Tbx3 Gene Detail

Summary

• Symbol
  Tbx3
• Name
  T-box 3
• Synonyms
  D5Ertd189e

• Feature Type
  protein coding gene
• IDs
  MGI:98495
  NCBI Gene: 21386
• Alliance
  gene page
• Transcription Start Sites
  25 TSS
• Candidate for QTL
  1 QTL

Location &
Maps

• Sequence Map
  Chr5:119808734-119822789 bp, + strand

  From Ensembl annotation of GRCm39
  

• View this region in JBrowse
  

• Genome Browsers
  Ensembl | UCSC | NCBI

• Genetic Map
  Chromosome 5, 60.34 cM
• Mapping Data
  8 experiments

Strain
Comparison

• SNPs within 2kb
  62 from dbSNP Build 142
• Strain Annotations
  18

Strain	Gene Model ID	Feature Type	Coordinates
C57BL/6J	MGI_C57BL6J_98495	protein coding gene	Chr5:119808600-119822789 (+)
129S1/SvImJ	MGP_129S1SvImJ_G0029998	protein coding gene	Chr5:122954973-122969033 (+)
A/J	MGP_AJ_G0029962	protein coding gene	Chr5:117890159-117904968 (+)
AKR/J	MGP_AKRJ_G0029901	protein coding gene	Chr5:121697510-121711426 (+)
BALB/cJ	MGP_BALBcJ_G0029973	protein coding gene	Chr5:119313077-119327180 (+)
C3H/HeJ	MGP_C3HHeJ_G0029693	protein coding gene	Chr5:122233838-122247969 (+)
C57BL/6NJ	MGP_C57BL6NJ_G0030428	protein coding gene	Chr5:127587314-127603408 (+)
CAROLI/EiJ	MGP_CAROLIEiJ_G0027654	protein coding gene	Chr5:112627918-112641945 (+)
CAST/EiJ	MGP_CASTEiJ_G0029102	protein coding gene	Chr5:121317421-121333411 (+)
CBA/J	MGP_CBAJ_G0029661	protein coding gene	Chr5:132547312-132561321 (+)
DBA/2J	MGP_DBA2J_G0029811	protein coding gene	Chr5:117985364-117999859 (+)
FVB/NJ	MGP_FVBNJ_G0029767	protein coding gene	Chr5:116895314-116909389 (+)
LP/J	MGP_LPJ_G0029899	protein coding gene	Chr5:123442141-123456182 (+)
NOD/ShiLtJ	MGP_NODShiLtJ_G0029798	protein coding gene	Chr5:136576594-136590629 (+)
NZO/HlLtJ	MGP_NZOHlLtJ_G0030469	protein coding gene	Chr5:121265083-121279108 (+)
PWK/PhJ	MGP_PWKPhJ_G0028815	protein coding gene	Chr5:116731048-116745526 (+)
SPRET/EiJ	MGP_SPRETEiJ_G0028653	protein coding gene	Chr5:118904566-118918546 (+)
WSB/EiJ	MGP_WSBEiJ_G0029177	protein coding gene	Chr5:121854546-121868578 (+)

Homology

• Human Ortholog
  TBX3, T-box transcription factor 3

• Vertebrate Orthologs
  3

Vertebrate Orthology Source

Alliance of Genome Resources

• Human Ortholog
  TBX3, T-box transcription factor 3
  
• Synonyms
  TBX3-ISO, UMS, XHL
• Links
  HGNC:11602

  NCBI Gene ID: 6926

  neXtProt AC: NX_O15119

  UniProt: O15119

  
  
• Chr Location
  12q24.21; chr12:114670255-114684175 (-)  GRCh38

---

• MGI Vertebrate Homology
  Tbx3 stringent orthology
  1 human;1 mouse;1 rat;1 zebrafish
  
• HCOP
  vertebrate homology predictions: TBX3
• Gene Tree
  Tbx3
  

Human Diseases

• Diseases
  1 with Tbx3 mouse models; 1 with human TBX3 associations

Human Disease

Mouse Models

ulnar-mammary syndrome

IDs

ulnar-mammary syndrome      

DOID:0060614
MESH:C536937
OMIM:181450
ORDO:3138
UMLS_CUI:C1866994

View 1 model

Mouse Models

Human Disease Modeled: ulnar-mammary syndrome

Allelic Composition	Genetic Background	Reference	Phenotypes
Tbx3tm1Pa/Tbx3tm1Pa	either: (involves: 129 * 129S1/Sv * 129X1/SvJ) or (involves: 129 * 129S1/Sv * 129X1/SvJ * C57BL/6NTac)	J:82458	View

Click on a disease name to see all genes associated with that disease.

