Mutagenetix > Incidental Mutation

Incidental Mutation 'R7423:Apaf1'

575842

Institutional Source

Beutler Lab

Gene Symbol

Apaf1

Ensembl Gene

ENSMUSG00000019979

Gene Name

apoptotic peptidase activating factor 1

Synonyms

6230400I06Rik, Apaf1l

MMRRC Submission

045501-MU

Accession Numbers

Essential gene?

Essential (E-score: 1.000) question?

Stock #

R7423 (G1)

Quality Score

225.009

Status

Validated

Chromosome

Chromosomal Location

90825173-90918632 bp(-) (GRCm39)

Type of Mutation

missense

DNA Base Change (assembly)

A to T at 90895468 bp (GRCm39)

Zygosity

Heterozygous

Amino Acid Change

Aspartic acid to Glutamic Acid at position 443 (D443E)

Ref Sequence

ENSEMBL: ENSMUSP00000020157 (fasta)

Gene Model

predicted gene model for transcript(s): [ENSMUST00000020157] [ENSMUST00000159110] [ENSMUST00000162618]

AlphaFold

O88879

Predicted Effect

probably damaging
Transcript: ENSMUST00000020157
AA Change: D443E

PolyPhen 2 Score 0.997 (Sensitivity: 0.41; Specificity: 0.98)

SMART Domains

Protein: ENSMUSP00000020157
Gene: ENSMUSG00000019979
AA Change: D443E

Domain	Start	End	E-Value	Type
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 damaging
Transcript: ENSMUST00000159110
AA Change: D443E

PolyPhen 2 Score 0.997 (Sensitivity: 0.41; Specificity: 0.98)

SMART Domains

Protein: ENSMUSP00000125291
Gene: ENSMUSG00000019979
AA Change: D443E

Domain	Start	End	E-Value	Type
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 damaging
Transcript: ENSMUST00000162618
AA Change: D432E

PolyPhen 2 Score 0.988 (Sensitivity: 0.73; Specificity: 0.96)

SMART Domains

Protein: ENSMUSP00000124134
Gene: ENSMUSG00000019979
AA Change: D432E

Domain	Start	End	E-Value	Type
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

Coding Region Coverage

1x: 100.0%
3x: 100.0%
10x: 99.7%
20x: 98.8%

Validation Efficiency

96% (91/95)

