Incidental Mutation 'R0333:Smad2'
| ID |
38364 |
| Institutional Source |
Beutler Lab
|
| Gene Symbol |
Smad2
|
| Ensembl Gene |
ENSMUSG00000024563 |
| Gene Name |
SMAD family member 2 |
| Synonyms |
Madr2, Madh2, Smad 2, 7120426M23Rik |
| MMRRC Submission |
038542-MU
|
| Accession Numbers |
|
| Essential gene? |
Essential
(E-score: 1.000)
|
| Stock # |
R0333 (G1)
|
| Quality Score |
199 |
|
Status
|
Validated
|
| Chromosome |
18 |
| Chromosomal Location |
76374651-76444034 bp(+) (GRCm39) |
| Type of Mutation |
missense |
| DNA Base Change (assembly) |
G to A
at 76395692 bp (GRCm39)
|
| Zygosity |
Heterozygous |
| Amino Acid Change |
Alanine to Threonine
at position 44
(A44T)
|
| Ref Sequence |
ENSEMBL: ENSMUSP00000125883
(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: A44T
PolyPhen 2
Score 0.999 (Sensitivity: 0.14; Specificity: 0.99)
|
| SMART Domains |
Protein: ENSMUSP00000025453
Gene: ENSMUSG00000024563
AA Change: A44T
| Domain | Start | End | E-Value | Type |
|---|
|
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: A44T
PolyPhen 2
Score 0.999 (Sensitivity: 0.14; Specificity: 0.99)
|
| SMART Domains |
Protein: ENSMUSP00000089439
Gene: ENSMUSG00000024563
AA Change: A44T
| Domain | Start | End | E-Value | Type |
|---|
|
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: A44T
PolyPhen 2
Score 0.999 (Sensitivity: 0.14; Specificity: 0.99)
|
| SMART Domains |
Protein: ENSMUSP00000109563
Gene: ENSMUSG00000024563
AA Change: A44T
| Domain | Start | End | E-Value | Type |
|---|
|
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: A44T
PolyPhen 2
Score 1.000 (Sensitivity: 0.00; Specificity: 1.00)
|
| SMART Domains |
Protein: ENSMUSP00000132851
Gene: ENSMUSG00000024563
AA Change: A44T
| Domain | Start | End | E-Value | Type |
|---|
|
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: A44T
PolyPhen 2
Score 0.999 (Sensitivity: 0.14; Specificity: 0.99)
|
| SMART Domains |
Protein: ENSMUSP00000130115
Gene: ENSMUSG00000024563
AA Change: A44T
| Domain | Start | End | E-Value | Type |
|---|
|
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: A44T
PolyPhen 2
Score 1.000 (Sensitivity: 0.00; Specificity: 1.00)
|
| SMART Domains |
Protein: ENSMUSP00000125883
Gene: ENSMUSG00000024563
AA Change: A44T
| Domain | Start | End | E-Value | Type |
|---|
|
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
| Domain | Start | End | E-Value | Type |
|---|
|
Pfam:MH2
|
28 |
58 |
1.8e-10 |
PFAM |
|
| Meta Mutation Damage Score |
0.7109 |
| Coding Region Coverage |
- 1x: 99.2%
- 3x: 98.4%
- 10x: 96.7%
- 20x: 93.8%
|
| Validation Efficiency |
100% (53/53) |
| 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: 49 list
| Gene | Ref | Var | Chr/Loc | Mutation | Predicted Effect | Zygosity |
|---|
| Alas1 |
T |
C |
9: 106,118,480 (GRCm39) |
N214S |
probably benign |
Het |
| Antxr1 |
A |
G |
6: 87,165,820 (GRCm39) |
|
probably benign |
Het |
| Atxn7l3 |
A |
T |
11: 102,185,818 (GRCm39) |
|
probably null |
Het |
| Cab39l |
A |
G |
14: 59,737,060 (GRCm39) |
E60G |
probably damaging |
Het |
| Cdc5l |
G |
T |
17: 45,704,142 (GRCm39) |
|
probably benign |
Het |
| Cux2 |
T |
C |
5: 121,998,671 (GRCm39) |
E1423G |
probably benign |
Het |
| Dbndd1 |
G |
T |
8: 124,233,512 (GRCm39) |
Q165K |
probably damaging |
Het |
| Drd1 |
C |
A |
13: 54,208,082 (GRCm39) |
C37F |
probably damaging |
Het |
| Elp3 |
G |
A |
14: 65,828,042 (GRCm39) |
P11L |
probably benign |
Het |
| F830045P16Rik |
A |
G |
2: 129,314,777 (GRCm39) |
