Mutagenetix > Incidental Mutation

Incidental Mutation 'R1511:Apaf1'

168340

Institutional Source

Beutler Lab

Gene Symbol

Apaf1

Ensembl Gene

ENSMUSG00000019979

Gene Name

apoptotic peptidase activating factor 1

Synonyms

Apaf1l, 6230400I06Rik

MMRRC Submission

039558-MU

Accession Numbers

Essential gene?

Essential (E-score: 1.000) question?

Stock #

R1511 (G1)

Quality Score

225

Status

Not validated

Chromosome

Chromosomal Location

90989311-91082770 bp(-) (GRCm38)

Type of Mutation

missense

DNA Base Change (assembly)

T to C at 91060185 bp (GRCm38)

Zygosity

Heterozygous

Amino Acid Change

Isoleucine to Valine at position 342 (I342V)

Ref Sequence

ENSEMBL: ENSMUSP00000124134 (fasta)

Gene Model

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

AlphaFold

O88879

Predicted Effect

possibly damaging
Transcript: ENSMUST00000020157
AA Change: I353V

PolyPhen 2 Score 0.808 (Sensitivity: 0.84; Specificity: 0.93)

SMART Domains

Protein: ENSMUSP00000020157
Gene: ENSMUSG00000019979
AA Change: I353V

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

possibly damaging
Transcript: ENSMUST00000159110
AA Change: I353V

PolyPhen 2 Score 0.808 (Sensitivity: 0.84; Specificity: 0.93)

SMART Domains

Protein: ENSMUSP00000125291
Gene: ENSMUSG00000019979
AA Change: I353V

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

possibly damaging
Transcript: ENSMUST00000162618
AA Change: I342V

PolyPhen 2 Score 0.808 (Sensitivity: 0.84; Specificity: 0.93)

SMART Domains

Protein: ENSMUSP00000124134
Gene: ENSMUSG00000019979
AA Change: I342V

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: 99.0%
3x: 98.0%
10x: 95.4%
20x: 89.7%

