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Symbol TBX5 contributors: mct - updated : 05-03-2015
HGNC name T-box 5
HGNC id 11604
Corresponding disease
HOS1 Holt-Oram syndrome 1
Location 12q24.21      Physical location : 114.791.735 - 114.846.247
Synonym name
  • T-box transcription factor TBX5
  • T-box protein 5
  • Synonym symbol(s) HOS
    TYPE functioning gene
    STRUCTURE 54.51 kb     9 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    regulatory sequence Promoter
    Binding site   transcription factor
    text structure
  • one GC box, three potential T-box-like binding elements (TBE-A, -B, and -C), and one NKX2.5 binding site necessary for the promoter activity and its regulation
  • three elements (CREs 2, 9, 16) with patterns of enhancer activity overlapping the endogenous expression pattern of TBX5, and strong expression in ventricles, the interventricular septum (IVS), and in both atria, atrial septum or AVC
  • MAPPING cloned Y linked   status confirmed
    Map cen - (D12S1344 ,D12S1333 ) - D12S2309 - D12S2310 - PTPN11 - D12S821 - D12S2311 - D12S1857 - D12S861 - D12S1616 - D12S1340 - D12S2300 - OAS1 - D12S1895 - D12S809 - D12S129 - TBX3 - D12S1646 - TBX5 - D12S184 - D12S1984 - (D12S1341 ,D12S1319 ) - D12S354 - (D12S1023 - D12S839 ) - D12S369 - D12S1602 - D12S1665 - D12S79 - qter
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    9 - 3921 57.6 518 more prominent in embryonic hearts 2015 25623069
  • TBX5a
  • has a stronger binding affinity for GATA4 and is the only isoform to interact with NKX25, resulting in isoform-specific activation of NPPA
  • roles in regulating cardiomyocyte growth
  • 7 splicing 1050 39.1 349 - 1999 10199965
    8 splicing 3736 52.5 468 predominant isoform in skeletal myoblasts 2015 25623069
  • TBX5c
  • lacking exon 2
  • different N terminus
  • antagonizes TBX5a regulation of pro-proliferative signals such as IGF1, FGF10 and BMP4.
  • 9 - 3749 57.6 518 - 1999 10199965
    - - - - 255 more prominent in adult hearts 2011 21856288
  • role in regulating cardiomyocyte growth arrest
    Type restricted
       expressed in (based on citations)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Reproductivefemale systemplacenta   
    Respiratorylung   predominantly
     respiratory tractlarynx   
     respiratory tracttrachea   
    Skeletonappendicular skeletonupper limb   
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    cell lineage
    cell lines
    at STAGE
    physiological period embryo
    Text involved in the initiation of limb outgrow (upper limb bud) and heart (atrial walls, septa and valves), developing retina
  • a large N terminal DNA binding domain (T-box)
  • a C-terminal transactivation/repression domain (C-terminal region is a transcriptional activator), involved in antagonizing the splicing activity of SFRS2
  • mono polymer homomer , dimer
    interspecies homolog to murine T-box gene Tbx5 (T,brachyury)
    homolog to Drosophila optomotor-blind gene (omb)
    intraspecies homolog to highly in TBX4
  • T box family
  • CATEGORY DNA associated , transcription factor
    SUBCELLULAR LOCALIZATION     intracellular
    basic FUNCTION
  • playing a role in regulating limb development and specification of limb identity (especially in forelimb growth and patterning)
  • functional cooperation of TBX5 and MEF2C links MEF2C to the higher-order protein complex regulating heart development
  • regulates ventricular myocyte relaxation in a cell-autonomous manner by direct modulation of the expression of ATP2A2
  • acting as a regulator of apoptosis and cell growth
  • activating a cardiac-specific promoter (atrial natriuretic factor (NPPA) alone and synergistically with other transcription factors
  • playing an important role in modulating migration of vascular progenitor cells in the developing heart
  • having a function in pre-mRNA splicing, and this function is relevant to the pathogenesis of Holt-Oram syndrome
  • having a dual role in both transcriptional activation and pre-mRNA splicing
  • acts cooperatively with NKX2.5 to regulate the expression of SHOX2 and BMP4
