Mutagenetix > Incidental Mutation

Incidental Mutation 'R4849:App'

373425

Institutional Source

Beutler Lab

Gene Symbol

App

Ensembl Gene

ENSMUSG00000022892

Gene Name

amyloid beta precursor protein

Synonyms

E030013M08Rik, Adap, betaAPP, Abeta, appican, protease nexin II, Cvap

MMRRC Submission

042461-MU

Accession Numbers

Essential gene?

Possibly essential (E-score: 0.557) question?

Stock #

R4849 (G1)

Quality Score

225

Status

Validated

Chromosome

Chromosomal Location

84751236-84972187 bp(-) (GRCm39)

Type of Mutation

missense

DNA Base Change (assembly)

T to C at 84853322 bp (GRCm39)

Zygosity

Heterozygous

Amino Acid Change

Aspartic acid to Glycine at position 252 (D252G)

Ref Sequence

ENSEMBL: ENSMUSP00000154401 (fasta)

Gene Model

predicted gene model for transcript(s): [ENSMUST00000005406] [ENSMUST00000226232] [ENSMUST00000226801] [ENSMUST00000227021] [ENSMUST00000227723] [ENSMUST00000227737]

AlphaFold

P12023

Predicted Effect

unknown
Transcript: ENSMUST00000005406
AA Change: D252G

SMART Domains

Protein: ENSMUSP00000005406
Gene: ENSMUSG00000022892
AA Change: D252G

Domain	Start	End	E-Value	Type
signal peptide	1	17	N/A	INTRINSIC
A4_EXTRA	24	188	5.33e-129	SMART
low complexity region	190	208	N/A	INTRINSIC
Pfam:APP_E2	291	473	2.5e-77	PFAM
Pfam:Beta-APP	600	638	3.4e-28	PFAM
Pfam:APP_amyloid	641	691	8.6e-28	PFAM

Predicted Effect

unknown
Transcript: ENSMUST00000226232
AA Change: D252G

Predicted Effect

unknown
Transcript: ENSMUST00000226801
AA Change: D252G

Predicted Effect

unknown
Transcript: ENSMUST00000227021
AA Change: D252G

Predicted Effect

unknown
Transcript: ENSMUST00000227723
AA Change: D252G

Predicted Effect

unknown
Transcript: ENSMUST00000227737
AA Change: D252G

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000227990

Meta Mutation Damage Score

0.0621

Coding Region Coverage

1x: 99.2%
3x: 98.5%
10x: 96.9%
20x: 94.2%

Validation Efficiency

98% (90/92)

MGI Phenotype

FUNCTION: [Summary is not available for the mouse gene. This summary is for the human ortholog.] This gene encodes a cell surface receptor and transmembrane precursor protein that is cleaved by secretases to form a number of peptides. Some of these peptides are secreted and can bind to the acetyltransferase complex APBB1/TIP60 to promote transcriptional activation, while others form the protein basis of the amyloid plaques found in the brains of patients with Alzheimer disease. In addition, two of the peptides are antimicrobial peptides, having been shown to have bacteriocidal and antifungal activities. Mutations in this gene have been implicated in autosomal dominant Alzheimer disease and cerebroarterial amyloidosis (cerebral amyloid angiopathy). Multiple transcript variants encoding several different isoforms have been found for this gene. [provided by RefSeq, Aug 2014]
PHENOTYPE: Mice homozygous for disruptions in this gene exhibit reduced body weight, brain weight, size of forebrain commissures, locomotor activity, forelimb grip strength, and spatial learning scores. Many mice also exhibit agenesis of the corpus callosum, and extensive reactive gliosis. [provided by MGI curators]

