Incidental Mutation 'R5347:Tcf3'
ID 422691
Institutional Source Beutler Lab
Gene Symbol Tcf3
Ensembl Gene ENSMUSG00000020167
Gene Name transcription factor 3
Synonyms E2A, Pan1, Pan2, A1, bHLHb21, ALF2, E47, E12, Tcfe2a
MMRRC Submission 042926-MU
Accession Numbers
Essential gene? Probably essential (E-score: 0.951) question?
Stock # R5347 (G1)
Quality Score 225
Status Not validated
Chromosome 10
Chromosomal Location 80245348-80269481 bp(-) (GRCm39)
Type of Mutation missense
DNA Base Change (assembly) A to G at 80246045 bp (GRCm39)
Zygosity Heterozygous
Amino Acid Change Valine to Alanine at position 626 (V626A)
Ref Sequence ENSEMBL: ENSMUSP00000100983 (fasta)
Gene Model predicted gene model for transcript(s): [ENSMUST00000020372] [ENSMUST00000020377] [ENSMUST00000020379] [ENSMUST00000105339] [ENSMUST00000105340] [ENSMUST00000105341] [ENSMUST00000105342] [ENSMUST00000105343] [ENSMUST00000105344] [ENSMUST00000105345] [ENSMUST00000105346]
AlphaFold P15806
Predicted Effect probably benign
Transcript: ENSMUST00000020372
SMART Domains Protein: ENSMUSP00000020372
Gene: ENSMUSG00000020163

DomainStartEndE-ValueType
Pfam:UCR_6-4kD 1 55 1.2e-36 PFAM
Predicted Effect probably damaging
Transcript: ENSMUST00000020377
AA Change: V627A

PolyPhen 2 Score 1.000 (Sensitivity: 0.00; Specificity: 1.00)
SMART Domains Protein: ENSMUSP00000020377
Gene: ENSMUSG00000020167
AA Change: V627A

DomainStartEndE-ValueType
low complexity region 55 73 N/A INTRINSIC
low complexity region 125 148 N/A INTRINSIC
low complexity region 242 265 N/A INTRINSIC
low complexity region 340 355 N/A INTRINSIC
low complexity region 462 480 N/A INTRINSIC
low complexity region 495 506 N/A INTRINSIC
low complexity region 528 539 N/A INTRINSIC
HLH 553 606 2.66e-10 SMART
Predicted Effect probably damaging
Transcript: ENSMUST00000020379
AA Change: V624A

PolyPhen 2 Score 0.998 (Sensitivity: 0.27; Specificity: 0.99)
SMART Domains Protein: ENSMUSP00000020379
Gene: ENSMUSG00000020167
AA Change: V624A

DomainStartEndE-ValueType
low complexity region 55 73 N/A INTRINSIC
low complexity region 125 148 N/A INTRINSIC
low complexity region 241 264 N/A INTRINSIC
low complexity region 339 354 N/A INTRINSIC
low complexity region 462 480 N/A INTRINSIC
low complexity region 495 506 N/A INTRINSIC
HLH 550 603 8.79e-11 SMART
Predicted Effect probably damaging
Transcript: ENSMUST00000105339
AA Change: V623A

PolyPhen 2 Score 0.996 (Sensitivity: 0.55; Specificity: 0.98)
SMART Domains Protein: ENSMUSP00000100976
Gene: ENSMUSG00000020167
AA Change: V623A

DomainStartEndE-ValueType
low complexity region 55 73 N/A INTRINSIC
low complexity region 125 148 N/A INTRINSIC
low complexity region 241 264 N/A INTRINSIC
low complexity region 336 351 N/A INTRINSIC
low complexity region 458 476 N/A INTRINSIC
low complexity region 491 502 N/A INTRINSIC
low complexity region 524 535 N/A INTRINSIC
HLH 549 602 2.66e-10 SMART
Predicted Effect probably benign
Transcript: ENSMUST00000105340
AA Change: V623A

PolyPhen 2 Score 0.167 (Sensitivity: 0.92; Specificity: 0.87)
SMART Domains Protein: ENSMUSP00000100977
Gene: ENSMUSG00000020167
AA Change: V623A

