Incidental Mutation 'R4278:Rapgef4'
ID 322755
Institutional Source Beutler Lab
Gene Symbol Rapgef4
Ensembl Gene ENSMUSG00000049044
Gene Name Rap guanine nucleotide exchange factor (GEF) 4
Synonyms 5730402K07Rik, 6330581N18Rik, Epac2, cAMP-GEFII, 1300003D15Rik
MMRRC Submission 068968-MU
Accession Numbers
Essential gene? Possibly essential (E-score: 0.648) question?
Stock # R4278 (G1)
Quality Score 225
Status Not validated
Chromosome 2
Chromosomal Location 71811584-72087818 bp(+) (GRCm39)
Type of Mutation missense
DNA Base Change (assembly) T to A at 72028739 bp (GRCm39)
Zygosity Heterozygous
Amino Acid Change Asparagine to Lysine at position 385 (N385K)
Ref Sequence ENSEMBL: ENSMUSP00000099759 (fasta)
Gene Model predicted gene model for transcript(s): [ENSMUST00000028525] [ENSMUST00000090826] [ENSMUST00000102698]
AlphaFold Q9EQZ6
Predicted Effect possibly damaging
Transcript: ENSMUST00000028525
AA Change: N259K

PolyPhen 2 Score 0.810 (Sensitivity: 0.84; Specificity: 0.93)
SMART Domains Protein: ENSMUSP00000028525
Gene: ENSMUSG00000049044
AA Change: N259K

DomainStartEndE-ValueType
DEP 72 147 3.43e-27 SMART
low complexity region 158 167 N/A INTRINSIC
cNMP 212 331 4.02e-15 SMART
RasGEFN 351 486 3.61e-7 SMART
Blast:RasGEF 534 607 1e-33 BLAST
RasGEF 624 866 8.09e-105 SMART
Predicted Effect possibly damaging
Transcript: ENSMUST00000090826
AA Change: N403K

PolyPhen 2 Score 0.672 (Sensitivity: 0.86; Specificity: 0.91)
SMART Domains Protein: ENSMUSP00000088336
Gene: ENSMUSG00000049044
AA Change: N403K

DomainStartEndE-ValueType
low complexity region 3 13 N/A INTRINSIC
cNMP 43 162 4.62e-15 SMART
DEP 216 291 3.43e-27 SMART
low complexity region 302 311 N/A INTRINSIC
cNMP 356 475 4.02e-15 SMART
RasGEFN 495 630 3.61e-7 SMART
Blast:RasGEF 678 751 2e-33 BLAST
RasGEF 768 1010 8.09e-105 SMART
Predicted Effect possibly damaging
Transcript: ENSMUST00000102698
AA Change: N385K

PolyPhen 2 Score 0.950 (Sensitivity: 0.79; Specificity: 0.95)
SMART Domains Protein: ENSMUSP00000099759
Gene: ENSMUSG00000049044
AA Change: N385K