Allele List at MGI

Other mutations in this stock

Total: 82 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
Acp7	G	T	7: 28,314,877 (GRCm39)	R239S	possibly damaging	Het
Angptl1	C	A	1: 156,684,735 (GRCm39)	N301K	probably benign	Het
Ankrd26	T	A	6: 118,509,257 (GRCm39)	T603S	probably benign	Het
Atxn3	A	G	12: 101,900,627 (GRCm39)	S219P	probably benign	Het
Birc6	T	C	17: 74,954,383 (GRCm39)	S3397P	probably damaging	Het
Bivm	A	G	1: 44,182,033 (GRCm39)	I414V	possibly damaging	Het
Cemip	A	G	7: 83,584,945 (GRCm39)	F1324L	possibly damaging	Het
Ckap5	T	A	2: 91,445,616 (GRCm39)	N1724K	probably damaging	Het
Corin	T	A	5: 72,460,178 (GRCm39)	M1035L	probably damaging	Het
Ctnna3	T	C	10: 64,709,094 (GRCm39)	I711T	probably damaging	Het
Cts6	A	T	13: 61,349,415 (GRCm39)	W98R	probably null	Het
Dip2a	A	G	10: 76,130,367 (GRCm39)	S580P	probably damaging	Het
Dock6	A	G	9: 21,723,068 (GRCm39)		probably null	Het
Dusp15	T	A	2: 152,791,002 (GRCm39)	T32S	probably damaging	Het
Eogt	T	A	6: 97,093,016 (GRCm39)	N387I	probably damaging	Het
Evx2	T	C	2: 74,489,675 (GRCm39)	D29G	probably benign	Het
Fat1	A	G	8: 45,466,007 (GRCm39)	N1422S	probably benign	Het
Fat2	T	C	11: 55,201,463 (GRCm39)	D537G	probably damaging	Het
Fat3	A	C	9: 16,289,244 (GRCm39)	I93S	probably benign	Het
Fem1b	T	C	9: 62,704,576 (GRCm39)	E228G	probably damaging	Het
Fh1	A	G	1: 175,448,072 (GRCm39)	T25A	probably benign	Het
Fndc3b	A	G	3: 27,514,097 (GRCm39)	W695R	probably damaging	Het
Gaa	G	A	11: 119,163,813 (GRCm39)	V222I	possibly damaging	Het
Ggnbp1	T	C	17: 27,251,947 (GRCm39)		probably null	Het
Gipc1	A	G	8: 84,388,756 (GRCm39)	Y154C	probably benign	Het
Gm5356	G	T	8: 89,913,670 (GRCm39)		noncoding transcript	Het
Gnl1	T	A	17: 36,298,603 (GRCm39)		probably null	Het
Gpcpd1	C	T	2: 132,376,019 (GRCm39)	G605R	probably damaging	Het
Guca1a	T	C	17: 47,705,662 (GRCm39)	T177A	possibly damaging	Het
Ifit1bl1	T	C	19: 34,572,076 (GRCm39)	E127G	probably damaging	Het
Ift81	A	T	5: 122,729,282 (GRCm39)	I350N	probably damaging	Het
Ikbke	GCC	G	1: 131,203,004 (GRCm39)		probably null	Het
Ing4	A	G	6: 125,020,946 (GRCm39)	R23G	probably damaging	Het
Ins1	A	G	19: 52,253,384 (GRCm39)	N108S	probably damaging	Het
Iqce	A	T	5: 140,679,214 (GRCm39)	M72K	possibly damaging	Het
Itga3	C	A	11: 94,967,097 (GRCm39)	M22I	probably benign	Het
Kctd18	T	C	1: 58,001,152 (GRCm39)	E201G	probably damaging	Het
Klc1	A	G	12: 111,748,129 (GRCm39)	N344S	probably damaging	Het
Klrb1f	A	T	6: 129,033,347 (GRCm39)	I192F	probably damaging	Het
Klrg2	A	T	6: 38,607,214 (GRCm39)		probably null	Het
