Incidental Mutation 'R9681:Rasgrp4'
ID 728554
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 # R9681 (G1)
Quality Score 225.009
Status Not validated
Chromosome 7
Chromosomal Location 28834358-28853386 bp(+) (GRCm39)
Type of Mutation missense
DNA Base Change (assembly) T to C at 28849687 bp (GRCm39)
Zygosity Heterozygous
Amino Acid Change Serine to Proline at position 651 (S651P)
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 benign
Transcript: ENSMUST00000032811
AA Change: S646P

PolyPhen 2 Score 0.000 (Sensitivity: 1.00; Specificity: 0.00)
SMART Domains Protein: ENSMUSP00000032811
Gene: ENSMUSG00000030589
AA Change: S646P

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 benign
Transcript: ENSMUST00000094617
AA Change: S652P

PolyPhen 2 Score 0.001 (Sensitivity: 0.99; Specificity: 0.15)
SMART Domains Protein: ENSMUSP00000092200
Gene: ENSMUSG00000030589
AA Change: S652P

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 benign
Transcript: ENSMUST00000159351
SMART Domains Protein: ENSMUSP00000124183
Gene: ENSMUSG00000030589

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 benign
Transcript: ENSMUST00000159975
AA Change: S651P

PolyPhen 2 Score 0.000 (Sensitivity: 1.00; Specificity: 0.00)
SMART Domains Protein: ENSMUSP00000125137
Gene: ENSMUSG00000030589
AA Change: S651P

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 benign
Transcript: ENSMUST00000160194
SMART Domains Protein: ENSMUSP00000124908
Gene: ENSMUSG00000030589

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: ENSMUST00000160396
AA Change: S23P

PolyPhen 2 Score 0.827 (Sensitivity: 0.84; Specificity: 0.93)
Predicted Effect probably benign
Transcript: ENSMUST00000161522
AA Change: S632P

PolyPhen 2 Score 0.000 (Sensitivity: 1.00; Specificity: 0.00)
SMART Domains Protein: ENSMUSP00000123718
Gene: ENSMUSG00000030589
AA Change: S632P

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: S554P

PolyPhen 2 Score 0.734 (Sensitivity: 0.85; Specificity: 0.92)
SMART Domains Protein: ENSMUSP00000145352
Gene: ENSMUSG00000030589
AA Change: S554P

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: S577P

PolyPhen 2 Score 0.000 (Sensitivity: 1.00; Specificity: 0.00)
SMART Domains Protein: ENSMUSP00000144753
Gene: ENSMUSG00000030589
AA Change: S577P

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: S549P

PolyPhen 2 Score 0.001 (Sensitivity: 0.99; Specificity: 0.15)
SMART Domains Protein: ENSMUSP00000145259
Gene: ENSMUSG00000030589
AA Change: S549P

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: S612P

PolyPhen 2 Score 0.000 (Sensitivity: 1.00; Specificity: 0.00)
SMART Domains Protein: ENSMUSP00000144774
Gene: ENSMUSG00000030589
AA Change: S612P

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: S457P

PolyPhen 2 Score 0.007 (Sensitivity: 0.96; Specificity: 0.75)
SMART Domains Protein: ENSMUSP00000145186
Gene: ENSMUSG00000030589
AA Change: S457P