Validation Efficiency

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: 105 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
Aacs	C	A	5: 125,514,977	N576K	probably benign	Het
Abca5	T	A	11: 110,299,986	H766L	possibly damaging	Het
Abca5	G	T	11: 110,299,978	L769M	probably damaging	Het
Acvr1c	A	G	2: 58,287,884	I191T	probably damaging	Het
Agps	A	T	2: 75,866,779	E314D	probably damaging	Het
Agxt	G	A	1: 93,135,768	G131R	probably damaging	Het
Ak8	A	G	2: 28,742,746	T326A	probably benign	Het
Aldoart2	T	A	12: 55,566,277	I329N	probably benign	Het
Arhgap40	T	C	2: 158,527,161	S68P	probably benign	Het
Arsi	G	A	18: 60,916,651	G202E	probably benign	Het
AU022252	C	T	4: 119,228,097	R71Q	possibly damaging	Het
Baz1b	T	C	5: 135,217,782	L695P	probably damaging	Het
Baz2b	A	T	2: 59,962,024	S587T	probably benign	Het
Cep76	T	C	18: 67,624,958	M421V	probably benign	Het
Clk2	A	G	3: 89,168,703	D60G	probably damaging	Het
Clstn3	G	T	6: 124,462,169	T6K	probably damaging	Het
Cluap1	T	A	16: 3,919,558	D180E	probably benign	Het
Col12a1	T	C	9: 79,699,552	I530V	probably benign	Het
Cpt1a	T	C	19: 3,365,788		probably benign	Het
Cr2	T	G	1: 195,155,272	K797Q	possibly damaging	Het
Crybg3	C	A	16: 59,554,112	V2260L	probably benign	Het
Csnk1a1	T	A	18: 61,585,250		probably benign	Het
Cxcr1	T	C	1: 74,192,770	D31G	probably benign	Het
Cyp2a5	G	T	7: 26,835,936	D108Y	probably damaging	Het
Dnajc1	A	G	2: 18,222,727	V376A	possibly damaging	Het
Eif4enif1	T	C	11: 3,236,278	V462A	probably benign	Het
Elmo1	A	G	13: 20,290,477	K357R	possibly damaging	Het
Eml6	T	A	11: 29,818,374	H771L	probably damaging	Het
Epb41l4a	A	G	18: 33,832,664	I370T	probably benign	Het
Esp36	A	T	17: 38,417,281	N79K	possibly damaging	Het
Fam229b	A	G	10: 39,118,919	*81Q	probably null	Het
Fat4	T	C	3: 38,983,076	Y3626H	probably damaging	Het
Fbn1	A	T	2: 125,306,285	F2681Y	probably benign	Het
Gad1-ps	A	G	10: 99,445,469		noncoding transcript	Het
Galm	C	A	17: 80,183,267	N284K	probably damaging	Het
Gtf3c2	A	T	5: 31,159,102	S735T	probably benign	Het
Hsph1	A	T	5: 149,630,383	S207T	probably benign	Het
Il33	C	T	19: 29,955,215	R159C	probably damaging	Het
Invs	A	G	4: 48,382,148	N106S	possibly damaging	Het
Kif21b	G	T	1: 136,169,324		probably null	Het
Kirrel2	A	G	7: 30,456,498	C42R	probably damaging	Het
Letm1	A	C	5: 33,752,555	C378W	probably damaging	Het
Lrrc71	T	A	3: 87,745,484	K160N	probably benign	Het
Lrrtm3	A	G	10: 64,089,025	I121T	probably damaging	Het
Lztr1	T	A	16: 17,509,670	V79E	probably damaging	Het
Mmp8	T	G	9: 7,566,278	D378E	probably damaging	Het
Mpzl3	A	G	9: 45,066,529	E145G	probably damaging	Het
Mrps2	C	T	2: 28,469,664	L178F	probably damaging	Het
Mzb1	A	G	18: 35,647,822		probably null	Het
Nckap1	T	C	2: 80,553,415	D135G	probably damaging	Het
Ndst1	A	G	18: 60,697,170	F623L	possibly damaging	Het
