Incidental Mutation 'R9142:App'
ID 694425
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 068934-MU
Accession Numbers
Essential gene? Possibly essential (E-score: 0.557) question?
Stock # R9142 (G1)
Quality Score 225.009
Status Validated
Chromosome 16
Chromosomal Location 84751236-84972187 bp(-) (GRCm39)
Type of Mutation missense
DNA Base Change (assembly) G to A at 84900127 bp (GRCm39)
Zygosity Heterozygous
Amino Acid Change Histidine to Tyrosine at position 108 (H108Y)
Ref Sequence ENSEMBL: ENSMUSP00000153907 (fasta)
Gene Model predicted gene model for transcript(s): [ENSMUST00000005406] [ENSMUST00000226232] [ENSMUST00000226801] [ENSMUST00000227021] [ENSMUST00000227723] [ENSMUST00000227737]
AlphaFold P12023
Predicted Effect
SMART Domains Protein: ENSMUSP00000005406
Gene: ENSMUSG00000022892
AA Change: H108Y

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: H108Y
Predicted Effect unknown
Transcript: ENSMUST00000226801
AA Change: H108Y
Predicted Effect probably damaging
Transcript: ENSMUST00000227021
AA Change: H108Y

PolyPhen 2 Score 0.998 (Sensitivity: 0.27; Specificity: 0.99)
Predicted Effect unknown
Transcript: ENSMUST00000227723
AA Change: H108Y
Predicted Effect unknown
Transcript: ENSMUST00000227737
AA Change: H108Y
Predicted Effect noncoding transcript
Transcript: ENSMUST00000227990
Coding Region Coverage
  • 1x: 100.0%
  • 3x: 99.9%
  • 10x: 99.7%
  • 20x: 99.1%
Validation Efficiency 100% (64/64)
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: 68 list
GeneRefVarChr/LocMutationPredicted EffectZygosity
Adprs C A 4: 126,215,360 (GRCm39) G35V probably damaging Het
Apob A C 12: 8,062,705 (GRCm39) D3729A possibly damaging Het
Arap3 G A 18: 38,112,934 (GRCm39) A1092V possibly damaging Het
Arid3a T C 10: 79,787,612 (GRCm39) S550P unknown Het
Armc2 T G 10: 41,851,404 (GRCm39) E259D probably benign Het
Atp13a2 A G 4: 140,729,364 (GRCm39) D566G probably damaging Het
Bnc2 A G 4: 84,474,111 (GRCm39) C12R probably benign Het
Btbd16 C T 7: 130,417,516 (GRCm39) R344C probably damaging Het
Cc2d2b C T 19: 40,753,845 (GRCm39) R123* probably null Het
Cdc37l1 T A 19: 28,989,402 (GRCm39) H286Q possibly damaging Het
Cfap54 A T 10: 92,820,097 (GRCm39) L1239Q possibly damaging Het
Cfap58 T C 19: 47,974,993 (GRCm39) probably null Het
Col6a3 A T 1: 90,706,566 (GRCm39) D2789E unknown Het
Ctnna2 G T 6: 76,879,423 (GRCm39) probably benign Het
Dazl A G 17: 50,590,178 (GRCm39) V271A probably benign Het
Dennd4c A T 4: 86,755,637 (GRCm39) N1610Y probably benign Het
Dusp13b T A 14: 21,792,756 (GRCm39) K56N probably benign Het
Erbb2 T A 11: 98,312,884 (GRCm39) I149N probably damaging Het
Erbb4 A T 1: 68,388,552 (GRCm39) C217S probably damaging Het
Fbxw21 A G 9: 108,985,413 (GRCm39) C122R probably damaging Het
Fktn G A 4: 53,734,854 (GRCm39) G125D probably benign Het
Foxm1 T A 6: 128,344,298 (GRCm39) I182N probably damaging Het
Ggnbp2 T C 11: 84,730,886 (GRCm39) N381S possibly damaging Het
Gja3 T C 14: 57,274,048 (GRCm39) E108G probably benign Het
