Incidental Mutation 'R8872:Rasgrp4'
ID 676353
Institutional Source Beutler Lab
Gene Symbol Rasgrp4
Ensembl Gene ENSMUSG00000030589
Gene Name RAS guanyl releasing protein 4
Synonyms
MMRRC Submission 068743-MU
Accession Numbers
Essential gene? Non essential (E-score: 0.000) question?
Stock # R8872 (G1)
Quality Score 225.009
Status Validated
Chromosome 7
Chromosomal Location 28834358-28853386 bp(+) (GRCm39)
Type of Mutation missense
DNA Base Change (assembly) A to G at 28838521 bp (GRCm39)
Zygosity Heterozygous
Amino Acid Change Tyrosine to Cysteine at position 123 (Y123C)
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 possibly damaging
Transcript: ENSMUST00000032811
AA Change: Y123C

PolyPhen 2 Score 0.783 (Sensitivity: 0.85; Specificity: 0.93)
SMART Domains Protein: ENSMUSP00000032811
Gene: ENSMUSG00000030589
AA Change: Y123C

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 possibly damaging
Transcript: ENSMUST00000094617
AA Change: Y124C

PolyPhen 2 Score 0.783 (Sensitivity: 0.85; Specificity: 0.93)
SMART Domains Protein: ENSMUSP00000092200
Gene: ENSMUSG00000030589
AA Change: Y124C

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 possibly damaging
Transcript: ENSMUST00000159351
AA Change: Y123C

PolyPhen 2 Score 0.710 (Sensitivity: 0.86; Specificity: 0.92)
SMART Domains Protein: ENSMUSP00000124183
Gene: ENSMUSG00000030589
AA Change: Y123C

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 possibly damaging
Transcript: ENSMUST00000159975
AA Change: Y123C

PolyPhen 2 Score 0.861 (Sensitivity: 0.83; Specificity: 0.93)
SMART Domains Protein: ENSMUSP00000125137
Gene: ENSMUSG00000030589
AA Change: Y123C

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 possibly damaging
Transcript: ENSMUST00000160194
AA Change: Y123C

PolyPhen 2 Score 0.586 (Sensitivity: 0.88; Specificity: 0.91)
SMART Domains Protein: ENSMUSP00000124908
Gene: ENSMUSG00000030589
AA Change: Y123C

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: ENSMUST00000161522
AA Change: Y123C

PolyPhen 2 Score 0.004 (Sensitivity: 0.98; Specificity: 0.59)
SMART Domains Protein: ENSMUSP00000123718
Gene: ENSMUSG00000030589
AA Change: Y123C

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: ENSMUST00000203070
AA Change: Y123C

PolyPhen 2 Score 0.006 (Sensitivity: 0.97; Specificity: 0.75)
SMART Domains Protein: ENSMUSP00000145352
Gene: ENSMUSG00000030589
AA Change: Y123C

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 benign
Transcript: ENSMUST00000203380
AA Change: Y123C

PolyPhen 2 Score 0.003 (Sensitivity: 0.98; Specificity: 0.44)
SMART Domains Protein: ENSMUSP00000144753
Gene: ENSMUSG00000030589
AA Change: Y123C

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 probably benign
Transcript: ENSMUST00000204194
AA Change: Y123C

PolyPhen 2 Score 0.030 (Sensitivity: 0.95; Specificity: 0.82)
SMART Domains Protein: ENSMUSP00000145259
Gene: ENSMUSG00000030589
AA Change: Y123C

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 benign
Transcript: ENSMUST00000204845
AA Change: Y123C

PolyPhen 2 Score 0.001 (Sensitivity: 0.99; Specificity: 0.15)
SMART Domains Protein: ENSMUSP00000144774
Gene: ENSMUSG00000030589
AA Change: Y123C

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 benign
Transcript: ENSMUST00000205027
AA Change: Y123C

PolyPhen 2 Score 0.117 (Sensitivity: 0.93; Specificity: 0.86)
SMART Domains Protein: ENSMUSP00000145186
Gene: ENSMUSG00000030589
AA Change: Y123C

