Mutagenetix > Incidental Mutation

Incidental Mutation 'R0554:Raf1'

45345

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

038746-MU

Accession Numbers

Essential gene?

Essential (E-score: 1.000) question?

Stock #

R0554 (G1)

Quality Score

225

Status

Not validated

Chromosome

Chromosomal Location

115595530-115653596 bp(-) (GRCm39)

Type of Mutation

missense

DNA Base Change (assembly)

A to G at 115600491 bp (GRCm39)

Zygosity

Heterozygous

Amino Acid Change

Isoleucine to Threonine at position 376 (I376T)

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

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 benign
Transcript: ENSMUST00000000451
AA Change: I376T

PolyPhen 2 Score 0.049 (Sensitivity: 0.94; Specificity: 0.83)

SMART Domains

Protein: ENSMUSP00000000451
Gene: ENSMUSG00000000441
AA Change: I376T

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 benign
Transcript: ENSMUST00000112949
AA Change: I376T

PolyPhen 2 Score 0.049 (Sensitivity: 0.94; Specificity: 0.83)

SMART Domains

Protein: ENSMUSP00000108571
Gene: ENSMUSG00000000441
AA Change: I376T

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: ENSMUST00000124553

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000130528

Predicted Effect

unknown
Transcript: ENSMUST00000147979
AA Change: I202T

SMART Domains

Protein: ENSMUSP00000115424
Gene: ENSMUSG00000000441
AA Change: I202T

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

unknown
Transcript: ENSMUST00000203142
AA Change: I5T

Predicted Effect

probably benign
Transcript: ENSMUST00000203759

SMART Domains

Protein: ENSMUSP00000145520
Gene: ENSMUSG00000000441

Domain	Start	End	E-Value	Type
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: ENSMUST00000204512

