Incidental Mutation 'R7524:Smad4'
ID 582886
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 045596-MU
Accession Numbers
Essential gene? Essential (E-score: 1.000) question?
Stock # R7524 (G1)
Quality Score 225.009
Status Validated
Chromosome 18
Chromosomal Location 73772080-73836851 bp(-) (GRCm39)
Type of Mutation missense
DNA Base Change (assembly) T to G at 73808942 bp (GRCm39)
Zygosity Heterozygous
Amino Acid Change Glutamic Acid to Aspartic acid at position 108 (E108D)
Ref Sequence ENSEMBL: ENSMUSP00000025393 (fasta)
Gene Model predicted gene model for transcript(s): [ENSMUST00000025393] [ENSMUST00000114939]
AlphaFold P97471
PDB Structure Structural basis for DNA recognition by constitutive Smad4 MH1 dimers [X-RAY DIFFRACTION]
Predicted Effect probably damaging
Transcript: ENSMUST00000025393
AA Change: E108D

PolyPhen 2 Score 1.000 (Sensitivity: 0.00; Specificity: 1.00)
SMART Domains Protein: ENSMUSP00000025393
Gene: ENSMUSG00000024515
AA Change: E108D

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 damaging
Transcript: ENSMUST00000114939
AA Change: E108D

PolyPhen 2 Score 1.000 (Sensitivity: 0.00; Specificity: 1.00)
SMART Domains Protein: ENSMUSP00000110589
Gene: ENSMUSG00000024515
AA Change: E108D

