Incidental Mutation 'R9314:Rapgef4'
ID 705755
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
Accession Numbers
Essential gene? Possibly essential (E-score: 0.648) question?
Stock # R9314 (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 T at 72064983 bp (GRCm39)
Zygosity Heterozygous
Amino Acid Change Histidine to Leucine at position 804 (H804L)
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 possibly damaging
Transcript: ENSMUST00000028525
AA Change: H660L

PolyPhen 2 Score 0.671 (Sensitivity: 0.86; Specificity: 0.91)
SMART Domains Protein: ENSMUSP00000028525
Gene: ENSMUSG00000049044
AA Change: H660L

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: H804L

PolyPhen 2 Score 0.522 (Sensitivity: 0.88; Specificity: 0.90)
SMART Domains Protein: ENSMUSP00000088336
Gene: ENSMUSG00000049044
AA Change: H804L

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: H786L

PolyPhen 2 Score 0.466 (Sensitivity: 0.89; Specificity: 0.90)
SMART Domains Protein: ENSMUSP00000099759
Gene: ENSMUSG00000049044
AA Change: H786L

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: 99.9%
  • 10x: 99.7%
  • 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: 66 list
GeneRefVarChr/LocMutationPredicted EffectZygosity
Abca17 A C 17: 24,547,593 (GRCm39) N260K possibly damaging Het
Anapc1 G A 2: 128,464,420 (GRCm39) S1692L possibly damaging Het
Brca2 A G 5: 150,474,359 (GRCm39) R2421G probably damaging Het
Cad A G 5: 31,234,988 (GRCm39) Y2143C probably damaging Het
Calr3 T A 8: 73,178,535 (GRCm39) D356V possibly damaging Het
Cd207 T A 6: 83,652,699 (GRCm39) T144S probably damaging Het
Cntln T C 4: 84,924,719 (GRCm39) L608P probably damaging Het
Dnah8 A T 17: 30,990,857 (GRCm39) Y3300F probably benign Het
Emb T C 13: 117,408,604 (GRCm39) I315T probably damaging Het
Esr1 T A 10: 4,916,181 (GRCm39) V456E possibly damaging Het
Evpl A T 11: 116,118,503 (GRCm39) H701Q probably benign Het
F5 C T 1: 164,029,146 (GRCm39) T1715I probably benign Het
Fut10 T A 8: 31,691,504 (GRCm39) H116Q probably damaging Het
Gm40460 ACAACCCCCACAGGAGCCACAGCCTCCCTTGCAGCCCCCACAGGAGCCACAGCCTCCCTTGCAGCCCCCACAGGAGCCACAGCCTCCCTTGCAGCCCCCACAGGAGCCACAGCCTCCCTTGCAGCCCCCACAGGAACTACAGCCTCCCTTGCAGCCCCCACAGGAACTACAGCCTCCCTTGCAGCCCCCACAGGAACTACAGCCTCCCTTGCAGCCCCCACAG ACAGCCCCCACAGGAGCCACAGCCTCCCTTGCAGCCCCCACAGGAGCCACAGCCTCCCTTGCAGCCCCCACAGGAACTACAGCCTCCCTTGCAGCCCCCACAGGAACTACAGCCTCCCTTGCAGCCCCCACAGGAACTACAGCCTCCCTTGCAGCCCCCACAG 7: 141,794,447 (GRCm39) probably benign Het
Gm5591 T C 7: 38,221,884 (GRCm39) T62A probably benign Het
Hectd4 T C 5: 121,437,708 (GRCm39) probably null Het
Ifit1bl1 G C 19: 34,576,693 (GRCm39) Q3E probably benign Het
Ighg3 A T 12: 113,323,946 (GRCm39) D147E Het
Ighv8-13 A G 12: 115,728,996 (GRCm39) V87A possibly damaging Het
Kdelr1 A G 7: 45,531,050 (GRCm39) T160A probably benign Het
Kdm2a A G 19: 4,372,510 (GRCm39) L945P probably damaging Het
Krt36 C T 11: 99,994,227 (GRCm39) W283* probably null Het
