This gene is a member of a phylogenetically conserved family of genes that share a common DNA-binding domain, the T-box. T-box genes encode transcription factors involved in the regulation of developmental processes. This gene is the human homolog of mouse Tbx4, which is closely linked to Tbx2 on mouse chromosome 11. Similarly this gene, like TBX2, maps to human chromosome 17. ... See more...

Aliases for TBX4 Gene

Aliases for TBX4 Gene

  • T-Box Transcription Factor 4 2 3 5
  • T-Box Transcription Factor TBX4 3 4
  • T-Box Protein 4 3 4
  • T-Box 4 2 3
  • PAPPAS 3
  • ICPPS 3
  • TBX4 5
  • SPS 3

External Ids for TBX4 Gene

Previous GeneCards Identifiers for TBX4 Gene

  • GC17P059297
  • GC17P062019
  • GC17P059875
  • GC17P060008
  • GC17P056888
  • GC17P059533
  • GC17P054900

Summaries for TBX4 Gene

Entrez Gene Summary for TBX4 Gene

  • This gene is a member of a phylogenetically conserved family of genes that share a common DNA-binding domain, the T-box. T-box genes encode transcription factors involved in the regulation of developmental processes. This gene is the human homolog of mouse Tbx4, which is closely linked to Tbx2 on mouse chromosome 11. Similarly this gene, like TBX2, maps to human chromosome 17. Expression studies in mouse and chicken show that Tbx4 is expressed in developing hindlimb, but not in forelimb buds, suggesting a role for this gene in regulating limb development and specification of limb identity. [provided by RefSeq, Jul 2008]

GeneCards Summary for TBX4 Gene

TBX4 (T-Box Transcription Factor 4) is a Protein Coding gene. Diseases associated with TBX4 include Ischiocoxopodopatellar Syndrome With Or Without Pulmonary Arterial Hypertension and Amelia, Posterior, With Pelvic And Pulmonary Hypoplasia Syndrome. Gene Ontology (GO) annotations related to this gene include DNA-binding transcription factor activity. An important paralog of this gene is TBX5.

UniProtKB/Swiss-Prot Summary for TBX4 Gene

  • Transcriptional regulator that has an essential role in the organogenesis of lungs, pelvis, and hindlimbs.

No data available for CIViC Summary , Tocris Summary , Gene Wiki entry , PharmGKB "VIP" Summary , Rfam classification and piRNA Summary for TBX4 Gene

Genomics for TBX4 Gene

GeneHancer (GH) Regulatory Elements Pubs

Promoters and enhancers for TBX4 Gene
GeneHancer (GH) Identifier GH Type GH
Score
GH Sources Gene Association Score Total Score TSS distance (kb) Number of Genes Away Size (kb) Transcription Factor
Binding Sites
Gene Targets
GH17J061450 Promoter/Enhancer 1.7 EPDnew Ensembl ENCODE dbSUPER 250.7 +2.6 2617 8.3 SSRP1 CEBPA THAP11 FOXA2 KDM6A SMAD4 ZNF511 SAP130 RARA ZSCAN9 TBX4 HSALNG0117886 ENSG00000267137 NACA2
GH17J061478 Promoter 0.5 EPDnew 262 +25.9 25852 0.1 MAFK BCLAF1 TBX4 NACA2 lnc-NACA2-3 ENSG00000267137
GH17J061393 Promoter/Enhancer 2.6 EPDnew FANTOM5 Ensembl ENCODE CraniofacialAtlas dbSUPER 11.9 -46.9 -46921 24.1 ZNF600 ZNF654 ZNF580 KLF9 CEBPA ZNF223 ZIC2 CHD4 ZBTB10 MXD4 TBX2-AS1 TBX2 PPM1D MED13 APPBP2 TBX4 LINC02875 HSALNG0117880 lnc-TBX2-2 5EW4_A-023
GH17J061247 Enhancer 2.1 VISTA UCNEbase FANTOM5 Ensembl ENCODE CraniofacialAtlas dbSUPER 9.9 -200.2 -200242 10.2 JUND ZNF580 ZNF10 BRCA1 ZIC2 YY1 CEBPB FEZF1 MAX EP300 TBX4 LOC101927855 NACA2 HSALNG0117871 HSALNG0117872 NONHSAG022404.2 TBX2 BCAS3
GH17J061426 Enhancer 1.2 Ensembl ENCODE dbSUPER 11.8 -25.5 -25501 2.6 JUND ZMYM3 ZIC2 CHD4 HOMEZ THAP11 FOXA2 KDM6A SMAD4 ZNF511 TBX2 TBX4 NACA2 HSALNG0117883 HSALNG0117884 HSALNG0117885
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around TBX4 on the GeneHancer Hub at the UCSC Golden Path