DomainStartEndE-ValueType
low complexity region 55 73 N/A INTRINSIC
low complexity region 125 148 N/A INTRINSIC
low complexity region 241 264 N/A INTRINSIC
low complexity region 339 354 N/A INTRINSIC
low complexity region 462 480 N/A INTRINSIC
low complexity region 495 506 N/A INTRINSIC
HLH 549 602 8.79e-11 SMART
Predicted Effect probably benign
Transcript: ENSMUST00000105341
AA Change: V620A

PolyPhen 2 Score 0.420 (Sensitivity: 0.89; Specificity: 0.90)
SMART Domains Protein: ENSMUSP00000100978
Gene: ENSMUSG00000020167
AA Change: V620A

DomainStartEndE-ValueType
low complexity region 55 73 N/A INTRINSIC
low complexity region 125 148 N/A INTRINSIC
low complexity region 241 264 N/A INTRINSIC
low complexity region 336 351 N/A INTRINSIC
low complexity region 458 476 N/A INTRINSIC
low complexity region 491 502 N/A INTRINSIC
HLH 546 599 8.79e-11 SMART
Predicted Effect probably damaging
Transcript: ENSMUST00000105342
AA Change: V628A

PolyPhen 2 Score 0.998 (Sensitivity: 0.27; Specificity: 0.99)
SMART Domains Protein: ENSMUSP00000100979
Gene: ENSMUSG00000020167
AA Change: V628A

DomainStartEndE-ValueType
low complexity region 55 73 N/A INTRINSIC
low complexity region 125 148 N/A INTRINSIC
low complexity region 242 265 N/A INTRINSIC
low complexity region 340 355 N/A INTRINSIC
low complexity region 463 481 N/A INTRINSIC
low complexity region 496 507 N/A INTRINSIC
low complexity region 529 540 N/A INTRINSIC
HLH 554 607 2.66e-10 SMART
Predicted Effect probably benign
Transcript: ENSMUST00000105343
AA Change: V624A

PolyPhen 2 Score 0.075 (Sensitivity: 0.93; Specificity: 0.85)
SMART Domains Protein: ENSMUSP00000100980
Gene: ENSMUSG00000020167
AA Change: V624A

DomainStartEndE-ValueType
low complexity region 55 73 N/A INTRINSIC
low complexity region 125 148 N/A INTRINSIC
low complexity region 242 265 N/A INTRINSIC
low complexity region 340 355 N/A INTRINSIC
low complexity region 462 480 N/A INTRINSIC
low complexity region 495 506 N/A INTRINSIC
HLH 550 603 8.79e-11 SMART
Predicted Effect probably damaging
Transcript: ENSMUST00000105344
AA Change: V625A

PolyPhen 2 Score 0.998 (Sensitivity: 0.27; Specificity: 0.99)
SMART Domains Protein: ENSMUSP00000100981
Gene: ENSMUSG00000020167
AA Change: V625A

DomainStartEndE-ValueType
low complexity region 55 73 N/A INTRINSIC
low complexity region 125 148 N/A INTRINSIC
low complexity region 242 265 N/A INTRINSIC
low complexity region 340 355 N/A INTRINSIC
low complexity region 463 481 N/A INTRINSIC
low complexity region 496 507 N/A INTRINSIC
HLH 551 604 8.79e-11 SMART
Predicted Effect probably benign
Transcript: ENSMUST00000105345
AA Change: V623A

PolyPhen 2 Score 0.013 (Sensitivity: 0.96; Specificity: 0.78)
SMART Domains Protein: ENSMUSP00000100982
Gene: ENSMUSG00000020167
AA Change: V623A

DomainStartEndE-ValueType
low complexity region 55 73 N/A INTRINSIC
low complexity region 125 148 N/A INTRINSIC
low complexity region 241 264 N/A INTRINSIC
low complexity region 339 354 N/A INTRINSIC
low complexity region 461 479 N/A INTRINSIC
low complexity region 494 505 N/A INTRINSIC
HLH 549 602 8.79e-11 SMART
Predicted Effect probably damaging
Transcript: ENSMUST00000105346
AA Change: V626A

