Mutagenetix > Incidental Mutation

Incidental Mutation 'R7792:Rasgrp4'

599939

Institutional Source

Beutler Lab

Gene Symbol

Rasgrp4

Ensembl Gene

ENSMUSG00000030589

Gene Name

RAS guanyl releasing protein 4

Synonyms

MMRRC Submission

045848-MU

Accession Numbers

Essential gene?

Non essential (E-score: 0.000) question?

Stock #

R7792 (G1)

Quality Score

225.009

Status

Validated

Chromosome

Chromosomal Location

28834358-28853386 bp(+) (GRCm39)

Type of Mutation

missense

DNA Base Change (assembly)

G to T at 28842527 bp (GRCm39)

Zygosity

Heterozygous

Amino Acid Change

Arginine to Leucine at position 267 (R267L)

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 damaging
Transcript: ENSMUST00000032811
AA Change: R267L

PolyPhen 2 Score 1.000 (Sensitivity: 0.00; Specificity: 1.00)

SMART Domains

Protein: ENSMUSP00000032811
Gene: ENSMUSG00000030589
AA Change: R267L

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 damaging
Transcript: ENSMUST00000094617
AA Change: R268L

PolyPhen 2 Score 0.997 (Sensitivity: 0.41; Specificity: 0.98)

SMART Domains

Protein: ENSMUSP00000092200
Gene: ENSMUSG00000030589
AA Change: R268L

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 damaging
Transcript: ENSMUST00000159351
AA Change: R267L

PolyPhen 2 Score 1.000 (Sensitivity: 0.00; Specificity: 1.00)

SMART Domains

Protein: ENSMUSP00000124183
Gene: ENSMUSG00000030589
AA Change: R267L

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 damaging
Transcript: ENSMUST00000159975
AA Change: R267L

PolyPhen 2 Score 0.996 (Sensitivity: 0.55; Specificity: 0.98)

SMART Domains

Protein: ENSMUSP00000125137
Gene: ENSMUSG00000030589
AA Change: R267L

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 damaging
Transcript: ENSMUST00000160194
AA Change: R257L

PolyPhen 2 Score 0.997 (Sensitivity: 0.41; Specificity: 0.98)

SMART Domains

Protein: ENSMUSP00000124908
Gene: ENSMUSG00000030589
AA Change: R257L

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 damaging
Transcript: ENSMUST00000161522
AA Change: R253L

PolyPhen 2 Score 1.000 (Sensitivity: 0.00; Specificity: 1.00)

SMART Domains

Protein: ENSMUSP00000123718
Gene: ENSMUSG00000030589
AA Change: R253L

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 damaging
Transcript: ENSMUST00000203070
AA Change: R267L

PolyPhen 2 Score 1.000 (Sensitivity: 0.00; Specificity: 1.00)

SMART Domains

Protein: ENSMUSP00000145352
Gene: ENSMUSG00000030589
AA Change: R267L

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 damaging
Transcript: ENSMUST00000203380
AA Change: R267L

PolyPhen 2 Score 1.000 (Sensitivity: 0.00; Specificity: 1.00)

SMART Domains

Protein: ENSMUSP00000144753
Gene: ENSMUSG00000030589
AA Change: R267L

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

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

probably damaging
Transcript: ENSMUST00000204845
AA Change: R233L

PolyPhen 2 Score 1.000 (Sensitivity: 0.00; Specificity: 1.00)

SMART Domains

Protein: ENSMUSP00000144774
Gene: ENSMUSG00000030589
AA Change: R233L

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

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

Meta Mutation Damage Score

0.9505

Coding Region Coverage

1x: 100.0%
3x: 99.9%
10x: 99.7%
20x: 98.9%

Validation Efficiency

100% (97/97)

