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Target: TUBB1


Research on TUBB1

1. Target Summary:

TUBB1 (Tubulin Beta 1 Class VI) is a protein-coding gene that encodes a member of the beta-tubulin protein family. It plays a crucial role in microtubule formation, which is essential for various cellular processes, including cell division, intracellular transport, and maintaining cell shape. Mutations in TUBB1 have been associated with several diseases, including congenital hypothyroidism, thrombocytopenia, and neurodevelopmental disorders.

2. Mechanism:

TUBB1 is involved in the assembly of microtubules, which are dynamic structures composed of alpha- and beta-tubulin heterodimers. The proper functioning of TUBB1 is critical for microtubule stability and dynamics. Mutations in TUBB1 can lead to the formation of non-functional alpha/beta-tubulin dimers that cannot be incorporated into microtubules, disrupting microtubule integrity. For instance, TUBB1 mutations have been shown to impair thyroid hormone secretion and cause abnormal platelet physiology by affecting proplatelet formation and leading to macroplatelet formation (Stoupa et al., 2018; Wang et al., 2025). Additionally, specific single nucleotide polymorphisms (SNPs) in TUBB1, such as R307H, have been linked to altered microtubule dynamics, which can exacerbate conditions like hereditary thrombocytopenia (Basciano et al., 2015).

3. Approved Drugs:

Currently, there are no specific drugs approved that target TUBB1 directly. However, TUBB1 has been identified as a potential therapeutic target in various cancers, including breast cancer, where it is involved in pathways related to tumor progression (Ye, 2024).

4. Hypotheses:

  1. Microtubule Dysfunction Hypothesis: Mutations in TUBB1 disrupt normal microtubule dynamics, leading to cellular dysfunction that manifests as specific diseases such as congenital hypothyroidism and thrombocytopenia (Stoupa et al., 2018).
  2. Therapeutic Target Hypothesis: Targeting TUBB1 could provide therapeutic benefits in conditions characterized by microtubule dysfunction, such as certain cancers and hematological disorders (Ye, 2024).
  3. Polymorphism Impact Hypothesis: Specific polymorphisms in TUBB1 may influence individual susceptibility to diseases and the severity of symptoms, particularly in conditions like intracerebral hemorrhage (Navarro-Nunez et al., 2007).

5. Validation:

The role of TUBB1 in various diseases has been validated through genetic studies linking specific mutations to clinical phenotypes. For example, TUBB1 mutations have been shown to co-segregate with congenital hypothyroidism in affected families (Stoupa et al., 2018). Additionally, the association of TUBB1 polymorphisms with increased risk of intracerebral hemorrhage has been documented, providing further validation of its role in disease (Navarro-Nunez et al., 2007).

6. Clinical Trials:

While there are no specific clinical trials targeting TUBB1 directly, ongoing research is exploring its role in various diseases, including cancer. Studies are investigating the potential of TUBB1 as a biomarker for prognosis and treatment response in breast cancer (Ye, 2024).

7. Involved Pathways:

TUBB1 is involved in several critical cellular pathways, including:
  • Microtubule Dynamics: Essential for cell division and intracellular transport.
  • Cell Signaling Pathways: TUBB1 expression has been linked to pathways involved in immune response and cellular metabolism (Chen et al., 2024).
  • Tumor Progression Pathways: In cancer, TUBB1 is associated with pathways that regulate cell migration and invasion (Ye, 2024).

8. Associated Genes:

TUBB1 interacts with several other genes involved in microtubule dynamics and cellular processes, including:
  • TUBA1A: Alpha-tubulin gene that forms heterodimers with TUBB1.
  • TUBB2A, TUBB3: Other beta-tubulin isotypes that may compensate for TUBB1 dysfunction.
  • MYH9: Associated with thrombocytopenia and linked to TUBB1 mutations (Balduini & Savoia, 2012).

9. Target Expression:

TUBB1 is expressed in various tissues, with significant expression in the developing and adult thyroid, as well as in megakaryocytes and platelets (Stoupa et al., 2018). Its expression levels can vary based on developmental stages and pathological conditions.

10. Additional Context:

TUBB1 mutations have been implicated in a range of disorders, highlighting its importance in both developmental and adult physiology. Understanding the functional consequences of TUBB1 mutations can provide insights into the underlying mechanisms of associated diseases and inform potential therapeutic strategies.

11. References:

  • Stoupa, A., Adam, F., & Kariyawasam, D. (2018). TUBB1 mutations cause thyroid dysgenesis associated with abnormal platelet physiology. EMBO Molecular Medicine, PMID: 30446499.
  • Wang, F., Sun, C., & Wang, Y. (2025). Genetic and functional analysis of TUBB1 variants in congenital hypothyroidism. Endokrynologia Polska, PMID: 40071799.
  • Basciano, P. A., Matakas, J., & Pecci, A. (2015). beta-1 tubulin R307H SNP alters microtubule dynamics and affects severity of a hereditary thrombocytopenia. Journal of Thrombosis and Haemostasis, PMID: 25529050.
  • Navarro-Nunez, L., Lozano, M. L., & Rivera, J. (2007). The association of the beta1-tubulin Q43P polymorphism with intracerebral hemorrhage in men. Haematologica, PMID: 17488662.
  • Ye, C. (2024). Exploring the role of aggrephagy-related signatures in immune microenvironment, prognosis, and therapeutic strategies of breast cancer. Medicine, PMID: 39432642.
  • Chen, J., Xu, J., & Gou, L. (2024). Integrating transcriptomic and proteomic data for a comprehensive molecular perspective on the association between sarcopenia and osteoporosis. Archives of Gerontology and Geriatrics, PMID: 38761527.
  • Balduini, C. L., & Savoia, A. (2012). Genetics of familial forms of thrombocytopenia. Human Genetics, PMID: 22886561.