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: 93 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
Acsbg2	A	T	17: 57,175,257 (GRCm39)	M85K	probably benign	Het
Actn4	C	T	7: 28,593,680 (GRCm39)	A905T	probably damaging	Het
Aff1	T	A	5: 103,994,967 (GRCm39)	V1055D	probably damaging	Het
Aox3	A	G	1: 58,160,228 (GRCm39)	E137G	possibly damaging	Het
Arl5b	C	A	2: 15,072,983 (GRCm39)	A28E	probably damaging	Het
Atg16l1	T	C	1: 87,714,023 (GRCm39)	V478A	probably damaging	Het
Atp6v1f	G	C	6: 29,468,105 (GRCm39)	E13Q	probably null	Het
Atpaf1	A	T	4: 115,647,827 (GRCm39)	K162M	probably damaging	Het
C3	A	T	17: 57,521,767 (GRCm39)	L1100Q	probably damaging	Het
Ccr1	A	G	9: 123,764,422 (GRCm39)	L36P	probably damaging	Het
Cct3	T	C	3: 88,216,503 (GRCm39)	L153S	probably benign	Het
Chd4	A	G	6: 125,105,822 (GRCm39)	D1813G	possibly damaging	Het
Chrm3	T	C	13: 9,928,845 (GRCm39)	I64V	probably benign	Het
Cnot2	A	T	10: 116,328,303 (GRCm39)	V477E	probably damaging	Het
Csf2rb2	T	A	15: 78,176,760 (GRCm39)	I211F	possibly damaging	Het
Dnah8	T	C	17: 30,923,743 (GRCm39)	L1237P	possibly damaging	Het
Dnttip2	T	C	3: 122,069,175 (GRCm39)	V130A	probably benign	Het
Dock10	G	A	1: 80,501,497 (GRCm39)	A1852V	possibly damaging	Het
Dock3	A	G	9: 106,844,370 (GRCm39)	V910A	probably damaging	Het
Drgx	A	G	14: 32,350,778 (GRCm39)	S205G	probably damaging	Het
Fbrs	G	A	7: 127,088,633 (GRCm39)	W738*	probably null	Het
Fmnl3	T	A	15: 99,227,281 (GRCm39)	D162V	probably damaging	Het
Fosl2	A	G	5: 32,307,807 (GRCm39)	R133G	probably damaging	Het
Frmpd1	A	G	4: 45,256,948 (GRCm39)	Q172R	probably damaging	Het
Fsd1l	A	T	4: 53,686,406 (GRCm39)	D273V	probably damaging	Het
Fstl4	T	A	11: 52,959,382 (GRCm39)	M141K	possibly damaging	Het
Gcfc2	A	G	6: 81,923,541 (GRCm39)	D535G	probably damaging	Het
Gm19410	A	C	8: 36,271,761 (GRCm39)	D1277A	probably benign	Het
Gnmt	T	A	17: 47,037,066 (GRCm39)	N211Y	probably damaging	Het
Hic2	A	G	16: 17,075,993 (GRCm39)	D274G	probably damaging	Het
Hnrnpu	A	G	1: 178,156,849 (GRCm39)		probably benign	Het
Icam5	T	C	9: 20,948,201 (GRCm39)	S670P	probably benign	Het
Ighv5-4	A	T	12: 113,561,120 (GRCm39)	L100Q	probably damaging	Het
Il17rb	A	T	14: 29,719,072 (GRCm39)	S337T	probably damaging	Het
Inf2	G	T	12: 112,576,172 (GRCm39)	R883L	unknown	Het
Inhbc	C	T	10: 127,193,275 (GRCm39)	C247Y	probably damaging	Het
Ints4	A	G	7: 97,156,926 (GRCm39)	K333E	probably damaging	Het
Iyd	A	T	10: 3,497,088 (GRCm39)	I148F	probably damaging	Het
Klk1b26	A	T	7: 43,664,193 (GRCm39)	D16V	probably damaging	Het
Krt15	A	T	11: 100,026,386 (GRCm39)	V100E	possibly damaging	Het
Lama2	A	T	10: 27,088,222 (GRCm39)	S852T	probably benign	Het
Mbtd1	A	G	11: 93,834,622 (GRCm39)	E600G	probably benign	Het
Mfap3	T	G	11: 57,420,329 (GRCm39)	N103K	probably damaging	Het
Mtor	G	A	4: 148,640,801 (GRCm39)	E2536K	possibly damaging	Het
Mug2	G	A	6: 122,056,685 (GRCm39)	S1210N	probably benign	Het
Nat8	G	A	6: 85,807,477 (GRCm39)	L219F	probably benign	Het
Nisch	A	G	14: 30,893,658 (GRCm39)	V1305A	probably benign	Het
Nup153	A	T	13: 46,850,120 (GRCm39)		probably null	Het
Or3a1b	G	A	11: 74,012,811 (GRCm39)	R232H	probably benign	Het
