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FLASH GENE

Symbol

TBX4

contributors: mct - updated : 28-01-2020

HGNC name	T-box 4
HGNC id	11603

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

RNA

TRANSCRIPTS	type	messenger

identification nb exons type bp product Protein kDa AA specific expression Year Pubmed NM_018488 8 - 2470 NP_060958 - 545 - 2018 28971975 NM_001321120 9 - 3394 NP_001308049 - 546 - 2018 28971975

EXPRESSION

Type

expressed in	(based on citations)
organ(s)	System Organ level 1 Organ level 2 Organ level 3 Organ level 4 Level Pubmed Species Stage Rna symbol Respiratory lung       highly Homo sapiens Skeleton appendicular skeleton lower limbs

tissue

System Tissue Tissue level 1 Tissue level 2 Level Pubmed Species Stage Rna symbol Connective bone

cells

System Cell Pubmed Species Stage Rna symbol not specific fibroblast Homo sapiens

cell lineage

cell lines

fluid/secretion

at STAGE

physiological period

embryo

Text	embryonic, developing hindlimb

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains	a T-box domain, DNA-binding domain
	a C-terminal transactivation/repression domain

HOMOLOGY

interspecies

homolog to murine Tbx4

intraspecies

homolog to TBX5,highly

Homologene

FAMILY

T box family

CATEGORY

transcription factor

SUBCELLULAR LOCALIZATION	intracellular
	intracellular,nucleus,chromatin/chromosome

basic FUNCTION	involved in the transcriptional regulation of genes required for mesoderm differentiation and the initiation of hindlimb outgrow
	TBX4 and TBX5 play similar roles in the initiation of hindlimb and forelimb outgrowth, respectively
	TBX5 and TBX4, two genes expressed in forelimb and hindlimb-forming regions respectively, play crucial roles in the initiation of limb outgrowth
	is a mesenchymal transcription factor that drives accumulation of myofibroblasts and the development of lung fibrosis
	TBX2, TBX3, TBX4, TBX5 and three members of TBX1 (TBX1, TBX15, TBX18), Brachyury (T) and Eomes (TBR2) are expressed in the developing limb
	importance of T-box transcription factors, especially TBX4, and super-enhancers in the roles of lung fibroblasts in pulmonary physiology and pathogenesis
	TBX4, TBX5 are thus crucial in the specification of hindlimbs and forelimbs, respectively
	role of a TBX4-FGF10-FGFR2 epithelial-mesenchymal signaling in lung organogenesis
	is an essential transcription factor for organogenesis of the lungs, pelvis, and hindlimbs

CELLULAR PROCESS

nucleotide, transcription

PHYSIOLOGICAL PROCESS

development

text	anteroposterior axis; developing hindlimb

PATHWAY

metabolism

signaling

a component

INTERACTION

DNA	binding through T-box

RNA

small molecule

protein	ELAVL1 bind and control the FGF10 and TBX4 mRNAs
	TBX4 and TBX5 interact with FGF10 during the process of lung growth and branching but not during tracheal/bronchial cartilage development
	activates SHOX2 expression in fore- and hindlimbs, suggesting SHOX2 as a feedback modulator of TBX4
	TBX4, TBX5 are both upstream regulators of FGF10 and RSPO2, which drive the outgrowth of all four limb buds

cell & other

REGULATION

ASSOCIATED DISORDERS

corresponding disease(s)

PTLAH , DEL17Q23 , DUP17QO , PAPPAS

Other morbid association(s)

Type Gene Modification Chromosome rearrangement Protein expression Protein Function constitutional   amplification     familial isolated clubfoot is associated with recurrent chromosome 17q23.1q23.2 microduplications containing TBX4 (Alvarado 2010) constitutional germinal mutation       associated with childhood-onset pulmonary arterial hypertension constitutional germinal mutation       in developmental lung disease manifesting with severe, often biphasic pulmonary hypertension (PH) at birth and/or later in infancy and childhood, often associated with skeletal anomalies, cardiac defects, neurodevelopmental disability and other anomalies

Susceptibility

to lethal lung maldevelopment, including acinar dysplasia (AcDys), congenital alveolar dysplasia (CAD) spectrum to pulmonary arterial hypertension (PAH)

Variant & Polymorphism other	SNVs or CNVs involving TBX4 in our subjects with lethal lung maldevelopment, including acinar dysplasia (AcDys), congenital alveolar dysplasia (CAD)spectrum
	common genetic variants underlying PAH susceptibility

Candidate gene

Marker

Therapy target

ANIMAL & CELL MODELS

in mice, a homozygous Tbx4-null allele entirely abrogates hindlimb development while forelimbs remain unaffected (pMID: 31761294)