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    TSC1 TSC complex subunit 1 [ Homo sapiens (human) ]

    Gene ID: 7248, updated on 19-Jul-2021

    Summary

    Official Symbol
    TSC1provided by HGNC
    Official Full Name
    TSC complex subunit 1provided by HGNC
    Primary source
    HGNC:HGNC:12362
    See related
    Ensembl:ENSG00000165699 MIM:605284
    Gene type
    protein coding
    RefSeq status
    REVIEWED
    Organism
    Homo sapiens
    Lineage
    Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
    Also known as
    LAM; TSC
    Summary
    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]
    Expression
    Ubiquitous expression in testis (RPKM 9.2), brain (RPKM 8.5) and 25 other tissues See more
    Orthologs
    NEW
    Try the new Gene table
    Try the new Transcript table

    Genomic context

    See TSC1 in Genome Data Viewer
    Location:
    9q34.13
    Exon count:
    25
    Annotation release Status Assembly Chr Location
    109.20210514 current GRCh38.p13 (GCF_000001405.39) 9 NC_000009.12 (132891349..132945269, complement)
    105.20201022 previous assembly GRCh37.p13 (GCF_000001405.25) 9 NC_000009.11 (135766736..135820003, complement)

    Chromosome 9 - NC_000009.12Genomic Context describing neighboring genes Neighboring gene adenylate kinase 8 Neighboring gene Sharpr-MPRA regulatory region 7884 Neighboring gene sperm acrosome associated 9 Neighboring gene microRNA 548aw Neighboring gene growth factor independent 1B transcriptional repressor Neighboring gene ribosomal protein L39 pseudogene 24

    Genomic regions, transcripts, and products

    Expression

    • Project title: HPA RNA-seq normal tissues
    • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
    • BioProject: PRJEB4337
    • Publication: PMID 24309898
    • Analysis date: Wed Apr 4 07:08:55 2018

    Bibliography

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?

    Phenotypes

    Professional guidelines

    Description
    Professional guideline
    ACMG 2013

    The ACMG recommends that laboratories performing clinical sequencing seek and report mutations in TSC1 that are pathogenic or expected to be pathogenic.

    GuidelinePubMed

    Associated conditions

    Description Tests
    Focal cortical dysplasia type II
    MedGen: C1846385 OMIM: 607341 GeneReviews: Not available
    Compare labs
    Genome-wide meta-analysis identifies new susceptibility loci for migraine.
    GeneReviews: Not available
    Genome-wide scan reveals association of psoriasis with IL-23 and NF-kappaB pathways.
    GeneReviews: Not available
    Lymphangiomyomatosis
    MedGen: C0751674 OMIM: 606690 GeneReviews: Not available
    Compare labs
    Tuberous sclerosis 1
    MedGen: C1854465 OMIM: 191100 GeneReviews: Tuberous Sclerosis Complex
    Compare labs

    Copy number response

    Description
    Copy number response
    Triplosensitivity

    No evidence available (Last evaluated 2020-10-13)

    ClinGen Genome Curation Page
    Haploinsufficency

    Sufficient evidence for dosage pathogenicity (Last evaluated 2020-10-13)

    ClinGen Genome Curation PagePubMed

    Pathways from PubChem

    Interactions

    Products Interactant Other Gene Complex Source Pubs Description

    General gene information

    Markers

    Homology

    Clone Names

    • KIAA0243, MGC86987

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    enables ATPase inhibitor activity IDA
    Inferred from Direct Assay
    more info
    PubMed 
    enables GTPase activating protein binding IEA
    Inferred from Electronic Annotation
    more info
     
    enables Hsp70 protein binding IDA
    Inferred from Direct Assay
    more info
    PubMed 
    enables Hsp90 protein binding IPI
    Inferred from Physical Interaction
    more info
    PubMed 
    enables chaperone binding IPI
    Inferred from Physical Interaction
    more info
    PubMed 
    enables protein N-terminus binding IPI
    Inferred from Physical Interaction
    more info
    PubMed 
    enables protein binding IPI
    Inferred from Physical Interaction
    more info
    PubMed 
    enables protein-containing complex binding IEA
    Inferred from Electronic Annotation
    more info
     
