Mutagenetix > Incidental Mutation

Incidental Mutation 'R5214:Raf1'

403337

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

042787-MU

Accession Numbers

Essential gene?

Essential (E-score: 1.000) question?

Stock #

R5214 (G1)

Quality Score

225

Status

Validated

Chromosome

Chromosomal Location

115595530-115653596 bp(-) (GRCm39)

Type of Mutation

missense

DNA Base Change (assembly)

G to T at 115614583 bp (GRCm39)

Zygosity

Heterozygous

Amino Acid Change

Phenylalanine to Leucine at position 99 (F99L)

Ref Sequence

ENSEMBL: ENSMUSP00000108571 (fasta)

Gene Model

predicted gene model for transcript(s): [ENSMUST00000000451] [ENSMUST00000112949]

AlphaFold

Q99N57

Predicted Effect

possibly damaging
Transcript: ENSMUST00000000451
AA Change: F99L

PolyPhen 2 Score 0.821 (Sensitivity: 0.84; Specificity: 0.93)

SMART Domains

Protein: ENSMUSP00000000451
Gene: ENSMUSG00000000441
AA Change: F99L

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

possibly damaging
Transcript: ENSMUST00000112949
AA Change: F99L

PolyPhen 2 Score 0.821 (Sensitivity: 0.84; Specificity: 0.93)

SMART Domains

Protein: ENSMUSP00000108571
Gene: ENSMUSG00000000441
AA Change: F99L

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

noncoding transcript
Transcript: ENSMUST00000119165

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000127503

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000130528

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

Meta Mutation Damage Score

0.5097

Coding Region Coverage

1x: 99.3%
3x: 98.7%
10x: 97.5%
20x: 95.9%

Validation Efficiency

100% (77/77)

