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 : 26-09-2024

HGNC name	T-box 1
HGNC id	11592

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

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
	TBX1 regulates extracellular matrix-cell interactions in the second heart field
	functions of TBX1 during later stages of inner ear development
	TBX1 acts as a regulator of chondrocyte maturation and osteogenesis during the spheno-occipital synchondrosis development
	TBX1 may regulate myoblast muscle differentiation by enhancing the expression of SMAD2 and SMAD3
	likely regulatory divergence within the TBX1 locus plays an essential role in shaping the distinctive posterior skull base and vertebral structures found in Homo sapiens

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)

Type Gene Modification Chromosome rearrangement Protein expression Protein 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

to modification of basicranial morphology

Variant & Polymorphism SNP	rs41298798 is the most likely causal SNP contributing to basicranial morphology

Candidate gene	for congenital heart defects such as TOF,PTA and IAA in del 22q11
Marker
Therapy target
	System Type Disorder Pubmed neuromuscular myopathy   may be a therapeutic target for muscular dystrophy

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
	in Tbx1-deficient mice, the spheno-occipital synchondrosis was completely mineralized at birth
	Tbx1-knockout mice exhibited skull base and vertebral abnormalities similar to those seen in DiGeorge syndrome