Mutagenetix > Incidental Mutations

Incidental Mutation 'R7369:Apaf1'

572012

Institutional Source

Beutler Lab

Gene Symbol

Apaf1

Ensembl Gene

ENSMUSG00000019979

Gene Name

apoptotic peptidase activating factor 1

Synonyms

Apaf1l, 6230400I06Rik

MMRRC Submission

Accession Numbers

Is this an essential gene?

Essential (E-score: 1.000) question?

Stock #

R7369 (G1)

Quality Score

225.009

Status

Validated

Chromosome

Chromosomal Location

90989311-91082770 bp(-) (GRCm38)

Type of Mutation

missense

DNA Base Change (assembly)

A to G at 91001036 bp

Zygosity

Heterozygous

Amino Acid Change

Serine to Proline at position 1060 (S1060P)

Ref Sequence

ENSEMBL: ENSMUSP00000020157 (fasta)

Gene Model

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

Predicted Effect

probably damaging
Transcript: ENSMUST00000020157
AA Change: S1060P

PolyPhen 2 Score 0.974 (Sensitivity: 0.76; Specificity: 0.96)

SMART Domains

Protein: ENSMUSP00000020157
Gene: ENSMUSG00000019979
AA Change: S1060P

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: S1060P

PolyPhen 2 Score 0.974 (Sensitivity: 0.76; Specificity: 0.96)

SMART Domains

Protein: ENSMUSP00000125291
Gene: ENSMUSG00000019979
AA Change: S1060P

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: S1049P

PolyPhen 2 Score 0.974 (Sensitivity: 0.76; Specificity: 0.96)

SMART Domains

Protein: ENSMUSP00000124134
Gene: ENSMUSG00000019979
AA Change: S1049P

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: 99.8%
20x: 99.3%

Validation Efficiency

100% (77/77)