PolyPhen 2 Score 1.000 (Sensitivity: 0.00; Specificity: 1.00)
SMART Domains Protein: ENSMUSP00000100983
Gene: ENSMUSG00000020167
AA Change: V626A

DomainStartEndE-ValueType
low complexity region 55 73 N/A INTRINSIC
low complexity region 125 148 N/A INTRINSIC
low complexity region 241 264 N/A INTRINSIC
low complexity region 339 354 N/A INTRINSIC
low complexity region 461 479 N/A INTRINSIC
low complexity region 494 505 N/A INTRINSIC
low complexity region 527 538 N/A INTRINSIC
HLH 552 605 2.66e-10 SMART
Predicted Effect unknown
Transcript: ENSMUST00000156990
AA Change: V612A
SMART Domains Protein: ENSMUSP00000121172
Gene: ENSMUSG00000020167
AA Change: V612A

DomainStartEndE-ValueType
low complexity region 47 65 N/A INTRINSIC
low complexity region 117 140 N/A INTRINSIC
low complexity region 234 257 N/A INTRINSIC
low complexity region 329 344 N/A INTRINSIC
low complexity region 451 469 N/A INTRINSIC
low complexity region 484 495 N/A INTRINSIC
HLH 539 592 8.79e-11 SMART
Predicted Effect noncoding transcript
Transcript: ENSMUST00000141683
Predicted Effect noncoding transcript
Transcript: ENSMUST00000129027
Predicted Effect noncoding transcript
Transcript: ENSMUST00000138428
Coding Region Coverage
  • 1x: 99.3%
  • 3x: 98.8%
  • 10x: 97.6%
  • 20x: 96.0%
Validation Efficiency
MGI Phenotype FUNCTION: [Summary is not available for the mouse gene. This summary is for the human ortholog.] This gene encodes a member of the E protein (class I) family of helix-loop-helix transcription factors. E proteins activate transcription by binding to regulatory E-box sequences on target genes as heterodimers or homodimers, and are inhibited by heterodimerization with inhibitor of DNA-binding (class IV) helix-loop-helix proteins. E proteins play a critical role in lymphopoiesis, and the encoded protein is required for B and T lymphocyte development. Deletion of this gene or diminished activity of the encoded protein may play a role in lymphoid malignancies. This gene is also involved in several chromosomal translocations that are associated with lymphoid malignancies including pre-B-cell acute lymphoblastic leukemia (t(1;19), with PBX1), childhood leukemia (t(19;19), with TFPT) and acute leukemia (t(12;19), with ZNF384). Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene, and a pseudogene of this gene is located on the short arm of chromosome 9. [provided by RefSeq, Sep 2011]
PHENOTYPE: Homozygotes for targeted null mutations are devoid of mature B cells, have a partial early block in T-lymphocyte development, and show high postnatal mortality. Many survivors develop T-cell lymphomas between 3 and 10 months of age. [provided by MGI curators]
Allele List at MGI
Other mutations in this stock
Total: 66 list
GeneRefVarChr/LocMutationPredicted EffectZygosity
Acvr2a A G 2: 48,782,166 (GRCm39) Y233C probably damaging Het
Agl A G 3: 116,584,814 (GRCm39) S169P probably damaging Het
