Mutagenetix > Incidental Mutation

Incidental Mutation 'R0092:Rasgrp4'

20278

Institutional Source

Beutler Lab

Gene Symbol

Rasgrp4

Ensembl Gene

ENSMUSG00000030589

Gene Name

RAS guanyl releasing protein 4

Synonyms

MMRRC Submission

038379-MU

Accession Numbers

Essential gene?

Non essential (E-score: 0.000) question?

Stock #

R0092 (G1)

Quality Score

170

Status

Validated (trace)

Chromosome

Chromosomal Location

28834358-28853386 bp(+) (GRCm39)

Type of Mutation

missense

DNA Base Change (assembly)

A to G at 28844557 bp (GRCm39)

Zygosity

Heterozygous

Amino Acid Change

Arginine to Glycine at position 280 (R280G)

Ref Sequence

ENSEMBL: ENSMUSP00000145352 (fasta)

Gene Model

predicted gene model for transcript(s): [ENSMUST00000032811] [ENSMUST00000094617] [ENSMUST00000159351] [ENSMUST00000159975] [ENSMUST00000160194] [ENSMUST00000161522] [ENSMUST00000203070] [ENSMUST00000203380] [ENSMUST00000204845] [ENSMUST00000205027] [ENSMUST00000204194]

AlphaFold

Q8BTM9

Predicted Effect

probably benign
Transcript: ENSMUST00000032811
AA Change: R280G

PolyPhen 2 Score 0.112 (Sensitivity: 0.93; Specificity: 0.86)

SMART Domains

Protein: ENSMUSP00000032811
Gene: ENSMUSG00000030589
AA Change: R280G

Domain	Start	End	E-Value	Type
low complexity region	15	29	N/A	INTRINSIC
low complexity region	51	65	N/A	INTRINSIC
Blast:RasGEFN	66	162	1e-30	BLAST
low complexity region	163	188	N/A	INTRINSIC
RasGEF	197	433	2.92e-70	SMART
C1	541	590	4.12e-12	SMART
low complexity region	600	609	N/A	INTRINSIC

Predicted Effect

probably benign
Transcript: ENSMUST00000094617
AA Change: R281G

PolyPhen 2 Score 0.222 (Sensitivity: 0.91; Specificity: 0.88)

SMART Domains

Protein: ENSMUSP00000092200
Gene: ENSMUSG00000030589
AA Change: R281G

Domain	Start	End	E-Value	Type
low complexity region	15	29	N/A	INTRINSIC
low complexity region	51	65	N/A	INTRINSIC
Blast:RasGEFN	66	163	2e-29	BLAST
low complexity region	164	189	N/A	INTRINSIC
RasGEF	198	434	2.92e-70	SMART
C1	542	596	1.81e-8	SMART
low complexity region	606	615	N/A	INTRINSIC

Predicted Effect

probably benign
Transcript: ENSMUST00000159351
AA Change: R280G

PolyPhen 2 Score 0.112 (Sensitivity: 0.93; Specificity: 0.86)

SMART Domains

Protein: ENSMUSP00000124183
Gene: ENSMUSG00000030589
AA Change: R280G

Domain	Start	End	E-Value	Type
low complexity region	15	29	N/A	INTRINSIC
low complexity region	51	65	N/A	INTRINSIC
Blast:RasGEFN	66	162	7e-31	BLAST
low complexity region	163	188	N/A	INTRINSIC
RasGEF	197	433	2.92e-70	SMART
Blast:RasGEF	449	553	7e-25	BLAST
SCOP:d1ptq__	541	573	1e-10	SMART

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000159898

Predicted Effect

probably benign
Transcript: ENSMUST00000159975
AA Change: R280G

PolyPhen 2 Score 0.112 (Sensitivity: 0.93; Specificity: 0.86)

SMART Domains

Protein: ENSMUSP00000125137
Gene: ENSMUSG00000030589
AA Change: R280G

Domain	Start	End	E-Value	Type
low complexity region	15	29	N/A	INTRINSIC
low complexity region	51	65	N/A	INTRINSIC
Blast:RasGEFN	66	162	1e-30	BLAST
low complexity region	163	188	N/A	INTRINSIC
RasGEF	197	433	2.92e-70	SMART
C1	541	595	1.81e-8	SMART
low complexity region	605	614	N/A	INTRINSIC

