Incidental Mutation 'IGL02221:Tcf4'
ID 285148
Institutional Source Australian Phenomics Network (link to record)
Gene Symbol Tcf4
Ensembl Gene ENSMUSG00000053477
Gene Name transcription factor 4
Synonyms SEF2-1, TFE, E2.2, MITF-2A, 5730422P05Rik, MITF-2B, bHLHb19, ME2, ASP-I2, SEF-2, ITF-2b, ITF-2, E2-2
Accession Numbers
Essential gene? Essential (E-score: 1.000) question?
Stock # IGL02221
Quality Score
Status
Chromosome 18
Chromosomal Location 69476500-69821038 bp(+) (GRCm39)
Type of Mutation missense
DNA Base Change (assembly) T to A at 69480438 bp (GRCm39)
Zygosity Heterozygous
Amino Acid Change Serine to Arginine at position 23 (S23R)
Ref Sequence ENSEMBL: ENSMUSP00000144512 (fasta)
Gene Model predicted gene model for transcript(s): [ENSMUST00000066717] [ENSMUST00000078486] [ENSMUST00000114980] [ENSMUST00000114982] [ENSMUST00000114985] [ENSMUST00000128706] [ENSMUST00000202116] [ENSMUST00000201288] [ENSMUST00000201235] [ENSMUST00000201781] [ENSMUST00000201299] [ENSMUST00000201537] [ENSMUST00000201124] [ENSMUST00000201631] [ENSMUST00000202074] [ENSMUST00000202610] [ENSMUST00000203002] [ENSMUST00000202772] [ENSMUST00000202674] [ENSMUST00000202354] [ENSMUST00000202435]
AlphaFold Q60722
Predicted Effect probably benign
Transcript: ENSMUST00000066717
AA Change: S23R

PolyPhen 2 Score 0.000 (Sensitivity: 1.00; Specificity: 0.00)
SMART Domains Protein: ENSMUSP00000067318
Gene: ENSMUSG00000053477
AA Change: S23R

DomainStartEndE-ValueType
low complexity region 244 252 N/A INTRINSIC
low complexity region 358 369 N/A INTRINSIC
low complexity region 452 464 N/A INTRINSIC
low complexity region 488 501 N/A INTRINSIC
low complexity region 524 542 N/A INTRINSIC
low complexity region 546 564 N/A INTRINSIC
HLH 595 648 3.57e-11 SMART
Predicted Effect probably damaging
Transcript: ENSMUST00000078486
AA Change: S23R

PolyPhen 2 Score 1.000 (Sensitivity: 0.00; Specificity: 1.00)
SMART Domains Protein: ENSMUSP00000077577
Gene: ENSMUSG00000053477
AA Change: S23R

DomainStartEndE-ValueType
low complexity region 222 230 N/A INTRINSIC
low complexity region 336 347 N/A INTRINSIC
low complexity region 430 442 N/A INTRINSIC
low complexity region 466 479 N/A INTRINSIC
low complexity region 502 520 N/A INTRINSIC
low complexity region 524 542 N/A INTRINSIC
HLH 573 626 3.57e-11 SMART
Predicted Effect probably damaging
Transcript: ENSMUST00000114980
AA Change: S23R

PolyPhen 2 Score 1.000 (Sensitivity: 0.00; Specificity: 1.00)
SMART Domains Protein: ENSMUSP00000110631
Gene: ENSMUSG00000053477
AA Change: S23R

DomainStartEndE-ValueType
low complexity region 222 230 N/A INTRINSIC
low complexity region 336 347 N/A INTRINSIC
low complexity region 430 442 N/A INTRINSIC
low complexity region 466 479 N/A INTRINSIC
low complexity region 502 520 N/A INTRINSIC
low complexity region 524 545 N/A INTRINSIC
HLH 569 622 3.57e-11 SMART
Predicted Effect probably damaging
Transcript: ENSMUST00000114982
AA Change: S23R