• Mutations/Alleles
  1 with disease annotations

• References
  1 with disease annotations

Mutations,
Alleles, and
Phenotypes

• Phenotype Summary
  83 phenotypes from 9 alleles in 9 genetic backgrounds
  6 phenotypes from multigenic genotypes
  6 images
  58 phenotype references
  

• All Mutations and Alleles
  32
• Chemically induced (other)
  1
• Endonuclease-mediated
  3
• Gene trapped
  13
• Radiation induced
  1
• Targeted
  14
• Genomic Mutations
  2 involving Tbx3
• Incidental Mutations
  Mutagenetix , APF
• Find Mice (IMSR)
  49 strains or lines available
• Comparison Matrix
  Gene Expression + Phenotype
• Recombinase Activity
  Comparison Matrix Gene Expression + Recombinase Activity

Homozygous null mice die are embryonic lethal exhibiting defects in the yolk sac and limb defects. Female embryos show impaired mammary bud induction. Mice homozygous for hypomorphic alleles exhibit varying degrees of prenatal lethality and premature death, heart defects and limb abnormalities.

Gene Ontology
(GO)
Classifications

• All GO Annotations
  116
• GO References
  29

Expression

• Assay Results
  1458
• Tissues
  367
• cDNA Data
  26
• Literature Summary
  186

Images

Tissue x Stage Matrix

Comparison Matrix

Gene Expression + Phenotype

• Other Mouse Links
  Allen Institute
  GENSAT
  GEO
  Expression Atlas
• Other Vertebrate Links
  GEISHA TBX3
  Xenbase tbx3
  ZFIN tbx3a

Sequences &
Gene Models

• All Sequences
  66
• RefSeq
  6
• UniProt
  8
• CCDS
  CCDS19613.1, CCDS19614.1

• Ensembl
  ENSMUSG00000018604 (Evidence)
• NCBI Gene
  21386

Representative Sequences			Length	Strain/Species
genomic	ENSMUSG00000018604	Ensembl Gene Model | MGI Sequence Detail	14056	C57BL/6J
transcript	ENSMUST00000018748	Ensembl | MGI Sequence Detail	4856	Not Applicable
polypeptide	ENSMUSP00000018748	Ensembl | MGI Sequence Detail	741	Not Applicable

Protein
Information

• UniProt
  8 Sequences
• Protein Ontology
  PR:000016151 T-box transcription factor TBX3
  (term hierarchy)
• InterPro Domains
  IPR008967 p53-like transcription factor, DNA-binding domain superfamily
  IPR036960 T-box superfamily
  IPR001699 T-box transcription factor
  IPR048387 T-box transcription factor 2/3, repressor domain
  IPR022582 T-box transcription factor 2/3, transcription activation domain
  IPR046360 T-box transcription factor, DNA-binding domain
  IPR002070 Transcription factor, Brachyury
  IPR018186 Transcription factor, T-box, conserved site

Molecular
Reagents

• All nucleic 59

  cDNA 27

  Primer pair 14

  Other 18

  
  

  Microarray probesets 7

Other
Accession IDs

MGD-MRK-14732, MGI:1098785

References

• Summaries
  All 266

  Developmental Gene Expression 186

  Diseases 1

  Gene Ontology 29

  Phenotypes 58
• Earliest
  J:134667 Roderick TH, et al., Two radiation-induced chromosomal inversions in mice (Mus musculus). Proc Natl Acad Sci U S A. 1970 Oct;67(2):961-7
• Latest
  J:338900 Huang R, et al., ISL1 regulates lung branching morphogenesis via Shh signaling pathway. J Biol Chem. 2023 Jul 11;299(8):105034

TSS for Tbx3:

(View these features in JBrowse)

