Incidental Mutation 'I2289:T'
ID 590
Institutional Source Beutler Lab
Gene Symbol T
Ensembl Gene ENSMUSG00000062327
Gene Name brachyury, T-box transcription factor T
Synonyms Tbxt, Bra, T1
Accession Numbers
Essential gene? Probably essential (E-score: 0.961) question?
Stock # I2289 (G3) of strain 633
Quality Score
Status Validated
Chromosome 17
Chromosomal Location 8653255-8661328 bp(+) (GRCm39)
Type of Mutation missense
DNA Base Change (assembly) A to T at 8657474 bp (GRCm39)
Zygosity Homozygous
Amino Acid Change Threonine to Serine at position 112 (T112S)
Ref Sequence ENSEMBL: ENSMUSP00000135526 (fasta)
Gene Model predicted gene model for transcript(s): [ENSMUST00000074667] [ENSMUST00000136922] [ENSMUST00000177118]
AlphaFold P20293
Predicted Effect probably benign
Transcript: ENSMUST00000074667
AA Change: T253S

PolyPhen 2 Score 0.000 (Sensitivity: 1.00; Specificity: 0.00)
SMART Domains Protein: ENSMUSP00000074236
Gene: ENSMUSG00000062327
AA Change: T253S

DomainStartEndE-ValueType
TBOX 41 224 5.53e-120 SMART
low complexity region 391 400 N/A INTRINSIC
Predicted Effect probably benign
Transcript: ENSMUST00000136922
SMART Domains Protein: ENSMUSP00000119581
Gene: ENSMUSG00000062327

DomainStartEndE-ValueType
TBOX 1 137 3.02e-62 SMART
Predicted Effect probably benign
Transcript: ENSMUST00000177118
AA Change: T112S

PolyPhen 2 Score 0.000 (Sensitivity: 1.00; Specificity: 0.00)
SMART Domains Protein: ENSMUSP00000135526
Gene: ENSMUSG00000062327
AA Change: T112S

DomainStartEndE-ValueType
TBOX 1 82 3.3e-7 SMART
Meta Mutation Damage Score 0.0662 question?
Coding Region Coverage
  • 1x: 87.8%
  • 3x: 75.8%
Het Detection Efficiency 55.8%
Validation Efficiency 88% (46/52)
MGI Phenotype FUNCTION: [Summary is not available for the mouse gene. This summary is for the human ortholog.] The protein encoded by this gene is an embryonic nuclear transcription factor that binds to a specific DNA element, the palindromic T-site. It binds through a region in its N-terminus, called the T-box, and effects transcription of genes required for mesoderm formation and differentiation. The protein is localized to notochord-derived cells. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2012]
PHENOTYPE: Homozygous mice die during embryonice development. Heterozygous mice have skeletal abnormalities. On specific genetic backgrounds, some alleles cause partial or complete sex-reversal of chromosomally XY mice. [provided by MGI curators]
Allele List at MGI

