Incidental Mutation 'R4669:Raf1'
ID 352251
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 041925-MU
Accession Numbers
Essential gene? Essential (E-score: 1.000) question?
Stock # R4669 (G1)
Quality Score 225
Status Not validated
Chromosome 6
Chromosomal Location 115595530-115653596 bp(-) (GRCm39)
Type of Mutation missense
DNA Base Change (assembly) A to G at 115609880 bp (GRCm39)
Zygosity Heterozygous
Amino Acid Change Serine to Proline at position 220 (S220P)
Ref Sequence ENSEMBL: ENSMUSP00000108571 (fasta)
Gene Model predicted gene model for transcript(s): [ENSMUST00000000451] [ENSMUST00000112949]
AlphaFold Q99N57
Predicted Effect probably damaging
Transcript: ENSMUST00000000451
AA Change: S220P

PolyPhen 2 Score 0.998 (Sensitivity: 0.27; Specificity: 0.99)
SMART Domains Protein: ENSMUSP00000000451
Gene: ENSMUSG00000000441
AA Change: S220P

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 damaging
Transcript: ENSMUST00000112949
AA Change: S220P

PolyPhen 2 Score 0.998 (Sensitivity: 0.27; Specificity: 0.99)
SMART Domains Protein: ENSMUSP00000108571
Gene: ENSMUSG00000000441
AA Change: S220P

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: ENSMUST00000127503
Predicted Effect noncoding transcript
Transcript: ENSMUST00000130528
Predicted Effect unknown
Transcript: ENSMUST00000147979
AA Change: S26P
SMART Domains Protein: ENSMUSP00000115424
Gene: ENSMUSG00000000441
AA Change: S26P

