Incidental Mutation 'R4428:Tardbp'
ID 328267
Institutional Source Beutler Lab
Gene Symbol Tardbp
Ensembl Gene ENSMUSG00000041459
Gene Name TAR DNA binding protein
Synonyms Tdp43, TDP-43, 1190002A23Rik
MMRRC Submission 041698-MU
Accession Numbers
Essential gene? Essential (E-score: 1.000) question?
Stock # R4428 (G1)
Quality Score 225
Status Validated
Chromosome 4
Chromosomal Location 148696839-148711476 bp(-) (GRCm39)
Type of Mutation missense
DNA Base Change (assembly) A to G at 148709659 bp (GRCm39)
Zygosity Heterozygous
Amino Acid Change Valine to Alanine at position 54 (V54A)
Ref Sequence ENSEMBL: ENSMUSP00000140832 (fasta)
Gene Model predicted gene model for transcript(s): [ENSMUST00000045180] [ENSMUST00000084125] [ENSMUST00000095719] [ENSMUST00000105699] [ENSMUST00000105700] [ENSMUST00000105702] [ENSMUST00000165113] [ENSMUST00000189048] [ENSMUST00000188134] [ENSMUST00000190696] [ENSMUST00000186947] [ENSMUST00000185673] [ENSMUST00000172073] [ENSMUST00000187939] [ENSMUST00000140897] [ENSMUST00000190552] [ENSMUST00000191450]
AlphaFold Q921F2
Predicted Effect possibly damaging
Transcript: ENSMUST00000045180
AA Change: V54A

PolyPhen 2 Score 0.883 (Sensitivity: 0.82; Specificity: 0.94)
SMART Domains Protein: ENSMUSP00000038113
Gene: ENSMUSG00000041459
AA Change: V54A

DomainStartEndE-ValueType
RRM 105 176 1.38e-17 SMART
RRM 192 258 7.03e-10 SMART
Predicted Effect possibly damaging
Transcript: ENSMUST00000084125
AA Change: V54A

PolyPhen 2 Score 0.695 (Sensitivity: 0.86; Specificity: 0.92)
SMART Domains Protein: ENSMUSP00000081142
Gene: ENSMUSG00000041459
AA Change: V54A

DomainStartEndE-ValueType
RRM 105 176 1.38e-17 SMART
RRM 192 258 7.03e-10 SMART
low complexity region 273 316 N/A INTRINSIC
low complexity region 321 329 N/A INTRINSIC
low complexity region 342 358 N/A INTRINSIC
low complexity region 368 380 N/A INTRINSIC
low complexity region 386 404 N/A INTRINSIC
Predicted Effect possibly damaging
Transcript: ENSMUST00000095719
AA Change: V54A

PolyPhen 2 Score 0.883 (Sensitivity: 0.82; Specificity: 0.94)
SMART Domains Protein: ENSMUSP00000093386
Gene: ENSMUSG00000041459
AA Change: V54A

DomainStartEndE-ValueType
RRM 105 176 1.38e-17 SMART
RRM 192 258 7.03e-10 SMART
low complexity region 274 285 N/A INTRINSIC
Predicted Effect possibly damaging
Transcript: ENSMUST00000105699
AA Change: V54A

PolyPhen 2 Score 0.883 (Sensitivity: 0.82; Specificity: 0.94)
SMART Domains Protein: ENSMUSP00000101324
Gene: ENSMUSG00000041459
AA Change: V54A

DomainStartEndE-ValueType
RRM 105 176 1.38e-17 SMART
RRM 192 258 7.03e-10 SMART
Predicted Effect possibly damaging
Transcript: ENSMUST00000105700
AA Change: V54A

PolyPhen 2 Score 0.883 (Sensitivity: 0.82; Specificity: 0.94)
SMART Domains Protein: ENSMUSP00000101325
Gene: ENSMUSG00000041459
AA Change: V54A

