TSC1 (Tuberous Sclerosis 1)

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

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

Identity

HGNC

TSC1

LOCATION

9q34.13

LOCUSID

7248

ALIAS

LAM,TSC

FUSION GENES

Show Gene Fusions

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.

Article Bibliography

Pubmed ID	Last Year	Title	Authors
11290735	2001	Tuberin phosphorylation regulates its interaction with hamartin. Two proteins involved in tuberous sclerosis.	Aicher LD et al
11175345	2000	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 et al
11444800	2001	Hamartin and tuberin interaction with the G2/M cyclin-dependent kinase CDK1 and its regulatory cyclins A and B.	Catania MG et al
11130985	2000	Genomic organization and comparative analysis of the mouse tuberous sclerosis 1 (Tsc1) locus.	Cheadle JP et al
11112665	2001	Mutational 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
11013439	2000	Mutations of the calcium-sensing receptor (CASR) in familial hypocalciuric hypercalcemia, neonatal severe hyperparathyroidism, and autosomal dominant hypocalcemia.	Hendy GN et al
11266527	2001	Hamartin and tuberin expression in human tissues.	Johnson MW et al
10205261	1999	Comprehensive mutation analysis of TSC1 and TSC2-and phenotypic correlations in 150 families with tuberous sclerosis.	Jones AC et al
11438694	2001	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 et al
10806479	2000	The TSC1 tumour suppressor hamartin regulates cell adhesion through ERM proteins and the GTPase Rho.	Lamb RF et al
10915759	2000	The TSC1 gene product, hamartin, negatively regulates cell proliferation.	Miloloza A et al
10585443	1999	Characterization of the cytosolic tuberin-hamartin complex. Tuberin is a cytosolic chaperone for hamartin.	Nellist M et al
10349994	1999	The expression of hamartin, the product of the TSC1 gene, in normal human tissues and in TSC1- and TSC2-linked angiomyolipomas.	Plank TL et al
9809973	1998	Hamartin, the product of the tuberous sclerosis 1 (TSC1) gene, interacts with tuberin and appears to be localized to cytoplasmic vesicles.	Plank TL et al
11348592	2001	Drosophila Tsc1 functions with Tsc2 to antagonize insulin signaling in regulating cell growth, cell proliferation, and organ size.	Potter CJ et al
11348591	2001	The Drosophila tuberous sclerosis complex gene homologs restrict cell growth and cell proliferation.	Tapon N et al
10227394	1999	Mutational 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 ID	Transcript ID	Uniprot
ENSG00000165699	ENST00000298552	Q92574
ENSG00000165699	ENST00000298552	X5D9D2
ENSG00000165699	ENST00000403810	Q86WV8
ENSG00000165699	ENST00000440111	Q92574
ENSG00000165699	ENST00000440111	X5D9D2
ENSG00000165699	ENST00000475903	A0A2R8YGL0
ENSG00000165699	ENST00000490179	A0A2R8Y6S8
ENSG00000165699	ENST00000545250	Q92574
ENSG00000165699	ENST00000642261	A0A2R8Y5U8
ENSG00000165699	ENST00000642344	A0A2R8Y5J1
ENSG00000165699	ENST00000642617	A0A2R8Y5S3
ENSG00000165699	ENST00000642627	A0A2R8YFV7
ENSG00000165699	ENST00000642646	Q59IT9
ENSG00000165699	ENST00000642745	Q59IT9
ENSG00000165699	ENST00000642811	A0A2R8Y419
ENSG00000165699	ENST00000642854	A0A2R8Y5Q4
ENSG00000165699	ENST00000643072	Q92574
ENSG00000165699	ENST00000643275	A0A2R8YEH9
ENSG00000165699	ENST00000643362	A0A2R8YGX7
ENSG00000165699	ENST00000643583	A0A2R8Y5N2
ENSG00000165699	ENST00000643625	A0A2R8Y6T5
ENSG00000165699	ENST00000643691	A0A2R8Y5M3
ENSG00000165699	ENST00000643875	Q92574
ENSG00000165699	ENST00000643875	X5D9D2
ENSG00000165699	ENST00000644097	A0A2R8Y5S3
ENSG00000165699	ENST00000644184	A0A2R8Y6S1
ENSG00000165699	ENST00000644255	A0A2R8Y419
ENSG00000165699	ENST00000644997	A0A2R8Y6N1
ENSG00000165699	ENST00000645129	A0A2R8YD74
ENSG00000165699	ENST00000645150	Q59IT9
ENSG00000165699	ENST00000646391	A0A2R8Y419
ENSG00000165699	ENST00000646440	A0A2R8Y756
ENSG00000165699	ENST00000646625	Q92574
ENSG00000165699	ENST00000646625	X5D9D2
ENSG00000165699	ENST00000647078	A0A2R8Y7E9
ENSG00000165699	ENST00000647279	A0A2R8Y5F8
ENSG00000165699	ENST00000647462	A0A2R8Y6W1

Expression (GTEx)

