TBX5 (gene)

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TBX5
Protein TBX5 PDB 2X6U.png
Available structures
PDB Ortholog search: PDBe RCSB
Identifiers
Aliases TBX5, HOS, T-box 5
External IDs MGI: 102541 HomoloGene: 160 GeneCards: 6910
RNA expression pattern
PBB GE TBX5 207155 at tn.png

PBB GE TBX5 211886 s at tn.png
More reference expression data
Orthologs
Species Human Mouse
Entrez
Ensembl
UniProt
RefSeq (mRNA)

NM_181486
NM_000192
NM_080717
NM_080718

NM_011537

RefSeq (protein)

NP_000183.2
NP_542448.1
NP_852259.1

NP_035667.1

Location (UCSC) Chr 12: 114.35 – 114.41 Mb Chr 5: 119.83 – 119.89 Mb
PubMed search [1] [2]
Wikidata
View/Edit Human View/Edit Mouse

T-box transcription factor TBX5 is a protein that in humans is encoded by the TBX5 gene.[1][2][3]

This gene is a member of a phylogenetically conserved family of genes that share a common DNA-binding domain, the T-box. T-box genes encode transcription factors involved in the regulation of developmental processes. This gene is closely linked[clarification needed] to related family member T-box 3 (ulnar mammary syndrome) on human chromosome 12.

Function[edit]

The encoded protein may play a role in heart development and specification of limb identity. Mutations in this gene have been associated with Holt-Oram syndrome, a developmental disorder affecting the heart and upper limbs. Skeletally there may be abnormally bent fingers, sloping shoulders, and phocomelia. Cardiac defects include ventral and atrial septation and problems with the conduction system.[4] Several transcript variants encoding different isoforms have been described for this gene.[3]

Clinical significance[edit]

In studies done in mutant mice without the TBX5 gene it has been shown that the homozygous mice did not survive gestation due to the heart not developing past E9.5. Also the heterozygous mice were born with morphological problems such as enlarged hearts, atrial and ventral septum defects, and limb malformations similar to those found in the Holt-Oram Syndrome.[5] Supporting the essential role of TBX5 in the heart development.

Interactions[edit]

TBX5 (gene) has been shown to interact with:

Other Information[edit]

Tbx5 is a gene that is located on the long arm of chromosome 12.[8] Tbx5 produces a protein called T-box 5 that acts as a transcription factor.[9] The Tbx5 gene is involved with forelimb and heart development. This gene impacts the early development of the forelimb by triggering FGF-10 (Fibroblast Growth Factor 10).[10] Tbx5 is involved with the development of the four chambers in the heart, the electrical conducting system, and the septum separating the right and left sides of the heart.[11] A mutation in this gene can cause Holt-Oram syndrome or Amelia syndrome. Holt-Oram syndrome can cause several different defects. One effect of Holt-Oram syndrome is a hole in the septum.[12] Another symptom of this syndrome is bone abnormalities in the fingers, wrists, or arms.[13] An additional defect that Holt-Oram syndrome can cause is a conduction disease leading to abnormal heart rates and arrhythmias.[14] Amelia syndrome is a condition where forelimb malformation occurs because FGF-10 is not triggered due to Tbx5 mutations.[15] This condition can lead to the absence of one or both forelimbs.

References[edit]

