Incidental Mutation 'R0927:Tcf7l2'
ID 80579
Institutional Source Beutler Lab
Gene Symbol Tcf7l2
Ensembl Gene ENSMUSG00000024985
Gene Name transcription factor 7 like 2, T cell specific, HMG box
Synonyms Tcf4, TCF4E, Tcf-4, mTcf-4B, mTcf-4E, TCF4B
MMRRC Submission 039074-MU
Accession Numbers
Essential gene? Essential (E-score: 1.000) question?
Stock # R0927 (G1)
Quality Score 225
Status Not validated
Chromosome 19
Chromosomal Location 55730252-55922086 bp(+) (GRCm39)
Type of Mutation missense
DNA Base Change (assembly) A to G at 55907387 bp (GRCm39)
Zygosity Heterozygous
Amino Acid Change Methionine to Valine at position 340 (M340V)
Ref Sequence ENSEMBL: ENSMUSP00000107287 (fasta)
Gene Model predicted gene model for transcript(s): [ENSMUST00000041717] [ENSMUST00000061496] [ENSMUST00000111646] [ENSMUST00000111653] [ENSMUST00000111654] [ENSMUST00000111656] [ENSMUST00000111662] [ENSMUST00000142291] [ENSMUST00000111657] [ENSMUST00000148666] [ENSMUST00000153888] [ENSMUST00000111658] [ENSMUST00000111659]
AlphaFold no structure available at present
Predicted Effect probably damaging
Transcript: ENSMUST00000041717
AA Change: M335V

PolyPhen 2 Score 0.999 (Sensitivity: 0.14; Specificity: 0.99)
SMART Domains Protein: ENSMUSP00000042950
Gene: ENSMUSG00000024985
AA Change: M335V

DomainStartEndE-ValueType
Pfam:CTNNB1_binding 1 236 1.5e-95 PFAM
HMG 326 396 1.16e-22 SMART
low complexity region 402 410 N/A INTRINSIC
Predicted Effect probably damaging
Transcript: ENSMUST00000061496
AA Change: M335V

PolyPhen 2 Score 1.000 (Sensitivity: 0.00; Specificity: 1.00)
SMART Domains Protein: ENSMUSP00000050081
Gene: ENSMUSG00000024985
AA Change: M335V

DomainStartEndE-ValueType
Pfam:CTNNB1_binding 1 236 1.7e-95 PFAM
HMG 326 396 1.16e-22 SMART
low complexity region 402 410 N/A INTRINSIC
Predicted Effect probably damaging
Transcript: ENSMUST00000111646
AA Change: M175V

PolyPhen 2 Score 0.999 (Sensitivity: 0.14; Specificity: 0.99)
SMART Domains Protein: ENSMUSP00000107273
Gene: ENSMUSG00000024985
AA Change: M175V

DomainStartEndE-ValueType
Pfam:CTNNB1_binding 1 76 2.4e-37 PFAM
HMG 166 236 1.16e-22 SMART
low complexity region 242 250 N/A INTRINSIC
c-clamp 278 298 2.25e-1 SMART
Predicted Effect probably damaging
Transcript: ENSMUST00000111653
AA Change: M340V

PolyPhen 2 Score 0.996 (Sensitivity: 0.55; Specificity: 0.98)
SMART Domains Protein: ENSMUSP00000107280
Gene: ENSMUSG00000024985
AA Change: M340V

DomainStartEndE-ValueType
Pfam:CTNNB1_binding 1 236 2.1e-95 PFAM
HMG 331 401 1.16e-22 SMART
low complexity region 407 415 N/A INTRINSIC
low complexity region 439 452 N/A INTRINSIC
Predicted Effect probably damaging
Transcript: ENSMUST00000111654
AA Change: M354V

PolyPhen 2 Score 1.000 (Sensitivity: 0.00; Specificity: 1.00)
SMART Domains Protein: ENSMUSP00000107281
Gene: ENSMUSG00000024985
AA Change: M354V

DomainStartEndE-ValueType
Pfam:CTNNB1_binding 1 259 4.2e-93 PFAM
HMG 345 415 1.16e-22 SMART
low complexity region 421 429 N/A INTRINSIC
low complexity region 453 466 N/A INTRINSIC
Predicted Effect probably damaging
Transcript: ENSMUST00000111656
AA Change: M335V

PolyPhen 2 Score 0.993 (Sensitivity: 0.70; Specificity: 0.97)
SMART Domains Protein: ENSMUSP00000107283
Gene: ENSMUSG00000024985
AA Change: M335V

DomainStartEndE-ValueType
Pfam:CTNNB1_binding 1 236 1.5e-95 PFAM
HMG 326 396 1.16e-22 SMART
low complexity region 402 410 N/A INTRINSIC
c-clamp 438 458 2.25e-1 SMART
Predicted Effect probably damaging
Transcript: ENSMUST00000111662
AA Change: M335V

