TBX5 (gene): Difference between revisions

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{{DISPLAYTITLE:''TBX5'' (gene)}}
{{PBB_Controls
{{Infobox gene}}
| update_page = yes
'''T-box transcription factor TBX5''' is a [[protein]] that in humans is encoded by the ''TBX5'' [[gene]].<ref name="pmid8988165">{{cite journal | vauthors = 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 | title = Mutations in human TBX5 [corrected] cause limb and cardiac malformation in Holt-Oram syndrome | journal = Nat Genet | volume = 15 | issue = 1 | pages = 30–5 |date=January 1997 | pmid = 8988165 | pmc =  | doi = 10.1038/ng0197-30 }}</ref><ref name="pmid8054982">{{cite journal | vauthors = Terrett JA, Newbury-Ecob R, Cross GS, Fenton I, Raeburn JA, Young ID, Brook JD | title = Holt-Oram syndrome is a genetically heterogeneous disease with one locus mapping to human chromosome 12q | journal = Nat Genet | volume = 6 | issue = 4 | pages = 401–4 |date=September 1994 | pmid = 8054982 | pmc = | doi = 10.1038/ng0494-401 }}</ref><ref name="entrez">{{cite web | title = Entrez Gene: TBX5 T-box 5| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=6910| accessdate = }}</ref>
| require_manual_inspection = no
| update_protein_box = yes
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| update_citations = yes
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<!-- The GNF_Protein_box is automatically maintained by Protein Box Bot. See Template:PBB_Controls to Stop updates. -->
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{{clarify|date=April 2013}} to related family member T-box 3 (ulnar mammary syndrome) on human chromosome 12.
{{GNF_Protein_box
| image = 
| image_source = 
| PDB =
| Name = T-box 5
| HGNCid = 11604
| Symbol = TBX5
| AltSymbols =; HOS
| OMIM = 601620
| ECnumber = 
| Homologene = 160
| MGIid = 102541
| GeneAtlas_image1 = PBB_GE_TBX5_211886_s_at_tn.png
| GeneAtlas_image2 = PBB_GE_TBX5_207155_at_tn.png
| Function = {{GNF_GO|id=GO:0003700 |text = transcription factor activity}} {{GNF_GO|id=GO:0003702 |text = RNA polymerase II transcription factor activity}} {{GNF_GO|id=GO:0005515 |text = protein binding}}
| Component = {{GNF_GO|id=GO:0005634 |text = nucleus}}
| Process = {{GNF_GO|id=GO:0002009 |text = morphogenesis of an epithelium}} {{GNF_GO|id=GO:0006350 |text = transcription}} {{GNF_GO|id=GO:0006355 |text = regulation of transcription, DNA-dependent}} {{GNF_GO|id=GO:0007389 |text = pattern specification process}} {{GNF_GO|id=GO:0007507 |text = heart development}} {{GNF_GO|id=GO:0030324 |text = lung development}} {{GNF_GO|id=GO:0030326 |text = embryonic limb morphogenesis}} {{GNF_GO|id=GO:0045944 |text = positive regulation of transcription from RNA polymerase II promoter}}
  | Orthologs = {{GNF_Ortholog_box
    | Hs_EntrezGene = 6910
    | Hs_Ensembl = ENSG00000089225
    | Hs_RefseqProtein = NP_000183
    | Hs_RefseqmRNA = NM_000192
    | Hs_GenLoc_db =
    | Hs_GenLoc_chr = 12
    | Hs_GenLoc_start = 113276119
    | Hs_GenLoc_end = 113330630
    | Hs_Uniprot = Q99593
    | Mm_EntrezGene = 21388
    | Mm_Ensembl = ENSMUSG00000018263
    | Mm_RefseqmRNA = NM_011537
    | Mm_RefseqProtein = NP_035667
    | Mm_GenLoc_db = 
    | Mm_GenLoc_chr = 5
    | Mm_GenLoc_start = 120095280
    | Mm_GenLoc_end = 120145102
    | Mm_Uniprot = Q5CZX7
  }}
}}
'''T-box 5''', also known as '''TBX5''', is a human [[gene]].<ref name="entrez">{{cite web | title = Entrez Gene: TBX5 T-box 5| url = http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=6910| accessdate = }}</ref>