DomainStartEndE-ValueType
DWA 31 140 5.77e-65 SMART
low complexity region 286 299 N/A INTRINSIC
DWB 320 529 1.41e-123 SMART
Meta Mutation Damage Score 0.7579 question?
Coding Region Coverage
  • 1x: 100.0%
  • 3x: 100.0%
  • 10x: 99.7%
  • 20x: 99.0%
Validation Efficiency 100% (79/79)
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: 78 list
GeneRefVarChr/LocMutationPredicted EffectZygosity
Adam29 C T 8: 56,325,395 (GRCm39) C353Y probably damaging Het
Afap1l2 T A 19: 56,906,543 (GRCm39) E452V probably damaging Het
Ak6 A G 13: 100,800,415 (GRCm39) D45G probably benign Het
Arhgap17 G A 7: 122,905,643 (GRCm39) P334L probably damaging Het
Asns G T 6: 7,677,259 (GRCm39) probably null Het
Bend7 A G 2: 4,804,791 (GRCm39) T424A probably benign Het
Btbd2 C T 10: 80,482,278 (GRCm39) E241K probably damaging Het
Commd2 A C 3: 57,557,569 (GRCm39) L99W probably damaging Het
Cpne9 A T 6: 113,279,025 (GRCm39) D473V probably damaging Het
Cuzd1 A T 7: 130,913,347 (GRCm39) F423L probably damaging Het
Cyp2d9 T C 15: 82,340,146 (GRCm39) F390L probably damaging Het
Dcaf5 T A 12: 80,423,470 (GRCm39) Q234L probably benign Het
Dennd3 T G 15: 73,396,095 (GRCm39) Y201* probably null Het
Dnah17 T C 11: 118,012,307 (GRCm39) D485G probably benign Het
Dnah5 A T 15: 28,297,212 (GRCm39) T1469S possibly damaging Het
Dnah6 T C 6: 73,095,082 (GRCm39) D2167G probably damaging Het
Dst T C 1: 34,330,974 (GRCm39) V4921A possibly damaging Het
Ephb2 A G 4: 136,387,020 (GRCm39) Y736H probably damaging Het
Eri2 C G 7: 119,384,972 (GRCm39) V510L probably benign Het
Eya2 G A 2: 165,611,246 (GRCm39) probably null Het
Fastkd5 G T 2: 130,458,048 (GRCm39) Q181K probably benign Het
Fcgbp T C 7: 27,802,391 (GRCm39) S1440P probably damaging Het
Fkbp9 G A 6: 56,845,725 (GRCm39) V354M probably damaging Het
Frmpd1 T A 4: 45,271,181 (GRCm39) S304T probably benign Het
Gtf2a2 T A 9: 69,922,629 (GRCm39) Y3* probably null Het
Hagh G A 17: 25,080,314 (GRCm39) V226I probably benign Het
Hemk1 T A 9: 107,205,484 (GRCm39) I293F probably benign Het
Kcna3 A G 3: 106,944,523 (GRCm39) E262G probably damaging Het
Kcnt2 A T 1: 140,511,793 (GRCm39) T983S probably damaging Het
Klhdc3 A T 17: 46,989,340 (GRCm39) H7Q probably damaging Het
Knl1 A T 2: 118,896,460 (GRCm39) Q94L probably damaging Het
Krt12 T C 11: 99,310,485 (GRCm39) D224G probably damaging Het
Lats1 T A 10: 7,577,742 (GRCm39) S289T possibly damaging Het
Man2a2 G C 7: 80,018,613 (GRCm39) A82G probably benign Het
Map1a G A 2: 121,120,293 (GRCm39) V60M probably damaging Het
Mms22l T A 4: 24,536,138 (GRCm39) F536I possibly damaging Het
Ms4a14 T C 19: 11,281,200 (GRCm39) T453A unknown Het
Muc3a A C 5: 137,245,020 (GRCm39) I151S probably benign Het
Myorg C A 4: 41,498,779 (GRCm39) V284L probably benign Het
Oaf G A 9: 43,134,077 (GRCm39) R215C probably damaging Het
Or4c112 T A 2: 88,854,315 (GRCm39) I11L probably benign Het
Or4c125 A G 2: 89,170,221 (GRCm39) C142R probably benign Het
Or4e5 T C 14: 52,727,750 (GRCm39) I224V probably damaging Het
Or5ar1 T A 2: 85,671,701 (GRCm39) M145L probably benign Het
Or6z7 T C 7: 6,483,586 (GRCm39) N190D probably benign Het
Or7a42 T A 10: 78,791,325 (GRCm39) Y95* probably null Het
Pcdhgb4 A T 18: 37,854,661 (GRCm39) D352V probably benign Het
Pced1a A G 2: 130,263,948 (GRCm39) F235L probably benign Het
Pclo A G 5: 14,728,317 (GRCm39) I2392V unknown Het
Pld1 A T 3: 28,078,470 (GRCm39) D43V possibly damaging Het
Ppp1r1b C A 11: 98,241,720 (GRCm39) A51D possibly damaging Het
Prr23a1 T A 9: 98,724,917 (GRCm39) L93H probably damaging Het
Psg20 T C 7: 18,418,584 (GRCm39) D61G probably benign Het
Rab40b T A 11: 121,278,878 (GRCm39) I31F probably damaging Het
Rasd2 T C 8: 75,948,709 (GRCm39) F212L probably benign Het
Rbl2 A G 8: 91,841,821 (GRCm39) I1006V probably benign Het
Sema6c A G 3: 95,074,371 (GRCm39) E59G probably benign Het
Slc22a2 G T 17: 12,824,944 (GRCm39) V269L possibly damaging Het
Slc2a1 C T 4: 118,989,809 (GRCm39) P149S probably damaging Het
Sorbs2 T A 8: 46,248,693 (GRCm39) I648K probably benign Het
Suclg1 A T 6: 73,240,824 (GRCm39) I118F probably damaging Het
Tasor T A 14: 27,188,160 (GRCm39) C869S probably damaging Het
Tet2 A G 3: 133,185,990 (GRCm39) I1149T probably benign Het
Tfr2 T A 5: 137,569,751 (GRCm39) Y82* probably null Het
Tfr2 G T 5: 137,581,751 (GRCm39) V613L probably benign Het
Tg A T 15: 66,568,010 (GRCm39) M1305L probably benign Het
Tmem176a A T 6: 48,821,039 (GRCm39) M170L probably benign Het
Trim71 T C 9: 114,342,230 (GRCm39) N684S probably benign Het
Tspan9 A G 6: 127,942,214 (GRCm39) I212T probably benign Het
Ttn A G 2: 76,773,319 (GRCm39) V2361A possibly damaging Het
Uqcrc1 C T 9: 108,765,827 (GRCm39) T14M possibly damaging Het
Vmn2r11 T C 5: 109,201,848 (GRCm39) I219V probably benign Het
Vmn2r76 T C 7: 85,874,577 (GRCm39) H800R probably benign Het
Vmn2r76 C T 7: 85,879,374 (GRCm39) G309R probably benign Het
Xpc A T 6: 91,476,513 (GRCm39) C529S probably benign Het
Zfp455 T A 13: 67,355,688 (GRCm39) S254T possibly damaging Het
Zfp746 T C 6: 48,041,823 (GRCm39) H301R possibly damaging Het
Zyg11a A T 4: 108,049,271 (GRCm39) I490N probably damaging 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
R1616:Smad4 UTSW 18 73,773,333 (GRCm39) missense probably benign 0.41
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
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'- CTTCATTTGAAGTCTTGAGTAGTCCTC -3'
(R):5'- GATGTTGGAGCAAAGCCGTG -3'

Sequencing Primer
(F):5'- GTCCTCAAGTACAAACTTTAAGTAGG -3'
(R):5'- CAAAGCCGTGTGTGCTCTG -3'
Posted On 2019-10-17