Incidental Mutation 'R7269:Rasgrp4'
ID 565148
Institutional Source Beutler Lab
Gene Symbol Rasgrp4
Ensembl Gene ENSMUSG00000030589
Gene Name RAS guanyl releasing protein 4
Synonyms
MMRRC Submission 045320-MU
Accession Numbers
Essential gene? Non essential (E-score: 0.000) question?
Stock # R7269 (G1)
Quality Score 225.009
Status Validated
Chromosome 7
Chromosomal Location 28834358-28853386 bp(+) (GRCm39)
Type of Mutation missense
DNA Base Change (assembly) C to A at 28847855 bp (GRCm39)
Zygosity Heterozygous
Amino Acid Change Arginine to Serine at position 432 (R432S)
Ref Sequence ENSEMBL: ENSMUSP00000125137 (fasta)
Gene Model predicted gene model for transcript(s): [ENSMUST00000032811] [ENSMUST00000094617] [ENSMUST00000123416] [ENSMUST00000134176] [ENSMUST00000159351] [ENSMUST00000159975] [ENSMUST00000160194] [ENSMUST00000160396] [ENSMUST00000161522] [ENSMUST00000164589] [ENSMUST00000203070] [ENSMUST00000203380] [ENSMUST00000204194] [ENSMUST00000204845] [ENSMUST00000205027]
AlphaFold Q8BTM9
Predicted Effect probably damaging
Transcript: ENSMUST00000032811
AA Change: R432S

PolyPhen 2 Score 0.993 (Sensitivity: 0.70; Specificity: 0.97)
SMART Domains Protein: ENSMUSP00000032811
Gene: ENSMUSG00000030589
AA Change: R432S

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: R433S

PolyPhen 2 Score 0.993 (Sensitivity: 0.70; Specificity: 0.97)
SMART Domains Protein: ENSMUSP00000092200
Gene: ENSMUSG00000030589
AA Change: R433S

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 benign
Transcript: ENSMUST00000123416
SMART Domains Protein: ENSMUSP00000122992
Gene: ENSMUSG00000030590

DomainStartEndE-ValueType
Pfam:DUF2465 6 125 8.9e-12 PFAM
Predicted Effect probably benign
Transcript: ENSMUST00000134176
SMART Domains Protein: ENSMUSP00000120165
Gene: ENSMUSG00000030590

DomainStartEndE-ValueType
Pfam:DUF2465 1 125 5.9e-45 PFAM
Predicted Effect probably benign
Transcript: ENSMUST00000144795
SMART Domains Protein: ENSMUSP00000121796
Gene: ENSMUSG00000030590

DomainStartEndE-ValueType
Pfam:DUF2465 5 175 1.7e-30 PFAM
Pfam:DUF2465 172 213 1.3e-14 PFAM
Pfam:DUF2465 211 242 6.9e-13 PFAM
Predicted Effect probably benign
Transcript: ENSMUST00000153251
SMART Domains Protein: ENSMUSP00000117500
Gene: ENSMUSG00000030590

DomainStartEndE-ValueType
Pfam:DUF2465 1 114 1.9e-22 PFAM
Pfam:DUF2465 111 196 1.1e-32 PFAM
Predicted Effect probably damaging
Transcript: ENSMUST00000159351
AA Change: R432S

PolyPhen 2 Score 0.996 (Sensitivity: 0.55; Specificity: 0.98)
SMART Domains Protein: ENSMUSP00000124183
Gene: ENSMUSG00000030589
AA Change: R432S

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 probably damaging
Transcript: ENSMUST00000159975
AA Change: R432S

PolyPhen 2 Score 0.996 (Sensitivity: 0.55; Specificity: 0.98)
SMART Domains Protein: ENSMUSP00000125137
Gene: ENSMUSG00000030589
AA Change: R432S

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: R422S

PolyPhen 2 Score 0.996 (Sensitivity: 0.55; Specificity: 0.98)
SMART Domains Protein: ENSMUSP00000124908
Gene: ENSMUSG00000030589
AA Change: R422S

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 probably benign
Transcript: ENSMUST00000160396
Predicted Effect probably damaging
Transcript: ENSMUST00000161522
AA Change: R418S

PolyPhen 2 Score 0.992 (Sensitivity: 0.70; Specificity: 0.97)
SMART Domains Protein: ENSMUSP00000123718
Gene: ENSMUSG00000030589
AA Change: R418S

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 benign
Transcript: ENSMUST00000164589
SMART Domains Protein: ENSMUSP00000131477
Gene: ENSMUSG00000030590

DomainStartEndE-ValueType
Pfam:DUF2465 8 327 3.8e-95 PFAM
Predicted Effect possibly damaging
Transcript: ENSMUST00000203070
AA Change: R340S