Otud6b	A	T	4: 14,825,858 (GRCm39)		probably null	Het
Pbld2	A	G	10: 62,883,783 (GRCm39)	T83A	probably damaging	Het
Pcx	A	T	19: 4,671,206 (GRCm39)	M1144L	probably benign	Het
Pdpk1	C	A	17: 24,329,874 (GRCm39)	R81L	probably benign	Het
Pik3cd	A	T	4: 149,736,220 (GRCm39)		probably null	Het
Plch2	A	C	4: 155,068,194 (GRCm39)	D1477E	probably damaging	Het
Plek2	A	G	12: 78,946,884 (GRCm39)	I51T	probably damaging	Het
Plekhn1	A	G	4: 156,315,142 (GRCm39)	V505A	probably benign	Het
Pofut2	T	C	10: 77,098,273 (GRCm39)	S129P	possibly damaging	Het
Prdx5	C	A	19: 6,887,370 (GRCm39)		probably benign	Het
Proca1	G	T	11: 78,085,643 (GRCm39)		probably benign	Het
Ptprs	A	C	17: 56,721,793 (GRCm39)	Y1752D	probably damaging	Het
Pum1	G	A	4: 130,501,856 (GRCm39)	V1127M	probably damaging	Het
Ralbp1	T	C	17: 66,165,976 (GRCm39)	R403G	probably damaging	Het
Reps1	A	T	10: 17,969,635 (GRCm39)	H246L	possibly damaging	Het
Rps6kc1	A	C	1: 190,531,293 (GRCm39)	M903R	probably damaging	Het
Rubcnl	A	G	14: 75,287,083 (GRCm39)	T584A	probably benign	Het
Samd9l	A	T	6: 3,374,408 (GRCm39)	V951E	probably damaging	Het
Sbf2	A	G	7: 110,038,055 (GRCm39)	F463L	possibly damaging	Het
Sdr16c6	G	A	4: 4,076,921 (GRCm39)		probably benign	Het
Shoc1	A	T	4: 59,076,264 (GRCm39)	S560T	probably benign	Het
Slc26a8	A	G	17: 28,867,177 (GRCm39)	I548T	probably benign	Het
Slc2a13	T	A	15: 91,456,883 (GRCm39)	I140F	probably damaging	Het
Smtn	A	T	11: 3,481,200 (GRCm39)		probably null	Het
Sobp	G	T	10: 42,898,564 (GRCm39)	C340*	probably null	Het
Sox6	A	T	7: 115,149,258 (GRCm39)	V413E	probably benign	Het
Spin1	T	C	13: 51,277,326 (GRCm39)		probably null	Het
Sra1	T	C	18: 36,800,536 (GRCm39)	T224A	probably benign	Het
Sv2c	A	T	13: 96,185,056 (GRCm39)	F207Y	probably benign	Het
Tcp10c	T	A	17: 13,581,503 (GRCm39)		probably null	Het
Tkt	G	A	14: 30,292,992 (GRCm39)	G490S	possibly damaging	Het
Tpgs1	G	T	10: 79,511,655 (GRCm39)	A266S	probably damaging	Het
Tprg1	T	G	16: 25,241,003 (GRCm39)	S260A	probably damaging	Het
Trdv2-1	T	A	14: 54,183,935 (GRCm39)	W56R	probably damaging	Het
Trgv6	G	T	13: 19,374,814 (GRCm39)	G40W	possibly damaging	Het
Trpc4	T	A	3: 54,225,450 (GRCm39)	V933E	probably benign	Het
Ulk4	A	T	9: 120,932,687 (GRCm39)	M1051K	possibly damaging	Het
Unc119b	A	G	5: 115,272,743 (GRCm39)	L76P	probably damaging	Het
Vmn2r15	G	A	5: 109,445,394 (GRCm39)	S10F	probably benign	Het
Vwce	A	G	19: 10,641,704 (GRCm39)	E810G	probably benign	Het
Wdr7	T	A	18: 63,910,451 (GRCm39)		probably null	Het
Wnk2	T	A	13: 49,191,608 (GRCm39)	E1283V	probably benign	Het
Zfp28	T	C	7: 6,396,956 (GRCm39)	C464R	probably damaging	Het
Zpld1	C	T	16: 55,054,027 (GRCm39)	C255Y	probably damaging	Het

Other mutations in Apaf1

Allele	Source	Chr	Coord	Type	Predicted Effect	PPH 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
R3835:Apaf1	UTSW	10	90,895,449 (GRCm39)	missense	probably benign	0.07
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
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'- ACTTACTGCTCATTGTCCTTTTATGG -3'

Sequencing Primer
(F):5'- TGGAACTCACTCTGTAGACCAGG -3'
(R):5'- CCTTTTATGGTCTGCTAAATGCTAG -3'

Posted On

2019-10-07