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: 69 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
1700061I17Rik	A	G	3: 116,861,424 (GRCm39)		noncoding transcript	Het
4930449A18Rik	A	T	3: 59,733,305 (GRCm39)		noncoding transcript	Het
Acsbg3	T	C	17: 57,193,493 (GRCm39)	V613A	probably benign	Het
Adgrl1	G	A	8: 84,642,202 (GRCm39)		probably null	Het
Aldh1l1	A	G	6: 90,540,399 (GRCm39)	D228G	probably damaging	Het
Ankrd17	T	C	5: 90,431,319 (GRCm39)	I822V	possibly damaging	Het
Atm	C	A	9: 53,402,327 (GRCm39)	A1382S	probably benign	Het
Bltp3a	G	A	17: 28,106,489 (GRCm39)	S1005N	probably benign	Het
Cacna1e	T	A	1: 154,577,110 (GRCm39)	I96F	possibly damaging	Het
Calhm5	A	G	10: 33,968,487 (GRCm39)	S189P	probably damaging	Het
Ccar1	G	A	10: 62,606,740 (GRCm39)	R335C	probably damaging	Het
Ccdc113	T	C	8: 96,272,601 (GRCm39)	I236T	possibly damaging	Het
Ccdc14	T	A	16: 34,525,225 (GRCm39)	S125T	probably benign	Het
Cdc45	C	T	16: 18,614,647 (GRCm39)	R205H	probably damaging	Het
Cdon	T	C	9: 35,394,504 (GRCm39)	C917R	probably damaging	Het
Ckap2l	T	C	2: 129,127,389 (GRCm39)	D263G	probably benign	Het
Cntnap3	G	T	13: 64,909,824 (GRCm39)	H760Q	probably damaging	Het
Dennd2d	G	A	3: 106,393,637 (GRCm39)		probably null	Het
Dock4	A	G	12: 40,754,465 (GRCm39)	I485V	probably benign	Het
Dspp	A	G	5: 104,326,364 (GRCm39)	D909G	unknown	Het
Eps8	A	T	6: 137,504,490 (GRCm39)	M81K	probably damaging	Het
Fras1	T	C	5: 96,917,452 (GRCm39)	S3491P	probably damaging	Het
Gm17669	C	T	18: 67,695,479 (GRCm39)	T8I	possibly damaging	Het
Gm5114	G	T	7: 39,057,792 (GRCm39)	T609K	probably benign	Het
Gm973	A	G	1: 59,565,880 (GRCm39)	N32S	probably damaging	Het
Herpud1	G	T	8: 95,117,479 (GRCm39)		probably null	Het
Jcad	T	A	18: 4,674,134 (GRCm39)	L632Q	probably damaging	Het
Kcnh8	T	C	17: 53,205,486 (GRCm39)	L527S	probably damaging	Het
Klk1b11	C	A	7: 43,647,266 (GRCm39)	H67N	probably benign	Het
Ldhb	T	A	6: 142,441,321 (GRCm39)	I190F	probably damaging	Het
Lrrc34	A	T	3: 30,690,397 (GRCm39)	C168*	probably null	Het
Lrtm1	C	T	14: 28,743,651 (GRCm39)	H40Y	possibly damaging	Het
Mageb3	T	C	2: 121,785,319 (GRCm39)	M128V	possibly damaging	Het
Miga2	A	G	2: 30,261,208 (GRCm39)	T90A	probably benign	Het
Msantd5	C	A	11: 51,125,675 (GRCm39)	H199Q	possibly damaging	Het
Ndrg1	G	A	15: 66,831,239 (GRCm39)	T24I	probably damaging	Het
Nos2	T	C	11: 78,846,267 (GRCm39)	L878P	probably damaging	Het
Or11g27	T	G	14: 50,771,804 (GRCm39)	*312E	probably null	Het
Pcdhgb1	T	A	18: 37,814,478 (GRCm39)	I323N	probably damaging	Het
Plec	A	G	15: 76,061,921 (GRCm39)	I2537T	probably damaging	Het
Pnpo	C	A	11: 96,833,295 (GRCm39)	E68D	probably benign	Het
Ppp6r1	C	T	7: 4,646,176 (GRCm39)	R175Q	probably benign	Het
Prnp	C	T	2: 131,778,924 (GRCm39)	T192I	probably damaging	Het
Ptprb	T	C	10: 116,205,229 (GRCm39)	I2148T	possibly damaging	Het
Rbks	A	G	5: 31,807,736 (GRCm39)		probably benign	Het
Rlf	T	C	4: 121,007,897 (GRCm39)	D361G	probably damaging	Het
Rnpepl1	G	T	1: 92,847,001 (GRCm39)	D608Y	probably benign	Het
Scaf1	G	A	7: 44,652,662 (GRCm39)		probably benign	Het
Sh3rf1	A	T	8: 61,825,765 (GRCm39)	M587L	probably damaging	Het
Slc22a21	A	T	11: 53,843,869 (GRCm39)	S473T	probably damaging	Het
Syt15	A	G	14: 33,943,703 (GRCm39)	D84G	possibly damaging	Het
Tbc1d19	T	C	5: 54,007,183 (GRCm39)	L236P	probably benign	Het
Tbx2	G	T	11: 85,729,263 (GRCm39)	A549S	probably benign	Het
Tc2n	A	T	12: 101,659,461 (GRCm39)	C157*	probably null	Het
Tecta	C	T	9: 42,256,964 (GRCm39)	V1571I	probably benign	Het
Them4	A	G	3: 94,224,818 (GRCm39)	K65R	probably benign	Het
Tmc5	C	T	7: 118,247,155 (GRCm39)	T553M	probably damaging	Het
Tmem200c	C	T	17: 69,148,122 (GRCm39)	A235V	probably damaging	Het
Tmem8b	G	A	4: 43,673,992 (GRCm39)	V208I	probably benign	Het
Tmf1	G	C	6: 97,144,253 (GRCm39)	A701G	possibly damaging	Het
Tomm70a	G	A	16: 56,942,300 (GRCm39)	G26S	unknown	Het
Treh	T	C	9: 44,594,173 (GRCm39)	Y140H	probably damaging	Het
Ttc28	A	G	5: 111,325,489 (GRCm39)		probably benign	Het
Uba7	T	C	9: 107,854,713 (GRCm39)		probably benign	Het
Ube4a	T	C	9: 44,860,166 (GRCm39)	I299V	probably benign	Het
Zfhx4	A	C	3: 5,468,701 (GRCm39)	K2953T	probably damaging	Het
Zfp280d	T	A	9: 72,215,395 (GRCm39)		probably benign	Het
Zscan20	G	A	4: 128,482,109 (GRCm39)	R518C	probably benign	Het
Zw10	T	C	9: 48,975,463 (GRCm39)	I296T	possibly damaging	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
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'- TCCATCCCTGGACAATGCTATTAG -3'
(R):5'- ACCATTTTATATGTCGTGCGTG -3'

Sequencing Primer
(F):5'- GCTTTTAAGACAATGTCCAGGC -3'
(R):5'- CATTTTATATGTCGTGCGTGTATTTC -3'

Posted On

2016-07-22