PolyPhen 2 Score 0.682 (Sensitivity: 0.86; Specificity: 0.92)
SMART Domains Protein: ENSMUSP00000145352
Gene: ENSMUSG00000030589
AA Change: R340S

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 probably damaging
Transcript: ENSMUST00000203380
AA Change: R363S

PolyPhen 2 Score 0.960 (Sensitivity: 0.78; Specificity: 0.95)
SMART Domains Protein: ENSMUSP00000144753
Gene: ENSMUSG00000030589
AA Change: R363S

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: ENSMUST00000204194
AA Change: R335S

PolyPhen 2 Score 0.896 (Sensitivity: 0.82; Specificity: 0.94)
SMART Domains Protein: ENSMUSP00000145259
Gene: ENSMUSG00000030589
AA Change: R335S

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
Predicted Effect probably damaging
Transcript: ENSMUST00000204845
AA Change: R398S

PolyPhen 2 Score 0.999 (Sensitivity: 0.14; Specificity: 0.99)
SMART Domains Protein: ENSMUSP00000144774
Gene: ENSMUSG00000030589
AA Change: R398S

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 probably damaging
Transcript: ENSMUST00000205027
AA Change: R243S

PolyPhen 2 Score 0.993 (Sensitivity: 0.70; Specificity: 0.97)
SMART Domains Protein: ENSMUSP00000145186
Gene: ENSMUSG00000030589
AA Change: R243S