Cistromic (ChIP-Seq) regulation report from SPP (The Signaling Pathways Project) for TBX4

Top Transcription factor binding sites by QIAGEN in the TBX4 gene promoter:
  • c-Rel
  • E2F
  • E2F-1
  • E2F-2
  • E2F-3a
  • E2F-4
  • E2F-5
  • MyoD
  • NF-AT
  • POU3F1

Genomic Locations for TBX4 Gene

Latest Assembly
chr17:61,452,404-61,485,110
(GRCh38/hg38)
Size:
32,707 bases
Orientation:
Plus strand

Previous Assembly
chr17:59,529,783-59,562,471
(GRCh37/hg19 by Entrez Gene)
Size:
32,689 bases
Orientation:
Plus strand

chr17:59,529,765-59,562,471
(GRCh37/hg19 by Ensembl)
Size:
32,707 bases
Orientation:
Plus strand

Genomic View for TBX4 Gene

Genes around TBX4 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
TBX4 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for TBX4 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for TBX4 Gene

Proteins for TBX4 Gene

  • Protein details for TBX4 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    P57082-TBX4_HUMAN
    Recommended name:
    T-box transcription factor TBX4
    Protein Accession:
    P57082
    Secondary Accessions:
    • A5PKU7
    • B2RMT1
    • B7ZLV3

    Protein attributes for TBX4 Gene

    Size:
    545 amino acids
    Molecular mass:
    60204 Da
    Quaternary structure:
    No Data Available

    Alternative splice isoforms for TBX4 Gene

    UniProtKB/Swiss-Prot:

neXtProt entry for TBX4 Gene

Post-translational modifications for TBX4 Gene

  • Modification sites at PhosphoSitePlus
  • Modification sites at neXtProt

No data available for DME Specific Peptides for TBX4 Gene

Domains & Families for TBX4 Gene

Gene Families for TBX4 Gene

HGNC:
Human Protein Atlas (HPA):
  • Disease related genes
  • Predicted intracellular proteins
  • Transcription factors

Protein Domains for TBX4 Gene

InterPro:
Blocks:
  • Transcription factor, T-box
  • Brachyury protein family signature

Suggested Antigen Peptide Sequences for TBX4 Gene

GenScript: Design optimal peptide antigens:
  • TBX4 protein (B7ZLV3_HUMAN)
  • T-box transcription factor TBX4 (TBX4_HUMAN)
genes like me logo Genes that share domains with TBX4: view

No data available for Graphical View of Domain Structure and UniProtKB/Swiss-Prot for TBX4 Gene

Function for TBX4 Gene

Molecular function for TBX4 Gene

UniProtKB/Swiss-Prot Function:
Transcriptional regulator that has an essential role in the organogenesis of lungs, pelvis, and hindlimbs.

Phenotypes From GWAS Catalog for TBX4 Gene

Gene Ontology (GO) - Molecular Function for TBX4 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000978 RNA polymerase II proximal promoter sequence-specific DNA binding IBA 21873635
GO:0000981 DNA-binding transcription factor activity, RNA polymerase II-specific ISA --
GO:0003677 DNA binding NAS 15106123
GO:0003700 DNA-binding transcription factor activity TAS 10945475
genes like me logo Genes that share ontologies with TBX4: view
genes like me logo Genes that share phenotypes with TBX4: view

Human Phenotype Ontology for TBX4 Gene

HPO Id HPO Name Alternative Ids Definition Synonyms

Animal Models for TBX4 Gene

MGI Knock Outs for TBX4:
  • Tbx4 Tbx4<tm4b(EUCOMM)Wtsi>
  • Tbx4 Tbx4<tm1.1Pa>

Inhibitory RNAs for research

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for TBX4

No data available for Enzyme Numbers (IUBMB) , Transcription Factor Targets and HOMER Transcription for TBX4 Gene