Adipose - Subcutaneous

Adipose - Visceral

Adrenal Gland

Artery - Aorta

Artery - Tibial

Bladder

Brain - Amygdala

Brain - Anterior cingulate cortex

Brain - Caudate

Brain - Cerebellar Hemisphere

Brain - Cerebellum

Brain - Cortex

Brain - Frontal Cortex

Brain - Hippocampus

Brain - Hypothalamus

Brain - Nucleus accumbens

Brain - Putamen

Brain - Spinal cord

Brain - Substantia nigra

Breast - Mammary Tissue

Cells - Cultured fibroblasts

Cells - EBV - transformed lymphocytes

Cervix - Ectocervix

Cervix - Endocervix

Colon - Sigmoid

Colon - Transverse

Esophagus - Gastroesophageal Junction

Esophagus - Mucosa

Esophagus - Muscularis

Fallopian Tube

Heart - Atrial Appendage

Heart - Left Ventricle

Kidney - Cortex

Kidney - Medulla

Liver

Lung

Minor Salivary Gland

Muscle - Skeletal

Nerve - Tibial

Ovary

Pancreas

Pituitary

Prostate

Skin - Not Sun Exposed

Skin - Sun Exposed

Small Intestine - Terminal Ileum

Spleen

Stomach

Testis

Thyroid

Uterus

Vagina

Whole Blood

Pathways

Pathway	Source	External ID
Autophagy - animal	KEGG	ko04140
mTOR signaling pathway	KEGG	ko04150
Insulin signaling pathway	KEGG	ko04910
Autophagy - animal	KEGG	hsa04140
mTOR signaling pathway	KEGG	hsa04150
Insulin signaling pathway	KEGG	hsa04910
PI3K-Akt signaling pathway	KEGG	hsa04151
PI3K-Akt signaling pathway	KEGG	ko04151
AMPK signaling pathway	KEGG	hsa04152
AMPK signaling pathway	KEGG	ko04152
Choline metabolism in cancer	KEGG	hsa05231
Choline metabolism in cancer	KEGG	ko05231
Signal Transduction	REACTOME	R-HSA-162582
Signaling by Insulin receptor	REACTOME	R-HSA-74752
Insulin receptor signalling cascade	REACTOME	R-HSA-74751
IRS-mediated signalling	REACTOME	R-HSA-112399
PI3K Cascade	REACTOME	R-HSA-109704
PKB-mediated events	REACTOME	R-HSA-109703
mTOR signalling	REACTOME	R-HSA-165159
Inhibition of TSC complex formation by PKB	REACTOME	R-HSA-165181
Energy dependent regulation of mTOR by LKB1-AMPK	REACTOME	R-HSA-380972
Signaling by Type 1 Insulin-like Growth Factor 1 Receptor (IGF1R)	REACTOME	R-HSA-2404192
IGF1R signaling cascade	REACTOME	R-HSA-2428924
IRS-related events triggered by IGF1R	REACTOME	R-HSA-2428928
Gene Expression	REACTOME	R-HSA-74160
Generic Transcription Pathway	REACTOME	R-HSA-212436
Transcriptional Regulation by TP53	REACTOME	R-HSA-3700989
TP53 Regulates Metabolic Genes	REACTOME	R-HSA-5628897
Vesicle-mediated transport	REACTOME	R-HSA-5653656
Membrane Trafficking	REACTOME	R-HSA-199991
Cellular responses to stress	REACTOME	R-HSA-2262752
Macroautophagy	REACTOME	R-HSA-1632852
Phospholipase D signaling pathway	KEGG	ko04072
Phospholipase D signaling pathway	KEGG	hsa04072
Longevity regulating pathway	KEGG	hsa04211
TBC/RABGAPs	REACTOME	R-HSA-8854214

Protein levels (Protein atlas)

Not detected

Low

Medium

High

PharmGKB

Entity ID	Name	Type	Evidence	Association	PD	PMIDs
PA131285571	aspirin-induced asthma	Disease	ClinicalAnnotation	associated	PD
PA37035	TSC2	Gene	DataAnnotation	associated
PA443450	Asthma	Disease	ClinicalAnnotation	associated	PD
PA445965	Tuberous Sclerosis	Disease	DataAnnotation, Literature, MultilinkAnnotation	associated		23788249
PA448497	aspirin	Chemical	ClinicalAnnotation	associated	PD

References

Pubmed ID	Year	Title	Citations
38212374	2024	The role of TSC1 and TSC2 proteins in neuronal axons.	0
38212374	2024	The role of TSC1 and TSC2 proteins in neuronal axons.	0
36592877	2023	TSC/MTOR mutated renal cell carcinoma with leiomyomatous stroma is a distinct entity: a comprehensive study of 12 cases.	1
36719021	2023	Refractive Errors, Retinal Findings, and Genotype of Tuberous Sclerosis Complex: A Retrospective Cohort Study.	0
36727758	2023	TSC/MTOR -associated Eosinophilic Renal Tumors Exhibit a Heterogeneous Clinicopathologic Spectrum : Several Distinct Entities or a Tumor Family?	1
37020385	2023	Tuberous sclerosis complex-1 (TSC1) contributes to selective neuronal vulnerability in Alzheimer's disease.	1
37949232	2023	CBAP regulates the function of Akt-associated TSC protein complexes to modulate mTORC1 signaling.	0
36592877	2023	TSC/MTOR mutated renal cell carcinoma with leiomyomatous stroma is a distinct entity: a comprehensive study of 12 cases.	1
36719021	2023	Refractive Errors, Retinal Findings, and Genotype of Tuberous Sclerosis Complex: A Retrospective Cohort Study.	0
36727758	2023	TSC/MTOR -associated Eosinophilic Renal Tumors Exhibit a Heterogeneous Clinicopathologic Spectrum : Several Distinct Entities or a Tumor Family?	1
37020385	2023	Tuberous sclerosis complex-1 (TSC1) contributes to selective neuronal vulnerability in Alzheimer's disease.	1
37949232	2023	CBAP regulates the function of Akt-associated TSC protein complexes to modulate mTORC1 signaling.	0
34131293	2022	Uterine PEComas: correlation between melanocytic marker expression and TSC alterations/TFE3 fusions.	6
34728310	2022	Long noncoding RNA KB-1460A1.5 inhibits glioma tumorigenesis via miR-130a-3p/TSC1/mTOR/YY1 feedback loop.	6
34756499	2022	Somatic mutations involving TSC 1 and TSC2 genes in two children with focal cortical dysplasia.	2

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/tsc1id183