Incidental Mutation 'R5926:Raf1'
ID 459889
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 044121-MU
Accession Numbers
Essential gene? Essential (E-score: 1.000) question?
Stock # R5926 (G1)
Quality Score 225
Status Not validated
Chromosome 6
Chromosomal Location 115595530-115653596 bp(-) (GRCm39)
Type of Mutation missense
DNA Base Change (assembly) T to C at 115596859 bp (GRCm39)
Zygosity Heterozygous
Amino Acid Change Methionine to Valine at position 519 (M519V)
Ref Sequence ENSEMBL: ENSMUSP00000108571 (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

DomainStartEndE-ValueType
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 benign
Transcript: ENSMUST00000000451
AA Change: M519V

PolyPhen 2 Score 0.448 (Sensitivity: 0.89; Specificity: 0.90)
SMART Domains Protein: ENSMUSP00000000451
Gene: ENSMUSG00000000441
AA Change: M519V

DomainStartEndE-ValueType
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 benign
Transcript: ENSMUST00000112949
AA Change: M519V

PolyPhen 2 Score 0.448 (Sensitivity: 0.89; Specificity: 0.90)
SMART Domains Protein: ENSMUSP00000108571
Gene: ENSMUSG00000000441
AA Change: M519V

DomainStartEndE-ValueType
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 noncoding transcript
Transcript: ENSMUST00000124553
Predicted Effect noncoding transcript
Transcript: ENSMUST00000130528
Predicted Effect probably benign
Transcript: ENSMUST00000147979
SMART Domains Protein: ENSMUSP00000115424
Gene: ENSMUSG00000000441

DomainStartEndE-ValueType
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: ENSMUST00000203759
SMART Domains Protein: ENSMUSP00000145520
Gene: ENSMUSG00000000441

DomainStartEndE-ValueType
Pfam:Pkinase_Tyr 1 58 1e-6 PFAM
Pfam:Pkinase 1 60 1e-7 PFAM
Predicted Effect noncoding transcript
Transcript: ENSMUST00000203826
Predicted Effect noncoding transcript
Transcript: ENSMUST00000203276
Predicted Effect noncoding transcript
Transcript: ENSMUST00000204512
Predicted Effect probably benign
Transcript: ENSMUST00000203142
Coding Region Coverage
  • 1x: 99.9%
  • 3x: 99.5%
  • 10x: 97.7%
  • 20x: 93.0%
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: 45 list
GeneRefVarChr/LocMutationPredicted EffectZygosity
A2ml1 T A 6: 128,537,608 (GRCm39) Y701F probably benign Het
Abra T A 15: 41,729,650 (GRCm39) H250L probably damaging Het
Acer2 T C 4: 86,792,805 (GRCm39) V27A probably benign Het
Arhgef15 A G 11: 68,842,781 (GRCm39) L343S possibly damaging Het
Arnt2 G T 7: 83,993,154 (GRCm39) H129N probably damaging Het
Atp9a T A 2: 168,548,191 (GRCm39) Y63F probably damaging Het
Brca2 A G 5: 150,458,087 (GRCm39) T213A probably benign Het
Cdk5r1 T C 11: 80,369,128 (GRCm39) probably null Het
Cyb5r4 C T 9: 86,939,314 (GRCm39) L366F probably benign Het
Cyp20a1 T A 1: 60,402,401 (GRCm39) I162K possibly damaging Het
Dcaf1 T C 9: 106,715,561 (GRCm39) V226A probably benign Het
Ddx41 A T 13: 55,682,112 (GRCm39) M232K probably damaging Het
Dnm1 C T 2: 32,205,816 (GRCm39) V99I probably benign Het
Doc2a T C 7: 126,448,697 (GRCm39) V134A probably damaging Het
Ghdc C T 11: 100,659,063 (GRCm39) V380M possibly damaging Het
Gldn A G 9: 54,245,722 (GRCm39) I424M possibly damaging Het
Haus6 A T 4: 86,517,553 (GRCm39) H270Q probably benign Het
Hfe A T 13: 23,892,247 (GRCm39) M39K probably damaging Het
Jakmip1 C T 5: 37,242,624 (GRCm39) probably benign Het
Kcnb2 A G 1: 15,383,235 (GRCm39) N187S probably benign Het
Kcnd2 A G 6: 21,217,084 (GRCm39) S263G probably damaging Het
Kcnh1 A G 1: 192,095,385 (GRCm39) N481S probably benign Het
Kcnn2 A G 18: 45,818,351 (GRCm39) I343V probably benign Het
L3hypdh T A 12: 72,123,959 (GRCm39) S300C probably damaging Het
Lrit1 T A 14: 36,776,966 (GRCm39) C29S probably damaging Het
Mark3 T A 12: 111,559,168 (GRCm39) V70E probably damaging Het
Med16 C T 10: 79,738,362 (GRCm39) V319M probably damaging Het
Mindy3 T C 2: 12,352,911 (GRCm39) Y430C probably damaging Het
Mup5 A T 4: 61,751,286 (GRCm39) F121I probably benign Het
Myt1l G A 12: 29,882,331 (GRCm39) G509R unknown Het
Notch1 A G 2: 26,366,116 (GRCm39) Y813H probably benign Het
Or10a3m T C 7: 108,312,794 (GRCm39) L66S probably damaging Het
Or5p53 T C 7: 107,533,110 (GRCm39) S128P probably damaging Het
Or6b2b A T 1: 92,419,288 (GRCm39) L63Q probably damaging Het
Pi4kb A G 3: 94,906,307 (GRCm39) Y301C probably damaging Het
Ptch1 A G 13: 63,692,869 (GRCm39) S244P probably benign Het
Ptprn G A 1: 75,231,242 (GRCm39) T554I probably damaging Het
Ptprt T C 2: 161,406,606 (GRCm39) I969V probably benign Het
Ryr1 A G 7: 28,803,785 (GRCm39) V622A probably damaging Het
Spaca4 G T 7: 45,374,719 (GRCm39) H94Q probably benign Het
Spata31 A G 13: 65,068,539 (GRCm39) D229G possibly damaging Het
Tbx6 G A 7: 126,384,025 (GRCm39) A359T possibly damaging Het
Trpm8 T A 1: 88,258,469 (GRCm39) Y251N probably damaging Het
Vps16 T A 2: 130,285,476 (GRCm39) N806K probably damaging Het
Vwf T C 6: 125,581,137 (GRCm39) F592L probably damaging Het
Other mutations in Raf1
AlleleSourceChrCoordTypePredicted EffectPPH 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
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
R7969:Raf1 UTSW 6 115,597,249 (GRCm39) missense probably damaging 1.00
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'- CGGCCTACCATGAAGATGATC -3'
(R):5'- TATCCTGGCAAAGCAACAGAGG -3'

Sequencing Primer
(F):5'- CGGCCTACCATGAAGATGATCTAAAG -3'
(R):5'- CAAAGCAACAGAGGCCAGCG -3'
Posted On 2017-02-28