Kntc1	A	C	5: 123,897,128 (GRCm39)	I164L	probably benign	Het
Ltf	T	A	9: 110,855,058 (GRCm39)	I357K	probably benign	Het
Mr1	T	C	1: 155,006,436 (GRCm39)	T304A	probably benign	Het
Msh6	C	T	17: 88,290,947 (GRCm39)	R178C	possibly damaging	Het
Mtch1	T	C	17: 29,566,565 (GRCm39)	D66G	probably benign	Het
Mtmr7	A	G	8: 41,062,040 (GRCm39)	V15A	probably benign	Het
Mtss2	A	T	8: 111,452,875 (GRCm39)	H40L	possibly damaging	Het
Mxra8	A	G	4: 155,925,331 (GRCm39)		probably benign	Het
Myo3b	T	C	2: 70,075,253 (GRCm39)	L535P	probably damaging	Het
Neurl2	T	A	2: 164,674,739 (GRCm39)		probably null	Het
Nfia	A	C	4: 97,970,048 (GRCm39)	T503P	probably damaging	Het
Noa1	T	C	5: 77,454,179 (GRCm39)	E487G	possibly damaging	Het
Nuak1	A	T	10: 84,211,143 (GRCm39)	V315D	probably damaging	Het
Nup205	A	G	6: 35,207,505 (GRCm39)	N1519S	possibly damaging	Het
Or10x1	T	A	1: 174,196,966 (GRCm39)	I161K	probably damaging	Het
Or1l4b	T	C	2: 37,036,266 (GRCm39)	L14P	probably damaging	Het
Or1o1	T	C	17: 37,716,589 (GRCm39)	V50A	probably benign	Het
Or51f1e	A	G	7: 102,747,526 (GRCm39)	I193V	possibly damaging	Het
Or6b13	G	T	7: 139,782,340 (GRCm39)	C114*	probably null	Het
Or9s18	G	A	13: 65,300,493 (GRCm39)	V152M	possibly damaging	Het
Peli1	T	A	11: 21,098,528 (GRCm39)		probably benign	Het
Ppp6r1	A	G	7: 4,646,206 (GRCm39)	L175P	probably damaging	Het
Prkcd	A	G	14: 30,321,700 (GRCm39)	L498P	probably damaging	Het
Prss30	T	A	17: 24,191,769 (GRCm39)	I251F	probably benign	Het
Psme3	A	T	11: 101,207,907 (GRCm39)	N21Y	probably benign	Het
Ptpra	T	C	2: 130,374,081 (GRCm39)	Y271H	probably damaging	Het
Ralgapa1	T	A	12: 55,745,588 (GRCm39)	N1303Y	probably damaging	Het
Rims4	T	C	2: 163,707,463 (GRCm39)	I121V	probably benign	Het
Rnf123	A	T	9: 107,933,290 (GRCm39)	L1149Q	probably damaging	Het
Ryr3	T	A	2: 112,738,807 (GRCm39)	L593F	probably damaging	Het
Sec23b	T	C	2: 144,427,519 (GRCm39)	F582S	probably damaging	Het
Sgpl1	T	C	10: 60,940,297 (GRCm39)	K335R	probably benign	Het
Sirpa	C	T	2: 129,451,163 (GRCm39)	T141I	probably damaging	Het
Slit1	G	T	19: 41,637,983 (GRCm39)	A270E	probably benign	Het
Snap91	T	C	9: 86,674,613 (GRCm39)	T533A	possibly damaging	Het
Sphkap	T	G	1: 83,255,105 (GRCm39)	E881D	probably benign	Het
Sptan1	C	A	2: 29,901,054 (GRCm39)	R1407S	probably damaging	Het
Tfdp1	A	G	8: 13,423,895 (GRCm39)	T353A	probably benign	Het
Ttyh1	A	G	7: 4,125,533 (GRCm39)	I62V	possibly damaging	Het
Vwde	A	T	6: 13,196,047 (GRCm39)	V326D	possibly damaging	Het
Zfp398	T	C	6: 47,836,446 (GRCm39)	I82T	possibly damaging	Het
Zp1	A	G	19: 10,896,198 (GRCm39)	Y176H	possibly damaging	Het