Arid1b C T 17: 5,341,332 (GRCm39) Q879* probably null Het
Bbs2 A G 8: 94,819,178 (GRCm39) S64P probably damaging Het
Bend7 G A 2: 4,768,052 (GRCm39) R336Q probably damaging Het
Cacna2d2 A G 9: 107,391,313 (GRCm39) T447A probably benign Het
Ccdc168 T A 1: 44,096,955 (GRCm39) Y1381F probably benign Het
Ccdc169 A T 3: 55,049,740 (GRCm39) probably benign Het
Cdan1 A G 2: 120,560,546 (GRCm39) S275P possibly damaging Het
Cdh15 A G 8: 123,588,802 (GRCm39) N292S probably null Het
Cmtm1 CGGCACGTACTGAAGGTCGCTGACTGGATGGTGTGGCACGTACTGAAGGTCGCTGACTGGATGGTGTGGCACGTACTGAAGGTCGCTGACTGGATGGT CGGCACGTACTGAAGGTCGCTGACTGGATGGTGTGGCACGTACTGAAGGTCGCTGACTGGATGGT 8: 105,036,102 (GRCm39) probably benign Het
Cnnm1 A G 19: 43,430,301 (GRCm39) H473R probably benign Het
Cplx4 G A 18: 66,103,157 (GRCm39) probably benign Het
Crb1 C T 1: 139,265,109 (GRCm39) G103E probably damaging Het
Dnaja3 T A 16: 4,512,346 (GRCm39) V250E possibly damaging Het
Dync2h1 T G 9: 7,129,727 (GRCm39) Q1757P probably damaging Het
Edem3 A G 1: 151,683,202 (GRCm39) Q626R probably damaging Het
Eif2b1 T C 5: 124,716,862 (GRCm39) probably benign Het
Esf1 T A 2: 139,996,801 (GRCm39) K521* probably null Het
Fbxl3 A C 14: 103,320,730 (GRCm39) V239G probably damaging Het
Fhip2a A G 19: 57,367,051 (GRCm39) D198G probably benign Het
Fto A G 8: 92,118,107 (GRCm39) probably benign Het
Gm5773 T C 3: 93,681,090 (GRCm39) L254P probably damaging Het
Gm5916 A T 9: 36,032,012 (GRCm39) W91R probably benign Het
Gpam A T 19: 55,077,269 (GRCm39) L174H probably damaging Het
Grk1 G A 8: 13,464,478 (GRCm39) R450Q probably damaging Het
Hc G A 2: 34,927,636 (GRCm39) A326V probably benign Het
Hectd4 T C 5: 121,442,511 (GRCm39) I1317T probably benign Het
Hlcs A G 16: 94,068,383 (GRCm39) V426A possibly damaging Het
Ighv1-23 T C 12: 114,728,376 (GRCm39) probably benign Het
Itgax G A 7: 127,740,474 (GRCm39) V754I probably benign Het
Krt24 T A 11: 99,173,556 (GRCm39) D255V probably damaging Het
Lnpk T C 2: 74,403,935 (GRCm39) probably benign Het
Loxhd1 G T 18: 77,454,237 (GRCm39) R478L probably damaging Het
Lrrc56 A G 7: 140,789,537 (GRCm39) Q518R probably benign Het
Mbl1 A T 14: 40,880,786 (GRCm39) I225F probably damaging Het
Mmp21 T C 7: 133,277,651 (GRCm39) S392G probably benign Het
Mug2 T G 6: 122,058,551 (GRCm39) F1318V probably damaging Het
Myo5c A G 9: 75,202,487 (GRCm39) N1447S probably null Het
Nbea A C 3: 55,948,297 (GRCm39) V543G probably damaging Het
Necap1 A G 6: 122,857,706 (GRCm39) I96V probably benign Het
Nr3c2 T A 8: 77,937,377 (GRCm39) M872K possibly damaging Het
Nrf1 C T 6: 30,118,967 (GRCm39) T362M probably benign Het
Or14j2 T C 17: 37,885,618 (GRCm39) E232G probably damaging Het
Pcare A G 17: 72,056,930 (GRCm39) S916P probably benign Het
Plekhm3 T C 1: 64,859,149 (GRCm39) E685G probably damaging Het
Robo4 CGG CG 9: 37,322,786 (GRCm39) probably null Het
Sbk3 A T 7: 4,970,422 (GRCm39) S316T probably benign Het
Serpinb9e T C 13: 33,441,767 (GRCm39) L233P probably damaging Het