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: 75 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
4922502D21Rik	T	A	6: 129,331,533	Q11L	possibly damaging	Het
A930017K11Rik	G	A	17: 25,947,960	S201L	probably damaging	Het
Ahr	A	T	12: 35,504,660	W487R	possibly damaging	Het
Atf7	G	T	15: 102,553,809	P126H	probably damaging	Het
B3gnt5	C	A	16: 19,769,660	Q210K	probably benign	Het
Begain	T	C	12: 109,033,927	Y306C	possibly damaging	Het
Car5a	T	C	8: 121,923,834	K157R	probably benign	Het
Car5b	A	C	X: 164,014,840	S35R	probably benign	Het
Cdh6	A	G	15: 13,042,638	V478A	probably damaging	Het
Cdyl	A	G	13: 35,816,009	E91G	probably damaging	Het
Cep135	A	C	5: 76,593,253	K59Q	possibly damaging	Het
Cnot3	T	A	7: 3,653,331	D205E	possibly damaging	Het
Dgkd	G	A	1: 87,921,622	G379R	probably damaging	Het
Dppa1	T	A	11: 46,616,117		probably null	Het
Dsp	G	T	13: 38,197,525	V2749F	possibly damaging	Het
E2f4	A	G	8: 105,300,334	K177E	probably benign	Het
Efcab5	G	A	11: 77,117,835	P819L	possibly damaging	Het
Ercc5	T	A	1: 44,180,860	S1097R	probably benign	Het
Erp44	T	C	4: 48,218,183	N162S	probably benign	Het
Evl	A	G	12: 108,686,565	Y423C	unknown	Het
Fam78a	T	A	2: 32,069,687	N137I	probably damaging	Het
Fcrla	T	G	1: 170,922,317	D57A	probably benign	Het
Fcrls	T	C	3: 87,256,701	N374D	possibly damaging	Het
Gm7145	A	T	1: 117,986,108	H240L	probably benign	Het
Kdm5a	T	A	6: 120,432,004	N1549K	possibly damaging	Het
Kirrel	C	T	3: 87,141,084	R9H	probably benign	Het
Klf7	T	C	1: 64,121,141		probably null	Het
Lce1d	G	A	3: 92,686,083	Q8*	probably null	Het
Lcn4	T	C	2: 26,667,894	H180R	probably benign	Het
Lmntd1	T	A	6: 145,413,575	Y283F	probably damaging	Het
Lrp1b	C	T	2: 41,282,039	R1646K		Het
Map3k21	C	A	8: 125,911,116	A147E	possibly damaging	Het
Mapk8ip2	T	C	15: 89,454,251	S11P	probably benign	Het
Mdn1	T	A	4: 32,773,375	F5518L	probably damaging	Het
Mfsd7a	A	G	5: 108,445,528	V148A	probably benign	Het
Msh3	T	A	13: 92,299,262	T510S	probably benign	Het
Myh1	A	T	11: 67,220,698	Q1654H	probably damaging	Het
Ncbp3	T	C	11: 73,077,921	V506A	probably benign	Het
Nfkbiz	A	G	16: 55,821,846	S70P	probably damaging	Het
Nmi	T	C	2: 51,950,084	D215G	possibly damaging	Het
Nphp3	T	C	9: 104,018,250	S496P	probably damaging	Het
Nrp1	T	A	8: 128,431,915	C228S	probably damaging	Het
Olfr787	A	T	10: 129,463,521	M282L	probably benign	Het
Pcdh9	C	A	14: 93,886,367	R789L	possibly damaging	Het
Pigr	A	T	1: 130,841,766	T105S	probably benign	Het
Polr2a	A	C	11: 69,745,977	S383A	probably benign	Het
Psd3	T	A	8: 67,904,166	H634L	possibly damaging	Het
Ptgr2	T	G	12: 84,292,306		probably benign	Het
Ptk6	A	G	2: 181,198,461	Y251H	possibly damaging	Het
Rnf213	A	G	11: 119,430,468	T1251A		Het
Rtkn2	A	G	10: 68,041,429	K443E	probably damaging	Het
Rundc3a	T	A	11: 102,399,895	L268Q	probably damaging	Het
Serpinb5	A	G	1: 106,875,149	E138G	probably benign	Het
Shroom1	A	T	11: 53,465,248	D375V	probably benign	Het
Siglecf	A	G	7: 43,351,817	T70A	probably damaging	Het
Slc20a2	A	T	8: 22,561,400	E483V	probably benign	Het
Sort1	G	A	3: 108,351,680	G676D	probably damaging	Het
Spef2	T	C	15: 9,584,207	S1581G	probably benign	Het
Stx6	C	T	1: 155,197,384	R214*	probably null	Het
Stxbp5l	A	G	16: 37,134,341	I950T	probably benign	Het
Tdrd7	T	A	4: 46,013,239	C660S	possibly damaging	Het
Tgm4	T	A	9: 123,056,684		probably null	Het
Thap8	C	T	7: 30,289,952	L196F	unknown	Het
Tmem67	T	C	4: 12,053,535	Y671C	probably damaging	Het
Ttc6	A	T	12: 57,672,931		probably null	Het
Uba2	A	G	7: 34,150,814	S405P	possibly damaging	Het
Usp34	T	C	11: 23,432,361	I2043T		Het
Vmn1r12	T	A	6: 57,159,698	I260N	possibly damaging	Het
Vmn1r172	C	T	7: 23,660,605	T305I	unknown	Het
Vmn2r24	T	C	6: 123,815,679	V655A	probably damaging	Het
Wdr33	T	C	18: 31,886,666	S464P	probably benign	Het
Zcchc6	A	G	13: 59,782,053	I1458T	possibly damaging	Het
Zfp260	T	A	7: 30,105,325	C217S	probably damaging	Het
Zfp760	A	G	17: 21,723,233	E463G	probably benign	Het
Zhx1	A	G	15: 58,053,300	Y517H	probably damaging	Het

