Incidental Mutation 'R7430:Smad2'
ID 576429
Institutional Source Beutler Lab
Gene Symbol Smad2
Ensembl Gene ENSMUSG00000024563
Gene Name SMAD family member 2
Synonyms Madr2, Madh2, Smad 2, 7120426M23Rik
MMRRC Submission 045508-MU
Accession Numbers
Essential gene? Essential (E-score: 1.000) question?
Stock # R7430 (G1)
Quality Score 225.009
Status Not validated
Chromosome 18
Chromosomal Location 76374651-76444034 bp(+) (GRCm39)
Type of Mutation missense
DNA Base Change (assembly) T to A at 76421151 bp (GRCm39)
Zygosity Heterozygous
Amino Acid Change Valine to Glutamic Acid at position 160 (V160E)
Ref Sequence ENSEMBL: ENSMUSP00000025453 (fasta)
Gene Model predicted gene model for transcript(s): [ENSMUST00000025453] [ENSMUST00000091831] [ENSMUST00000113930] [ENSMUST00000165084] [ENSMUST00000168423] [ENSMUST00000171256] [ENSMUST00000172198]
AlphaFold Q62432
Predicted Effect probably damaging
Transcript: ENSMUST00000025453
AA Change: V160E

PolyPhen 2 Score 0.997 (Sensitivity: 0.41; Specificity: 0.98)
SMART Domains Protein: ENSMUSP00000025453
Gene: ENSMUSG00000024563
AA Change: V160E

DomainStartEndE-ValueType
DWA 36 174 1e-64 SMART
Blast:DWB 230 261 2e-10 BLAST
DWB 272 443 2.25e-108 SMART
Predicted Effect probably damaging
Transcript: ENSMUST00000091831
AA Change: V130E

PolyPhen 2 Score 0.996 (Sensitivity: 0.55; Specificity: 0.98)
SMART Domains Protein: ENSMUSP00000089439
Gene: ENSMUSG00000024563
AA Change: V130E

DomainStartEndE-ValueType
DWA 36 144 1.68e-66 SMART
Blast:DWB 200 231 1e-10 BLAST
DWB 242 413 2.25e-108 SMART
Predicted Effect probably damaging
Transcript: ENSMUST00000113930
AA Change: V130E

PolyPhen 2 Score 0.999 (Sensitivity: 0.14; Specificity: 0.99)
SMART Domains Protein: ENSMUSP00000109563
Gene: ENSMUSG00000024563
AA Change: V130E

DomainStartEndE-ValueType
DWA 36 144 1.68e-66 SMART
Blast:DWB 200 231 9e-11 BLAST
DWB 242 408 4.38e-88 SMART
Predicted Effect probably damaging
Transcript: ENSMUST00000165084
AA Change: V130E

PolyPhen 2 Score 1.000 (Sensitivity: 0.00; Specificity: 1.00)
SMART Domains Protein: ENSMUSP00000132851
Gene: ENSMUSG00000024563
AA Change: V130E

DomainStartEndE-ValueType
DWA 36 144 7.85e-67 SMART
PDB:1KHX|A 166 204 3e-19 PDB
SCOP:d1khxa_ 190 204 7e-4 SMART
Predicted Effect probably damaging
Transcript: ENSMUST00000168423
AA Change: V160E

PolyPhen 2 Score 0.997 (Sensitivity: 0.41; Specificity: 0.98)
SMART Domains Protein: ENSMUSP00000130115
Gene: ENSMUSG00000024563
AA Change: V160E

DomainStartEndE-ValueType
DWA 36 174 1e-64 SMART
Blast:DWB 230 261 2e-10 BLAST
DWB 272 443 2.25e-108 SMART
Predicted Effect probably damaging
Transcript: ENSMUST00000171256
AA Change: V160E

PolyPhen 2 Score 0.997 (Sensitivity: 0.41; Specificity: 0.98)
SMART Domains Protein: ENSMUSP00000125883
Gene: ENSMUSG00000024563
AA Change: V160E

DomainStartEndE-ValueType
DWA 36 174 1e-64 SMART
Blast:DWA 182 213 3e-13 BLAST
Predicted Effect probably benign
Transcript: ENSMUST00000172198
SMART Domains Protein: ENSMUSP00000129232
Gene: ENSMUSG00000024563

