Mutagenetix > Incidental Mutations

Incidental Mutation 'R4851:App'

373587

Institutional Source

Beutler Lab

Gene Symbol

App

Ensembl Gene

ENSMUSG00000022892

Gene Name

amyloid beta (A4) precursor protein

Synonyms

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

MMRRC Submission

042463-MU

Accession Numbers

Is this an essential gene?

Possibly essential (E-score: 0.546) question?

Stock #

R4851 (G1)

Quality Score

225

Status

Validated

Chromosome

Chromosomal Location

84949685-85173766 bp(-) (GRCm38)

Type of Mutation

missense

DNA Base Change (assembly)

T to C at 85056434 bp (GRCm38)

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: 99.1%
3x: 98.5%
10x: 96.8%
20x: 94.0%

Validation Efficiency

100% (99/99)

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: 87 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
4930451G09Rik	A	G	16: 4,976,274		noncoding transcript	Het
Abca13	A	T	11: 9,483,890	R4148S	probably benign	Het
Acoxl	T	A	2: 128,044,391	L182Q	possibly damaging	Het
Aldh7a1	T	C	18: 56,532,016	T364A	possibly damaging	Het
Arid1a	A	G	4: 133,681,361	I1945T	unknown	Het
Arsk	C	T	13: 76,065,279		probably null	Het
Atad2b	G	A	12: 4,943,251	G257S	probably benign	Het
Best1	C	A	19: 9,991,698	R218L	probably damaging	Het
Cacna1e	A	T	1: 154,436,554		probably null	Het
Cdh13	C	T	8: 118,757,390	T130I	possibly damaging	Het
Cela2a	T	C	4: 141,825,591	E25G	probably benign	Het
Cgnl1	T	A	9: 71,725,032	I346F	probably damaging	Het
Chil6	C	T	3: 106,389,928	G299D	possibly damaging	Het
Cic	G	A	7: 25,272,902	R686H	probably damaging	Het
Cnpy1	T	C	5: 28,245,740	I23V	probably benign	Het
Col6a3	T	A	1: 90,779,289	Y2034F	unknown	Het
Coq10b	T	C	1: 55,071,744	Y224H	probably benign	Het
Cryge	G	T	1: 65,051,052		probably benign	Het
Cyb5rl	T	G	4: 107,084,313	S252A	probably benign	Het
Cyp2ab1	T	A	16: 20,315,064	R125S	probably damaging	Het
Dclk1	G	A	3: 55,480,390	G86R	probably damaging	Het
Dmtn	A	G	14: 70,604,814	M382T	probably damaging	Het
Dnah12	T	A	14: 26,716,629	L471*	probably null	Het
Dock10	A	T	1: 80,549,157	S782T	probably benign	Het
Egfem1	C	A	3: 29,151,883	H90N	possibly damaging	Het
Ephb6	T	A	6: 41,618,145	W698R	probably benign	Het
Exoc4	T	A	6: 33,918,408	C787S	probably damaging	Het
Exosc8	A	T	3: 54,732,102		probably benign	Het
Galc	T	A	12: 98,227,274	Q352L	probably benign	Het
Galns	A	G	8: 122,600,533	Y167H	probably damaging	Het
Glb1l	T	C	1: 75,208,884		probably benign	Het
Gm6185	A	T	1: 161,206,180		noncoding transcript	Het
Gm7694	T	C	1: 170,301,225	N245S	probably benign	Het
Gmcl1	T	G	6: 86,704,556	K385N	possibly damaging	Het
Gramd1c	A	T	16: 43,989,837	W463R	probably damaging	Het
Gtpbp8	C	G	16: 44,746,070	A90P	probably benign	Het
Hcar1	T	C	5: 123,878,668	E320G	probably benign	Het
Hhatl	T	C	9: 121,789,011	D226G	probably damaging	Het
Hist1h2bj	G	T	13: 22,043,251		probably benign	Het
Hoxc5	T	A	15: 103,015,369	I199N	probably damaging	Het
Iars2	T	C	1: 185,327,648	D121G	probably damaging	Het
Il5ra	T	A	6: 106,738,471	H134L	probably benign	Het
Isl2	T	A	9: 55,544,987	I281N	possibly damaging	Het
Kcnk13	T	C	12: 99,966,124	F60L	probably damaging	Het
Kdelr3	C	T	15: 79,524,865	T85M	possibly damaging	Het
Kdf1	A	T	4: 133,528,365	H131L	probably damaging	Het
Mipol1	T	A	12: 57,332,301	L182I	probably damaging	Het
Morc1	T	G	16: 48,561,617	S513R	probably benign	Het
Moxd2	A	T	6: 40,878,822	L611H	probably damaging	Het
Mpped2	T	C	2: 106,699,379		probably benign	Het
Mrpl51	T	C	6: 125,193,307	V92A	probably benign	Het
Mrps26	G	A	2: 130,563,761		probably benign	Het
Mrps5	A	G	2: 127,590,745	T29A	probably benign	Het
Mustn1	A	G	14: 30,879,560		probably benign	Het
Ncor2	G	A	5: 125,033,367	P858S	possibly damaging	Het
Nfasc	A	G	1: 132,602,021	F807S	probably damaging	Het
Nup50	G	A	15: 84,939,711	V422I	probably benign	Het
Olfr1044	T	A	2: 86,171,671	I49F	probably damaging	Het
Olfr1212	A	G	2: 88,958,586	N40S	probably damaging	Het
Olfr384	A	T	11: 73,603,057	H159L	probably damaging	Het
Olfr411	C	A	11: 74,346,943	V214L	probably benign	Het
Olfr417	T	A	1: 174,368,996	F26L	probably benign	Het
Olfr539	A	T	7: 140,667,313	M2L	probably benign	Het
Olfr695	A	T	7: 106,874,014	V77D	probably damaging	Het
Olfr907	T	A	9: 38,499,023	M118K	probably damaging	Het
Osbpl8	T	A	10: 111,204,800	M1K	probably null	Het
Pcdhb22	A	C	18: 37,519,034	D185A	possibly damaging	Het
Pcdhga8	G	T	18: 37,816,404	R291L	probably damaging	Het
Saysd1	A	T	14: 20,077,604	L84Q	possibly damaging	Het
Slc41a1	T	C	1: 131,830,770	I50T	probably benign	Het
Smg7	G	A	1: 152,844,269	P834S	probably benign	Het
Speer4a	C	T	5: 26,038,212	V92M	probably damaging	Het
Srf	T	C	17: 46,549,474	T461A	probably benign	Het
Ssu72	A	G	4: 155,715,596	D72G	possibly damaging	Het
Suco	T	C	1: 161,834,192	E890G	probably damaging	Het
Tenm3	A	G	8: 48,310,621		probably null	Het
Tm6sf1	A	G	7: 81,865,343	E7G	probably null	Het
Tm9sf2	A	G	14: 122,141,204	K240R	probably benign	Het
Tmem52	T	A	4: 155,470,368	Y149*	probably null	Het
Tpgs2	A	T	18: 25,151,248	Y68N	possibly damaging	Het
Vmn1r205	T	A	13: 22,592,904	E9D	probably benign	Het
Vmn2r32	A	G	7: 7,479,954	V7A	possibly damaging	Het
Vmn2r80	T	C	10: 79,194,322	Y661H	possibly damaging	Het
Vps39	G	A	2: 120,321,831		probably benign	Het
Vwde	A	T	6: 13,196,048	V326D	possibly damaging	Het
Zfp641	T	A	15: 98,288,717	S342C	probably damaging	Het
Zfp961	T	C	8: 71,969,003		probably benign	Het

