Incidental Mutation 'R4499:Ache'
| ID |
331748 |
| Institutional Source |
Beutler Lab
|
| Gene Symbol |
Ache
|
| Ensembl Gene |
ENSMUSG00000023328 |
| Gene Name |
acetylcholinesterase |
| Synonyms |
|
| MMRRC Submission |
041752-MU
|
| Accession Numbers |
|
| Essential gene? |
Possibly essential
(E-score: 0.683)
|
| Stock # |
R4499 (G1)
|
| Quality Score |
225 |
|
Status
|
Validated
|
| Chromosome |
5 |
| Chromosomal Location |
137286516-137292728 bp(+) (GRCm39) |
| Type of Mutation |
missense |
| DNA Base Change (assembly) |
A to C
at 137290194 bp (GRCm39)
|
| Zygosity |
Heterozygous |
| Amino Acid Change |
Methionine to Leucine
at position 508
(M508L)
|
| Ref Sequence |
ENSEMBL: ENSMUSP00000083097
(fasta)
|
| Gene Model |
predicted gene model for transcript(s):
[ENSMUST00000024099]
[ENSMUST00000040873]
[ENSMUST00000052825]
[ENSMUST00000085934]
[ENSMUST00000125195]
[ENSMUST00000132191]
[ENSMUST00000137126]
[ENSMUST00000196208]
[ENSMUST00000199243]
[ENSMUST00000196109]
[ENSMUST00000198526]
[ENSMUST00000197466]
[ENSMUST00000138591]
[ENSMUST00000141123]
|
| AlphaFold |
P21836 |
| Predicted Effect |
probably damaging
Transcript: ENSMUST00000024099
AA Change: M508L
PolyPhen 2
Score 0.982 (Sensitivity: 0.75; Specificity: 0.96)
|
| SMART Domains |
Protein: ENSMUSP00000024099
Gene: ENSMUSG00000023328
AA Change: M508L
| Domain | Start | End | E-Value | Type |
|---|
|
Pfam:COesterase
|
14 |
563 |
2e-186 |
PFAM |
|
Pfam:Abhydrolase_3
|
146 |
276 |
7.5e-9 |
PFAM |
|
Pfam:AChE_tetra
|
578 |
614 |
3.2e-26 |
PFAM |
|
| Predicted Effect |
probably benign
Transcript: ENSMUST00000040873
|
| SMART Domains |
Protein: ENSMUSP00000043123
Gene: ENSMUSG00000037364
| Domain | Start | End | E-Value | Type |
|---|
|
low complexity region
|
3 |
65 |
N/A |
INTRINSIC |
|
low complexity region
|
95 |
116 |
N/A |
INTRINSIC |
|
Pfam:DUF3546
|
153 |
262 |
3.8e-44 |
PFAM |
|
low complexity region
|
269 |
276 |
N/A |
INTRINSIC |
|
low complexity region
|
326 |
350 |
N/A |
INTRINSIC |
|
coiled coil region
|
367 |
402 |
N/A |
INTRINSIC |
|
Blast:RRM
|
421 |
491 |
2e-31 |
BLAST |
|
low complexity region
|
566 |
595 |
N/A |
INTRINSIC |
|
low complexity region
|
603 |
615 |
N/A |
INTRINSIC |
|
Pfam:ARS2
|
645 |
850 |
9.7e-94 |
PFAM |
|
| Predicted Effect |
probably benign
Transcript: ENSMUST00000052825
|
| SMART Domains |
Protein: ENSMUSP00000056156
Gene: ENSMUSG00000051502
| Domain | Start | End | E-Value | Type |
|---|
|
Pfam:Peptidase_C78
|
27 |
212 |
5.4e-37 |
PFAM |
|
| Predicted Effect |
probably damaging
Transcript: ENSMUST00000085934
AA Change: M508L
PolyPhen 2
Score 0.982 (Sensitivity: 0.75; Specificity: 0.96)
|
| SMART Domains |
Protein: ENSMUSP00000083097
Gene: ENSMUSG00000023328
AA Change: M508L
| Domain | Start | End | E-Value | Type |
|---|
|
Pfam:COesterase
|
15 |
563 |
3e-178 |
PFAM |
|
Pfam:Abhydrolase_3
|
146 |
260 |
1.4e-7 |
PFAM |
|
Pfam:AChE_tetra
|
578 |
613 |
3.2e-23 |
PFAM |
|
| Predicted Effect |
probably benign
Transcript: ENSMUST00000125195
|
| Predicted Effect |
probably benign
Transcript: ENSMUST00000132191
|
| Predicted Effect |
probably benign
Transcript: ENSMUST00000137126
|
| Predicted Effect |
noncoding transcript
Transcript: ENSMUST00000150983
|
| Predicted Effect |
possibly damaging
Transcript: ENSMUST00000196208
AA Change: M420L
PolyPhen 2
Score 0.536 (Sensitivity: 0.88; Specificity: 0.90)
|
| SMART Domains |
Protein: ENSMUSP00000142427
Gene: ENSMUSG00000023328
AA Change: M420L
| Domain | Start | End | E-Value | Type |
|---|
|
Pfam:COesterase
|
14 |
359 |
6.5e-134 |
PFAM |
|
Pfam:Abhydrolase_3
|
146 |
284 |
4.1e-7 |
PFAM |
|
Pfam:COesterase
|
355 |
475 |
1.5e-25 |
PFAM |
|
Pfam:AChE_tetra
|
490 |
526 |
2.2e-23 |
PFAM |
|
| Predicted Effect |
