Gene: TSC1

Alternate names for this Gene: LAM|TSC

Gene 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.

Gene is located in Chromosome: 9

Location in Chromosome : 9q34.13

Description of this Gene: TSC complex subunit 1

Type of Gene: protein-coding

rs1060505021 in TSC1 gene and FOCAL CORTICAL DYSPLASIA OF TAYLOR PMID 28215400 2017 Somatic Mutations in TSC1 and TSC2 Cause Focal Cortical Dysplasia.

rs118203434 in TSC1 gene and Neoplastic Syndromes, Hereditary PMID 27470532 2016 Tuberous Sclerosis Complex Associated with Vascular Anomalies or Overgrowth.

PMID 10363127 1998 Comprehensive mutation analysis of TSC1 using two-dimensional DNA electrophoresis with DGGE.

PMID 15798777 2005 Mutational analysis of the TSC1 and TSC2 genes in a diagnostic setting: genotype--phenotype correlations and comparison of diagnostic DNA techniques in Tuberous Sclerosis Complex.

PMID 10533066 1999 Mutation screening of the entire coding regions of the TSC1 and the TSC2 gene with the protein truncation test (PTT) identifies frequent splicing defects.

PMID 17304050 2007 Genotype/phenotype correlation in 325 individuals referred for a diagnosis of tuberous sclerosis complex in the United States.

PMID 9242607 1997 Identification of the tuberous sclerosis gene TSC1 on chromosome 9q34.

PMID 9924605 1998 Comprehensive mutational analysis of the TSC1 gene: observations on frequency of mutation, associated features, and nonpenetrance.

PMID 23341583 2013 Multiple pulmonary artery aneurysms in tuberous sclerosis complex.

PMID 10570911 1999 Mutational analysis of TSC1 and TSC2 genes in Japanese patients with tuberous sclerosis complex.

PMID 10227394 1999 Mutational spectrum of the TSC1 gene in a cohort of 225 tuberous sclerosis complex patients: no evidence for genotype-phenotype correlation.

PMID 18032745 2008 Overlapping neurologic and cognitive phenotypes in patients with TSC1 or TSC2 mutations.

PMID 11112665 2001 Mutational analysis in a cohort of 224 tuberous sclerosis patients indicates increased severity of TSC2, compared with TSC1, disease in multiple organs.

PMID 16981987 2006 Molecular and clinical analyses of 84 patients with tuberous sclerosis complex.

PMID 12015165 2002 Novel TSC1 and TSC2 mutations in Japanese patients with tuberous sclerosis complex.

PMID 9803264 1998 A mutation screen of the TSC1 gene reveals 26 protein truncating mutations and 1 splice site mutation in a panel of 79 tuberous sclerosis patients.

rs118203342 in TSC1 gene and TUBEROUS SCLEROSIS 1 (disorder) PMID 27854360 2017 Recommendations for reporting of secondary findings in clinical exome and genome sequencing, 2016 update (ACMG SF v2.0): a policy statement of the American College of Medical Genetics and Genomics.

PMID 23788249 2013 ACMG recommendations for reporting of incidental findings in clinical exome and genome sequencing.

PMID 23519317 2013 Clinical genetics evaluation in identifying the etiology of autism spectrum disorders: 2013 guideline revisions.

PMID 25356965 2015 ACMG policy statement: updated recommendations regarding analysis and reporting of secondary findings in clinical genome-scale sequencing.

PMID 25394175 2015 A practice guideline from the American College of Medical Genetics and Genomics and the National Society of Genetic Counselors: referral indications for cancer predisposition assessment.

PMID 15798777 2005 Mutational analysis of the TSC1 and TSC2 genes in a diagnostic setting: genotype--phenotype correlations and comparison of diagnostic DNA techniques in Tuberous Sclerosis Complex.

PMID 10227394 1999 Mutational spectrum of the TSC1 gene in a cohort of 225 tuberous sclerosis complex patients: no evidence for genotype-phenotype correlation.