Localization for TBX4 Gene

Subcellular locations from UniProtKB/Swiss-Prot for TBX4 Gene

Subcellular locations from

COMPARTMENTS
Extracellular space Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi Apparatus Nucleus Mitochondrion 0 1 2 3 4 5 Confidence
COMPARTMENTS Subcellular localization image for TBX4 gene
Compartment Confidence
nucleus 4
extracellular 2
cytoskeleton 2
cytosol 2
plasma membrane 1
mitochondrion 1
endoplasmic reticulum 1
lysosome 1

Subcellular locations from the

Human Protein Atlas (HPA)

Gene Ontology (GO) - Cellular Components for TBX4 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000785 chromatin ISA --
GO:0005634 nucleus IEA --
genes like me logo Genes that share ontologies with TBX4: view

Pathways & Interactions for TBX4 Gene

PathCards logo

SuperPathways for TBX4 Gene

No Data Available

Gene Ontology (GO) - Biological Process for TBX4 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0001525 angiogenesis IBA 21873635
GO:0001708 cell fate specification IBA 21873635
GO:0002009 morphogenesis of an epithelium IEA --
GO:0006355 regulation of transcription, DNA-templated NAS 10945475
GO:0006357 regulation of transcription by RNA polymerase II IBA 21873635
genes like me logo Genes that share ontologies with TBX4: view

No data available for Pathways by source and SIGNOR curated interactions for TBX4 Gene

Drugs & Compounds for TBX4 Gene

No Compound Related Data Available

Transcripts for TBX4 Gene

mRNA/cDNA for TBX4 Gene

2 REFSEQ mRNAs :
6 NCBI additional mRNA sequence :
8 Ensembl transcripts including schematic representations, and UCSC links to gene/alias where relevant :

Inhibitory RNAs for research

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for TBX4

Alternative Splicing Database (ASD) splice patterns (SP) for TBX4 Gene

ExUns: 1 ^ 2 ^ 3 ^ 4 ^ 5 ^ 6a · 6b · 6c ^ 7a · 7b ^ 8 ^ 9 ^ 10
SP1: - - - -
SP2: - - -
SP3:
SP4: -

Relevant External Links for TBX4 Gene

GeneLoc Exon Structure for
TBX4

Expression for TBX4 Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and SAGE for TBX4 Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

mRNA differential expression in normal tissues according to GTEx for TBX4 Gene

This gene is overexpressed in Lung (x27.6), Bladder (x8.4), and Prostate (x8.2).

Protein differential expression in normal tissues from HIPED for TBX4 Gene

This gene is overexpressed in Bone (52.7) and Tlymphocyte (14.1).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB and MOPED for TBX4 Gene



Protein tissue co-expression partners for TBX4 Gene

Transcriptomic regulation report from SPP (The Signaling Pathways Project) for TBX4

SOURCE GeneReport for Unigene cluster for TBX4 Gene:

Hs.143907

Evidence on tissue expression from TISSUES for TBX4 Gene

  • Lung(2.5)
  • Muscle(2)
  • Heart(2)

Phenotype-based relationships between genes and organs from Gene ORGANizer for TBX4 Gene

Germ Layers:
  • ectoderm
  • endoderm
  • mesoderm
Systems:
  • cardiovascular
  • digestive
  • integumentary
  • nervous
  • respiratory
  • skeleton
Regions:
Head and neck:
  • brain
  • chin
  • ear
  • face
  • forehead
  • head
  • jaw
  • mandible
  • maxilla
  • mouth
  • skull
Thorax:
  • aorta
  • heart
  • heart valve
  • lung
Pelvis:
  • pelvis
Limb:
  • ankle
  • digit
  • femur
  • finger
  • foot
  • hand
  • hip
  • knee
  • lower limb
  • nail
  • shin
  • thigh
  • tibia
  • toe
  • upper limb
General:
  • blood
  • blood vessel
  • skin
genes like me logo Genes that share expression patterns with TBX4: view

Primer products for research

No data available for mRNA Expression by UniProt/SwissProt for TBX4 Gene

Orthologs for TBX4 Gene

This gene was present in the common ancestor of animals.

