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TBX5 gene
Reviewed by Medicinsk Expert•Last updated: 2026-10-22•Gene

TBX5 gene

The TBX5 gene encodes a transcription factor essential for the development of the heart and upper limbs, and mutations in this gene cause Holt‑Oram syndrome.

Overview

The TBX5 gene provides instructions for making a protein called T-box 5 that plays an important role in the formation of tissues and organs during embryonic development. This protein regulates the activity of other genes by attaching (binding) to specific regions of DNA. On the basis of this action, the T-box 5 protein is called a transcription factor.

During embryonic development, the T-box 5 protein turns on (activates) genes involved in the normal development of the hands and arms (upper limbs). The T-box 5 protein also activates genes that play an important role in the growth and development of the heart. This protein appears to be particularly important for the formation of the wall (septum) that separates the right and left sides of the heart. The T-box 5 protein is also critical to the formation of the electrical system that coordinates contractions of the heart chambers.

Health Conditions Related to Genetic Changes

Holt‑Oram syndrome

More than 70 mutations in the TBX5 gene have been found to cause Holt‑Oram syndrome. Most of these mutations prevent the production of the T-box 5 protein. Other mutations change one of the protein building blocks (amino acids) used to make the T-box 5 protein. Researchers believe that a change in amino acids impairs the protein's ability to bind to DNA. As a result of TBX5 mutations, genes that are important for development of the heart and upper limbs are probably not activated. Abnormal development of the heart and upper limbs is characteristic of Holt‑Oram syndrome.

Other Names for This Gene

  • HOS
  • T-box transcription factor TBX5
  • TBX5_HUMAN

Additional Information & Resources

Tests Listed in the Genetic Testing Registry

  • Tests of TBX5

Scientific Articles on PubMed

  • PubMed

Catalog of Genes and Diseases from OMIM

  • T-BOX TRANSCRIPTION FACTOR 5; TBX5

Gene and Variant Databases

  • NCBI Gene
  • ClinVar

References

  • Cerbai E, Sartiani L. Holt-oram syndrome and atrial fibrillation: opening the (T)-box. Circ Res. 2008 Jun 6;102(11):1304-6. doi: 10.1161/CIRCRESAHA.108.178079. No abstract available. Citation on PubMed
  • Debeer P, Race V, Gewillig M, Devriendt K, Frijns JP. Novel TBX5 mutations in patients with Holt-Oram syndrome. Clin Orthop Relat Res. 2007 Sep;462:20-6. doi:10.1097/BLO.0b013e3181123ffe. Citation on PubMed
  • Hatcher CJ, McDermott DA. Using the TBX5 transcription factor to grow and sculpt the heart. Am J Med Genet A. 2006 Jul 1;140(13):1414-8. doi:10.1002/ajmg.a.31256. Citation on PubMed
  • McDermott DA, Bressan MC, He J, Lee JS, Aftimos S, Brueckner M, Gilbert F, Graham GE, Hannibal MC, Innis JW, Pierpont ME, Raas-Rothschild A, Shanske AL, Smith WE, Spencer RH, St John-Sutton MG, van Maldergem L, Waggoner DJ, Weber M, Basson CT. TBX5 genetic testing validates strict clinical criteria for Holt-Oram syndrome. Pediatr Res. 2005 Nov;58(5):981-6. doi:10.1203/01.PDR.0000182593.95441.64. Epub 2005 Sep 23. Citation on PubMed
  • Mori AD, Bruneau BG. TBX5 mutations and congenital heart disease: Holt-Oram syndrome revealed. Curr Opin Cardiol. 2004 May;19(3):211-5. doi:10.1097/00001573-200405000-00004. Citation on PubMed
  • Stennard FA, Harvey RP. T-box transcription factors and their roles in regulatory hierarchies in the developing heart. Development. 2005 Nov;132(22):4897-910. doi: 10.1242/dev.02099. Citation on PubMed

Genomic Location

The TBX5 gene is found on chromosome 12.

MEDICAL ENCYCLOPEDIA

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  • Genetics

Understanding Genetics

  • What is DNA?
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  • What is a gene variant and how do variants occur?

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Frequently Asked Questions

TBX5 mutations frequently affect the heart's electrical conduction system, leading to conditions such as atrioventricular block, where the electrical signal between the upper and lower chambers of the heart is delayed or blocked. Patients may also experience atrial fibrillation or other arrhythmias. Management typically involves regular cardiac monitoring, including electrocardiograms (ECGs) and potentially Holter monitors. In cases of significant conduction delay or block, the implantation of a permanent pacemaker may be necessary to maintain a safe heart rate.
Life expectancy for individuals with Holt-Oram syndrome varies significantly depending on the severity of the heart defects. Many individuals with mild cardiac involvement live normal lifespans, while those with severe structural heart defects or complex conduction issues may face greater health challenges. There are no specific universal lifestyle restrictions, but patients are generally advised to avoid extreme physical exertion if they have significant arrhythmias or structural defects. Regular follow-up with a cardiologist is essential to monitor for changes in heart function and to adjust treatment plans as needed.
Yes, it is possible to have Holt-Oram syndrome with cardiac involvement but no visible upper limb defects. While the hallmark of the condition is the combination of heart and hand anomalies, the expression of the genetic mutation is variable. Some individuals may present primarily with heart defects, such as atrial septal defects or conduction abnormalities, without the characteristic hand or arm malformations. This variability can sometimes make diagnosis more challenging if clinicians are not aware of the genetic link.
Holt-Oram syndrome is inherited in an autosomal dominant pattern, meaning only one copy of the altered TBX5 gene is needed to cause the condition. If one parent has the syndrome, there is a 50 percent chance with each pregnancy that the child will inherit the genetic change. However, because the severity of symptoms can vary widely even within the same family, genetic counseling is recommended to understand specific family risks and potential outcomes.
Source: MedlinePlus, National Library of Medicine

MedlinePlus brings together authoritative health information from the National Library of Medicine (NLM), the National Institutes of Health (NIH), and other government agencies and health-related organizations.

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