Nlrp5	A	T	7: 23,413,347	D143V	probably damaging	Het
Olfr1225	A	G	2: 89,170,937	S92P	probably damaging	Het
Olfr1241	T	C	2: 89,482,248	M296V	probably null	Het
Olfr1311	A	G	2: 112,021,404	V150A	probably benign	Het
Olfr146	T	C	9: 39,019,025	D172G	probably benign	Het
Olfr307	T	C	7: 86,336,345	D17G	possibly damaging	Het
Olfr32	A	G	2: 90,138,404	V245A	probably benign	Het
Olfr548-ps1	T	C	7: 102,542,125	L63P	probably damaging	Het
Olfr907	A	G	9: 38,498,818	I50V	probably benign	Het
Parp14	T	G	16: 35,857,224	E791D	probably benign	Het
Pcdh8	C	T	14: 79,769,389	R578H	possibly damaging	Het
Phrf1	T	A	7: 141,259,801		probably benign	Het
Polr3b	C	A	10: 84,680,385	H626N	probably benign	Het
Ppp1r12a	A	G	10: 108,251,859	T58A	probably benign	Het
Ppp4r3b	T	A	11: 29,182,460	V33D	probably damaging	Het
Ppp5c	A	G	7: 17,009,982	Y176H	probably damaging	Het
R3hdm1	A	G	1: 128,197,005	Y343C	probably damaging	Het
Rabac1	C	T	7: 24,972,130	V122M	probably damaging	Het
Rasef	G	T	4: 73,735,748	Q561K	probably damaging	Het
Rbl1	A	G	2: 157,195,634	S198P	probably damaging	Het
Rbm12	A	T	2: 156,097,536	M272K	probably damaging	Het
Rexo1	T	G	10: 80,550,050	K391N	possibly damaging	Het
Rnf43	T	C	11: 87,731,347	S384P	probably benign	Het
Rpsa	A	T	9: 120,131,000	I210F	possibly damaging	Het
Rslcan18	A	G	13: 67,098,952	Y75H	possibly damaging	Het
Scn9a	T	A	2: 66,526,813	D1048V	probably benign	Het
Sec11a	T	C	7: 80,927,734		probably null	Het
Sidt2	A	G	9: 45,950,089	V19A	probably damaging	Het
Snx14	G	A	9: 88,398,364	Q522*	probably null	Het
Stx1b	A	G	7: 127,814,972	L74S	probably damaging	Het
Tm7sf3	A	T	6: 146,609,878	M371K	probably benign	Het
Tmem115	T	C	9: 107,534,975	V166A	probably benign	Het
Traf5	T	A	1: 191,999,951	T310S	probably benign	Het
Trdn	A	G	10: 33,466,452	K619E	probably benign	Het
Trmt10a	T	A	3: 138,152,184		probably null	Het
Txk	A	C	5: 72,707,671	I287R	probably damaging	Het
Txndc16	T	C	14: 45,151,887	D452G	probably damaging	Het
Ube2f	G	A	1: 91,262,301		probably null	Het
Ubtfl1	T	G	9: 18,410,193	I339R	probably benign	Het
Upf1	A	G	8: 70,338,505	I529T	probably damaging	Het
Vmn1r197	A	G	13: 22,328,653	D248G	possibly damaging	Het
Vmn1r5	A	T	6: 56,985,786	T149S	probably benign	Het
Vmn1r83	C	T	7: 12,321,270	V287I	possibly damaging	Het
Vmn2r118	G	A	17: 55,608,496	R485*	probably null	Het
Vmn2r-ps130	A	G	17: 23,063,801	T152A	probably benign	Het
Vps13b	T	C	15: 35,839,975	F2448L	probably damaging	Het
Vps13b	A	G	15: 35,841,573	N2583S	probably benign	Het
Wscd1	C	T	11: 71,788,675	P458L	probably damaging	Het
Xylt2	T	A	11: 94,670,433	D168V	probably damaging	Het
Zdhhc2	A	G	8: 40,467,972	T306A	probably benign	Het
Zfp804b	A	T	5: 6,769,771	D1097E	possibly damaging	Het
Zfp93	T	A	7: 24,275,731	C380*	probably null	Het
Zfp960	T	A	17: 17,088,256	C411S	probably damaging	Het
Zmynd15	T	A	11: 70,464,793	V430E	probably damaging	Het