Predicted Effect

probably benign
Transcript: ENSMUST00000160194
AA Change: R270G

PolyPhen 2 Score 0.222 (Sensitivity: 0.91; Specificity: 0.88)

SMART Domains

Protein: ENSMUSP00000124908
Gene: ENSMUSG00000030589
AA Change: R270G

Domain	Start	End	E-Value	Type
low complexity region	15	29	N/A	INTRINSIC
low complexity region	51	65	N/A	INTRINSIC
Blast:RasGEFN	66	162	8e-32	BLAST
low complexity region	163	188	N/A	INTRINSIC
RasGEF	197	423	6.73e-61	SMART

Predicted Effect

probably benign
Transcript: ENSMUST00000161522
AA Change: R266G

PolyPhen 2 Score 0.009 (Sensitivity: 0.96; Specificity: 0.77)

SMART Domains

Protein: ENSMUSP00000123718
Gene: ENSMUSG00000030589
AA Change: R266G

Domain	Start	End	E-Value	Type
low complexity region	15	29	N/A	INTRINSIC
low complexity region	51	65	N/A	INTRINSIC
Blast:RasGEFN	66	165	7e-32	BLAST
RasGEF	183	419	2.92e-70	SMART
C1	527	576	4.12e-12	SMART
low complexity region	586	595	N/A	INTRINSIC

Predicted Effect

possibly damaging
Transcript: ENSMUST00000203070
AA Change: R280G

PolyPhen 2 Score 0.739 (Sensitivity: 0.85; Specificity: 0.92)

SMART Domains

Protein: ENSMUSP00000145352
Gene: ENSMUSG00000030589
AA Change: R280G

Domain	Start	End	E-Value	Type
low complexity region	15	29	N/A	INTRINSIC
RasGEFN	48	172	2.6e-3	SMART
RasGEF	197	504	1.8e-20	SMART
C1	449	498	2.1e-14	SMART
low complexity region	508	517	N/A	INTRINSIC

Predicted Effect

probably benign
Transcript: ENSMUST00000203380
AA Change: R280G

PolyPhen 2 Score 0.017 (Sensitivity: 0.95; Specificity: 0.80)

SMART Domains

Protein: ENSMUSP00000144753
Gene: ENSMUSG00000030589
AA Change: R280G

Domain	Start	End	E-Value	Type
low complexity region	15	29	N/A	INTRINSIC
RasGEFN	48	172	2.6e-3	SMART
RasGEF	197	364	3e-25	SMART
C1	472	521	2.1e-14	SMART
low complexity region	531	540	N/A	INTRINSIC

Predicted Effect

probably benign
Transcript: ENSMUST00000204845
AA Change: R246G

PolyPhen 2 Score 0.102 (Sensitivity: 0.93; Specificity: 0.86)

SMART Domains

Protein: ENSMUSP00000144774
Gene: ENSMUSG00000030589
AA Change: R246G

Domain	Start	End	E-Value	Type
low complexity region	15	29	N/A	INTRINSIC
RasGEFN	48	172	2.6e-3	SMART
RasGEF	197	399	8.7e-49	SMART
C1	507	556	2.1e-14	SMART
low complexity region	566	575	N/A	INTRINSIC

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000162946

Predicted Effect

probably benign
Transcript: ENSMUST00000205027

SMART Domains

Protein: ENSMUSP00000145186
Gene: ENSMUSG00000030589

Domain	Start	End	E-Value	Type
low complexity region	15	29	N/A	INTRINSIC
RasGEFN	48	172	2.6e-3	SMART
C1	352	401	2.1e-14	SMART
low complexity region	411	420	N/A	INTRINSIC

Predicted Effect

probably benign
Transcript: ENSMUST00000204194

SMART Domains

Protein: ENSMUSP00000145259
Gene: ENSMUSG00000030589

Domain	Start	End	E-Value	Type
low complexity region	15	29	N/A	INTRINSIC
RasGEFN	48	172	2.6e-3	SMART
RasGEF	85	336	1e-7	SMART
C1	444	493	2.1e-14	SMART
low complexity region	503	512	N/A	INTRINSIC