    Process Evidence Code Pubs
    involved_in activation of GTPase activity IDA
    Inferred from Direct Assay
    more info
    PubMed 
    involved_in adaptive immune response IEA
    Inferred from Electronic Annotation
    more info
     
    involved_in adult locomotory behavior ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    involved_in cardiac muscle cell differentiation IEA
    Inferred from Electronic Annotation
    more info
     
    involved_in cell projection organization IEA
    Inferred from Electronic Annotation
    more info
     
    involved_in cell-matrix adhesion IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    involved_in cellular response to oxygen-glucose deprivation ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    involved_in cerebral cortex development IEA
    Inferred from Electronic Annotation
    more info
     
    involved_in glucose import IEA
    Inferred from Electronic Annotation
    more info
     
    involved_in hippocampus development IEA
    Inferred from Electronic Annotation
    more info
     
    involved_in kidney development IEA
    Inferred from Electronic Annotation
    more info
     
    involved_in memory T cell differentiation IEA
    Inferred from Electronic Annotation
    more info
     
    involved_in myelination IEA
    Inferred from Electronic Annotation
    more info
     
    involved_in negative regulation of ATPase activity IDA
    Inferred from Direct Assay
    more info
    PubMed 
    involved_in negative regulation of GTPase activity IEA
    Inferred from Electronic Annotation
    more info
     
    involved_in negative regulation of TOR signaling IBA
    Inferred from Biological aspect of Ancestor
    more info
    PubMed 
    involved_in negative regulation of TOR signaling IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    involved_in negative regulation of TOR signaling ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    involved_in negative regulation of cell population proliferation IBA
    Inferred from Biological aspect of Ancestor
    more info
    PubMed 
    involved_in negative regulation of cell population proliferation IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    involved_in negative regulation of cell size IEA
    Inferred from Electronic Annotation
    more info
     
    involved_in negative regulation of macroautophagy ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    involved_in negative regulation of neuron projection development IEA
    Inferred from Electronic Annotation
    more info
     
    involved_in negative regulation of oxidative stress-induced neuron death IEA
    Inferred from Electronic Annotation
    more info
     
    involved_in negative regulation of translation IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    involved_in neural tube closure IEA
    Inferred from Electronic Annotation
    more info
     
    involved_in positive regulation of focal adhesion assembly IDA
    Inferred from Direct Assay
    more info
    PubMed 
    involved_in positive regulation of macroautophagy IEA
    Inferred from Electronic Annotation
    more info
     
    involved_in positive regulation of stress fiber assembly IEA
    Inferred from Electronic Annotation
    more info
     
    involved_in potassium ion transport IEA
    Inferred from Electronic Annotation
    more info
     
    involved_in protein stabilization IDA
    Inferred from Direct Assay
    more info
    PubMed 
    involved_in protein stabilization IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    involved_in rRNA export from nucleus IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    involved_in regulation of cell cycle IBA
    Inferred from Biological aspect of Ancestor
    more info
    PubMed 
    involved_in regulation of cell-matrix adhesion IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    involved_in regulation of neuron death ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    involved_in regulation of phosphoprotein phosphatase activity IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    involved_in regulation of protein kinase activity IEA
    Inferred from Electronic Annotation
    more info
     
    involved_in regulation of stress fiber assembly IDA
    Inferred from Direct Assay
    more info
    PubMed 
    involved_in regulation of translation IDA
    Inferred from Direct Assay
    more info
    PubMed 
    involved_in response to insulin IDA
    Inferred from Direct Assay
    more info
    PubMed 
    involved_in synapse organization IEA
    Inferred from Electronic Annotation
    more info
     
    Component Evidence Code Pubs
    part_of TSC1-TSC2 complex IBA
    Inferred from Biological aspect of Ancestor
    more info
    PubMed 
    part_of TSC1-TSC2 complex IDA
    Inferred from Direct Assay
    more info
    PubMed 
    colocalizes_with actin filament IDA
    Inferred from Direct Assay
    more info
    PubMed 
    located_in cell cortex IDA
    Inferred from Direct Assay
    more info
    PubMed 
    part_of chaperone complex IDA
    Inferred from Direct Assay
    more info
    PubMed 
    located_in cytoplasm IDA
    Inferred from Direct Assay
    more info
    PubMed 
    located_in cytosol IDA
    Inferred from Direct Assay
    more info
    PubMed 
    located_in cytosol TAS
    Traceable Author Statement
    more info
     
    located_in growth cone IEA
    Inferred from Electronic Annotation
    more info
     
    located_in lamellipodium IDA
    Inferred from Direct Assay
    more info
    PubMed 
    located_in lipid droplet IDA
    Inferred from Direct Assay
    more info
     
    located_in membrane IDA
    Inferred from Direct Assay
    more info
    PubMed 
    located_in nucleus ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    located_in perinuclear region of cytoplasm ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    located_in plasma membrane TAS
    Traceable Author Statement
    more info
     
    located_in postsynaptic density IEA
    Inferred from Electronic Annotation
    more info
     
    part_of protein-containing complex IDA
    Inferred from Direct Assay
    more info
    PubMed 

