Mutagenetix > Incidental Mutation

Incidental Mutation 'R7535:Rasgrp4'

583513

Institutional Source

Beutler Lab

Gene Symbol

Rasgrp4

Ensembl Gene

ENSMUSG00000030589

Gene Name

RAS guanyl releasing protein 4

Synonyms

MMRRC Submission

Accession Numbers

Essential gene?

Non essential (E-score: 0.000) question?

Stock #

R7535 (G1)

Quality Score

225.009

Status

Validated

Chromosome

Chromosomal Location

29134851-29153961 bp(+) (GRCm38)

Type of Mutation

missense

DNA Base Change (assembly)

A to G at 29139059 bp (GRCm38)

Zygosity

Heterozygous

Amino Acid Change

Lysine to Glutamic Acid at position 111 (K111E)

Ref Sequence

ENSEMBL: ENSMUSP00000125137 (fasta)

Gene Model

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

AlphaFold

Q8BTM9

Predicted Effect

probably benign
Transcript: ENSMUST00000032811
AA Change: K111E

PolyPhen 2 Score 0.000 (Sensitivity: 1.00; Specificity: 0.00)

SMART Domains

Protein: ENSMUSP00000032811
Gene: ENSMUSG00000030589
AA Change: K111E

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: K112E

PolyPhen 2 Score 0.000 (Sensitivity: 1.00; Specificity: 0.00)

SMART Domains

Protein: ENSMUSP00000092200
Gene: ENSMUSG00000030589
AA Change: K112E

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: K111E

PolyPhen 2 Score 0.000 (Sensitivity: 1.00; Specificity: 0.00)

SMART Domains

Protein: ENSMUSP00000124183
Gene: ENSMUSG00000030589
AA Change: K111E

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

probably benign
Transcript: ENSMUST00000159975
AA Change: K111E

PolyPhen 2 Score 0.000 (Sensitivity: 1.00; Specificity: 0.00)

SMART Domains

Protein: ENSMUSP00000125137
Gene: ENSMUSG00000030589
AA Change: K111E

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: K111E

PolyPhen 2 Score 0.000 (Sensitivity: 1.00; Specificity: 0.00)

SMART Domains

Protein: ENSMUSP00000124908
Gene: ENSMUSG00000030589
AA Change: K111E

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: K111E

PolyPhen 2 Score 0.000 (Sensitivity: 1.00; Specificity: 0.00)

SMART Domains

Protein: ENSMUSP00000123718
Gene: ENSMUSG00000030589
AA Change: K111E

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

probably benign
Transcript: ENSMUST00000203070
AA Change: K111E

PolyPhen 2 Score 0.000 (Sensitivity: 1.00; Specificity: 0.00)

SMART Domains

Protein: ENSMUSP00000145352
Gene: ENSMUSG00000030589
AA Change: K111E

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: K111E

PolyPhen 2 Score 0.001 (Sensitivity: 0.99; Specificity: 0.15)

SMART Domains

Protein: ENSMUSP00000144753
Gene: ENSMUSG00000030589
AA Change: K111E

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: ENSMUST00000204194
AA Change: K111E

PolyPhen 2 Score 0.001 (Sensitivity: 0.99; Specificity: 0.15)

SMART Domains

Protein: ENSMUSP00000145259
Gene: ENSMUSG00000030589
AA Change: K111E

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

probably benign
Transcript: ENSMUST00000204845
AA Change: K111E

PolyPhen 2 Score 0.000 (Sensitivity: 1.00; Specificity: 0.00)

SMART Domains

Protein: ENSMUSP00000144774
Gene: ENSMUSG00000030589
AA Change: K111E

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

probably benign
Transcript: ENSMUST00000205027
AA Change: K111E

PolyPhen 2 Score 0.000 (Sensitivity: 1.00; Specificity: 0.00)

SMART Domains

Protein: ENSMUSP00000145186
Gene: ENSMUSG00000030589
AA Change: K111E

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

Coding Region Coverage

1x: 100.0%
3x: 100.0%
10x: 99.7%
20x: 99.1%

Validation Efficiency

100% (82/82)