Other mutations in Apaf1

Allele	Source	Chr	Coord	Type	Predicted Effect	PPH Score
IGL00590:Apaf1	APN	10	91,023,788 (GRCm38)	missense	probably damaging	0.99
IGL00819:Apaf1	APN	10	90,997,340 (GRCm38)	splice site	probably null
IGL01481:Apaf1	APN	10	91,031,588 (GRCm38)	missense	possibly damaging	0.84
IGL01713:Apaf1	APN	10	91,061,832 (GRCm38)	splice site	probably benign
IGL01715:Apaf1	APN	10	91,058,354 (GRCm38)	missense	probably benign	0.20
IGL02152:Apaf1	APN	10	91,061,819 (GRCm38)	missense	probably benign	0.24
IGL02331:Apaf1	APN	10	91,059,619 (GRCm38)	missense	probably damaging	1.00
IGL03071:Apaf1	APN	10	90,997,255 (GRCm38)	missense	possibly damaging	0.88
IGL03101:Apaf1	APN	10	91,031,559 (GRCm38)	missense	possibly damaging	0.89
IGL03244:Apaf1	APN	10	91,049,349 (GRCm38)	splice site	probably benign
Bedlam	UTSW	10	91,060,271 (GRCm38)	missense	probably damaging	0.99
Mayhem	UTSW	10	90,999,719 (GRCm38)	missense	probably damaging	0.99
Wipeout	UTSW	10	91,056,000 (GRCm38)	missense	probably damaging	1.00
R0520:Apaf1	UTSW	10	91,079,989 (GRCm38)	missense	probably damaging	0.99
R0600:Apaf1	UTSW	10	91,060,052 (GRCm38)	missense	probably damaging	1.00
R0607:Apaf1	UTSW	10	91,009,203 (GRCm38)	missense	probably damaging	1.00
R0688:Apaf1	UTSW	10	91,061,705 (GRCm38)	missense	possibly damaging	0.94
R0734:Apaf1	UTSW	10	91,037,021 (GRCm38)	missense	probably benign	0.02
R1256:Apaf1	UTSW	10	91,058,406 (GRCm38)	missense	probably benign
R1459:Apaf1	UTSW	10	91,062,160 (GRCm38)	missense	probably benign	0.00
R1485:Apaf1	UTSW	10	91,060,243 (GRCm38)	missense	probably benign	0.02
R1531:Apaf1	UTSW	10	91,054,521 (GRCm38)	missense	probably damaging	1.00
R1705:Apaf1	UTSW	10	91,067,271 (GRCm38)	splice site	probably benign
R1919:Apaf1	UTSW	10	91,077,614 (GRCm38)	nonsense	probably null
R1925:Apaf1	UTSW	10	90,999,719 (GRCm38)	missense	probably damaging	0.99
R2001:Apaf1	UTSW	10	91,061,814 (GRCm38)	missense	possibly damaging	0.94
R2002:Apaf1	UTSW	10	91,061,814 (GRCm38)	missense	possibly damaging	0.94
R2006:Apaf1	UTSW	10	91,061,772 (GRCm38)	missense	probably damaging	1.00
R2043:Apaf1	UTSW	10	91,037,028 (GRCm38)	missense	probably damaging	1.00
R2073:Apaf1	UTSW	10	91,031,694 (GRCm38)	nonsense	probably null
R2101:Apaf1	UTSW	10	91,060,080 (GRCm38)	missense	probably benign	0.26
R2130:Apaf1	UTSW	10	91,060,165 (GRCm38)	nonsense	probably null
R2153:Apaf1	UTSW	10	91,048,090 (GRCm38)	missense	probably damaging	1.00
R2377:Apaf1	UTSW	10	91,079,893 (GRCm38)	missense	possibly damaging	0.95
R2421:Apaf1	UTSW	10	91,020,723 (GRCm38)	missense	probably damaging	1.00
R3835:Apaf1	UTSW	10	91,059,587 (GRCm38)	missense	probably benign	0.07
R4750:Apaf1	UTSW	10	91,060,188 (GRCm38)	missense	probably damaging	1.00
R5100:Apaf1	UTSW	10	90,997,287 (GRCm38)	missense	probably benign
R5135:Apaf1	UTSW	10	91,060,094 (GRCm38)	missense	probably damaging	1.00
R5497:Apaf1	UTSW	10	90,999,656 (GRCm38)	missense	probably damaging	1.00
R5511:Apaf1	UTSW	10	91,054,392 (GRCm38)	missense	probably damaging	1.00
R5659:Apaf1	UTSW	10	91,062,153 (GRCm38)	nonsense	probably null
R5730:Apaf1	UTSW	10	91,020,771 (GRCm38)	missense	possibly damaging	0.62
R6176:Apaf1	UTSW	10	91,059,571 (GRCm38)	critical splice donor site	probably null
R6242:Apaf1	UTSW	10	91,062,163 (GRCm38)	missense	probably damaging	1.00
R6292:Apaf1	UTSW	10	90,991,563 (GRCm38)	missense	possibly damaging	0.86
R6376:Apaf1	UTSW	10	91,023,811 (GRCm38)	missense	probably damaging	1.00
R6534:Apaf1	UTSW	10	91,056,000 (GRCm38)	missense	probably damaging	1.00
R6975:Apaf1	UTSW	10	91,020,734 (GRCm38)	missense	probably damaging	0.97
R7218:Apaf1	UTSW	10	91,037,002 (GRCm38)	missense	probably damaging	1.00
R7369:Apaf1	UTSW	10	91,001,036 (GRCm38)	missense	probably damaging	0.97
R7409:Apaf1	UTSW	10	91,067,246 (GRCm38)	missense	probably damaging	1.00
R7413:Apaf1	UTSW	10	90,995,680 (GRCm38)	missense	probably benign	0.28
R7418:Apaf1	UTSW	10	91,023,835 (GRCm38)	missense	probably benign	0.09
R7423:Apaf1	UTSW	10	91,059,606 (GRCm38)	missense	probably damaging	1.00
R7488:Apaf1	UTSW	10	91,054,380 (GRCm38)	missense	probably benign	0.35
R7765:Apaf1	UTSW	10	91,023,782 (GRCm38)	missense	probably benign	0.34
R7913:Apaf1	UTSW	10	91,060,271 (GRCm38)	missense	probably damaging	0.99
R7914:Apaf1	UTSW	10	91,060,233 (GRCm38)	missense	probably damaging	1.00
R7922:Apaf1	UTSW	10	90,999,753 (GRCm38)	missense	probably benign
R8131:Apaf1	UTSW	10	91,077,558 (GRCm38)	missense	possibly damaging	0.93
R8158:Apaf1	UTSW	10	91,059,658 (GRCm38)	missense	probably benign	0.05
R8673:Apaf1	UTSW	10	90,995,668 (GRCm38)	missense	probably damaging	1.00
R8682:Apaf1	UTSW	10	90,995,670 (GRCm38)	missense	probably damaging	1.00
R8962:Apaf1	UTSW	10	91,067,204 (GRCm38)	missense	probably damaging	1.00
R9069:Apaf1	UTSW	10	91,023,718 (GRCm38)	critical splice donor site	probably null
R9200:Apaf1	UTSW	10	91,009,240 (GRCm38)	missense	probably benign	0.24
R9516:Apaf1	UTSW	10	91,079,954 (GRCm38)	missense	probably damaging	1.00
R9623:Apaf1	UTSW	10	91,077,601 (GRCm38)	nonsense	probably null

Predicted Primers

PCR Primer
(F):5'- TGCACATGCCATAAGGACCCAGTG -3'
(R):5'- GAGTATCTGCGAGTGAAAGCTGCC -3'

Sequencing Primer
(F):5'- TGCCATAAGGACCCAGTGATAAG -3'
(R):5'- ccttcatacactcataccccc -3'

Posted On

2014-04-13