Gene: TPM1

Alternate names for this Gene: C15orf13|CMD1Y|CMH3|HEL-S-265|HTM-alpha|LVNC9|TMSA

Gene Summary: This gene is a member of the tropomyosin family of highly conserved, widely distributed actin-binding proteins involved in the contractile system of striated and smooth muscles and the cytoskeleton of non-muscle cells. Tropomyosin is composed of two alpha-helical chains arranged as a coiled-coil. It is polymerized end to end along the two grooves of actin filaments and provides stability to the filaments. The encoded protein is one type of alpha helical chain that forms the predominant tropomyosin of striated muscle, where it also functions in association with the troponin complex to regulate the calcium-dependent interaction of actin and myosin during muscle contraction. In smooth muscle and non-muscle cells, alternatively spliced transcript variants encoding a range of isoforms have been described. Mutations in this gene are associated with type 3 familial hypertrophic cardiomyopathy.

Gene is located in Chromosome: 15

Location in Chromosome : 15q22.2

Description of this Gene: tropomyosin 1

Type of Gene: protein-coding

rs1114167356 in TPM1 gene and ATRIAL SEPTAL DEFECT 1 PMID 28359939 2017 Tropomyosin 1: Multiple roles in the developing heart and in the formation of congenital heart defects.

rs104894502 in TPM1 gene and CARDIOMYOPATHY, FAMILIAL HYPERTROPHIC, 3 (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 25356965 2015 ACMG policy statement: updated recommendations regarding analysis and reporting of secondary findings in clinical genome-scale sequencing.

PMID 9822100 1998 The cardiac beta-myosin heavy chain gene is not the predominant gene for hypertrophic cardiomyopathy in the Finnish population.

PMID 8523464 1995 Novel missense mutation in alpha-tropomyosin gene found in Japanese patients with hypertrophic cardiomyopathy.

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

PMID 21267010 2011 Clinical utility gene card for: hypertrophic cardiomyopathy (type 1-14).

PMID 7898523 1995 Mutations in the genes for cardiac troponin T and alpha-tropomyosin in hypertrophic cardiomyopathy.

PMID 8205619 1994 Alpha-tropomyosin and cardiac troponin T mutations cause familial hypertrophic cardiomyopathy: a disease of the sarcomere.

PMID 23170982 2012 α-Tropomyosin with a D175N or E180G mutation in only one chain differs from tropomyosin with mutations in both chains.

PMID 12974739 2003 Mutation spectrum in a large cohort of unrelated consecutive patients with hypertrophic cardiomyopathy.

PMID 18414213 2008 ACMG recommendations for standards for interpretation and reporting of sequence variations: Revisions 2007.

PMID 27376658 2016 Investigating the effects of tropomyosin mutations on its flexibility and interactions with filamentous actin using molecular dynamics simulation.

PMID 23771913 2013 Deep basal inferoseptal crypts occur more commonly in patients with hypertrophic cardiomyopathy due to disease-causing myofilament mutations.

PMID 21310275 2011 Development and validation of a computational method for assessment of missense variants in hypertrophic cardiomyopathy.

PMID 23396983 2013 Genetic complexity in hypertrophic cardiomyopathy revealed by high-throughput sequencing.

PMID 20031602 2009 Echocardiographic strain imaging to assess early and late consequences of sarcomere mutations in hypertrophic cardiomyopathy.

PMID 26960954 2016 Next Generation Sequencing and Linkage Analysis for the Molecular Diagnosis of a Novel Overlapping Syndrome Characterized by Hypertrophic Cardiomyopathy and Typical Electrical Instability of Brugada Syndrome.

PMID 24033266 2013 A systematic approach to assessing the clinical significance of genetic variants.

PMID 18409188 2008 A DNA resequencing array for pathogenic mutation detection in hypertrophic cardiomyopathy.

PMID 12860912 2003 Prevalence and spectrum of thin filament mutations in an outpatient referral population with hypertrophic cardiomyopathy.

PMID 24510615 2014 Distinguishing hypertrophic cardiomyopathy-associated mutations from background genetic noise.

PMID 21551322 2011 Sarcomere gene mutations in isolated left ventricular noncompaction cardiomyopathy do not predict clinical phenotype.

PMID 16365313 2005 Structure of the mid-region of tropomyosin: bending and binding sites for actin.

PMID 25524337 2014 Clinical phenotype and outcome of hypertrophic cardiomyopathy associated with thin-filament gene mutations.