PolyPhen 2 Score 1.000 (Sensitivity: 0.00; Specificity: 1.00)
SMART Domains Protein: ENSMUSP00000110633
Gene: ENSMUSG00000053477
AA Change: S23R

DomainStartEndE-ValueType
low complexity region 222 230 N/A INTRINSIC
low complexity region 336 347 N/A INTRINSIC
low complexity region 430 442 N/A INTRINSIC
low complexity region 466 479 N/A INTRINSIC
low complexity region 502 520 N/A INTRINSIC
low complexity region 524 545 N/A INTRINSIC
HLH 569 622 3.57e-11 SMART
Predicted Effect probably damaging
Transcript: ENSMUST00000114985
AA Change: S23R

PolyPhen 2 Score 1.000 (Sensitivity: 0.00; Specificity: 1.00)
SMART Domains Protein: ENSMUSP00000110636
Gene: ENSMUSG00000053477
AA Change: S23R

DomainStartEndE-ValueType
low complexity region 222 230 N/A INTRINSIC
low complexity region 336 347 N/A INTRINSIC
low complexity region 430 442 N/A INTRINSIC
low complexity region 466 479 N/A INTRINSIC
low complexity region 502 520 N/A INTRINSIC
low complexity region 524 542 N/A INTRINSIC
HLH 573 626 3.57e-11 SMART
Predicted Effect probably benign
Transcript: ENSMUST00000128706
Predicted Effect probably damaging
Transcript: ENSMUST00000202116
AA Change: S23R

PolyPhen 2 Score 1.000 (Sensitivity: 0.00; Specificity: 1.00)
SMART Domains Protein: ENSMUSP00000144512
Gene: ENSMUSG00000053477
AA Change: S23R

DomainStartEndE-ValueType
low complexity region 222 230 N/A INTRINSIC
low complexity region 336 347 N/A INTRINSIC
low complexity region 430 442 N/A INTRINSIC
low complexity region 466 479 N/A INTRINSIC
low complexity region 502 520 N/A INTRINSIC
low complexity region 524 545 N/A INTRINSIC
HLH 569 622 3.57e-11 SMART
Predicted Effect probably damaging
Transcript: ENSMUST00000201288
AA Change: S23R

PolyPhen 2 Score 0.988 (Sensitivity: 0.73; Specificity: 0.96)
Predicted Effect noncoding transcript
Transcript: ENSMUST00000200902
Predicted Effect noncoding transcript
Transcript: ENSMUST00000155695
Predicted Effect noncoding transcript
Transcript: ENSMUST00000202058
Predicted Effect probably benign
Transcript: ENSMUST00000201235
Predicted Effect probably benign
Transcript: ENSMUST00000201781
SMART Domains Protein: ENSMUSP00000144209
Gene: ENSMUSG00000053477

DomainStartEndE-ValueType
low complexity region 198 206 N/A INTRINSIC
low complexity region 312 323 N/A INTRINSIC
low complexity region 406 418 N/A INTRINSIC
low complexity region 442 455 N/A INTRINSIC
low complexity region 478 496 N/A INTRINSIC
low complexity region 500 518 N/A INTRINSIC
HLH 549 602 1.6e-13 SMART
Predicted Effect probably benign
Transcript: ENSMUST00000201299
Predicted Effect probably benign
Transcript: ENSMUST00000201537
Predicted Effect probably benign
Transcript: ENSMUST00000201124
SMART Domains Protein: ENSMUSP00000144080
Gene: ENSMUSG00000053477

DomainStartEndE-ValueType
low complexity region 145 153 N/A INTRINSIC
Predicted Effect probably benign
Transcript: ENSMUST00000201631
SMART Domains Protein: ENSMUSP00000144285
Gene: ENSMUSG00000053477

