Incidental Mutation 'R7275:Rapgef4'
ID 565497
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 045358-MU
Accession Numbers
Essential gene? Possibly essential (E-score: 0.648) question?
Stock # R7275 (G1)
Quality Score 225.009
Status Validated
Chromosome 2
Chromosomal Location 71811584-72087818 bp(+) (GRCm39)
Type of Mutation missense
DNA Base Change (assembly) A to G at 72038445 bp (GRCm39)
Zygosity Heterozygous
Amino Acid Change Aspartic acid to Glycine at position 532 (D532G)
Ref Sequence ENSEMBL: ENSMUSP00000088336 (fasta)
Gene Model predicted gene model for transcript(s): [ENSMUST00000028525] [ENSMUST00000090826] [ENSMUST00000102698]
AlphaFold Q9EQZ6
PDB Structure CRYSTAL STRUCTURE OF THE REGULATORY DOMAIN OF EPAC2 [X-RAY DIFFRACTION]
STRUCTURE OF THE CAMP RESPONSIVE EXCHANGE FACTOR EPAC2 IN ITS AUTO-INHIBITED STATE [X-RAY DIFFRACTION]
Structure of Epac2 in complex with cyclic-AMP and Rap [X-RAY DIFFRACTION]
Conformational dynamics of exchange protein directly activated by cAMP [X-RAY DIFFRACTION]
Selective activation of Epac1 and Epac2 [X-RAY DIFFRACTION]
Selective activation of Epac1 and Epac2 [X-RAY DIFFRACTION]
Selective activation of Epac1 and Epac2 [X-RAY DIFFRACTION]
Selective activation of Epac1 and Epac2 [X-RAY DIFFRACTION]
Selective activation of Epac1 and Epac2 [X-RAY DIFFRACTION]
Predicted Effect probably damaging
Transcript: ENSMUST00000028525
AA Change: D388G

PolyPhen 2 Score 0.990 (Sensitivity: 0.72; Specificity: 0.97)
SMART Domains Protein: ENSMUSP00000028525
Gene: ENSMUSG00000049044
AA Change: D388G

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 probably damaging
Transcript: ENSMUST00000090826
AA Change: D532G

PolyPhen 2 Score 1.000 (Sensitivity: 0.00; Specificity: 1.00)
SMART Domains Protein: ENSMUSP00000088336
Gene: ENSMUSG00000049044
AA Change: D532G

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 probably damaging
Transcript: ENSMUST00000102698
AA Change: D514G

PolyPhen 2 Score 1.000 (Sensitivity: 0.00; Specificity: 1.00)
SMART Domains Protein: ENSMUSP00000099759
Gene: ENSMUSG00000049044
AA Change: D514G

