Incidental Mutation 'R1953:Smad2'
ID 217517
Institutional Source Beutler Lab
Gene Symbol Smad2
Ensembl Gene ENSMUSG00000024563
Gene Name SMAD family member 2
Synonyms Madr2, Madh2, Smad 2, 7120426M23Rik
MMRRC Submission 039967-MU
Accession Numbers
Essential gene? Essential (E-score: 1.000) question?
Stock # R1953 (G1)
Quality Score 225
Status Not validated
Chromosome 18
Chromosomal Location 76374651-76444034 bp(+) (GRCm39)
Type of Mutation missense
DNA Base Change (assembly) A to G at 76395776 bp (GRCm39)
Zygosity Heterozygous
Amino Acid Change Threonine to Alanine at position 72 (T72A)
Ref Sequence ENSEMBL: ENSMUSP00000125883 (fasta)
Gene Model predicted gene model for transcript(s): [ENSMUST00000025453] [ENSMUST00000091831] [ENSMUST00000113930] [ENSMUST00000165084] [ENSMUST00000168423] [ENSMUST00000171256] [ENSMUST00000172198]
AlphaFold Q62432
Predicted Effect possibly damaging
Transcript: ENSMUST00000025453
AA Change: T72A

PolyPhen 2 Score 0.599 (Sensitivity: 0.87; Specificity: 0.91)
SMART Domains Protein: ENSMUSP00000025453
Gene: ENSMUSG00000024563
AA Change: T72A

DomainStartEndE-ValueType
DWA 36 174 1e-64 SMART
Blast:DWB 230 261 2e-10 BLAST
DWB 272 443 2.25e-108 SMART
Predicted Effect possibly damaging
Transcript: ENSMUST00000091831
AA Change: T72A

PolyPhen 2 Score 0.599 (Sensitivity: 0.87; Specificity: 0.91)
SMART Domains Protein: ENSMUSP00000089439
Gene: ENSMUSG00000024563
AA Change: T72A

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 benign
Transcript: ENSMUST00000113930
AA Change: T72A

PolyPhen 2 Score 0.190 (Sensitivity: 0.92; Specificity: 0.87)
SMART Domains Protein: ENSMUSP00000109563
Gene: ENSMUSG00000024563
AA Change: T72A

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 possibly damaging
Transcript: ENSMUST00000165084
AA Change: T72A

PolyPhen 2 Score 0.858 (Sensitivity: 0.83; Specificity: 0.93)
SMART Domains Protein: ENSMUSP00000132851
Gene: ENSMUSG00000024563
AA Change: T72A

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 possibly damaging
Transcript: ENSMUST00000168423
AA Change: T72A

PolyPhen 2 Score 0.599 (Sensitivity: 0.87; Specificity: 0.91)
SMART Domains Protein: ENSMUSP00000130115
Gene: ENSMUSG00000024563
AA Change: T72A

DomainStartEndE-ValueType
DWA 36 174 1e-64 SMART
Blast:DWB 230 261 2e-10 BLAST
DWB 272 443 2.25e-108 SMART
Predicted Effect possibly damaging
Transcript: ENSMUST00000171256
AA Change: T72A

PolyPhen 2 Score 0.897 (Sensitivity: 0.82; Specificity: 0.94)
SMART Domains Protein: ENSMUSP00000125883
Gene: ENSMUSG00000024563
AA Change: T72A

