Incidental Mutation 'R1616:Smad4'
ID 174311
Institutional Source Beutler Lab
Gene Symbol Smad4
Ensembl Gene ENSMUSG00000024515
Gene Name SMAD family member 4
Synonyms Dpc4, D18Wsu70e, DPC4, Smad 4, Madh4
MMRRC Submission 039653-MU
Accession Numbers
Essential gene? Essential (E-score: 1.000) question?
Stock # R1616 (G1)
Quality Score 225
Status Not validated
Chromosome 18
Chromosomal Location 73772080-73836851 bp(-) (GRCm39)
Type of Mutation missense
DNA Base Change (assembly) T to C at 73773333 bp (GRCm39)
Zygosity Heterozygous
Amino Acid Change Aspartic acid to Glycine at position 551 (D551G)
Ref Sequence ENSEMBL: ENSMUSP00000110589 (fasta)
Gene Model predicted gene model for transcript(s): [ENSMUST00000025393] [ENSMUST00000114939]
AlphaFold P97471
Predicted Effect probably benign
Transcript: ENSMUST00000025393
AA Change: D551G

PolyPhen 2 Score 0.407 (Sensitivity: 0.89; Specificity: 0.90)
SMART Domains Protein: ENSMUSP00000025393
Gene: ENSMUSG00000024515
AA Change: D551G

DomainStartEndE-ValueType
DWA 31 140 5.77e-65 SMART
low complexity region 286 299 N/A INTRINSIC
DWB 320 529 1.41e-123 SMART
Predicted Effect probably benign
Transcript: ENSMUST00000114939
AA Change: D551G

PolyPhen 2 Score 0.407 (Sensitivity: 0.89; Specificity: 0.90)
SMART Domains Protein: ENSMUSP00000110589
Gene: ENSMUSG00000024515
AA Change: D551G