  • TBX5 function is critical for the expression of SHOX2 in cardiac tissues
  • acts upstream of SHOX2, which, in turn, activates BMP4 in thei nflow trac of the heart
  • regulates transcriptional networks required for mature CCS (Cardiac conduction system) function
  • TBX4 and TBX5 play similar roles in the initiation of hindlimb and forelimb outgrowth, respectively
  • YAP1, CTNNB1 and TBX5 form a complex that regulates the expression of genes that promote survival, including BIRC5 and BCL2L1
  • TBX5 and TBX4, two genes expressed in forelimb and hindlimb-forming regions respectively, play crucial roles in the initiation of limb outgrowth
  • essential role for the T-box transcription factor gene TBX5 in sternum and forelimb formation and both structures share an embryological origin within the lateral plate mesoderm
  • crucial for proper cardiovascular development
  • TBX2, TBX3, TBX4, TBX5 and three members of TBX1 (TBX1, TBX15, TBX18), Brachyury (T) and Eomes (TBR2) are expressed in the developing limb
  • CELLULAR PROCESS cell life, cell death/apoptosis
    nucleotide, transcription
    text controlling fore limb identity, promoting cardiomyocyte differentiation in synergy with CSX
  • anteroposterior axis
    TBX5-dependent pathway for the transcriptional control of diastolic function
    a component
  • pairing with TBX3
  • can form a complex with splicing factor SFRS2 and plays an important role in constitutive pre-mRNA splicing, alternative splicing, and transcriptional activation
  • having a role in the development of the heart
    DNA binding to both major and minor grooves of their DNA targets (T-box)
    small molecule
  • binding to CSX (NKX2.5), lacking in Holt-Oram syndrome
  • binding to GATA4
  • co-expressed with TBX20 in the heart-forming region but then become differentially expressed as heart morphogenesis progresses
  • interacting with HEY2
  • interaction between TBX5 and MEF2C leading to a synergistic activation of the -cardiac myosin heavy chain (MYH6)
  • physically associates with MEF2C and cooperatively activates transcription from the MYH6 promoter
  • Myocardin and TBX5 physically interact and their interaction domains were mapped to the basic domain and the coil domain of myocardin and TBX5, respectively
  • direct molecular link between TBX5 and SCN5A, implicated in the function of the mature ventricular conduction system (VCS)
  • TBX4 and TBX5 interact with FGF10 during the process of lung growth and branching but not during tracheal/bronchial cartilage development
  • HDAC3 physically interacts with TBX5 and modulates its acetylation to repress TBX5-dependent activation of cardiomyocyte lineage-specific genes
  • FBXO25 directly interacts with TBX5 and NKX2-5, and controls TBX5 and NKX2-5 transcriptional activity to regulate cardiomyocyte development
  • TBX2, TBX3, TBX4, TBX5 and three members of TBX1 (TBX1, TBX15, TBX18), Brachyury (T) and Eomes (TBR2) are expressed in the developing limb
  • TBX4, TBX5 are both upstream regulators of FGF10 and RSPO2, which drive the outgrowth of all four limb buds
  • cell & other
    Other autoregulated as part of the mechanism of its transcription
    corresponding disease(s) HOS1
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    constitutional germinal mutation     loss of function
    interacting with GATA4 in causing inherited heart septation defects (ASD)
  • to development of retinopathy of prematurity (ROP)
  • to familial dilated cardiomyopathy (DCM)
  • to isolated congenital heart disease (CHD)
  • Variant & Polymorphism SNP
  • association between SNPs gene and the development of ROP
  • low-frequency single-nucleotide polymorphism (SNP) that abrogates a cardiac-specific TBX5 enhancer, having the potential to lead to as many CHDs
  • TBX5 loss-of-function mutation associated with enhanced susceptibility to DCM
  • Candidate gene
    Therapy target
  • deletion of Tbx5 from the mature murine ventricular conduction system (VCS), including the AV bundle and bundle branches, resulted in severe VCS functional consequences, including loss of fast conduction, arrhythmias, and sudden death