TSC1 (Tuberous Sclerosis 1)

Identity

Other names	KIAA0234
HGNC	TSC1
Location	9q34
Location_base_pair	Starts at 134756557 and ends at 134809841 bp from pter ( according to hg18-Mar_2006).
Local_order	between D9S1199 and D9S1830

Note	tumor-suppressor

DNA/RNA

Description	23 exons, of which 21 are coding; start codon is in exon 3. Different splice variants in the 5'UTR
Transcription	1 major detected transcript at 8.6 kb, 2 additional transcripts at 4 and 2.5 kb respectively; open reading frame : 3492 bp

Protein

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	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. PROGNOSIS Renal cell carcinoma develops occasionally in TSC patients. Life expectancy largely depends on complications caused by the lesions in the brain and the kidneys.

External links

	Nomenclature
HGNC	TSC1   12362
Entrez_Gene	TSC1  7248  tuberous sclerosis 1
	Cards
Atlas	TSC1ID183
GeneCards	TSC1
Ensembl	ENSG00000165699 [Gene_View]  TSC1 [Vega]
Genatlas	TSC1
	Genomic and cartography
GoldenPath	TSC1  -  9q34   chr9:134756557-134809841 -  9q34   [Description]    (hg18-Mar_2006)
Ensembl	TSC1 - 9q34 [CytoView]
NCBI	Mapview
OMIM	191100 Disease map [OMIM]
OMIM	605284 Disease map [OMIM]
OMIM	606690 Disease map [OMIM]
OMIM	607341 Disease map [OMIM]
HomoloGene	TSC1
	Gene and transcription
Genbank	AA215977 [ ENTREZ ]
Genbank	AB190910 [ ENTREZ ]
Genbank	AF013168 [ ENTREZ ]
Genbank	AK308412 [ ENTREZ ]
Genbank	BC047772 [ ENTREZ ]
RefSeq	NM_000368 [ SRS ]    NM_000368 [ ENTREZ ]
RefSeq	NM_001008567 [ SRS ]    NM_001008567 [ ENTREZ ]
RefSeq	AC_000052 [ SRS ]    AC_000052 [ ENTREZ ]
RefSeq	AC_000141 [ SRS ]    AC_000141 [ ENTREZ ]
RefSeq	NC_000009 [ SRS ]    NC_000009 [ ENTREZ ]
RefSeq	NT_035014 [ SRS ]    NT_035014 [ ENTREZ ]
RefSeq	NW_001839241 [ SRS ]    NW_001839241 [ ENTREZ ]
RefSeq	NW_924573 [ SRS ]    NW_924573 [ ENTREZ ]
CCDS	TSC1 CCDS - NCBI
AceView	TSC1 AceView - NCBI
Unigene	Hs.370854 [ SRS ]    Hs.370854 [ NCBI ]
Fast-db	16309 (alternative variants)
	Protein : pattern, domain, 3D structure
SwissProt	Q0VAM5 [ SRS]    Q0VAM5 [ EXPASY ]     Q0VAM5 [ INTERPRO ]     Q0VAM5 [ UNIPROT ] Q0VAM5 [ VarSplice FASTA ]
Interpro	IPR007483 Hamartin [ SRS ]    IPR007483 Hamartin [ EBI ]
CluSTr	Q0VAM5
Pfam	PF04388 Hamartin [ SRS ]    PF04388 Hamartin [ Sanger ]    pfam04388 [ NCBI-CDD ]
Blocks	Q0VAM5
HPRD	05594
	Protein Interaction databases
DIP	Q0VAM5
IntAct	Q0VAM5
	Polymorphism : SNP, mutations, diseases
OMIM	191100    [ map ]
OMIM	605284    [ map ]
OMIM	606690    [ map ]
OMIM	607341    [ map ]
GENETests	191100
GENETests	605284
GENETests	606690
GENETests	607341
SNP	TSC1 [dbSNP-NCBI]
SNP	NM_000368 [SNP-NCI]
SNP	NM_001008567 [SNP-NCI]
SNP	TSC1 [GeneSNPs - Utah]  TSC1] [HGBASE - SRS]
HAPMAP	TSC1 [HAPMAP]
COSMIC	TSC1 [Somatic mutation (COSMIC-CGP-Sanger)]
HGMD	TSC1
Genetic Association	TSC1
CDC HuGE	TSC1
	General knowledge
Family Browser	TSC1 [UCSC Family Browser]
SOURCE	NM_000368
SOURCE	NM_001008567
SMD	Hs.370854
SAGE	Hs.370854
GO	kidney development [Amigo]  kidney development
GO	neural tube closure [Amigo]  neural tube closure
GO	regulation of cell-matrix adhesion [Amigo]  regulation of cell-matrix adhesion
GO	membrane fraction [Amigo]  membrane fraction
GO	cytoplasm [Amigo]  cytoplasm
GO	cytosol [Amigo]  cytosol
GO	cytosol [Amigo]  cytosol
GO	actin filament [Amigo]  actin filament
GO	cell cortex [Amigo]  cell cortex
GO	rRNA export from nucleus [Amigo]  rRNA export from nucleus
GO	potassium ion transport [Amigo]  potassium ion transport
GO	nervous system development [Amigo]  nervous system development
GO	negative regulation of cell proliferation [Amigo]  negative regulation of cell proliferation
GO	embryonic development [Amigo]  embryonic development
GO	membrane [Amigo]  membrane
GO	negative regulation of translation [Amigo]  negative regulation of translation
GO	hippocampus development [Amigo]  hippocampus development
GO	cerebral cortex development [Amigo]  cerebral cortex development
GO	lamellipodium [Amigo]  lamellipodium
GO	cell projection organization and biogenesis [Amigo]  cell projection organization and biogenesis
GO	negative regulation of protein ubiquitination [Amigo]  negative regulation of protein ubiquitination
GO	negative regulation of TOR signaling pathway [Amigo]  negative regulation of TOR signaling pathway
GO	activation of Rho GTPase activity [Amigo]  activation of Rho GTPase activity
GO	response to insulin stimulus [Amigo]  response to insulin stimulus
GO	TSC1-TSC2 complex [Amigo]  TSC1-TSC2 complex
GO	myelination [Amigo]  myelination
GO	regulation of phosphoprotein phosphatase activity [Amigo]  regulation of phosphoprotein phosphatase activity
GO	negative regulation of cell cycle [Amigo]  negative regulation of cell cycle
GO	negative regulation of cell size [Amigo]  negative regulation of cell size
GO	regulation of protein kinase activity [Amigo]  regulation of protein kinase activity
GO	protein N-terminus binding [Amigo]  protein N-terminus binding
GO	synapse organization and biogenesis [Amigo]  synapse organization and biogenesis
GO	chaperone binding [Amigo]  chaperone binding
GO	regulation of stress fiber formation [Amigo]  regulation of stress fiber formation
GO	positive regulation of focal adhesion formation [Amigo]  positive regulation of focal adhesion formation
GO	cardiac muscle cell differentiation [Amigo]  cardiac muscle cell differentiation
BIOCARTA	mTOR Signaling Pathway    [Genes]
KEGG	mTOR signaling pathway
KEGG	Insulin signaling pathway
PubGene	TSC1
TreeFam	TSC1
CTD	7248 [Comparative ToxicoGenomics Database]
	Other databases
	Probes
Probe	TSC1 Related clones (RZPD - Berlin)
	PubMed
PubMed	81 Pubmed reference(s) in Entrez

