Incidental Mutation 'R6254:App'
ID 506024
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 044371-MU
Accession Numbers
Essential gene? Possibly essential (E-score: 0.557) question?
Stock # R6254 (G1)
Quality Score 225.009
Status Validated
Chromosome 16
Chromosomal Location 84751236-84972187 bp(-) (GRCm39)
Type of Mutation missense
DNA Base Change (assembly) T to C at 84775065 bp (GRCm39)
Zygosity Heterozygous
Amino Acid Change Glutamic Acid to Glycine at position 599 (E599G)
Ref Sequence ENSEMBL: ENSMUSP00000154061 (fasta)
Gene Model predicted gene model for transcript(s): [ENSMUST00000005406] [ENSMUST00000226232] [ENSMUST00000226801] [ENSMUST00000227021] [ENSMUST00000227723] [ENSMUST00000227737]
AlphaFold P12023
Predicted Effect possibly damaging
Transcript: ENSMUST00000005406
AA Change: E524G

PolyPhen 2 Score 0.795 (Sensitivity: 0.85; Specificity: 0.93)
SMART Domains Protein: ENSMUSP00000005406
Gene: ENSMUSG00000022892
AA Change: E524G

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 probably damaging
Transcript: ENSMUST00000226232
AA Change: E580G

PolyPhen 2 Score 0.997 (Sensitivity: 0.41; Specificity: 0.98)
Predicted Effect probably damaging
Transcript: ENSMUST00000226801
AA Change: E599G

PolyPhen 2 Score 1.000 (Sensitivity: 0.00; Specificity: 1.00)
Predicted Effect unknown
Transcript: ENSMUST00000227021
AA Change: E580G
Predicted Effect probably damaging
Transcript: ENSMUST00000227723
AA Change: E599G