Set T A 2: 29,959,422 (GRCm39) S132T possibly damaging Het
Slc17a4 C T 13: 24,092,800 (GRCm39) E11K possibly damaging Het
Slc22a6 T A 19: 8,595,917 (GRCm39) N86K possibly damaging Het
Slco1a6 A G 6: 142,032,325 (GRCm39) L600P probably damaging Het
Sp8 A G 12: 118,812,246 (GRCm39) K34E possibly damaging Het
Spen T A 4: 141,198,796 (GRCm39) E3254V probably benign Het
Tcf12 G A 9: 71,792,525 (GRCm39) P53S probably damaging Het
Trpc4ap A G 2: 155,514,908 (GRCm39) probably null Het
Ttc3 T A 16: 94,230,479 (GRCm39) V892D probably damaging Het
Tub G T 7: 108,625,978 (GRCm39) R243L possibly damaging Het
Tubgcp5 A G 7: 55,473,433 (GRCm39) Y837C probably damaging Het
Utp25 A T 1: 192,810,687 (GRCm39) D105E probably benign Het
Wdhd1 A T 14: 47,506,181 (GRCm39) Y244* probably null Het
Xdh T A 17: 74,232,027 (GRCm39) T228S probably benign Het
Zfp418 A C 7: 7,185,534 (GRCm39) Q499P probably benign Het
Zfpm1 G A 8: 123,062,269 (GRCm39) E443K possibly damaging Het
Zfy1 T C Y: 725,950 (GRCm39) H605R possibly damaging Het
Other mutations in Tcf3
AlleleSourceChrCoordTypePredicted EffectPPH Score
IGL01798:Tcf3 APN 10 80,249,043 (GRCm39) missense probably benign 0.30
IGL02676:Tcf3 APN 10 80,256,925 (GRCm39) missense probably damaging 1.00
IGL03066:Tcf3 APN 10 80,248,879 (GRCm39) missense probably damaging 0.97
R0165:Tcf3 UTSW 10 80,248,831 (GRCm39) missense probably damaging 1.00
R0401:Tcf3 UTSW 10 80,256,992 (GRCm39) missense probably damaging 0.99
R0624:Tcf3 UTSW 10 80,249,168 (GRCm39) missense probably damaging 1.00
R2114:Tcf3 UTSW 10 80,246,040 (GRCm39) missense probably damaging 1.00
R5034:Tcf3 UTSW 10 80,253,377 (GRCm39) missense possibly damaging 0.46
R5144:Tcf3 UTSW 10 80,251,071 (GRCm39) missense probably damaging 0.98
R5418:Tcf3 UTSW 10 80,263,517 (GRCm39) missense probably damaging 1.00
R5771:Tcf3 UTSW 10 80,257,450 (GRCm39) intron probably benign
R5786:Tcf3 UTSW 10 80,255,333 (GRCm39) missense probably benign 0.06
R5941:Tcf3 UTSW 10 80,248,878 (GRCm39) missense probably benign 0.06
R6857:Tcf3 UTSW 10 80,252,733 (GRCm39) splice site probably null
R6982:Tcf3 UTSW 10 80,253,384 (GRCm39) missense probably damaging 1.00
R7178:Tcf3 UTSW 10 80,257,433 (GRCm39) missense unknown
R7840:Tcf3 UTSW 10 80,246,301 (GRCm39) missense possibly damaging 0.87
R8336:Tcf3 UTSW 10 80,257,000 (GRCm39) missense probably benign
R8958:Tcf3 UTSW 10 80,246,091 (GRCm39) missense probably damaging 1.00
R9090:Tcf3 UTSW 10 80,253,191 (GRCm39) missense probably benign 0.28
R9271:Tcf3 UTSW 10 80,253,191 (GRCm39) missense probably benign 0.28
R9429:Tcf3 UTSW 10 80,252,436 (GRCm39) missense probably benign 0.00
X0022:Tcf3 UTSW 10 80,253,292 (GRCm39) missense probably damaging 1.00
Predicted Primers PCR Primer
(F):5'- CTCATGCTTCGATGGAGACC -3'
(R):5'- AGACCAAGCTGCTCATCCTG -3'

Sequencing Primer
(F):5'- GACCTGTCTCATCCAGAACCGTC -3'
(R):5'- AGGCGGTGCAGGTCATC -3'
Posted On 2016-08-04