DomainStartEndE-ValueType
RRM 105 176 1.38e-17 SMART
RRM 192 258 7.03e-10 SMART
Predicted Effect possibly damaging
Transcript: ENSMUST00000105702
AA Change: V54A

PolyPhen 2 Score 0.883 (Sensitivity: 0.82; Specificity: 0.94)
SMART Domains Protein: ENSMUSP00000101327
Gene: ENSMUSG00000041459
AA Change: V54A

DomainStartEndE-ValueType
RRM 105 176 1.38e-17 SMART
RRM 192 258 7.03e-10 SMART
Predicted Effect noncoding transcript
Transcript: ENSMUST00000190478
Predicted Effect possibly damaging
Transcript: ENSMUST00000165113
AA Change: V54A

PolyPhen 2 Score 0.883 (Sensitivity: 0.82; Specificity: 0.94)
SMART Domains Protein: ENSMUSP00000129342
Gene: ENSMUSG00000041459
AA Change: V54A

DomainStartEndE-ValueType
RRM 105 176 1.38e-17 SMART
RRM 192 258 7.03e-10 SMART
Predicted Effect possibly damaging
Transcript: ENSMUST00000189048
AA Change: V54A

PolyPhen 2 Score 0.883 (Sensitivity: 0.82; Specificity: 0.94)
SMART Domains Protein: ENSMUSP00000140364
Gene: ENSMUSG00000041459
AA Change: V54A

DomainStartEndE-ValueType
RRM 105 176 1.38e-17 SMART
RRM 192 258 7.03e-10 SMART
Predicted Effect possibly damaging
Transcript: ENSMUST00000188134
AA Change: V54A

PolyPhen 2 Score 0.883 (Sensitivity: 0.82; Specificity: 0.94)
SMART Domains Protein: ENSMUSP00000139476
Gene: ENSMUSG00000041459
AA Change: V54A

DomainStartEndE-ValueType
RRM 105 176 1.38e-17 SMART
RRM 192 258 7.03e-10 SMART
Predicted Effect probably benign
Transcript: ENSMUST00000190696
AA Change: V54A

PolyPhen 2 Score 0.426 (Sensitivity: 0.89; Specificity: 0.90)
SMART Domains Protein: ENSMUSP00000139637
Gene: ENSMUSG00000041459
AA Change: V54A

DomainStartEndE-ValueType
Blast:RRM_2 55 79 8e-11 BLAST
Predicted Effect possibly damaging
Transcript: ENSMUST00000186947
AA Change: V54A

PolyPhen 2 Score 0.883 (Sensitivity: 0.82; Specificity: 0.94)
SMART Domains Protein: ENSMUSP00000140529
Gene: ENSMUSG00000041459
AA Change: V54A

DomainStartEndE-ValueType
RRM 105 176 5.8e-20 SMART
low complexity region 215 243 N/A INTRINSIC
Predicted Effect possibly damaging
Transcript: ENSMUST00000185673
AA Change: V54A

PolyPhen 2 Score 0.695 (Sensitivity: 0.86; Specificity: 0.92)
SMART Domains Protein: ENSMUSP00000141010
Gene: ENSMUSG00000041459
AA Change: V54A

DomainStartEndE-ValueType
Pfam:RRM_1 106 149 3e-12 PFAM
Pfam:RRM_6 106 149 1.3e-6 PFAM
Predicted Effect possibly damaging
Transcript: ENSMUST00000172073
AA Change: V54A

PolyPhen 2 Score 0.883 (Sensitivity: 0.82; Specificity: 0.94)
SMART Domains Protein: ENSMUSP00000130963
Gene: ENSMUSG00000041459
AA Change: V54A

DomainStartEndE-ValueType
RRM 105 176 1.38e-17 SMART
RRM 192 258 7.03e-10 SMART
low complexity region 274 285 N/A INTRINSIC
Predicted Effect probably benign
Transcript: ENSMUST00000187939
SMART Domains Protein: ENSMUSP00000140928
Gene: ENSMUSG00000041459