<!-- The PBB_Summary template is automatically maintained by Protein Box Bot.  See Template:PBB_Controls to Stop updates. -->
== Function ==
{{PBB_Summary
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.<ref name="pmid12668595">{{cite journal | vauthors = Packham EA, Brook JD | title = T-box genes in human disorders | journal = Hum. Mol. Genet. | volume = 12 | issue = Spec No 1 | pages = R37–44 | year = 2003 | pmid = 12668595 | doi =  10.1093/hmg/ddg077}}</ref> Several transcript variants encoding different isoforms have been described for this gene.<ref name="entrez" />
| section_title =  
 
| summary_text = 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. 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. Several transcript variants encoding different isoforms have been described for this gene.<ref name="entrez">{{cite web | title = Entrez Gene: TBX5 T-box 5| url = http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=6910| accessdate = }}</ref>
== 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.<ref name="pmid14573514">{{cite journal | vauthors = Takeuchi JK, Ohgi M, Koshiba-Takeuchi K, Shiratori H, Sakaki I, Ogura K, Saijoh Y, Ogura T | title = Tbx5 specifies the left/right ventricles and ventricular septum position during cardiogenesis | journal = Development | volume = 130 | issue = 24 | pages = 5953–64 | year = 2003 | pmid = 14573514 | doi = 10.1242/dev.00797 }}</ref> Supporting the essential role of TBX5 in the heart development.
 
==Interactions==
TBX5 (gene) has been shown to [[Protein-protein interaction|interact]] with:
* [[GATA4]]<ref name = pmid12845333>{{cite journal | date = July 2003 | vauthors = 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 | title = GATA4 mutations cause human congenital heart defects and reveal an interaction with TBX5 | journal = Nature | volume = 424 | issue = 6947 | pages = 443–7 | pmid = 12845333 | doi = 10.1038/nature01827}}</ref>  and
* [[NKX2-5]].<ref name = pmid12845333/><ref name = pmid11431700>{{cite journal | date = July 2001 | vauthors = Hiroi Y, Kudoh S, Monzen K, Ikeda Y, Yazaki Y, Nagai R, Komuro I | title = Tbx5 associates with Nkx2-5 and synergistically promotes cardiomyocyte differentiation | journal = Nat. Genet. | volume = 28 | issue = 3 | pages = 276–80 | pmid = 11431700 | doi = 10.1038/90123}}</ref>
 