PolyPhen 2 Score 0.998 (Sensitivity: 0.27; Specificity: 0.99)
SMART Domains Protein: ENSMUSP00000107291
Gene: ENSMUSG00000024985
AA Change: M335V

DomainStartEndE-ValueType
Pfam:CTNNB1_binding 1 236 1.7e-103 PFAM
HMG 326 396 1.16e-22 SMART
low complexity region 402 410 N/A INTRINSIC
c-clamp 421 442 1.23e-2 SMART
c-clamp 446 476 1.35e-13 SMART
low complexity region 479 506 N/A INTRINSIC
low complexity region 527 547 N/A INTRINSIC
low complexity region 572 586 N/A INTRINSIC
Predicted Effect possibly damaging
Transcript: ENSMUST00000142291
AA Change: M175V

PolyPhen 2 Score 0.879 (Sensitivity: 0.82; Specificity: 0.94)
SMART Domains Protein: ENSMUSP00000118042
Gene: ENSMUSG00000024985
AA Change: M175V

DomainStartEndE-ValueType
Pfam:CTNNB1_binding 1 76 5e-40 PFAM
SCOP:d1j46a_ 164 178 5e-3 SMART
Predicted Effect probably damaging
Transcript: ENSMUST00000111657
AA Change: M335V

PolyPhen 2 Score 0.998 (Sensitivity: 0.27; Specificity: 0.99)
SMART Domains Protein: ENSMUSP00000107284
Gene: ENSMUSG00000024985
AA Change: M335V

DomainStartEndE-ValueType
Pfam:CTNNB1_binding 1 236 2.1e-95 PFAM
HMG 326 396 1.16e-22 SMART
low complexity region 402 410 N/A INTRINSIC
c-clamp 438 468 2.08e-14 SMART
low complexity region 471 498 N/A INTRINSIC
low complexity region 519 539 N/A INTRINSIC
low complexity region 564 578 N/A INTRINSIC
Predicted Effect probably damaging
Transcript: ENSMUST00000148666
AA Change: M205V

PolyPhen 2 Score 0.998 (Sensitivity: 0.27; Specificity: 0.99)
SMART Domains Protein: ENSMUSP00000119759
Gene: ENSMUSG00000024985
AA Change: M205V

DomainStartEndE-ValueType
Pfam:CTNNB1_binding 10 106 5.7e-39 PFAM
HMG 196 265 1.02e-18 SMART
Predicted Effect probably damaging
Transcript: ENSMUST00000153888
AA Change: M316V

PolyPhen 2 Score 0.967 (Sensitivity: 0.77; Specificity: 0.95)
SMART Domains Protein: ENSMUSP00000118661
Gene: ENSMUSG00000024985
AA Change: M316V

DomainStartEndE-ValueType
Pfam:CTNNB1_binding 1 217 1.2e-64 PFAM
HMG 307 377 1.16e-22 SMART
low complexity region 383 391 N/A INTRINSIC
c-clamp 402 432 5.29e-7 SMART
Predicted Effect probably damaging
Transcript: ENSMUST00000111658
AA Change: M359V

PolyPhen 2 Score 0.999 (Sensitivity: 0.14; Specificity: 0.99)
SMART Domains Protein: ENSMUSP00000107286
Gene: ENSMUSG00000024985
AA Change: M359V

DomainStartEndE-ValueType
Pfam:CTNNB1_binding 1 259 4.5e-93 PFAM
HMG 350 420 1.16e-22 SMART
Predicted Effect probably damaging
Transcript: ENSMUST00000111659
AA Change: M340V

PolyPhen 2 Score 1.000 (Sensitivity: 0.00; Specificity: 1.00)
SMART Domains Protein: ENSMUSP00000107287
Gene: ENSMUSG00000024985
AA Change: M340V

DomainStartEndE-ValueType
Pfam:CTNNB1_binding 1 236 1.7e-96 PFAM
HMG 331 401 1.16e-22 SMART
low complexity region 407 415 N/A INTRINSIC
Predicted Effect unknown
Transcript: ENSMUST00000127233
AA Change: M327V
SMART Domains Protein: ENSMUSP00000123428
Gene: ENSMUSG00000024985
AA Change: M327V

