Incidental Mutation 'R6409:Rapgef4'
ID 514762
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 044554-MU
Accession Numbers
Essential gene? Possibly essential (E-score: 0.648) question?
Stock # R6409 (G1)
Quality Score 176.009
Status Not validated
Chromosome 2
Chromosomal Location 71811584-72087818 bp(+) (GRCm39)
Type of Mutation missense
DNA Base Change (assembly) A to G at 72008581 bp (GRCm39)
Zygosity Heterozygous
Amino Acid Change Histidine to Arginine at position 253 (H253R)
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: H109R

PolyPhen 2 Score 0.006 (Sensitivity: 0.97; Specificity: 0.75)
SMART Domains Protein: ENSMUSP00000028525
Gene: ENSMUSG00000049044
AA Change: H109R

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: H253R

PolyPhen 2 Score 0.006 (Sensitivity: 0.97; Specificity: 0.75)
SMART Domains Protein: ENSMUSP00000088336
Gene: ENSMUSG00000049044
AA Change: H253R

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: H235R

PolyPhen 2 Score 0.001 (Sensitivity: 0.99; Specificity: 0.15)
SMART Domains Protein: ENSMUSP00000099759
Gene: ENSMUSG00000049044
AA Change: H235R

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
Coding Region Coverage
  • 1x: 100.0%
  • 3x: 99.9%
  • 10x: 99.5%
  • 20x: 98.3%
Validation Efficiency 97% (32/33)
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: 35 list
GeneRefVarChr/LocMutationPredicted EffectZygosity
Aatk G T 11: 119,902,558 (GRCm39) Q556K probably benign Het
Adgrf3 A G 5: 30,402,312 (GRCm39) V572A probably damaging Het
Ahnak G A 19: 8,986,938 (GRCm39) V2741M probably benign Het
Ascc3 T C 10: 50,721,676 (GRCm39) V2043A probably benign Het
B3glct C T 5: 149,658,916 (GRCm39) R239C probably benign Het
Cacna2d4 T A 6: 119,259,189 (GRCm39) V626E probably damaging Het
Cdcp3 G A 7: 130,863,800 (GRCm39) probably benign Het
Cfap54 T C 10: 92,803,354 (GRCm39) N1563D probably benign Het
Duox2 G C 2: 122,115,148 (GRCm39) H1110D probably damaging Het
Inppl1 A T 7: 101,478,168 (GRCm39) F648I probably damaging Het
Mefv C A 16: 3,528,657 (GRCm39) probably null Het
Ms4a4b T C 19: 11,438,724 (GRCm39) probably null Het
Mtus2 T C 5: 148,014,425 (GRCm39) V406A probably benign Het
Nup88 T C 11: 70,835,798 (GRCm39) R554G probably null Het
Or1x2 A G 11: 50,918,015 (GRCm39) Y62C probably damaging Het
Or4d10 C T 19: 12,052,111 (GRCm39) probably benign Het
Or8h8 A T 2: 86,753,515 (GRCm39) Y120* probably null Het
Pde10a A G 17: 9,168,270 (GRCm39) D246G probably damaging Het
Pmm1 T C 15: 81,845,008 (GRCm39) T9A probably benign Het
Pramel19 C T 4: 101,797,874 (GRCm39) Q91* probably null Het
Psg18 T C 7: 18,087,446 (GRCm39) M71V probably benign Het
Rfc4 T C 16: 22,932,823 (GRCm39) *371W probably null Het
Rgs18 T A 1: 144,650,931 (GRCm39) K17* probably null Het
Rsrc1 C T 3: 66,901,982 (GRCm39) P44L unknown Het
Sertm1 T C 3: 54,806,788 (GRCm39) Y79C probably benign Het
Sfrp1 T C 8: 23,907,394 (GRCm39) I198T possibly damaging Het
Slc15a2 T A 16: 36,582,232 (GRCm39) I254F probably benign Het
Slc29a4 A G 5: 142,697,826 (GRCm39) D93G probably damaging Het
Smo T C 6: 29,736,113 (GRCm39) L35S unknown Het
Tbc1d8 A G 1: 39,411,669 (GRCm39) S1056P probably benign Het
Ttll9 A G 2: 152,841,261 (GRCm39) D286G probably damaging Het
Vmn2r14 A G 5: 109,364,096 (GRCm39) Y607H probably benign Het
Vps8 T A 16: 21,297,189 (GRCm39) C564S probably benign Het
Zc3h12d A G 10: 7,743,082 (GRCm39) H284R probably benign Het
Zfp106 A T 2: 120,362,585 (GRCm39) S79T probably 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
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'- TGCCATACTCTTTGGAAGGTTC -3'
(R):5'- AATGAAGATGCTAGCTTGGTGG -3'

Sequencing Primer
(F):5'- AAGGTTCTGCTCTGGAAGATTATTC -3'
(R):5'- GGTTCTTTAAGGGGATCGTAATTC -3'
Posted On 2018-05-04