DomainStartEndE-ValueType
low complexity region 198 206 N/A INTRINSIC
low complexity region 312 323 N/A INTRINSIC
low complexity region 406 418 N/A INTRINSIC
low complexity region 442 455 N/A INTRINSIC
low complexity region 478 496 N/A INTRINSIC
low complexity region 500 521 N/A INTRINSIC
HLH 545 598 1.6e-13 SMART
Predicted Effect probably benign
Transcript: ENSMUST00000202074
Predicted Effect probably benign
Transcript: ENSMUST00000202610
AA Change: S23R

PolyPhen 2 Score 0.022 (Sensitivity: 0.95; Specificity: 0.81)
SMART Domains Protein: ENSMUSP00000144670
Gene: ENSMUSG00000053477
AA Change: S23R

DomainStartEndE-ValueType
low complexity region 162 170 N/A INTRINSIC
low complexity region 276 287 N/A INTRINSIC
low complexity region 370 382 N/A INTRINSIC
low complexity region 406 419 N/A INTRINSIC
low complexity region 442 460 N/A INTRINSIC
low complexity region 464 482 N/A INTRINSIC
HLH 513 566 1.6e-13 SMART
Predicted Effect probably benign
Transcript: ENSMUST00000203002
AA Change: S23R

PolyPhen 2 Score 0.001 (Sensitivity: 0.99; Specificity: 0.15)
Predicted Effect probably benign
Transcript: ENSMUST00000202772
AA Change: S23R

PolyPhen 2 Score 0.000 (Sensitivity: 1.00; Specificity: 0.00)
SMART Domains Protein: ENSMUSP00000143987
Gene: ENSMUSG00000053477
AA Change: S23R

DomainStartEndE-ValueType
low complexity region 162 170 N/A INTRINSIC
low complexity region 276 287 N/A INTRINSIC
low complexity region 370 382 N/A INTRINSIC
low complexity region 406 419 N/A INTRINSIC
low complexity region 442 460 N/A INTRINSIC
low complexity region 464 485 N/A INTRINSIC
HLH 509 562 1.6e-13 SMART
Predicted Effect probably benign
Transcript: ENSMUST00000202674
SMART Domains Protein: ENSMUSP00000144221
Gene: ENSMUSG00000053477

DomainStartEndE-ValueType
low complexity region 197 205 N/A INTRINSIC
low complexity region 311 322 N/A INTRINSIC
low complexity region 405 417 N/A INTRINSIC
low complexity region 441 454 N/A INTRINSIC
low complexity region 477 495 N/A INTRINSIC
low complexity region 499 520 N/A INTRINSIC
HLH 544 597 1.6e-13 SMART
Predicted Effect probably benign
Transcript: ENSMUST00000202354
SMART Domains Protein: ENSMUSP00000144646
Gene: ENSMUSG00000053477

DomainStartEndE-ValueType
low complexity region 198 206 N/A INTRINSIC
low complexity region 312 323 N/A INTRINSIC
low complexity region 405 417 N/A INTRINSIC
low complexity region 441 454 N/A INTRINSIC
low complexity region 477 495 N/A INTRINSIC
low complexity region 499 520 N/A INTRINSIC
HLH 544 597 1.6e-13 SMART
Predicted Effect probably benign
Transcript: ENSMUST00000202435
SMART Domains Protein: ENSMUSP00000144407
Gene: ENSMUSG00000053477