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
Coding Region Coverage
  • 1x: 99.2%
  • 3x: 98.6%
  • 10x: 97.3%
  • 20x: 95.4%
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: 98 list
GeneRefVarChr/LocMutationPredicted EffectZygosity
Acad8 A G 9: 26,901,923 (GRCm39) L147P probably damaging Het
Acan A G 7: 78,750,890 (GRCm39) E464G probably benign Het
Agap1 A G 1: 89,765,528 (GRCm39) probably null Het
Akap13 A G 7: 75,378,842 (GRCm39) T2128A probably damaging Het
Ap2a1 A T 7: 44,552,343 (GRCm39) probably benign Het
Arap3 T C 18: 38,129,307 (GRCm39) D217G probably benign Het
Arl2 C A 19: 6,184,716 (GRCm39) R179L probably damaging Het
Atg2a T A 19: 6,309,017 (GRCm39) probably null Het
B3gat1 T A 9: 26,663,052 (GRCm39) L6Q probably benign Het
Bcl10 A G 3: 145,636,327 (GRCm39) N75S probably damaging Het
Bmpr2 T C 1: 59,906,875 (GRCm39) L656S probably damaging Het
Brms1l A G 12: 55,888,356 (GRCm39) E48G possibly damaging Het
C2cd2l A T 9: 44,226,322 (GRCm39) N414K possibly damaging Het
Capn2 C T 1: 182,298,345 (GRCm39) C640Y probably benign Het
Ccdc153 G T 9: 44,157,021 (GRCm39) R99M probably damaging Het
Ccdc51 A G 9: 108,920,030 (GRCm39) N142S probably benign Het
Cdipt A G 7: 126,577,578 (GRCm39) H108R possibly damaging Het
Ceacam20 T C 7: 19,719,952 (GRCm39) Y495H probably damaging Het
Celf2 T C 2: 6,726,339 (GRCm39) I47V probably benign Het
Cts3 C T 13: 61,714,637 (GRCm39) E223K probably benign Het
Cyp2a22 T C 7: 26,637,280 (GRCm39) D168G possibly damaging Het
Cyp2c67 T A 19: 39,632,098 (GRCm39) H90L probably benign Het
Ddx4 T C 13: 112,758,778 (GRCm39) Y261C probably damaging Het
Dnah17 T C 11: 117,965,119 (GRCm39) T2308A probably benign Het
Dnah6 T C 6: 73,014,671 (GRCm39) T3587A probably damaging Het
Dpy19l1 C T 9: 24,343,664 (GRCm39) V494I possibly damaging Het
Dse T G 10: 34,029,008 (GRCm39) Y694S probably damaging Het
Emilin3 T C 2: 160,752,717 (GRCm39) I78V probably benign Het
Esam T A 9: 37,447,952 (GRCm39) Y195* probably null Het
Extl3 T A 14: 65,313,745 (GRCm39) N479I possibly damaging Het
Fat2 A G 11: 55,202,441 (GRCm39) V211A probably benign Het
Ganc G T 2: 120,261,548 (GRCm39) V343F probably benign Het
Ggt5 T C 10: 75,438,865 (GRCm39) L121P probably damaging Het
Gnmt A T 17: 47,037,225 (GRCm39) C186* probably null Het
Gpr75 A T 11: 30,842,072 (GRCm39) I326F probably damaging Het
Gsdme C T 6: 50,185,102 (GRCm39) V451M probably damaging Het
H2-T23 G T 17: 36,342,690 (GRCm39) D149E probably damaging Het
Hmcn2 G T 2: 31,325,804 (GRCm39) R4277L probably benign Het
Irf9 C A 14: 55,843,223 (GRCm39) H94N probably benign Het
Jhy T C 9: 40,872,449 (GRCm39) N20S probably benign Het
Klf17 C A 4: 117,617,568 (GRCm39) C263F probably damaging Het
Lama5 T C 2: 179,822,430 (GRCm39) Y2881C probably damaging Het
Lig1 T G 7: 13,044,953 (GRCm39) I882S probably damaging Het
Ltn1 A T 16: 87,215,375 (GRCm39) M420K possibly damaging Het
Mael T C 1: 166,063,077 (GRCm39) E125G probably damaging Het
Mib2 C T 4: 155,741,872 (GRCm39) D275N possibly damaging Het
Mical3 C T 6: 120,934,664 (GRCm39) R1805Q probably damaging Het
Mix23 A G 16: 35,903,089 (GRCm39) D27G probably damaging Het
Mllt10 A G 2: 18,208,444 (GRCm39) D158G probably damaging Het
Mocs1 A G 17: 49,761,613 (GRCm39) D569G possibly damaging Het
Msh6 T C 17: 88,292,234 (GRCm39) S330P possibly damaging Het
Mtmr2 T C 9: 13,707,260 (GRCm39) S199P probably damaging Het
Ndufaf5 T C 2: 140,029,675 (GRCm39) V164A probably benign Het
Nek9 T C 12: 85,360,978 (GRCm39) E518G probably benign Het
Nfatc2 T C 2: 168,413,410 (GRCm39) I72V probably benign Het
Nlrp9c C T 7: 26,074,793 (GRCm39) A746T possibly damaging Het
Nup42 A G 5: 24,387,415 (GRCm39) R402G probably benign Het
Ogdh G T 11: 6,290,600 (GRCm39) C406F probably benign Het
Or3a1d A G 11: 74,237,789 (GRCm39) V207A probably benign Het
Or4c120 G A 2: 89,001,245 (GRCm39) H104Y probably damaging Het
Or8b35 A T 9: 37,904,381 (GRCm39) I198F possibly damaging Het
Or8g17 T A 9: 38,930,675 (GRCm39) Y54F probably benign Het
Or8j3 A T 2: 86,028,277 (GRCm39) M273K possibly damaging Het
Otof A G 5: 30,578,318 (GRCm39) probably null Het
Pcdhb17 T C 18: 37,619,259 (GRCm39) S350P probably damaging Het
Phf3 T C 1: 30,869,027 (GRCm39) T674A probably damaging Het
Pikfyve T A 1: 65,289,432 (GRCm39) C1235S probably damaging Het
Ppfia3 T C 7: 45,001,517 (GRCm39) E465G probably damaging Het
Prkg1 T A 19: 31,641,639 (GRCm39) I15F probably damaging Het
Rab5c A G 11: 100,610,843 (GRCm39) F22L probably damaging Het
Rgl1 T G 1: 152,397,122 (GRCm39) R716S probably damaging Het
Rhbg C A 3: 88,153,273 (GRCm39) W205L probably damaging Het
Rimbp3 A G 16: 17,027,053 (GRCm39) E159G possibly damaging Het
Ryr1 T C 7: 28,759,256 (GRCm39) D3338G probably null Het
Sash1 T C 10: 8,606,149 (GRCm39) N747S probably benign Het
Serpina3g A T 12: 104,205,479 (GRCm39) I73F probably damaging Het
Sfxn2 C A 19: 46,574,213 (GRCm39) N134K probably damaging Het
Slc12a6 A G 2: 112,184,640 (GRCm39) H853R probably damaging Het
Slc16a12 C T 19: 34,649,965 (GRCm39) D357N probably damaging Het
Slc39a8 T C 3: 135,561,772 (GRCm39) Y164H probably benign Het
Snx9 A G 17: 5,977,499 (GRCm39) K518E probably damaging Het
Spdye4c G A 2: 128,434,273 (GRCm39) V5I possibly damaging Het
Spef2 A G 15: 9,676,459 (GRCm39) V704A probably benign Het
Stard3nl T A 13: 19,560,689 (GRCm39) N29Y probably damaging Het
Strap C A 6: 137,712,384 (GRCm39) S11* probably null Het
Synpo2 A G 3: 122,906,712 (GRCm39) L868P probably damaging Het
Tenm2 A G 11: 35,901,314 (GRCm39) V2474A probably damaging Het
Tm9sf4 T A 2: 153,029,228 (GRCm39) V92D probably damaging Het
Tmf1 A T 6: 97,147,388 (GRCm39) M526K probably benign Het
Top2b T G 14: 16,409,189 (GRCm38) I777M probably damaging Het
Ttc39d A G 17: 80,525,068 (GRCm39) I576V probably benign Het
Upk1a T G 7: 30,304,554 (GRCm39) T193P probably benign Het
Vmn2r67 A T 7: 84,799,732 (GRCm39) V502E probably benign Het
Wdr17 A G 8: 55,143,083 (GRCm39) V189A possibly damaging Het
Wrap73 A T 4: 154,236,153 (GRCm39) S161C probably benign Het
Zfp568 A G 7: 29,722,702 (GRCm39) H549R probably damaging Het
Zfp605 T A 5: 110,275,227 (GRCm39) M115K possibly damaging Het
Zp1 T A 19: 10,896,269 (GRCm39) H152L probably benign 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
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
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'- TGCAGTCAAAATCACTTTCCAG -3'
(R):5'- TAGCAGGTGACTAAAGCACTTG -3'

Sequencing Primer
(F):5'- TTCCAGAATATAAGTACGCTGGGACC -3'
(R):5'- GAATCAAGGACAGTTGGGTTTTTGC -3'
Posted On 2015-10-08