Incidental Mutation 'R3835:Apaf1'
ID 275593
Institutional Source Beutler Lab
Gene Symbol Apaf1
Ensembl Gene ENSMUSG00000019979
Gene Name apoptotic peptidase activating factor 1
Synonyms 6230400I06Rik, Apaf1l
MMRRC Submission 040890-MU
Accession Numbers
Essential gene? Essential (E-score: 1.000) question?
Stock # R3835 (G1)
Quality Score 225
Status Validated
Chromosome 10
Chromosomal Location 90825173-90918632 bp(-) (GRCm39)
Type of Mutation missense
DNA Base Change (assembly) G to A at 90895449 bp (GRCm39)
Zygosity Heterozygous
Amino Acid Change Arginine to Cysteine at position 439 (R439C)
Ref Sequence ENSEMBL: ENSMUSP00000124134 (fasta)
Gene Model predicted gene model for transcript(s): [ENSMUST00000020157] [ENSMUST00000159110] [ENSMUST00000162618]
AlphaFold O88879
Predicted Effect probably benign
Transcript: ENSMUST00000020157
AA Change: R450C

PolyPhen 2 Score 0.074 (Sensitivity: 0.93; Specificity: 0.85)
SMART Domains Protein: ENSMUSP00000020157
Gene: ENSMUSG00000019979
AA Change: R450C

DomainStartEndE-ValueType
Pfam:CARD 6 90 7.3e-22 PFAM
Pfam:NB-ARC 129 414 1.7e-77 PFAM
WD40 604 643 1.35e-5 SMART
WD40 646 685 1.04e-11 SMART
WD40 688 729 2.98e-7 SMART
WD40 732 771 9.88e-13 SMART
WD40 780 825 1.28e1 SMART
WD40 828 868 1.43e0 SMART
WD40 871 910 3.24e-8 SMART
WD40 952 989 2.57e0 SMART
WD40 992 1031 1.09e-5 SMART
WD40 1033 1071 2.09e-2 SMART
WD40 1074 1113 2.93e-6 SMART
WD40 1116 1155 8.55e-8 SMART
WD40 1168 1204 4.55e-3 SMART
Blast:WD40 1207 1246 5e-18 BLAST
Predicted Effect probably benign
Transcript: ENSMUST00000159110
AA Change: R450C

PolyPhen 2 Score 0.074 (Sensitivity: 0.93; Specificity: 0.85)
SMART Domains Protein: ENSMUSP00000125291
Gene: ENSMUSG00000019979
AA Change: R450C

DomainStartEndE-ValueType
Pfam:CARD 6 90 7.4e-21 PFAM
Pfam:NB-ARC 129 414 6.9e-71 PFAM
WD40 604 643 1.35e-5 SMART
WD40 646 685 1.04e-11 SMART
WD40 688 729 2.98e-7 SMART
WD40 732 771 9.88e-13 SMART
WD40 780 825 1.28e1 SMART
WD40 828 868 1.43e0 SMART
WD40 871 910 3.24e-8 SMART
WD40 952 989 2.57e0 SMART
WD40 992 1031 1.09e-5 SMART
WD40 1033 1071 2.09e-2 SMART
WD40 1074 1113 2.93e-6 SMART
WD40 1116 1155 8.55e-8 SMART
WD40 1168 1204 4.55e-3 SMART
Blast:WD40 1207 1246 5e-18 BLAST
Predicted Effect probably benign
Transcript: ENSMUST00000162618
AA Change: R439C

PolyPhen 2 Score 0.074 (Sensitivity: 0.93; Specificity: 0.85)
SMART Domains Protein: ENSMUSP00000124134
Gene: ENSMUSG00000019979
AA Change: R439C

