Mutagenetix > Incidental Mutations

Incidental Mutation 'R0520:Apaf1'

48465

Institutional Source

Beutler Lab

Gene Symbol

Apaf1

Ensembl Gene

ENSMUSG00000019979

Gene Name

apoptotic peptidase activating factor 1

Synonyms

Apaf1l, 6230400I06Rik

MMRRC Submission

038713-MU

Accession Numbers

Is this an essential gene?

Essential (E-score: 1.000) question?

Stock #

R0520 (G1)

Quality Score

225

Status

Validated

Chromosome

Chromosomal Location

90989311-91082770 bp(-) (GRCm38)

Type of Mutation

missense

DNA Base Change (assembly)

A to T at 91079989 bp

Zygosity

Heterozygous

Amino Acid Change

Histidine to Glutamine at position 12 (H12Q)

Ref Sequence

ENSEMBL: ENSMUSP00000124422 (fasta)

Gene Model

predicted gene model for transcript(s): [ENSMUST00000020149] [ENSMUST00000020150] [ENSMUST00000020157] [ENSMUST00000159110] [ENSMUST00000160788] [ENSMUST00000161987] [ENSMUST00000162618]

Predicted Effect

probably benign
Transcript: ENSMUST00000020149

SMART Domains

Protein: ENSMUSP00000020149
Gene: ENSMUSG00000019975

Domain	Start	End	E-Value	Type
low complexity region	42	58	N/A	INTRINSIC
coiled coil region	80	154	N/A	INTRINSIC
coiled coil region	175	257	N/A	INTRINSIC

Predicted Effect

probably benign
Transcript: ENSMUST00000020150

SMART Domains

Protein: ENSMUSP00000020150
Gene: ENSMUSG00000019975

Domain	Start	End	E-Value	Type
low complexity region	42	58	N/A	INTRINSIC
coiled coil region	89	109	N/A	INTRINSIC
coiled coil region	234	261	N/A	INTRINSIC

Predicted Effect

possibly damaging
Transcript: ENSMUST00000020157
AA Change: H12Q

PolyPhen 2 Score 0.731 (Sensitivity: 0.86; Specificity: 0.92)

SMART Domains

Protein: ENSMUSP00000020157
Gene: ENSMUSG00000019979
AA Change: H12Q

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

noncoding transcript
Transcript: ENSMUST00000128371

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000135152

Predicted Effect

possibly damaging
Transcript: ENSMUST00000159110
AA Change: H12Q

PolyPhen 2 Score 0.731 (Sensitivity: 0.86; Specificity: 0.92)

SMART Domains

Protein: ENSMUSP00000125291
Gene: ENSMUSG00000019979
AA Change: H12Q

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: ENSMUST00000160788
AA Change: H12Q

PolyPhen 2 Score 0.986 (Sensitivity: 0.74; Specificity: 0.96)

SMART Domains

Protein: ENSMUSP00000124968
Gene: ENSMUSG00000019979
AA Change: H12Q

Domain	Start	End	E-Value	Type
Pfam:CARD	6	90	1e-21	PFAM
Pfam:NB-ARC	129	238	6.9e-24	PFAM

Predicted Effect

probably damaging
Transcript: ENSMUST00000161987
AA Change: H12Q

PolyPhen 2 Score 0.986 (Sensitivity: 0.74; Specificity: 0.96)

SMART Domains

Protein: ENSMUSP00000124422
Gene: ENSMUSG00000019979
AA Change: H12Q

Domain	Start	End	E-Value	Type
Pfam:CARD	6	90	1e-21	PFAM
Pfam:NB-ARC	129	238	6.9e-24	PFAM

Predicted Effect

possibly damaging
Transcript: ENSMUST00000162618
AA Change: H12Q

PolyPhen 2 Score 0.517 (Sensitivity: 0.88; Specificity: 0.90)

SMART Domains

Protein: ENSMUSP00000124134
Gene: ENSMUSG00000019979
AA Change: H12Q

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

Meta Mutation Damage Score

0.1662

Coding Region Coverage

1x: 99.2%
3x: 98.5%
10x: 96.8%
20x: 94.2%

Validation Efficiency

100% (72/72)