DomainStartEndE-ValueType
low complexity region 3 13 N/A INTRINSIC
cNMP 43 162 4.62e-15 SMART
DEP 198 273 3.43e-27 SMART
low complexity region 284 293 N/A INTRINSIC
cNMP 338 457 4.02e-15 SMART
RasGEFN 477 612 3.61e-7 SMART
Blast:RasGEF 660 733 2e-33 BLAST
RasGEF 750 992 8.09e-105 SMART
Predicted Effect noncoding transcript
Transcript: ENSMUST00000122975
Predicted Effect noncoding transcript
Transcript: ENSMUST00000153887
Predicted Effect noncoding transcript
Transcript: ENSMUST00000156031
Coding Region Coverage
  • 1x: 99.3%
  • 3x: 98.7%
  • 10x: 97.4%
  • 20x: 95.4%
Validation Efficiency
MGI Phenotype PHENOTYPE: Mice homozygous for a null allele exhibit decreased insulin granule fusion in pancreatic islet cells during the first phase of cAMP-dependent insulin granule exocytosis. Mice homozygous for a knock-out allele exhibit impaired isoproterenol-induced SR calcium leak and arrhythmia. [provided by MGI curators]
Allele List at MGI
Other mutations in this stock
Total: 30 list
GeneRefVarChr/LocMutationPredicted EffectZygosity
Anln A G 9: 22,245,296 (GRCm39) probably null Het
Arl6ip1 AAAATAAATAAATAAATAAATAAATA AAAATAAATAAATAAATAAATAAATAAATA 7: 117,721,122 (GRCm39) probably benign Het
Bltp3b T G 10: 89,642,571 (GRCm39) probably null Het
Capza3 T A 6: 139,987,786 (GRCm39) Y128* probably null Het
Ccdc187 T A 2: 26,172,239 (GRCm39) probably benign Het
Dpp4 T C 2: 62,209,667 (GRCm39) R119G probably damaging Het
Espn T C 4: 152,218,874 (GRCm39) D308G probably damaging Het
Gm9857 T C 3: 108,847,419 (GRCm39) probably benign Het
Hhatl G A 9: 121,613,285 (GRCm39) A470V probably benign Het
Igfals A T 17: 25,100,191 (GRCm39) E427D probably benign Het
Il22ra1 C T 4: 135,478,024 (GRCm39) A365V possibly damaging Het
Kctd6 G C 14: 8,222,806 (GRCm38) R216P probably damaging Het
Lama1 A T 17: 68,098,512 (GRCm39) M1864L probably null Het
Mbd5 T G 2: 49,162,305 (GRCm39) I37S probably damaging Het
Nsf C A 11: 103,821,632 (GRCm39) A5S probably damaging Het
Nsun5 A G 5: 135,398,914 (GRCm39) Y26C probably damaging Het
Or9q1 A G 19: 13,805,793 (GRCm39) probably benign Het
Pitpnm3 C T 11: 71,965,342 (GRCm39) V164I probably damaging Het
Plk2 A G 13: 110,532,637 (GRCm39) K117R probably benign Het
Ppp1r13b G T 12: 111,796,818 (GRCm39) N908K probably damaging Het
Rbp3 G A 14: 33,680,607 (GRCm39) V1070I probably benign Het
Rhbdd3 C T 11: 5,055,329 (GRCm39) T226I probably benign Het
Slc27a3 C T 3: 90,296,495 (GRCm39) probably benign Het
Slc30a2 G A 4: 134,073,360 (GRCm39) E136K probably null Het
Sptlc2 A C 12: 87,382,925 (GRCm39) I393R probably benign Het
Tmem260 C T 14: 48,715,093 (GRCm39) T249M probably damaging Het
Ttn T A 2: 76,585,168 (GRCm39) I22042F probably damaging Het
Vmn1r80 G T 7: 11,927,454 (GRCm39) C188F probably benign Het
Vwa2 C A 19: 56,891,915 (GRCm39) Q283K probably benign Het
Zfp52 A G 17: 21,782,132 (GRCm39) K660R probably benign Het
Other mutations in Rapgef4
AlleleSourceChrCoordTypePredicted EffectPPH Score
IGL00467:Rapgef4 APN 2 72,086,656 (GRCm39) missense possibly damaging 0.75
IGL00858:Rapgef4 APN 2 72,029,241 (GRCm39) missense probably damaging 1.00
IGL01408:Rapgef4 APN 2 72,005,185 (GRCm39) nonsense probably null
IGL01673:Rapgef4 APN 2 72,071,781 (GRCm39) missense probably damaging 0.99
IGL01678:Rapgef4 APN 2 72,072,569 (GRCm39) splice site probably benign
IGL01725:Rapgef4 APN 2 72,005,218 (GRCm39) missense probably benign 0.24
IGL01871:Rapgef4 APN 2 72,028,704 (GRCm39) missense possibly damaging 0.69
IGL01935:Rapgef4 APN 2 72,064,467 (GRCm39) missense probably benign 0.05
IGL02001:Rapgef4 APN 2 72,055,396 (GRCm39) splice site probably benign
IGL02041:Rapgef4 APN 2 72,029,140 (GRCm39) missense probably damaging 1.00
IGL02134:Rapgef4 APN 2 72,010,405 (GRCm39) missense probably damaging 0.97
IGL02410:Rapgef4 APN 2 72,056,938 (GRCm39) missense possibly damaging 0.51
IGL02807:Rapgef4 APN 2 72,035,993 (GRCm39) splice site probably benign
IGL03066:Rapgef4 APN 2 71,971,523 (GRCm39) splice site probably benign
IGL03282:Rapgef4 APN 2 72,036,096 (GRCm39) splice site probably benign
IGL03291:Rapgef4 APN 2 72,026,047 (GRCm39) missense probably damaging 1.00
P0033:Rapgef4 UTSW 2 71,967,675 (GRCm39) intron probably benign