PMID 11112665 2001 Mutational analysis in a cohort of 224 tuberous sclerosis patients indicates increased severity of TSC2, compared with TSC1, disease in multiple organs.

PMID 17304050 2007 Genotype/phenotype correlation in 325 individuals referred for a diagnosis of tuberous sclerosis complex in the United States.

PMID 21520333 2011 LOVD v.2.0: the next generation in gene variant databases.

PMID 22161988 2012 Functional assessment of TSC1 missense variants identified in individuals with tuberous sclerosis complex.

PMID 18830229 2009 Missense mutations to the TSC1 gene cause tuberous sclerosis complex.

PMID 10570911 1999 Mutational analysis of TSC1 and TSC2 genes in Japanese patients with tuberous sclerosis complex.

PMID 10874311 2000 Tuberous sclerosis type 1: three novel mutations detected in exon 15 by a combination of HDA and TGGE.

PMID 10533069 1999 Protein truncation test for screening hamartin gene mutations and report of new disease-causing mutations.

PMID 9328481 1997 Molecular genetic and phenotypic analysis reveals differences between TSC1 and TSC2 associated familial and sporadic tuberous sclerosis.

PMID 11829138 2002 Mutation analysis of the TSC1 and TSC2 genes in Japanese patients with pulmonary lymphangioleiomyomatosis.

PMID 19419980 2009 TSC1 and TSC2 mutations in patients with lymphangioleiomyomatosis and tuberous sclerosis complex.

PMID 16114042 2005 Analysis of 65 tuberous sclerosis complex (TSC) patients by TSC2 DGGE, TSC1/TSC2 MLPA, and TSC1 long-range PCR sequencing, and report of 28 novel mutations.

PMID 10363127 1998 Comprehensive mutation analysis of TSC1 using two-dimensional DNA electrophoresis with DGGE.

PMID 9924605 1998 Comprehensive mutational analysis of the TSC1 gene: observations on frequency of mutation, associated features, and nonpenetrance.

PMID 9803264 1998 A mutation screen of the TSC1 gene reveals 26 protein truncating mutations and 1 splice site mutation in a panel of 79 tuberous sclerosis patients.

PMID 10533067 1999 Analysis of both TSC1 and TSC2 for germline mutations in 126 unrelated patients with tuberous sclerosis.

PMID 10090883 1999 Germ-line mosaicism in tuberous sclerosis: how common?

PMID 28968464 2017 Molecular analysis of TSC1 and TSC2 genes and phenotypic correlations in Brazilian families with tuberous sclerosis.

PMID 22791573 2013 Molecular genetic, cardiac and neurodevelopmental findings in cases of prenatally diagnosed rhabdomyoma associated with tuberous sclerosis complex.

PMID 21309039 2011 Functional assessment of variants in the TSC1 and TSC2 genes identified in individuals with Tuberous Sclerosis Complex.

PMID 29196670 2017 Mutational analysis of TSC1 and TSC2 genes in Tuberous Sclerosis Complex patients from Greece.

PMID 23341583 2013 Multiple pulmonary artery aneurysms in tuberous sclerosis complex.

PMID 26540169 2015 Mosaic and Intronic Mutations in TSC1/TSC2 Explain the Majority of TSC Patients with No Mutation Identified by Conventional Testing.

PMID 20547222 2010 Analysis of TSC1 truncations defines regions involved in TSC1 stability, aggregation and interaction.

PMID 25900779 2015 TSC1 R509X Mutation in a Chinese Family with Tuberous Sclerosis Complex.

PMID 9863590 1998 Mutations in the TSC1 gene account for a minority of patients with tuberous sclerosis.

PMID 9242607 1997 Identification of the tuberous sclerosis gene TSC1 on chromosome 9q34.

PMID 16981987 2006 Molecular and clinical analyses of 84 patients with tuberous sclerosis complex.

PMID 10053179 1999 Mosaicism in tuberous sclerosis as a potential cause of the failure of molecular diagnosis.