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: 99.9%
  • 10x: 99.7%
  • 20x: 99.1%
Validation Efficiency
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
0610030E20Rik A G 6: 72,324,450 (GRCm39) D20G probably damaging Het
Acbd3 T A 1: 180,566,082 (GRCm39) Y258* probably null Het
Adamts1 T A 16: 85,599,498 (GRCm39) H34L Het
Ankmy1 G T 1: 92,813,882 (GRCm39) N432K possibly damaging Het
Ano1 A G 7: 144,143,893 (GRCm39) M966T possibly damaging Het
Ark2n A T 18: 77,722,989 (GRCm39) V349D possibly damaging Het
C2cd3 A G 7: 100,023,662 (GRCm39) T83A probably benign Het
Cdk1 T A 10: 69,178,449 (GRCm39) D137V possibly damaging Het
Cfap299 T A 5: 98,477,214 (GRCm39) M1K probably null Het
Chia1 A G 3: 106,037,996 (GRCm39) Y326C probably damaging Het
Ciz1 A G 2: 32,260,974 (GRCm39) D295G possibly damaging Het
Clrn1 C T 3: 58,792,251 (GRCm39) V71I probably benign Het
Cr1l T C 1: 194,800,149 (GRCm39) D175G probably damaging Het
Crem A T 18: 3,268,067 (GRCm39) V87E probably damaging Het
Cyp2b19 T A 7: 26,466,328 (GRCm39) L377Q probably benign Het
Ddx42 T A 11: 106,125,679 (GRCm39) V243D probably damaging Het
Dnah14 T C 1: 181,562,414 (GRCm39) V2658A possibly damaging Het
Dnah3 T G 7: 119,677,611 (GRCm39) M437L probably benign Het
Flrt2 T A 12: 95,745,425 (GRCm39) probably benign Het
Gm10142 T A 10: 77,551,880 (GRCm39) C80* probably null Het
Gpr158 A G 2: 21,831,315 (GRCm39) E805G probably damaging Het
Grwd1 T C 7: 45,479,473 (GRCm39) E134G probably benign Het
Hdac11 T A 6: 91,150,068 (GRCm39) V289D probably benign Het
Hsdl1 T C 8: 120,293,081 (GRCm39) E118G possibly damaging Het
Igdcc4 T A 9: 65,041,858 (GRCm39) L1095Q possibly damaging Het
Ildr1 T A 16: 36,528,749 (GRCm39) C65S probably damaging Het
Itgal T C 7: 126,929,422 (GRCm39) F1113S probably damaging Het
Itsn2 G T 12: 4,683,499 (GRCm39) V341F unknown Het
Jak1 G A 4: 101,019,085 (GRCm39) R723C probably damaging Het
Limch1 A G 5: 67,126,422 (GRCm39) T8A probably damaging Het
Limd1 T A 9: 123,345,903 (GRCm39) C561S possibly damaging Het
Map3k19 A G 1: 127,750,097 (GRCm39) F1085L possibly damaging Het
Mcm7 A T 5: 138,164,220 (GRCm39) Y600* probably null Het
Mecom A T 3: 30,033,803 (GRCm39) D300E probably benign Het
Mfap4 T A 11: 61,376,925 (GRCm39) Y51* probably null Het
Mug1 T A 6: 121,833,254 (GRCm39) N286K probably benign Het
Myl2 A T 5: 122,240,783 (GRCm39) R40* probably null Het
Nom1 A G 5: 29,642,623 (GRCm39) S375G probably damaging Het
Nrcam C A 12: 44,598,133 (GRCm39) P368Q probably null Het
Oca2 G C 7: 55,943,623 (GRCm39) Q265H probably null Het
Or52a20 T A 7: 103,366,475 (GRCm39) F225I probably damaging Het
Or52n2c T C 7: 104,574,075 (GRCm39) T299A probably damaging Het
Or5k8 T A 16: 58,644,176 (GRCm39) N299Y possibly damaging Het
Or6c88 A T 10: 129,406,664 (GRCm39) T47S probably damaging Het
Or7a41 G A 10: 78,871,577 (GRCm39) D316N probably benign Het
Palmd T C 3: 116,717,120 (GRCm39) E459G probably benign Het
Pde1a G T 2: 79,695,465 (GRCm39) A494D probably benign Het
Pds5a T C 5: 65,808,587 (GRCm39) Y428C probably damaging Het
Pgm2 T C 5: 64,254,391 (GRCm39) F59L probably benign Het
Plekhm1 A G 11: 103,258,950 (GRCm39) V980A possibly damaging Het
Polb T C 8: 23,118,346 (GRCm39) D318G possibly damaging Het
Rasgef1c T A 11: 49,861,040 (GRCm39) M335K probably damaging Het
Robo3 A C 9: 37,334,558 (GRCm39) I624S possibly damaging Het
Robo3 T A 9: 37,339,087 (GRCm39) H290L probably benign Het
Rps6kl1 T C 12: 85,183,599 (GRCm39) H482R probably damaging Het
Slc26a9 A T 1: 131,681,691 (GRCm39) E168V probably benign Het
Slc3a2 T C 19: 8,691,226 (GRCm39) probably benign Het
Slc4a4 A T 5: 89,102,723 (GRCm39) K54* probably null Het
Slitrk6 A G 14: 110,988,258 (GRCm39) L483P probably damaging Het
Svep1 T A 4: 58,084,959 (GRCm39) N1793I probably damaging Het
Ttn T C 2: 76,612,723 (GRCm39) I17119V possibly damaging Het
Tulp4 T C 17: 6,274,500 (GRCm39) L617P possibly damaging Het
Uhrf1 A G 17: 56,625,083 (GRCm39) N542S possibly damaging Het
Vmn1r151 T A 7: 22,198,368 (GRCm39) T246S probably damaging Het
Vmn1r57 T A 7: 5,224,069 (GRCm39) V198E probably damaging Het
Vmn2r99 A T 17: 19,598,889 (GRCm39) Q191L probably damaging Het
Vrk3 C T 7: 44,403,356 (GRCm39) T39M possibly damaging Het
Zc3h3 C A 15: 75,681,470 (GRCm39) R537L probably damaging Het
Zfp64 A T 2: 168,793,680 (GRCm39) V22E probably damaging Het
Zwint T C 10: 72,493,112 (GRCm39) L218P probably 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
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
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
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'- GCAGAGGATGGGGCTCAC -3'
(R):5'- CCGCTATTATTCTCTGTCCACAATAAA -3'

Sequencing Primer
(F):5'- TCACTCCTAAGGTCATGGGGTC -3'
(R):5'- AGGCACTCCCTTGATGAATG -3'
Posted On 2022-10-06