Incidental Mutation 'R6007:Rapgef4'
ID 479522
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 044184-MU
Accession Numbers
Essential gene? Possibly essential (E-score: 0.648) question?
Stock # R6007 (G1)
Quality Score 225.009
Status Validated
Chromosome 2
Chromosomal Location 71811584-72087818 bp(+) (GRCm39)
Type of Mutation missense
DNA Base Change (assembly) T to C at 72010293 bp (GRCm39)
Zygosity Heterozygous
Amino Acid Change Tyrosine to Histidine at position 284 (Y284H)
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: Y140H

PolyPhen 2 Score 0.455 (Sensitivity: 0.89; Specificity: 0.90)
SMART Domains Protein: ENSMUSP00000028525
Gene: ENSMUSG00000049044
AA Change: Y140H

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: Y284H

PolyPhen 2 Score 0.545 (Sensitivity: 0.88; Specificity: 0.91)
SMART Domains Protein: ENSMUSP00000088336
Gene: ENSMUSG00000049044
AA Change: Y284H

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: Y266H

PolyPhen 2 Score 0.200 (Sensitivity: 0.92; Specificity: 0.88)
SMART Domains Protein: ENSMUSP00000099759
Gene: ENSMUSG00000049044
AA Change: Y266H

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
Meta Mutation Damage Score 0.0753 question?
Coding Region Coverage
  • 1x: 99.9%
  • 3x: 99.4%
  • 10x: 97.1%
  • 20x: 90.6%
Validation Efficiency 100% (54/54)
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: 53 list
GeneRefVarChr/LocMutationPredicted EffectZygosity
1700003E16Rik G T 6: 83,137,900 (GRCm39) A9S possibly damaging Het
4930407I10Rik C G 15: 81,946,940 (GRCm39) T279S probably benign Het
A830018L16Rik A G 1: 11,582,140 (GRCm39) probably null Het
Abcg5 T G 17: 84,976,392 (GRCm39) I482L probably benign Het
Adgrf5 T A 17: 43,748,462 (GRCm39) D44E probably damaging Het
Amh A G 10: 80,641,305 (GRCm39) N75S probably benign Het
Arl8a T C 1: 135,080,606 (GRCm39) probably null Het
Bpifb4 T C 2: 153,784,480 (GRCm39) Y63H possibly damaging Het
Chd5 A T 4: 152,463,878 (GRCm39) E1449V probably null Het
Chml A G 1: 175,515,594 (GRCm39) V109A probably benign Het
Crybg3 G T 16: 59,374,837 (GRCm39) S2139* probably null Het
Cyp2c68 T C 19: 39,722,780 (GRCm39) D256G probably damaging Het
Dchs2 G T 3: 83,253,534 (GRCm39) V2315L probably damaging Het
Ddx20 T C 3: 105,590,736 (GRCm39) I227V possibly damaging Het
Drg2 T C 11: 60,353,451 (GRCm39) V266A possibly damaging Het
Flcn C A 11: 59,683,448 (GRCm39) E576D probably benign Het
Fstl5 T A 3: 76,317,899 (GRCm39) D188E probably damaging Het
Gm14496 A G 2: 181,639,323 (GRCm39) Q471R probably benign Het
Gm43772 T C 5: 66,332,334 (GRCm39) probably benign Het
Gpc6 C T 14: 118,188,673 (GRCm39) H436Y probably damaging Het
Gpr179 A T 11: 97,226,628 (GRCm39) C1842* probably null Het
Ints8 G A 4: 11,208,845 (GRCm39) T934I possibly damaging Het
Iqsec1 G T 6: 90,637,969 (GRCm39) C1050* probably null Het
Larp4b T C 13: 9,218,793 (GRCm39) V510A probably benign Het
Map3k13 A T 16: 21,723,933 (GRCm39) D305V possibly damaging Het
Mc5r A T 18: 68,472,318 (GRCm39) I226F possibly damaging Het
Mme G A 3: 63,250,929 (GRCm39) W323* probably null Het
Mrpl24 A G 3: 87,829,705 (GRCm39) Y97C probably benign Het
Mslnl G A 17: 25,965,749 (GRCm39) S541N probably benign Het
Npepl1 T C 2: 173,962,850 (GRCm39) V412A probably benign Het
Nrg3 T A 14: 39,194,409 (GRCm39) K117* probably null Het
Or11j4 G T 14: 50,630,948 (GRCm39) C245F probably damaging Het
Or4f52 T C 2: 111,061,275 (GRCm39) T288A probably benign Het
Orc2 A T 1: 58,506,851 (GRCm39) M447K probably benign Het
Phf3 A T 1: 30,843,426 (GRCm39) H1844Q probably damaging Het
Plxnc1 T C 10: 94,629,152 (GRCm39) I1541V possibly damaging Het
Rnf180 C A 13: 105,317,957 (GRCm39) probably null Het
Secisbp2 T C 13: 51,819,395 (GRCm39) I325T probably damaging Het
Sertad2 G A 11: 20,597,884 (GRCm39) G27S probably benign Het
Slc4a10 A G 2: 62,099,216 (GRCm39) M625V probably benign Het
Synpo T A 18: 60,736,687 (GRCm39) M420L probably benign Het
Tmem116 A C 5: 121,655,955 (GRCm39) *147C probably null Het
Top2b G A 14: 16,423,779 (GRCm38) probably null Het
Trp53bp2 T A 1: 182,283,305 (GRCm39) C1014S probably damaging Het
Unc5b A G 10: 60,601,139 (GRCm39) F896L probably damaging Het
Vil1 T C 1: 74,459,026 (GRCm39) W177R probably damaging Het
Vmn2r107 A T 17: 20,595,316 (GRCm39) Y623F probably benign Het
Vmn2r86 T C 10: 130,289,535 (GRCm39) Y120C probably damaging Het
Wdr18 A G 10: 79,801,177 (GRCm39) T197A possibly damaging Het
Ylpm1 A G 12: 85,076,064 (GRCm39) M472V probably benign Het
Zfp647 G A 15: 76,796,285 (GRCm39) P125L probably damaging Het
Zfp677 A G 17: 21,617,918 (GRCm39) Y325C probably damaging Het
Zfyve1 A G 12: 83,605,478 (GRCm39) F407S 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
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'- GGCTGTGGCAGAAATGACTG -3'
(R):5'- AGATGAGATGCTCCTGGCTCTC -3'

Sequencing Primer
(F):5'- AGTTGGCATGGCGTCAC -3'
(R):5'- CACTTACGGTTTTCGCAGGATC -3'
Posted On 2017-06-26