    General protein information

    Preferred Names
    hamartin
    Names
    truncated hemartin
    tuberous sclerosis 1 protein

    NCBI Reference Sequences (RefSeq)

    NEW Try the new Transcript table

    RefSeqs maintained independently of Annotated Genomes

    These reference sequences exist independently of genome builds. Explain

    These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

    Genomic

    1. NG_012386.1 RefSeqGene

      Range
      5001..58286
      Download
      GenBank, FASTA, Sequence Viewer (Graphics), LRG_486

    mRNA and Protein(s)

    1. NM_000368.5NP_000359.1  hamartin isoform 1

      See identical proteins and their annotated locations for NP_000359.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (1) represents the longest transcript and encodes the longest isoform (1).
      Source sequence(s)
      AF013168, BC070032, D87683, N63914
      Consensus CDS
      CCDS6956.1
      UniProtKB/Swiss-Prot
      Q92574
      UniProtKB/TrEMBL
      Q86WV8, X5D9D2
      Related
      ENSP00000298552.3, ENST00000298552.9
      Conserved Domains (4) summary
      pfam04388
      Location:7719
      Hamartin; Hamartin protein
      pfam05837
      Location:863957
      CENP-H; Centromere protein H (CENP-H)
      pfam14988
      Location:766932
      DUF4515; Domain of unknown function (DUF4515)
      cl21588
      Location:779881
      Snf7; Snf7
    2. NM_001162426.2NP_001155898.1  hamartin isoform 3

      Status: REVIEWED

      Description
      Transcript Variant: This variant (3) uses an alternate in-frame splice site in the 3' coding region, compared to variant 1. This results in a shorter protein (isoform 3), compared to isoform 1.
      Source sequence(s)
      AF013168, BC108668, D87683, N63914
      Consensus CDS
      CCDS87703.1
      UniProtKB/Swiss-Prot
      Q92574
      UniProtKB/TrEMBL
      Q32NF0
      Related
      ENSP00000493773.1, ENST00000642617.1
      Conserved Domains (4) summary
      pfam04388
      Location:7718
      Hamartin; Hamartin protein
      pfam05837
      Location:862956
      CENP-H; Centromere protein H (CENP-H)
      pfam14988
      Location:765931
      DUF4515; Domain of unknown function (DUF4515)
      cl21588
      Location:778880
      Snf7; Snf7
    3. NM_001162427.2NP_001155899.1  hamartin isoform 4

      See identical proteins and their annotated locations for NP_001155899.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (4) lacks an alternate in-frame exon in the 5' coding region, compared to variant 1. This results in a shorter protein (isoform 3), compared to isoform 1.
      Source sequence(s)
      AF013168, AK303030, D87683, N63914
      Consensus CDS
      CCDS55350.1
      UniProtKB/Swiss-Prot
      Q92574
      Related
      ENSP00000496691.1, ENST00000643072.1
      Conserved Domains (4) summary
      pfam04388
      Location:7668
      Hamartin; Hamartin protein
      pfam05837
      Location:812906
      CENP-H; Centromere protein H (CENP-H)
      pfam14988
      Location:715881
      DUF4515; Domain of unknown function (DUF4515)
      cl21588
      Location:728830
      Snf7; Snf7
    4. NM_001362177.2NP_001349106.1  hamartin isoform 5

      Status: REVIEWED

      Description
      Transcript Variant: This variant (5) lacks a 5' exon which results in the use of a downstream AUG compared to variant 1. The encoded isoform (5) is shorter and has a distinct N-terminus compared to isoform 1.
      Source sequence(s)
      AL445645, N63914
      Conserved Domains (2) summary
      pfam04388
      Location:16598
      Hamartin; Hamartin protein
      cl25732
      Location:630850
      SMC_N; RecF/RecN/SMC N terminal domain

    RefSeqs of Annotated Genomes: Homo sapiens Updated Annotation Release 109.20210514

