Incidental Mutation 'R7969:Raf1'
| ID |
650501 |
| Institutional Source |
Beutler Lab
|
| Gene Symbol |
Raf1
|
| Ensembl Gene |
ENSMUSG00000000441 |
| Gene Name |
v-raf-leukemia viral oncogene 1 |
| Synonyms |
c-Raf, sarcoma 3611 oncogene, Craf1, Raf-1, v-Raf, 6430402F14Rik |
| MMRRC Submission |
046012-MU
|
| Accession Numbers |
|
| Essential gene? |
Essential
(E-score: 1.000)
|
| Stock # |
R7969 (G1)
|
| Quality Score |
225.009 |
|
Status
|
Not validated
|
| Chromosome |
6 |
| Chromosomal Location |
115595530-115653596 bp(-) (GRCm39) |
| Type of Mutation |
missense |
| DNA Base Change (assembly) |
T to C
at 115597249 bp (GRCm39)
|
| Zygosity |
Heterozygous |
| Amino Acid Change |
Aspartic acid to Glycine
at position 486
(D486G)
|
| Ref Sequence |
ENSEMBL: ENSMUSP00000000451
(fasta)
|
| Gene Model |
predicted gene model for transcript(s):
[ENSMUST00000000449]
[ENSMUST00000000451]
[ENSMUST00000112949]
[ENSMUST00000203759]
|
| AlphaFold |
Q99N57 |
| Predicted Effect |
probably benign
Transcript: ENSMUST00000000449
|
| SMART Domains |
Protein: ENSMUSP00000000449
Gene: ENSMUSG00000000439
| Domain | Start | End | E-Value | Type |
|---|
|
ZnF_C3H1
|
2 |
28 |
5.02e-6 |
SMART |
|
ZnF_C3H1
|
32 |
57 |
1.75e-5 |
SMART |
|
low complexity region
|
58 |
85 |
N/A |
INTRINSIC |
|
ZnF_C3H1
|
165 |
191 |
2.79e-4 |
SMART |
|
RING
|
238 |
291 |
5.82e-6 |
SMART |
|
ZnF_C3H1
|
322 |
349 |
5.5e-3 |
SMART |
|
| Predicted Effect |
probably damaging
Transcript: ENSMUST00000000451
AA Change: D486G
PolyPhen 2
Score 0.997 (Sensitivity: 0.41; Specificity: 0.98)
|
| SMART Domains |
Protein: ENSMUSP00000000451
Gene: ENSMUSG00000000441
AA Change: D486G
| Domain | Start | End | E-Value | Type |
|---|
|
RBD
|
56 |
131 |
6.95e-35 |
SMART |
|
C1
|
139 |
184 |
1.2e-13 |
SMART |
|
low complexity region
|
283 |
301 |
N/A |
INTRINSIC |
|
Pfam:Pkinase
|
349 |
606 |
7.2e-61 |
PFAM |
|
Pfam:Pkinase_Tyr
|
349 |
606 |
3.5e-65 |
PFAM |
|
Pfam:Kinase-like
|
400 |
596 |
3.8e-9 |
PFAM |
|
| Predicted Effect |
probably damaging
Transcript: ENSMUST00000112949
AA Change: D486G
PolyPhen 2
Score 0.997 (Sensitivity: 0.41; Specificity: 0.98)
|
| SMART Domains |
Protein: ENSMUSP00000108571
Gene: ENSMUSG00000000441
AA Change: D486G
| Domain | Start | End | E-Value | Type |
|---|
|
RBD
|
56 |
131 |
6.95e-35 |
SMART |
|
C1
|
139 |
184 |
1.2e-13 |
SMART |
|
low complexity region
|
283 |
301 |
N/A |
INTRINSIC |
|
Pfam:Pkinase_Tyr
|
349 |
606 |
3.4e-64 |
PFAM |
|
Pfam:Pkinase
|
349 |
608 |
1.1e-61 |
PFAM |
|
Pfam:Kinase-like
|
399 |
596 |
2e-9 |
PFAM |
|
| Predicted Effect |
probably benign
Transcript: ENSMUST00000147979
|
| SMART Domains |
Protein: ENSMUSP00000115424