DomainStartEndE-ValueType
low complexity region 198 206 N/A INTRINSIC
low complexity region 312 323 N/A INTRINSIC
low complexity region 406 418 N/A INTRINSIC
low complexity region 442 455 N/A INTRINSIC
low complexity region 478 496 N/A INTRINSIC
low complexity region 500 518 N/A INTRINSIC
HLH 549 602 1.6e-13 SMART
Coding Region Coverage
Validation Efficiency
MGI Phenotype FUNCTION: [Summary is not available for the mouse gene. This summary is for the human ortholog.] This gene encodes transcription factor 4, a basic helix-loop-helix transcription factor. The encoded protein recognizes an Ephrussi-box ('E-box') binding site ('CANNTG') - a motif first identified in immunoglobulin enhancers. This gene is broadly expressed, and may play an important role in nervous system development. Defects in this gene are a cause of Pitt-Hopkins syndrome. In addition, an intronic CTG repeat normally numbering 10-37 repeat units can expand to >50 repeat units and cause Fuchs endothelial corneal dystrophy. Multiple alternatively spliced transcript variants that encode different proteins have been described. [provided by RefSeq, Jul 2016]
PHENOTYPE: Homozygotes for a null allele show a partial block in early thymopoiesis, increased double-negative T cell count, and increased sensitivity to anti-CD3 induced apoptosis. Homozygotes for another null allele show neonatal or postnatal lethality, reduced pro-B cell number, and abnormal pontine nuclei. [provided by MGI curators]
Allele List at MGI
Other mutations in this stock
Total: 35 list
GeneRefVarChr/LocMutationPredicted EffectZygosity
1700013D24Rik T C 6: 124,333,907 (GRCm39) I24M probably benign Het
Ano5 G A 7: 51,220,071 (GRCm39) D390N probably damaging Het
Atp2c2 A G 8: 120,471,073 (GRCm39) Y407C probably damaging Het
B430306N03Rik T C 17: 48,631,223 (GRCm39) probably benign Het
Cd44 A T 2: 102,676,858 (GRCm39) M269K probably benign Het
Cdin1 T C 2: 115,469,547 (GRCm39) probably null Het
Cpped1 G T 16: 11,646,392 (GRCm39) P144Q probably damaging Het
Epas1 C T 17: 87,135,275 (GRCm39) T636M possibly damaging Het
Hsd17b3 G T 13: 64,236,865 (GRCm39) H26Q probably benign Het
Ighv8-9 A G 12: 115,431,947 (GRCm39) probably benign Het
Itih1 A T 14: 30,651,544 (GRCm39) C883S probably damaging Het
Krt16 A T 11: 100,137,162 (GRCm39) probably benign Het
Lcn3 A T 2: 25,656,172 (GRCm39) M76L probably benign Het
Lin9 A T 1: 180,478,399 (GRCm39) M53L probably benign Het
Mast1 A G 8: 85,645,384 (GRCm39) V687A possibly damaging Het
Mmd2 C T 5: 142,555,212 (GRCm39) probably benign Het
Mroh2b T C 15: 4,953,123 (GRCm39) L619S probably damaging Het
Ngef T C 1: 87,468,418 (GRCm39) T114A probably benign Het
Nlrp12 T C 7: 3,289,597 (GRCm39) D305G possibly damaging Het
Nlrp1a A T 11: 71,013,944 (GRCm39) F435L possibly damaging Het
Nup188 A G 2: 30,220,653 (GRCm39) I909V possibly damaging Het
Osbpl3 A C 6: 50,304,347 (GRCm39) probably benign Het
P2ry2 G T 7: 100,647,321 (GRCm39) P328H possibly damaging Het
Prex2 A T 1: 11,131,569 (GRCm39) N46I probably benign Het
Prss42 T C 9: 110,632,243 (GRCm39) F325L possibly damaging Het
Reep5 A G 18: 34,482,850 (GRCm39) F120L probably damaging Het
Scg3 G T 9: 75,590,939 (GRCm39) F23L probably damaging Het