Y167H |
probably damaging |
Het |
| Gimap3 |
G |
A |
6: 48,742,664 (GRCm39) |
Q89* |
probably null |
Het |
| H2ac25 |
C |
A |
11: 58,845,685 (GRCm39) |
S41* |
probably null |
Het |
| Herc1 |
G |
A |
9: 66,371,981 (GRCm39) |
|
probably null |
Het |
| Ipo11 |
A |
G |
13: 107,007,271 (GRCm39) |
V603A |
probably benign |
Het |
| Kifap3 |
G |
A |
1: 163,624,833 (GRCm39) |
A130T |
probably damaging |
Het |
| Klhl23 |
A |
G |
2: 69,664,241 (GRCm39) |
Y530C |
probably damaging |
Het |
| Map4k1 |
C |
T |
7: 28,699,186 (GRCm39) |
|
probably benign |
Het |
| Mroh2b |
T |
A |
15: 4,960,600 (GRCm39) |
L778M |
probably damaging |
Het |
| Mtdh |
T |
C |
15: 34,118,247 (GRCm39) |
S344P |
possibly damaging |
Het |
| Ncoa3 |
T |
G |
2: 165,896,211 (GRCm39) |
N371K |
probably damaging |
Het |
| Ncor2 |
C |
A |
5: 125,111,408 (GRCm39) |
|
probably benign |
Het |
| Nrn1l |
A |
G |
8: 106,621,052 (GRCm39) |
E48G |
probably benign |
Het |
| Nudcd1 |
A |
G |
15: 44,264,683 (GRCm39) |
I271T |
probably benign |
Het |
| Or1e17 |
A |
T |
11: 73,831,593 (GRCm39) |
I174F |
possibly damaging |
Het |
| Or2t1 |
T |
C |
14: 14,328,498 (GRCm38) |
L129P |
probably damaging |
Het |
| Pard3b |
A |
G |
1: 62,269,371 (GRCm39) |
N653S |
probably benign |
Het |
| Plekhg1 |
A |
C |
10: 3,914,419 (GRCm39) |
K1380N |
probably damaging |
Het |
| Ppara |
T |
A |
15: 85,675,161 (GRCm39) |
I210N |
probably damaging |
Het |
| Ppp2r5b |
A |
G |
19: 6,279,077 (GRCm39) |
|
probably benign |
Het |
| Prkn |
T |
C |
17: 11,286,027 (GRCm39) |
F6L |
probably damaging |
Het |
| Prr14l |
A |
G |
5: 32,985,337 (GRCm39) |
L1386P |
probably damaging |
Het |
| Ralgapa1 |
A |
G |
12: 55,829,685 (GRCm39) |
|
probably benign |
Het |
| Reln |
A |
T |
5: 22,134,240 (GRCm39) |
L2563I |
probably damaging |
Het |
| Rps7 |
A |
G |
12: 28,681,200 (GRCm39) |
|
probably benign |
Het |
| Rslcan18 |
T |
C |
13: 67,246,686 (GRCm39) |
K309E |
probably damaging |
Het |
| Sec14l5 |
C |
T |
16: 4,984,930 (GRCm39) |
T92M |
probably damaging |
Het |
| Slc22a8 |
G |
A |
19: 8,585,514 (GRCm39) |
|
probably benign |
Het |
| Smcr8 |
T |
C |
11: 60,671,048 (GRCm39) |
V732A |
possibly damaging |
Het |
| Spata2l |
A |
G |
8: 123,960,371 (GRCm39) |
F306S |
probably damaging |
Het |
| Stab2 |
T |
C |
10: 86,677,491 (GRCm39) |
D2552G |
probably benign |
Het |
| Tctn3 |
A |
T |
19: 40,595,711 (GRCm39) |
L358H |
possibly damaging |
Het |
| Tk2 |
C |
T |
8: 104,975,146 (GRCm39) |
|
probably benign |
Het |
| Tm6sf2 |
C |
T |
8: 70,530,564 (GRCm39) |
R215C |
probably damaging |
Het |
| Tmbim6 |
T |
C |
15: 99,304,555 (GRCm39) |
I204T |
probably damaging |
Het |
| Tubgcp2 |
C |
A |
7: 139,579,260 (GRCm39) |
W675C |
probably damaging |
Het |
| Usp48 |
T |
A |
4: 137,321,794 (GRCm39) |
I62N |
probably damaging |
Het |
| Vmn2r74 |
T |
C |
7: 85,601,491 (GRCm39) |
T716A |
probably benign |
Het |
| Vps13b |
C |
A |
15: 35,879,949 (GRCm39) |
T3008K |
probably damaging |
Het |
| Wnk1 |
G |
A |
6: 119,905,124 (GRCm39) |
|
probably benign |
Het |
|
| Other mutations in Smad2 |
| Allele | Source | Chr | Coord | Type | Predicted Effect | PPH 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 |
|
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 |
|
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'- TTGCCCAGAGCGTTGACAAAGA -3'
(R):5'- GCGAAAGGAAACTACTAGCCAGCAC -3'
Sequencing Primer
(F):5'- AGACAGCATCGTCATCAGTATAG -3'
(R):5'- TACTAGCCAGCACTTGTCAG -3'
|
| Posted On |
2013-05-23 |
Incidental Mutation