PMID 26231267 2015 Hemispherectomy for Hemimegalencephaly Due to Tuberous Sclerosis and a Review of the Literature.

PMID 22707517 2012 Leydig cell tumor of the testis in tuberous sclerosis: lack of second hit events.

PMID 24633152 2014 Monoallelic germline TSC1 mutations are permissive for T lymphocyte development and homeostasis in tuberous sclerosis complex individuals.

PMID 18772611 2008 Novel mutations in 21 patients with tuberous sclerosis complex and variation of tandem splice-acceptor sites in TSC1 exon 14.

PMID 21811971 2011 [Mutation screening and prenatal diagnosis of tuberous sclerosis complex].

PMID 23728315 2013 [Novel TSC1 mutation associated with variable phenotypes in tuberous sclerosis].

PMID 27174333 2016 Comparison of Color Fundus Photography, Infrared Fundus Photography, and Optical Coherence Tomography in Detecting Retinal Hamartoma in Patients with Tuberous Sclerosis Complex.

PMID 23487808 2013 TS or not TS?

PMID 28762286 2018 Childhood-Onset Epileptic Encephalopathy Associated With Isolated Focal Cortical Dysplasia and a Novel TSC1 Germline Mutation.

PMID 29932062 2018 Molecular genetic diagnostics of tuberous sclerosis complex in Bulgaria: six novel mutations in the TSC1 and TSC2 genes.

PMID 28087349 2017 Combination of Multiple Ligation-Dependent Probe Amplification and Illumina MiSeq Amplicon Sequencing for TSC1/TSC2 Gene Analyses in Patients with Tuberous Sclerosis Complex.

PMID 23389244 2013 Mutational analysis of TSC1 and TSC2 in Japanese patients with tuberous sclerosis complex revealed higher incidence of TSC1 patients than previously reported.

PMID 18032745 2008 Overlapping neurologic and cognitive phenotypes in patients with TSC1 or TSC2 mutations.

rs118203434 in TSC1 gene and Tuberous Sclerosis PMID 10363127 1998 Comprehensive mutation analysis of TSC1 using two-dimensional DNA electrophoresis with DGGE.

PMID 11112665 2001 Mutational analysis in a cohort of 224 tuberous sclerosis patients indicates increased severity of TSC2, compared with TSC1, disease in multiple organs.

PMID 28065512 2017 Assessment of Tuberous Sclerosis Complex Associated With Renal Lesions by Targeted Next-generation Sequencing in Mainland China.

PMID 15121797 2004 Somatic mosaicism is rare in unaffected parents of patients with sporadic tuberous sclerosis.

PMID 10533066 1999 Mutation screening of the entire coding regions of the TSC1 and the TSC2 gene with the protein truncation test (PTT) identifies frequent splicing defects.

PMID 26231267 2015 Hemispherectomy for Hemimegalencephaly Due to Tuberous Sclerosis and a Review of the Literature.

PMID 18830229 2009 Missense mutations to the TSC1 gene cause tuberous sclerosis complex.

PMID 24633152 2014 Monoallelic germline TSC1 mutations are permissive for T lymphocyte development and homeostasis in tuberous sclerosis complex individuals.

PMID 20547222 2010 Analysis of TSC1 truncations defines regions involved in TSC1 stability, aggregation and interaction.

PMID 27425891 2016 Those include hamartin(R692X) and hamartin(R786X), stop mutants frequent in TSC patients and hamartin(H732Y) frequent in FCDIIb.

PMID 27494029 2016 Whole Exome Sequencing Identifies TSC1/TSC2 Biallelic Loss as the Primary and Sufficient Driver Event for Renal Angiomyolipoma Development.

PMID 29221145 2017 Subependymal giant cell astrocytomas in Tuberous Sclerosis Complex have consistent TSC1/TSC2 biallelic inactivation, and no BRAF mutations.

PMID 9242607 1997 Identification of the tuberous sclerosis gene TSC1 on chromosome 9q34.

PMID 16981987 2006 Molecular and clinical analyses of 84 patients with tuberous sclerosis complex.