Other mutations in App

Allele	Source	Chr	Coord	Type	Predicted Effect	PPH Score
IGL00834:App	APN	16	84,762,599 (GRCm39)	missense	probably damaging	0.99
IGL01457:App	APN	16	84,900,127 (GRCm39)	missense	probably damaging	1.00
IGL02016:App	APN	16	84,853,409 (GRCm39)	missense	unknown
IGL02135:App	APN	16	84,876,726 (GRCm39)	critical splice donor site	probably null
IGL02338:App	APN	16	84,970,407 (GRCm39)	missense	probably benign	0.01
IGL02377:App	APN	16	84,879,719 (GRCm39)	missense	probably benign	0.07
IGL02516:App	APN	16	84,752,305 (GRCm39)	missense	probably damaging	1.00
IGL02565:App	APN	16	84,822,308 (GRCm39)	splice site	probably null
IGL03179:App	APN	16	84,879,735 (GRCm39)	missense	probably damaging	1.00
BB005:App	UTSW	16	84,775,134 (GRCm39)	missense	probably benign	0.05
BB015:App	UTSW	16	84,775,134 (GRCm39)	missense	probably benign	0.05
LCD18:App	UTSW	16	84,822,300 (GRCm39)	splice site	probably benign
R0349:App	UTSW	16	84,810,568 (GRCm39)	missense	probably damaging	1.00
R0440:App	UTSW	16	84,853,302 (GRCm39)	nonsense	probably null
R0515:App	UTSW	16	84,900,232 (GRCm39)	splice site	probably benign
R0730:App	UTSW	16	84,876,840 (GRCm39)	missense	probably damaging	0.98
R1609:App	UTSW	16	84,876,837 (GRCm39)	missense	probably damaging	0.97
R1703:App	UTSW	16	84,762,656 (GRCm39)	missense	probably damaging	1.00
R2516:App	UTSW	16	84,775,117 (GRCm39)	missense	probably damaging	0.97
R4366:App	UTSW	16	84,853,321 (GRCm39)	missense	unknown
R4735:App	UTSW	16	84,900,202 (GRCm39)	missense	probably damaging	0.99
R4851:App	UTSW	16	84,853,322 (GRCm39)	missense	unknown
R6254:App	UTSW	16	84,775,065 (GRCm39)	missense	probably damaging	1.00
R6489:App	UTSW	16	84,853,408 (GRCm39)	missense	unknown
R6796:App	UTSW	16	84,917,455 (GRCm39)	missense	probably damaging	0.98
R7132:App	UTSW	16	84,853,370 (GRCm39)	missense	unknown
R7194:App	UTSW	16	84,822,319 (GRCm39)	missense	probably benign	0.40
R7456:App	UTSW	16	84,970,448 (GRCm39)
R7528:App	UTSW	16	84,775,146 (GRCm39)	missense	possibly damaging	0.89
R7594:App	UTSW	16	84,876,890 (GRCm39)	missense	unknown
R7699:App	UTSW	16	84,837,197 (GRCm39)	critical splice acceptor site	probably null
R7700:App	UTSW	16	84,837,197 (GRCm39)	critical splice acceptor site	probably null
R7928:App	UTSW	16	84,775,134 (GRCm39)	missense	probably benign	0.05
R8086:App	UTSW	16	84,917,428 (GRCm39)	missense	unknown
R8346:App	UTSW	16	84,900,145 (GRCm39)	missense	unknown
R8506:App	UTSW	16	84,879,704 (GRCm39)	missense	unknown
R8902:App	UTSW	16	84,876,767 (GRCm39)	missense	unknown
R9142:App	UTSW	16	84,900,127 (GRCm39)	missense	probably damaging	1.00
R9244:App	UTSW	16	84,759,629 (GRCm39)	missense	probably damaging	0.99
R9477:App	UTSW	16	84,853,392 (GRCm39)	missense	unknown
Z1176:App	UTSW	16	84,821,805 (GRCm39)	missense	probably damaging	1.00

Predicted Primers

PCR Primer
(F):5'- AGAGGAAGAAGCCTTGTGATTTTG -3'
(R):5'- ACGCATTACCAAAGTCCCTTG -3'

Sequencing Primer
(F):5'- CTGGAGAAGGGAAGCACTGATTG -3'
(R):5'- ACCAAAGTCCCTTGATTCTTTTTC -3'

Posted On

2016-03-01