Incidental Mutation 'R3013:Smad4'
| ID |
257582 |
| 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 |
040534-MU
|
| Accession Numbers |
|
| Essential gene? |
Essential
(E-score: 1.000)
|
| Stock # |
R3013 (G1)
|
| Quality Score |
225 |
|
Status
|
Validated
|
| Chromosome |
18 |
| Chromosomal Location |
73772080-73836851 bp(-) (GRCm39) |
| Type of Mutation |
missense |
| DNA Base Change (assembly) |
T to C
at 73781975 bp (GRCm39)
|
| Zygosity |
Heterozygous |
| Amino Acid Change |
Tyrosine to Cysteine
at position 429
(Y429C)
|
| Ref Sequence |
ENSEMBL: ENSMUSP00000110589
(fasta)
|
| Gene Model |
predicted gene model for transcript(s):
[ENSMUST00000025393]
[ENSMUST00000114939]
|
| AlphaFold |
P97471 |
| Predicted Effect |
probably damaging
Transcript: ENSMUST00000025393
AA Change: Y429C
PolyPhen 2
Score 0.999 (Sensitivity: 0.14; Specificity: 0.99)
|
| SMART Domains |
Protein: ENSMUSP00000025393
Gene: ENSMUSG00000024515
AA Change: Y429C
| Domain | Start | End | E-Value | Type |
|---|
|
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: Y429C
PolyPhen 2
Score 0.999 (Sensitivity: 0.14; Specificity: 0.99)
|
| SMART Domains |
Protein: ENSMUSP00000110589
Gene: ENSMUSG00000024515
AA Change: Y429C
| Domain | Start | End | E-Value | Type |
|---|
|
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: ENSMUST00000142672
|
| Predicted Effect |
noncoding transcript
Transcript: ENSMUST00000147315
|
| Meta Mutation Damage Score |
0.9627 |
| Coding Region Coverage |
- 1x: 99.2%
- 3x: 98.6%
- 10x: 97.2%
- 20x: 94.9%
|
| Validation Efficiency |
97% (32/33) |
| 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: 29 list
| Gene | Ref | Var | Chr/Loc | Mutation | Predicted Effect | Zygosity |
|---|
| Afg3l1 |
C |
T |
8: 124,211,416 (GRCm39) |
R126W |
probably benign |
Het |
| Alg10b |
T |
A |
15: 90,111,759 (GRCm39) |
I201N |
possibly damaging |
Het |
| Arid2 |
T |
C |
15: 96,259,817 (GRCm39) |
S326P |
probably damaging |
Het |
| Ash2l |
T |
C |
8: 26,329,792 (GRCm39) |
D122G |
probably damaging |
Het |
| Bpifb5 |
T |
C |
2: 154,070,775 (GRCm39) |
S189P |
possibly damaging |
Het |
| Ccdc39 |
C |
T |
3: 33,868,817 (GRCm39) |
R798Q |
probably damaging |
Het |
| Ccdc57 |
A |
G |
11: 120,752,025 (GRCm39) |
V852A |
probably benign |
Het |
| Ces1e |
G |
A |
8: 93,929,915 (GRCm39) |
S455L |
probably benign |
Het |
| Cyp4f14 |
T |
C |
17: 33,128,139 (GRCm39) |
K292R |
probably benign |
Het |
| Dnah7b |
T |
C |
1: 46,227,847 (GRCm39) |
|
probably null |
Het |
| Eml5 |
T |
C |
12: 98,847,067 (GRCm39) |
|
probably null |
Het |
| Gtf2i |
T |
C |
5: 134,324,358 (GRCm39) |
|
probably benign |
Het |
| Hip1 |
T |
A |
5: 135,463,893 (GRCm39) |
E37V |
possibly damaging |
Het |
| Hspbp1 |
G |
T |
7: 4,666,483 (GRCm39) |
T299K |
probably benign |
Het |
| Lrpprc |
T |
C |
17: 85,074,497 (GRCm39) |
D470G |
probably benign |
Het |
| Mkx |
A |
T |
18: 6,936,929 (GRCm39) |
I334N |
probably damaging |
Het |
| Obscn |
A |
T |
11: 58,951,744 (GRCm39) |
L4003Q |
probably damaging |
Het |
| Pcnx2 |
C |
A |
8: 126,614,509 (GRCm39) |
C314F |
probably benign |
Het |
| Pramel31 |
T |
A |
4: 144,089,025 (GRCm39) |
D114E |
probably damaging |
Het |
| Prr5l |
A |
G |
2: 101,565,050 (GRCm39) |
F162S |
probably damaging |
Het |
| Rbfox2 |
T |
C |
15: 77,017,120 (GRCm39) |
T17A |
probably damaging |
Het |
| Rsf1 |
ATGGCG |
ATGGCGACGGTGGCG |
7: 97,229,111 (GRCm39) |
|
probably benign |
Het |
| Ryr3 |
A |
T |
2: 112,470,626 (GRCm39) |
F4610L |
probably damaging |
Het |
| Scp2 |
T |
A |
4: 107,928,554 (GRCm39) |
R379W |
probably damaging |
Het |
| Serpina3j |
A |
G |
12: 104,285,966 (GRCm39) |
T374A |
probably damaging |
Het |
| Ttn |
T |
C |
2: 76,565,025 (GRCm39) |
T28401A |
probably damaging |
Het |
| Wdr49 |
A |
G |
3: 75,358,154 (GRCm39) |
I260T |
probably damaging |
Het |
| Xirp1 |
T |
C |
9: 119,848,851 (GRCm39) |
T11A |
probably benign |
Het |
| Zfp235 |
A |
G |
7: 23,840,157 (GRCm39) |
D262G |
probably damaging |
Het |
|
| Other mutations in Smad4 |
| Allele | Source | Chr | Coord | Type | Predicted Effect | PPH 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 |
|
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 |
|
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'- TGAGCTCACAATTCTCCTGC -3'
(R):5'- ATGCACCTGAACTGAAACCTG -3'
Sequencing Primer
(F):5'- GCCGTCTGTTGAATGTGCCC -3'
(R):5'- GCACCTGAACTGAAACCTGTTATAAC -3'
|
| Posted On |
2015-01-11 |
Incidental Mutation