Orthologs for TBX4 Gene

Organism Taxonomy Gene Similarity Type Details
Chimpanzee
(Pan troglodytes)
Mammalia TBX4 29 30
  • 99.33 (n)
OneToOne
Dog
(Canis familiaris)
Mammalia TBX4 29 30
  • 90.4 (n)
OneToOne
Cow
(Bos Taurus)
Mammalia TBX4 29 30
  • 89.72 (n)
OneToOne
Mouse
(Mus musculus)
Mammalia Tbx4 29 16 30
  • 88.87 (n)
OneToOne
Rat
(Rattus norvegicus)
Mammalia Tbx4 29
  • 88.42 (n)
Platypus
(Ornithorhynchus anatinus)
Mammalia TBX4 30
  • 88 (a)
OneToOne
Oppossum
(Monodelphis domestica)
Mammalia TBX4 30
  • 80 (a)
OneToOne
Chicken
(Gallus gallus)
Aves TBX4 29 30
  • 79.78 (n)
OneToOne
Lizard
(Anolis carolinensis)
Reptilia TBX4 30
  • 82 (a)
OneToOne
Tropical Clawed Frog
(Silurana tropicalis)
Amphibia tbx4 29
  • 74.34 (n)
Zebrafish
(Danio rerio)
Actinopterygii tbx4 29 30
  • 63.39 (n)
OneToOne
Fruit Fly
(Drosophila melanogaster)
Insecta Doc1 30 31
  • 34 (a)
ManyToMany
Doc3 30 31
  • 30 (a)
ManyToMany
Doc2 30 31
  • 28 (a)
ManyToMany
Worm
(Caenorhabditis elegans)
Secernentea mab-9 31
  • 52 (a)
tbx-8 31
  • 40 (a)
tbx-9 31
  • 38 (a)
Species where no ortholog for TBX4 was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Eremothecium gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African clawed frog (Xenopus laevis)
  • African malaria mosquito (Anopheles gambiae)
  • Alicante grape (Vitis vinifera)
  • Alpha proteobacteria (Wolbachia pipientis)
  • Amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • Baker's yeast (Saccharomyces cerevisiae)
  • Barley (Hordeum vulgare)
  • Beta proteobacteria (Neisseria meningitidis)
  • Bread mold (Neurospora crassa)
  • Chromalveolata (Phytophthora infestans)
  • Common water flea (Daphnia pulex)
  • Corn (Zea mays)
  • E. coli (Escherichia coli)
  • Filamentous fungi (Aspergillus nidulans)
  • Firmicute Bacteria (Streptococcus pneumoniae)
  • Fission Yeast (Schizosaccharomyces pombe)
  • Green Algae (Chlamydomonas reinhardtii)
  • Honey Bee (Apis mellifera)
  • K. Lactis Yeast (Kluyveromyces lactis)
  • Loblloly Pine (Pinus taeda)
  • Malaria Parasite (Plasmodium falciparum)
  • Medicago Trunc (Medicago Truncatula)
  • Moss (Physcomitrella patens)
  • Orangutan (Pongo pygmaeus)
  • Pig (Sus scrofa)
  • Rainbow Trout (Oncorhynchus mykiss)
  • Rice (Oryza sativa)
  • Rice Blast Fungus (Magnaporthe grisea)
  • Schistosome Parasite (Schistosoma mansoni)
  • Sea Anemone (Nematostella vectensis)
  • Sea Vase (Ciona intestinalis)
  • Sea Squirt (Ciona savignyi)
  • Sea Urchin (Strongylocentrotus purpuratus)
  • Sorghum (Sorghum bicolor)
  • Soybean (Glycine max)
  • Stem Rust Fungus (Puccinia graminis)
  • Sugarcane (Saccharum officinarum)
  • Thale Cress (Arabidopsis thaliana)
  • Tomato (Lycopersicon esculentum)
  • Toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • Wheat (Triticum aestivum)

Evolution for TBX4 Gene

ENSEMBL:
Gene Tree for TBX4 (if available)
TreeFam:
Gene Tree for TBX4 (if available)
Aminode:
Evolutionary constrained regions (ECRs) for TBX4: view image
Alliance of Genome Resources:
Additional Orthologs for TBX4

Paralogs for TBX4 Gene

(10) SIMAP similar genes for TBX4 Gene using alignment to 4 proteins:

  • TBX4_HUMAN
  • A5PKU7_HUMAN
  • B7ZLV3_HUMAN
  • K7EPY2_HUMAN
genes like me logo Genes that share paralogs with TBX4: view

Variants for TBX4 Gene

Sequence variations, with clinical significance, from ClinVar and Humsavar, with links to dbSNP for TBX4 Gene