Other mutations in App

Allele	Source	Chr	Coord	Type	Predicted Effect	PPH Score
IGL00834:App	APN	16	84965711	missense	probably damaging	0.99
IGL01457:App	APN	16	85103239	missense	probably damaging	1.00
IGL02016:App	APN	16	85056521	missense	unknown
IGL02135:App	APN	16	85079838	critical splice donor site	probably null
IGL02338:App	APN	16	85173519	missense	probably benign	0.01
IGL02377:App	APN	16	85082831	missense	probably benign	0.07
IGL02516:App	APN	16	84955417	missense	probably damaging	1.00
IGL02565:App	APN	16	85025420	splice site	probably null
IGL03179:App	APN	16	85082847	missense	probably damaging	1.00
BB005:App	UTSW	16	84978246	missense	probably benign	0.05
BB015:App	UTSW	16	84978246	missense	probably benign	0.05
LCD18:App	UTSW	16	85025412	splice site	probably benign
R0349:App	UTSW	16	85013680	missense	probably damaging	1.00
R0440:App	UTSW	16	85056414	nonsense	probably null
R0515:App	UTSW	16	85103344	splice site	probably benign
R0730:App	UTSW	16	85079952	missense	probably damaging	0.98
R1609:App	UTSW	16	85079949	missense	probably damaging	0.97
R1703:App	UTSW	16	84965768	missense	probably damaging	1.00
R2516:App	UTSW	16	84978229	missense	probably damaging	0.97
R4366:App	UTSW	16	85056433	missense	unknown
R4735:App	UTSW	16	85103314	missense	probably damaging	0.99
R4849:App	UTSW	16	85056434	missense	unknown
R6254:App	UTSW	16	84978177	missense	probably damaging	1.00
R6489:App	UTSW	16	85056520	missense	unknown
R6796:App	UTSW	16	85120567	missense	probably damaging	0.98
R7132:App	UTSW	16	85056482	missense	unknown
R7194:App	UTSW	16	85025431	missense	probably benign	0.40
R7456:App	UTSW	16	85173560
R7528:App	UTSW	16	84978258	missense	possibly damaging	0.89
R7594:App	UTSW	16	85080002	missense	unknown
R7699:App	UTSW	16	85040309	critical splice acceptor site	probably null
R7700:App	UTSW	16	85040309	critical splice acceptor site	probably null
R7928:App	UTSW	16	84978246	missense	probably benign	0.05
R8086:App	UTSW	16	85120540	missense	unknown
R8346:App	UTSW	16	85103257	missense	unknown
R8506:App	UTSW	16	85082816	missense	unknown
R8902:App	UTSW	16	85079879	missense	unknown
R9142:App	UTSW	16	85103239	missense	probably damaging	1.00
R9244:App	UTSW	16	84962741	missense	probably damaging	0.99
Z1176:App	UTSW	16	85024917	missense	probably damaging	1.00

Predicted Primers

PCR Primer
(F):5'- AGGAAGAAGCCTTGTGATTTTG -3'
(R):5'- CACGCATTACCAAAGTCCCTTG -3'

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

Posted On

2016-03-01