Gene: ENSMUSG00000000441
| Domain | Start | End | E-Value | Type |
|---|
|
Blast:RBD
|
2 |
28 |
9e-7 |
BLAST |
|
PDB:4IHL|P
|
36 |
71 |
1e-9 |
PDB |
|
low complexity region
|
110 |
128 |
N/A |
INTRINSIC |
|
PDB:3OMV|B
|
150 |
205 |
6e-33 |
PDB |
|
SCOP:d1b6cb_
|
153 |
205 |
3e-9 |
SMART |
|
| Predicted Effect |
probably benign
Transcript: ENSMUST00000203142
|
| Predicted Effect |
possibly damaging
Transcript: ENSMUST00000203759
AA Change: D17G
PolyPhen 2
Score 0.922 (Sensitivity: 0.81; Specificity: 0.94)
|
| SMART Domains |
Protein: ENSMUSP00000145520
Gene: ENSMUSG00000000441
AA Change: D17G
| Domain | Start | End | E-Value | Type |
|---|
|
Pfam:Pkinase_Tyr
|
1 |
58 |
1e-6 |
PFAM |
|
Pfam:Pkinase
|
1 |
60 |
1e-7 |
PFAM |
|
| Coding Region Coverage |
- 1x: 100.0%
- 3x: 99.9%
- 10x: 99.6%
- 20x: 98.7%
|
| Validation Efficiency |
|
| MGI Phenotype |
FUNCTION: [Summary is not available for the mouse gene. This summary is for the human ortholog.] This gene is the cellular homolog of viral raf gene (v-raf). The encoded protein is a MAP kinase kinase kinase (MAP3K), which functions downstream of the Ras family of membrane associated GTPases to which it binds directly. Once activated, the cellular RAF1 protein can phosphorylate to activate the dual specificity protein kinases MEK1 and MEK2, which in turn phosphorylate to activate the serine/threonine specific protein kinases, ERK1 and ERK2. Activated ERKs are pleiotropic effectors of cell physiology and play an important role in the control of gene expression involved in the cell division cycle, apoptosis, cell differentiation and cell migration. Mutations in this gene are associated with Noonan syndrome 5 and LEOPARD syndrome 2. [provided by RefSeq, Jul 2008]
PHENOTYPE: Homozygotes for targeted null mutations are growth retarded, with hypocellular fetal livers, placental anomalies, and defects of skin and lungs, resulting in lethality around mid-gestation. Mice heterozygous for a knock-in allele exhibit hypertrophic cardiomyopathy. [provided by MGI curators]
|
| Allele List at MGI |
|
| Other mutations in this stock |
Total: 39 list
| Gene | Ref | Var | Chr/Loc | Mutation | Predicted Effect | Zygosity |
|---|
| Adgrv1 |
A |
T |
13: 81,588,344 (GRCm39) |
V4414E |
possibly damaging |
Het |
| Ahcyl2 |
T |
A |
6: 29,870,663 (GRCm39) |
I193N |
probably damaging |
Het |
| Amotl2 |
C |
T |
9: 102,600,968 (GRCm39) |
T345I |
probably benign |
Het |
| Atf6b |
A |
T |
17: 34,867,549 (GRCm39) |
|
probably null |
Het |
| Cacna1s |
T |
G |
1: 136,004,470 (GRCm39) |
F337C |
probably damaging |
Het |
| Cep85l |
T |
C |
10: 53,174,280 (GRCm39) |
I488V |
probably damaging |
Het |
| Cmas |
T |
A |