DomainStartEndE-ValueType
Pfam:MH2 28 58 1.8e-10 PFAM
Coding Region Coverage
  • 1x: 100.0%
  • 3x: 99.9%
  • 10x: 99.6%
  • 20x: 98.6%
Validation Efficiency
MGI Phenotype FUNCTION: [Summary is not available for the mouse gene. This summary is for the human ortholog.] The protein encoded by this gene belongs to the SMAD, a family of proteins similar to the gene products of the Drosophila gene 'mothers against decapentaplegic' (Mad) and the C. elegans gene Sma. SMAD proteins are signal transducers and transcriptional modulators that mediate multiple signaling pathways. This protein mediates the signal of the transforming growth factor (TGF)-beta, and thus regulates multiple cellular processes, such as cell proliferation, apoptosis, and differentiation. This protein is recruited to the TGF-beta receptors through its interaction with the SMAD anchor for receptor activation (SARA) protein. In response to TGF-beta signal, this protein is phosphorylated by the TGF-beta receptors. The phosphorylation induces the dissociation of this protein with SARA and the association with the family member SMAD4. The association with SMAD4 is important for the translocation of this protein into the nucleus, where it binds to target promoters and forms a transcription repressor complex with other cofactors. This protein can also be phosphorylated by activin type 1 receptor kinase, and mediates the signal from the activin. Alternatively spliced transcript variants have been observed for this gene. [provided by RefSeq, May 2012]
PHENOTYPE: Homozygous mutant embryos die at day 6.5-8.5 with multiple defects, including failed gastrulation, lack of mesoderm, visceral endoderm dysfunction and failure to form anterior-posterior axis. Heterozygotes may show gastrulation defects and lack mandible or eyes. [provided by MGI curators]
Allele List at MGI
Other mutations in this stock
Total: 76 list
GeneRefVarChr/LocMutationPredicted EffectZygosity
Abca3 G C 17: 24,583,932 (GRCm39) probably null Het
Ankrd17 C G 5: 90,443,516 (GRCm39) E384Q possibly damaging Het
Atp8b4 A T 2: 126,245,291 (GRCm39) V286E possibly damaging Het
BC028528 CTCACTGGTTCTGTGGTCACTGGTTCTGTGGTCACTGGTTCTGTGGTCACTGGTT CTCACTGGTTCTGTGGTCACTGGTTCTGTGGTCACTGGTTCTGTGGTCACTGGTTCTGTGGTCACTGGTT 3: 95,795,448 (GRCm39) probably benign Het
BC028528 ACTGGTTCTGTGGTC ACTGGTTCTGTGGTCTCTGGTTCTGTGGTC 3: 95,795,481 (GRCm39) probably benign Het
Brms1l T C 12: 55,892,084 (GRCm39) L126P probably damaging Het
C2cd4d G A 3: 94,271,657 (GRCm39) V308M possibly damaging Het
Calcr A G 6: 3,708,586 (GRCm39) L200S probably damaging Het
Card6 G T 15: 5,128,682 (GRCm39) Q905K probably benign Het
Chka A G 19: 3,942,787 (GRCm39) Y415C probably damaging Het
Cimap3 T C 3: 105,921,834 (GRCm39) R30G probably benign Het
Cnih1 C T 14: 47,017,679 (GRCm39) V52I possibly damaging Het
Cox4i1 T A 8: 121,400,770 (GRCm39) M145K probably damaging Het
Cubn G T 2: 13,327,804 (GRCm39) R2674S possibly damaging Het
Cyfip1 A G 7: 55,550,341 (GRCm39) E692G probably damaging Het
Dnah8 T C 17: 30,925,363 (GRCm39) F1266S probably damaging Het
