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10 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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TBXT
T-box transcription factor T
Chromosome 6 · 6q27
NCBI Gene: 6862Ensembl: ENSG00000164458.10HGNC: HGNC:11515UniProt: J3KP65
92PubMed Papers
23Diseases
0Drugs
2Pathogenic Variants
FUNCTIONAL ROLE
Transcription Factor
CLINICAL
OMIM Disease Gene
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
heart morphogenesisnucleusRNA polymerase II cis-regulatory region sequence-specific DNA bindingchromatinsacral agenesis-abnormal ossification of the vertebral bodies-persistent notochordal canal syndromespina bifidachordomaliver disease
✦AI Summary

TBXT (T-box transcription factor T) is a critical transcription factor that regulates mesoderm formation and early embryonic development. TBXT binds to palindromic T-site DNA sequences (5'-TTCACACCTAGGTGTGAA-3') and activates transcription of genes required for mesodermal differentiation 1. During gastrulation, TBXT expression initiates at the primitive streak and its dosage must be precisely regulated to ensure proper cell fate specification and anterior-posterior axis patterning 1. TBXT plays essential roles in notochord formation, with conserved enhancers controlling its cell-type-specific expression through auto-regulatory mechanisms 2. In nascent mesoderm, TBXT dosage directly influences the temporal progression of epithelial-to-mesenchymal transition (EMT) and persistence of cell-cell adhesions, though mesodermal identity can be acquired independently of complete EMT 3. TBXT is expressed in notochordal and nucleus pulposus cells during intervertebral disc formation, where it functions in extracellular matrix homeostasis 4. Pathologically, TBXT alterations associate with multiple congenital conditions: an evolutionary Alu-element insertion affecting TBXT splicing in hominoids correlates with tail-loss but increases neural tube defect susceptibility 5. Disease-associated variants in TBXT have been identified in patients with sacral agenesis and vertebral anomalies 6.

Sources cited
1
TBXT activation marks primitive streak formation during early gastrulation in 3D-cultured blastoids
PMID: 37683602
2
TBXT induction occurs through WNT pathway activation during notochord and trunk tissue specification
PMID: 39695233
3
TBXT expression identifies notochordal and nucleus pulposus cell populations involved in extracellular matrix homeostasis during intervertebral disc formation
PMID: 36965031
4
TBXT alternative splicing variants affect tail development and neural tube patterning in vertebrates
PMID: 38418917
5
Homozygous deleterious TBXT variants are associated with human disease phenotypes
PMID: 30237576
6
TBXT dosage regulates EMT progression timing and cell-cell adhesion persistence in nascent mesoderm
PMID: 37986746
7
TBXT expression dosage controls epithelial-to-mesenchymal transition progression independent of mesodermal specification
PMID: 38411343
8
Conserved notochord-specific enhancers control TBXT expression through auto-regulatory mechanisms essential for proper axis development
PMID: 37852970
Disease Associationsⓘ23
sacral agenesis-abnormal ossification of the vertebral bodies-persistent notochordal canal syndromeOpen Targets
0.55Moderate
spina bifidaOpen Targets
0.47Moderate
chordomaOpen Targets
0.39Weak
liver diseaseOpen Targets
0.17Weak
neural tube defectOpen Targets
0.12Weak
smoking initiationOpen Targets
0.12Weak
neoplasmOpen Targets
0.12Weak
thyroiditisOpen Targets
0.11Weak
non-small cell lung carcinomaOpen Targets
0.11Weak
cancerOpen Targets
0.10Weak
hepatocellular carcinomaOpen Targets
0.10Suggestive
breast cancerOpen Targets
0.10Suggestive
lung cancerOpen Targets
0.09Suggestive
paralytic strabismusOpen Targets
0.09Suggestive
respiratory tract infectious disorderOpen Targets
0.08Suggestive
type 1 diabetes mellitusOpen Targets
0.08Suggestive
head and neck squamous cell carcinomaOpen Targets
0.08Suggestive
liver cancerOpen Targets
0.08Suggestive
coronary artery diseaseOpen Targets
0.07Suggestive
central nervous system diseaseOpen Targets
0.07Suggestive
ChordomaUniProt
Neural tube defectsUniProt
Sacral agenesis with vertebral anomaliesUniProt
Pathogenic Variants2
NM_001366285.2(TBXT):c.816dup (p.Ser273fs)Likely pathogenic
not provided
★☆☆☆2021→ Residue 273
NM_001366285.2(TBXT):c.512A>G (p.His171Arg)Pathogenic
Sacral agenesis-abnormal ossification of the vertebral bodies-persistent notochordal canal syndrome
☆☆☆☆2014→ Residue 171
View on ClinVar ↗
Related Genes
FOXH1Protein interaction87%NOTOProtein interaction82%EOMESProtein interaction82%SNAI1Protein interaction82%DLL1Protein interaction77%CENPTProtein interaction76%
Tissue Expression6 tissues
Heart
0%
Lung
0%
Bone Marrow
0%
Ovary
0%
Liver
0%
Brain
0%
Gene Interaction Network
Click a node to explore
TBXTFOXH1NOTOEOMESSNAI1DLL1CENPT
PROTEIN STRUCTURE
Preparing viewer…
PDB7HI9 · 1.42 Å · X-ray
View on RCSB ↗
Constraintⓘ
LOEUFⓘ
0.67LoF Tolerant
pLIⓘ
0.03Tolerant
Observed/Expected LoF0.46 [0.32–0.67]
RankingsWhere TBXT stands among ~20K protein-coding genes
  • #5,220of 20,598
    Most Researched92
  • #4,338of 5,498
    Most Pathogenic Variants2
  • #4,902of 17,882
    Most Constrained (LOEUF)0.67
Genes detectedTBXT
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
3D-cultured blastoids model human embryogenesis from pre-implantation to early gastrulation stages.
PMID: 37683602
Cell Stem Cell · 2023
1.00
2
Timely TGFβ signalling inhibition induces notochord.
PMID: 39695233
Nature · 2025
0.90
3
Spatiotemporal Characterization of Human Early Intervertebral Disc Formation at Single-Cell Resolution.
PMID: 36965031
Adv Sci (Weinh) · 2023
0.80
4
On the genetic basis of tail-loss evolution in humans and apes.
PMID: 38418917
Nature · 2024
0.70
5
Autozygome and high throughput confirmation of disease genes candidacy.
PMID: 30237576
Genet Med · 2019
0.60