Incidental Mutation 'R3974:Smad4'
ID 312560
Institutional Source Beutler Lab
Gene Symbol Smad4
Ensembl Gene ENSMUSG00000024515
Gene Name SMAD family member 4
Synonyms Dpc4, D18Wsu70e, DPC4, Smad 4, Madh4
Accession Numbers
Essential gene? Essential (E-score: 1.000) question?
Stock # R3974 (G1)
Quality Score 225
Status Not validated
Chromosome 18
Chromosomal Location 73772080-73836851 bp(-) (GRCm39)
Type of Mutation missense
DNA Base Change (assembly) G to T at 73810807 bp (GRCm39)
Zygosity Heterozygous
Amino Acid Change Threonine to Lysine at position 59 (T59K)
Ref Sequence ENSEMBL: ENSMUSP00000110589 (fasta)
Gene Model predicted gene model for transcript(s): [ENSMUST00000025393] [ENSMUST00000114939]
AlphaFold P97471
Predicted Effect possibly damaging
Transcript: ENSMUST00000025393
AA Change: T59K

PolyPhen 2 Score 0.494 (Sensitivity: 0.88; Specificity: 0.90)
SMART Domains Protein: ENSMUSP00000025393
Gene: ENSMUSG00000024515
AA Change: T59K

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 possibly damaging
Transcript: ENSMUST00000114939
AA Change: T59K

PolyPhen 2 Score 0.494 (Sensitivity: 0.88; Specificity: 0.90)
SMART Domains Protein: ENSMUSP00000110589
Gene: ENSMUSG00000024515
AA Change: T59K

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: ENSMUST00000129326
Meta Mutation Damage Score 0.3351 question?
Coding Region Coverage
  • 1x: 99.1%
  • 3x: 98.5%
  • 10x: 96.9%
  • 20x: 93.8%
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: 53 list
GeneRefVarChr/LocMutationPredicted EffectZygosity
2510039O18Rik T C 4: 148,029,488 (GRCm39) I486T probably damaging Het
Abca8a A T 11: 109,974,328 (GRCm39) M202K probably damaging Het
Abhd4 T A 14: 54,500,417 (GRCm39) I117N probably damaging Het
Adam23 T A 1: 63,586,888 (GRCm39) Y416* probably null Het
Cenpe A G 3: 134,940,986 (GRCm39) probably null Het
Cenph A G 13: 100,900,075 (GRCm39) V151A probably damaging Het
Cfap54 A G 10: 92,675,333 (GRCm39) S2863P possibly damaging Het
Clca3a1 A T 3: 144,738,400 (GRCm39) V36D probably damaging Het
Cnbd1 G A 4: 18,887,693 (GRCm39) R274C probably benign Het
Crot T C 5: 9,027,541 (GRCm39) T264A probably benign Het
Dll4 A G 2: 119,164,573 (GRCm39) D664G probably damaging Het
Ehbp1 C T 11: 22,087,867 (GRCm39) A406T probably benign Het
Far2 T A 6: 148,052,252 (GRCm39) I177N probably damaging Het
Flt4 T G 11: 49,527,567 (GRCm39) V910G probably damaging Het
Fmod A G 1: 133,968,496 (GRCm39) R179G probably benign Het
Gdf2 T A 14: 33,666,791 (GRCm39) V171D probably damaging Het
Gpx6 C A 13: 21,501,828 (GRCm39) S150Y probably damaging Het
Grik2 A T 10: 49,298,750 (GRCm39) Y37N probably damaging Het
Grn T C 11: 102,327,165 (GRCm39) V559A probably damaging Het
Lrrc37 A T 11: 103,509,927 (GRCm39) probably benign Het
Muc2 T A 7: 141,300,541 (GRCm39) probably benign Het
Myo5b T C 18: 74,767,552 (GRCm39) Y287H probably damaging Het
Nbeal2 T C 9: 110,462,914 (GRCm39) T1350A probably damaging Het
Nfkbiz T C 16: 55,638,799 (GRCm39) I220M probably benign Het
Nt5dc2 T C 14: 30,860,832 (GRCm39) S439P probably damaging Het
Omg T A 11: 79,393,224 (GRCm39) E211D probably benign Het
Or52ab7 T G 7: 102,978,285 (GRCm39) D197E probably damaging Het
Or8k18 A T 2: 86,085,935 (GRCm39) I34N possibly damaging Het
Pcdhb4 A G 18: 37,441,901 (GRCm39) T404A possibly damaging Het
Plcl1 T A 1: 55,737,374 (GRCm39) M905K probably benign Het
Plod2 G T 9: 92,480,672 (GRCm39) G422* probably null Het
Ppp1r12a T C 10: 108,089,341 (GRCm39) V660A probably benign Het
Prdm6 T C 18: 53,673,278 (GRCm39) I186T possibly damaging Het
Ptprq T G 10: 107,547,923 (GRCm39) K158N possibly damaging Het
Rimbp2 A G 5: 128,874,862 (GRCm39) V243A probably damaging Het
Rp1l1 T A 14: 64,267,758 (GRCm39) Y1115N probably damaging Het
Rtn4 C T 11: 29,657,505 (GRCm39) T553I probably damaging Het
Scrn3 T C 2: 73,166,121 (GRCm39) S385P possibly damaging Het
Serpina1f C A 12: 103,659,830 (GRCm39) G151* probably null Het
Sis T C 3: 72,850,968 (GRCm39) T577A probably damaging Het
Slco1a1 A T 6: 141,854,819 (GRCm39) S611T probably benign Het
Syne1 T C 10: 4,993,630 (GRCm39) D8370G probably benign Het
Tigd4 G A 3: 84,502,585 (GRCm39) A501T possibly damaging Het
Tjp1 A T 7: 64,947,387 (GRCm39) C1724* probably null Het
Tmem107 G T 11: 68,962,301 (GRCm39) probably null Het
Tsc22d1 T C 14: 76,656,049 (GRCm39) S761P probably damaging Het
Tyw5 A T 1: 57,430,687 (GRCm39) D165E probably damaging Het
U2af2 T A 7: 5,072,438 (GRCm39) probably null Het
Ube3b T A 5: 114,550,491 (GRCm39) D839E probably benign Het
Ush2a A G 1: 188,113,698 (GRCm39) D639G probably benign Het
Veph1 A T 3: 66,065,648 (GRCm39) M473K probably benign Het
Vmn2r72 A T 7: 85,399,017 (GRCm39) N445K probably damaging Het
Vps37d T C 5: 135,105,393 (GRCm39) M77V probably null 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
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'- ATCTGGGAATGCTCTCTTCTCG -3'
(R):5'- GGCCATTGGTTTTCACTGCC -3'

Sequencing Primer
(F):5'- GCCTCTTTCAGTATCTGTACACAC -3'
(R):5'- GGTTTTCACTGCCTTCAAAAGATC -3'
Posted On 2015-04-30