Incidental Mutation 'R6268:Rasgrp4'
ID 507153
Institutional Source Beutler Lab
Gene Symbol Rasgrp4
Ensembl Gene ENSMUSG00000030589
Gene Name RAS guanyl releasing protein 4
Synonyms
MMRRC Submission 044439-MU
Accession Numbers
Essential gene? Non essential (E-score: 0.000) question?
Stock # R6268 (G1)
Quality Score 225.009
Status Validated
Chromosome 7
Chromosomal Location 28834358-28853386 bp(+) (GRCm39)
Type of Mutation missense
DNA Base Change (assembly) G to A at 28842493 bp (GRCm39)
Zygosity Heterozygous
Amino Acid Change Valine to Isoleucine at position 246 (V246I)
Ref Sequence ENSEMBL: ENSMUSP00000124908 (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 damaging
Transcript: ENSMUST00000032811
AA Change: V256I

PolyPhen 2 Score 0.996 (Sensitivity: 0.55; Specificity: 0.98)
SMART Domains Protein: ENSMUSP00000032811
Gene: ENSMUSG00000030589
AA Change: V256I

DomainStartEndE-ValueType
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: V257I

PolyPhen 2 Score 0.997 (Sensitivity: 0.41; Specificity: 0.98)
SMART Domains Protein: ENSMUSP00000092200
Gene: ENSMUSG00000030589
AA Change: V257I

DomainStartEndE-ValueType
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: V256I

PolyPhen 2 Score 0.996 (Sensitivity: 0.55; Specificity: 0.98)
SMART Domains Protein: ENSMUSP00000124183
Gene: ENSMUSG00000030589
AA Change: V256I

DomainStartEndE-ValueType
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 damaging
Transcript: ENSMUST00000159975
AA Change: V256I

PolyPhen 2 Score 0.997 (Sensitivity: 0.41; Specificity: 0.98)
SMART Domains Protein: ENSMUSP00000125137
Gene: ENSMUSG00000030589
AA Change: V256I

DomainStartEndE-ValueType
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: V246I

PolyPhen 2 Score 0.997 (Sensitivity: 0.41; Specificity: 0.98)
SMART Domains Protein: ENSMUSP00000124908
Gene: ENSMUSG00000030589
AA Change: V246I

DomainStartEndE-ValueType
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 possibly damaging
Transcript: ENSMUST00000161522
AA Change: V242I

PolyPhen 2 Score 0.456 (Sensitivity: 0.89; Specificity: 0.90)
SMART Domains Protein: ENSMUSP00000123718
Gene: ENSMUSG00000030589
AA Change: V242I

DomainStartEndE-ValueType
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: V256I

PolyPhen 2 Score 0.959 (Sensitivity: 0.78; Specificity: 0.95)
SMART Domains Protein: ENSMUSP00000145352
Gene: ENSMUSG00000030589
AA Change: V256I

DomainStartEndE-ValueType
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 possibly damaging
Transcript: ENSMUST00000203380
AA Change: V256I

PolyPhen 2 Score 0.520 (Sensitivity: 0.88; Specificity: 0.90)
SMART Domains Protein: ENSMUSP00000144753
Gene: ENSMUSG00000030589
AA Change: V256I

DomainStartEndE-ValueType
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 possibly damaging
Transcript: ENSMUST00000204845
AA Change: V222I

PolyPhen 2 Score 0.912 (Sensitivity: 0.81; Specificity: 0.94)
SMART Domains Protein: ENSMUSP00000144774
Gene: ENSMUSG00000030589
AA Change: V222I

DomainStartEndE-ValueType
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

DomainStartEndE-ValueType
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 noncoding transcript
Transcript: ENSMUST00000162641
Predicted Effect probably benign
Transcript: ENSMUST00000204194
SMART Domains Protein: ENSMUSP00000145259
Gene: ENSMUSG00000030589