PolyPhen 2 Score 1.000 (Sensitivity: 0.00; Specificity: 1.00)
Predicted Effect probably benign
Transcript: ENSMUST00000227737
Predicted Effect noncoding transcript
Transcript: ENSMUST00000228375
Predicted Effect noncoding transcript
Transcript: ENSMUST00000227835
Meta Mutation Damage Score 0.1616 question?
Coding Region Coverage
  • 1x: 99.9%
  • 3x: 99.6%
  • 10x: 98.2%
  • 20x: 94.4%
Validation Efficiency 100% (82/82)
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
GeneRefVarChr/LocMutationPredicted EffectZygosity
Adam6b A T 12: 113,453,190 (GRCm39) L2F probably damaging Het
Ank2 T A 3: 126,735,453 (GRCm39) probably benign Het
Anpep T G 7: 79,488,981 (GRCm39) D369A probably damaging Het
Asphd1 C T 7: 126,548,040 (GRCm39) V88I probably benign Het
Atad5 A T 11: 80,018,215 (GRCm39) I1389F probably damaging Het
Blm T C 7: 80,130,090 (GRCm39) N950S probably benign Het
Bsn A T 9: 107,989,065 (GRCm39) M2229K probably damaging Het
Cacna2d2 A G 9: 107,386,415 (GRCm39) M181V probably benign Het
Cadps2 T A 6: 23,329,162 (GRCm39) probably null Het
Cdh1 T A 8: 107,390,430 (GRCm39) V590D probably damaging Het
Cdk5rap2 G A 4: 70,282,269 (GRCm39) T160M probably damaging Het
Cfap97d2 A G 8: 13,756,043 (GRCm39) D26G possibly damaging Het
Cfhr4 A G 1: 139,682,128 (GRCm39) I156T probably damaging Het
Chrna5 A G 9: 54,913,740 (GRCm39) M325V probably benign Het
Clca3a2 A G 3: 144,507,895 (GRCm39) I116T probably benign Het
Cyp2c23 T C 19: 43,993,902 (GRCm39) K488R probably benign Het
Edil3 T A 13: 89,467,848 (GRCm39) I451N probably damaging Het
Exph5 T G 9: 53,284,010 (GRCm39) S364A possibly damaging Het
Fam98c A G 7: 28,853,942 (GRCm39) S209P probably damaging Het
Fat3 G A 9: 15,907,441 (GRCm39) L2854F probably benign Het
Fbxo38 T C 18: 62,638,571 (GRCm39) probably null Het
Fermt2 T C 14: 45,713,516 (GRCm39) D205G probably damaging Het
Fmnl1 G A 11: 103,087,141 (GRCm39) probably benign Het
Fn3k A G 11: 121,325,894 (GRCm39) E27G probably damaging Het
Foxj2 A G 6: 122,815,098 (GRCm39) H378R probably damaging Het
Fubp1 A G 3: 151,938,045 (GRCm39) K140E possibly damaging Het
Gm7694 A T 1: 170,130,103 (GRCm39) C98* probably null Het
Golgb1 T C 16: 36,734,340 (GRCm39) S1196P probably damaging Het
Gpm6a G A 8: 55,500,431 (GRCm39) probably null Het
Hltf T A 3: 20,117,993 (GRCm39) N80K possibly damaging Het
Il1rap G A 16: 26,514,020 (GRCm39) R251H probably benign Het
Ipo7 T A 7: 109,648,267 (GRCm39) D688E probably benign Het
Itgal T A 7: 126,924,375 (GRCm39) N897K probably damaging Het
Itsn2 A G 12: 4,674,982 (GRCm39) probably null Het
Kcnk13 A G 12: 99,931,631 (GRCm39) probably benign Het
Kdm7a A G 6: 39,147,203 (GRCm39) L248P probably damaging Het
Kmt2c T C 5: 25,554,872 (GRCm39) E1254G possibly damaging Het
Ldah G A 12: 8,325,912 (GRCm39) probably benign Het
Lingo1 T A 9: 56,527,371 (GRCm39) D406V possibly damaging Het
Lratd2 A G 15: 60,695,650 (GRCm39) I32T probably damaging Het
Lrriq1 A T 10: 103,051,312 (GRCm39) V480E probably benign Het
Mtcl1 C T 17: 66,665,129 (GRCm39) R1142H probably benign Het
Mtmr3 G A 11: 4,447,381 (GRCm39) Q360* probably null Het
Muc6 T C 7: 141,237,380 (GRCm39) N252S probably benign Het
Naa20 T C 2: 145,745,240 (GRCm39) L4P probably damaging Het
Neb T A 2: 52,112,973 (GRCm39) I4274L probably benign Het
Noa1 A T 5: 77,457,516 (GRCm39) F130I probably benign Het
Nrg4 G T 9: 55,143,796 (GRCm39) H87N possibly damaging Het
Or51ai2 T A 7: 103,586,741 (GRCm39) H51Q probably benign Het
Or5m12 T A 2: 85,734,849 (GRCm39) Y183F probably damaging Het
P3h3 C T 6: 124,822,564 (GRCm39) E536K probably damaging Het
Pcdhb11 T C 18: 37,554,771 (GRCm39) S34P probably damaging Het
Pik3r1 T C 13: 101,825,914 (GRCm39) T71A possibly damaging Het
Plaur T A 7: 24,166,225 (GRCm39) C99S possibly damaging Het
Plekha5 G A 6: 140,532,162 (GRCm39) G501E probably damaging Het
Plxnd1 C T 6: 115,954,921 (GRCm39) V614M probably benign Het
Ppp2r3d T C 9: 101,025,786 (GRCm39) D307G possibly damaging Het
Prl3d3 C T 13: 27,341,453 (GRCm39) S28F possibly damaging Het
Prpf40a T C 2: 53,047,927 (GRCm39) M197V probably benign Het
Ptk7 C A 17: 46,883,568 (GRCm39) Q832H probably damaging Het
Qser1 T C 2: 104,620,435 (GRCm39) S126G probably benign Het
Rab3ip A T 10: 116,751,772 (GRCm39) C332S probably damaging Het
Raly C A 2: 154,699,286 (GRCm39) T30K probably damaging Het
Rbp2 G T 9: 98,372,700 (GRCm39) S13I probably benign Het
Rps6ka1 C T 4: 133,594,535 (GRCm39) M159I possibly damaging Het
Rufy3 C T 5: 88,732,168 (GRCm39) T57I probably benign Het
Samd4 A G 14: 47,254,088 (GRCm39) D184G probably damaging Het
Slc35f3 T C 8: 127,047,833 (GRCm39) C58R possibly damaging Het
Smarca4 T C 9: 21,611,173 (GRCm39) I1467T probably damaging Het
Spag17 T G 3: 99,972,901 (GRCm39) I1371S probably benign Het
Sptan1 T C 2: 29,897,561 (GRCm39) L1228P possibly damaging Het
Stk31 C T 6: 49,398,631 (GRCm39) A344V probably benign Het
Supt16 A G 14: 52,408,291 (GRCm39) W885R probably damaging Het
Tdrd9 T A 12: 111,992,334 (GRCm39) probably null Het
Tmod1 A G 4: 46,078,469 (GRCm39) probably null Het
Tnfsf13 A C 11: 69,575,309 (GRCm39) probably null Het
Trim75 C A 8: 65,436,094 (GRCm39) E119* probably null Het
Wdr6 T C 9: 108,452,110 (GRCm39) Y591C probably damaging Het
Wdr86 C T 5: 24,923,281 (GRCm39) R137H probably benign Het
Ythdf1 T A 2: 180,552,943 (GRCm39) Y424F probably damaging Het
Zfp984 G T 4: 147,840,643 (GRCm39) S69R possibly damaging Het
Zyg11a A G 4: 108,038,991 (GRCm39) F743L 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
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'- ACCAGGTCCTTCTCTCAAAAG -3'
(R):5'- CACACGGCATGTAGTCAGTAG -3'

Sequencing Primer
(F):5'- GCAACTGTTACCATGGGGAC -3'
(R):5'- TCAGTAGGAATGGCCGCTG -3'
Posted On 2018-02-28