TBX5 (gene)

TBX5
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 2X6U, 2X6V, 4S0H, 5BQD
Identifiers
Aliases	TBX5, HOS, T-box 5, T-box transcription factor 5
External IDs	OMIM: 601620 MGI: 102541 HomoloGene: 160 GeneCards: TBX5
Gene location (Human) Chr. Chromosome 12 (human)[1] Band 12q24.21 Start 114,353,911 bp[1] End 114,408,442 bp[1]
Gene location (Mouse) Chr. Chromosome 5 (mouse)[2] Band 5 F|5 60.42 cM Start 119,832,668 bp[2] End 119,885,219 bp[2]
RNA expression pattern Bgee Top expressed in tendon upper lobe of lung visceral pleura myocardium right lung right ventricle heart More reference expression data BioGPS More reference expression data
Gene ontology Molecular function sequence-specific DNA binding RNA polymerase II transcription regulatory region sequence-specific DNA binding GO:0001077, GO:0001212, GO:0001213, GO:0001211, GO:0001205 DNA-binding transcription activator activity, RNA polymerase II-specific transcription factor binding GO:0001948 protein binding GO:0001131, GO:0001151, GO:0001130, GO:0001204 DNA-binding transcription factor activity DNA binding GO:0000980 RNA polymerase II cis-regulatory region sequence-specific DNA binding GO:0001200, GO:0001133, GO:0001201 DNA-binding transcription factor activity, RNA polymerase II-specific Cellular component nucleoplasm nucleus protein-containing complex protein-DNA complex cytoplasm Biological process pattern specification process forelimb morphogenesis ventricular cardiac muscle tissue development regulation of transcription, DNA-templated bundle of His development lung development endocardial cushion development cardiac muscle cell differentiation cell-cell signaling transcription, DNA-templated morphogenesis of an epithelium atrial septum morphogenesis multicellular organism development negative regulation of cell migration positive regulation of cardiac muscle cell proliferation atrioventricular valve morphogenesis cell migration involved in coronary vasculogenesis embryonic limb morphogenesis pericardium development positive regulation of cardioblast differentiation positive regulation of secondary heart field cardioblast proliferation transcription initiation from RNA polymerase II promoter negative regulation of cardiac muscle cell proliferation atrial septum development embryonic forelimb morphogenesis negative regulation of epithelial to mesenchymal transition negative regulation of cell population proliferation cardiac left ventricle formation ventricular septum development heart development positive regulation of transcription, DNA-templated positive regulation of transcription by RNA polymerase II Sources:Amigo / QuickGO
Orthologs
Species	Human	Mouse
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 Mb	Chr 5: 119.83 – 119.89 Mb
PubMed search	[3]	[4]
Wikidata
View/Edit Human View/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^{[clarification needed]} to related family member T-box 3 (ulnar mammary syndrome) on human chromosome 12.

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.^[10] This gene impacts the early development of the forelimb by triggering fibroblast growth factor, FGF10.^[11]

Function[]

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.^[12] The Tbx5 gene is a transcription factor that codes for the protein called T-box 5. Along with playing roles in the development of the heart, septum, and electrical system of the heart, it also activates genes that are involved in the development of the upper limbs, the arms and hands. This gene is involved in patterning major aspects of the heart; however, it is also involved in the muscle connective tissue for muscle and tendon patterning. A study showed that deletion of Tbx5 in forelimbs causes disruption in the muscle and tendon patterning without affecting the skeletons development.^[13] Tbx5 expression is in the cells of the lateral plate mesoderm which form the forelimb bud and the cascade of limb initiation. In its absence no forelimb bud forms. Diseases and defects associated with this gene are Holt-Oram syndrome, both have to do with limb defects and several other abnormalities. The cardiac defects include defects in the septum dividing the left and right sides of the heart, conduction system abnormalities, and other problems. The exact mechanism that Tbx5 activates gene expression is still being discovered and is actively being understood.

Clinical significance[]

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.^[10][14] Skeletally there may be abnormally bent fingers, sloping shoulders, and phocomelia. Cardiac defects include ventral and atrial septation and problems with the conduction system.^[15] Several transcript variants encoding different isoforms have been described for this gene.^[7]

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 embryonic day 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.^[16] Supporting the essential role of TBX5 in the heart development.

The encoded protein plays a major role in limb development, specifically during limb bud initiation.^[17] For instance, in chickens Tbx5 specifies forelimb status.^[18] The activation of Tbx5 and other T-box proteins by Hox genes activates signaling cascades that involve the Wnt signaling pathway and FGF signals in limb buds.^[17] Ultimately, Tbx5 leads to the development of apical ectodermal ridge (AER) and zone of polarizing activity (ZPA) signaling centers in the developing limb bud, which specify the orientation growth of the developing limb.^[17] Together with Tbx4, Tbx5 plays a role in patterning the soft tissues (muscles and tendons) of the musculoskeletal system.^[19]

A mutation in this gene can cause Holt-Oram syndrome or Amelia syndrome.^[10] Holt-Oram syndrome can cause several different defects. One effect of Holt-Oram syndrome is a hole in the septum.^[9] Another symptom of this syndrome is bone abnormalities in the fingers, wrists, or arms.^[20] An additional defect that Holt-Oram syndrome can cause is a conduction disease leading to abnormal heart rates and arrhythmias.^[8] Amelia syndrome is a condition where forelimb malformation occurs because FGF-10 is not triggered due to Tbx5 mutations.^[21] This condition can lead to the absence of one or both forelimbs.

Interactions[]

TBX5 (gene) has been shown to interact with:

• GATA4^[22] and
• NKX2-5.^[22][23]

References[]

^[1]

Further reading[]

External links[]

• GeneReviews/NCBI/NIH/UW entry on Holt-Oram Syndrome
• TBX5+protein,+human at the US National Library of Medicine Medical Subject Headings (MeSH)