Lamp3 T C 16: 19,492,192 (GRCm39) M351V probably benign Het
Lox C G 18: 52,653,911 (GRCm39) R395P probably damaging Het
Lrrtm3 T C 10: 63,925,499 (GRCm39) probably benign Het
Madcam1 C A 10: 79,501,481 (GRCm39) T182K probably damaging Het
Megf8 T A 7: 25,029,297 (GRCm39) H280Q probably damaging Het
Mrgprb5 A G 7: 47,818,174 (GRCm39) I187T probably benign Het
Muc1 T C 3: 89,138,825 (GRCm39) V478A probably damaging Het
Mug1 T G 6: 121,834,296 (GRCm39) V359G probably damaging Het
Myh4 A G 11: 67,151,141 (GRCm39) H1932R probably benign Het
Naaladl1 A C 19: 6,162,401 (GRCm39) N448H probably damaging Het
Or52b1 A T 7: 104,979,081 (GRCm39) I106N probably damaging Het
Or5a1 C T 19: 12,097,144 (GRCm39) E311K probably benign Het
Pkd1l1 A T 11: 8,829,153 (GRCm39) Y1480N Het
Poll T C 19: 45,547,091 (GRCm39) E127G probably benign Het
Ppl T C 16: 4,922,367 (GRCm39) N305S possibly damaging Het
Prss53 A G 7: 127,490,039 (GRCm39) V17A probably benign Het
Ptprj A G 2: 90,301,631 (GRCm39) V74A possibly damaging Het
Rassf8 A G 6: 145,762,296 (GRCm39) T356A probably damaging Het
Rptor T C 11: 119,786,772 (GRCm39) S1246P probably benign Het
Setdb2 A T 14: 59,650,240 (GRCm39) I458N probably benign Het
Sgtb A G 13: 104,254,933 (GRCm39) K68E possibly damaging Het
Slc19a3 T G 1: 83,000,094 (GRCm39) I308L possibly damaging Het
Slc22a5 T C 11: 53,762,487 (GRCm39) D320G possibly damaging Het
Slc34a2 T C 5: 53,218,143 (GRCm39) S141P possibly damaging Het
Slc37a2 T C 9: 37,150,482 (GRCm39) T158A possibly damaging Het
Slc7a1 T C 5: 148,269,327 (GRCm39) I598V probably benign Het
Sphk2 T C 7: 45,361,158 (GRCm39) D282G probably damaging Het
Spty2d1 G T 7: 46,648,486 (GRCm39) P148T probably damaging Het
Supt3 A G 17: 45,352,250 (GRCm39) T310A probably benign Het
Supt5 T A 7: 28,019,799 (GRCm39) D457V probably damaging Het
Svep1 C T 4: 58,070,347 (GRCm39) G2480R probably damaging Het
Tbcd T C 11: 121,487,297 (GRCm39) V803A probably benign Het
Tex2 A T 11: 106,435,075 (GRCm39) C784S unknown Het
Thrb A G 14: 17,963,208 (GRCm38) H57R probably benign Het
Tmc4 T C 7: 3,679,723 (GRCm39) T34A possibly damaging Het
Tmprss2 T C 16: 97,400,459 (GRCm39) N4S probably benign Het
Trank1 A G 9: 111,195,049 (GRCm39) I1024M probably damaging Het
Trnau1ap C A 4: 132,056,697 (GRCm39) probably benign Het
Ttn A G 2: 76,566,710 (GRCm39) V28061A probably damaging Het
Txnl4b C A 8: 110,299,331 (GRCm39) P97Q probably benign Het
Ube4a T C 9: 44,854,023 (GRCm39) T573A probably benign Het
Vit A T 17: 78,927,044 (GRCm39) T330S probably benign Het
Wdr3 T C 3: 100,050,288 (GRCm39) I750V probably benign Het
Zfp59 C T 7: 27,554,029 (GRCm39) L494F possibly damaging 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
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
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'- GCCCTTCAAATCTATATGACAAGG -3'
(R):5'- GGTGTTTTCCATGAGAACAGAG -3'

Sequencing Primer
(F):5'- TCTATATGACAAGGTACATCCGGG -3'
(R):5'- GTTTTCCATGAGAACAGAGTTCAGG -3'
Posted On 2022-03-25