==Other information==
Tbx5 is a gene that is located on the long arm of chromosome 12.<ref>{{cite journal|author=Patel, C.|author2=Silcock, L.|author3=Mcmullan, D.|author4=Brueton, L.|author5=Cox, H|last-author-amp=yes|title=TBX5 intragenic duplication: a family with an atypical Holt–Oram syndrome phenotype|journal=European Journal of Human Genetics|date=15 February 2012|volume=20|issue=8|pages=863–869|doi=10.1038/ejhg.2012.16|pmid=22333898|pmc=3400730}}<!--|accessdate=10 April 2016--></ref> Tbx5 produces a protein called T-box 5 that acts as a transcription factor.<ref>{{cite journal|author=Jhang, W. K.|author2=Lee, B. H.|author3=Kim, G.|author4=Lee, J.|author5=Yoo, H|last-author-amp=yes|title=Clinical and molecular characterisation of Holt–Oram syndrome focusing on cardiac manifestations|journal=Cardiology in the Young|volume=25|issue=6|pages=1093–1098|doi=10.1017/s1047951114001656}}<!--|accessdate=10 April 2016--></ref> 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).<ref>{{cite journal|author=Nishimoto, S.|author2=Wilde, S.|author3=Wood, S.|author4=Logan, M.|last-author-amp=yes|title=RA Acts in a Coherent Feed-Forward Mechanism with Tbx5 to Control Limb Bud Induction and Initiation|journal=Cell Reports|date=2015|volume=12|issue=5|pages=879–891|doi=10.1016/j.celrep.2015.06.068|pmid=26212321|pmc=4553633}}</ref> 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.<ref>{{cite journal|vauthors=Boogerd CJ, Evans SM|title=TBX5 and NuRD Divide the Heart|journal=Developmental Cell|date=8 February 2016|volume=36|issue=3|pages=242–244|doi=10.1016/j.devcel.2016.01.015|pmid=26859347}}<!--|accessdate=10 April 2016--></ref> 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.<ref>{{cite journal|author=Jhang, W. K.|author2=Lee, B. H.|author3=Kim, G.|author4=Lee, J.|author5=Yoo, H|last-author-amp=yes|title=Clinical and molecular characterisation of Holt–Oram syndrome focusing on cardiac manifestations|journal=Cardiology in the Young|volume=25|issue=6|pages=1093–1098|doi=10.1017/s1047951114001656}}<!--|accessdate=10 April 2016--></ref> Another symptom of this syndrome is bone abnormalities in the fingers, wrists, or arms.<ref>{{cite journal|author=Pizard, A.|author2=Burgon, P. G.|author3=Paul, D. L.|author4=Bruneau, B. G.|author5=Seidman, C. E.|author6=Seidman, J. G.|last-author-amp=yes|title=Connexin 40, a Target of Transcription Factor Tbx5, Patterns Wrist, Digits, and Sternum|journal=Molecular and Cellular Biology|date=2005|volume=25|issue=12|pages=5073–5083|doi=10.1128/mcb.25.12.5073-5083.2005|pmid=15923624|pmc=1140596}}<!--|accessdate=10 April 2016--></ref> An additional defect that Holt-Oram syndrome can cause is a conduction disease leading to abnormal heart rates and arrhythmias.<ref>{{cite journal|author=Patel, C.|author2=Silcock, L.|author3=Mcmullan, D.|author4=Brueton, L.|author5=Cox, H|last-author-amp=yes|title=TBX5 intragenic duplication: a family with an atypical Holt–Oram syndrome phenotype|journal=European Journal of Human Genetics|date=15 February 2012|volume=20|issue=8|pages=863–869|doi=10.1038/ejhg.2012.16|pmid=22333898|pmc=3400730}}<!--|accessdate=10 April 2016--></ref> Amelia syndrome is a condition where forelimb malformation occurs because FGF-10 is not triggered due to Tbx5 mutations.<ref>{{cite journal|last1=Niemann|first1=Stephan, MD|title=Tetra-Amelia Syndrome|journal=Gene Reviews|date=28 August 2007|pmid=20301453}}<!--|accessdate=10 April 2016--></ref> This condition can lead to the absence of one or both forelimbs.