PMID 25611685 2015 Results of clinical genetic testing of 2,912 probands with hypertrophic cardiomyopathy: expanded panels offer limited additional sensitivity.

PMID 25241052 2014 Energy landscapes reveal the myopathic effects of tropomyosin mutations.

PMID 27532257 2017 Reassessment of Mendelian gene pathogenicity using 7,855 cardiomyopathy cases and 60,706 reference samples.

PMID 25548289 2015 Mechanistic heterogeneity in contractile properties of α-tropomyosin (TPM1) mutants associated with inherited cardiomyopathies.

PMID 25525159 2015 RNA splicing. The human splicing code reveals new insights into the genetic determinants of disease.

PMID 20117437 2010 Familial dilated cardiomyopathy caused by an alpha-tropomyosin mutation: the distinctive natural history of sarcomeric dilated cardiomyopathy.

PMID 23539503 2013 Familial dilated cardiomyopathy mutations uncouple troponin I phosphorylation from changes in myofibrillar Ca²⁺ sensitivity.

rs397516373 in TPM1 gene and Cardiomyopathies PMID 29517769 2018 Toward an effective exome-based genetic testing strategy in pediatric dilated cardiomyopathy.

PMID 29024827 2018 Left ventricular non-compaction with Ebstein anomaly attributed to a TPM1 mutation.

PMID 27177193 2016 Ebstein anomaly, left ventricular non-compaction, and early onset heart failure associated with a de novo α-tropomyosin gene mutation.

PMID 28359939 2017 Tropomyosin 1: Multiple roles in the developing heart and in the formation of congenital heart defects.

PMID 27532257 2017 Reassessment of Mendelian gene pathogenicity using 7,855 cardiomyopathy cases and 60,706 reference samples.

rs199476310 in TPM1 gene and Cardiomyopathy, Dilated PMID 21483645 2011 Rare variant mutations identified in pediatric patients with dilated cardiomyopathy.

PMID 20215591 2010 Coding sequence rare variants identified in MYBPC3, MYH6, TPM1, TNNC1, and TNNI3 from 312 patients with familial or idiopathic dilated cardiomyopathy.

PMID 20530761 2010 The importance of genetic counseling, DNA diagnostics, and cardiologic family screening in left ventricular noncompaction cardiomyopathy.

PMID 20117437 2010 Familial dilated cardiomyopathy caused by an alpha-tropomyosin mutation: the distinctive natural history of sarcomeric dilated cardiomyopathy.

PMID 11106625 2000 Alteration of tropomyosin function and folding by a nemaline myopathy-causing mutation.

PMID 21310275 2011 Development and validation of a computational method for assessment of missense variants in hypertrophic cardiomyopathy.

rs104894501 in TPM1 gene and Cardiomyopathy, Dilated, 1y PMID 11273725 2001 Mutations that alter the surface charge of alpha-tropomyosin are associated with dilated cardiomyopathy.

PMID 21551322 2011 Sarcomere gene mutations in isolated left ventricular noncompaction cardiomyopathy do not predict clinical phenotype.

PMID 25241052 2014 Energy landscapes reveal the myopathic effects of tropomyosin mutations.

PMID 21310275 2011 Development and validation of a computational method for assessment of missense variants in hypertrophic cardiomyopathy.

PMID 27532257 2017 Reassessment of Mendelian gene pathogenicity using 7,855 cardiomyopathy cases and 60,706 reference samples.

PMID 25525159 2015 RNA splicing. The human splicing code reveals new insights into the genetic determinants of disease.

PMID 23539503 2013 Familial dilated cardiomyopathy mutations uncouple troponin I phosphorylation from changes in myofibrillar Ca²⁺ sensitivity.

PMID 20117437 2010 Familial dilated cardiomyopathy caused by an alpha-tropomyosin mutation: the distinctive natural history of sarcomeric dilated cardiomyopathy.

PMID 25548289 2015 Mechanistic heterogeneity in contractile properties of α-tropomyosin (TPM1) mutants associated with inherited cardiomyopathies.

rs104894503 in TPM1 gene and Cardiomyopathy, Hypertrophic, Familial PMID 9245729 1997 The functional properties of wild type alpha-tropomyosin expressed in E. coli with an alanine-serine N-terminal leader (AS-alpha-Tm) were compared with those of AS-alpha-Tm with either of two missense mutations (Asp175Asn and Glu180Gly) shown to cause familial hypertrophic cardiomyopathy (FHC).