Edc4 T C 8: 106,618,216 (GRCm39) S1245P probably damaging Het
Enpp1 G T 10: 24,587,848 (GRCm39) H14Q probably benign Het
Fam181b G A 7: 92,729,403 (GRCm39) V59M probably benign Het
Fat4 T A 3: 38,941,599 (GRCm39) I164N probably damaging Het
Fat4 A G 3: 39,063,793 (GRCm39) D4583G probably damaging Het
Fgb C T 3: 82,954,014 (GRCm39) V75I probably benign Het
Fign T C 2: 63,809,404 (GRCm39) D622G probably damaging Het
Frmd3 A G 4: 74,063,342 (GRCm39) D223G probably damaging Het
Gclm G A 3: 122,039,729 (GRCm39) R32Q probably benign Het
Grsf1 A T 5: 88,811,086 (GRCm39) I428N possibly damaging Het
Hnrnpll T A 17: 80,357,276 (GRCm39) I247F probably damaging Het
Hscb T A 5: 110,977,024 (GRCm39) I223L probably benign Het
Ifi204 C T 1: 173,583,247 (GRCm39) A324T probably benign Het
Itgav G A 2: 83,624,602 (GRCm39) V731M probably damaging Het
Loricrin C T 3: 91,989,206 (GRCm39) G27S unknown Het
Lpin3 A G 2: 160,740,586 (GRCm39) D377G probably benign Het
Marveld3 A G 8: 110,675,100 (GRCm39) S239P possibly damaging Het
Mast3 A C 8: 71,232,947 (GRCm39) C1122G probably damaging Het
Ms4a4d A G 19: 11,535,297 (GRCm39) I198M probably benign Het
Mup14 C T 4: 61,259,447 (GRCm39) G35E probably damaging Het
Myh1 C T 11: 67,096,393 (GRCm39) Q291* probably null Het
Myo1a T A 10: 127,542,716 (GRCm39) V118E probably damaging Het
Nfatc3 A G 8: 106,835,035 (GRCm39) T794A probably benign Het
Nkx6-2 T C 7: 139,161,916 (GRCm39) T154A probably damaging Het
Or51g2 A T 7: 102,622,969 (GRCm39) S77T probably damaging Het
Or7g16 T C 9: 18,726,650 (GRCm39) *313W probably null Het
Ovgp1 G C 3: 105,893,618 (GRCm39) A464P probably damaging Het
Ovgp1 C T 3: 105,893,619 (GRCm39) A464V possibly damaging Het
Pde6c T A 19: 38,129,887 (GRCm39) Y266N probably damaging Het
Per2 C A 1: 91,351,705 (GRCm39) E934* probably null Het
Pgm1 T A 4: 99,813,192 (GRCm39) M1K probably null Het
Plcb4 T C 2: 135,810,242 (GRCm39) Y626H probably damaging Het
Postn T A 3: 54,277,623 (GRCm39) V206D probably damaging Het
Prss29 T A 17: 25,540,113 (GRCm39) probably null Het
Ptges3l C A 11: 101,314,641 (GRCm39) V85L possibly damaging Het
Riok2 T C 17: 17,607,802 (GRCm39) L450S probably benign Het
Rpap3 A T 15: 97,586,031 (GRCm39) L320Q possibly damaging Het
Rptor T C 11: 119,737,654 (GRCm39) W576R probably damaging Het
Sgk3 A G 1: 9,942,483 (GRCm39) D85G probably benign Het
Slc2a1 A G 4: 118,993,510 (GRCm39) Y449C probably damaging Het
Slco1a5 A T 6: 142,194,438 (GRCm39) S402T probably benign Het
Snx13 T C 12: 35,183,357 (GRCm39) V760A possibly damaging Het
Sugt1 T A 14: 79,857,241 (GRCm39) probably null Het
Syne2 C T 12: 75,980,770 (GRCm39) T1509M probably damaging Het
Syne2 T A 12: 76,087,184 (GRCm39) L214* probably null Het
Tmem120a T A 5: 135,764,990 (GRCm39) probably null Het
Tmem161b A G 13: 84,430,866 (GRCm39) probably null Het
Trim33 T C 3: 103,218,219 (GRCm39) I256T possibly damaging Het
Tspan17 G A 13: 54,943,785 (GRCm39) E213K probably benign Het
Ttc6 T A 12: 57,704,888 (GRCm39) I631N probably benign Het
Ttn T A 2: 76,641,283 (GRCm39) L13574F probably damaging Het