DomainStartEndE-ValueType
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
Meta Mutation Damage Score 0.6329 question?
Coding Region Coverage
  • 1x: 99.9%
  • 3x: 99.6%
  • 10x: 98.3%
  • 20x: 95.5%
Validation Efficiency 99% (68/69)
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: 70 list
GeneRefVarChr/LocMutationPredicted EffectZygosity
4921504E06Rik A G 2: 19,545,219 (GRCm39) I78T probably benign Het
Afg3l1 A T 8: 124,219,665 (GRCm39) I398F probably damaging Het
Ahctf1 T C 1: 179,591,048 (GRCm39) H1244R probably benign Het
Ank1 A T 8: 23,599,687 (GRCm39) K797N probably damaging Het
Anxa6 G T 11: 54,877,903 (GRCm39) probably null Het
Aoc1l1 T A 6: 48,954,616 (GRCm39) Y585N probably benign Het
Ap1b1 T A 11: 4,969,493 (GRCm39) V310E probably damaging Het
C2cd2l T C 9: 44,228,963 (GRCm39) I123V probably damaging Het
Cars2 TCCCC TCCC 8: 11,579,599 (GRCm39) probably null Het
Cfap54 T A 10: 92,874,771 (GRCm39) I542F probably damaging Het
Cfap57 G T 4: 118,426,648 (GRCm39) Y1100* probably null Het
Coq9 A G 8: 95,576,862 (GRCm39) E158G probably benign Het
Cox15 A T 19: 43,728,365 (GRCm39) W303R possibly damaging Het
Cpa5 A G 6: 30,615,172 (GRCm39) Y103C probably damaging Het
Crygn A T 5: 24,961,189 (GRCm39) V39E probably damaging Het
Csf1 G T 3: 107,654,473 (GRCm39) S132R possibly damaging Het
Dapk1 G A 13: 60,909,580 (GRCm39) V1398M possibly damaging Het
Degs2 C A 12: 108,658,839 (GRCm39) V47L probably damaging Het
Dock5 C A 14: 68,027,724 (GRCm39) E1057* probably null Het
Dsg1b C A 18: 20,521,220 (GRCm39) Q26K probably benign Het
Elp1 T C 4: 56,762,305 (GRCm39) Y1098C probably damaging Het
Fam181a T C 12: 103,282,803 (GRCm39) V236A possibly damaging Het
Fam78b C A 1: 166,906,122 (GRCm39) P94T probably damaging Het
Fbxw25 T G 9: 109,483,718 (GRCm39) T165P probably damaging Het
Flg C A 3: 93,195,482 (GRCm39) probably benign Het
Frrs1 G T 3: 116,696,748 (GRCm39) V573F probably damaging Het
Gm7298 A G 6: 121,756,032 (GRCm39) T964A possibly damaging Het
Hoxd9 G T 2: 74,528,433 (GRCm39) V12L probably damaging Het
Kcnt1 A G 2: 25,793,609 (GRCm39) probably null Het
Klhl3 G T 13: 58,161,656 (GRCm39) R480S probably damaging Het
Klhl36 A G 8: 120,597,406 (GRCm39) D369G probably damaging Het
Lama3 T A 18: 12,657,794 (GRCm39) N303K probably damaging Het
Lhcgr T C 17: 89,050,132 (GRCm39) T465A probably damaging Het
Llgl1 T C 11: 60,602,989 (GRCm39) V888A probably benign Het
Lrp1b T A 2: 40,711,729 (GRCm39) T3164S probably benign Het
Mmp3 T G 9: 7,447,622 (GRCm39) D202E possibly damaging Het
Mocs1 C A 17: 49,742,183 (GRCm39) T104K probably damaging Het
Mrpl42 A T 10: 95,332,569 (GRCm39) probably null Het
Mtch2 T C 2: 90,693,992 (GRCm39) C279R probably benign Het
Muc4 A T 16: 32,589,141 (GRCm39) D2836V probably damaging Het
Myh7 T C 14: 55,226,741 (GRCm39) E370G probably benign Het
Naa11 A G 5: 97,540,069 (GRCm39) Y30H probably damaging Het
Ntng1 T C 3: 109,842,351 (GRCm39) T141A probably damaging Het
Or5h26 A C 16: 58,987,656 (GRCm39) probably null Het
Or8c11 T C 9: 38,289,384 (GRCm39) I69T probably benign Het
Or9i14 A T 19: 13,792,671 (GRCm39) Y94* probably null Het
Pcdha12 G A 18: 37,155,477 (GRCm39) C732Y possibly damaging Het
Plekhm2 G A 4: 141,359,652 (GRCm39) Q392* probably null Het
Prr22 G A 17: 57,078,587 (GRCm39) V247M probably damaging Het
Rapgef6 T A 11: 54,540,073 (GRCm39) L716Q probably damaging Het
Rhbdd2 C T 5: 135,672,114 (GRCm39) T323I probably benign Het
Rsf1 CG CGACGGCGGTG 7: 97,229,115 (GRCm39) probably benign Homo
Scgb2b20 A T 7: 33,063,973 (GRCm39) I99K possibly damaging Het
Scyl3 C T 1: 163,773,786 (GRCm39) R324* probably null Het
Slc23a1 T C 18: 35,752,624 (GRCm39) Y551C probably damaging Het
Slc5a5 A T 8: 71,341,264 (GRCm39) S358R probably damaging Het
Sorcs3 T A 19: 48,778,605 (GRCm39) N1007K probably damaging Het
Stxbp4 T A 11: 90,431,027 (GRCm39) K428* probably null Het
Tmem63c T A 12: 87,128,727 (GRCm39) I584N probably damaging Het
Traf3ip3 C T 1: 192,880,344 (GRCm39) probably benign Het
Trgv2 G A 13: 19,521,001 (GRCm39) T31I probably benign Het
Ttll3 C T 6: 113,369,524 (GRCm39) R23C probably benign Het
Ugt2a3 A C 5: 87,477,472 (GRCm39) L309R probably damaging Het
Urb1 A G 16: 90,550,807 (GRCm39) M2015T probably benign Het
Vmn2r14 A C 5: 109,369,283 (GRCm39) S97A possibly damaging Het
Vps13c C A 9: 67,858,731 (GRCm39) T2727K probably benign Het
Xrn1 T A 9: 95,846,067 (GRCm39) I40K probably damaging Het
Zc3h11a A G 1: 133,552,295 (GRCm39) V604A probably benign Het
Zfp410 G A 12: 84,378,612 (GRCm39) R259H probably benign Het
Zfp748 A G 13: 67,690,705 (GRCm39) V185A possibly damaging Het
Other mutations in Rasgrp4
AlleleSourceChrCoordTypePredicted EffectPPH 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
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'- GATGTTGGGTCTGCCAGAAAG -3'
(R):5'- TCTACAGTCCCAGAAGTGAGGAG -3'

Sequencing Primer
(F):5'- TCTGCCAGAAAGATGGAATGG -3'
(R):5'- GGGCACGCCTTTAATAATCTCAGG -3'
Posted On 2018-03-15