Other mutations in Apaf1

Allele	Source	Chr	Coord	Type	Predicted Effect	PPH Score
IGL00590:Apaf1	APN	10	91023788	missense	probably damaging	0.99
IGL00819:Apaf1	APN	10	90997340	splice site	probably null
IGL01481:Apaf1	APN	10	91031588	missense	possibly damaging	0.84
IGL01713:Apaf1	APN	10	91061832	splice site	probably benign
IGL01715:Apaf1	APN	10	91058354	missense	probably benign	0.20
IGL02152:Apaf1	APN	10	91061819	missense	probably benign	0.24
IGL02331:Apaf1	APN	10	91059619	missense	probably damaging	1.00
IGL03071:Apaf1	APN	10	90997255	missense	possibly damaging	0.88
IGL03101:Apaf1	APN	10	91031559	missense	possibly damaging	0.89
IGL03244:Apaf1	APN	10	91049349	splice site	probably benign
Mayhem	UTSW	10	90999719	missense	probably damaging	0.99
Wipeout	UTSW	10	91056000	missense	probably damaging	1.00
R0520:Apaf1	UTSW	10	91079989	missense	probably damaging	0.99
R0600:Apaf1	UTSW	10	91060052	missense	probably damaging	1.00
R0607:Apaf1	UTSW	10	91009203	missense	probably damaging	1.00
R0688:Apaf1	UTSW	10	91061705	missense	possibly damaging	0.94
R0734:Apaf1	UTSW	10	91037021	missense	probably benign	0.02
R1256:Apaf1	UTSW	10	91058406	missense	probably benign
R1459:Apaf1	UTSW	10	91062160	missense	probably benign	0.00
R1485:Apaf1	UTSW	10	91060243	missense	probably benign	0.02
R1511:Apaf1	UTSW	10	91060185	missense	possibly damaging	0.81
R1531:Apaf1	UTSW	10	91054521	missense	probably damaging	1.00
R1705:Apaf1	UTSW	10	91067271	splice site	probably benign
R1919:Apaf1	UTSW	10	91077614	nonsense	probably null
R1925:Apaf1	UTSW	10	90999719	missense	probably damaging	0.99
R2001:Apaf1	UTSW	10	91061814	missense	possibly damaging	0.94
R2002:Apaf1	UTSW	10	91061814	missense	possibly damaging	0.94
R2006:Apaf1	UTSW	10	91061772	missense	probably damaging	1.00
R2043:Apaf1	UTSW	10	91037028	missense	probably damaging	1.00
R2073:Apaf1	UTSW	10	91031694	nonsense	probably null
R2101:Apaf1	UTSW	10	91060080	missense	probably benign	0.26
R2130:Apaf1	UTSW	10	91060165	nonsense	probably null
R2153:Apaf1	UTSW	10	91048090	missense	probably damaging	1.00
R2377:Apaf1	UTSW	10	91079893	missense	possibly damaging	0.95
R2421:Apaf1	UTSW	10	91020723	missense	probably damaging	1.00
R3835:Apaf1	UTSW	10	91059587	missense	probably benign	0.07
R4750:Apaf1	UTSW	10	91060188	missense	probably damaging	1.00
R5100:Apaf1	UTSW	10	90997287	missense	probably benign
R5135:Apaf1	UTSW	10	91060094	missense	probably damaging	1.00
R5497:Apaf1	UTSW	10	90999656	missense	probably damaging	1.00
R5511:Apaf1	UTSW	10	91054392	missense	probably damaging	1.00
R5659:Apaf1	UTSW	10	91062153	nonsense	probably null
R5730:Apaf1	UTSW	10	91020771	missense	possibly damaging	0.62
R6176:Apaf1	UTSW	10	91059571	critical splice donor site	probably null
R6242:Apaf1	UTSW	10	91062163	missense	probably damaging	1.00
R6292:Apaf1	UTSW	10	90991563	missense	possibly damaging	0.86
R6376:Apaf1	UTSW	10	91023811	missense	probably damaging	1.00
R6534:Apaf1	UTSW	10	91056000	missense	probably damaging	1.00
R6975:Apaf1	UTSW	10	91020734	missense	probably damaging	0.97
R7218:Apaf1	UTSW	10	91037002	missense	probably damaging	1.00
R7409:Apaf1	UTSW	10	91067246	missense	probably damaging	1.00
R7413:Apaf1	UTSW	10	90995680	missense	probably benign	0.28
R7418:Apaf1	UTSW	10	91023835	missense	probably benign	0.09
R7423:Apaf1	UTSW	10	91059606	missense	probably damaging	1.00
R7488:Apaf1	UTSW	10	91054380	missense	probably benign	0.35
R7765:Apaf1	UTSW	10	91023782	missense	probably benign	0.34
R7913:Apaf1	UTSW	10	91060271	missense	probably damaging	0.99
R7914:Apaf1	UTSW	10	91060233	missense	probably damaging	1.00
R7922:Apaf1	UTSW	10	90999753	missense	probably benign
R8131:Apaf1	UTSW	10	91077558	missense	possibly damaging	0.93
R8158:Apaf1	UTSW	10	91059658	missense	probably benign	0.05

Predicted Primers

PCR Primer
(F):5'- ACTGCACGATCCGAATGTTTTC -3'
(R):5'- CCTTCTCTGTTTGAAACACTGTGAC -3'

Sequencing Primer
(F):5'- TCTGTGAGTTCAAGACCAGC -3'
(R):5'- ACACTGTGACAAGAATTAAGACTAC -3'

Posted On

2019-09-13