Incidental Mutation 'R2516:App'
| ID |
253855 |
| 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 |
040420-MU
|
| Accession Numbers |
|
| Essential gene? |
Possibly essential
(E-score: 0.557)
|
| Stock # |
R2516 (G1)
|
| Quality Score |
225 |
|
Status
|
Validated
|
| Chromosome |
16 |
| Chromosomal Location |
84751236-84972187 bp(-) (GRCm39) |
| Type of Mutation |
missense |
| DNA Base Change (assembly) |
T to C
at 84775117 bp (GRCm39)
|
| Zygosity |
Heterozygous |
| Amino Acid Change |
Serine to Glycine
at position 582
(S582G)
|
| 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: S507G
PolyPhen 2
Score 0.955 (Sensitivity: 0.79; Specificity: 0.95)
|
| SMART Domains |
Protein: ENSMUSP00000005406
Gene: ENSMUSG00000022892
AA Change: S507G
| 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 |
possibly damaging
Transcript: ENSMUST00000226232
AA Change: S563G
PolyPhen 2
Score 0.911 (Sensitivity: 0.81; Specificity: 0.94)
|
| Predicted Effect |
probably damaging
Transcript: ENSMUST00000226801
AA Change: S582G
PolyPhen 2
Score 0.965 (Sensitivity: 0.78; Specificity: 0.95)
|
| Predicted Effect |
unknown
Transcript: ENSMUST00000227021
AA Change: S563G
|
| Predicted Effect |
probably damaging
Transcript: ENSMUST00000227723
AA Change: S582G
PolyPhen 2
Score 0.972 (Sensitivity: 0.77; Specificity: 0.96)
|
| Predicted Effect |
probably benign
Transcript: ENSMUST00000227737
|
| Predicted Effect |
noncoding transcript
Transcript: ENSMUST00000227835
|
| Predicted Effect |
noncoding transcript
Transcript: ENSMUST00000228375
|
| Meta Mutation Damage Score |
0.0680 |
| Coding Region Coverage |
- 1x: 99.2%
- 3x: 98.6%
- 10x: 97.3%
- 20x: 95.1%
|
| Validation Efficiency |
98% (65/66) |
| 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: 66 list
| Gene | Ref | Var | Chr/Loc | Mutation | Predicted Effect | Zygosity |
|---|
| Abcb11 |
A |
T |
2: 69,159,673 (GRCm39) |
I6N |
possibly damaging |
Het |
| Aen |
T |
C |
7: 78,555,616 (GRCm39) |
V188A |
probably damaging |
Het |
| Afg3l1 |
A |
G |
8: 124,228,693 (GRCm39) |
E753G |
probably damaging |
Het |
| Alas1 |
G |
A |
9: 106,115,859 (GRCm39) |
T385I |
probably damaging |
Het |
| Alms1 |
C |
A |
6: 85,644,945 (GRCm39) |
|
probably benign |
Het |
| Ankrd65 |
A |
G |
4: 155,875,868 (GRCm39) |
T30A |
possibly damaging |
Het |
| Arfgef1 |
A |
T |
1: 10,223,879 (GRCm39) |
V1473E |
possibly damaging |
Het |
| Arhgap21 |
G |
A |
2: 20,859,809 (GRCm39) |
P1196S |
probably damaging |
Het |
| Arhgap24 |
A |
G |
5: 103,039,776 (GRCm39) |
T238A |
probably benign |
Het |
| Atf7 |
T |
C |
15: 102,437,439 (GRCm39) |
|
probably benign |
Het |
| Best1 |
G |
T |
19: 9,970,675 (GRCm39) |
S55* |
probably null |
Het |
| Capn11 |
A |
G |
17: 45,944,725 (GRCm39) |
V514A |
probably damaging |
Het |
| Cep104 |
T |
A |
4: 154,073,603 (GRCm39) |
M52K |
probably damaging |
Het |
| Clca3a1 |
C |
T |
3: 144,443,619 (GRCm39) |
|
probably null |
Het |
| Cyp3a25 |
T |
C |
5: 145,939,837 (GRCm39) |
|
probably null |
Het |
| Dmxl2 |
G |
A |
9: 54,307,378 (GRCm39) |
P2197S |
probably damaging |
Het |
| Drosha |
T |
C |
15: 12,859,551 (GRCm39) |
|
probably null |
Het |
| Exosc9 |
A |
G |
3: 36,617,311 (GRCm39) |
K355R |
probably benign |
Het |
| Fut1 |
A |
C |
7: 45,268,622 (GRCm39) |
H192P |
probably benign |
Het |
| Gm572 |
T |
A |
4: 148,748,841 (GRCm39) |
V166D |
possibly damaging |
Het |
| Gm9966 |
C |
T |
7: 95,607,735 (GRCm39) |
P19S |
unknown |
Het |
| Gmds |
C |
T |
13: 32,284,456 (GRCm39) |
V219I |
probably damaging |
Het |
| Gsn |
G |
A |
2: 35,173,965 (GRCm39) |
E25K |
probably benign |