    The following sections contain reference sequences that belong to a specific genome build. Explain

    Reference GRCh38.p13 Primary Assembly

    Genomic

    1. NC_000009.12 Reference GRCh38.p13 Primary Assembly

      Range
      132891349..132945269 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_011518979.2XP_011517281.1  hamartin isoform X1

      See identical proteins and their annotated locations for XP_011517281.1

      UniProtKB/Swiss-Prot
      Q92574
      UniProtKB/TrEMBL
      X5D9D2
      Conserved Domains (4) summary
      pfam04388
      Location:7719
      Hamartin; Hamartin protein
      pfam05837
      Location:863957
      CENP-H; Centromere protein H (CENP-H)
      pfam14988
      Location:766932
      DUF4515; Domain of unknown function (DUF4515)
      cl21588
      Location:779881
      Snf7; Snf7
    2. XM_017015101.1XP_016870590.1  hamartin isoform X4

    3. XM_017015100.1XP_016870589.1  hamartin isoform X3

      Conserved Domains (2) summary
      pfam04388
      Location:16598
      Hamartin; Hamartin protein
      cl25732
      Location:630850
      SMC_N; RecF/RecN/SMC N terminal domain
    4. XM_017015097.1XP_016870586.1  hamartin isoform X1

      UniProtKB/Swiss-Prot
      Q92574
      UniProtKB/TrEMBL
      X5D9D2
      Conserved Domains (4) summary
      pfam04388
      Location:7719
      Hamartin; Hamartin protein
      pfam05837
      Location:863957
      CENP-H; Centromere protein H (CENP-H)
      pfam14988
      Location:766932
      DUF4515; Domain of unknown function (DUF4515)
      cl21588
      Location:779881
      Snf7; Snf7
    5. XM_017015096.1XP_016870585.1  hamartin isoform X1

      UniProtKB/Swiss-Prot
      Q92574
      UniProtKB/TrEMBL
      X5D9D2
      Conserved Domains (4) summary
      pfam04388
      Location:7719
      Hamartin; Hamartin protein
      pfam05837
      Location:863957
      CENP-H; Centromere protein H (CENP-H)
      pfam14988
      Location:766932
      DUF4515; Domain of unknown function (DUF4515)
      cl21588
      Location:779881
      Snf7; Snf7
    6. XM_017015098.1XP_016870587.1  hamartin isoform X2

      Related
      ENSP00000494682.1, ENST00000644097.1
      Conserved Domains (4) summary
      pfam04388
      Location:7718
      Hamartin; Hamartin protein
      pfam05837
      Location:862956
      CENP-H; Centromere protein H (CENP-H)
      pfam14988
      Location:765931
      DUF4515; Domain of unknown function (DUF4515)
      cl21588
      Location:778880
      Snf7; Snf7
    7. XM_005272211.1XP_005272268.1  hamartin isoform X1

      See identical proteins and their annotated locations for XP_005272268.1

      UniProtKB/Swiss-Prot
      Q92574
      UniProtKB/TrEMBL
      X5D9D2
      Related
      ENSP00000496263.1, ENST00000646625.1
      Conserved Domains (4) summary
      pfam04388
      Location:7719
      Hamartin; Hamartin protein
      pfam05837
      Location:863957
      CENP-H; Centromere protein H (CENP-H)
      pfam14988
      Location:766932
      DUF4515; Domain of unknown function (DUF4515)
      cl21588
      Location:779881
      Snf7; Snf7
    8. XM_006717271.1XP_006717334.1  hamartin isoform X1

      See identical proteins and their annotated locations for XP_006717334.1

      UniProtKB/Swiss-Prot
      Q92574
      UniProtKB/TrEMBL
      X5D9D2
      Related
      ENSP00000495158.1, ENST00000643875.1
      Conserved Domains (4) summary
      pfam04388
      Location:7719
      Hamartin; Hamartin protein
      pfam05837
      Location:863957
      CENP-H; Centromere protein H (CENP-H)
      pfam14988
      Location:766932
      DUF4515; Domain of unknown function (DUF4515)
      cl21588
      Location:779881
      Snf7; Snf7

    Suppressed Reference Sequence(s)

    The following Reference Sequences have been suppressed. Explain

    1. NM_001008567.1: Suppressed sequence

      Description
      NM_001008567.1: This RefSeq was permanently suppressed because currently there is support for the transcript but not for the protein.
    Support Center