6: 142,720,892 (GRCm39) |
D375E |
probably damaging |
Het |
| Cnga4 |
T |
C |
7: 105,055,253 (GRCm39) |
F279S |
probably damaging |
Het |
| Cyp4f37 |
T |
C |
17: 32,844,181 (GRCm39) |
V95A |
probably benign |
Het |
| Dao |
AGG |
AG |
5: 114,153,270 (GRCm39) |
|
probably benign |
Het |
| Dlg2 |
T |
C |
7: 92,066,466 (GRCm39) |
F235S |
probably benign |
Het |
| Dmxl2 |
T |
C |
9: 54,354,165 (GRCm39) |
D427G |
possibly damaging |
Het |
| Efl1 |
T |
C |
7: 82,342,178 (GRCm39) |
Y529H |
probably benign |
Het |
| Epx |
C |
T |
11: 87,763,547 (GRCm39) |
M224I |
probably benign |
Het |
| Fetub |
A |
G |
16: 22,748,449 (GRCm39) |
R101G |
possibly damaging |
Het |
| Fubp1 |
T |
A |
3: 151,927,883 (GRCm39) |
|
probably null |
Het |
| Impdh2 |
C |
T |
9: 108,439,505 (GRCm39) |
R153* |
probably null |
Het |
| Kcnj12 |
C |
T |
11: 60,960,430 (GRCm39) |
Q243* |
probably null |
Het |
| Lrrn1 |
T |
A |
6: 107,544,811 (GRCm39) |
V203E |
probably damaging |
Het |
| Meikin |
T |
C |
11: 54,300,536 (GRCm39) |
S338P |
possibly damaging |
Het |
| Myl10 |
A |
T |
5: 136,729,707 (GRCm39) |
|
probably null |
Het |
| Nt5c3b |
T |
C |
11: 100,325,567 (GRCm39) |
K120E |
possibly damaging |
Het |
| Or10al2 |
T |
A |
17: 37,983,547 (GRCm39) |
L211H |
probably damaging |
Het |
| Or2h1b |
T |
A |
17: 37,462,077 (GRCm39) |
N262I |
possibly damaging |
Het |
| Or6c1 |
G |
A |
10: 129,517,699 (GRCm39) |
T303I |
probably benign |
Het |
| Or6c75 |
T |
C |
10: 129,337,716 (GRCm39) |
L313S |
probably benign |
Het |
| Pdzd7 |
A |
G |
19: 45,024,664 (GRCm39) |
S452P |
probably benign |
Het |
| Prune2 |
A |
G |
19: 17,179,034 (GRCm39) |
I2982V |
probably damaging |
Het |
| Ptpdc1 |
G |
A |
13: 48,740,577 (GRCm39) |
R285C |
probably damaging |
Het |
| Rbm27 |
A |
T |
18: 42,408,545 (GRCm39) |
|
probably benign |
Het |
| Slit2 |
A |
G |
5: 48,461,378 (GRCm39) |
Y1475C |
possibly damaging |
Het |
| Snx14 |
G |
A |
9: 88,295,613 (GRCm39) |
T184M |
probably damaging |
Het |
| Tgm5 |
G |
T |
2: 120,905,650 (GRCm39) |
N168K |
probably damaging |
Het |
| Ugt2b38 |
A |
G |
5: 87,571,891 (GRCm39) |
V47A |
probably benign |
Het |
| Ush2a |
A |
G |
1: 188,558,568 (GRCm39) |
H3599R |
probably benign |
Het |
| Veph1 |
T |
C |
3: 66,122,896 (GRCm39) |
E211G |
possibly damaging |
Het |
| Wapl |
T |
A |
14: 34,452,604 (GRCm39) |
H832Q |
probably damaging |
Het |
| Zfp281 |
T |
A |
1: 136,553,772 (GRCm39) |
V250D |
probably benign |
Het |
| Zfp36l2 |
A |
G |
17: 84,493,252 (GRCm39) |
S462P |
unknown |
Het |
|
| Other mutations in Raf1 |
| Allele | Source | Chr | Coord | Type | Predicted Effect | PPH Score |
|---|
|
IGL01973:Raf1
|
APN |
6 |
115,653,530 (GRCm39) |
unclassified |