Bibliography

Identification of the tuberous sclerosis gene TSC1 on chromosome 9q34.

van Slegtenhorst M, de Hoogt R, Hermans C, Nellist M, Janssen B, Verhoef S, Lindhout D, van den Ouweland A, Halley D, Young J, Burley M, Jeremiah S, Woodward K, Nahmias J, Fox M, Ekong R, Osborne J, Wolfe J, Povey S, Snell RG, Cheadle JP, Jones AC, Tachataki M, Ravine D, Sampson JR, Reeve MP, Richardson P, Wilmer F, Munro C, Hawkins TL, Sepp T, Ali JB, Ward S, Green AJ, Yates JR, Kwiatkowska J, Henske EP, Short MP, Haines JH, Jozwiak S, Kwiatkowski DJ

Science (New York, N.Y.). 1997 ; 277 (5327) : 805-808.

PMID 9242607

Interaction between hamartin and tuberin, the TSC1 and TSC2 gene products.

van Slegtenhorst M, Nellist M, Nagelkerken B, Cheadle J, Snell R, van den Ouweland A, Reuser A, Sampson J, Halley D, van der Sluijs P

Human molecular genetics. 1998 ; 7 (6) : 1053-1057.

PMID 9580671

Hamartin, the product of the tuberous sclerosis 1 (TSC1) gene, interacts with tuberin and appears to be localized to cytoplasmic vesicles.

Plank TL, Yeung RS, Henske EP

Cancer research. 1998 ; 58 (21) : 4766-4770.

PMID 9809973

Mutational spectrum of the TSC1 gene in a cohort of 225 tuberous sclerosis complex patients: no evidence for genotype-phenotype correlation.

van Slegtenhorst M, Verhoef S, Tempelaars A, Bakker L, Wang Q, Wessels M, Bakker R, Nellist M, Lindhout D, Halley D, van den Ouweland A

Journal of medical genetics. 1999 ; 36 (4) : 285-289.

PMID 10227394

Comprehensive mutation analysis of TSC1 and TSC2-and phenotypic correlations in 150 families with tuberous sclerosis.

Jones AC, Shyamsundar MM, Thomas MW, Maynard J, Idziaszczyk S, Tomkins S, Sampson JR, Cheadle JP

American journal of human genetics. 1999 ; 64 (5) : 1305-1315.

PMID 10205261

Characterization of the cytosolic tuberin-hamartin complex. Tuberin is a cytosolic chaperone for hamartin.