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: 84 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
0610037L13Rik	T	G	4: 107,894,900	S159A	probably benign	Het
Abca7	T	A	10: 80,001,629	L449Q	probably benign	Het
Agtpbp1	T	C	13: 59,504,253	T415A	probably benign	Het
Akt3	A	T	1: 177,097,034	V165D	probably damaging	Het
Cbr2	T	A	11: 120,729,802	I219F	probably damaging	Het
Cdh20	T	A	1: 104,975,043	D486E	probably damaging	Het
Cenpe	A	G	3: 135,243,762	S103G	possibly damaging	Het
Chd4	T	A	6: 125,128,873	S1818T	probably benign	Het
Chst5	T	C	8: 111,890,163	D275G	probably damaging	Het
Clca1	A	G	3: 145,018,567	I244T	probably damaging	Het
Cyp2c54	A	G	19: 40,070,272	Y239H	probably benign	Het
Ddx25	A	G	9: 35,543,655	F446L	possibly damaging	Het
Dgkb	T	C	12: 38,136,647	L265P	probably damaging	Het
Dis3	A	G	14: 99,089,979	S363P	probably benign	Het
Disp3	T	C	4: 148,242,866	E1187G	probably damaging	Het
Dopey2	G	A	16: 93,806,361	G2061R	probably damaging	Het
Dsp	T	C	13: 38,192,789	S1517P	probably benign	Het
Epg5	T	A	18: 78,032,926	V2513E	probably benign	Het
Fryl	T	A	5: 73,098,196	T831S	probably benign	Het
Gm6309	A	T	5: 146,168,290	V271D	probably damaging	Het
H2-M2	G	T	17: 37,482,637	S159R	probably benign	Het
Helq	A	G	5: 100,790,133		probably null	Het
Herc1	G	C	9: 66,474,853	D3621H	probably damaging	Het
Hsd11b2	A	T	8: 105,519,123	I87F	probably damaging	Het
Ice2	A	G	9: 69,432,078	N959S	probably damaging	Het
Ifi47	T	A	11: 49,096,625	D406E	probably damaging	Het
Ifit3	T	G	19: 34,587,880	S275R	probably damaging	Het
Insl5	C	A	4: 103,018,198	K118N	probably damaging	Het
Irf7	A	T	7: 141,264,637	F158I	probably benign	Het
Kat2b	T	C	17: 53,624,403	L143P	probably damaging	Het
Klk1b1	A	T	7: 43,970,322	N102Y	probably damaging	Het
Krt13	C	T	11: 100,117,998	G410S	unknown	Het
Larp6	A	T	9: 60,724,154	T70S	probably benign	Het
Lrrc37a	T	C	11: 103,501,857	E914G	possibly damaging	Het
Mindy4	T	C	6: 55,297,753		probably null	Het
Myl10	G	C	5: 136,697,971	V70L	probably benign	Het
Myom2	A	G	8: 15,117,679	Y1088C	probably damaging	Het
Mysm1	T	C	4: 94,952,215	N655D	probably benign	Het
Nbas	T	A	12: 13,279,389	S112T	probably damaging	Het
Neb	A	G	2: 52,165,103		probably null	Het
Noxred1	G	A	12: 87,233,432	A42V	probably benign	Het
Olfm5	G	A	7: 104,154,237	P340S	possibly damaging	Het
Olfr1031	T	A	2: 85,991,901	V28E	probably benign	Het
Olfr1039	A	G	2: 86,131,264	V133A	probably benign	Het
Olfr1505	A	G	19: 13,919,085	K22E	probably benign	Het
Olfr167	T	C	16: 19,514,794	T281A	probably damaging	Het
Olfr749	G	A	14: 50,736,665	P166S	probably benign	Het
Pccb	A	T	9: 100,994,562		probably null	Het
Pnn	T	A	12: 59,072,137	V502E	probably benign	Het
Pole2	A	T	12: 69,222,429	I98K	probably benign	Het
Ptpn18	G	A	1: 34,473,364	D417N	possibly damaging	Het
Rbbp6	G	A	7: 122,990,143	M351I	probably benign	Het
Rgs19	T	G	2: 181,691,308	H53P	probably damaging	Het
Rin1	A	T	19: 5,052,536	T369S	probably benign	Het
Rnaset2b	G	A	17: 6,991,739	E135K	possibly damaging	Het
Rprd2	G	A	3: 95,776,587	P379S	probably damaging	Het
Sbno1	A	G	5: 124,413,279	L47P	possibly damaging	Het
Slamf6	T	A	1: 171,919,758	L29Q	unknown	Het
Slc16a14	T	C	1: 84,913,122	Y154C	probably damaging	Het
Slc22a29	A	G	19: 8,169,978	F340S	probably damaging	Het
Slc6a4	T	G	11: 77,015,150	I259S	possibly damaging	Het
Smarca4	G	A	9: 21,647,625	V651I	possibly damaging	Het
Susd5	C	T	9: 114,064,040	A62V	possibly damaging	Het
Syt1	T	A	10: 108,627,422		probably null	Het
Taf10	T	C	7: 105,740,910	I218T	probably benign	Het
Tas1r1	C	A	4: 152,028,362	V745F	probably benign	Het
Tas2r125	C	A	6: 132,910,324	T225K	probably damaging	Het
Tcp11l2	G	T	10: 84,594,659	R216L	possibly damaging	Het
Tnks1bp1	C	T	2: 85,063,280	Q1184*	probably null	Het
Treml2	T	A	17: 48,302,819	V93D	probably damaging	Het
Trim11	G	A	11: 58,982,065	E192K	probably damaging	Het
Trim43a	A	G	9: 88,588,148	K336E	probably damaging	Het
Tspan33	T	A	6: 29,717,589	I268N	possibly damaging	Het
Tstd2	C	T	4: 46,116,960	C458Y	probably damaging	Het
Ttc6	A	G	12: 57,576,519	S235G	probably benign	Het
Usp29	A	C	7: 6,961,220	T21P	possibly damaging	Het
Usp36	A	T	11: 118,262,046	S1084T	possibly damaging	Het
Vps39	T	A	2: 120,324,695	N550I	probably damaging	Het
Wdr47	A	G	3: 108,629,711	I572V	probably benign	Het
Zfp112	A	T	7: 24,126,710	Y705F	probably damaging	Het
Zfp282	A	G	6: 47,904,944	T522A	probably benign	Het
Zfp292	T	C	4: 34,811,487	D524G	probably benign	Het
Zfp90	A	T	8: 106,424,268	K204N	possibly damaging	Het
Zmym2	T	C	14: 56,957,079	S1265P	probably damaging	Het