SNP ID Clinical significance and condition Chr 17 pos Variation AA Info Type
1013135 Uncertain Significance: not provided 61,483,164(+) A/G
NM_001321120.2(TBX4):c.1289A>G (p.Tyr430Cys)
MISSENSE
1013136 Likely Benign: not provided 61,483,372(+) C/A
NM_001321120.2(TBX4):c.1497C>A (p.Pro499=)
SYNONYMOUS
842729 Likely Pathogenic: not provided 61,483,454(+) C/T
NM_001321120.2(TBX4):c.1579C>T (p.Arg527Ter)
NONSENSE
889395 Uncertain Significance: Coxopodopatellar syndrome 61,456,537(+) C/T
NM_001321120.2(TBX4):c.47C>T (p.Ala16Val)
MISSENSE
889448 Uncertain Significance: Coxopodopatellar syndrome 61,482,984(+) C/A
NM_001321120.2(TBX4):c.1109C>A (p.Ser370Tyr)
MISSENSE

dbSNP identifiers (rs#s) for variants without ClinVar clinical significance for TBX4 Gene

All consequence types are included: molecular consequences (e.g. missense, synonymous), and location-based (e.g. intron, upstream).

Structural Variations from Database of Genomic Variants (DGV) for TBX4 Gene

Variant ID Type Subtype PubMed ID
dgv43n68 CNV loss 17160897
nsv2113 CNV insertion 18451855

Variation tolerance for TBX4 Gene

Residual Variation Intolerance Score: 33.7% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 12.21; 93.98% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for TBX4 Gene

Human Gene Mutation Database (HGMD)
TBX4
SNPedia medical, phenotypic, and genealogical associations of SNPs for
TBX4
Leiden Open Variation Database (LOVD)
TBX4

SNP Genotyping and Copy Number Assays for research

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for TBX4 Gene

Disorders for TBX4 Gene

MalaCards: The human disease database

(38) MalaCards diseases for TBX4 Gene - From: OMI, CVR, GTR, ORP, SWI, COP, and GCD

UniProtKB/Swiss-Prot

TBX4_HUMAN
  • Ischiocoxopodopatellar syndrome with or without pulmonary arterial hypertension (ICPPS) [MIM:147891]: An autosomal dominant bone disease characterized by patellar aplasia or hypoplasia and by anomalies of the pelvis and feet, including disrupted ossification of the ischia and inferior pubic rami. {ECO:0000269 PubMed:15106123}. Note=The disease is caused by variants affecting the gene represented in this entry.
  • Amelia, posterior, with pelvic and pulmonary hypoplasia syndrome (PAPPAS) [MIM:601360]: An autosomal recessive, lethal embryonic syndrome characterized by absent hindlimbs, pulmonary hypoplasia, severely hypoplastic or absent pelvic bones, hypoplasia of the sacrum, and ambiguous genitalia. {ECO:0000269 PubMed:31761294}. Note=The disease may be caused by variants affecting the gene represented in this entry.

Additional Disease Information for TBX4

Human Genome Epidemiology Navigator
(HuGE)
Atlas
ATLAS of Genetics and Cytogenetics in Oncology and Haematology
Open Targets Platform
Open Targets Platform
genes like me logo Genes that share disorders with TBX4: view

No data available for Genatlas for TBX4 Gene

Publications for TBX4 Gene

  1. Mutations in the human TBX4 gene cause small patella syndrome. (PMID: 15106123) Bongers EM … van Bokhoven H (American journal of human genetics 2004) 3 4 22 72
  2. Virtual cloning and physical mapping of a human T-box gene, TBX4. (PMID: 10945475) Yi CH … Brook JD (Genomics 2000) 2 3 4 22
  3. Homozygous Null TBX4 Mutations Lead to Posterior Amelia with Pelvic and Pulmonary Hypoplasia. (PMID: 31761294) Kariminejad A … Reversade B (American journal of human genetics 2019) 3 4 72
  4. TBX4 mutations (small patella syndrome) are associated with childhood-onset pulmonary arterial hypertension. (PMID: 23592887) Kerstjens-Frederikse WS … Berger RM (Journal of medical genetics 2013) 3 72
  5. Microdeletion of 17q22q23.2 encompassing TBX2 and TBX4 in a patient with congenital microcephaly, thyroid duct cyst, sensorineural hearing loss, and pulmonary hypertension. (PMID: 21271665) Nimmakayalu M … Shchelochkov OA (American journal of medical genetics. Part A 2011) 3 72

Products for TBX4 Gene

Sources for TBX4 Gene