Selected-GenAtlas references SOURCE GeneCards NCBI Gene Swiss-Prot Orphanet Ensembl
HGNC UniGene Nucleotide OMIM UCSC
Home Page
FLASH GENE
Symbol TBX1 contributors: mct/npt - updated : 29-03-2017
HGNC name T-box 1
HGNC id 11592
Corresponding disease
CTHMT conotruncal heart malformations TBX1 related
DEL22Q11 chromosome 22q11.2 microdeletion syndrome
Location 22q11.21      Physical location : 19.744.225 - 19.771.110
Synonym name
  • brachyury
  • testis specific T-box protein
  • T-box 1 transcription factor C
  • Synonym symbol(s) TBX1C, CAFS, CTHM, DGCR, DGS, DORV, TGA, VCFS, CATCH22, VCF
    DNA
    TYPE functioning gene
    STRUCTURE 26.89 kb     9 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    MAPPING cloned Y linked N status confirmed
    Physical map
    DGCR6 22q11.21 DiGeorge syndrome critical region gene 6 PRODH 22q11.21 proline dehydrogenase (oxidase) 1 DGCR5 22q11 DiGeorge syndrome critical region gene 5 (non-coding) LOC391294 22 similar to POM121 membrane glycoprotein-like 1 LOC343830 22q11.21 similar to carbonic anhydrase XV DGCR2 22q11.21 DiGeorge syndrome critical region gene 2 LOC391295 22 similar to serine/threonine kinase FKSG81; spermiogenesis associated 4 STK22B 22q11.2 serine/threonine kinase 22B (spermiogenesis associated) DGCR14 22q11.21 DiGeorge syndrome critical region gene 14 GSCL 22q11.21 goosecoid-like SLC25A1 22q11.21 solute carrier family 25 (mitochondrial carrier; citrate transporter), member 1 CLTCL1 22q11.21 clathrin, heavy polypeptide-like 1 HIRA 22q11.21-q11.23 HIR histone cell cycle regulation defective homolog A (S. cerevisiae) MRPL40 22q11.2 mitochondrial ribosomal protein L40 LOC128977 22q11.21 hypothetical protein LOC128977 UFD1L 22q11.21 ubiquitin fusion degradation 1-like CDC45L 22q11.2 CDC45 cell division cycle 45-like (S. cerevisiae) CLDN5 22q11.21 claudin 5 (transmembrane protein deleted in velocardiofacial syndrome) PNUTL1 22q11.21 peanut-like 1 (Drosophila) GP1BB 22q11.21 glycoprotein Ib (platelet), beta polypeptide LOC391296 22 similar to contains similarity to cell wall-plasma membrane linker protein~gene_id:MKA23.5 TBX1 22q11.21 T-box 1 GNB1L 22q11.2 guanine nucleotide binding protein (G protein), beta polypeptide 1-like FLJ21125 22q11.21 hypothetical protein FLJ21125 TXNRD2 22q11.21 thioredoxin reductase 2 COMT 22q11.2 catechol-O-methyltransferase ARVCF 22q11.21 armadillo repeat gene deletes in velocardiofacial syndrome DKFZp761P1121 22q11.21 hypothetical protein DKFZp761P1121 DGCR8 22q11.2 DiGeorge syndrome critical region gene 8 HTF9C 22q11.2 DiGeorge syndrome critical region gene 8 RANBP1 22q11.21 RAN binding protein 1 ZDHHC8 22q11.1 zinc finger, DHHC domain containing 8 LOC388849 22 LOC388849 FLJ32575 22q11.21 hypothetical protein FLJ32575 RTN4R 22q11.21 reticulon 4 receptor LOC388850 22 similar to proline dehydrogenase (oxidase) 1; proline oxidase 2; p53 induced protein; tumor protein p53 inducible protein 6 DGCR6L 22q11.2 DiGeorge syndrome critical region gene 6-like LOC391297 22 LOC391297 LOC284859 22q11.21 hypothetical gene supported by BC039313 GGT2 22q11 gamma-glutamyltransferase 2 LOC284874 22q11.21 hypothetical LOC284874 LOC388851 22 similar to phosphatidylinositol 4-kinase, catalytic, alpha polypeptide isoform 2; phosphatidylinositol 4-kinase, type II, alpha; phosphatidylinositol 4-kinase, type III, alpha; phosphatidylinositol 4-kinase 230 LOC388852 22 similar to hypothetical protein LOC388853 22 similar to Sushi domain (SCR repeat) containing LOC391298 22 similar to KIAA0649 gene product LOC388854 22 similar to Gamma-glutamyltranspeptidase 1 precursor (Gamma-glutamyltransferase 1) (CD224 antigen)
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    9 splicing 1480 43.1 398 fetal lung 1997 9268629
    exon 1-9a
    9 splicing 1538 40.2 372 skeletal muscle, testis, fetal lung 1997 9268629
    exon 1-9b, 10
    9 - 2082 53.4 495 - 1997 9268629
    EXPRESSION
    Type restricted
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Digestivemouthtongue   
    Nervousbrain     Mus musculus
     braindiencephalonamygdala   Mus musculus
     brainforebraincerebral cortexfrontal cortex  Mus musculus
     brainlimbic systemhippocampus   Mus musculus
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    physiological period embryo, fetal
    Text lateral plate mesoderm and pharyngeal endoderm, the branchial arches, the otic vesicles, the optic cup, embryonic fetal vertebral column and tooth bud
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • a large N terminal DNA binding domain (T-box)
  • a C-terminal transactivation/repression domain
  • a nuclear localization signal
  • HOMOLOGY
    interspecies homolog to murine T-box gene Tbx1 (T,brachyury)
    Homologene
    FAMILY
  • T box family
  • CATEGORY DNA associated , transcription factor
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,nucleus,chromatin/chromosome
    basic FUNCTION
  • required for formation and early remodeling of the arch arteries, for neural crest cell distribution and patterning and for inner ear morphogenesis
  • RNA polymerase 2, DNA binding transcription factor
  • may be regulating expression of FGF8 to ensure correct differentiation of neural crest in the pharyngeal area
  • regulating the onset of branchiomeric myogenesis and pharyngeal tonus
  • regulates intermediate steps of thyroid development by a non-cell-autonomous mechanism