DomainStartEndE-ValueType
RRM 18 84 3e-12 SMART
Predicted Effect probably benign
Transcript: ENSMUST00000140897
SMART Domains Protein: ENSMUSP00000135135
Gene: ENSMUSG00000041459

DomainStartEndE-ValueType
Blast:RRM_2 1 28 2e-13 BLAST
RRM 44 110 3e-12 SMART
Predicted Effect probably benign
Transcript: ENSMUST00000190552
SMART Domains Protein: ENSMUSP00000141052
Gene: ENSMUSG00000041459

DomainStartEndE-ValueType
RRM_2 1 56 6.1e-4 SMART
RRM 72 138 3e-12 SMART
Predicted Effect probably benign
Transcript: ENSMUST00000185824
Predicted Effect possibly damaging
Transcript: ENSMUST00000191450
AA Change: V54A

PolyPhen 2 Score 0.883 (Sensitivity: 0.82; Specificity: 0.94)
SMART Domains Protein: ENSMUSP00000140832
Gene: ENSMUSG00000041459
AA Change: V54A

DomainStartEndE-ValueType
RRM 105 176 5.8e-20 SMART
RRM 192 258 3e-12 SMART
Predicted Effect probably benign
Transcript: ENSMUST00000191378
Meta Mutation Damage Score 0.6521 question?
Coding Region Coverage
  • 1x: 99.2%
  • 3x: 98.6%
  • 10x: 97.4%
  • 20x: 95.5%
Validation Efficiency 100% (46/46)
MGI Phenotype FUNCTION: [Summary is not available for the mouse gene. This summary is for the human ortholog.] HIV-1, the causative agent of acquired immunodeficiency syndrome (AIDS), contains an RNA genome that produces a chromosomally integrated DNA during the replicative cycle. Activation of HIV-1 gene expression by the transactivator Tat is dependent on an RNA regulatory element (TAR) located downstream of the transcription initiation site. The protein encoded by this gene is a transcriptional repressor that binds to chromosomally integrated TAR DNA and represses HIV-1 transcription. In addition, this protein regulates alternate splicing of the CFTR gene. A similar pseudogene is present on chromosome 20. [provided by RefSeq, Jul 2008]
PHENOTYPE: Homozygous deficient mice display embryonic lethality before somite formation with impaired inner cell mass proliferation. [provided by MGI curators]
Allele List at MGI
Other mutations in this stock
Total: 41 list
GeneRefVarChr/LocMutationPredicted EffectZygosity
0610040J01Rik G T 5: 64,056,182 (GRCm39) probably benign Het
Abcc1 T A 16: 14,263,164 (GRCm39) V708E probably damaging Het
Bag4 C T 8: 26,259,516 (GRCm39) A228T probably benign Het
Ccdc18 A G 5: 108,283,943 (GRCm39) Y82C probably benign Het
Cd82 T C 2: 93,250,214 (GRCm39) Y266C probably damaging Het
Chrna4 A G 2: 180,670,413 (GRCm39) S448P probably damaging Het
Cldn8 A C 16: 88,359,619 (GRCm39) M102R probably damaging Het
Cmpk1 T C 4: 114,820,559 (GRCm39) E180G probably benign Het
Dock8 T C 19: 25,177,863 (GRCm39) I2066T probably damaging Het
Dock8 T C 19: 25,042,754 (GRCm39) V112A probably benign Het
Fgf3 T C 7: 144,394,444 (GRCm39) V86A probably damaging Het
Frem2 A G 3: 53,561,759 (GRCm39) I916T probably benign Het
Gsk3b T A 16: 38,014,298 (GRCm39) L252Q probably damaging Het
Kif18a A G 2: 109,118,466 (GRCm39) T94A probably damaging Het