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: 71 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
2010005H15Rik	A	G	16: 36,253,091	I16V	probably benign	Het
Acod1	T	C	14: 103,051,516	I154T	possibly damaging	Het
Acr	G	T	15: 89,573,227	C226F	probably damaging	Het
Aff1	C	T	5: 103,847,751	R1070*	probably null	Het
Aldh9a1	C	T	1: 167,361,391		probably benign	Het
Asic1	A	T	15: 99,695,535	I291F	probably damaging	Het
Aspm	T	A	1: 139,478,820	M1815K	possibly damaging	Het
Asxl3	A	T	18: 22,522,986	D1351V	probably damaging	Het
Atg9a	C	T	1: 75,186,534	W299*	probably null	Het
B3gntl1	C	A	11: 121,623,488	V313F	possibly damaging	Het
B4galnt4	T	A	7: 141,067,373	C345*	probably null	Het
Bicc1	A	T	10: 70,957,190	F211L	probably damaging	Het
Cachd1	T	G	4: 100,897,703	V117G	probably damaging	Het
Cdc16	G	A	8: 13,760,569		probably null	Het
Cers6	C	T	2: 69,105,091	Q312*	probably null	Het
Dclre1c	A	G	2: 3,436,475	H115R	probably damaging	Het
Ddx20	T	C	3: 105,687,376	T18A	probably benign	Het
Dhx57	A	G	17: 80,258,175	V816A	possibly damaging	Het
Dlgap1	C	T	17: 70,516,994	Q325*	probably null	Het
Dnaja1	A	T	4: 40,728,072	M178L	probably benign	Het
Ecd	A	T	14: 20,328,664	S454T	probably benign	Het
Efcab6	G	A	15: 83,950,046	H454Y	probably benign	Het
Exo1	T	A	1: 175,899,465	D447E	probably benign	Het
F5	T	G	1: 164,209,587	I1965S	probably benign	Het
Fbn2	A	G	18: 58,013,749	C2692R	probably damaging	Het
Fggy	T	A	4: 95,601,103	L152Q	probably damaging	Het
Glb1	ACCC	ACC	9: 114,421,744		probably null	Het
Gm9871	A	G	6: 101,801,579		noncoding transcript	Het
Gnai2	A	T	9: 107,620,173	D7E	probably benign	Het
Gon7	C	T	12: 102,757,788		probably benign	Het
H2-K1	A	T	17: 33,997,416	V272E	probably damaging	Het
Hectd4	G	T	5: 121,331,707	R2555L	possibly damaging	Het
Hexb	T	C	13: 97,181,110	R360G	probably benign	Het
Igsf9b	C	A	9: 27,323,250	S470R	probably benign	Het
Inpp5d	T	C	1: 87,705,920		probably benign	Het
Inpp5k	C	A	11: 75,639,530	Y265*	probably null	Het
Klhl33	T	G	14: 50,891,683	E436D	probably damaging	Het
Krt80	A	G	15: 101,370,017	L13P	probably benign	Het
Krtap19-2	C	T	16: 88,873,861		probably benign	Het
March10	T	C	11: 105,389,882	T526A	probably benign	Het
Mcrs1	A	G	15: 99,248,455		probably null	Het
Msh2	G	T	17: 87,717,544	V617F	possibly damaging	Het
Nckap1	A	C	2: 80,541,530		probably benign	Het
Nek4	T	A	14: 30,959,306		probably benign	Het
Olfr1054	G	T	2: 86,333,131	T75K	probably damaging	Het
Olfr1410	T	A	1: 92,608,749	V304E	probably damaging	Het
Olfr871	G	A	9: 20,212,495	V49I	probably benign	Het
Olfr875	T	C	9: 37,773,553	V298A	probably benign	Het
Osgin1	A	G	8: 119,442,508	H48R	probably damaging	Het
Pam	T	A	1: 97,884,195	T369S	probably benign	Het
Pclo	C	T	5: 14,713,830	Q821*	probably null	Het
Plekhm1	T	C	11: 103,394,944	I222V	probably benign	Het
Ptprg	T	G	14: 12,199,783	N65K	possibly damaging	Het
Pum2	T	A	12: 8,721,710	V351E	probably damaging	Het
Slc25a54	T	A	3: 109,107,230		probably benign	Het
Smchd1	A	T	17: 71,429,543	D587E	possibly damaging	Het
Stap1	A	G	5: 86,090,964	M164V	probably benign	Het
Stat5a	T	C	11: 100,861,426	V30A	probably damaging	Het
Stk36	T	G	1: 74,602,206		probably benign	Het
Tiam1	G	T	16: 89,817,951		probably benign	Het
Tmc5	T	C	7: 118,666,576	M553T	probably damaging	Het
Tmem14a	T	A	1: 21,229,412	Y89N	possibly damaging	Het
Tpp2	A	G	1: 43,990,530	Y991C	probably damaging	Het
Ttc7	A	G	17: 87,359,151	K615E	possibly damaging	Het
Ubac2	C	T	14: 121,994,342	P227S	probably damaging	Het
Vit	A	C	17: 78,625,159	K565T	probably damaging	Het
Vps13c	T	C	9: 67,945,851	F2409L	possibly damaging	Het
Wdr64	A	G	1: 175,726,392	T173A	probably damaging	Het
Zfp759	T	C	13: 67,137,355	I60T	probably benign	Het
Zfp81	A	G	17: 33,334,377	S488P	probably damaging	Het
Zic2	CCCACCACCACCATCACCACCACCACC	CCCACCATCACCACCACCACC	14: 122,476,364		probably benign	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
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
R7369:Apaf1	UTSW	10	91001036	missense	probably damaging	0.97
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

Predicted Primers

PCR Primer
(F):5'- AGAACGAACAGGCGAATATGTCTGC -3'
(R):5'- TGAAGTTACACATCCGGCGCTCAC -3'

Sequencing Primer
(F):5'- aattcaattcccagcaaccac -3'
(R):5'- GCGCTCACACATCCTGTTG -3'

Posted On

2013-06-12