PMID 9060904 1997 We studied the clinical and genetic features of familial hypertrophic cardiomyopathy (FHC) caused by an Asp175Asn mutation in the alpha-tropomyosin gene in affected subjects from three unrelated families.

PMID 8205619 1994 We demonstrate that missense mutations (Asp175Asn; Glu180Gly) in the alpha-tropomyosin gene cause familial hypertrophic cardiomyopathy (FHC) linked to chromosome 15q2.

PMID 8523464 1995 Novel missense mutation in alpha-tropomyosin gene found in Japanese patients with hypertrophic cardiomyopathy.

PMID 7729014 1995 A de novo mutation in alpha-tropomyosin that causes hypertrophic cardiomyopathy.

PMID 25548289 2015 Mechanistic heterogeneity in contractile properties of α-tropomyosin (TPM1) mutants associated with inherited cardiomyopathies.

PMID 14734051 2004 Inducibility of life-threatening ventricular arrhythmias is related to maximum left ventricular thickness and clinical markers of sudden cardiac death in patients with hypertrophic cardiomyopathy attributable to the Asp175Asn mutation in the alpha-tropomyosin gene.

PMID 11606294 2001 Disease-causing mutations in cardiac troponin T: identification of a critical tropomyosin-binding region.

PMID 7898523 1995 Mutations in the genes for cardiac troponin T and alpha-tropomyosin in hypertrophic cardiomyopathy.

PMID 9822100 1998 The cardiac beta-myosin heavy chain gene is not the predominant gene for hypertrophic cardiomyopathy in the Finnish population.

PMID 10400910 1999 Mouse model of a familial hypertrophic cardiomyopathy mutation in alpha-tropomyosin manifests cardiac dysfunction.

PMID 22462493 2013 Two founder mutations in the alpha-tropomyosin and the cardiac myosin-binding protein C genes are common causes of hypertrophic cardiomyopathy in the Finnish population.

PMID 21310275 2011 Development and validation of a computational method for assessment of missense variants in hypertrophic cardiomyopathy.

PMID 24510615 2014 Distinguishing hypertrophic cardiomyopathy-associated mutations from background genetic noise.

PMID 23771913 2013 Deep basal inferoseptal crypts occur more commonly in patients with hypertrophic cardiomyopathy due to disease-causing myofilament mutations.

PMID 21551322 2011 Sarcomere gene mutations in isolated left ventricular noncompaction cardiomyopathy do not predict clinical phenotype.

PMID 26960954 2016 Next Generation Sequencing and Linkage Analysis for the Molecular Diagnosis of a Novel Overlapping Syndrome Characterized by Hypertrophic Cardiomyopathy and Typical Electrical Instability of Brugada Syndrome.

PMID 12860912 2003 Prevalence and spectrum of thin filament mutations in an outpatient referral population with hypertrophic cardiomyopathy.

PMID 27639548 2016 Multiplexed Reference Materials as Controls for Diagnostic Next-Generation Sequencing: A Pilot Investigating Applications for Hypertrophic Cardiomyopathy.

PMID 18409188 2008 A DNA resequencing array for pathogenic mutation detection in hypertrophic cardiomyopathy.

PMID 20031602 2009 Echocardiographic strain imaging to assess early and late consequences of sarcomere mutations in hypertrophic cardiomyopathy.

PMID 23700264 2013 A study of tropomyosin's role in cardiac function and disease using thin-filament reconstituted myocardium.

PMID 18403758 2008 Shared genetic causes of cardiac hypertrophy in children and adults.

PMID 25607779 2015 Coexistence of Digenic Mutations in Both Thin (TPM1) and Thick (MYH7) Filaments of Sarcomeric Genes Leads to Severe Hypertrophic Cardiomyopathy in a South Indian FHCM.

PMID 23204897 2012 Genetic variations of α-cardiac actin and cardiac muscle LIM protein in hypertrophic cardiomyopathy in South India.

PMID 27600940 2016 Targeted next-generation sequencing helps to decipher the genetic and phenotypic heterogeneity of hypertrophic cardiomyopathy.

PMID 28600229 2017 The structural basis of alpha-tropomyosin linked (Asp230Asn) familial dilated cardiomyopathy.

PMID 23539503 2013 Familial dilated cardiomyopathy mutations uncouple troponin I phosphorylation from changes in myofibrillar Ca²⁺ sensitivity.

