ArticleThe Journal of clinical investigation2017
Mutations in tropomyosin 4 underlie a rare form of human macrothrombocytopenia.
Article in The Journal of clinical investigation, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
41 citing papers in PubMed, 78 citations in OpenAlex.
- Hi-C informed kernel association test for integrating 3D genome structure into variant-set analysis.Briefings in bioinformatics · 2026Article
- Hemostatic and platelet proteins are associated with bleeding grade and time to major bleed in hemato-oncological patients.Blood vessels, thrombosis & hemostasis · 2026Article
- Knock-out of Tpm4.2/Actin Filaments Alters Neuronal Signaling, Neurite Outgrowth, and Behavioral Phenotypes in Mice.Molecular neurobiology · 2025Article
- Hi-C informed kernel association test: integrating 3-dimensional genome structure into variant-set association for whole-genome sequencing data.bioRxiv : the preprint server for biology · 2025Article
- α-Actinin-1 in Megakaryocytes: Its Structure, Interacting Proteins and Implications for Thrombopoiesis.Biomedicines · 2025Review
- Sparse matrix factorization robust to sample sharing across GWASs reveals interpretable genetic components.American journal of human genetics · 2025Article
- Leveraging local ancestry and cross-ancestry genetic architecture to improve genetic prediction of complex traits in admixed populations.American journal of human genetics · 2025Article
- Deciphering the omicron variant: integrated omics analysis reveals critical biomarkers and pathophysiological pathways.Journal of translational medicine · 2024Article
- Article
- Highly efficient platelet generation in lung vasculature reproduced by microfluidics.Nature communications · 2023Article
- Distinct actin-tropomyosin cofilament populations drive the functional diversification of cytoskeletal myosin motor complexes.iScience · 2022Article
- Don't you forget about me(gakaryocytes).Blood · 2022Article
- Genetics of inherited thrombocytopenias.Blood · 2022Review
- A novel nonsense variant in TPM4 caused dominant macrothrombocytopenia, mild bleeding tendency and disrupted cytoskeleton remodeling.Journal of thrombosis and haemostasis : JTH · 2022Article
- Article
- Essential role of zyxin in platelet biogenesis and glycoprotein Ib-IX surface expression.Cell death & disease · 2021Article
- Novel human cell expression method reveals the role and prevalence of posttranslational modification in nonmuscle tropomyosins.The Journal of biological chemistry · 2021Article
- The miR-133a, TPM4 and TAp63γ Role in Myocyte Differentiation Microfilament Remodelling and Colon Cancer Progression.International journal of molecular sciences · 2021Article
- Inherited Platelet Disorders: An Updated Overview.International journal of molecular sciences · 2021Review
- Learning the Ropes of Platelet Count Regulation: Inherited Thrombocytopenias.Journal of clinical medicine · 2021Review
Corrections and comments
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Authors and funding
30 authors at 9 institutions in 4 countries.
Funding
Abstract
Platelets are anuclear cells that are essential for blood clotting. They are produced by large polyploid precursor cells called megakaryocytes. Previous genome-wide association studies in nearly 70,000 individuals indicated that single nucleotide variants (SNVs) in the gene encoding the actin cytoskeletal regulator tropomyosin 4 (TPM4) exert an effect on the count and volume of platelets. Platelet number and volume are independent risk factors for heart attack and stroke. Here, we have identified 2 unrelated families in the BRIDGE Bleeding and Platelet Disorders (BPD) collection who carry a TPM4 variant that causes truncation of the TPM4 protein and segregates with macrothrombocytopenia, a disorder characterized by low platelet count. N-Ethyl-N-nitrosourea-induced (ENU-induced) missense mutations in Tpm4 or targeted inactivation of the Tpm4 locus led to gene dosage-dependent macrothrombocytopenia in mice. All other blood cell counts in Tpm4-deficient mice were normal. Insufficient TPM4 expression in human and mouse megakaryocytes resulted in a defect in the terminal stages of platelet production and had a mild effect on platelet function. Together, our findings demonstrate a nonredundant role for TPM4 in platelet biogenesis in humans and mice and reveal that truncating variants in TPM4 cause a previously undescribed dominant Mendelian platelet disorder.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.