==References==
==References==
{{reflist|2}}
{{Reflist}}
 
==Further reading==
==Further reading==
{{refbegin | 2}}
{{Refbegin | 2}}
{{PBB_Further_reading
*{{cite journal  | author=Simon H |title=T-box genes and the formation of vertebrate forelimb- and hindlimb specific pattern |journal=Cell Tissue Res. |volume=296 |issue= 1 |pages= 57–66 |year= 1999 |pmid= 10199965 |doi=10.1007/s004410051266 }}
| citations =
*{{cite journal  | vauthors=Packham EA, Brook JD |title=T-box genes in human disorders |journal=Hum. Mol. Genet. |volume=12 |issue= Spec No 1|pages= R37–44 |year= 2003 |pmid= 12668595 |doi=10.1093/hmg/ddg077  }}
*{{cite journal  | author=Simon H |title=T-box genes and the formation of vertebrate forelimb- and hindlimb specific pattern. |journal=Cell Tissue Res. |volume=296 |issue= 1 |pages= 57-66 |year= 1999 |pmid= 10199965 |doi=  }}
*{{cite journal   |vauthors=Li QY, Newbury-Ecob RA, Terrett JA, etal |title=Holt-Oram syndrome is caused by mutations in TBX5, a member of the Brachyury (T) gene family |journal=Nat. Genet. |volume=15 |issue= 1 |pages= 21–9 |year= 1997 |pmid= 8988164 |doi= 10.1038/ng0197-21 }}
*{{cite journal  | author=Packham EA, Brook JD |title=T-box genes in human disorders. |journal=Hum. Mol. Genet. |volume=12 Spec No 1 |issue=  |pages= R37-44 |year= 2003 |pmid= 12668595 |doi=  }}
*{{cite journal   |vauthors=Basson CT, Huang T, Lin RC, etal |title=Different TBX5 interactions in heart and limb defined by Holt-Oram syndrome mutations |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=96 |issue= 6 |pages= 2919–24 |year= 1999 |pmid= 10077612 |doi=10.1073/pnas.96.6.2919  | pmc=15870 }}
*{{cite journal  | author=Terrett JA, Newbury-Ecob R, Cross GS, ''et al.'' |title=Holt-Oram syndrome is a genetically heterogeneous disease with one locus mapping to human chromosome 12q. |journal=Nat. Genet. |volume=6 |issue= 4 |pages= 401-4 |year= 1994 |pmid= 8054982 |doi= 10.1038/ng0494-401 }}
*{{cite journal   |vauthors=Yang J, Hu D, Xia J, etal |title=Three novel TBX5 mutations in Chinese patients with Holt-Oram syndrome |journal=Am. J. Med. Genet. |volume=92 |issue= 4 |pages= 237–40 |year= 2000 |pmid= 10842287 |doi=10.1002/(SICI)1096-8628(20000605)92:4<237::AID-AJMG2>3.0.CO;2-G }}
*{{cite journal | author=Li QY, Newbury-Ecob RA, Terrett JA, ''et al.'' |title=Holt-Oram syndrome is caused by mutations in TBX5, a member of the Brachyury (T) gene family. |journal=Nat. Genet. |volume=15 |issue= 1 |pages= 21-9 |year= 1997 |pmid= 8988164 |doi= 10.1038/ng0197-21 }}
*{{cite journal   |vauthors=Hatcher CJ, Goldstein MM, Mah CS, etal |title=Identification and localization of TBX5 transcription factor during human cardiac morphogenesis |journal=Dev. Dyn. |volume=219 |issue= 1 |pages= 90–5 |year= 2000 |pmid= 10974675 |doi= 10.1002/1097-0177(200009)219:1<90::AID-DVDY1033>3.0.CO;2-L }}
*{{cite journal | author=Basson CT, Bachinsky DR, Lin RC, ''et al.'' |title=Mutations in human TBX5 [corrected] cause limb and cardiac malformation in Holt-Oram syndrome. |journal=Nat. Genet. |volume=15 |issue= 1 |pages= 30-5 |year= 1997 |pmid= 8988165 |doi= 10.1038/ng0197-30 }}
*{{cite journal   |vauthors=Hatcher CJ, Kim MS, Mah CS, etal |title=TBX5 transcription factor regulates cell proliferation during cardiogenesis |journal=Dev. Biol. |volume=230 |issue= 2 |pages= 177–88 |year= 2001 |pmid= 11161571 |doi= 10.1006/dbio.2000.0134 }}
*{{cite journal  | author=Basson CT, Huang T, Lin RC, ''et al.'' |title=Different TBX5 interactions in heart and limb defined by Holt-Oram syndrome mutations. |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=96 |issue= 6 |pages= 2919-24 |year= 1999 |pmid= 10077612 |doi=  }}
*{{cite journal   |vauthors=Cross SJ, Ching YH, Li QY, etal |title=The mutation spectrum in Holt-Oram syndrome |journal=J. Med. Genet. |volume=37 |issue= 10 |pages= 785–7 |year= 2001 |pmid= 11183182 |doi=10.1136/jmg.37.10.785  | pmc=1757164 }}
*{{cite journal | author=Yang J, Hu D, Xia J, ''et al.'' |title=Three novel TBX5 mutations in Chinese patients with Holt-Oram syndrome. |journal=Am. J. Med. Genet. |volume=92 |issue= 4 |pages= 237-40 |year= 2000 |pmid= 10842287 |doi=  }}
*{{cite journal   |vauthors=Hiroi Y, Kudoh S, Monzen K, etal |title=Tbx5 associates with Nkx2-5 and synergistically promotes cardiomyocyte differentiation |journal=Nat. Genet. |volume=28 |issue= 3 |pages= 276–80 |year= 2001 |pmid= 11431700 |doi= 10.1038/90123 }}