DomainStartEndE-ValueType
DWA 31 140 5.77e-65 SMART
low complexity region 286 299 N/A INTRINSIC
DWB 320 529 1.41e-123 SMART
Predicted Effect noncoding transcript
Transcript: ENSMUST00000131339
Predicted Effect noncoding transcript
Transcript: ENSMUST00000142672
Predicted Effect noncoding transcript
Transcript: ENSMUST00000147315
Meta Mutation Damage Score 0.2913 question?
Coding Region Coverage
  • 1x: 98.8%
  • 3x: 97.8%
  • 10x: 94.3%
  • 20x: 85.3%
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 Smad family of signal transduction proteins. Smad proteins are phosphorylated and activated by transmembrane serine-threonine receptor kinases in response to TGF-beta signaling. The product of this gene forms homomeric complexes and heteromeric complexes with other activated Smad proteins, which then accumulate in the nucleus and regulate the transcription of target genes. This protein binds to DNA and recognizes an 8-bp palindromic sequence (GTCTAGAC) called the Smad-binding element (SBE). The Smad proteins are subject to complex regulation by post-translational modifications. Mutations or deletions in this gene have been shown to result in pancreatic cancer, juvenile polyposis syndrome, and hereditary hemorrhagic telangiectasia syndrome. [provided by RefSeq, Oct 2009]
PHENOTYPE: Homozygotes for targeted null mutations exhibit impaired formation of extraembryonic membrane and endoderm and die prior to gastrulation. Heterozygotes develop polyposis of the glandular stomach and duodenum. [provided by MGI curators]
Allele List at MGI
Other mutations in this stock
Total: 90 list
GeneRefVarChr/LocMutationPredicted EffectZygosity
4933406P04Rik T C 10: 20,187,087 (GRCm39) probably benign Het
A1cf A G 19: 31,912,175 (GRCm39) E430G probably damaging Het
Aacs T A 5: 125,561,590 (GRCm39) probably null Het
Acot12 G A 13: 91,920,886 (GRCm39) V331I probably benign Het
Acp7 A G 7: 28,310,503 (GRCm39) W445R probably damaging Het
Actl11 C A 9: 107,809,135 (GRCm39) Q1153K probably benign Het
Actr8 A G 14: 29,704,601 (GRCm39) T34A possibly damaging Het
Ahnak A G 19: 8,986,351 (GRCm39) D2545G possibly damaging Het
Ap5z1 A G 5: 142,457,991 (GRCm39) Y388C probably benign Het
Apol7a C T 15: 77,273,806 (GRCm39) G219S probably damaging Het
Arid1b T A 17: 5,389,569 (GRCm39) I1705N probably damaging Het
Bod1l T C 5: 41,966,058 (GRCm39) Q2669R probably benign Het
Braf A T 6: 39,620,067 (GRCm39) S504T probably benign Het
Cbl A T 9: 44,064,197 (GRCm39) Y780N probably damaging Het
Cd86 T C 16: 36,449,338 (GRCm39) I20V probably benign Het
Cep290 T G 10: 100,404,698 (GRCm39) D2353E probably benign Het
Ckmt2 G A 13: 92,007,328 (GRCm39) R289C probably benign Het
Col3a1 T C 1: 45,367,648 (GRCm39) probably null Het
Cyp4f16 T A 17: 32,761,942 (GRCm39) Y163* probably null Het
Dimt1 T C 13: 107,089,958 (GRCm39) V227A possibly damaging Het
Dnah6 A T 6: 73,077,095 (GRCm39) M2338K probably benign Het
Dock4 T G 12: 40,719,044 (GRCm39) I274S probably damaging Het
Enthd1 T C 15: 80,336,586 (GRCm39) D616G probably damaging Het
Fignl2 T C 15: 100,951,997 (GRCm39) E95G probably damaging Het
Foxn1 A G 11: 78,249,692 (GRCm39) M611T probably benign Het
Foxs1 T C 2: 152,774,559 (GRCm39) S165G probably benign Het
Fzd3 G T 14: 65,472,956 (GRCm39) Q271K probably benign Het
Hadhb A T 5: 30,371,713 (GRCm39) I55F probably damaging Het
Hipk3 G A 2: 104,264,090 (GRCm39) Q824* probably null Het
Hps1 G A 19: 42,755,624 (GRCm39) R201W probably damaging Het
Kif21b T C 1: 136,099,423 (GRCm39) S1477P probably damaging Het
Kif26a A T 12: 112,123,680 (GRCm39) probably null Het
Krt90 T C 15: 101,469,026 (GRCm39) E172G possibly damaging Het
Lama4 T G 10: 38,951,446 (GRCm39) F1064V probably damaging Het
Leng9 A G 7: 4,151,902 (GRCm39) V258A probably benign Het
Lgi2 A C 5: 52,703,980 (GRCm39) V217G probably benign Het
Lpgat1 T C 1: 191,495,741 (GRCm39) I310T possibly damaging Het
Ltbp3 A G 19: 5,796,995 (GRCm39) Y374C probably damaging Het
Magi2 C A 5: 20,814,324 (GRCm39) T1075K probably damaging Het
Man2c1 T C 9: 57,042,793 (GRCm39) I221T probably benign Het
Mydgf A G 17: 56,486,415 (GRCm39) M72T possibly damaging Het
Myo1b T C 1: 51,815,474 (GRCm39) N624S probably damaging Het
Myo5c T A 9: 75,203,299 (GRCm39) M1465K probably damaging Het
Nek4 A T 14: 30,709,094 (GRCm39) D716V probably damaging Het
Nfxl1 T A 5: 72,686,380 (GRCm39) Q607L probably benign Het
Nlrp9c A T 7: 26,083,862 (GRCm39) D572E probably benign Het
Nop14 G T 5: 34,807,757 (GRCm39) Q402K possibly damaging Het
Npy5r C G 8: 67,134,052 (GRCm39) C247S probably damaging Het
Nrap T A 19: 56,378,255 (GRCm39) I19F probably damaging Het
Or4c102 A G 2: 88,422,352 (GRCm39) D68G probably damaging Het
