Incidental Mutation 'R1420:Rasgrp4'
ID 160041
Institutional Source Beutler Lab
Gene Symbol Rasgrp4
Ensembl Gene ENSMUSG00000030589
Gene Name RAS guanyl releasing protein 4
Synonyms
MMRRC Submission 039476-MU
Accession Numbers
Essential gene? Non essential (E-score: 0.000) question?
Stock # R1420 (G1)
Quality Score 225
Status Not validated
Chromosome 7
Chromosomal Location 28834358-28853386 bp(+) (GRCm39)
Type of Mutation missense
DNA Base Change (assembly) C to A at 28839770 bp (GRCm39)
Zygosity Heterozygous
Amino Acid Change Glutamine to Lysine at position 161 (Q161K)
Ref Sequence ENSEMBL: ENSMUSP00000125137 (fasta)
Gene Model predicted gene model for transcript(s): [ENSMUST00000032811] [ENSMUST00000094617] [ENSMUST00000159351] [ENSMUST00000159975] [ENSMUST00000160194] [ENSMUST00000161522] [ENSMUST00000204194] [ENSMUST00000203070] [ENSMUST00000203380] [ENSMUST00000205027] [ENSMUST00000204845]
AlphaFold Q8BTM9
Predicted Effect probably damaging
Transcript: ENSMUST00000032811
AA Change: Q161K

PolyPhen 2 Score 0.972 (Sensitivity: 0.77; Specificity: 0.96)
SMART Domains Protein: ENSMUSP00000032811
Gene: ENSMUSG00000030589
AA Change: Q161K

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: Q162K

PolyPhen 2 Score 0.972 (Sensitivity: 0.77; Specificity: 0.96)
SMART Domains Protein: ENSMUSP00000092200
Gene: ENSMUSG00000030589
AA Change: Q162K

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: Q161K

PolyPhen 2 Score 0.972 (Sensitivity: 0.77; Specificity: 0.96)
SMART Domains Protein: ENSMUSP00000124183
Gene: ENSMUSG00000030589
AA Change: Q161K

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: Q161K

PolyPhen 2 Score 0.984 (Sensitivity: 0.74; Specificity: 0.96)
SMART Domains Protein: ENSMUSP00000125137
Gene: ENSMUSG00000030589
AA Change: Q161K

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: Q161K

PolyPhen 2 Score 0.972 (Sensitivity: 0.77; Specificity: 0.96)
SMART Domains Protein: ENSMUSP00000124908
Gene: ENSMUSG00000030589
AA Change: Q161K

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: Q161K

PolyPhen 2 Score 0.707 (Sensitivity: 0.86; Specificity: 0.92)
SMART Domains Protein: ENSMUSP00000123718
Gene: ENSMUSG00000030589
AA Change: Q161K

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: ENSMUST00000204194
AA Change: Q161K

PolyPhen 2 Score 0.235 (Sensitivity: 0.91; Specificity: 0.88)
SMART Domains Protein: ENSMUSP00000145259
Gene: ENSMUSG00000030589
AA Change: Q161K

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 possibly damaging
Transcript: ENSMUST00000203070
AA Change: Q161K

PolyPhen 2 Score 0.933 (Sensitivity: 0.80; Specificity: 0.94)
SMART Domains Protein: ENSMUSP00000145352
Gene: ENSMUSG00000030589
AA Change: Q161K

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: Q161K

PolyPhen 2 Score 0.088 (Sensitivity: 0.93; Specificity: 0.85)
SMART Domains Protein: ENSMUSP00000144753
Gene: ENSMUSG00000030589
AA Change: Q161K

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: ENSMUST00000205027
AA Change: Q161K

PolyPhen 2 Score 0.177 (Sensitivity: 0.92; Specificity: 0.87)
SMART Domains Protein: ENSMUSP00000145186
Gene: ENSMUSG00000030589
AA Change: Q161K

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 possibly damaging
Transcript: ENSMUST00000204845
AA Change: Q161K

PolyPhen 2 Score 0.803 (Sensitivity: 0.84; Specificity: 0.93)
SMART Domains Protein: ENSMUSP00000144774
Gene: ENSMUSG00000030589
AA Change: Q161K