Nellist M, van Slegtenhorst MA, Goedbloed M, van den Ouweland AM, Halley DJ, van der Sluijs P

The Journal of biological chemistry. 1999 ; 274 (50) : 35647-35652.

PMID 10585443

The expression of hamartin, the product of the TSC1 gene, in normal human tissues and in TSC1- and TSC2-linked angiomyolipomas.

Plank TL, Logginidou H, Klein-Szanto A, Henske EP

Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc. 1999 ; 12 (5) : 539-545.

PMID 10349994

The 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, Li S, Brown SJ, Braverman R, Vass WC, Cheadle JP, Halley DJ, Sampson JR, Wienecke R, DeClue JE

Oncogene. 2000 ; 19 (54) : 6306-6316.

PMID 11175345

Genomic organization and comparative analysis of the mouse tuberous sclerosis 1 (Tsc1) locus.

Cheadle JP, Dobbie L, Idziaszczyk S, Hodges AK, Smith AJ, Sampson JR, Young J

Mammalian genome : official journal of the International Mammalian Genome Society. 2000 ; 11 (12) : 1135-1138.

PMID 11130985

The TSC1 tumour suppressor hamartin regulates cell adhesion through ERM proteins and the GTPase Rho.

Lamb RF, Roy C, Diefenbach TJ, Vinters HV, Johnson MW, Jay DG, Hall A

Nature cell biology. 2000 ; 2 (5) : 281-287.

PMID 10806479

The TSC1 gene product, hamartin, negatively regulates cell proliferation.

Miloloza A, Rosner M, Nellist M, Halley D, Bernaschek G, Hengstschlˆ§ger M

Human molecular genetics. 2000 ; 9 (12) : 1721-1727.

PMID 10915759

Mutations of the calcium-sensing receptor (CASR) in familial hypocalciuric hypercalcemia, neonatal severe hyperparathyroidism, and autosomal dominant hypocalcemia.

Hendy GN, D'Souza-Li L, Yang B, Canaff L, Cole DE

Human mutation. 2000 ; 16 (4) : 281-296.

PMID 11013439

Tuberin phosphorylation regulates its interaction with hamartin. Two proteins involved in tuberous sclerosis.

Aicher LD, Campbell JS, Yeung RS

The Journal of biological chemistry. 2001 ; 276 (24) : 21017-21021.

PMID 11290735

Hamartin expression and interaction with tuberin in tumor cell lines and primary cultures.

Catania MG, Johnson MW, Liau LM, Kremen TJ, deVellis JS, Vinters HV

Journal of neuroscience research. 2001 ; 63 (3) : 276-283.

PMID 11170177

Hamartin and tuberin interaction with the G2/M cyclin-dependent kinase CDK1 and its regulatory cyclins A and B.

Catania MG, Mischel PS, Vinters HV

Journal of neuropathology and experimental neurology. 2001 ; 60 (7) : 711-723.

PMID 11444800

Mutational analysis in a cohort of 224 tuberous sclerosis patients indicates increased severity of TSC2, compared with TSC1, disease in multiple organs.

Dabora SL, Jozwiak S, Franz DN, Roberts PS, Nieto A, Chung J, Choy YS, Reeve MP, Thiele E, Egelhoff JC, Kasprzyk-Obara J, Domanska-Pakiela D, Kwiatkowski DJ

American journal of human genetics. 2001 ; 68 (1) : 64-80.

PMID 11112665

A 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, Minowa O, Sugitani Y, Takai S, Mitani H, Kobayashi E, Noda T, Hino O

Proceedings of the National Academy of Sciences of the United States of America. 2001 ; 98 (15) : 8762-8767.

PMID 11438694

Hamartin and tuberin expression in human tissues.

Johnson MW, Kerfoot C, Bushnell T, Li M, Vinters HV

Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc. 2001 ; 14 (3) : 202-210.

PMID 11266527

Drosophila Tsc1 functions with Tsc2 to antagonize insulin signaling in regulating cell growth, cell proliferation, and organ size.

Potter CJ, Huang H, Xu T

Cell. 2001 ; 105 (3) : 357-368.

PMID 11348592

The Drosophila tuberous sclerosis complex gene homologs restrict cell growth and cell proliferation.

Tapon N, Ito N, Dickson BJ, Treisman JE, Hariharan IK

Cell. 2001 ; 105 (3) : 345-355.

PMID 11348591

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Contributor(s)

Written	11-2001	Marjon van Slegtenhorst and Elizabeth Petri Henske
		Fox Chase Cancer Center, 7701 Burholme Ave, Philadelphia PA 19111, USA

Citation

This paper should be referenced as such :

van Slegtenhorst M, Petri Henske E . TSC1 (Tuberous Sclerosis 1). Atlas Genet Cytogenet Oncol Haematol. November 2001 . URL : http://AtlasGeneticsOncology.org/Genes/TSC1ID183.html

© Atlas of Genetics and Cytogenetics in Oncology and Haematology

indexed on : Thu Nov 27 13:31:00 2008