''TBX5'' (gene)

TBX5
Available structures
PDBOrtholog search: PDBe RCSB
Identifiers
AliasesTBX5, HOS, T-box 5
External IDsMGI: 102541 HomoloGene: 160 GeneCards: TBX5
Gene location (Human)
Chr.Chromosome 12 (human)[1]
BandNo data availableStart114,353,931 bp[1]
End114,408,442 bp[1]
RNA expression pattern


More reference expression data
Orthologs
SpeciesHumanMouse
Entrez

6910

21388

Ensembl

ENSG00000089225

ENSMUSG00000018263

UniProt

Q99593

P70326

RefSeq (mRNA)

NM_181486
NM_000192
NM_080717
NM_080718

NM_011537

RefSeq (protein)

NP_000183
NP_542448
NP_852259

NP_035667

Location (UCSC)Chr 12: 114.35 – 114.41 MbChr 12: 119.83 – 119.89 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

T-box transcription factor TBX5 is a protein that in humans is encoded by the TBX5 gene.[5][6][7]

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 to related family member T-box 3 (ulnar mammary syndrome) on human chromosome 12.

Function

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.[8] Several transcript variants encoding different isoforms have been described for this gene.[7]

Clinical significance

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.[9] Supporting the essential role of TBX5 in the heart development.

Interactions

TBX5 (gene) has been shown to interact with:

Other information

Tbx5 is a gene that is located on the long arm of chromosome 12.[12] Tbx5 produces a protein called T-box 5 that acts as a transcription factor.[13] 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).[14] 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.[15] 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.[16] Another symptom of this syndrome is bone abnormalities in the fingers, wrists, or arms.[17] An additional defect that Holt-Oram syndrome can cause is a conduction disease leading to abnormal heart rates and arrhythmias.[18] Amelia syndrome is a condition where forelimb malformation occurs because FGF-10 is not triggered due to Tbx5 mutations.[19] This condition can lead to the absence of one or both forelimbs.

References

  1. 1 2 3 GRCh38: Ensembl release 89: ENSG00000089225 - Ensembl, May 2017
  2. 1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000018263 - Ensembl, May 2017
  3. ↑ "Human PubMed Reference:".
  4. ↑ "Mouse PubMed Reference:".
  5. ↑ 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. PMID 8988165. doi:10.1038/ng0197-30.
  6. ↑ 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. PMID 8054982. doi:10.1038/ng0494-401.
  7. 1 2 "Entrez Gene: TBX5 T-box 5".
  8. ↑ Packham EA, Brook JD (2003). "T-box genes in human disorders". Hum. Mol. Genet. 12 (Spec No 1): R37–44. PMID 12668595. doi:10.1093/hmg/ddg077.
  9. ↑ 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. PMID 14573514. doi:10.1242/dev.00797.
  10. 1 2 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. PMID 12845333. doi:10.1038/nature01827.
  11. ↑ 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. PMID 11431700. doi:10.1038/90123.
  12. ↑ 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. PMC 3400730 Freely accessible. PMID 22333898. doi:10.1038/ejhg.2012.16.
  13. ↑ 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.
  14. ↑ 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. PMC 4553633 Freely accessible. PMID 26212321. doi:10.1016/j.celrep.2015.06.068.
  15. ↑ Boogerd CJ, Evans SM (8 February 2016). "TBX5 and NuRD Divide the Heart". Developmental Cell. 36 (3): 242–244. PMID 26859347. doi:10.1016/j.devcel.2016.01.015.
  16. ↑ 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.
  17. ↑ 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. PMC 1140596 Freely accessible. PMID 15923624. doi:10.1128/mcb.25.12.5073-5083.2005.
  18. ↑ 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. PMC 3400730 Freely accessible. PMID 22333898. doi:10.1038/ejhg.2012.16.
  19. ↑ Niemann, Stephan, MD (28 August 2007). "Tetra-Amelia Syndrome". Gene Reviews. PMID 20301453.

Further reading

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