Incidental Mutation 'R7703:Rapgef4'
ID 594101
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 045764-MU
Accession Numbers
Essential gene? Possibly essential (E-score: 0.648) question?
Stock # R7703 (G1)
Quality Score 225.009
Status Not validated
Chromosome 2
Chromosomal Location 71811584-72087818 bp(+) (GRCm39)
Type of Mutation missense
DNA Base Change (assembly) A to G at 72010315 bp (GRCm39)
Zygosity Heterozygous
Amino Acid Change Aspartic acid to Glycine at position 291 (D291G)
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 benign
Transcript: ENSMUST00000028525
AA Change: D147G

PolyPhen 2 Score 0.044 (Sensitivity: 0.94; Specificity: 0.83)
SMART Domains Protein: ENSMUSP00000028525
Gene: ENSMUSG00000049044
AA Change: D147G

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 benign
Transcript: ENSMUST00000090826
AA Change: D291G

PolyPhen 2 Score 0.280 (Sensitivity: 0.91; Specificity: 0.88)
SMART Domains Protein: ENSMUSP00000088336
Gene: ENSMUSG00000049044
AA Change: D291G

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 benign
Transcript: ENSMUST00000102698
AA Change: D273G

PolyPhen 2 Score 0.152 (Sensitivity: 0.92; Specificity: 0.87)
SMART Domains Protein: ENSMUSP00000099759
Gene: ENSMUSG00000049044
AA Change: D273G