R0045:Rapgef4 UTSW 2 72,029,122 (GRCm39) missense possibly damaging 0.80
R0045:Rapgef4 UTSW 2 72,029,122 (GRCm39) missense possibly damaging 0.80
R0309:Rapgef4 UTSW 2 72,056,374 (GRCm39) missense probably benign 0.02
R0398:Rapgef4 UTSW 2 71,861,385 (GRCm39) missense probably damaging 0.99
R0747:Rapgef4 UTSW 2 72,053,417 (GRCm39) missense possibly damaging 0.66
R1216:Rapgef4 UTSW 2 72,038,492 (GRCm39) missense possibly damaging 0.51
R1264:Rapgef4 UTSW 2 71,861,449 (GRCm39) missense possibly damaging 0.48
R1302:Rapgef4 UTSW 2 71,875,504 (GRCm39) missense probably benign 0.31
R1460:Rapgef4 UTSW 2 71,861,520 (GRCm39) critical splice donor site probably null
R1483:Rapgef4 UTSW 2 71,885,370 (GRCm39) critical splice donor site probably null
R1682:Rapgef4 UTSW 2 72,056,912 (GRCm39) missense possibly damaging 0.80
R1768:Rapgef4 UTSW 2 72,056,131 (GRCm39) splice site probably benign
R1858:Rapgef4 UTSW 2 71,861,408 (GRCm39) missense possibly damaging 0.67
R1860:Rapgef4 UTSW 2 72,065,064 (GRCm39) missense probably benign 0.05
R1952:Rapgef4 UTSW 2 72,038,471 (GRCm39) missense probably benign 0.07
R2025:Rapgef4 UTSW 2 72,073,083 (GRCm39) missense probably benign 0.01
R2128:Rapgef4 UTSW 2 72,056,897 (GRCm39) missense possibly damaging 0.87
R2159:Rapgef4 UTSW 2 72,005,225 (GRCm39) missense probably damaging 1.00
R2201:Rapgef4 UTSW 2 71,875,533 (GRCm39) missense probably damaging 0.96
R2883:Rapgef4 UTSW 2 71,861,469 (GRCm39) missense probably benign
R3015:Rapgef4 UTSW 2 72,028,717 (GRCm39) missense probably damaging 1.00
R5256:Rapgef4 UTSW 2 71,864,378 (GRCm39) missense probably damaging 0.97
R5572:Rapgef4 UTSW 2 71,864,464 (GRCm39) critical splice donor site probably null
R5574:Rapgef4 UTSW 2 71,864,464 (GRCm39) critical splice donor site probably null
R5575:Rapgef4 UTSW 2 71,864,464 (GRCm39) critical splice donor site probably null
R5749:Rapgef4 UTSW 2 72,073,101 (GRCm39) missense probably damaging 1.00
R6007:Rapgef4 UTSW 2 72,010,293 (GRCm39) missense possibly damaging 0.55
R6084:Rapgef4 UTSW 2 72,026,622 (GRCm39) critical splice donor site probably null
R6192:Rapgef4 UTSW 2 71,811,661 (GRCm39) missense probably benign 0.00
R6409:Rapgef4 UTSW 2 72,008,581 (GRCm39) missense probably benign 0.01
R6683:Rapgef4 UTSW 2 71,885,123 (GRCm39) intron probably benign
R6774:Rapgef4 UTSW 2 72,056,119 (GRCm39) missense probably benign 0.01
R6844:Rapgef4 UTSW 2 72,064,970 (GRCm39) missense probably damaging 0.99
R6999:Rapgef4 UTSW 2 72,069,469 (GRCm39) missense probably damaging 1.00
R7077:Rapgef4 UTSW 2 72,071,820 (GRCm39) missense probably damaging 0.96
R7138:Rapgef4 UTSW 2 72,028,707 (GRCm39) missense probably damaging 1.00
R7275:Rapgef4 UTSW 2 72,038,445 (GRCm39) missense probably damaging 1.00
R7352:Rapgef4 UTSW 2 72,010,435 (GRCm39) missense probably damaging 1.00
R7397:Rapgef4 UTSW 2 72,036,010 (GRCm39) missense probably benign 0.23
R7508:Rapgef4 UTSW 2 72,036,077 (GRCm39) missense probably benign 0.00
R7620:Rapgef4 UTSW 2 72,059,422 (GRCm39) missense probably damaging 0.99
R7703:Rapgef4 UTSW 2 72,010,315 (GRCm39) missense probably benign 0.28
R7770:Rapgef4 UTSW 2 72,028,739 (GRCm39) missense possibly damaging 0.95
R7814:Rapgef4 UTSW 2 72,053,461 (GRCm39) missense probably benign
R7868:Rapgef4 UTSW 2 72,031,481 (GRCm39) missense probably benign 0.11
R8210:Rapgef4 UTSW 2 72,056,364 (GRCm39) missense probably benign 0.00
R8967:Rapgef4 UTSW 2 72,056,854 (GRCm39) missense possibly damaging 0.72
R9113:Rapgef4 UTSW 2 71,861,493 (GRCm39) missense probably benign 0.43
R9157:Rapgef4 UTSW 2 72,005,212 (GRCm39) missense probably benign 0.06
R9314:Rapgef4 UTSW 2 72,064,983 (GRCm39) missense possibly damaging 0.52
R9552:Rapgef4 UTSW 2 72,008,561 (GRCm39) missense probably benign
R9578:Rapgef4 UTSW 2 72,026,052 (GRCm39) missense probably damaging 1.00
R9620:Rapgef4 UTSW 2 72,036,051 (GRCm39) missense probably benign 0.01
R9665:Rapgef4 UTSW 2 72,036,018 (GRCm39) missense probably benign 0.17
X0062:Rapgef4 UTSW 2 72,056,951 (GRCm39) missense probably benign 0.05
Predicted Primers PCR Primer
(F):5'- CCTGAATTAGTTAGGATTTGCCGG -3'
(R):5'- ATGACTCTGAGTGCAATAATTGAGG -3'

Sequencing Primer
(F):5'- AACTCTGGAGCCTGAAAG -3'
(R):5'- GGAGTAACAATGCCATGGT -3'
Posted On 2015-06-20