Incidental Mutation 'R1609:App'
ID 176694
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 039646-MU
Accession Numbers
Essential gene? Possibly essential (E-score: 0.557) question?
Stock # R1609 (G1)
Quality Score 203
Status Validated
Chromosome 16
Chromosomal Location 84751236-84972187 bp(-) (GRCm39)
Type of Mutation missense
DNA Base Change (assembly) C to A at 84876837 bp (GRCm39)
Zygosity Heterozygous
Amino Acid Change Valine to Leucine at position 185 (V185L)
Ref Sequence ENSEMBL: ENSMUSP00000153907 (fasta)
Gene Model predicted gene model for transcript(s): [ENSMUST00000005406] [ENSMUST00000226232] [ENSMUST00000226801] [ENSMUST00000227021] [ENSMUST00000227723] [ENSMUST00000227737]
AlphaFold P12023
Predicted Effect unknown
Transcript: ENSMUST00000005406
AA Change: V185L
SMART Domains Protein: ENSMUSP00000005406
Gene: ENSMUSG00000022892
AA Change: V185L

DomainStartEndE-ValueType
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: V185L
Predicted Effect unknown
Transcript: ENSMUST00000226801
AA Change: V185L
Predicted Effect probably damaging
Transcript: ENSMUST00000227021
AA Change: V185L

PolyPhen 2 Score 0.970 (Sensitivity: 0.77; Specificity: 0.96)
Predicted Effect unknown
Transcript: ENSMUST00000227723
AA Change: V185L
Predicted Effect unknown
Transcript: ENSMUST00000227737
AA Change: V185L
Predicted Effect noncoding transcript
Transcript: ENSMUST00000227918
Predicted Effect noncoding transcript
Transcript: ENSMUST00000227990
Meta Mutation Damage Score 0.4569 question?
Coding Region Coverage
  • 1x: 98.9%
  • 3x: 98.0%
  • 10x: 95.1%
  • 20x: 88.1%
Validation Efficiency 96% (49/51)
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: 38 list
GeneRefVarChr/LocMutationPredicted EffectZygosity
Acot2 C T 12: 84,039,630 (GRCm39) R380C possibly damaging Het
Allc A T 12: 28,603,993 (GRCm39) D363E probably damaging Het
Anxa2 TCCC TCC 9: 69,397,036 (GRCm39) probably null Het
Atp5if1 T C 4: 132,258,078 (GRCm39) D47G probably benign Het
Auh G A 13: 52,989,532 (GRCm39) P308L probably benign Het
Cbr4 T A 8: 61,956,192 (GRCm39) Y220N probably damaging Het
Ccdc6 C A 10: 70,002,877 (GRCm39) Q203K probably damaging Het
Cntnap2 T C 6: 45,992,264 (GRCm39) V397A probably benign Het
Dmxl2 A G 9: 54,316,547 (GRCm39) I1613T possibly damaging Het
Dnah14 T C 1: 181,577,742 (GRCm39) S3020P probably damaging Het
Dnah7b T C 1: 46,392,126 (GRCm39) L3829P probably damaging Het
Fbxw25 C T 9: 109,492,578 (GRCm39) C53Y probably benign Het
Fndc1 G T 17: 7,991,598 (GRCm39) H699Q unknown Het
Gnaq G A 19: 16,360,618 (GRCm39) V314M possibly damaging Het
Gpr158 A G 2: 21,788,104 (GRCm39) T582A possibly damaging Het
Mapk1 T C 16: 16,856,170 (GRCm39) probably benign Het
Med1 T A 11: 98,051,996 (GRCm39) H456L possibly damaging Het
Myo6 G A 9: 80,195,499 (GRCm39) probably null Het
Nipbl A G 15: 8,396,148 (GRCm39) Y142H probably damaging Het
Or4c113 A T 2: 88,885,688 (GRCm39) F27L probably benign Het
Or8k24 A G 2: 86,215,838 (GRCm39) I308T probably benign Het
Or8k33 A C 2: 86,383,949 (GRCm39) V173G probably damaging Het
Pgbd5 T C 8: 125,160,750 (GRCm39) D39G probably benign Het
Pnisr G T 4: 21,871,440 (GRCm39) G387* probably null Het
Pnpla6 T C 8: 3,567,135 (GRCm39) L61P probably damaging Het
Prkra A T 2: 76,463,936 (GRCm39) I242N probably benign Het
Rp1 A G 1: 4,419,424 (GRCm39) S563P probably damaging Het
Rtp3 A G 9: 110,815,085 (GRCm39) probably benign Het
Sema3d A G 5: 12,591,023 (GRCm39) T301A probably damaging Het
Setmar A G 6: 108,053,076 (GRCm39) D190G probably benign Het
Sf3b2 A G 19: 5,345,061 (GRCm39) probably benign Het
Taf4b A G 18: 14,968,938 (GRCm39) K692E probably damaging Het
Tktl2 A G 8: 66,965,504 (GRCm39) E354G probably benign Het
Tspan4 A G 7: 141,071,557 (GRCm39) T135A probably damaging Het
Vmn1r22 G T 6: 57,877,733 (GRCm39) Y81* probably null Het
Vmn2r31 T C 7: 7,387,888 (GRCm39) E561G probably damaging Het
Xrn1 A T 9: 95,856,946 (GRCm39) K389N probably benign Het
Zfp277 A T 12: 40,378,719 (GRCm39) N379K probably damaging Het
Other mutations in App
AlleleSourceChrCoordTypePredicted EffectPPH 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
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
R4849:App UTSW 16 84,853,322 (GRCm39) missense unknown
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'- GAGATGGCTCAGCCAATCTGAGAC -3'
(R):5'- CAACTGTGGCGTGTTCGATTGC -3'

Sequencing Primer
(F):5'- TCAGCCAATCTGAGACCCATC -3'
(R):5'- ATGGCTGCTGTCCGACTC -3'
Posted On 2014-04-24