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
Coding Region Coverage
  • 1x: 100.0%
  • 3x: 100.0%
  • 10x: 99.8%
  • 20x: 99.2%
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: 65 list
GeneRefVarChr/LocMutationPredicted EffectZygosity
1810065E05Rik T C 11: 58,316,593 (GRCm39) I191T probably damaging Het
2310003L06Rik T C 5: 88,120,671 (GRCm39) L476P possibly damaging Het
Aasdh T C 5: 77,035,924 (GRCm39) D387G probably damaging Het
Ahsa2 T A 11: 23,440,415 (GRCm39) T327S probably benign Het
Ap3d1 A T 10: 80,553,678 (GRCm39) V523E probably damaging Het
Baz2b C A 2: 59,747,769 (GRCm39) R1298L probably damaging Het
Cacna2d3 T C 14: 28,765,503 (GRCm39) T802A possibly damaging Het
Cdh23 G T 10: 60,173,043 (GRCm39) T1714K probably damaging Het
Chrna3 A T 9: 54,923,408 (GRCm39) D133E probably benign Het
Cnot1 C T 8: 96,486,726 (GRCm39) probably null Het
Col16a1 A T 4: 129,990,295 (GRCm39) N1396Y unknown Het
Cox11 A G 11: 90,529,245 (GRCm39) N77S probably benign Het
Ctsf T G 19: 4,906,567 (GRCm39) F165V probably damaging Het
Cytip A G 2: 58,037,920 (GRCm39) V148A probably damaging Het
Diaph1 T C 18: 38,023,862 (GRCm39) I659V unknown Het
Dmxl2 A T 9: 54,368,370 (GRCm39) M26K probably benign Het
Erp44 T A 4: 48,196,904 (GRCm39) I340F probably benign Het
Fam186a A G 15: 99,852,678 (GRCm39) M180T unknown Het
Frem2 C T 3: 53,429,589 (GRCm39) V2793I probably benign Het
Gm19410 A G 8: 36,266,539 (GRCm39) E1064G probably damaging Het
Gria4 T C 9: 4,503,588 (GRCm39) I343V probably benign Het
Grsf1 T A 5: 88,819,150 (GRCm39) N228Y probably damaging Het
H3c13 C A 3: 96,176,309 (GRCm39) Y100* probably null Het
Ighv1-18 A T 12: 114,646,381 (GRCm39) N74K probably benign Het
Kcnh6 A T 11: 105,914,703 (GRCm39) T703S probably benign Het
Lrp1b T A 2: 41,000,798 (GRCm39) D2256V Het
Lrrc63 T C 14: 75,360,447 (GRCm39) T352A possibly damaging Het
Lztfl1 T C 9: 123,531,194 (GRCm39) E258G probably damaging Het
Mcph1 T C 8: 18,721,122 (GRCm39) I650T possibly damaging Het
Mep1a T C 17: 43,788,997 (GRCm39) D606G possibly damaging Het
Muc16 T C 9: 18,516,578 (GRCm39) I313M Het
Myh7b A G 2: 155,462,356 (GRCm39) Y353C probably null Het
Nfatc1 A G 18: 80,725,504 (GRCm39) L420P probably damaging Het
Olfml1 A G 7: 107,170,392 (GRCm39) E93G probably damaging Het
Or6b1 A T 6: 42,814,938 (GRCm39) E41V probably damaging Het
Or8c11 A G 9: 38,289,357 (GRCm39) H54R probably benign Het
Pax1 A T 2: 147,208,034 (GRCm39) N214I probably damaging Het
Pcdhb17 C A 18: 37,619,801 (GRCm39) H530Q probably benign Het
Pcdhgb7 A T 18: 37,885,321 (GRCm39) M164L probably benign Het
Pcolce T C 5: 137,603,474 (GRCm39) N453S probably benign Het
Prr36 T C 8: 4,262,982 (GRCm39) T895A probably benign Het
Ptprq C T 10: 107,480,007 (GRCm39) V1088I probably benign Het
Rab5a T A 17: 53,807,485 (GRCm39) F174I probably damaging Het
Rbm25 A T 12: 83,721,864 (GRCm39) K683N possibly damaging Het
Rbpj T C 5: 53,803,240 (GRCm39) I156T probably damaging Het
Rgsl1 A G 1: 153,669,610 (GRCm39) S259P possibly damaging Het
Ring1 T C 17: 34,242,109 (GRCm39) D100G probably damaging Het
Ryr3 A T 2: 112,690,110 (GRCm39) D1166E probably damaging Het
Sacs A G 14: 61,443,539 (GRCm39) K1862E possibly damaging Het
Scamp5 A G 9: 57,354,465 (GRCm39) I63T possibly damaging Het
Septin14 C T 5: 129,763,092 (GRCm39) A334T possibly damaging Het
Sh3rf2 A T 18: 42,289,201 (GRCm39) Q706L probably benign Het
Skap2 A T 6: 51,884,934 (GRCm39) H242Q probably benign Het
Spmap2l T C 5: 77,164,444 (GRCm39) I149T probably benign Het
Tfpt A G 7: 3,623,744 (GRCm39) probably null Het
Thg1l T G 11: 45,846,120 (GRCm39) D58A probably damaging Het
Thyn1 A G 9: 26,918,143 (GRCm39) E177G probably benign Het
Tmem151b C T 17: 45,856,724 (GRCm39) A239T probably damaging Het
Ttc21a T C 9: 119,788,095 (GRCm39) V840A probably benign Het
Usp32 A T 11: 84,968,153 (GRCm39) V170E probably damaging Het
Vmn2r29 A G 7: 7,234,864 (GRCm39) V674A probably benign Het
Vwa8 A G 14: 79,263,513 (GRCm39) N781S probably damaging Het
Zbtb7c C A 18: 76,270,433 (GRCm39) Q174K probably benign Het
Zeb1 T C 18: 5,766,917 (GRCm39) I476T probably benign Het
Zfp91 A T 19: 12,754,241 (GRCm39) D282E 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
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
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
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'- AGGACTCTGACTCTGCTGTTAG -3'
(R):5'- GGGAAGACCAGGACTTTTGC -3'

Sequencing Primer
(F):5'- AGCTGCACAACTCTTGTCAG -3'
(R):5'- GACCAGGACTTTTGCTGCCTTG -3'
Posted On 2019-11-12