Or51t4 T A 7: 102,597,721 (GRCm39) N16K probably damaging Het
Or6z3 T G 7: 6,463,744 (GRCm39) S79A probably damaging Het
Pcdh9 A T 14: 94,124,405 (GRCm39) Y588* probably null Het
Ppp1r12a A G 10: 108,096,728 (GRCm39) E183G probably damaging Het
Ppp2r2b T A 18: 42,821,375 (GRCm39) H261L probably benign Het
Ptch1 G T 13: 63,687,656 (GRCm39) T374K possibly damaging Het
Ptpn13 A T 5: 103,713,103 (GRCm39) N1742I possibly damaging Het
Rab33a C T X: 47,608,521 (GRCm39) S15L probably benign Het
Ralb T C 1: 119,405,744 (GRCm39) Y75C probably damaging Het
Rassf7 T A 7: 140,796,645 (GRCm39) V2D probably damaging Het
Rbm10 A G X: 20,512,230 (GRCm39) N397S probably benign Het
Rbm15 T C 3: 107,238,197 (GRCm39) T734A probably benign Het
Rbm8a G T 3: 96,539,046 (GRCm39) probably benign Het
Rock2 T C 12: 17,022,986 (GRCm39) I1095T probably benign Het
Rxfp3 T A 15: 11,036,389 (GRCm39) T328S probably damaging Het
Sec31a T A 5: 100,534,054 (GRCm39) K505N possibly damaging Het
Selenof A G 3: 144,302,642 (GRCm39) *122W probably null Het
Sh3pxd2b T C 11: 32,331,441 (GRCm39) M55T possibly damaging Het
Slc15a2 T C 16: 36,574,843 (GRCm39) D522G probably benign Het
Slc2a1 T C 4: 118,993,503 (GRCm39) F447L probably damaging Het
Slc45a2 T A 15: 11,022,214 (GRCm39) C319S probably null Het
Smarcc2 A G 10: 128,318,662 (GRCm39) Y648C probably damaging Het
Snrnp40 C G 4: 130,271,836 (GRCm39) probably null Het
Stab2 A T 10: 86,721,582 (GRCm39) probably null Het
Tanc1 A G 2: 59,615,731 (GRCm39) D246G probably damaging Het
Tekt3 T G 11: 62,978,024 (GRCm39) probably null Het
Them5 G A 3: 94,253,567 (GRCm39) probably null Het
Tlr4 T A 4: 66,757,717 (GRCm39) F170Y probably damaging Het
Tmem214 T G 5: 31,028,907 (GRCm39) Y165* probably null Het
Tmem94 T C 11: 115,686,971 (GRCm39) probably null Het
Tom1l1 A G 11: 90,547,177 (GRCm39) L301S possibly damaging Het
Trpm3 A G 19: 22,960,076 (GRCm39) E1237G probably damaging Het
Ube2d1 C A 10: 71,092,523 (GRCm39) C107F probably damaging Het
Ugt3a1 C T 15: 9,306,330 (GRCm39) R160* probably null Het
Vcan G A 13: 89,853,782 (GRCm39) P393S probably damaging Het
Virma T C 4: 11,544,954 (GRCm39) F1638L probably damaging Het
Vmn1r31 G A 6: 58,449,043 (GRCm39) T274I probably damaging Het
Xylt2 C T 11: 94,559,035 (GRCm39) S445N probably damaging Het
Zfp457 A G 13: 67,444,375 (GRCm39) F43L possibly damaging Het
Zfp879 T A 11: 50,723,473 (GRCm39) M455L probably benign Het
Other mutations in Smad4
AlleleSourceChrCoordTypePredicted EffectPPH Score
IGL01012:Smad4 APN 18 73,808,880 (GRCm39) missense probably damaging 1.00
IGL01647:Smad4 APN 18 73,773,544 (GRCm39) splice site probably benign
IGL02055:Smad4 APN 18 73,774,999 (GRCm39) splice site probably benign
IGL02101:Smad4 APN 18 73,791,723 (GRCm39) missense probably benign 0.02
IGL02306:Smad4 APN 18 73,795,940 (GRCm39) critical splice acceptor site probably null
R0391:Smad4 UTSW 18 73,791,720 (GRCm39) missense probably benign
R1118:Smad4 UTSW 18 73,773,333 (GRCm39) missense probably benign 0.41
R1163:Smad4 UTSW 18 73,781,978 (GRCm39) missense probably damaging 0.99
R1211:Smad4 UTSW 18 73,782,982 (GRCm39) critical splice acceptor site probably null
R1742:Smad4 UTSW 18 73,808,968 (GRCm39) missense probably damaging 1.00
R1829:Smad4 UTSW 18 73,774,965 (GRCm39) missense probably benign 0.20
R2045:Smad4 UTSW 18 73,782,877 (GRCm39) nonsense probably null
R2126:Smad4 UTSW 18 73,795,815 (GRCm39) missense probably benign 0.02
R3013:Smad4 UTSW 18 73,781,975 (GRCm39) missense probably damaging 1.00
R3973:Smad4 UTSW 18 73,810,807 (GRCm39) missense possibly damaging 0.49
R3974:Smad4 UTSW 18 73,810,807 (GRCm39) missense possibly damaging 0.49
R3975:Smad4 UTSW 18 73,810,807 (GRCm39) missense possibly damaging 0.49
R4879:Smad4 UTSW 18 73,774,974 (GRCm39) missense probably damaging 1.00
R5101:Smad4 UTSW 18 73,808,931 (GRCm39) missense probably benign 0.41
R5597:Smad4 UTSW 18 73,795,898 (GRCm39) missense probably benign
R5984:Smad4 UTSW 18 73,810,982 (GRCm39) start codon destroyed probably benign 0.29
R6450:Smad4 UTSW 18 73,810,817 (GRCm39) missense possibly damaging 0.73
R7450:Smad4 UTSW 18 73,810,924 (GRCm39) missense probably damaging 1.00
R7524:Smad4 UTSW 18 73,808,942 (GRCm39) missense probably damaging 1.00
R8001:Smad4 UTSW 18 73,774,881 (GRCm39) missense probably damaging 0.99
R8526:Smad4 UTSW 18 73,790,330 (GRCm39) splice site probably null
R9110:Smad4 UTSW 18 73,782,941 (GRCm39) missense probably damaging 1.00
R9151:Smad4 UTSW 18 73,782,806 (GRCm39) missense probably damaging 1.00
Predicted Primers PCR Primer
(F):5'- CTGATCTTCAAGCACTGAGCCACAC -3'
(R):5'- ATGACCTCCGGCGATTGTGCATTC -3'

Sequencing Primer
(F):5'- GCCACACCTGAAAGTTCTAAAATAG -3'
(R):5'- ATTGTGCATTCTCAGGATGAGC -3'
Posted On 2014-04-24