Tufm A G 7: 126,088,299 (GRCm39) D228G probably benign Het
Usf1 T A 1: 171,245,295 (GRCm39) S236T probably benign Het
Usp39 T C 6: 72,319,900 (GRCm39) Y106C probably damaging Het
Usp46 T A 5: 74,163,849 (GRCm39) Y296F probably damaging Het
Vmn2r82 A G 10: 79,217,087 (GRCm39) N473S probably damaging Het
Washc5 A T 15: 59,241,762 (GRCm39) Y51* probably null Het
Zbtb47 G A 9: 121,592,732 (GRCm39) D351N probably benign Het
Zfp763 T A 17: 33,238,506 (GRCm39) Y213F possibly damaging Het
Zswim5 A G 4: 116,833,054 (GRCm39) T596A possibly damaging Het
Other mutations in Smad2
AlleleSourceChrCoordTypePredicted EffectPPH Score
IGL00429:Smad2 APN 18 76,431,566 (GRCm39) missense possibly damaging 0.94
IGL00978:Smad2 APN 18 76,432,846 (GRCm39) splice site probably benign
IGL01295:Smad2 APN 18 76,435,501 (GRCm39) missense probably benign 0.05
IGL01887:Smad2 APN 18 76,432,965 (GRCm39) missense probably damaging 1.00
IGL01960:Smad2 APN 18 76,395,555 (GRCm39) intron probably benign
IGL02881:Smad2 APN 18 76,432,851 (GRCm39) splice site probably null
IGL02977:Smad2 APN 18 76,422,235 (GRCm39) missense possibly damaging 0.64
R0333:Smad2 UTSW 18 76,395,692 (GRCm39) missense probably damaging 1.00
R0391:Smad2 UTSW 18 76,422,108 (GRCm39) critical splice acceptor site probably null
R0523:Smad2 UTSW 18 76,395,623 (GRCm39) missense probably benign
R0570:Smad2 UTSW 18 76,422,250 (GRCm39) splice site probably benign
R0624:Smad2 UTSW 18 76,433,064 (GRCm39) missense probably damaging 1.00
R1573:Smad2 UTSW 18 76,395,657 (GRCm39) missense possibly damaging 0.89
R1953:Smad2 UTSW 18 76,395,776 (GRCm39) missense possibly damaging 0.90
R2132:Smad2 UTSW 18 76,421,155 (GRCm39) nonsense probably null
R2213:Smad2 UTSW 18 76,437,697 (GRCm39) missense probably damaging 1.00
R3021:Smad2 UTSW 18 76,395,703 (GRCm39) missense probably damaging 1.00
R3917:Smad2 UTSW 18 76,421,008 (GRCm39) missense probably benign 0.42
R4503:Smad2 UTSW 18 76,435,663 (GRCm39) missense probably benign 0.23
R5253:Smad2 UTSW 18 76,421,124 (GRCm39) missense probably damaging 1.00
R5290:Smad2 UTSW 18 76,395,795 (GRCm39) missense probably damaging 1.00
R5891:Smad2 UTSW 18 76,433,046 (GRCm39) missense probably damaging 1.00
R6294:Smad2 UTSW 18 76,422,233 (GRCm39) missense probably benign 0.31
R6879:Smad2 UTSW 18 76,395,725 (GRCm39) missense possibly damaging 0.49
R7503:Smad2 UTSW 18 76,419,956 (GRCm39) missense probably benign
R7757:Smad2 UTSW 18 76,421,084 (GRCm39) missense probably benign 0.40
R8072:Smad2 UTSW 18 76,420,022 (GRCm39) critical splice donor site probably null
R9132:Smad2 UTSW 18 76,395,573 (GRCm39) missense possibly damaging 0.87
R9159:Smad2 UTSW 18 76,395,573 (GRCm39) missense possibly damaging 0.87
R9184:Smad2 UTSW 18 76,422,171 (GRCm39) missense probably benign 0.00
Z1177:Smad2 UTSW 18 76,421,074 (GRCm39) missense probably damaging 1.00
Z1177:Smad2 UTSW 18 76,421,073 (GRCm39) missense probably damaging 1.00
Predicted Primers PCR Primer
(F):5'- CCCTGTTGATGACACCTAGG -3'
(R):5'- GGACGTGTCCCTTTTCTAAGATAC -3'

Sequencing Primer
(F):5'- GACACCTAGGCTCTCCTTTTAAAAG -3'
(R):5'- TCAAGCTTCCCTGAGACA -3'
Posted On 2019-10-07