*{{cite journal | author=Hatcher CJ, Goldstein MM, Mah CS, ''et al.'' |title=Identification and localization of TBX5 transcription factor during human cardiac morphogenesis. |journal=Dev. Dyn. |volume=219 |issue= 1 |pages= 90-5 |year= 2000 |pmid= 10974675 |doi= 10.1002/1097-0177(200009)219:1<90::AID-DVDY1033>3.0.CO;2-L }}
*{{cite journal  | vauthors=Akrami SM, Winter RM, Brook JD, Armour JA |title=Detection of a large TBX5 deletion in a family with Holt-Oram syndrome |journal=J. Med. Genet. |volume=38 |issue= 12 |pages= E44 |year= 2002 |pmid= 11748310 |doi=10.1136/jmg.38.12.e44  | pmc=1734777 }}
*{{cite journal | author=Hatcher CJ, Kim MS, Mah CS, ''et al.'' |title=TBX5 transcription factor regulates cell proliferation during cardiogenesis. |journal=Dev. Biol. |volume=230 |issue= 2 |pages= 177-88 |year= 2001 |pmid= 11161571 |doi= 10.1006/dbio.2000.0134 }}
*{{cite journal   |vauthors=He ML, Chen Y, Peng Y, etal |title=Induction of apoptosis and inhibition of cell growth by developmental regulator hTBX5 |journal=Biochem. Biophys. Res. Commun. |volume=297 |issue= 2 |pages= 185–92 |year= 2002 |pmid= 12237100 |doi=10.1016/S0006-291X(02)02142-3 }}
*{{cite journal | author=Cross SJ, Ching YH, Li QY, ''et al.'' |title=The mutation spectrum in Holt-Oram syndrome. |journal=J. Med. Genet. |volume=37 |issue= 10 |pages= 785-7 |year= 2001 |pmid= 11183182 |doi=  }}
*{{cite journal   |vauthors=Strausberg RL, Feingold EA, Grouse LH, etal |title=Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=99 |issue= 26 |pages= 16899–903 |year= 2003 |pmid= 12477932 |doi= 10.1073/pnas.242603899 | pmc=139241 }}
*{{cite journal | author=Hiroi Y, Kudoh S, Monzen K, ''et al.'' |title=Tbx5 associates with Nkx2-5 and synergistically promotes cardiomyocyte differentiation. |journal=Nat. Genet. |volume=28 |issue= 3 |pages= 276-80 |year= 2001 |pmid= 11431700 |doi= 10.1038/90123 }}
*{{cite journal  | vauthors=Fan C, Liu M, Wang Q |title=Functional analysis of TBX5 missense mutations associated with Holt-Oram syndrome |journal=J. Biol. Chem. |volume=278 |issue= 10 |pages= 8780–5 |year= 2003 |pmid= 12499378 |doi= 10.1074/jbc.M208120200 | pmc=1579789 }}
*{{cite journal  | author=Akrami SM, Winter RM, Brook JD, Armour JA |title=Detection of a large TBX5 deletion in a family with Holt-Oram syndrome. |journal=J. Med. Genet. |volume=38 |issue= 12 |pages= E44 |year= 2002 |pmid= 11748310 |doi=  }}
*{{cite journal   |vauthors=Garg V, Kathiriya IS, Barnes R, etal |title=GATA4 mutations cause human congenital heart defects and reveal an interaction with TBX5 |journal=Nature |volume=424 |issue= 6947 |pages= 443–7 |year= 2003 |pmid= 12845333 |doi= 10.1038/nature01827 }}
*{{cite journal | author=He ML, Chen Y, Peng Y, ''et al.'' |title=Induction of apoptosis and inhibition of cell growth by developmental regulator hTBX5. |journal=Biochem. Biophys. Res. Commun. |volume=297 |issue= 2 |pages= 185-92 |year= 2002 |pmid= 12237100 |doi=  }}
*{{cite journal   |vauthors=Huang T, Lock JE, Marshall AC, etal |title=Causes of clinical diversity in human TBX5 mutations |journal=Cold Spring Harb. Symp. Quant. Biol. |volume=67 |issue=  |pages= 115–20 |year= 2003 |pmid= 12858531 |doi=10.1101/sqb.2002.67.115 }}
*{{cite journal | author=Strausberg RL, Feingold EA, Grouse LH, ''et al.'' |title=Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences. |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=99 |issue= 26 |pages= 16899-903 |year= 2003 |pmid= 12477932 |doi= 10.1073/pnas.242603899 }}
*{{cite journal   |vauthors=Collavoli A, Hatcher CJ, He J, etal |title=TBX5 nuclear localization is mediated by dual cooperative intramolecular signals |journal=J. Mol. Cell. Cardiol. |volume=35 |issue= 10 |pages= 1191–5 |year= 2004 |pmid= 14519429 |doi=10.1016/S0022-2828(03)00231-1  }}
*{{cite journal  | author=Fan C, Liu M, Wang Q |title=Functional analysis of TBX5 missense mutations associated with Holt-Oram syndrome. |journal=J. Biol. Chem. |volume=278 |issue= 10 |pages= 8780-5 |year= 2003 |pmid= 12499378 |doi= 10.1074/jbc.M208120200 }}
{{Refend}}
*{{cite journal | author=Garg V, Kathiriya IS, Barnes R, ''et al.'' |title=GATA4 mutations cause human congenital heart defects and reveal an interaction with TBX5. |journal=Nature |volume=424 |issue= 6947 |pages= 443-7 |year= 2003 |pmid= 12845333 |doi= 10.1038/nature01827 }}
 