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: 99 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
Aars1	G	T	8: 111,769,896 (GRCm39)	V332F	possibly damaging	Het
Abhd15	T	A	11: 77,409,560 (GRCm39)	S425T	probably benign	Het
Acads	A	T	5: 115,250,840 (GRCm39)	F152L	probably damaging	Het
Acp3	T	A	9: 104,204,165 (GRCm39)	H43L	probably damaging	Het
Adora2a	A	G	10: 75,169,480 (GRCm39)	S315G	probably benign	Het
Agxt2	A	T	15: 10,381,472 (GRCm39)	D242V	probably damaging	Het
Alx4	A	G	2: 93,473,056 (GRCm39)	D18G	probably damaging	Het
Ankrd11	A	G	8: 123,610,970 (GRCm39)	S2639P	probably damaging	Het
Arhgap35	A	T	7: 16,295,453 (GRCm39)	V1204D	possibly damaging	Het
Arid2	A	G	15: 96,267,256 (GRCm39)	T579A	probably benign	Het
B4galt1	C	T	4: 40,809,373 (GRCm39)	G332S	probably benign	Het
B4galt4	C	A	16: 38,578,172 (GRCm39)	Y206*	probably null	Het
Bcl2l14	A	T	6: 134,409,277 (GRCm39)	T284S	possibly damaging	Het
Bop1	C	T	15: 76,338,548 (GRCm39)	V465M	probably damaging	Het
Cacna1b	A	T	2: 24,567,977 (GRCm39)	L1037H	probably damaging	Het
Cadm2	G	A	16: 66,568,523 (GRCm39)	T254M	probably benign	Het
Ccdc180	T	C	4: 45,890,389 (GRCm39)		probably null	Het
Ccdc7a	A	T	8: 129,618,918 (GRCm39)	D875E	possibly damaging	Het
Cenpu	A	G	8: 47,015,502 (GRCm39)	D139G	possibly damaging	Het
Cep57l1	A	T	10: 41,598,936 (GRCm39)	C292*	probably null	Het
Cep89	G	A	7: 35,129,353 (GRCm39)	R630H	probably damaging	Het
Chst14	A	G	2: 118,758,256 (GRCm39)	H350R	probably benign	Het
Clca3a1	T	A	3: 144,455,492 (GRCm39)	I434F	possibly damaging	Het
Crispld2	A	G	8: 120,757,809 (GRCm39)	T385A	probably benign	Het
Crmp1	A	C	5: 37,441,439 (GRCm39)	N507T	probably damaging	Het
Cyp4f40	T	A	17: 32,890,143 (GRCm39)	I271N	probably damaging	Het
D630003M21Rik	G	T	2: 158,052,082 (GRCm39)	Q670K	possibly damaging	Het
Ddx42	T	C	11: 106,127,822 (GRCm39)	I342T	probably damaging	Het
Dnah9	T	A	11: 65,740,839 (GRCm39)	I4116F	probably damaging	Het
Ehd2	T	C	7: 15,684,683 (GRCm39)	H372R	probably benign	Het
Gja8	C	A	3: 96,827,092 (GRCm39)	C190F	probably damaging	Het
Gm8297	A	T	14: 16,165,939 (GRCm39)	D72V	possibly damaging	Het
Golgb1	A	G	16: 36,739,092 (GRCm39)	D2518G	probably benign	Het
Hsd17b12	C	A	2: 93,863,986 (GRCm39)	M285I	probably benign	Het
Hus1	T	C	11: 8,950,133 (GRCm39)	E196G	probably damaging	Het
Ift70a2	T	C	2: 75,807,273 (GRCm39)	N413S	probably benign	Het
Irf2	G	A	8: 47,260,314 (GRCm39)	R82Q	probably damaging	Het
Irx2	A	G	13: 72,779,493 (GRCm39)	D259G	possibly damaging	Het
Jph1	T	A	1: 17,074,602 (GRCm39)	Q472L	probably benign	Het
Kif2a	T	C	13: 107,124,490 (GRCm39)	Q142R	probably benign	Het
Lonp1	T	C	17: 56,929,515 (GRCm39)	Y174C	probably damaging	Het
Mapk14	T	C	17: 28,965,271 (GRCm39)	F348L	probably damaging	Het
Marchf10	G	T	11: 105,281,054 (GRCm39)	D410E	probably benign	Het
Mff	A	T	1: 82,724,802 (GRCm39)		probably null	Het
Mtrex	A	T	13: 113,009,443 (GRCm39)	D985E	probably benign	Het
Necab3	G	A	2: 154,388,200 (GRCm39)	R271C	probably damaging	Het
Nlrp4e	T	A	7: 23,021,182 (GRCm39)	F556L	possibly damaging	Het
Nt5c2	T	C	19: 46,878,385 (GRCm39)	K425E	probably benign	Het
Ofcc1	A	T	13: 40,296,302 (GRCm39)	W511R	probably damaging	Het
Or1j18	A	C	2: 36,624,342 (GRCm39)	E3A	probably benign	Het
Or2v1	T	A	11: 49,025,496 (GRCm39)	I159N	possibly damaging	Het
Or4k77	T	C	2: 111,199,748 (GRCm39)	I257T	probably benign	Het