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: 99.2%
  • 3x: 98.5%
  • 10x: 96.9%
  • 20x: 94.4%
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: 71 list
GeneRefVarChr/LocMutationPredicted EffectZygosity
5730455P16Rik A T 11: 80,268,772 (GRCm39) D12E probably damaging Het
Abca15 C T 7: 119,960,655 (GRCm39) R706C probably damaging Het
Actr1a G A 19: 46,369,387 (GRCm39) S209F probably benign Het
Adcy1 A G 11: 7,028,991 (GRCm39) N247S probably benign Het
Anapc4 T C 5: 52,997,030 (GRCm39) L101S probably damaging Het
Asap3 C T 4: 135,954,767 (GRCm39) R60* probably null Het
Ascc3 T C 10: 50,721,726 (GRCm39) S2060P probably benign Het
Atp9b G A 18: 80,797,522 (GRCm39) T851I possibly damaging Het
Borcs5 A G 6: 134,687,230 (GRCm39) H196R unknown Het
Bpifb9b A C 2: 154,153,234 (GRCm39) D100A probably damaging Het
Cant1 G C 11: 118,299,609 (GRCm39) P247A probably damaging Het
Capza3 A T 6: 139,988,294 (GRCm39) I298L possibly damaging Het
Cdh10 T C 15: 18,966,997 (GRCm39) probably null Het
Celsr3 T C 9: 108,720,381 (GRCm39) V2551A probably benign Het
Ces4a G A 8: 105,864,729 (GRCm39) G69S probably damaging Het
Cmtr2 T C 8: 110,948,551 (GRCm39) L287P probably damaging Het
Crebbp G A 16: 3,997,313 (GRCm39) T257I probably benign Het
Crispld2 G A 8: 120,742,035 (GRCm39) V128M probably damaging Het
Crnkl1 G A 2: 145,770,120 (GRCm39) A241V probably damaging Het
Dmd T A X: 82,874,123 (GRCm39) I1342N probably damaging Het
Dnah10 A G 5: 124,859,332 (GRCm39) T2043A probably benign Het
Dscaml1 C T 9: 45,581,522 (GRCm39) T447I probably benign Het
Eif2ak3 A G 6: 70,869,538 (GRCm39) T742A probably benign Het
Farp1 A G 14: 121,492,894 (GRCm39) T499A probably benign Het
Fcgr1 G A 3: 96,194,386 (GRCm39) T167I probably damaging Het
Fgd5 C A 6: 92,001,611 (GRCm39) H935Q probably benign Het
Fhl4 A T 10: 84,934,171 (GRCm39) D203E probably benign Het
Gapt T G 13: 110,490,340 (GRCm39) T108P probably damaging Het
Gpt2 A G 8: 86,248,013 (GRCm39) T419A probably benign Het
Gucy2c A G 6: 136,681,291 (GRCm39) V907A probably damaging Het
Hmbs T C 9: 44,248,741 (GRCm39) D211G probably damaging Het
Irx5 A G 8: 93,086,438 (GRCm39) N174D probably damaging Het
Itfg1 A G 8: 86,557,860 (GRCm39) V170A probably benign Het
Itga2b T A 11: 102,349,009 (GRCm39) T732S probably benign Het
Klhl3 A G 13: 58,159,022 (GRCm39) Y546H probably damaging Het
Lama5 G A 2: 179,832,540 (GRCm39) H1670Y possibly damaging Het
Mlst8 AT ATT 17: 24,696,987 (GRCm39) probably null Het
Nbeal1 T C 1: 60,273,999 (GRCm39) V409A probably damaging Het
Nlgn1 T A 3: 25,490,464 (GRCm39) D421V probably damaging Het
Nlrp10 T C 7: 108,524,325 (GRCm39) D385G probably benign Het
Nr2e3 T A 9: 59,857,079 (GRCm39) D30V probably benign Het
Nyap1 A G 5: 137,733,294 (GRCm39) S580P probably benign Het
Or4c108 G A 2: 88,804,224 (GRCm39) Q4* probably null Het
Or4c12 A G 2: 89,774,267 (GRCm39) L64P probably damaging Het
Or4e2 T A 14: 52,688,344 (GRCm39) V158E probably benign Het
Pex1 A G 5: 3,680,038 (GRCm39) H952R probably damaging Het
Plin4 T A 17: 56,410,849 (GRCm39) I1061F possibly damaging Het
Pnkp C A 7: 44,512,026 (GRCm39) R517S probably benign Het
Polr2e T A 10: 79,874,388 (GRCm39) E39D probably benign Het
Pramel18 T C 4: 101,767,312 (GRCm39) I187T probably benign Het
Prokr1 T C 6: 87,565,575 (GRCm39) Y90C probably benign Het
Ptprm A T 17: 67,247,575 (GRCm39) S587T probably benign Het
Rere G A 4: 150,701,294 (GRCm39) E1225K probably damaging Het
Rsl24d1 G T 9: 73,021,896 (GRCm39) probably benign Het
Selp A G 1: 163,954,081 (GRCm39) N127S probably benign Het
Slc22a18 C T 7: 143,029,984 (GRCm39) T17I probably damaging Het
Snx29 G A 16: 11,217,647 (GRCm39) W149* probably null Het
Stk31 G T 6: 49,423,412 (GRCm39) probably null Het
Sult1e1 T G 5: 87,735,530 (GRCm39) probably null Het
Syngap1 G A 17: 27,163,661 (GRCm39) R41H possibly damaging Het
Tbc1d17 T A 7: 44,490,822 (GRCm39) probably null Het
Tex55 G T 16: 38,648,275 (GRCm39) T278K possibly damaging Het
Tie1 A T 4: 118,329,987 (GRCm39) probably null Het
Ttn A T 2: 76,641,587 (GRCm39) L5176Q possibly damaging Het
Usp47 T A 7: 111,692,083 (GRCm39) D848E probably benign Het
Vmn1r72 A G 7: 11,403,731 (GRCm39) L239P probably damaging Het
Vmn2r124 T C 17: 18,283,122 (GRCm39) I272T probably benign Het
Vwa1 C T 4: 155,857,571 (GRCm39) V76M probably damaging Het
Xrn1 G T 9: 95,906,274 (GRCm39) probably null Het
Zfp667 G T 7: 6,308,087 (GRCm39) V252F probably benign Het
Zranb3 A T 1: 127,927,136 (GRCm39) V343D probably 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
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
R7430:Smad2 UTSW 18 76,421,151 (GRCm39) missense probably damaging 1.00
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'- GCCAGTGGTGAAGAGACTTCTG -3'
(R):5'- GCCAGCACTTGTCAGCTATTTG -3'

Sequencing Primer
(F):5'- CAGTGGTGAAGAGACTTCTGGGATG -3'
(R):5'- CAGCACTTGTCAGCTATTTGTTTAAC -3'
Posted On 2014-08-01