Incidental Mutation 'R4721:Tcf7l2'
ID 354508
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 041986-MU
Accession Numbers
Essential gene? Essential (E-score: 1.000) question?
Stock # R4721 (G1)
Quality Score 225
Status Validated
Chromosome 19
Chromosomal Location 55730252-55922086 bp(+) (GRCm39)
Type of Mutation missense
DNA Base Change (assembly) G to T at 55919886 bp (GRCm39)
Zygosity Heterozygous
Amino Acid Change Arginine to Leucine at position 465 (R465L)
Ref Sequence ENSEMBL: ENSMUSP00000107284 (fasta)
Gene Model predicted gene model for transcript(s): [ENSMUST00000041717] [ENSMUST00000061496] [ENSMUST00000111646] [ENSMUST00000111656] [ENSMUST00000111657] [ENSMUST00000111658] [ENSMUST00000111659] [ENSMUST00000111662] [ENSMUST00000153888]
AlphaFold no structure available at present
Predicted Effect possibly damaging
Transcript: ENSMUST00000041717
AA Change: A424S

PolyPhen 2 Score 0.682 (Sensitivity: 0.86; Specificity: 0.92)
SMART Domains Protein: ENSMUSP00000042950
Gene: ENSMUSG00000024985
AA Change: A424S

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 possibly damaging
Transcript: ENSMUST00000061496
AA Change: A441S

PolyPhen 2 Score 0.757 (Sensitivity: 0.85; Specificity: 0.92)
SMART Domains Protein: ENSMUSP00000050081
Gene: ENSMUSG00000024985
AA Change: A441S

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 benign
Transcript: ENSMUST00000111646
SMART Domains Protein: ENSMUSP00000107273
Gene: ENSMUSG00000024985

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 benign
Transcript: ENSMUST00000111656
SMART Domains Protein: ENSMUSP00000107283
Gene: ENSMUSG00000024985

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 possibly damaging
Transcript: ENSMUST00000111657
AA Change: R465L

PolyPhen 2 Score 0.895 (Sensitivity: 0.82; Specificity: 0.94)
SMART Domains Protein: ENSMUSP00000107284
Gene: ENSMUSG00000024985
AA Change: R465L

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 silent
Transcript: ENSMUST00000111658
SMART Domains Protein: ENSMUSP00000107286
Gene: ENSMUSG00000024985

DomainStartEndE-ValueType
Pfam:CTNNB1_binding 1 259 4.5e-93 PFAM
HMG 350 420 1.16e-22 SMART
Predicted Effect probably benign
Transcript: ENSMUST00000111659
AA Change: A429S

PolyPhen 2 Score 0.002 (Sensitivity: 0.99; Specificity: 0.30)
SMART Domains Protein: ENSMUSP00000107287
Gene: ENSMUSG00000024985
AA Change: A429S

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 possibly damaging
Transcript: ENSMUST00000111662
AA Change: R473L

PolyPhen 2 Score 0.718 (Sensitivity: 0.86; Specificity: 0.92)
SMART Domains Protein: ENSMUSP00000107291
Gene: ENSMUSG00000024985
AA Change: R473L

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 probably benign
Transcript: ENSMUST00000127233
SMART Domains Protein: ENSMUSP00000123428
Gene: ENSMUSG00000024985

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 probably benign
Transcript: ENSMUST00000153888
SMART Domains Protein: ENSMUSP00000118661
Gene: ENSMUSG00000024985