All alleles(40) : Targeted, other(2) Transgenic(1) Spontaneous(17) Chemically induced(10) Radiation induced(15)
Other mutations in this stock
Total: 21 list
GeneRefVarChr/LocMutationPredicted EffectZygosity
Adamts12 T A 15: 11,071,894 (GRCm39) L146Q probably benign Homo
Adgrv1 A G 13: 81,585,643 (GRCm39) L4607P probably damaging Het
Amelx A G X: 167,961,009 (GRCm39) probably null Homo
Ankfy1 A G 11: 72,621,311 (GRCm39) K199R probably benign Het
Arfgef1 T C 1: 10,243,478 (GRCm39) K1024E probably damaging Het
Bank1 T A 3: 135,760,179 (GRCm39) D782V probably damaging Homo
Csmd1 A T 8: 15,962,381 (GRCm39) I3271K probably benign Homo
Fat1 A G 8: 45,478,033 (GRCm39) I2360V probably benign Homo
Gldc G A 19: 30,124,576 (GRCm39) R241* probably null Het
Golgb1 A G 16: 36,718,904 (GRCm39) H270R probably benign Het
Heg1 T C 16: 33,583,829 (GRCm39) I1212T probably damaging Het
Hes1 T A 16: 29,884,699 (GRCm39) S53R probably damaging Het
Ibsp G A 5: 104,450,353 (GRCm39) R57Q possibly damaging Homo
Lrp1b A T 2: 41,012,944 (GRCm39) I2001K probably damaging Het
Nf1 G A 11: 79,438,602 (GRCm39) R2181H probably damaging Het
Nrcam C A 12: 44,611,098 (GRCm39) H567Q probably benign Homo
Or51a10 T C 7: 103,698,961 (GRCm39) Y200C probably damaging Homo
Or5bw2 A T 7: 6,573,818 (GRCm39) Y276F probably damaging Het
Rraga T C 4: 86,494,522 (GRCm39) F123L probably damaging Het
Spam1 A G 6: 24,796,477 (GRCm39) I143V probably benign Het
Synj2 A G 17: 6,072,542 (GRCm39) probably benign Homo
Other mutations in T
AlleleSourceChrCoordTypePredicted EffectPPH Score
IGL00805:T APN 17 8,655,997 (GRCm39) missense probably benign 0.01
IGL01155:T APN 17 8,660,577 (GRCm39) splice site probably null
IGL02343:T APN 17 8,658,732 (GRCm39) splice site probably benign
IGL02626:T APN 17 8,654,069 (GRCm39) missense probably damaging 0.99
IGL02628:T APN 17 8,654,190 (GRCm39) missense probably damaging 1.00
IGL02970:T APN 17 8,654,217 (GRCm39) missense probably damaging 0.97
R0097:T UTSW 17 8,658,733 (GRCm39) splice site probably benign
R0097:T UTSW 17 8,658,733 (GRCm39) splice site probably benign
R1164:T UTSW 17 8,658,771 (GRCm39) missense probably benign 0.00
R1993:T UTSW 17 8,660,634 (GRCm39) missense probably benign 0.00
R5148:T UTSW 17 8,655,037 (GRCm39) missense probably damaging 1.00
R5423:T UTSW 17 8,660,597 (GRCm39) missense probably damaging 1.00
R5710:T UTSW 17 8,660,474 (GRCm39) missense probably benign 0.00
R6160:T UTSW 17 8,660,618 (GRCm39) missense probably benign 0.00
R6196:T UTSW 17 8,655,996 (GRCm39) missense possibly damaging 0.73
R6447:T UTSW 17 8,660,463 (GRCm39) missense possibly damaging 0.50
R8294:T UTSW 17 8,653,364 (GRCm39) start codon destroyed probably null 0.25
R8813:T UTSW 17 8,653,532 (GRCm39) missense probably benign 0.08
R9802:T UTSW 17 8,654,988 (GRCm39) missense probably damaging 0.99
RF010:T UTSW 17 8,660,540 (GRCm39) missense probably benign
Nature of Mutation

DNA sequencing using the SOLiD technique identified an A to T transversion at position 865 of the T transcript in exon 6 of 8 exons using Genbank record NM_009309.2.  Two transcripts of the T gene are displayed on Ensembl and Vega.  The mutated nucleotide causes a threonine to serine substitution at amino acid 253 of the encoded protein. The mutation has been confirmed by DNA sequencing using the Sanger method.

Protein Function and Prediction

The T gene encodes a 436 amino acid protein known as Brachyury that is involved in the transcriptional regulation of genes required for mesoderm formation and differentiation. Brachyury binds to a palindromic site (called T site) and activates gene transcription. The protein contains a T-box DNA binding domain at residues 51-219 (Uniprot P20293). Homozygote mice exhibit defects in notochord differentiation and mesoderm formation, lack a trunk and tail, and die around embryonic day 10. Heterozygotes have a shortened tail and abnormal sacral vertebrae. On specific genetic backgrounds, some alleles cause partial or complete sex-reversal of XY mice. In humans, a polymorphism in the T gene may cause susceptibility to neural tube defects (NTD; OMIM 182940).  Duplications of the human T gene are associated with increased susceptibility to the development of chordomas (OMIM 215400).  

The T253S alteration does not occur in any known domain.

Posted On 2011-03-08