Incidental Mutation 'YA93:Dntt'
ID84
Institutional Source Beutler Lab
Gene Symbol Dntt
Ensembl Gene ENSMUSG00000025014
Gene Namedeoxynucleotidyltransferase, terminal
SynonymsTdt
Accession Numbers

Genbank: NM_009345 ; MGI: 98659

Is this an essential gene? Non essential (E-score: 0.000) question?
Stock #YA93 of strain inept
Quality Score
Status Validated
Chromosome19
Chromosomal Location41029275-41059523 bp(+) (GRCm38)
Type of Mutationmissense
DNA Base Change (assembly) A to C at 41053187 bp
ZygosityHeterozygous
Amino Acid Change Methionine to Leucine at position 437 (M437L)
Ref Sequence ENSEMBL: ENSMUSP00000107819 (fasta)
Gene Model predicted gene model for transcript(s): [ENSMUST00000051806] [ENSMUST00000112200]
Predicted Effect probably benign
Transcript: ENSMUST00000051806
AA Change: M437L

PolyPhen 2 Score 0.000 (Sensitivity: 1.00; Specificity: 0.00)
SMART Domains Protein: ENSMUSP00000062078
Gene: ENSMUSG00000025014
AA Change: M437L

DomainStartEndE-ValueType
BRCT 29 114 3.05e-9 SMART
POLXc 163 529 5.68e-196 SMART
Predicted Effect probably benign
Transcript: ENSMUST00000112200
AA Change: M437L

PolyPhen 2 Score 0.000 (Sensitivity: 1.00; Specificity: 0.00)
SMART Domains Protein: ENSMUSP00000107819
Gene: ENSMUSG00000025014
AA Change: M437L

DomainStartEndE-ValueType
BRCT 29 114 3.05e-9 SMART
POLXc 163 509 1.19e-198 SMART
Meta Mutation Damage Score 0.0898 question?
Coding Region Coverage
  • 1x: 90.4%
  • 3x: 81.3%
Validation Efficiency 88% (101/115)
MGI Phenotype FUNCTION: [Summary is not available for the mouse gene. This summary is for the human ortholog.] This gene is a member of the DNA polymerase type-X family and encodes a template-independent DNA polymerase that catalyzes the addition of deoxynucleotides to the 3'-hydroxyl terminus of oligonucleotide primers. In vivo, the encoded protein is expressed in a restricted population of normal and malignant pre-B and pre-T lymphocytes during early differentiation, where it generates antigen receptor diversity by synthesizing non-germ line elements (N-regions) at the junctions of rearranged Ig heavy chain and T cell receptor gene segments. Alternatively spliced transcript variants encoding different isoforms of this gene have been described. [provided by RefSeq, Jul 2008]
PHENOTYPE: Homozygous inactivation of this gene results in lack of "N" nucleotide insertions at the junctions of immunoglobulin and T cell receptor V(D)J rearrangements. Forced expression of terminal deoxynucleotidyl transferase in fetal thymus leads to decreased gamma-delta T cell number. [provided by MGI curators]
Allele List at MGI

All alleles(4) : Targeted, knock-out(2) Targeted, other(2)