DomainStartEndE-ValueType
Pfam:CTNNB1_binding 1 229 9.3e-98 PFAM
HMG 319 389 1.16e-22 SMART
low complexity region 395 403 N/A INTRINSIC
c-clamp 414 434 2.25e-1 SMART
Predicted Effect noncoding transcript
Transcript: ENSMUST00000143334
Predicted Effect noncoding transcript
Transcript: ENSMUST00000145249
Coding Region Coverage
  • 1x: 99.3%
  • 3x: 98.7%
  • 10x: 97.0%
  • 20x: 93.7%
Validation Efficiency
MGI Phenotype FUNCTION: [Summary is not available for the mouse gene. This summary is for the human ortholog.] This gene encodes a high mobility group (HMG) box-containing transcription factor that plays a key role in the Wnt signaling pathway. The protein has been implicated in blood glucose homeostasis. Genetic variants of this gene are associated with increased risk of type 2 diabetes. Several transcript variants encoding multiple different isoforms have been found for this gene.[provided by RefSeq, Oct 2010]
PHENOTYPE: Animals homozygous for a targeted mutation exhibit intestinal epithelia abnormalities and die shortly after birth. Mice heterozygous for some mutations display abnormalities in glucose homeostasis. [provided by MGI curators]
Allele List at MGI
Other mutations in this stock
Total: 55 list
GeneRefVarChr/LocMutationPredicted EffectZygosity
Abcb8 T C 5: 24,607,317 (GRCm39) L363P probably damaging Het
Adam12 T A 7: 133,599,959 (GRCm39) H85L probably damaging Het
Adam34 A T 8: 44,104,621 (GRCm39) H341Q probably damaging Het
Adam34l A T 8: 44,078,160 (GRCm39) M688K probably benign Het
Adam7 A G 14: 68,754,133 (GRCm39) L322P probably damaging Het
Adcy5 T A 16: 34,976,613 (GRCm39) S49T probably benign Het
Arfgap2 T C 2: 91,104,150 (GRCm39) S374P probably benign Het
Arpp19 G A 9: 74,944,967 (GRCm39) probably benign Het
Baz1a T C 12: 54,941,773 (GRCm39) K1478E probably damaging Het
Cdc27 G T 11: 104,396,467 (GRCm39) A812E possibly damaging Het
Chtf8 G A 8: 107,612,150 (GRCm39) T263I probably damaging Het
Clcn6 T C 4: 148,113,849 (GRCm39) N70D probably benign Het
Cntnap5c A T 17: 58,349,553 (GRCm39) T289S possibly damaging Het
Dzip3 T C 16: 48,795,840 (GRCm39) N177S probably damaging Het
Edar G T 10: 58,465,313 (GRCm39) probably null Het
Enam T A 5: 88,641,919 (GRCm39) N244K possibly damaging Het
Fbxw10 A G 11: 62,767,770 (GRCm39) K874E probably damaging Het
Glra3 A G 8: 56,578,239 (GRCm39) E432G possibly damaging Het
Grin3b G A 10: 79,807,062 (GRCm39) R110Q probably benign Het
Herc3 T A 6: 58,845,748 (GRCm39) V423D possibly damaging Het
Ifit2 A T 19: 34,550,984 (GRCm39) T175S probably benign Het
Kcnj8 T G 6: 142,511,627 (GRCm39) I327L possibly damaging Het
Kcns2 A T 15: 34,839,242 (GRCm39) I202F probably benign Het
Kif12 T C 4: 63,087,010 (GRCm39) R305G possibly damaging Het
Limch1 A G 5: 67,154,576 (GRCm39) D362G probably damaging Het
Lrba T C 3: 86,687,540 (GRCm39) I2815T probably damaging Het
Lrrtm1 G T 6: 77,221,843 (GRCm39) M433I probably damaging Het
Myh7b A G 2: 155,462,040 (GRCm39) D312G probably damaging Het
Nrxn1 A T 17: 90,344,758 (GRCm39) I382N probably damaging Het
Nudt6 C T 3: 37,459,502 (GRCm39) R161H probably benign Het
Or10w1 T A 19: 13,631,816 (GRCm39) W8R probably damaging Het
Or11g2 A C 14: 50,856,044 (GRCm39) M122L possibly damaging Het
Or4m1 A T 14: 50,558,186 (GRCm39) Y35* probably null Het
Or7e166 C T 9: 19,624,945 (GRCm39) A274V probably benign Het
Pmf1 A T 3: 88,303,369 (GRCm39) V64D probably damaging Het
Pomgnt1 T A 4: 116,009,048 (GRCm39) V29D probably damaging Het
Pramel22 T A 4: 143,380,790 (GRCm39) H411L possibly damaging Het