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000162641

Meta Mutation Damage Score

0.2065

Coding Region Coverage

1x: 98.9%
3x: 97.9%
10x: 95.1%
20x: 88.6%

Validation Efficiency

99% (112/113)

MGI Phenotype

FUNCTION: [Summary is not available for the mouse gene. This summary is for the human ortholog.] The protein encoded by this gene is a member of the Ras guanyl nucleotide-releasing protein (RasGRP) family of Ras guanine nucleotide exchange factors. It contains a Ras exchange motif, a diacylglycerol-binding domain, and two calcium-binding EF hands. This protein was shown to activate H-Ras in a cation-dependent manner in vitro. Expression of this protein in myeloid cell lines was found to be correlated with elevated level of activated RAS protein, and the RAS activation can be greatly enhanced by phorbol ester treatment, which suggested a role of this protein in diacylglycerol regulated cell signaling pathways. Studies of a mast cell leukemia cell line expressing substantial amounts of abnormal transcripts of this gene indicated that this gene may play an important role in the final stages of mast cell development. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Apr 2009]
PHENOTYPE: Mice homozygous for a knock-out allele exhibit impaired neutrophil reactive oxygen species production and chemotaxis in vitro. Mice homozygous for another knock-out allele exhibit decreased susceptibility to induced colitis and arthritis. [provided by MGI curators]