Het |
| Il4i1 |
T |
C |
7: 44,489,315 (GRCm39) |
F368S |
probably damaging |
Het |
| Irak1bp1 |
T |
C |
9: 82,712,373 (GRCm39) |
L98P |
probably damaging |
Het |
| Khdrbs3 |
T |
C |
15: 68,896,544 (GRCm39) |
|
probably benign |
Het |
| Kndc1 |
T |
C |
7: 139,501,738 (GRCm39) |
I925T |
probably damaging |
Het |
| Laptm4a |
T |
C |
12: 8,988,151 (GRCm39) |
I296T |
probably benign |
Het |
| Lpl |
A |
T |
8: 69,340,170 (GRCm39) |
H55L |
probably benign |
Het |
| Lrrk2 |
C |
A |
15: 91,640,130 (GRCm39) |
N1558K |
probably benign |
Het |
| Mfsd2a |
A |
G |
4: 122,844,280 (GRCm39) |
L289P |
probably damaging |
Het |
| Mmrn2 |
T |
A |
14: 34,120,759 (GRCm39) |
M543K |
probably benign |
Het |
| Mnat1 |
T |
C |
12: 73,228,550 (GRCm39) |
|
probably benign |
Het |
| Msto1 |
A |
T |
3: 88,819,200 (GRCm39) |
|
probably null |
Het |
| Mtus1 |
A |
G |
8: 41,535,776 (GRCm39) |
Y647H |
probably damaging |
Het |
| Nars1 |
A |
T |
18: 64,638,087 (GRCm39) |
V289E |
probably damaging |
Het |
| Oit3 |
T |
A |
10: 59,264,167 (GRCm39) |
K322N |
probably damaging |
Het |
| Oit3 |
G |
A |
10: 59,277,507 (GRCm39) |
|
probably benign |
Het |
| Or4k1 |
T |
C |
14: 50,377,440 (GRCm39) |
I219V |
probably benign |
Het |
| Or5b113 |
T |
A |
19: 13,342,557 (GRCm39) |
C188* |
probably null |
Het |
| Or5m12 |
A |
G |
2: 85,734,900 (GRCm39) |
I166T |
probably benign |
Het |
| Or6c211 |
G |
A |
10: 129,506,155 (GRCm39) |
R78W |
probably damaging |
Het |
| Pecr |
A |
T |
1: 72,316,469 (GRCm39) |
C79S |
probably damaging |
Het |
| Plekhn1 |
T |
C |
4: 156,307,116 (GRCm39) |
D478G |
probably damaging |
Het |
| Pls1 |
A |
T |
9: 95,658,616 (GRCm39) |
M264K |
probably benign |
Het |
| Ptprj |
C |
A |
2: 90,305,340 (GRCm39) |
|
probably benign |
Het |
| Pygm |
A |
G |
19: 6,447,631 (GRCm39) |
D646G |
probably benign |
Het |
| Rif1 |
GCCACCA |
GCCA |
2: 52,000,336 (GRCm39) |
|
probably benign |
Het |
| Scn8a |
T |
C |
15: 100,867,043 (GRCm39) |
V283A |
probably benign |
Het |
| Shisa5 |
T |
C |
9: 108,885,575 (GRCm39) |
|
probably null |
Het |
| Slc10a4 |
A |
G |
5: 73,165,848 (GRCm39) |
I246V |
possibly damaging |
Het |
| Slc1a1 |
A |
T |
19: 28,870,312 (GRCm39) |
I104F |
probably benign |
Het |
| Slc22a8 |
A |
G |
19: 8,587,559 (GRCm39) |
Y511C |
probably benign |
Het |
| Slc6a5 |
A |
G |
7: 49,606,210 (GRCm39) |
N706S |
probably benign |
Het |
| Sos2 |
T |
C |
12: 69,697,433 (GRCm39) |
K96E |
probably damaging |
Het |
| Stom |
G |
A |
2: 35,205,977 (GRCm39) |
R251* |
probably null |
Het |
| Sycp1 |
T |
C |
3: 102,752,382 (GRCm39) |
E800G |
probably benign |
Het |
| Tab2 |
G |
A |
10: 7,783,245 (GRCm39) |
P679L |
probably damaging |
Het |
| Tiam2 |
G |
A |
17: 3,503,657 (GRCm39) |
V945I |
probably damaging |
Het |
| Trpm5 |
G |
T |
7: 142,628,254 (GRCm39) |
P1007Q |
probably damaging |
Het |
| Uchl1 |
T |
G |
5: 66,839,956 (GRCm39) |
I139S |
probably damaging |
Het |
| Vmn1r232 |
A |
G |
17: 21,134,288 (GRCm39) |
I104T |
possibly damaging |
Het |
| Vmn2r97 |
G |
A |
17: 19,167,814 (GRCm39) |
M689I |
probably benign |
Het |
| Zc3h18 |
A |
T |
8: 123,129,904 (GRCm39) |
|
probably benign |
Het |
| Zfhx4 |
C |
T |
3: 5,468,418 (GRCm39) |
P2859S |
probably benign |
Het |
| Zfp456 |
T |
C |
13: 67,510,491 (GRCm39) |
K99R |
probably benign |
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 |
|
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'- TTTTGGCTCCAGGTAGGGACTC -3'
(R):5'- GGGTCAACCACTAAGCTCTG -3'
Sequencing Primer
(F):5'- TCCAGGTAGGGACTCTTACC -3'
(R):5'- AAGCTCTGACTTTCCTTAAGGTG -3'
|
| Posted On |
2014-12-04 |
Incidental Mutation