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

Gene ID: 7248, updated on 24-Nov-2020

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

Genomic context

See TSC1 in Genome Data Viewer
Location:
9q34.13
Exon count:
25
Annotation release Status Assembly Chr Location
109.20201120 current GRCh38.p13 (GCF_000001405.39) 9 NC_000009.12 (132891349..132945269, complement)
105 previous assembly GRCh37.p13 (GCF_000001405.25) 9 NC_000009.11 (135766735..135820094, 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
ATPase inhibitor activity IDA
Inferred from Direct Assay
more info
PubMed 
Hsp70 protein binding IDA
Inferred from Direct Assay
more info
PubMed 
Hsp90 protein binding IPI
Inferred from Physical Interaction
more info
PubMed 
chaperone binding IPI
Inferred from Physical Interaction
more info
PubMed 
protein N-terminus binding IPI
Inferred from Physical Interaction
more info
PubMed 
protein binding IPI
Inferred from Physical Interaction
more info
PubMed 
Process Evidence Code Pubs
activation of GTPase activity IDA
Inferred from Direct Assay
more info
PubMed 
adaptive immune response IEA
Inferred from Electronic Annotation
more info
 
adult locomotory behavior ISS
Inferred from Sequence or Structural Similarity
more info
 
cardiac muscle cell differentiation IEA
Inferred from Electronic Annotation
more info
 
cell projection organization IEA
Inferred from Electronic Annotation
more info
 
cell-matrix adhesion IMP
Inferred from Mutant Phenotype
more info
PubMed 
cellular response to oxygen-glucose deprivation ISS
Inferred from Sequence or Structural Similarity
more info
 
cerebral cortex development IEA
Inferred from Electronic Annotation
more info
 
glucose import IEA
Inferred from Electronic Annotation
more info
 
hippocampus development IEA
Inferred from Electronic Annotation
more info
 
kidney development IEA
Inferred from Electronic Annotation
more info
 
memory T cell differentiation IEA
Inferred from Electronic Annotation
more info
 
myelination IEA
Inferred from Electronic Annotation
more info
 
negative regulation of ATPase activity IDA
Inferred from Direct Assay
more info
PubMed 
negative regulation of TOR signaling IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
negative regulation of TOR signaling IMP
Inferred from Mutant Phenotype
more info
PubMed 
negative regulation of TOR signaling ISS
Inferred from Sequence or Structural Similarity
more info
 
negative regulation of cell population proliferation IMP
Inferred from Mutant Phenotype
more info
PubMed 
negative regulation of cell size IEA
Inferred from Electronic Annotation
more info
 
negative regulation of insulin receptor signaling pathway IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
negative regulation of macroautophagy ISS
Inferred from Sequence or Structural Similarity
more info
 
negative regulation of translation IMP
Inferred from Mutant Phenotype
more info
PubMed 
neural tube closure IEA
Inferred from Electronic Annotation
more info
 
positive regulation of focal adhesion assembly IDA
Inferred from Direct Assay
more info
PubMed 
potassium ion transport IEA
Inferred from Electronic Annotation
more info
 
protein stabilization IDA
Inferred from Direct Assay
more info
PubMed 
protein stabilization IMP
Inferred from Mutant Phenotype
more info
PubMed 
rRNA export from nucleus IMP
Inferred from Mutant Phenotype
more info
PubMed 
regulation of cell cycle IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
regulation of cell-matrix adhesion IMP
Inferred from Mutant Phenotype
more info
PubMed 
regulation of neuron death ISS
Inferred from Sequence or Structural Similarity
more info
 
regulation of phosphoprotein phosphatase activity IMP
Inferred from Mutant Phenotype
more info
PubMed 
regulation of protein kinase activity IEA
Inferred from Electronic Annotation
more info
 
regulation of stress fiber assembly IDA
Inferred from Direct Assay
more info
PubMed 
regulation of translation IDA
Inferred from Direct Assay
more info
PubMed 
response to insulin IDA
Inferred from Direct Assay
more info
PubMed 
synapse organization IEA
Inferred from Electronic Annotation
more info
 
Component Evidence Code Pubs
TSC1-TSC2 complex IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
TSC1-TSC2 complex IDA
Inferred from Direct Assay
more info
PubMed 
colocalizes_with actin filament IDA
Inferred from Direct Assay
more info
PubMed 
cell cortex IDA
Inferred from Direct Assay
more info
PubMed 
chaperone complex IDA
Inferred from Direct Assay
more info
PubMed 
cytoplasm IDA
Inferred from Direct Assay
more info
PubMed 
cytosol IDA
Inferred from Direct Assay
more info
PubMed 
cytosol TAS
Traceable Author Statement
more info
 
lamellipodium IDA
Inferred from Direct Assay
more info
PubMed 
lipid droplet IDA
Inferred from Direct Assay
more info
 
membrane IDA
Inferred from Direct Assay
more info
PubMed 
nucleus ISS
Inferred from Sequence or Structural Similarity
more info
 
perinuclear region of cytoplasm ISS
Inferred from Sequence or Structural Similarity
more info
 
plasma membrane TAS
Traceable Author Statement
more info
 
postsynaptic density IEA
Inferred from Electronic Annotation
more info
 
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)

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 109.20201120

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.
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