Allele List at MGI

Other mutations in this stock

Total: 94 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
Abcg2	T	A	6: 58,662,762 (GRCm39)	S535T	probably benign	Het
Acad11	A	T	9: 103,967,540 (GRCm39)		probably benign	Het
Acadm	A	T	3: 153,647,512 (GRCm39)		probably benign	Het
Acot12	T	A	13: 91,889,684 (GRCm39)	M12K	probably damaging	Het
Actr2	A	T	11: 20,044,308 (GRCm39)	N99K	probably benign	Het
Adam2	G	A	14: 66,291,336 (GRCm39)	A314V	probably damaging	Het
Agl	C	T	3: 116,587,453 (GRCm39)	R34Q	probably damaging	Het
Agrn	C	T	4: 156,263,410 (GRCm39)	R338H	probably damaging	Het
AI661453	A	G	17: 47,778,440 (GRCm39)		probably benign	Het
Alpk3	A	G	7: 80,742,301 (GRCm39)	D706G	probably benign	Het
Apbb1	T	C	7: 105,208,361 (GRCm39)	E648G	probably damaging	Het
Astn2	C	A	4: 66,322,219 (GRCm39)	A127S	unknown	Het
Asxl2	T	C	12: 3,546,313 (GRCm39)	S366P	probably benign	Het
Bdh1	A	T	16: 31,266,380 (GRCm39)	K92*	probably null	Het
Bltp1	A	G	3: 37,082,308 (GRCm39)	D3790G	probably benign	Het
Cacna1g	C	T	11: 94,348,090 (GRCm39)	S666N	probably damaging	Het
Ces2b	A	G	8: 105,563,144 (GRCm39)	T361A	possibly damaging	Het
Col6a4	T	A	9: 105,890,513 (GRCm39)	E1927V	probably benign	Het
Ctnnb1	T	G	9: 120,781,929 (GRCm39)	I314S	possibly damaging	Het
Cyp2c66	T	C	19: 39,172,224 (GRCm39)		probably benign	Het
Dennd4c	T	A	4: 86,699,844 (GRCm39)	F232I	probably damaging	Het
Dennd5a	T	C	7: 109,499,013 (GRCm39)	N950S	possibly damaging	Het
Dhx30	T	C	9: 109,914,078 (GRCm39)	N14S	possibly damaging	Het
Dip2b	T	A	15: 100,100,146 (GRCm39)	V1004D	probably damaging	Het
Dnah1	A	C	14: 30,993,566 (GRCm39)	S2872A	probably benign	Het
Dnajc10	T	C	2: 80,156,026 (GRCm39)	V233A	probably damaging	Het
E230025N22Rik	A	G	18: 36,822,277 (GRCm39)	L162P	probably damaging	Het
Elmod3	T	C	6: 72,543,792 (GRCm39)	D333G	probably benign	Het
Epb41l3	T	A	17: 69,593,745 (GRCm39)	M846K	probably damaging	Het
Frem2	A	G	3: 53,497,217 (GRCm39)	Y1766H	probably benign	Het
Fxr2	T	C	11: 69,532,972 (GRCm39)		probably benign	Het
Gmpr2	A	G	14: 55,915,402 (GRCm39)	R258G	probably benign	Het
Helb	T	C	10: 119,925,713 (GRCm39)	Y888C	probably damaging	Het
Hephl1	TTCCAGATGTCC	TTCC	9: 15,001,899 (GRCm39)		probably null	Het
Hipk2	T	C	6: 38,720,164 (GRCm39)	D482G	probably damaging	Het
Itgb4	G	T	11: 115,869,950 (GRCm39)	R44L	probably damaging	Het
Itih1	T	C	14: 30,662,820 (GRCm39)		probably benign	Het
Kit	T	A	5: 75,808,414 (GRCm39)	S719R	possibly damaging	Het
Krt13	G	A	11: 100,012,258 (GRCm39)	Q22*	probably null	Het
L3mbtl4	A	C	17: 68,732,698 (GRCm39)	R59S	probably benign	Het
Lpp	A	G	16: 24,580,352 (GRCm39)	S23G	probably benign	Het
Magi3	G	A	3: 103,958,280 (GRCm39)	Q602*	probably null	Het
Man2a1	A	G	17: 64,966,079 (GRCm39)		probably benign	Het
Muc5ac	A	G	7: 141,372,367 (GRCm39)	E2667G	possibly damaging	Het
Myef2l	G	A	3: 10,153,633 (GRCm39)	C134Y	possibly damaging	Het
Myo15b	C	G	11: 115,753,812 (GRCm39)	S842C	possibly damaging	Het