DomainStartEndE-ValueType
Pfam:CARD 6 90 1.1e-20 PFAM
Pfam:NB-ARC 118 403 8.8e-72 PFAM
WD40 593 632 1.35e-5 SMART
WD40 635 674 1.04e-11 SMART
WD40 677 718 2.98e-7 SMART
WD40 721 760 9.88e-13 SMART
WD40 769 814 1.28e1 SMART
WD40 817 857 1.43e0 SMART
WD40 860 899 3.24e-8 SMART
WD40 941 978 2.57e0 SMART
WD40 981 1020 1.09e-5 SMART
WD40 1022 1060 2.09e-2 SMART
WD40 1063 1102 2.93e-6 SMART
WD40 1105 1144 8.55e-8 SMART
WD40 1157 1193 4.55e-3 SMART
Blast:WD40 1196 1235 5e-18 BLAST
Meta Mutation Damage Score 0.0898 question?
Coding Region Coverage
  • 1x: 99.2%
  • 3x: 98.7%
  • 10x: 97.5%
  • 20x: 95.9%
Validation Efficiency 98% (43/44)
MGI Phenotype FUNCTION: [Summary is not available for the mouse gene. This summary is for the human ortholog.] This gene encodes a cytoplasmic protein that initiates apoptosis. This protein contains several copies of the WD-40 domain, a caspase recruitment domain (CARD), and an ATPase domain (NB-ARC). Upon binding cytochrome c and dATP, this protein forms an oligomeric apoptosome. The apoptosome binds and cleaves caspase 9 preproprotein, releasing its mature, activated form. Activated caspase 9 stimulates the subsequent caspase cascade that commits the cell to apoptosis. Alternative splicing results in several transcript variants encoding different isoforms. [provided by RefSeq, Jul 2008]
PHENOTYPE: Homozygotes for targeted null mutations have defects in apoptosis resulting in brain overgrowth, craniofacial defects, interdigit webbing and altered lens and retina. Most mutants die by embryonic day 16.5 or perinatally, and male survivors are sterile. [provided by MGI curators]
Allele List at MGI
Other mutations in this stock
Total: 44 list
GeneRefVarChr/LocMutationPredicted EffectZygosity
Adgrl4 T C 3: 151,216,254 (GRCm39) I479T probably damaging Het
Adh6a G A 3: 138,033,275 (GRCm39) probably null Het
Anapc7 A G 5: 122,581,940 (GRCm39) T528A possibly damaging Het
Ap5b1 A G 19: 5,618,918 (GRCm39) T113A possibly damaging Het
Apoa5 A T 9: 46,181,878 (GRCm39) H318L probably damaging Het
Bltp2 A G 11: 78,169,911 (GRCm39) R1545G probably benign Het
Btnl9 T G 11: 49,071,512 (GRCm39) T104P probably damaging Het
Cimip3 AC A 17: 47,744,348 (GRCm39) probably benign Het
Dennd5a T C 7: 109,533,449 (GRCm39) K107R probably benign Het
Dthd1 A T 5: 63,007,128 (GRCm39) R610W probably damaging Het
Eno1 T C 4: 150,331,119 (GRCm39) S186P probably benign Het
Gipc2 C A 3: 151,833,823 (GRCm39) V153F probably damaging Het
Gpt A G 15: 76,582,783 (GRCm39) Y295C probably damaging Het
Kcnh5 T A 12: 74,945,044 (GRCm39) Q735L probably benign Het
Lrrc10 A G 10: 116,881,691 (GRCm39) N122D possibly damaging Het
Lrrc37 C A 11: 103,510,836 (GRCm39) L377F unknown Het
Meis2 T C 2: 115,752,228 (GRCm39) H301R probably damaging Het
Muc5b A T 7: 141,412,918 (GRCm39) I1955F unknown Het
Nalcn A T 14: 123,530,834 (GRCm39) probably benign Het
Nmt2 T C 2: 3,315,723 (GRCm39) probably benign Het
Nnt C T 13: 119,509,031 (GRCm39) G403R probably damaging Het
Or4a79 T G 2: 89,551,799 (GRCm39) I219L possibly damaging Het
Or4d6 T A 19: 12,086,764 (GRCm39) I49F possibly damaging Het
Or5b109 A T 19: 13,212,103 (GRCm39) D163V probably benign Het