PMID 20117437 2010 Familial dilated cardiomyopathy caused by an alpha-tropomyosin mutation: the distinctive natural history of sarcomeric dilated cardiomyopathy.

PMID 25242052 2014 An epidemiologic investigation of physical activity and breast cancer risk in Africa.

PMID 28603979 2017 Clinically Divergent Mutation Effects on the Structure and Function of the Human Cardiac Tropomyosin Overlap.

PMID 27532257 2017 Reassessment of Mendelian gene pathogenicity using 7,855 cardiomyopathy cases and 60,706 reference samples.

PMID 21835320 2011 Microvascular function is selectively impaired in patients with hypertrophic cardiomyopathy and sarcomere myofilament gene mutations.

PMID 25524337 2014 Clinical phenotype and outcome of hypertrophic cardiomyopathy associated with thin-filament gene mutations.

PMID 20965760 2011 Identification of a novel TPM1 mutation in a family with left ventricular noncompaction and sudden death.

PMID 22112859 2012 Prevalence and distribution of sarcomeric gene mutations in Japanese patients with familial hypertrophic cardiomyopathy.

PMID 18533079 2008 Myofilament protein gene mutation screening and outcome of patients with hypertrophic cardiomyopathy.

PMID 27177193 2016 Ebstein anomaly, left ventricular non-compaction, and early onset heart failure associated with a de novo α-tropomyosin gene mutation.

rs104894503 in TPM1 gene and Hypertrophic Cardiomyopathy PMID 21295541 2011 Several cardiomyopathy causing mutations on tropomyosin either destabilize the active state of actomyosin or alter the binding properties of tropomyosin.

PMID 21376702 2011 Hypertrophic cardiomyopathy-causing Asp175asn and Glu180gly Tpm1 mutations shift tropomyosin strands further towards the open position during the ATPase cycle.

PMID 22794249 2012 Long-range effects of familial hypertrophic cardiomyopathy mutations E180G and D175N on the properties of tropomyosin.

PMID 21320446 2011 Enhanced active cross-bridges during diastole: molecular pathogenesis of tropomyosin's HCM mutations.

PMID 9060904 1997 In contrast, prognosis reflected genotype; near normal life expectancy is found in hypertrophic cardiomyopathy caused by the alpha-tropomyosin mutation Asp175Asn.

PMID 8205619 1994 Alpha-tropomyosin and cardiac troponin T mutations cause familial hypertrophic cardiomyopathy: a disease of the sarcomere.

PMID 22462493 2013 Two founder mutations in the alpha-tropomyosin and the cardiac myosin-binding protein C genes are common causes of hypertrophic cardiomyopathy in the Finnish population.

PMID 7729014 1995 A de novo mutation in alpha-tropomyosin that causes hypertrophic cardiomyopathy.

PMID 22187526 2011 Facilitated cross-bridge interactions with thin filaments by familial hypertrophic cardiomyopathy mutations in α-tropomyosin.

PMID 22789852 2012 The flexibility of two tropomyosin mutants, D175N and E180G, that cause hypertrophic cardiomyopathy.

PMID 22155441 2012 The effect of the Asp175Asn and Glu180Gly TPM1 mutations on actin-myosin interaction during the ATPase cycle.

PMID 8523464 1995 Novel missense mutation in alpha-tropomyosin gene found in Japanese patients with hypertrophic cardiomyopathy.

PMID 10400910 1999 Mouse model of a familial hypertrophic cardiomyopathy mutation in alpha-tropomyosin manifests cardiac dysfunction.

PMID 14734051 2004 Inducibility of life-threatening ventricular arrhythmias is related to maximum left ventricular thickness and clinical markers of sudden cardiac death in patients with hypertrophic cardiomyopathy attributable to the Asp175Asn mutation in the alpha-tropomyosin gene.

PMID 12473556 2002 Genotype-phenotype correlative studies have implicated 8 particular mutations that cause hypertrophic cardiomyopathy (HCM) as "benign defects," associated with near-normal survival: N232S, G256E, F513C, V606M, R719Q, and L908V of beta-myosin heavy chain (MYH7); S179F of troponin T (TNNT2); and D175N of alpha-tropomyosin (TPM1).

PMID 16014439 2005 Cine MR imaging of myocardial contractile impairment in patients with hypertrophic cardiomyopathy attributable to Asp175Asn mutation in the alpha-tropomyosin gene.