Naf1	T	A	8: 67,341,760 (GRCm39)	S462T	probably benign	Het
Necab3	T	C	2: 154,400,659 (GRCm39)	D34G	possibly damaging	Het
Nisch	C	A	14: 30,913,410 (GRCm39)		probably benign	Het
Nlrc5	T	C	8: 95,216,222 (GRCm39)		probably benign	Het
Nmt1	T	C	11: 102,937,319 (GRCm39)	F119L	probably damaging	Het
Nod1	T	G	6: 54,921,526 (GRCm39)	D264A	probably damaging	Het
Nol8	C	T	13: 49,815,923 (GRCm39)	A677V	possibly damaging	Het
Nt5e	T	A	9: 88,252,338 (GRCm39)	F567I	probably benign	Het
Obscn	A	T	11: 58,942,073 (GRCm39)	M4434K	possibly damaging	Het
Opa1	A	T	16: 29,444,412 (GRCm39)	D866V	probably damaging	Het
Or10a3m	T	C	7: 108,313,031 (GRCm39)	V145A	probably benign	Het
Or10al3	T	G	17: 38,011,696 (GRCm39)	L45R	probably damaging	Het
Or10p1	A	G	10: 129,444,090 (GRCm39)	S87P	probably damaging	Het
Or1j21	A	G	2: 36,683,508 (GRCm39)	T87A	probably benign	Het
Or51ai2	T	C	7: 103,586,934 (GRCm39)	S116P	probably damaging	Het
Otop1	T	A	5: 38,457,174 (GRCm39)	V311E	probably damaging	Het
Pcsk2	A	G	2: 143,642,944 (GRCm39)	D407G	probably damaging	Het
Pdcd1	A	G	1: 93,980,149 (GRCm39)	W23R	possibly damaging	Het
Pigp	A	G	16: 94,166,321 (GRCm39)	V129A	probably damaging	Het
Pik3r5	A	G	11: 68,383,629 (GRCm39)	R483G	probably benign	Het
Pink1	A	G	4: 138,047,309 (GRCm39)	V225A	probably benign	Het
Plcl1	C	G	1: 55,735,924 (GRCm39)	Q422E	probably damaging	Het
Plec	T	C	15: 76,067,943 (GRCm39)	E1222G	probably benign	Het
Polr1a	T	C	6: 71,944,439 (GRCm39)		probably benign	Het
Prokr2	C	T	2: 132,215,517 (GRCm39)	V154M	probably damaging	Het
Rmnd5b	T	C	11: 51,520,419 (GRCm39)	E8G	possibly damaging	Het
Sbf2	T	A	7: 109,920,013 (GRCm39)		probably benign	Het
Sec23b	A	G	2: 144,408,830 (GRCm39)	M172V	probably benign	Het
Setx	T	C	2: 29,036,305 (GRCm39)	V930A	probably benign	Het
Sft2d2	G	A	1: 165,006,829 (GRCm39)	A159V	possibly damaging	Het
Sh3gl1	G	T	17: 56,325,088 (GRCm39)	R250S	probably benign	Het
Skor1	C	A	9: 63,053,277 (GRCm39)	D231Y	probably damaging	Het
Slc24a1	T	G	9: 64,856,034 (GRCm39)	E291A	unknown	Het
Slc28a2b	G	T	2: 122,348,078 (GRCm39)		probably benign	Het
Smc1b	A	T	15: 84,951,925 (GRCm39)		probably benign	Het
Tbccd1	A	T	16: 22,644,844 (GRCm39)	N177K	possibly damaging	Het
Tdp1	T	A	12: 99,921,248 (GRCm39)	Y595N	probably damaging	Het
Tle5	G	A	10: 81,397,054 (GRCm39)	G10D	possibly damaging	Het
Tmem108	T	C	9: 103,366,504 (GRCm39)	K496E	possibly damaging	Het
Tmprss7	T	C	16: 45,487,959 (GRCm39)	D490G	probably damaging	Het
Tnrc6b	A	T	15: 80,802,729 (GRCm39)	N1511Y	probably damaging	Het
Top2b	G	A	14: 16,409,263 (GRCm38)	R802Q	probably damaging	Het
Trip10	A	T	17: 57,557,798 (GRCm39)	K27N	possibly damaging	Het
Txlnb	A	G	10: 17,718,503 (GRCm39)	N445D	possibly damaging	Het
Txnrd1	T	A	10: 82,715,636 (GRCm39)	I159N	probably damaging	Het
Ulk1	C	A	5: 110,944,193 (GRCm39)	A164S	probably null	Het
Vmn2r83	T	C	10: 79,327,798 (GRCm39)	V802A	probably damaging	Het
Zbtb4	A	G	11: 69,670,177 (GRCm39)	I967V	probably benign	Het