Ovgp1 A G 3: 105,893,631 (GRCm39) E468G probably benign Het
Pax6 G A 2: 105,526,795 (GRCm39) E234K probably benign Het
Prkdc A G 16: 15,609,810 (GRCm39) E3138G probably damaging Het
Prmt6 T C 3: 110,158,121 (GRCm39) D56G possibly damaging Het
Ptprt A G 2: 161,389,307 (GRCm39) V1261A probably damaging Het
Qtrt2 A G 16: 43,701,435 (GRCm39) S42P probably damaging Het
Rab9b C T X: 135,762,259 (GRCm39) R47Q possibly damaging Het
Rpgrip1 A G 14: 52,384,710 (GRCm39) E606G probably damaging Het
Setx C T 2: 29,035,072 (GRCm39) S519L possibly damaging Het
Slc15a2 A T 16: 36,592,490 (GRCm39) C191* probably null Het
Snrk T C 9: 121,966,069 (GRCm39) probably benign Het
St6galnac1 T C 11: 116,657,109 (GRCm39) D422G probably damaging Het
Stag1 C T 9: 100,620,035 (GRCm39) T46I probably damaging Het
Tagln T C 9: 45,843,008 (GRCm39) I18V probably benign Het
Tasor2 T C 13: 3,625,292 (GRCm39) T1553A probably benign Het
Tbx18 C A 9: 87,611,689 (GRCm39) A114S probably benign Het
Ttc16 T C 2: 32,659,322 (GRCm39) D259G probably damaging Het
Vldlr A G 19: 27,212,214 (GRCm39) D76G probably damaging Het
Vmn2r24 G T 6: 123,764,412 (GRCm39) D430Y probably benign Het
Xlr3a T C X: 72,138,644 (GRCm39) E5G probably damaging Het
Other mutations in Apaf1
AlleleSourceChrCoordTypePredicted EffectPPH Score
IGL00590:Apaf1 APN 10 90,859,650 (GRCm39) missense probably damaging 0.99
IGL00819:Apaf1 APN 10 90,833,202 (GRCm39) splice site probably null
IGL01481:Apaf1 APN 10 90,867,450 (GRCm39) missense possibly damaging 0.84
IGL01713:Apaf1 APN 10 90,897,694 (GRCm39) splice site probably benign
IGL01715:Apaf1 APN 10 90,894,216 (GRCm39) missense probably benign 0.20
IGL02152:Apaf1 APN 10 90,897,681 (GRCm39) missense probably benign 0.24
IGL02331:Apaf1 APN 10 90,895,481 (GRCm39) missense probably damaging 1.00
IGL03071:Apaf1 APN 10 90,833,117 (GRCm39) missense possibly damaging 0.88
IGL03101:Apaf1 APN 10 90,867,421 (GRCm39) missense possibly damaging 0.89
IGL03244:Apaf1 APN 10 90,885,211 (GRCm39) splice site probably benign
Bedlam UTSW 10 90,896,133 (GRCm39) missense probably damaging 0.99
Mayhem UTSW 10 90,835,581 (GRCm39) missense probably damaging 0.99
Wipeout UTSW 10 90,891,862 (GRCm39) missense probably damaging 1.00
R0520:Apaf1 UTSW 10 90,915,851 (GRCm39) missense probably damaging 0.99
R0600:Apaf1 UTSW 10 90,895,914 (GRCm39) missense probably damaging 1.00
R0607:Apaf1 UTSW 10 90,845,065 (GRCm39) missense probably damaging 1.00
R0688:Apaf1 UTSW 10 90,897,567 (GRCm39) missense possibly damaging 0.94
R0734:Apaf1 UTSW 10 90,872,883 (GRCm39) missense probably benign 0.02
R1256:Apaf1 UTSW 10 90,894,268 (GRCm39) missense probably benign
R1459:Apaf1 UTSW 10 90,898,022 (GRCm39) missense probably benign 0.00
R1485:Apaf1 UTSW 10 90,896,105 (GRCm39) missense probably benign 0.02
R1511:Apaf1 UTSW 10 90,896,047 (GRCm39) missense possibly damaging 0.81
R1531:Apaf1 UTSW 10 90,890,383 (GRCm39) missense probably damaging 1.00
R1705:Apaf1 UTSW 10 90,903,133 (GRCm39) splice site probably benign
R1919:Apaf1 UTSW 10 90,913,476 (GRCm39) nonsense probably null
R1925:Apaf1 UTSW 10 90,835,581 (GRCm39) missense probably damaging 0.99
R2001:Apaf1 UTSW 10 90,897,676 (GRCm39) missense possibly damaging 0.94
