699ENST00000643072Q92574
    ENSG00000165699ENST00000643275A0A2R8YEH9
    ENSG00000165699ENST00000643362A0A2R8YGX7
    ENSG00000165699ENST00000643583A0A2R8Y5N2
    ENSG00000165699ENST00000643625A0A2R8Y6T5
    ENSG00000165699ENST00000643691A0A2R8Y5M3
    ENSG00000165699ENST00000643875Q92574
    ENSG00000165699ENST00000643875X5D9D2
    ENSG00000165699ENST00000644097A0A2R8Y5S3
    ENSG00000165699ENST00000644184A0A2R8Y6S1
    ENSG00000165699ENST00000644255A0A2R8Y419
    ENSG00000165699ENST00000644997A0A2R8Y6N1
    ENSG00000165699ENST00000645129A0A2R8YD74
    ENSG00000165699ENST00000645150Q59IT9
    ENSG00000165699ENST00000646391A0A2R8Y419
    ENSG00000165699ENST00000646440A0A2R8Y756
    ENSG00000165699ENST00000646625Q92574
    ENSG00000165699ENST00000646625X5D9D2
    ENSG00000165699ENST00000647078A0A2R8Y7E9
    ENSG00000165699ENST00000647279A0A2R8Y5F8
    ENSG00000165699ENST00000647462A0A2R8Y6W1

    Expression (GTEx)

    0
    10
    20
    30
    40
    50
    60

    Pathways

    PathwaySourceExternal ID
    Autophagy - animalKEGGko04140
    mTOR signaling pathwayKEGGko04150
    Insulin signaling pathwayKEGGko04910
    Autophagy - animalKEGGhsa04140
    mTOR signaling pathwayKEGGhsa04150
    Insulin signaling pathwayKEGGhsa04910
    PI3K-Akt signaling pathwayKEGGhsa04151
    PI3K-Akt signaling pathwayKEGGko04151
    AMPK signaling pathwayKEGGhsa04152
    AMPK signaling pathwayKEGGko04152
    Choline metabolism in cancerKEGGhsa05231
    Choline metabolism in cancerKEGGko05231
    Signal TransductionREACTOMER-HSA-162582
    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
    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
    PA131285571aspirin-induced asthmaDiseaseClinicalAnnotationassociatedPD
    PA37035TSC2GeneDataAnnotationassociated
    PA443450AsthmaDiseaseClinicalAnnotationassociatedPD
    PA445965Tuberous SclerosisDiseaseDataAnnotation, Literature, MultilinkAnnotationassociated23788249
    PA448497aspirinChemicalClinicalAnnotationassociatedPD

    References

    Pubmed IDYearTitleCitations
    128209602003Insulin activation of Rheb, a mediator of mTOR/S6K/4E-BP signaling, is inhibited by TSC1 and 2.349
    122711412002Tuberous sclerosis complex-1 and -2 gene products function together to inhibit mammalian target of rapamycin (mTOR)-mediated downstream signaling.243
    229234332012Genome sequencing identifies a basis for everolimus sensitivity.217
    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
    184113012008The TSC1-TSC2 complex is required for proper activation of mTOR complex 2.198
    175223002007A mouse model of tuberous sclerosis: neuronal loss of Tsc1 causes dysplastic and ectopic neurons, reduced myelination, seizure activity, and limited survival.190
    111126652001Mutational analysis in a cohort of 224 tuberous sclerosis patients indicates increased severity of TSC2, compared with TSC1, disease in multiple organs.179
    201466922010The tuberous sclerosis complex.129
    187943462008Tuberous sclerosis complex proteins control axon formation.117

    Citation

    Marjon van Slegtenhorst ; Elizabeth Petri Henske

    TSC1 (Tuberous Sclerosis 1)

    Atlas Genet Cytogenet Oncol Haematol. 2001-11-01

    Online version: http://atlasgeneticsoncology.org/gene/183/tsc1