Other mutations in this stock
Total: 15 list
GeneRefVarChr/LocMutationPredicted EffectZygosity
Arhgef4 C T 1: 34,732,217 R1202W probably benign Het
B4galnt4 T A 7: 141,067,411 I358K possibly damaging Homo
Chodl A G 16: 78,941,282 H46R probably benign Homo
Cubn C A 2: 13,383,992 R1468L probably benign Het
Dlg5 G A 14: 24,155,133 probably benign Het
Gm8251 A G 1: 44,065,085 probably benign Het
Grsf1 G A 5: 88,673,735 P157S probably damaging Het
Lct C T 1: 128,301,320 G812D probably damaging Het
Osbpl5 T A 7: 143,693,870 I720F probably benign Homo
Pbld2 T A 10: 63,054,445 Y211N possibly damaging Het
Peg3 T A 7: 6,711,647 E192V probably damaging Het
Ptbp3 T C 4: 59,524,413 T38A possibly damaging Het
Rpap3 T A 15: 97,693,233 E241V possibly damaging Het
Scara3 C A 14: 65,930,949 M406I probably damaging Het
Serpinf2 C A 11: 75,432,684 V399L probably benign Het
Other mutations in Dntt
AlleleSourceChrCoordTypePredicted EffectPPH Score
IGL00827:Dntt APN 19 41039823 missense probably benign 0.01
IGL01531:Dntt APN 19 41053238 nonsense probably null
IGL01859:Dntt APN 19 41037304 missense probably benign
IGL02053:Dntt APN 19 41046274 missense probably benign 0.00
IGL02411:Dntt APN 19 41052985 splice site probably null
IGL03180:Dntt APN 19 41029551 missense probably benign 0.09
R0106:Dntt UTSW 19 41055746 splice site probably benign
R0122:Dntt UTSW 19 41053038 missense possibly damaging 0.95
R0194:Dntt UTSW 19 41038970 missense possibly damaging 0.90
R0266:Dntt UTSW 19 41059127 missense probably damaging 0.99
R0377:Dntt UTSW 19 41047627 nonsense probably null
R0412:Dntt UTSW 19 41042933 missense probably damaging 1.00
R0604:Dntt UTSW 19 41053149 missense probably benign 0.01
R1350:Dntt UTSW 19 41037139 splice site probably benign
R1577:Dntt UTSW 19 41055785 missense probably damaging 1.00
R1677:Dntt UTSW 19 41029484 missense probably benign 0.26
R2567:Dntt UTSW 19 41041336 missense possibly damaging 0.81
R4380:Dntt UTSW 19 41053233 missense probably damaging 1.00
R4703:Dntt UTSW 19 41039803 missense probably benign 0.00
R4999:Dntt UTSW 19 41039856 missense probably damaging 0.99
R6257:Dntt UTSW 19 41053062 missense probably damaging 1.00
R6757:Dntt UTSW 19 41037162 missense probably damaging 1.00
R7340:Dntt UTSW 19 41058565 critical splice acceptor site probably null
R7388:Dntt UTSW 19 41038979 missense probably benign 0.01
R7553:Dntt UTSW 19 41029487 missense probably damaging 0.99
R7806:Dntt UTSW 19 41029632 missense probably benign 0.02
R8145:Dntt UTSW 19 41055785 missense probably damaging 1.00
Z1177:Dntt UTSW 19 41055815 missense probably damaging 1.00
Nature of Mutation
DNA sequencing using the SOLiD technique identified an A to C transversion at position 1473 of the Dntt transcript in exon 9 of 12 total exons. Two transcripts of the Dntt gene are displayed on Ensembl. The mutated nucleotide causes a methionine to leucine substitution at amino acid 437 of the encoded protein. The mutation has been confirmed by DNA sequencing using the Sanger method (Figure 1).
Protein Function and Prediction
The Dntt gene encodes a 530 amino acid protein that belongs to the DNA polymerase type-X family. Dntt or Tdt is a template-independent DNA polymerase which catalyzes the random addition of deoxynucleoside 5'-triphosphate to the 3'-end of a DNA initiator. One of the in vivo functions of this enzyme is the addition of nucleotides at the junction (N region) of rearranged Ig heavy chain and T-cell receptor (TCR) or BCR gene segments during the maturation of B- and T-cells. Tdt contains a BRCT domain at amino acids 27-124, which appears to act as a phospho-protein binding domain. Tdt needs magnesium to function and binds to this ion using amino acids 253, 255, 343, 345 and 434 (Uniprot P09838). 
 
The M437L change is predicted to be benign by the PolyPhen program.
Posted On2010-03-02