  1. ^ Basson CT, Bachinsky DR, Lin RC, Levi T, Elkins JA, Soults J, Grayzel D, Kroumpouzou E, Traill TA, Leblanc-Straceski J, Renault B, Kucherlapati R, Seidman JG, Seidman CE (January 1997). "Mutations in human TBX5 [corrected] cause limb and cardiac malformation in Holt-Oram syndrome". Nat Genet 15 (1): 30–5. doi:10.1038/ng0197-30. PMID 8988165. 
  2. ^ Terrett JA, Newbury-Ecob R, Cross GS, Fenton I, Raeburn JA, Young ID, Brook JD (September 1994). "Holt-Oram syndrome is a genetically heterogeneous disease with one locus mapping to human chromosome 12q". Nat Genet 6 (4): 401–4. doi:10.1038/ng0494-401. PMID 8054982. 
  3. ^ a b "Entrez Gene: TBX5 T-box 5". 
  4. ^ Packham EA, Brook JD (2003). "T-box genes in human disorders". Hum. Mol. Genet. 12 (Spec No 1): R37–44. doi:10.1093/hmg/ddg077. PMID 12668595. 
  5. ^ Takeuchi JK, Ohgi M, Koshiba-Takeuchi K, Shiratori H, Sakaki I, Ogura K, Saijoh Y, Ogura T (2003). "Tbx5 specifies the left/right ventricles and ventricular septum position during cardiogenesis". Development 130 (24): 5953–64. doi:10.1242/dev.00797. PMID 14573514. 
  6. ^ a b Garg V, Kathiriya IS, Barnes R, Schluterman MK, King IN, Butler CA, Rothrock CR, Eapen RS, Hirayama-Yamada K, Joo K, Matsuoka R, Cohen JC, Srivastava D (July 2003). "GATA4 mutations cause human congenital heart defects and reveal an interaction with TBX5". Nature 424 (6947): 443–7. doi:10.1038/nature01827. PMID 12845333. 
  7. ^ Hiroi Y, Kudoh S, Monzen K, Ikeda Y, Yazaki Y, Nagai R, Komuro I (July 2001). "Tbx5 associates with Nkx2-5 and synergistically promotes cardiomyocyte differentiation". Nat. Genet. 28 (3): 276–80. doi:10.1038/90123. PMID 11431700. 
  8. ^ Patel, C.; Silcock, L.; Mcmullan, D.; Brueton, L. & Cox, H (15 February 2012). "TBX5 intragenic duplication: a family with an atypical Holt–Oram syndrome phenotype". European Journal of Human Genetics 20 (8): 863–869. doi:10.1038/ejhg.2012.16. 
  9. ^ Jhang, W. K.; Lee, B. H.; Kim, G.; Lee, J. & Yoo, H. "Clinical and molecular characterisation of Holt–Oram syndrome focusing on cardiac manifestations". Cardiology in the Young 25 (6): 1093–1098. doi:10.1017/s1047951114001656. 
  10. ^ Nishimoto, S.; Wilde, S.; Wood, S. & Logan, M. (2015). "RA Acts in a Coherent Feed-Forward Mechanism with Tbx5 to Control Limb Bud Induction and Initiation". Cell Reports 12 (5): 879–891. doi:10.1016/j.celrep.2015.06.068. 
  11. ^ Boogerd CJ, Evans SM (8 February 2016). "TBX5 and NuRD Divide the Heart". Developmental Cell 36 (3): 242–244. doi:10.1016/j.devcel.2016.01.015. PMID 26859347. 
  12. ^ Jhang, W. K.; Lee, B. H.; Kim, G.; Lee, J. & Yoo, H. "Clinical and molecular characterisation of Holt–Oram syndrome focusing on cardiac manifestations". Cardiology in the Young 25 (6): 1093–1098. doi:10.1017/s1047951114001656. 
  13. ^ Pizard, A.; Burgon, P. G.; Paul, D. L.; Bruneau, B. G.; Seidman, C. E. & Seidman, J. G. (2005). "Connexin 40, a Target of Transcription Factor Tbx5, Patterns Wrist, Digits, and Sternum". Molecular and Cellular Biology 25 (12): 5073–5083. doi:10.1128/mcb.25.12.5073-5083.2005. 
  14. ^ Patel, C.; Silcock, L.; Mcmullan, D.; Brueton, L. & Cox, H (15 February 2012). "TBX5 intragenic duplication: a family with an atypical Holt–Oram syndrome phenotype". European Journal of Human Genetics 20 (8): 863–869. doi:10.1038/ejhg.2012.16. 
  15. ^ Niemann, Stephan, MD (28 August 2007). "Tetra-Amelia Syndrome". Gene Reviews. PMID 20301453. 

Further reading[edit]

External links[edit]