Scx A G 15: 76,343,295 (GRCm39) D200G probably benign Het
Setd5 C T 6: 113,098,131 (GRCm39) probably benign Het
Ttc4 A G 4: 106,533,793 (GRCm39) probably null Het
Tyro3 T A 2: 119,643,071 (GRCm39) C627S probably benign Het
Yipf2 T C 9: 21,502,764 (GRCm39) N106S possibly damaging Het
Zfp619 T C 7: 39,186,334 (GRCm39) L788P probably benign Het
Zfp831 G A 2: 174,485,519 (GRCm39) V65I probably benign Het
Zgpat T C 2: 181,020,651 (GRCm39) S275P probably benign Het
Other mutations in Tcf4
AlleleSourceChrCoordTypePredicted EffectPPH Score
IGL01413:Tcf4 APN 18 69,788,090 (GRCm39) missense probably damaging 1.00
IGL02131:Tcf4 APN 18 69,697,697 (GRCm39) splice site probably benign
IGL02420:Tcf4 APN 18 69,697,210 (GRCm39) missense probably damaging 1.00
IGL02560:Tcf4 APN 18 69,776,093 (GRCm39) unclassified probably benign
IGL02637:Tcf4 APN 18 69,480,421 (GRCm39) missense probably damaging 1.00
IGL03056:Tcf4 APN 18 69,784,283 (GRCm39) splice site probably benign
R0374:Tcf4 UTSW 18 69,814,883 (GRCm39) splice site probably benign
R1265:Tcf4 UTSW 18 69,776,003 (GRCm39) missense possibly damaging 0.93
R1739:Tcf4 UTSW 18 69,776,041 (GRCm39) missense probably damaging 1.00
R1794:Tcf4 UTSW 18 69,790,924 (GRCm39) missense probably benign 0.44
R4703:Tcf4 UTSW 18 69,790,981 (GRCm39) missense probably damaging 1.00
R4735:Tcf4 UTSW 18 69,697,226 (GRCm39) missense possibly damaging 0.59
R4993:Tcf4 UTSW 18 69,814,840 (GRCm39) missense probably damaging 1.00
R5191:Tcf4 UTSW 18 69,775,954 (GRCm39) missense probably damaging 1.00
R5318:Tcf4 UTSW 18 69,598,501 (GRCm39) missense probably benign
R5634:Tcf4 UTSW 18 69,769,918 (GRCm39) missense possibly damaging 0.88
R6337:Tcf4 UTSW 18 69,766,651 (GRCm39) missense probably damaging 1.00
R6658:Tcf4 UTSW 18 69,790,873 (GRCm39) missense probably null 1.00
R6868:Tcf4 UTSW 18 69,790,721 (GRCm39) splice site probably null
R6907:Tcf4 UTSW 18 69,785,484 (GRCm39) missense probably damaging 1.00
R7170:Tcf4 UTSW 18 69,766,649 (GRCm39) missense probably damaging 1.00
R7235:Tcf4 UTSW 18 69,790,866 (GRCm39) missense probably damaging 1.00
R7431:Tcf4 UTSW 18 69,480,249 (GRCm39) splice site probably null
R7589:Tcf4 UTSW 18 69,815,890 (GRCm39) makesense probably null
R7606:Tcf4 UTSW 18 69,776,054 (GRCm39) missense probably damaging 0.99
R7796:Tcf4 UTSW 18 69,697,140 (GRCm39) missense probably benign 0.02
R8193:Tcf4 UTSW 18 69,633,994 (GRCm39) start gained probably benign
R8461:Tcf4 UTSW 18 69,598,501 (GRCm39) missense probably benign
R8746:Tcf4 UTSW 18 69,654,572 (GRCm39) unclassified probably benign
R8900:Tcf4 UTSW 18 69,697,761 (GRCm39) splice site probably benign
R9095:Tcf4 UTSW 18 69,598,464 (GRCm39) missense possibly damaging 0.83
R9278:Tcf4 UTSW 18 69,766,652 (GRCm39) missense probably damaging 1.00
R9516:Tcf4 UTSW 18 69,652,944 (GRCm39) unclassified probably benign
R9633:Tcf4 UTSW 18 69,726,382 (GRCm39) intron probably benign
R9756:Tcf4 UTSW 18 69,790,830 (GRCm39) nonsense probably null
R9790:Tcf4 UTSW 18 69,770,007 (GRCm39) missense probably damaging 1.00
R9791:Tcf4 UTSW 18 69,770,007 (GRCm39) missense probably damaging 1.00
Z1176:Tcf4 UTSW 18 69,726,451 (GRCm39) intron probably benign
Posted On 2015-04-16