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
Meta Mutation Damage Score 0.1965 question?
Coding Region Coverage
  • 1x: 99.2%
  • 3x: 98.5%
  • 10x: 96.9%
  • 20x: 94.2%
Validation Efficiency 98% (90/92)
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: 77 list
GeneRefVarChr/LocMutationPredicted EffectZygosity
3425401B19Rik T C 14: 32,385,107 (GRCm39) D286G probably benign Het
Abca15 G A 7: 119,949,998 (GRCm39) E491K probably benign Het
Acsl5 A G 19: 55,268,962 (GRCm39) T208A probably benign Het
Adamts10 T A 17: 33,764,511 (GRCm39) probably null Het
Ahcyl1 T C 3: 107,577,233 (GRCm39) Q313R possibly damaging Het
Ccdc71 C T 9: 108,340,622 (GRCm39) S145L possibly damaging Het
Cep250 A G 2: 155,812,119 (GRCm39) T472A probably damaging Het
Copa T C 1: 171,931,841 (GRCm39) probably benign Het
Crybg1 C A 10: 43,873,883 (GRCm39) R1075L probably damaging Het
Ddr2 T A 1: 169,832,809 (GRCm39) K84* probably null Het
Ddx59 C T 1: 136,344,844 (GRCm39) P172S probably benign Het
Dhx34 T A 7: 15,931,307 (GRCm39) Q1118L possibly damaging Het
Dkkl1 T A 7: 44,857,232 (GRCm39) I112F probably damaging Het
Dnah8 T A 17: 30,944,140 (GRCm39) C1786S probably damaging Het
Eml6 T A 11: 29,788,525 (GRCm39) D520V possibly damaging Het
Ergic1 T A 17: 26,857,750 (GRCm39) V192E probably damaging Het
Fat3 T C 9: 15,941,262 (GRCm39) E1343G probably damaging Het
Fxr1 T C 3: 34,118,381 (GRCm39) S535P possibly damaging Het
Gkn3 C T 6: 87,360,507 (GRCm39) A163T probably damaging Het
Gm15446 C T 5: 110,090,866 (GRCm39) H373Y probably damaging Het
Gpr157 A T 4: 150,183,420 (GRCm39) N197Y probably benign Het
Grid2 G A 6: 64,643,185 (GRCm39) M982I probably benign Het
Hey2 G T 10: 30,710,304 (GRCm39) R150S possibly damaging Het
Hmcn1 T C 1: 150,648,322 (GRCm39) probably null Het
Ighv3-3 G A 12: 114,160,156 (GRCm39) R85* probably null Het
Ighv5-4 A T 12: 113,561,060 (GRCm39) probably benign Het
Igsf21 A G 4: 139,834,621 (GRCm39) S84P probably benign Het
Kif20b A G 19: 34,915,773 (GRCm39) T517A probably benign Het
Krt87 T C 15: 101,385,863 (GRCm39) E244G probably damaging Het
Lrp1 T C 10: 127,390,928 (GRCm39) T2990A possibly damaging Het
Lrp1b T A 2: 40,605,381 (GRCm39) probably null Het
Lrrc42 A T 4: 107,091,050 (GRCm39) S382T probably benign Het
Magi2 C T 5: 20,739,467 (GRCm39) R737W probably damaging Het
Mcc A G 18: 44,652,623 (GRCm39) L267P probably damaging Het
Mzf1 T A 7: 12,777,223 (GRCm39) Q727L possibly damaging Het
Mzf1 C T 7: 12,777,448 (GRCm39) R652Q possibly damaging Het
Nkain3 C T 4: 20,485,015 (GRCm39) A21T probably damaging Het
Nlrp4e T A 7: 23,020,521 (GRCm39) V336E possibly damaging Het
Nptn C T 9: 58,548,059 (GRCm39) R155C probably damaging Het
Nr2c2 T C 6: 92,116,828 (GRCm39) I10T possibly damaging Het
Or12e13 T A 2: 87,663,515 (GRCm39) I44N probably damaging Het
Or1e26 C T 11: 73,480,273 (GRCm39) C97Y probably damaging Het
Or1j13 T C 2: 36,369,836 (GRCm39) Y102C probably benign Het
Pdzk1 G T 3: 96,776,518 (GRCm39) E493* probably null Het
Plekhh1 GTCAAA G 12: 79,122,194 (GRCm39) probably null Het
Polr3b T C 10: 84,491,867 (GRCm39) V342A possibly damaging Het
Prg3 T C 2: 84,821,750 (GRCm39) V125A possibly damaging Het
Raph1 G A 1: 60,542,160 (GRCm39) probably benign Het
Rassf2 A G 2: 131,846,358 (GRCm39) V133A probably benign Het
Rbm22 G A 18: 60,697,463 (GRCm39) R56H probably damaging Het
Rbpjl A C 2: 164,246,447 (GRCm39) S31R probably benign Het
Reln A G 5: 22,124,220 (GRCm39) V2762A probably damaging Het
Rxrg T A 1: 167,452,621 (GRCm39) I141N probably damaging Het
Scn7a C A 2: 66,514,529 (GRCm39) G1082C probably damaging Het
Selenon C A 4: 134,270,387 (GRCm39) E322* probably null Het
Sipa1 C T 19: 5,710,413 (GRCm39) R199Q probably damaging Het
Slc26a7 A T 4: 14,510,261 (GRCm39) probably null Het
Slc37a4 T C 9: 44,312,787 (GRCm39) S314P possibly damaging Het
Smarce1 T C 11: 99,111,543 (GRCm39) I59V probably benign Het
Stk19 T C 17: 35,042,120 (GRCm39) probably null Het
Susd2 C T 10: 75,473,964 (GRCm39) D544N probably benign Het
Tfap2d T A 1: 19,174,984 (GRCm39) S146T possibly damaging Het
Tmem156 A G 5: 65,248,870 (GRCm39) F10S probably benign Het
Tmem63c G T 12: 87,103,954 (GRCm39) A68S possibly damaging Het
Tnfrsf21 T C 17: 43,396,395 (GRCm39) C560R probably damaging Het
Trav10n C T 14: 53,359,590 (GRCm39) T7I probably benign Het
Ttc38 C T 15: 85,722,947 (GRCm39) R132W probably benign Het
Tvp23a T C 16: 10,245,275 (GRCm39) K108R probably benign Het
Vmn1r233 T C 17: 21,214,879 (GRCm39) M24V probably benign Het
Vmn1r88 T A 7: 12,912,451 (GRCm39) L269* probably null Het
Vmn2r101 T A 17: 19,832,287 (GRCm39) M761K probably damaging Het
Vps13b C T 15: 35,910,864 (GRCm39) Q3543* probably null Het
Wdr37 T C 13: 8,904,065 (GRCm39) E101G possibly damaging Het
Zc3hc1 A G 6: 30,374,899 (GRCm39) V214A probably benign Het
Zcchc9 A T 13: 91,948,728 (GRCm39) probably null Het
Zdbf2 A T 1: 63,347,951 (GRCm39) Q2110L possibly damaging Het
Zfp516 T G 18: 82,975,236 (GRCm39) L478R 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
R0927:Tcf7l2 UTSW 19 55,907,387 (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
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'- CAAATCAGAGTGGACCTGGG -3'
(R):5'- TTGGTCACCAGAGACAGAGG -3'

Sequencing Primer
(F):5'- AGAGTGGACCTGGGAGCCTC -3'
(R):5'- TTCCAGCCAGCGAGTTGTG -3'
Posted On 2015-10-21