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
Coding Region Coverage
  • 1x: 100.0%
  • 3x: 100.0%
  • 10x: 99.8%
  • 20x: 99.2%
Validation Efficiency 98% (85/87)
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: 87 list
GeneRefVarChr/LocMutationPredicted EffectZygosity
2700062C07Rik A T 18: 24,606,013 (GRCm39) N36I probably damaging Het
A430033K04Rik T A 5: 138,645,014 (GRCm39) Y300N possibly damaging Het
Adipor2 T C 6: 119,347,205 (GRCm39) Q26R probably benign Het
Ahnak T A 19: 8,983,981 (GRCm39) M1755K probably damaging Het
Ahnak2 A T 12: 112,780,802 (GRCm38) V70E Het
AI837181 C A 19: 5,476,462 (GRCm39) S208R probably damaging Het
Arhgap35 T G 7: 16,295,652 (GRCm39) M1138L probably benign Het
Card14 T G 11: 119,228,573 (GRCm39) L633R probably damaging Het
Carmil3 A G 14: 55,731,352 (GRCm39) T144A probably benign Het
Cbfa2t2 T A 2: 154,357,895 (GRCm39) N223K probably benign Het
Ccdc39 T C 3: 33,884,254 (GRCm39) I363V probably benign Het
Ccng2 C G 5: 93,421,202 (GRCm39) S237R probably benign Het
Ccpg1 G T 9: 72,920,609 (GRCm39) R741S probably benign Het
Cenpc1 A G 5: 86,161,366 (GRCm39) F855L probably damaging Het
Cenpc1 A T 5: 86,180,277 (GRCm39) M665K probably benign Het
Cp A G 3: 20,037,641 (GRCm39) H832R probably damaging Het
Defa24 A G 8: 22,224,565 (GRCm39) I5V probably benign Het
Dlc1 A C 8: 37,046,407 (GRCm39) L730R probably damaging Het
Dmbt1 A T 7: 130,668,351 (GRCm39) I536F unknown Het
Dscam G A 16: 96,479,601 (GRCm39) T1182I probably benign Het
Eea1 A T 10: 95,854,000 (GRCm39) I553F probably damaging Het
Far1 T C 7: 113,160,654 (GRCm39) V400A probably benign Het
Fbrsl1 A T 5: 110,580,880 (GRCm39) S126T probably benign Het
Frmpd2 A T 14: 33,244,838 (GRCm39) E552V possibly damaging Het
Gm5431 T A 11: 48,779,237 (GRCm39) T562S probably benign Het
Gm5475 T C 15: 100,324,890 (GRCm39) F106S unknown Het
Gpr12 T C 5: 146,520,188 (GRCm39) T245A probably damaging Het
Gsta2 A G 9: 78,239,419 (GRCm39) Y166H probably benign Het
H6pd A G 4: 150,067,369 (GRCm39) V347A probably benign Het
Ifih1 T C 2: 62,475,977 (GRCm39) T100A probably benign Het
Ift70b A G 2: 75,767,838 (GRCm39) F305S probably damaging Het
Itga2 C T 13: 115,023,225 (GRCm39) W59* probably null Het
Knstrn T A 2: 118,661,869 (GRCm39) probably null Het
Kprp A G 3: 92,731,178 (GRCm39) V624A probably damaging Het
Lmbrd2 A G 15: 9,194,771 (GRCm39) Y591C probably damaging Het
Map7d1 A G 4: 126,126,666 (GRCm39) V842A unknown Het
Mboat2 A T 12: 24,881,708 (GRCm39) T4S probably benign Het
Mcph1 T A 8: 18,657,288 (GRCm39) probably null Het
Mrtfb A T 16: 13,218,898 (GRCm39) M515L possibly damaging Het
Muc5b A G 7: 141,411,272 (GRCm39) D1406G unknown Het
Mylk G A 16: 34,605,381 (GRCm39) G3D probably damaging Het
Ndst4 A G 3: 125,232,007 (GRCm39) D192G probably damaging Het
Nemp1 G T 10: 127,531,345 (GRCm39) R361L probably damaging Het
Nol4 A C 18: 23,172,846 (GRCm39) V85G probably benign Het
Nrbf2 G A 10: 67,103,605 (GRCm39) T166M probably damaging Het
Obscn T C 11: 58,933,838 (GRCm39) E5342G probably damaging Het
Or10al7 C A 17: 38,366,442 (GRCm39) C5F probably damaging Het
Or4f47 T A 2: 111,972,905 (GRCm39) F205Y probably damaging Het
Or4p19 C T 2: 88,242,839 (GRCm39) M54I possibly damaging Het
Or51d1 T G 7: 102,348,252 (GRCm39) L269R probably damaging Het
Or7d10 A G 9: 19,831,631 (GRCm39) N42S possibly damaging Het
Pakap G T 4: 57,855,217 (GRCm39) R182L probably damaging Het
Pde4dip A G 3: 97,674,275 (GRCm39) S214P probably damaging Het
Per3 A T 4: 151,116,393 (GRCm39) C278* probably null Het
Pi4k2a T C 19: 42,079,125 (GRCm39) L62P probably damaging Het
Plekha7 C A 7: 115,780,447 (GRCm39) G126W probably damaging Het
Ppp1r13b T C 12: 111,801,353 (GRCm39) K567E probably damaging Het
Pradc1 T A 6: 85,424,548 (GRCm39) Q134L probably benign Het
Pwp2 A G 10: 78,012,170 (GRCm39) F628L probably benign Het
Rab5c C T 11: 100,606,928 (GRCm39) G217D probably benign Het
Rad51ap2 G T 12: 11,506,807 (GRCm39) S243I possibly damaging Het
Rhot2 C T 17: 26,061,402 (GRCm39) probably null Het
Scn2a T A 2: 65,594,113 (GRCm39) L1654Q probably damaging Het
Skint6 A T 4: 112,711,686 (GRCm39) probably null Het
Slc22a28 T A 19: 8,094,491 (GRCm39) T177S probably benign Het
Slc25a24 G T 3: 109,065,960 (GRCm39) Q272H probably null Het
Slc3a1 A T 17: 85,339,873 (GRCm39) I144F probably damaging Het
Smg9 C T 7: 24,105,495 (GRCm39) R176C possibly damaging Het
Sorl1 A T 9: 41,948,499 (GRCm39) L762Q probably damaging Het
Srebf2 C A 15: 82,088,270 (GRCm39) P1079T probably benign Het
Sub1 A T 15: 11,993,937 (GRCm39) S4T probably benign Het
Tacr1 A T 6: 82,469,692 (GRCm39) Y192F probably benign Het
Tm4sf19 A T 16: 32,224,814 (GRCm39) H54L probably damaging Het
Tnxb T C 17: 34,914,428 (GRCm39) L1838P probably damaging Het
Trmt1l T C 1: 151,333,539 (GRCm39) S681P possibly damaging Het
Ttn A G 2: 76,738,176 (GRCm39) V4167A unknown Het
Unc13d T A 11: 115,959,056 (GRCm39) M702L probably benign Het
Vgll3 A G 16: 65,636,404 (GRCm39) H240R probably benign Het
Vmn1r189 C G 13: 22,286,737 (GRCm39) W33C probably benign Het
Vmn2r17 G A 5: 109,576,337 (GRCm39) A403T possibly damaging Het
Vmn2r2 G A 3: 64,033,998 (GRCm39) T508I probably benign Het
Vps54 T A 11: 21,227,670 (GRCm39) probably null Het
Wfs1 G A 5: 37,125,134 (GRCm39) Q586* probably null Het
Zbp1 A T 2: 173,055,665 (GRCm39) H166Q unknown Het
Zcchc3 G A 2: 152,256,294 (GRCm39) A135V probably benign Het
Zfp51 T C 17: 21,683,960 (GRCm39) Y192H probably benign Het
Zkscan2 T C 7: 123,088,994 (GRCm39) T426A probably benign 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
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
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'- TCGTATGGCCAGACAGATCC -3'
(R):5'- TGTTCCACATGCTGACCCAG -3'

Sequencing Primer
(F):5'- ACAGATCCCGAAGTCTCTGGAG -3'
(R):5'- ACCCAGAGTCACGCTGTCTG -3'
Posted On 2019-06-26