Or52p2	T	A	7: 102,238,090 (GRCm39)		probably benign	Het
P2rx2	G	C	5: 110,488,210 (GRCm39)	A448G	possibly damaging	Het
Pcnx2	A	T	8: 126,618,757 (GRCm39)	N56K	possibly damaging	Het
Pdzd7	A	C	19: 45,028,657 (GRCm39)	M162R	possibly damaging	Het
Phyhd1	A	G	2: 30,156,782 (GRCm39)	M1V	probably null	Het
Plaat3	T	C	19: 7,556,660 (GRCm39)	C154R	probably benign	Het
Plekha5	A	G	6: 140,534,950 (GRCm39)	E1126G	possibly damaging	Het
Plekhm1	A	T	11: 103,287,886 (GRCm39)	V87D	probably damaging	Het
Pole	G	A	5: 110,445,332 (GRCm39)		probably null	Het
Pramel22	A	G	4: 143,381,123 (GRCm39)	L300P	probably benign	Het
R3hcc1	T	C	14: 69,942,957 (GRCm39)	M207V	probably benign	Het
R3hcc1l	T	A	19: 42,552,403 (GRCm39)	S467T	probably damaging	Het
Rbm20	T	C	19: 53,838,567 (GRCm39)	I848T	probably benign	Het
Rims2	T	C	15: 39,061,923 (GRCm39)	S56P	possibly damaging	Het
Rmc1	G	A	18: 12,314,656 (GRCm39)	D289N	probably damaging	Het
Sacs	T	A	14: 61,447,222 (GRCm39)	D3089E	probably benign	Het
Sall2	C	T	14: 52,553,521 (GRCm39)	G16R	probably damaging	Het
Scgb1b19	G	A	7: 32,987,912 (GRCm39)	C93Y	probably damaging	Het
Scn3a	T	A	2: 65,297,334 (GRCm39)	K1442*	probably null	Het
Sepsecs	A	G	5: 52,801,391 (GRCm39)	S424P	probably damaging	Het
Set	G	T	2: 29,960,323 (GRCm39)	V219F	probably benign	Het
Sh3tc1	A	T	5: 35,868,295 (GRCm39)	F390I	probably damaging	Het
Simc1	G	A	13: 54,695,143 (GRCm39)	V1269M	probably damaging	Het
Ska3	T	G	14: 58,047,512 (GRCm39)	D341A	probably damaging	Het
Slc16a10	A	T	10: 39,913,411 (GRCm39)		probably null	Het
Srgap1	T	A	10: 121,761,872 (GRCm39)	N92I	probably damaging	Het
Sspo	T	C	6: 48,431,624 (GRCm39)	V639A	probably damaging	Het
Stk11	A	T	10: 79,961,271 (GRCm39)		probably benign	Het
Sult5a1	G	A	8: 123,872,180 (GRCm39)	H221Y	probably benign	Het
Sytl3	T	A	17: 7,003,977 (GRCm39)	M559K	probably benign	Het
Tab2	A	C	10: 7,794,897 (GRCm39)	D528E	possibly damaging	Het
Tbc1d15	A	G	10: 115,057,492 (GRCm39)	I218T	possibly damaging	Het
Tenm4	T	A	7: 96,423,221 (GRCm39)	M672K	possibly damaging	Het
Tent4b	A	T	8: 88,979,182 (GRCm39)	Q561L	probably benign	Het
Tfrc	A	G	16: 32,437,985 (GRCm39)	K346R	probably benign	Het
Thsd1	G	T	8: 22,733,114 (GRCm39)	G54W	probably damaging	Het
Tmprss15	A	T	16: 78,800,275 (GRCm39)	L618I	probably damaging	Het
Top3a	T	C	11: 60,633,790 (GRCm39)	S769G	probably benign	Het
Trp63	C	A	16: 25,686,974 (GRCm39)	P396Q	possibly damaging	Het
Uggt1	T	C	1: 36,247,065 (GRCm39)	S311G	probably damaging	Het
Usp10	G	A	8: 120,678,740 (GRCm39)	E574K	possibly damaging	Het
Wfdc6b	T	A	2: 164,459,822 (GRCm39)	I148K	probably damaging	Het
Zcchc2	T	G	1: 105,945,982 (GRCm39)	I474R	probably damaging	Het
Zdhhc2	A	G	8: 40,900,182 (GRCm39)	K82R	probably benign	Het
Zfp273	A	G	13: 67,974,135 (GRCm39)	D421G	possibly damaging	Het
Zfp280d	T	C	9: 72,238,601 (GRCm39)	I639T	probably damaging	Het
Zfp429	A	T	13: 67,538,558 (GRCm39)	C295*	probably null	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
R0092:Rasgrp4	UTSW	7	28,844,557 (GRCm39)	missense	possibly damaging	0.74
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
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'- TGGGAGCAACATGACACACC -3'
(R):5'- GTCTACAGTCCCAGAAGTGAGG -3'

Sequencing Primer
(F):5'- TGACACACCCTGACCAATCTTG -3'
(R):5'- GGGCACGCCTTTAATAATCTCAGG -3'

Posted On

2019-11-26