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000203276

Coding Region Coverage

1x: 99.2%
3x: 98.5%
10x: 96.7%
20x: 93.9%

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: 99 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
1700018F24Rik	T	A	5: 144,982,181 (GRCm39)	Y255*	probably null	Het
1810024B03Rik	A	G	2: 127,029,196 (GRCm39)	M1T	probably null	Het
4930503L19Rik	T	C	18: 70,600,451 (GRCm39)	D386G	probably damaging	Het
Ace2	T	A	X: 162,958,947 (GRCm39)	N601K	probably benign	Het
Adam4	A	C	12: 81,468,198 (GRCm39)	I141R	probably damaging	Het
Adcy10	G	A	1: 165,340,699 (GRCm39)	G235S	probably benign	Het
Adcy5	G	A	16: 35,114,387 (GRCm39)	V997I	probably benign	Het
Aff2	T	G	X: 68,907,680 (GRCm39)	W1221G	possibly damaging	Het
Ankrd44	T	C	1: 54,802,917 (GRCm39)	N194D	probably benign	Het
Apba2	T	G	7: 64,395,528 (GRCm39)	L668R	probably damaging	Het
Asph	T	C	4: 9,604,581 (GRCm39)	D152G	probably damaging	Het
Bcl3	C	G	7: 19,553,991 (GRCm39)	V126L	probably benign	Het
Cd163	A	G	6: 124,289,619 (GRCm39)	T446A	probably benign	Het
Cd209g	C	T	8: 4,184,995 (GRCm39)		probably benign	Het
Cdadc1	A	T	14: 59,823,901 (GRCm39)	V197E	probably damaging	Het
CN725425	T	C	15: 91,144,966 (GRCm39)	C610R	possibly damaging	Het
Col6a2	A	G	10: 76,446,995 (GRCm39)		probably null	Het
Coro7	A	G	16: 4,450,121 (GRCm39)	L576P	possibly damaging	Het
Dgkb	T	A	12: 38,266,030 (GRCm39)	V503E	probably benign	Het
Dhx57	A	T	17: 80,567,665 (GRCm39)	L806*	probably null	Het
Dlec1	T	C	9: 118,944,070 (GRCm39)	V373A	probably benign	Het
Dnah11	G	T	12: 117,894,913 (GRCm39)	R3645S	probably benign	Het
Dnhd1	T	C	7: 105,343,602 (GRCm39)	S1649P	probably benign	Het
Draxin	T	G	4: 148,192,420 (GRCm39)	K297N	probably damaging	Het
Epha7	T	C	4: 28,951,401 (GRCm39)	S841P	probably damaging	Het
Esp8	T	G	17: 40,841,166 (GRCm39)	D142E	unknown	Het
F5	T	G	1: 164,007,018 (GRCm39)	V274G	probably damaging	Het
Fancc	T	C	13: 63,465,283 (GRCm39)	S475G	probably benign	Het
Fmo3	T	C	1: 162,781,901 (GRCm39)	N484S	probably benign	Het
Focad	T	C	4: 88,267,126 (GRCm39)	Y1046H	unknown	Het
Furin	C	T	7: 80,041,032 (GRCm39)	G602D	probably damaging	Het
Fut8	A	T	12: 77,411,744 (GRCm39)	I69L	probably benign	Het
Gnai3	A	G	3: 108,030,928 (GRCm39)	I78T	probably benign	Het
Gpr182	T	C	10: 127,586,940 (GRCm39)	I4V	probably benign	Het
Gpr63	T	C	4: 25,007,447 (GRCm39)	M57T	probably benign	Het
Grm1	T	A	10: 10,595,667 (GRCm39)	T654S	probably benign	Het
Gtf2h4	T	C	17: 35,979,531 (GRCm39)	T371A	probably benign	Het
Helq	T	C	5: 100,938,066 (GRCm39)	N460S	probably benign	Het
Hmcn1	T	C	1: 150,594,868 (GRCm39)	N1867S	probably benign	Het
Hsh2d	G	A	8: 72,954,304 (GRCm39)	D229N	probably benign	Het
Iigp1c	G	A	18: 60,378,489 (GRCm39)	R8H	probably benign	Het
Inpp5j	A	G	11: 3,449,644 (GRCm39)	Y713H	probably damaging	Het
Ints6	A	T	14: 62,942,200 (GRCm39)	V511D	possibly damaging	Het
Irag2	G	A	6: 145,111,013 (GRCm39)	A237T	probably benign	Het
Itga4	A	G	2: 79,109,461 (GRCm39)	Y220C	probably damaging	Het
Itgav	T	G	2: 83,624,614 (GRCm39)	S735A	possibly damaging	Het
Kctd16	A	G	18: 40,391,492 (GRCm39)	I27V	probably benign	Het
Klhl6	T	C	16: 19,772,343 (GRCm39)	E334G	probably damaging	Het
Ltbp1	T	A	17: 75,532,274 (GRCm39)	L116H	probably damaging	Het
Magohb	T	A	6: 131,262,660 (GRCm39)	H98L	probably benign	Het