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: ENSMUST00000162641
Predicted Effect noncoding transcript
Transcript: ENSMUST00000162946
Coding Region Coverage
  • 1x: 98.9%
  • 3x: 98.0%
  • 10x: 95.6%
  • 20x: 90.6%
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: 52 list
GeneRefVarChr/LocMutationPredicted EffectZygosity
Aldh1l2 A G 10: 83,331,799 (GRCm39) Y669H probably damaging Het
Amotl2 A T 9: 102,601,982 (GRCm39) M409L possibly damaging Het
Ankrd35 A G 3: 96,592,054 (GRCm39) E780G probably benign Het
Brwd1 T C 16: 95,837,234 (GRCm39) Y866C probably damaging Het
Cul4b G C X: 37,653,918 (GRCm39) probably null Het
Daw1 A T 1: 83,137,548 (GRCm39) Y10F possibly damaging Het
Dgki A T 6: 37,027,204 (GRCm39) probably null Het
Dnah3 A T 7: 119,551,202 (GRCm39) V3039E probably damaging Het
Ercc4 C T 16: 12,948,073 (GRCm39) T340I probably benign Het
Fam83b T C 9: 76,399,894 (GRCm39) N403S possibly damaging Het
Fbh1 A G 2: 11,772,493 (GRCm39) F63L probably benign Het
Foxm1 G A 6: 128,349,884 (GRCm39) R395H possibly damaging Het
Gtpbp4 C T 13: 9,023,298 (GRCm39) A589T probably benign Het
Ifna7 C A 4: 88,734,906 (GRCm39) H148N probably damaging Het
Il23r T C 6: 67,463,181 (GRCm39) Y104C probably damaging Het
Il31ra A T 13: 112,668,286 (GRCm39) W347R probably damaging Het
Ints7 T G 1: 191,345,169 (GRCm39) F620V possibly damaging Het
Iqcd T C 5: 120,738,860 (GRCm39) L226P probably damaging Het
Jak3 G T 8: 72,134,182 (GRCm39) R428L possibly damaging Het
Kif28 C A 1: 179,529,962 (GRCm39) C733F probably damaging Het
Klkb1 C A 8: 45,729,183 (GRCm39) C347F probably damaging Het
Ksr2 A G 5: 117,552,904 (GRCm39) E4G probably benign Het
Lama1 T C 17: 68,097,942 (GRCm39) L1774P probably damaging Het
Lrriq3 A G 3: 154,893,349 (GRCm39) E350G probably benign Het
Nav3 G A 10: 109,659,115 (GRCm39) A834V probably benign Het
Ncoa6 G A 2: 155,263,073 (GRCm39) Q454* probably null Het
Nfatc2 C A 2: 168,346,585 (GRCm39) M836I probably benign Het
Nphp3 G T 9: 103,913,092 (GRCm39) probably null Het
Olfml2b C T 1: 170,496,596 (GRCm39) T409M probably benign Het
Oprk1 A G 1: 5,672,544 (GRCm39) K227R probably damaging Het
Or8g35 A T 9: 39,381,289 (GRCm39) H244Q probably damaging Het
Pate1 A T 9: 35,596,505 (GRCm39) W87R probably damaging Het
Pcnx4 T C 12: 72,602,760 (GRCm39) Y341H probably benign Het
Pde4c T A 8: 71,201,066 (GRCm39) H421Q probably damaging Het
Pglyrp4 T C 3: 90,636,021 (GRCm39) V82A probably damaging Het
Pnmt G T 11: 98,278,502 (GRCm39) R156L probably benign Het
Prdm9 C A 17: 15,764,638 (GRCm39) C714F probably damaging Het
Pwp1 T C 10: 85,712,402 (GRCm39) V80A probably damaging Het
Pxdn T C 12: 30,052,067 (GRCm39) L568P probably damaging Het
Rnf138 A G 18: 21,159,159 (GRCm39) E193G probably damaging Het
Slc16a6 A G 11: 109,345,772 (GRCm39) V413A probably damaging Het
Slc7a15 T C 12: 8,584,442 (GRCm39) T363A probably benign Het
Sufu T C 19: 46,385,623 (GRCm39) S28P probably benign Het
Tex19.1 T C 11: 121,037,872 (GRCm39) S77P probably damaging Het
Tmc7 A T 7: 118,165,440 (GRCm39) Y91* probably null Het
Ttbk2 C G 2: 120,576,393 (GRCm39) R792S probably benign Het
Tyw1 T C 5: 130,303,586 (GRCm39) probably null Het
U2surp A G 9: 95,344,856 (GRCm39) S907P probably benign Het
Vmn2r115 ATCTTCT ATCT 17: 23,578,962 (GRCm39) probably benign Het
Vps50 T A 6: 3,588,007 (GRCm39) L660* probably null Het
Wdr55 A G 18: 36,893,392 (GRCm39) E18G probably benign Het
Wipi1 A G 11: 109,469,198 (GRCm39) V331A 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
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
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'- CACCCGTGTAAATGCCCATAGTTCC -3'
(R):5'- TAAGTGAGGTGTTGTGCCAGCTCC -3'

Sequencing Primer
(F):5'- AGAATTCCTTGGCTTAAAGCCC -3'
(R):5'- CTGTCTCCAGGTGATCGAATAGC -3'
Posted On 2014-03-14