Incidental Mutation 'R8001:Smad4'
ID 616382
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 046041-MU
Accession Numbers
Essential gene? Essential (E-score: 1.000) question?
Stock # R8001 (G1)
Quality Score 225.009
Status Not validated
Chromosome 18
Chromosomal Location 73772080-73836851 bp(-) (GRCm39)
Type of Mutation missense
DNA Base Change (assembly) A to G at 73774881 bp (GRCm39)
Zygosity Heterozygous
Amino Acid Change Serine to Proline at position 473 (S473P)
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: S473P

PolyPhen 2 Score 0.994 (Sensitivity: 0.69; Specificity: 0.97)
SMART Domains Protein: ENSMUSP00000025393
Gene: ENSMUSG00000024515
AA Change: S473P

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: S473P

PolyPhen 2 Score 0.994 (Sensitivity: 0.69; Specificity: 0.97)
SMART Domains Protein: ENSMUSP00000110589
Gene: ENSMUSG00000024515
AA Change: S473P

DomainStartEndE-ValueType
DWA 31 140 5.77e-65 SMART
low complexity region 286 299 N/A INTRINSIC
DWB 320 529 1.41e-123 SMART
Coding Region Coverage
  • 1x: 100.0%
  • 3x: 100.0%
  • 10x: 99.8%
  • 20x: 99.3%
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: 38 list
GeneRefVarChr/LocMutationPredicted EffectZygosity
Acr A G 15: 89,458,165 (GRCm39) Y282C probably damaging Het
Alkbh4 A G 5: 136,169,123 (GRCm39) R136G probably damaging Het
Bptf C A 11: 106,938,166 (GRCm39) E2* probably null Het
Cse1l T A 2: 166,781,833 (GRCm39) F659Y probably damaging Het
Ctrc A T 4: 141,567,671 (GRCm39) L144Q probably damaging Het
Elmo1 A G 13: 20,470,902 (GRCm39) I265V probably benign Het
Erich3 T C 3: 154,419,553 (GRCm39) S19P probably benign Het
Hmcn1 A T 1: 150,540,629 (GRCm39) C2893* probably null Het
Hnrnpll G A 17: 80,346,152 (GRCm39) Q370* probably null Het
Itpkb T C 1: 180,160,059 (GRCm39) S62P probably damaging Het
Lig3 T A 11: 82,682,902 (GRCm39) C501S probably benign Het
Mab21l4 A G 1: 93,082,321 (GRCm39) L266P probably damaging Het
Nrxn1 C T 17: 91,395,964 (GRCm39) R64H possibly damaging Het
Ogfod2 T G 5: 124,252,946 (GRCm39) C319G probably damaging Het
Or51h1 A T 7: 102,308,241 (GRCm39) D71V probably damaging Het
Or5ac19 T C 16: 59,089,472 (GRCm39) N186S probably benign Het
Or5b118 A G 19: 13,448,786 (GRCm39) I109V probably benign Het
Or9k7 A G 10: 130,046,729 (GRCm39) V90A probably benign Het
Pabpc6 C A 17: 9,888,302 (GRCm39) R83L probably damaging Het
Pcdhgb2 A T 18: 37,823,687 (GRCm39) Q226L probably benign Het
Pole A T 5: 110,460,600 (GRCm39) I1127F probably damaging Het
Psg22 A T 7: 18,453,671 (GRCm39) Q161L possibly damaging Het
Slc17a7 A T 7: 44,818,212 (GRCm39) T46S probably benign Het
Snap47 T A 11: 59,329,180 (GRCm39) T41S probably benign Het
Snx21 T C 2: 164,628,657 (GRCm39) L100P probably benign Het
Stc1 T A 14: 69,275,844 (GRCm39) N212K probably benign Het
Stk32a A T 18: 43,448,209 (GRCm39) N396I possibly damaging Het
Stox2 G A 8: 47,639,512 (GRCm39) P894L probably benign Het
Trav16d-dv11 A G 14: 53,284,744 (GRCm39) M1V probably null Het
Trim33 T C 3: 103,218,831 (GRCm39) probably null Het
Tyrp1 T C 4: 80,758,907 (GRCm39) V260A probably benign Het
Ush2a T C 1: 188,643,261 (GRCm39) Y4208H probably damaging Het
Vmn1r25 T A 6: 57,956,065 (GRCm39) K75* probably null Het
Vmn2r117 T A 17: 23,698,381 (GRCm39) N64I possibly damaging Het
Wdfy4 C T 14: 32,695,492 (GRCm39) probably null Het
Wnt8a A T 18: 34,678,569 (GRCm39) I128F probably damaging Het
Zc3h7b C A 15: 81,663,461 (GRCm39) Y484* probably null Het
Zfp619 A G 7: 39,184,645 (GRCm39) K225R 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
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
R7524:Smad4 UTSW 18 73,808,942 (GRCm39) missense probably damaging 1.00
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'- ATGCCCTGATGCAAAGAGGC -3'
(R):5'- ATTGGCTTCTCATGAATGGAGTC -3'

Sequencing Primer
(F):5'- TGATGCAAAGAGGCTCCAATC -3'
(R):5'- CTTTGGCAGTGCACTCATATAG -3'
Posted On 2020-01-23