Transcription Start Site	Location	Distance from Gene 5'-end
Tssr48451	Chr5:119807941-119807981 (+)	-773 bp
Tssr48452	Chr5:119808008-119808019 (+)	-720 bp
Tssr48453	Chr5:119808465-119808472 (+)	-265 bp
Tssr48454	Chr5:119808723-119808741 (+)	-2 bp
Tssr48455	Chr5:119808764-119808769 (+)	33 bp
Tssr1615	Chr5:119808777-119808786 (+)	48 bp
Tssr1616	Chr5:119808791-119808795 (+)	59 bp
Tssr48456	Chr5:119808863-119808866 (+)	131 bp
Tssr48457	Chr5:119808890-119808901 (+)	162 bp
Tssr48458	Chr5:119809037-119809048 (+)	309 bp
Tssr1617	Chr5:119809049-119809056 (+)	319 bp
Tssr48459	Chr5:119809076-119809105 (+)	357 bp
Tssr48460	Chr5:119809147-119809156 (+)	418 bp
Tssr48461	Chr5:119809225-119809227 (+)	492 bp
Tssr48462	Chr5:119809318-119809338 (+)	594 bp
Tssr48463	Chr5:119809502-119809517 (+)	776 bp
Tssr48464	Chr5:119809655-119809678 (+)	933 bp
Tssr48465	Chr5:119809717-119809727 (+)	988 bp
Tssr48466	Chr5:119809748-119809764 (+)	1,022 bp
Tssr48467	Chr5:119809893-119809929 (+)	1,177 bp
Tssr48468	Chr5:119818286-119818301 (+)	9,560 bp
Tssr48469	Chr5:119818331-119818352 (+)	9,608 bp
Tssr48470	Chr5:119818433-119818488 (+)	9,727 bp
Tssr48471	Chr5:119819077-119819078 (+)	10,344 bp
Tssr1618	Chr5:119822595-119822610 (+)	13,869 bp

Tbx3 is Candidate Gene for:

QTL	Genetic Location*	Genome Location (GRCm39)	Reference	QTL Note
Eae39r	Chr5, syntenic		J:295093	Development of autoimmune diseases is the result of a complex interplay between hereditary and environmental factors, with multiple genes contributing to the pathogenesis in human disease and in experimental models for disease. The genetic locus Eae39, located on mouse chromosome 5, was previously linked to experimental autoimmune encephalomyelitis (EAE), an experimental model for multiple sclerosis. Subsequently, it was also shown to influence CIA development and severity [8, 10]. Eae39 congenic and sub-congenic lines were bred on the genetic background of the B10.RIII strain [7]. In the present study, the Eae39 sub-locus, Eae39r, was investigated. This locus comprises four protein-coding genes: Mediator complex subunit 13-like (Med13l), T-box transcription factor 3 (Tbx3), T-box transcription factor 5 (Tbx5), and Probable RNA-binding protein 19 (Rbm19). The authors previously showed that genetic polymorphisms in Med13L do not affect the immune phenotype in BR.RIIIS/J-Eae39r congenic mice and are predicted to be non-disease associated (Sardar et al., 2018). BR.RIIIS/J-Eae39r congenic mice were produced by introduction of the Eae39r fragment from the CIA-resistant RIIIS/J donor strain, purchased from Jackson Laboratory (Bar Harbor, ME, USA), to the CIA susceptible B10.RIII background strain, provided by J. Klein (Tbingen, Germany), as previously described [8]. The sub-congenic line BR.RIIIS/J-Eae39r2 was produced by further inter-crossing heterozygous BR.RIIIS/J-Eae39r mice. Purified genomic DNA was used for genotyping by high-resolution melting (HRM) SNP genotyping for rs33583463 (5:118596773 bp; mouse genome assembly GRCm38) and rs29824716 (5:120043597 bp; mouse genome assembly GRCm38). Gene expression studies have revealed differential expression of Tbx3 in B cells, where low expression was accompanied by a higher B cell response upon B cell receptor stimulation in vitro. Furthermore, we showed that serum TBX3 levels rise concomitantly with increasing severity of CIA. From these results, the authors suggest that TBX3 is a novel factor important for the regulation of gene transcription in the immune system and that genetic polymorphisms, resulting in lower expression of Tbx3, are contributing to a more severe form of CIA and high titers of autoantibodies. They also propose TBX3 as a putative diagnostic biomarker for rheumatoid arthritis.

*cM position of peak correlated region/marker