Klhdc1 T A 12: 69,315,000 (GRCm39) probably benign Het
Klhl25 T A 7: 75,515,162 (GRCm39) F23I probably damaging Het
Mapk7 T C 11: 61,380,055 (GRCm39) D701G possibly damaging Het
Mbd5 A T 2: 49,169,776 (GRCm39) Q47L possibly damaging Het
Nrcam A G 12: 44,623,558 (GRCm39) D1049G possibly damaging Het
Olfml2a G T 2: 38,831,755 (GRCm39) M111I probably damaging Het
Or3a1c T C 11: 74,046,025 (GRCm39) F15S probably damaging Het
Pld2 A T 11: 70,432,160 (GRCm39) H93L probably damaging Het
Pomgnt2 T C 9: 121,811,320 (GRCm39) E487G possibly damaging Het
Psg17 G T 7: 18,550,717 (GRCm39) N379K probably benign Het
Rfk T A 19: 17,375,959 (GRCm39) H84Q possibly damaging Het
Scn8a A G 15: 100,881,784 (GRCm39) Y617C probably damaging Het
Sema3d T C 5: 12,498,087 (GRCm39) F31S probably benign Het
Shq1 T C 6: 100,647,889 (GRCm39) Y45C probably damaging Het
Siglecg C T 7: 43,067,350 (GRCm39) P639L possibly damaging Het
Skp2 A T 15: 9,117,034 (GRCm39) N325K probably benign Het
Sost G A 11: 101,857,670 (GRCm39) P44S probably damaging Het
Sp8 T A 12: 118,812,938 (GRCm39) S264R possibly damaging Het
Sun1 T C 5: 139,220,230 (GRCm39) probably benign Het
Tert T A 13: 73,775,594 (GRCm39) F115Y probably damaging Het
Tmem181a T A 17: 6,346,061 (GRCm39) L185H probably damaging Het
Tmem68 A T 4: 3,569,534 (GRCm39) I52K probably benign Het
Trhde A T 10: 114,339,028 (GRCm39) L594Q probably damaging Het
Umps A C 16: 33,781,956 (GRCm39) V322G probably damaging Het
Vmn2r109 T C 17: 20,773,286 (GRCm39) D445G probably benign Het
Vmn2r22 T C 6: 123,614,817 (GRCm39) T258A possibly damaging Het
Vmn2r4 C T 3: 64,322,590 (GRCm39) G43E probably damaging Het
Other mutations in Tardbp
AlleleSourceChrCoordTypePredicted EffectPPH Score
IGL01472:Tardbp APN 4 148,706,521 (GRCm39) missense probably benign 0.03
IGL02569:Tardbp APN 4 148,703,639 (GRCm39) critical splice donor site probably null
R4690:Tardbp UTSW 4 148,697,078 (GRCm39) makesense probably null
R4824:Tardbp UTSW 4 148,702,050 (GRCm39) missense probably benign 0.33
R4925:Tardbp UTSW 4 148,703,108 (GRCm39) missense probably benign 0.11
R5057:Tardbp UTSW 4 148,703,813 (GRCm39) critical splice acceptor site probably null
R5137:Tardbp UTSW 4 148,706,494 (GRCm39) missense possibly damaging 0.77
R5488:Tardbp UTSW 4 148,703,097 (GRCm39) missense probably benign 0.03
R5833:Tardbp UTSW 4 148,702,117 (GRCm39) missense probably damaging 1.00
R8164:Tardbp UTSW 4 148,703,060 (GRCm39) missense probably benign 0.00
R8862:Tardbp UTSW 4 148,702,755 (GRCm39) missense possibly damaging 0.73
R8905:Tardbp UTSW 4 148,705,093 (GRCm39) missense probably benign 0.01
R9664:Tardbp UTSW 4 148,709,751 (GRCm39) missense probably damaging 0.98
Predicted Primers PCR Primer
(F):5'- GACTATTCTCCCAGCACACATG -3'
(R):5'- AGGAATCTTTTCAGGAAGTGGG -3'

Sequencing Primer
(F):5'- GAAGCCCTGGATATTATAGTCTCAC -3'
(R):5'- TCTTTTCAGGAAGTGGGAATAAAGTG -3'
Posted On 2015-07-07