Pramel26 A T 4: 143,539,378 (GRCm39) D38E probably benign Het
Prex1 C T 2: 166,428,457 (GRCm39) A925T probably benign Het
Pus3 A G 9: 35,476,327 (GRCm39) Y72C probably damaging Het
Rnf20 T C 4: 49,642,176 (GRCm39) S247P probably damaging Het
Rnf213 T A 11: 119,305,396 (GRCm39) D542E probably benign Het
Sidt1 T C 16: 44,063,895 (GRCm39) D786G probably benign Het
Sirt6 A T 10: 81,458,475 (GRCm39) D219E probably damaging Het
Slc36a2 A T 11: 55,072,411 (GRCm39) I67N probably damaging Het
Slc47a1 A G 11: 61,264,248 (GRCm39) F57S probably damaging Het
Spg11 T A 2: 121,924,968 (GRCm39) T756S probably damaging Het
Sptbn1 C A 11: 30,071,591 (GRCm39) R1447L probably damaging Het
Thap1 T C 8: 26,652,733 (GRCm39) V157A probably benign Het
Ubash3b G A 9: 40,934,853 (GRCm39) Q354* probably null Het
Ubtd1 G A 19: 42,020,460 (GRCm39) W68* probably null Het
Wdr64 G T 1: 175,620,647 (GRCm39) R793L probably damaging Het
Zbtb24 C T 10: 41,327,432 (GRCm39) T106I probably benign Het
Zbtb26 T C 2: 37,326,337 (GRCm39) N233S possibly damaging Het
Zcchc24 A T 14: 25,757,585 (GRCm39) N99K possibly damaging Het
Other mutations in Tcf7l2
AlleleSourceChrCoordTypePredicted EffectPPH Score
IGL00771:Tcf7l2 APN 19 55,905,853 (GRCm39) missense probably damaging 1.00
IGL01013:Tcf7l2 APN 19 55,908,059 (GRCm39) splice site probably benign
IGL02871:Tcf7l2 APN 19 55,907,429 (GRCm39) missense probably damaging 1.00
banned UTSW 19 55,919,864 (GRCm39) critical splice acceptor site probably null
Notable UTSW 19 55,915,172 (GRCm39) missense unknown
PIT4468001:Tcf7l2 UTSW 19 55,730,820 (GRCm39) missense probably damaging 1.00
R1078:Tcf7l2 UTSW 19 55,731,627 (GRCm39) missense probably benign 0.19
R4580:Tcf7l2 UTSW 19 55,907,468 (GRCm39) missense probably damaging 1.00
R4721:Tcf7l2 UTSW 19 55,919,886 (GRCm39) missense possibly damaging 0.89
R4814:Tcf7l2 UTSW 19 55,912,504 (GRCm39) nonsense probably null
R4957:Tcf7l2 UTSW 19 55,919,864 (GRCm39) critical splice acceptor site probably null
R5222:Tcf7l2 UTSW 19 55,887,044 (GRCm39) missense probably benign
R5484:Tcf7l2 UTSW 19 55,907,940 (GRCm39) splice site probably null
R5808:Tcf7l2 UTSW 19 55,896,973 (GRCm39) missense probably damaging 1.00
R5914:Tcf7l2 UTSW 19 55,886,992 (GRCm39) missense probably benign 0.00
R6077:Tcf7l2 UTSW 19 55,905,868 (GRCm39) nonsense probably null
R6116:Tcf7l2 UTSW 19 55,907,446 (GRCm39) missense probably damaging 1.00
R6861:Tcf7l2 UTSW 19 55,730,955 (GRCm39) missense probably damaging 1.00
R6970:Tcf7l2 UTSW 19 55,743,480 (GRCm39) missense probably benign 0.44
R7009:Tcf7l2 UTSW 19 55,883,165 (GRCm39) critical splice donor site probably null
R7382:Tcf7l2 UTSW 19 55,915,172 (GRCm39) missense unknown
R7669:Tcf7l2 UTSW 19 55,912,975 (GRCm39) nonsense probably null
R7761:Tcf7l2 UTSW 19 55,914,468 (GRCm39) missense probably damaging 1.00
R7823:Tcf7l2 UTSW 19 55,731,521 (GRCm39) missense possibly damaging 0.73
R7952:Tcf7l2 UTSW 19 55,886,989 (GRCm39) start codon destroyed probably benign 0.00
R8753:Tcf7l2 UTSW 19 55,920,195 (GRCm39) missense possibly damaging 0.60
R9333:Tcf7l2 UTSW 19 55,919,928 (GRCm39) nonsense probably null
R9342:Tcf7l2 UTSW 19 55,731,517 (GRCm39) missense probably benign
R9395:Tcf7l2 UTSW 19 55,920,200 (GRCm39) nonsense probably null
R9610:Tcf7l2 UTSW 19 55,899,038 (GRCm39) missense probably null 1.00
R9611:Tcf7l2 UTSW 19 55,899,038 (GRCm39) missense probably null 1.00
Predicted Primers PCR Primer
(F):5'- AAGAAGGAGCATGGGATCTGCTTTG -3'
(R):5'- TCCGGGCCAGCTCGTAGTATTTTG -3'

Sequencing Primer
(F):5'- GGATCTGCTTTGGGGGAAG -3'
(R):5'- ACCCATTGCTGTATCTATGACAGG -3'
Posted On 2013-11-07