PMID 9440709 1998 A mutant tropomyosin that causes hypertrophic cardiomyopathy is expressed in vivo and associated with an increased calcium sensitivity.

PMID 16504640 2006 Diastolic dysfunction without left ventricular hypertrophy is an early finding in children with hypertrophic cardiomyopathy-causing mutations in the beta-myosin heavy chain, alpha-tropomyosin, and myosin-binding protein C genes.

PMID 11136687 2001 Hypertrophic cardiomyopathy caused by a novel alpha-tropomyosin mutation (V95A) is associated with mild cardiac phenotype, abnormal calcium binding to troponin, abnormal myosin cycling, and poor prognosis.

PMID 25524337 2014 Clinical phenotype and outcome of hypertrophic cardiomyopathy associated with thin-filament gene mutations.

PMID 24510615 2014 Distinguishing hypertrophic cardiomyopathy-associated mutations from background genetic noise.

PMID 25241052 2014 Energy landscapes reveal the myopathic effects of tropomyosin mutations.

PMID 20031602 2009 Echocardiographic strain imaging to assess early and late consequences of sarcomere mutations in hypertrophic cardiomyopathy.

PMID 26960954 2016 Next Generation Sequencing and Linkage Analysis for the Molecular Diagnosis of a Novel Overlapping Syndrome Characterized by Hypertrophic Cardiomyopathy and Typical Electrical Instability of Brugada Syndrome.

PMID 21551322 2011 Sarcomere gene mutations in isolated left ventricular noncompaction cardiomyopathy do not predict clinical phenotype.

PMID 21310275 2011 Development and validation of a computational method for assessment of missense variants in hypertrophic cardiomyopathy.

PMID 16365313 2005 Structure of the mid-region of tropomyosin: bending and binding sites for actin.

PMID 18409188 2008 A DNA resequencing array for pathogenic mutation detection in hypertrophic cardiomyopathy.

PMID 12860912 2003 Prevalence and spectrum of thin filament mutations in an outpatient referral population with hypertrophic cardiomyopathy.

PMID 27532257 2017 Reassessment of Mendelian gene pathogenicity using 7,855 cardiomyopathy cases and 60,706 reference samples.

PMID 28615295 2017 Burden of Recurrent and Ancestral Mutations in Families With Hypertrophic Cardiomyopathy.

PMID 25611685 2015 Results of clinical genetic testing of 2,912 probands with hypertrophic cardiomyopathy: expanded panels offer limited additional sensitivity.

PMID 15249230 2004 Expression of a novel cardiac-specific tropomyosin isoform in humans.

PMID 21642532 2011 Evolutionarily conserved surface residues constitute actin binding sites of tropomyosin.

rs7162932 in TPM1 gene and Low density lipoprotein cholesterol measurement PMID 23063622 2012 Large-scale gene-centric meta-analysis across 32 studies identifies multiple lipid loci.

rs117267308 in TPM1 gene and Parkinson Disease PMID 27402877 2016 Identification of genetic modifiers of age-at-onset for familial Parkinson's disease.

rs3809566 in TPM1 gene and Platelet Count measurement PMID 22139419 2011 New gene functions in megakaryopoiesis and platelet formation.

rs1114167355 in TPM1 gene and Pulmonary Atresia with Intact Ventricular Septum PMID 28359939 2017 Tropomyosin 1: Multiple roles in the developing heart and in the formation of congenital heart defects.

rs12442826 in TPM1 gene and RDW - Red blood cell distribution width result PMID 30595370 2019 Leveraging Polygenic Functional Enrichment to Improve GWAS Power.

rs7166624 in TPM1 gene and Red Blood Cell Count measurement PMID 30595370 2019 Leveraging Polygenic Functional Enrichment to Improve GWAS Power.

rs12442826 in TPM1 gene and Red cell distribution width determination PMID 30595370 2019 Leveraging Polygenic Functional Enrichment to Improve GWAS Power.

rs7162932 in TPM1 gene and Serum LDL cholesterol measurement PMID 23063622 2012 Large-scale gene-centric meta-analysis across 32 studies identifies multiple lipid loci.

rs7162932 in TPM1 gene and Serum total cholesterol measurement PMID 23063622 2012 Large-scale gene-centric meta-analysis across 32 studies identifies multiple lipid loci.

rs1114167357 in TPM1 gene and Tetralogy of Fallot PMID 28359939 2017 Tropomyosin 1: Multiple roles in the developing heart and in the formation of congenital heart defects.