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
Meta Mutation Damage Score 0.9023 question?
Coding Region Coverage
  • 1x: 100.0%
  • 3x: 99.9%
  • 10x: 99.6%
  • 20x: 98.8%
Validation Efficiency 98% (64/65)
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: 65 list
GeneRefVarChr/LocMutationPredicted EffectZygosity
4930447C04Rik T A 12: 72,956,795 (GRCm39) T132S possibly damaging Het
4933412E24Rik A G 15: 59,887,738 (GRCm39) V234A probably benign Het
Abtb3 T A 10: 85,490,346 (GRCm39) L1004Q probably damaging Het
Acsm5 A G 7: 119,136,511 (GRCm39) T361A possibly damaging Het
Agxt2 G A 15: 10,358,753 (GRCm39) R24H probably benign Het
Asb16 G T 11: 102,159,935 (GRCm39) W96L probably damaging Het
Bche T A 3: 73,607,969 (GRCm39) T486S probably benign Het
Bpnt2 C A 4: 4,792,962 (GRCm39) G48W probably damaging Het
Cast T C 13: 74,875,453 (GRCm39) T382A probably benign Het
Cdcp1 T A 9: 123,014,119 (GRCm39) K218N possibly damaging Het
Ceacam18 G A 7: 43,291,308 (GRCm39) G250D probably damaging Het
Ciao3 T A 17: 25,994,108 (GRCm39) V52E possibly damaging Het
Ctnnd2 T C 15: 30,905,855 (GRCm39) I834T possibly damaging Het
Cyp11b2 C A 15: 74,725,840 (GRCm39) G136W probably damaging Het
Dis3 A G 14: 99,324,925 (GRCm39) V502A probably damaging Het
Dnai2 T A 11: 114,648,054 (GRCm39) M610K unknown Het
Drosha G A 15: 12,846,169 (GRCm39) V435I possibly damaging Het
Dsc2 T A 18: 20,184,236 (GRCm39) R51* probably null Het
Ergic2 A T 6: 148,096,757 (GRCm39) C170S probably damaging Het
Exoc7 A T 11: 116,195,688 (GRCm39) probably null Het
Fbxw25 G T 9: 109,483,660 (GRCm39) A184E Het
Gm4846 T A 1: 166,314,648 (GRCm39) T332S probably benign Het
Greb1l T A 18: 10,544,561 (GRCm39) M1385K probably benign Het
Grik1 T C 16: 87,709,708 (GRCm39) N871S probably benign Het
Il11ra1 T C 4: 41,765,109 (GRCm39) L145P probably damaging Het
Inpp5e A G 2: 26,298,104 (GRCm39) S166P probably benign Het
Kdm4b T A 17: 56,703,333 (GRCm39) L676H probably damaging Het
Lrp2 T A 2: 69,289,875 (GRCm39) K3655* probably null Het
Lrrc74a A G 12: 86,787,753 (GRCm39) N128S probably damaging Het
Map3k14 T C 11: 103,117,848 (GRCm39) E648G probably damaging Het
Mbtps1 A T 8: 120,269,489 (GRCm39) D200E probably benign Het
Mttp T C 3: 137,829,546 (GRCm39) D114G probably benign Het
Mup13 G A 4: 61,182,752 (GRCm39) T101M probably benign Het
Neb T A 2: 52,096,956 (GRCm39) T4953S probably benign Het
Nfasc A C 1: 132,562,001 (GRCm39) L147R probably damaging Het
Obox6 T C 7: 15,567,805 (GRCm39) E214G probably benign Het
Opn3 T C 1: 175,493,039 (GRCm39) N175S probably damaging Het
Or1j12 A T 2: 36,342,851 (GRCm39) M85L probably benign Het
Or8g22 T A 9: 38,958,815 (GRCm39) probably benign Het
Or8k22 C A 2: 86,163,136 (GRCm39) C188F possibly damaging Het
Osbpl3 G T 6: 50,323,410 (GRCm39) D224E probably benign Het
Osr2 A G 15: 35,301,032 (GRCm39) D196G probably damaging Het
Pde8b T A 13: 95,179,442 (GRCm39) N405Y probably damaging Het
Pirb A G 7: 3,719,177 (GRCm39) S571P probably benign Het
Psmc3 T A 2: 90,886,275 (GRCm39) I163N probably damaging Het
Retreg1 A G 15: 25,971,684 (GRCm39) D208G probably benign Het
Rgsl1 T G 1: 153,679,876 (GRCm39) probably null Het
Ripk4 T C 16: 97,545,157 (GRCm39) T497A probably benign Het
Slc30a2 T A 4: 134,076,581 (GRCm39) probably null Het
Slc6a19 T C 13: 73,834,197 (GRCm39) D335G probably benign Het
Slco4c1 G A 1: 96,799,497 (GRCm39) T113M probably benign Het
Speer1c T C 5: 10,295,192 (GRCm39) N71D Het
Stxbp6 A G 12: 44,948,786 (GRCm39) F108L probably benign Het
Sulf1 T A 1: 12,921,189 (GRCm39) probably null Het
Syt16 C T 12: 74,313,483 (GRCm39) R470C probably damaging Het
Tbc1d19 T A 5: 54,029,618 (GRCm39) D326E probably damaging Het
Trappc14 T C 5: 138,261,839 (GRCm39) S86G probably benign Het
Trgv3 A G 13: 19,427,188 (GRCm39) T24A probably benign Het
Trpm3 T A 19: 22,956,048 (GRCm39) M1170K possibly damaging Het
Tubgcp6 G A 15: 88,987,146 (GRCm39) Q1276* probably null Het
Tyrp1 A G 4: 80,755,821 (GRCm39) K197E possibly damaging Het
Ube3d T C 9: 86,322,679 (GRCm39) D165G probably damaging Het
Zfp212 A G 6: 47,897,678 (GRCm39) T7A probably benign Het
Zhx1 T C 15: 57,917,758 (GRCm39) T163A probably benign Het
Zp2 A T 7: 119,734,576 (GRCm39) probably null 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
R4278:Rapgef4 UTSW 2 72,028,739 (GRCm39) missense possibly damaging 0.95
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
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'- TGGCTAAAGTGACTGGTTCC -3'
(R):5'- AGCTATAATACTGCCTGAGCC -3'

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