  • expressed in both first and second branchial arch and also maintains the number of myocytes in the head and limb
  • acts upstream in a genetic network that positively regulates second heart field cell proliferation and negatively regulates differentiation, cell-autonomously in the caudal pharyngeal region
  • having functions in the inner ear that are to control, cell-autonomously, contribution, size and fate of a large population of otic epithelial cells, and, cell non-autonomously, cochlear morphogenesis
  • is a critical transcription factor that guides palatal elongation and elevation and FGF8 expression in the palate is TBX1-dependent
  • may have potentially a novel dual role as a negative regulator of tumor growth
  • role in suppressing cardiac progenitor cell differentiation and having also a negative effect on MEF2C during skeletal muscle differentiation
  • potentially regulates the balance between proliferation and differentiation of keratinocytes and is essential for palatal fusion and oral mucosal differentiation
  • TBX1 acts upstream of SMAD7 controlling vascular smooth muscle and extracellular matrix investment of the fourth arch artery
  • regulates brain angiogenesis
  • TBX1 coordinates the WNT-dependent epithelial destabilization of pouch-forming cells with their collective migration towards FGF8A-expressing mesodermal guideposts
  • regulates epithelial polarity and dynamic basal filopodia in the second heart field
  • has critical roles in maintaining proliferation and inhibiting differentiation of cardiac progenitor cells of the second heart field
  • TBX2, TBX3, TBX4, TBX5 and three members of TBX1 (TBX1, TBX15, TBX18), Brachyury (T) and Eomes (TBR2) are expressed in the developing limb
  • TBX18 and other members of the T-box gene family, namely, TBX1, TBX2, TBX3, and TBX20, play additional roles in development and homeostasis of other components of the excretory system
  • CELLULAR PROCESS nucleotide, transcription
    PHYSIOLOGICAL PROCESS development
    text organogenesis
    PATHWAY
    metabolism
    signaling
    a component
    INTERACTION
    DNA binding through T-box
    RNA
    small molecule
    protein
  • VEGF and FGF8
  • with PITX2 (molecular partners in different developmental fields including cranial, limb and heart) muscle lineages
  • interacting with CHRD (modifier for the craniofacial anomalies of TBX1 mutations, demonstrating the existence of a second-site modifier for a specific subset of the phenotypes associated with 22q11 Deletion syndrome) (Choi 2009)
  • genetic interaction between TBX1 and POU3F4 relevant to human disease, indicating a function of these genes in signaling from the periotic mesenchyme to the otic vesicle to direct proper coiling of the cochlear duct
  • physical interaction between TBX1 and ASH2L suggesting that at least some functions of TBX1 may be mediated by direct interactions with a histone methyltransferase complex
  • interacting with DSCR6
  • in the presence of RIPPLY3, TBX1 acts as a transcriptional repressor, and functions to restrict the positional expression of FGF8, a key regulator of pre-placodal ectoderm gene expression
  • interaction with MEF2C
  • interacts with, and probably recruits a specific subunit of, the BAF complex (SMARCD1) as well as histone methylases to activate or enhance transcription, enhancing SMARCD1 occupation at the WNT5A gene and its H3K4 monomethylation status
  • MYST3 regulates the TBX1 locus, and MYST3 mutation partially phenocopies DiGeorge syndrome in mouse
  • TBX1 down regulates the expression of KDR, during embryonic development
  • cell & other
    REGULATION
    ASSOCIATED DISORDERS
    corresponding disease(s) DEL22Q11 , CTHMT
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    constitutional       loss of function
    haploinsufficiency associated to psychiatric disorder in DEL22Q11
    constitutional       loss of function
    in thyroid dysgenesis
    constitutional       loss of function
    underlies specific prodromal and symptomatic elements of schizophrenia, as well as autism spectrum disorder
    constitutional   deletion    
    from the pharyngeal endoderm is sufficient to cause caudal pharyngeal arch segmentation defects by FGF-independent effectors
    Susceptibility
    Variant & Polymorphism
    Candidate gene for congenital heart defects such as TOF,PTA and IAA in del 22q11
    Marker
    Therapy target
    ANIMAL & CELL MODELS
  • null mutant mice have conotruncal defect and a phenotype reminiscent of the Di George syndrome. required for normal heart development of the pharyngeal arch arteries in a gene dosage-dependent manner, in mice
  • diminished dosage of 22q11 genes disrupts neurogenesis and cortical development in a mouse model of 22q11 deletion/DiGeorge syndrome (Meechan 2009)
  • impaired adhesion separation of the oral epithelium together with compromised palatal mesenchymal growth is an underlying cause for various forms of cleft palate phenotypes in Tbx1(-/-) mice
  • DiGeorge syndrome-like anomalies are present in mice with homozygous mutation of Moz and in heterozygous Moz mutants when combined with Tbx1 haploinsufficiency or oversupply of retinoic acid
  • constitutive Tbx1-deficient mice show hearing impairments and velopharyngeal dysfunction, and selectively showed lower levels of vocal sounds in complex vocal patterns only