probably benign |
|
|
IGL02379:Raf1
|
APN |
6 |
115,621,509 (GRCm39) |
missense |
probably benign |
|
|
IGL02427:Raf1
|
APN |
6 |
115,608,288 (GRCm39) |
missense |
probably benign |
|
|
IGL02586:Raf1
|
APN |
6 |
115,597,267 (GRCm39) |
missense |
probably damaging |
0.98 |
|
IGL02620:Raf1
|
APN |
6 |
115,609,848 (GRCm39) |
splice site |
probably benign |
|
|
P0028:Raf1
|
UTSW |
6 |
115,608,166 (GRCm39) |
splice site |
probably benign |
|
|
R0044:Raf1
|
UTSW |
6 |
115,600,476 (GRCm39) |
missense |
probably benign |
0.12 |
|
R0044:Raf1
|
UTSW |
6 |
115,600,476 (GRCm39) |
missense |
probably benign |
0.12 |
|
R0116:Raf1
|
UTSW |
6 |
115,603,344 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R0147:Raf1
|
UTSW |
6 |
115,609,934 (GRCm39) |
missense |
probably benign |
|
|
R0148:Raf1
|
UTSW |
6 |
115,609,934 (GRCm39) |
missense |
probably benign |
|
|
R0554:Raf1
|
UTSW |
6 |
115,600,491 (GRCm39) |
missense |
probably benign |
0.05 |
|
R0811:Raf1
|
UTSW |
6 |
115,603,671 (GRCm39) |
critical splice donor site |
probably null |
|
|
R0812:Raf1
|
UTSW |
6 |
115,603,671 (GRCm39) |
critical splice donor site |
probably null |
|
|
R1070:Raf1
|
UTSW |
6 |
115,614,660 (GRCm39) |
missense |
probably benign |
0.00 |
|
R4261:Raf1
|
UTSW |
6 |
115,600,015 (GRCm39) |
critical splice acceptor site |
probably null |
|
|
R4669:Raf1
|
UTSW |
6 |
115,609,880 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R4846:Raf1
|
UTSW |
6 |
115,621,544 (GRCm39) |
missense |
possibly damaging |
0.91 |
|
R5038:Raf1
|
UTSW |
6 |
115,597,196 (GRCm39) |
nonsense |
probably null |
|
|
R5214:Raf1
|
UTSW |
6 |
115,614,583 (GRCm39) |
missense |
possibly damaging |
0.82 |
|
R5472:Raf1
|
UTSW |
6 |
115,603,667 (GRCm39) |
splice site |
probably null |
|
|
R5511:Raf1
|
UTSW |
6 |
115,597,217 (GRCm39) |
missense |
probably benign |
0.32 |
|
R5539:Raf1
|
UTSW |
6 |
115,596,317 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R5926:Raf1
|
UTSW |
6 |
115,596,859 (GRCm39) |
missense |
probably benign |
0.45 |
|
R6424:Raf1
|
UTSW |
6 |
115,596,542 (GRCm39) |
missense |
probably benign |
0.02 |
|
R6649:Raf1
|
UTSW |
6 |
115,608,302 (GRCm39) |
missense |
probably benign |
0.03 |
|
R7021:Raf1
|
UTSW |
6 |
115,597,300 (GRCm39) |
splice site |
probably null |
|
|
R9182:Raf1
|
UTSW |
6 |
115,600,440 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R9614:Raf1
|
UTSW |
6 |
115,596,597 (GRCm39) |
missense |
probably benign |
|
|
| Predicted Primers |
PCR Primer
(F):5'- CCCATGGCTGTGCAGAAATG -3'
(R):5'- AGAAGTCACAATGTAGACCAGTTGG -3'
Sequencing Primer
(F):5'- CAGAAATGCTGTCAAATTTTGCACCC -3'
(R):5'- ACCTGAGTACCAAATGTAGGC -3'
|
| Posted On |
2020-09-15 |
Incidental Mutation