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: 99.5%
Validation Efficiency 99% (74/75)
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: 73 list
GeneRefVarChr/LocMutationPredicted EffectZygosity
1700067P10Rik A G 17: 48,401,164 (GRCm39) S150G possibly damaging Het
Alpk2 A T 18: 65,413,977 (GRCm39) S1579R probably damaging Het
Ank2 C T 3: 126,791,525 (GRCm39) E814K possibly damaging Het
Cep57 A G 9: 13,737,980 (GRCm39) probably benign Het
Cntnap4 A T 8: 113,585,759 (GRCm39) R1127S possibly damaging Het
Comt C A 16: 18,245,239 (GRCm39) probably benign Het
Crlf3 T C 11: 79,938,440 (GRCm39) N399S Het
Crls1 T A 2: 132,691,819 (GRCm39) S115T probably benign Het
Dixdc1 A G 9: 50,614,453 (GRCm39) S199P possibly damaging Het
Dsc3 T C 18: 20,122,679 (GRCm39) T82A probably benign Het
Efcab3 T G 11: 104,760,880 (GRCm39) L2411R probably benign Het
Exosc6 T A 8: 111,783,784 (GRCm39) V261E probably damaging Het
Fbxw17 C T 13: 50,586,300 (GRCm39) S361L probably benign Het
Gfap T A 11: 102,786,620 (GRCm39) N157Y possibly damaging Het
Gigyf2 A T 1: 87,307,725 (GRCm39) D177V unknown Het
Gls2 A T 10: 128,040,535 (GRCm39) Q312L probably benign Het
Gpr155 C T 2: 73,197,936 (GRCm39) V395I probably benign Het
Greb1l A T 18: 10,529,684 (GRCm39) M889L probably benign Het
Gucy1a1 T A 3: 82,016,049 (GRCm39) D313V probably damaging Het
H2-T5 T A 17: 36,476,293 (GRCm39) I324F probably benign Het
Herpud1 C T 8: 95,113,213 (GRCm39) probably benign Het
Idh2 TCCCAGG T 7: 79,748,079 (GRCm39) probably benign Het
Il27 A C 7: 126,190,194 (GRCm39) L140R probably damaging Het
Jarid2 T C 13: 45,055,984 (GRCm39) S397P possibly damaging Het
Kdm5a A C 6: 120,365,101 (GRCm39) D334A probably damaging Het
Lman2 T C 13: 55,496,197 (GRCm39) T283A probably benign Het
Lrfn2 C T 17: 49,378,277 (GRCm39) Q453* probably null Het
Lrrfip2 A G 9: 111,034,824 (GRCm39) E171G possibly damaging Het
Mboat1 T A 13: 30,410,397 (GRCm39) Y285N probably damaging Het
Med15 C A 16: 17,470,605 (GRCm39) S734I probably damaging Het
Mgat4c T A 10: 102,224,146 (GRCm39) I120N probably damaging Het
Ms4a4d T C 19: 11,530,251 (GRCm39) M104T possibly damaging Het
Mtf2 A T 5: 108,247,051 (GRCm39) M330L probably benign Het
Myoc T C 1: 162,475,013 (GRCm39) V188A probably benign Het
Nos2 T A 11: 78,839,949 (GRCm39) I686N probably damaging Het
Npffr1 T C 10: 61,461,794 (GRCm39) V310A probably benign Het
Nrap T C 19: 56,308,627 (GRCm39) *1729W probably null Het
Odam A G 5: 88,035,797 (GRCm39) probably null Het
Olfm4 G T 14: 80,258,943 (GRCm39) R397L probably damaging Het
Or1p1c T G 11: 74,160,120 (GRCm39) probably benign Het
Polr1b T C 2: 128,957,613 (GRCm39) V556A probably damaging Het
Prl3d3 A G 13: 27,346,324 (GRCm39) D186G possibly damaging Het
Psmc5 C A 11: 106,152,746 (GRCm39) Y189* probably null Het
Rtn4 A G 11: 29,658,633 (GRCm39) E929G probably benign Het
Scrn2 A T 11: 96,922,961 (GRCm39) I135F probably damaging Het
Sec24d T A 3: 123,148,585 (GRCm39) probably benign Het
Secisbp2l T C 2: 125,594,892 (GRCm39) T523A probably benign Het
Skic3 T C 13: 76,333,326 (GRCm39) L1525P probably damaging Het
Slain1 T A 14: 103,925,841 (GRCm39) probably null Het
Slc22a29 A G 19: 8,137,931 (GRCm39) V548A probably damaging Het
Slc25a32 T C 15: 38,969,339 (GRCm39) I65V probably benign Het
Slc30a7 A T 3: 115,740,317 (GRCm39) M378K possibly damaging Het
Smarcd1 T A 15: 99,608,975 (GRCm39) I383N probably damaging Het
Spata31h1 A T 10: 82,128,619 (GRCm39) S1464T probably benign Het
Spdye4b G T 5: 143,187,815 (GRCm39) K156N probably damaging Het
Sptb A G 12: 76,658,813 (GRCm39) Y1241H probably benign Het
Ssu2 G A 6: 112,357,956 (GRCm39) T129I probably damaging Het
Supt16 A G 14: 52,411,544 (GRCm39) V613A probably benign Het
Sycp3 A T 10: 88,302,388 (GRCm39) E126V probably damaging Het
Tatdn2 A T 6: 113,681,170 (GRCm39) Y401F probably damaging Het
Tigd4 T C 3: 84,501,547 (GRCm39) S155P probably benign Het
Tnrc6b A G 15: 80,802,290 (GRCm39) N1502S probably benign Het
Ttf2 A G 3: 100,870,644 (GRCm39) V143A probably benign Het
Ttn T A 2: 76,618,747 (GRCm39) D16179V probably damaging Het
Vmn2r106 A T 17: 20,488,401 (GRCm39) M666K probably benign Het
Vwa5b1 A T 4: 138,305,956 (GRCm39) V914D probably damaging Het
Wnk2 T C 13: 49,210,960 (GRCm39) M1632V probably benign Het
Zbtb26 T A 2: 37,326,913 (GRCm39) N41I probably damaging Het
Zc3h12a T C 4: 125,020,412 (GRCm39) N144D probably damaging Het
Zfp266 A T 9: 20,411,275 (GRCm39) C301S probably benign Het
Zfp580 A G 7: 5,056,216 (GRCm39) H192R possibly damaging Het
Zfp748 A G 13: 67,689,914 (GRCm39) C449R probably damaging Het
Zp2 T C 7: 119,733,025 (GRCm39) I612V 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
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
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'- TCATATCCTGCCAGAACCGG -3'
(R):5'- AATGGCATCTTAGCATGGGATTTTG -3'

Sequencing Primer
(F):5'- AGAACCGGGCTCTCCATCTAGAG -3'
(R):5'- AGTCCAGGCTAGCTTTGAAC -3'
Posted On 2021-07-15