Mgat2	A	G	12: 69,232,166 (GRCm39)	T247A	probably benign	Het
Mtif2	G	A	11: 29,483,398 (GRCm39)		probably null	Het
Myrfl	T	C	10: 116,664,878 (GRCm39)	E384G	probably damaging	Het
Nfam1	G	T	15: 82,917,410 (GRCm39)	R8S	probably benign	Het
Numa1	T	C	7: 101,644,731 (GRCm39)	S236P	possibly damaging	Het
Or14c46	A	T	7: 85,918,865 (GRCm39)	I44N	probably damaging	Het
Or2w3b	T	C	11: 58,623,865 (GRCm39)	N42S	probably damaging	Het
Or5m10b	T	C	2: 85,699,863 (GRCm39)	F309S	probably benign	Het
Or6c207	T	C	10: 129,104,368 (GRCm39)	T275A	probably benign	Het
Orc4	C	T	2: 48,795,433 (GRCm39)	S431N	probably benign	Het
Pax2	T	C	19: 44,750,300 (GRCm39)	V129A	probably damaging	Het
Pcdhb15	A	G	18: 37,607,572 (GRCm39)	D268G	probably damaging	Het
Pdcd1	G	A	1: 93,967,107 (GRCm39)	R264C	probably damaging	Het
Pi15	T	A	1: 17,691,872 (GRCm39)	M187K	probably benign	Het
Plag1	C	T	4: 3,904,546 (GRCm39)	C215Y	probably damaging	Het
Plagl1	A	G	10: 13,002,926 (GRCm39)	T65A	probably benign	Het
Pramel51	T	C	12: 88,144,328 (GRCm39)	T162A	probably benign	Het
Prss48	T	A	3: 85,908,228 (GRCm39)	Q18L	probably benign	Het
Prune2	T	A	19: 17,102,582 (GRCm39)	C2580*	probably null	Het
Rab40b	T	A	11: 121,250,432 (GRCm39)	Q74L	probably damaging	Het
Rbm46	A	T	3: 82,772,575 (GRCm39)	F186I	probably damaging	Het
Reps1	C	T	10: 17,998,867 (GRCm39)	T720M	possibly damaging	Het
Rgs22	A	G	15: 36,054,855 (GRCm39)	M649T	probably benign	Het
Rhot1	C	T	11: 80,134,264 (GRCm39)	R47*	probably null	Het
Rhox2f	A	G	X: 36,753,124 (GRCm39)	Y8C	possibly damaging	Het
Rnf17	A	G	14: 56,760,007 (GRCm39)	Y1604C	probably damaging	Het
Rnf40	T	C	7: 127,201,756 (GRCm39)	C943R	probably damaging	Het
Ropn1l	A	T	15: 31,451,295 (GRCm39)	M63K	probably benign	Het
Sbf2	C	A	7: 110,027,494 (GRCm39)	V501F	probably damaging	Het
Sh3bp1	T	A	15: 78,791,467 (GRCm39)	M354K	probably damaging	Het
Sipa1l3	T	C	7: 29,087,455 (GRCm39)	H590R	possibly damaging	Het
Slco6d1	T	A	1: 98,394,422 (GRCm39)	C369S	probably benign	Het
Sulf1	T	C	1: 12,875,418 (GRCm39)	Y143H	probably damaging	Het
Tiam2	A	T	17: 3,488,956 (GRCm39)	R755*	probably null	Het
Trim12c	C	A	7: 103,994,169 (GRCm39)	L228F	probably damaging	Het
Ttc23l	G	T	15: 10,530,743 (GRCm39)	Q290K	probably benign	Het
Uba3	T	C	6: 97,168,221 (GRCm39)		probably null	Het
Ugt1a10	A	G	1: 87,983,817 (GRCm39)	E205G	probably damaging	Het
Ugt3a1	T	A	15: 9,351,206 (GRCm39)	S72T	probably benign	Het
Upk3bl	C	T	5: 136,088,648 (GRCm39)	T113I	probably damaging	Het
Uspl1	T	A	5: 149,124,644 (GRCm39)	D20E	probably damaging	Het
Vmn2r19	G	A	6: 123,313,102 (GRCm39)	G724E	probably damaging	Het
Vmn2r63	T	A	7: 42,583,129 (GRCm39)	K29*	probably null	Het
Vwf	C	T	6: 125,619,744 (GRCm39)	A1474V	probably benign	Het
Xpc	C	T	6: 91,468,208 (GRCm39)	A860T	probably benign	Het
Zfp462	A	G	4: 55,013,689 (GRCm39)	H737R	probably damaging	Het
Zfp536	T	C	7: 37,180,244 (GRCm39)	D787G	probably damaging	Het
Zfp692	A	G	11: 58,205,053 (GRCm39)	H434R	probably damaging	Het
Zp1	C	A	19: 10,897,926 (GRCm39)	C5F	probably benign	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
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
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'- TGGAGGAGGACCGTCCCTTAAAAC -3'
(R):5'- GAGTAGCATTGAAGCGTCTCACCC -3'

Sequencing Primer
(F):5'- CCTTAAAACCCACAGCAGGTG -3'
(R):5'- tggggaggtagaaagggg -3'

Posted On

2013-06-11