Other mutations in Rasgrp4

Allele	Source	Chr	Coord	Type	Predicted Effect	PPH Score
IGL00594:Rasgrp4	APN	7	29148541	splice site	probably benign
IGL01145:Rasgrp4	APN	7	29151473	missense	possibly damaging	0.83
IGL01806:Rasgrp4	APN	7	29139050	missense	possibly damaging	0.83
IGL02023:Rasgrp4	APN	7	29138910	missense	probably damaging	1.00
IGL02499:Rasgrp4	APN	7	29151503	utr 3 prime	probably benign
IGL02989:Rasgrp4	APN	7	29148406	missense	probably damaging	1.00
IGL03281:Rasgrp4	APN	7	29146025	missense	possibly damaging	0.69
R0092:Rasgrp4	UTSW	7	29145132	missense	possibly damaging	0.74
R0390:Rasgrp4	UTSW	7	29145860	missense	probably damaging	1.00
R0614:Rasgrp4	UTSW	7	29145851	missense	probably damaging	1.00
R0628:Rasgrp4	UTSW	7	29140210	intron	probably benign
R1420:Rasgrp4	UTSW	7	29140345	missense	probably damaging	0.98
R1434:Rasgrp4	UTSW	7	29137727	critical splice donor site	probably null
R1664:Rasgrp4	UTSW	7	29140263	missense	probably benign	0.00
R1911:Rasgrp4	UTSW	7	29138877	missense	probably damaging	1.00
R2164:Rasgrp4	UTSW	7	29139045	missense	probably damaging	1.00
R4277:Rasgrp4	UTSW	7	29152594	unclassified	probably benign
R5024:Rasgrp4	UTSW	7	29148407	missense	probably damaging	1.00
R5423:Rasgrp4	UTSW	7	29145136	missense	probably damaging	1.00
R5813:Rasgrp4	UTSW	7	29145214	missense	probably damaging	1.00
R5823:Rasgrp4	UTSW	7	29137717	missense	probably benign	0.00
R6268:Rasgrp4	UTSW	7	29143068	missense	probably damaging	1.00
R6285:Rasgrp4	UTSW	7	29148383	missense	probably damaging	1.00
R7062:Rasgrp4	UTSW	7	29150194	missense	possibly damaging	0.92
R7269:Rasgrp4	UTSW	7	29148430	missense	probably damaging	1.00
R7471:Rasgrp4	UTSW	7	29145980	missense	probably damaging	1.00
R7792:Rasgrp4	UTSW	7	29143102	missense	probably damaging	1.00
R7854:Rasgrp4	UTSW	7	29150610	missense	unknown
R7855:Rasgrp4	UTSW	7	29150610	missense	unknown
R8052:Rasgrp4	UTSW	7	29149937	missense	probably damaging	1.00
R8144:Rasgrp4	UTSW	7	29149117	missense	probably damaging	1.00
R8253:Rasgrp4	UTSW	7	29138862	missense	possibly damaging	0.63
R8256:Rasgrp4	UTSW	7	29143075	missense	probably damaging	1.00
R8671:Rasgrp4	UTSW	7	29143027	missense	probably damaging	0.99
R8675:Rasgrp4	UTSW	7	29143027	missense	probably damaging	0.99
R8872:Rasgrp4	UTSW	7	29139096	missense	possibly damaging	0.86
R9647:Rasgrp4	UTSW	7	29140492	missense	probably damaging	0.99
R9681:Rasgrp4	UTSW	7	29150262	missense	probably benign
Z1088:Rasgrp4	UTSW	7	29150536	intron	probably benign
Z1186:Rasgrp4	UTSW	7	29137587	missense	probably benign
Z1186:Rasgrp4	UTSW	7	29138816	missense	probably benign	0.01
Z1186:Rasgrp4	UTSW	7	29145877	missense	probably benign	0.01
Z1186:Rasgrp4	UTSW	7	29148560	missense	probably benign	0.01
Z1186:Rasgrp4	UTSW	7	29148635	missense	probably damaging	1.00
Z1186:Rasgrp4	UTSW	7	29150592	intron	probably benign
Z1186:Rasgrp4	UTSW	7	29150596	intron	probably benign

Predicted Primers

PCR Primer
(F):5'- AGATGGTGCTCACGATGCAC -3'
(R):5'- CAATGGCATCTTAGCATGGGATTTTG -3'

Sequencing Primer
(F):5'- TGCTCACGATGCACAGCTG -3'
(R):5'- TTTGCCAGGATTACAGGCAC -3'

Posted On

2019-10-17