*{{cite journal | author=Huang T, Lock JE, Marshall AC, ''et al.'' |title=Causes of clinical diversity in human TBX5 mutations. |journal=Cold Spring Harb. Symp. Quant. Biol. |volume=67 |issue=  |pages= 115-20 |year= 2003 |pmid= 12858531 |doi=  }}
==External links==
*{{cite journal | author=Collavoli A, Hatcher CJ, He J, ''et al.'' |title=TBX5 nuclear localization is mediated by dual cooperative intramolecular signals. |journal=J. Mol. Cell. Cardiol. |volume=35 |issue= 10 |pages= 1191-5 |year= 2004 |pmid= 14519429 |doi=  }}
*[https://www.ncbi.nlm.nih.gov/bookshelf/br.fcgi?book=gene&part=hos GeneReviews/NCBI/NIH/UW entry on Holt-Oram Syndrome]
}}
* {{MeshName|TBX5+protein,+human}}
{{refend}}
 
{{Transcription factors|g4}}
{{Use dmy dates|date=April 2017}}


{{protein-stub}}
[[Category:Transcription factors]]
{{WikiDoc Sources}}

Revision as of 11:40, 15 September 2017

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Identifiers
Aliases
External IDsGeneCards: [1]
Orthologs
SpeciesHumanMouse
Entrez

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Ensembl

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UniProt

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RefSeq (mRNA)

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RefSeq (protein)

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Location (UCSC)n/an/a
PubMed searchn/an/a
Wikidata
View/Edit Human

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

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

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

TBX5 (gene) has been shown to interact with:

Other information

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

  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. ↑ 3.0 3.1 "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. ↑ 6.0 6.1 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. PMC 3400730. PMID 22333898.
  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. PMC 4553633. PMID 26212321.
  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. PMC 1140596. PMID 15923624.
  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. PMC 3400730. PMID 22333898.
  15. ↑ Niemann, Stephan, MD (28 August 2007). "Tetra-Amelia Syndrome". Gene Reviews. PMID 20301453.

Further reading

External links

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