Other mutations in Rasgrp4

Allele	Source	Chr	Coord	Type	Predicted Effect	PPH Score
IGL00594:Rasgrp4	APN	7	28,847,966 (GRCm39)	splice site	probably benign
IGL01145:Rasgrp4	APN	7	28,850,898 (GRCm39)	missense	possibly damaging	0.83
IGL01806:Rasgrp4	APN	7	28,838,475 (GRCm39)	missense	possibly damaging	0.83
IGL02023:Rasgrp4	APN	7	28,838,335 (GRCm39)	missense	probably damaging	1.00
IGL02499:Rasgrp4	APN	7	28,850,928 (GRCm39)	utr 3 prime	probably benign
IGL02989:Rasgrp4	APN	7	28,847,831 (GRCm39)	missense	probably damaging	1.00
IGL03281:Rasgrp4	APN	7	28,845,450 (GRCm39)	missense	possibly damaging	0.69
R0390:Rasgrp4	UTSW	7	28,845,285 (GRCm39)	missense	probably damaging	1.00
R0614:Rasgrp4	UTSW	7	28,845,276 (GRCm39)	missense	probably damaging	1.00
R0628:Rasgrp4	UTSW	7	28,839,635 (GRCm39)	intron	probably benign
R1420:Rasgrp4	UTSW	7	28,839,770 (GRCm39)	missense	probably damaging	0.98
R1434:Rasgrp4	UTSW	7	28,837,152 (GRCm39)	critical splice donor site	probably null
R1664:Rasgrp4	UTSW	7	28,839,688 (GRCm39)	missense	probably benign	0.00
R1911:Rasgrp4	UTSW	7	28,838,302 (GRCm39)	missense	probably damaging	1.00
R2164:Rasgrp4	UTSW	7	28,838,470 (GRCm39)	missense	probably damaging	1.00
R4277:Rasgrp4	UTSW	7	28,852,019 (GRCm39)	unclassified	probably benign
R5024:Rasgrp4	UTSW	7	28,847,832 (GRCm39)	missense	probably damaging	1.00
R5423:Rasgrp4	UTSW	7	28,844,561 (GRCm39)	missense	probably damaging	1.00
R5813:Rasgrp4	UTSW	7	28,844,639 (GRCm39)	missense	probably damaging	1.00
R5823:Rasgrp4	UTSW	7	28,837,142 (GRCm39)	missense	probably benign	0.00
R6268:Rasgrp4	UTSW	7	28,842,493 (GRCm39)	missense	probably damaging	1.00
R6285:Rasgrp4	UTSW	7	28,847,808 (GRCm39)	missense	probably damaging	1.00
R7062:Rasgrp4	UTSW	7	28,849,619 (GRCm39)	missense	possibly damaging	0.92
R7269:Rasgrp4	UTSW	7	28,847,855 (GRCm39)	missense	probably damaging	1.00
R7471:Rasgrp4	UTSW	7	28,845,405 (GRCm39)	missense	probably damaging	1.00
R7535:Rasgrp4	UTSW	7	28,838,484 (GRCm39)	missense	probably benign
R7792:Rasgrp4	UTSW	7	28,842,527 (GRCm39)	missense	probably damaging	1.00
R7854:Rasgrp4	UTSW	7	28,850,035 (GRCm39)	missense	unknown
R7855:Rasgrp4	UTSW	7	28,850,035 (GRCm39)	missense	unknown
R8052:Rasgrp4	UTSW	7	28,849,362 (GRCm39)	missense	probably damaging	1.00
R8144:Rasgrp4	UTSW	7	28,848,542 (GRCm39)	missense	probably damaging	1.00
R8253:Rasgrp4	UTSW	7	28,838,287 (GRCm39)	missense	possibly damaging	0.63
R8256:Rasgrp4	UTSW	7	28,842,500 (GRCm39)	missense	probably damaging	1.00
R8671:Rasgrp4	UTSW	7	28,842,452 (GRCm39)	missense	probably damaging	0.99
R8675:Rasgrp4	UTSW	7	28,842,452 (GRCm39)	missense	probably damaging	0.99
R8872:Rasgrp4	UTSW	7	28,838,521 (GRCm39)	missense	possibly damaging	0.86
R9647:Rasgrp4	UTSW	7	28,839,917 (GRCm39)	missense	probably damaging	0.99
R9681:Rasgrp4	UTSW	7	28,849,687 (GRCm39)	missense	probably benign
Z1088:Rasgrp4	UTSW	7	28,849,961 (GRCm39)	intron	probably benign
Z1186:Rasgrp4	UTSW	7	28,837,012 (GRCm39)	missense	probably benign
Z1186:Rasgrp4	UTSW	7	28,850,021 (GRCm39)	intron	probably benign
Z1186:Rasgrp4	UTSW	7	28,850,017 (GRCm39)	intron	probably benign
Z1186:Rasgrp4	UTSW	7	28,848,060 (GRCm39)	missense	probably damaging	1.00
Z1186:Rasgrp4	UTSW	7	28,847,985 (GRCm39)	missense	probably benign	0.01
Z1186:Rasgrp4	UTSW	7	28,845,302 (GRCm39)	missense	probably benign	0.01
Z1186:Rasgrp4	UTSW	7	28,838,241 (GRCm39)	missense	probably benign	0.01

Predicted Primers

PCR Primer
(F):5'- GAACCCTGACACCTGATACACTTCG -3'
(R):5'- TCCTTGAGTAGGGACTGATGGCAG -3'

Sequencing Primer
(F):5'- TGGCTGGCACATGCCTG -3'
(R):5'- CTGATGGCAGTTAAGGAGTGATG -3'

Posted On

2013-04-11