Gm40460 C A 7: 141,794,499 (GRCm39) G106V unknown Het
Gm9736 A G 10: 77,586,849 (GRCm39) C114R unknown Het
Gpbp1 A T 13: 111,563,033 (GRCm39) D492E unknown Het
Gper1 T C 5: 139,412,312 (GRCm39) V219A possibly damaging Het
Gtf2e1 C T 16: 37,356,364 (GRCm39) R56Q probably benign Het
H2ac10 T C 13: 23,718,151 (GRCm39) L24P probably damaging Het
Ide T C 19: 37,307,898 (GRCm39) N38S Het
Kat6a T A 8: 23,430,072 (GRCm39) M1809K unknown Het
Kdm2b A T 5: 123,127,112 (GRCm39) probably benign Het
Kif7 A T 7: 79,356,585 (GRCm39) M702K probably benign Het
Lrrtm4 T A 6: 79,999,426 (GRCm39) N279K probably damaging Het
Mcrip1 G A 11: 120,435,542 (GRCm39) P31L probably damaging Het
Mettl25b A G 3: 87,831,195 (GRCm39) I444T probably benign Het
Nf1 T A 11: 79,362,315 (GRCm39) S1497R probably damaging Het
Nf1 T A 11: 79,366,688 (GRCm39) I1607N probably damaging Het
Nrde2 G T 12: 100,117,518 (GRCm39) T47K probably benign Het
Or5w12 C T 2: 87,502,313 (GRCm39) V133I probably benign Het
Or6b2b T G 1: 92,419,411 (GRCm39) E22A probably benign Het
Or6c1 T C 10: 129,518,285 (GRCm39) T108A probably benign Het
Ppargc1a G A 5: 51,652,146 (GRCm39) T184I possibly damaging Het
Ppp1r15a T C 7: 45,173,920 (GRCm39) D296G probably damaging Het
Prl7c1 C T 13: 27,964,751 (GRCm39) probably benign Het
Prss42 G T 9: 110,628,228 (GRCm39) R124L possibly damaging Het
Psmd1 T G 1: 86,064,817 (GRCm39) Y950D probably damaging Het
Ptprr A T 10: 116,024,119 (GRCm39) L250F possibly damaging Het
Rabgef1 T A 5: 130,237,554 (GRCm39) M208K possibly damaging Het
Rps6ka2 A G 17: 7,437,793 (GRCm39) Y17C probably damaging Het
Scart2 T A 7: 139,877,806 (GRCm39) D929E probably damaging Het
Sec23ip T A 7: 128,363,226 (GRCm39) C463S probably damaging Het
Serpina3n A G 12: 104,379,710 (GRCm39) T368A probably damaging Het
Sez6l C T 5: 112,609,083 (GRCm39) A589T probably benign Het
Smok2b G A 17: 13,453,637 (GRCm39) probably null Het
Spag5 T A 11: 78,192,823 (GRCm39) Y52N possibly damaging Het
Tenm3 G A 8: 48,788,548 (GRCm39) S494L unknown Het
Top3b T C 16: 16,701,299 (GRCm39) Y204H probably damaging Het
Trim43b C T 9: 88,973,452 (GRCm39) V94M possibly damaging Het
Trps1 T G 15: 50,524,658 (GRCm39) I1091L probably damaging Het
Ttk G A 9: 83,725,741 (GRCm39) R221Q probably damaging Het
Ttn A C 2: 76,549,466 (GRCm39) M31737R probably damaging Het
Uso1 T A 5: 92,335,125 (GRCm39) L495* probably null Het
Usp19 A G 9: 108,372,284 (GRCm39) D447G possibly damaging Het
Zdhhc2 A G 8: 40,920,563 (GRCm39) E274G probably damaging Het
Zfp106 T A 2: 120,350,935 (GRCm39) Y1595F probably damaging Het
Zfp932 A T 5: 110,157,520 (GRCm39) H406L 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
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
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
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'- ACTGTTTGGAGTTTGCACTTCC -3'
(R):5'- GGTTCAACATGTACTCTGTGTG -3'

Sequencing Primer
(F):5'- GGATGAATCTGCAGATATGAAACTC -3'
(R):5'- AACATGTACTCTGTGTGCCAGC -3'
Posted On 2022-01-20