R2002:Apaf1 UTSW 10 90,897,676 (GRCm39) missense possibly damaging 0.94
R2006:Apaf1 UTSW 10 90,897,634 (GRCm39) missense probably damaging 1.00
R2043:Apaf1 UTSW 10 90,872,890 (GRCm39) missense probably damaging 1.00
R2073:Apaf1 UTSW 10 90,867,556 (GRCm39) nonsense probably null
R2101:Apaf1 UTSW 10 90,895,942 (GRCm39) missense probably benign 0.26
R2130:Apaf1 UTSW 10 90,896,027 (GRCm39) nonsense probably null
R2153:Apaf1 UTSW 10 90,883,952 (GRCm39) missense probably damaging 1.00
R2377:Apaf1 UTSW 10 90,915,755 (GRCm39) missense possibly damaging 0.95
R2421:Apaf1 UTSW 10 90,856,585 (GRCm39) missense probably damaging 1.00
R4750:Apaf1 UTSW 10 90,896,050 (GRCm39) missense probably damaging 1.00
R5100:Apaf1 UTSW 10 90,833,149 (GRCm39) missense probably benign
R5135:Apaf1 UTSW 10 90,895,956 (GRCm39) missense probably damaging 1.00
R5497:Apaf1 UTSW 10 90,835,518 (GRCm39) missense probably damaging 1.00
R5511:Apaf1 UTSW 10 90,890,254 (GRCm39) missense probably damaging 1.00
R5659:Apaf1 UTSW 10 90,898,015 (GRCm39) nonsense probably null
R5730:Apaf1 UTSW 10 90,856,633 (GRCm39) missense possibly damaging 0.62
R6176:Apaf1 UTSW 10 90,895,433 (GRCm39) critical splice donor site probably null
R6242:Apaf1 UTSW 10 90,898,025 (GRCm39) missense probably damaging 1.00
R6292:Apaf1 UTSW 10 90,827,425 (GRCm39) missense possibly damaging 0.86
R6376:Apaf1 UTSW 10 90,859,673 (GRCm39) missense probably damaging 1.00
R6534:Apaf1 UTSW 10 90,891,862 (GRCm39) missense probably damaging 1.00
R6975:Apaf1 UTSW 10 90,856,596 (GRCm39) missense probably damaging 0.97
R7218:Apaf1 UTSW 10 90,872,864 (GRCm39) missense probably damaging 1.00
R7369:Apaf1 UTSW 10 90,836,898 (GRCm39) missense probably damaging 0.97
R7409:Apaf1 UTSW 10 90,903,108 (GRCm39) missense probably damaging 1.00
R7413:Apaf1 UTSW 10 90,831,542 (GRCm39) missense probably benign 0.28
R7418:Apaf1 UTSW 10 90,859,697 (GRCm39) missense probably benign 0.09
R7423:Apaf1 UTSW 10 90,895,468 (GRCm39) missense probably damaging 1.00
R7488:Apaf1 UTSW 10 90,890,242 (GRCm39) missense probably benign 0.35
R7765:Apaf1 UTSW 10 90,859,644 (GRCm39) missense probably benign 0.34
R7913:Apaf1 UTSW 10 90,896,133 (GRCm39) missense probably damaging 0.99
R7914:Apaf1 UTSW 10 90,896,095 (GRCm39) missense probably damaging 1.00
R7922:Apaf1 UTSW 10 90,835,615 (GRCm39) missense probably benign
R8131:Apaf1 UTSW 10 90,913,420 (GRCm39) missense possibly damaging 0.93
R8158:Apaf1 UTSW 10 90,895,520 (GRCm39) missense probably benign 0.05
R8673:Apaf1 UTSW 10 90,831,530 (GRCm39) missense probably damaging 1.00
R8682:Apaf1 UTSW 10 90,831,532 (GRCm39) missense probably damaging 1.00
R8962:Apaf1 UTSW 10 90,903,066 (GRCm39) missense probably damaging 1.00
R9069:Apaf1 UTSW 10 90,859,580 (GRCm39) critical splice donor site probably null
R9200:Apaf1 UTSW 10 90,845,102 (GRCm39) missense probably benign 0.24
R9516:Apaf1 UTSW 10 90,915,816 (GRCm39) missense probably damaging 1.00
R9623:Apaf1 UTSW 10 90,913,463 (GRCm39) nonsense probably null
Predicted Primers PCR Primer
(F):5'- AGTGCCATCTCTCCAGCC -3'
(R):5'- ATGGTCTGCTAAATGCTAGGTG -3'

Sequencing Primer
(F):5'- TGGAACTCACTCTGTAGACCAGG -3'
(R):5'- CTGCTAAATGCTAGGTGTTGTGC -3'
Posted On 2015-04-06