noncoding transcript
Transcript: ENSMUST00000196840
|
| Predicted Effect |
noncoding transcript
Transcript: ENSMUST00000184134
|
| Predicted Effect |
noncoding transcript
Transcript: ENSMUST00000184197
|
| Predicted Effect |
noncoding transcript
Transcript: ENSMUST00000196960
|
| Predicted Effect |
noncoding transcript
Transcript: ENSMUST00000197409
|
| Predicted Effect |
noncoding transcript
Transcript: ENSMUST00000197144
|
| Predicted Effect |
probably benign
Transcript: ENSMUST00000199243
|
| SMART Domains |
Protein: ENSMUSP00000143232
Gene: ENSMUSG00000037364
| Domain | Start | End | E-Value | Type |
|---|
|
low complexity region
|
3 |
65 |
N/A |
INTRINSIC |
|
low complexity region
|
95 |
116 |
N/A |
INTRINSIC |
|
Pfam:DUF3546
|
151 |
264 |
9.5e-48 |
PFAM |
|
low complexity region
|
269 |
276 |
N/A |
INTRINSIC |
|
low complexity region
|
326 |
350 |
N/A |
INTRINSIC |
|
coiled coil region
|
367 |
402 |
N/A |
INTRINSIC |
|
Blast:RRM
|
421 |
491 |
2e-31 |
BLAST |
|
low complexity region
|
566 |
595 |
N/A |
INTRINSIC |
|
low complexity region
|
603 |
615 |
N/A |
INTRINSIC |
|
Pfam:ARS2
|
635 |
849 |
9.8e-115 |
PFAM |
|
| Predicted Effect |
probably benign
Transcript: ENSMUST00000196109
|
| SMART Domains |
Protein: ENSMUSP00000142351
Gene: ENSMUSG00000037364
| Domain | Start | End | E-Value | Type |
|---|
|
coiled coil region
|
11 |
46 |
N/A |
INTRINSIC |
|
Blast:RRM
|
65 |
133 |
2e-15 |
BLAST |
|
low complexity region
|
208 |
237 |
N/A |
INTRINSIC |
|
low complexity region
|
245 |
257 |
N/A |
INTRINSIC |
|
Pfam:ARS2
|
277 |
498 |
6.5e-111 |
PFAM |
|
| Predicted Effect |
probably benign
Transcript: ENSMUST00000198526
|
| SMART Domains |
Protein: ENSMUSP00000142435
Gene: ENSMUSG00000037364
| Domain | Start | End | E-Value | Type |
|---|
|
low complexity region
|
3 |
65 |
N/A |
INTRINSIC |
|
low complexity region
|
95 |
116 |
N/A |
INTRINSIC |
|
Pfam:DUF3546
|
151 |
264 |
2e-45 |
PFAM |
|
low complexity region
|
269 |
276 |
N/A |
INTRINSIC |
|
low complexity region
|
322 |
347 |
N/A |
INTRINSIC |
|
low complexity region
|
369 |
408 |
N/A |
INTRINSIC |
|
| Predicted Effect |
probably benign
Transcript: ENSMUST00000197466
|
| SMART Domains |
Protein: ENSMUSP00000142564
Gene: ENSMUSG00000037364
| Domain | Start | End | E-Value | Type |
|---|
|
low complexity region
|
3 |
65 |
N/A |
INTRINSIC |
|
low complexity region
|
95 |
116 |
N/A |
INTRINSIC |
|
Pfam:DUF3546
|
151 |
264 |
9.5e-48 |
PFAM |
|
low complexity region
|
269 |
276 |
N/A |
INTRINSIC |
|
low complexity region
|
326 |
350 |
N/A |
INTRINSIC |
|
coiled coil region
|
367 |
402 |
N/A |
INTRINSIC |
|
Blast:RRM
|
421 |
491 |
2e-31 |
BLAST |
|
low complexity region
|
566 |
595 |
N/A |
INTRINSIC |
|
low complexity region
|
603 |
615 |
N/A |
INTRINSIC |
|
Pfam:ARS2
|
635 |
845 |
5.5e-113 |
PFAM |
|
| Predicted Effect |
probably benign
Transcript: ENSMUST00000138591
|
| Predicted Effect |
probably benign
Transcript: ENSMUST00000141123
|
| Predicted Effect |
noncoding transcript
Transcript: ENSMUST00000200643
|
| Predicted Effect |
probably benign
Transcript: ENSMUST00000199756
|
| Meta Mutation Damage Score |
0.6705 |
| Coding Region Coverage |
- 1x: 99.2%
- 3x: 98.5%
- 10x: 97.1%
- 20x: 94.9%
|
| Validation Efficiency |
92% (47/51) |
| MGI Phenotype |
FUNCTION: [Summary is not available for the mouse gene. This summary is for the human ortholog.] Acetylcholinesterase hydrolyzes the neurotransmitter, acetylcholine at neuromuscular junctions and brain cholinergic synapses, and thus terminates signal transmission. It is also found on the red blood cell membranes, where it constitutes the Yt blood group antigen. Acetylcholinesterase exists in multiple molecular forms which possess similar catalytic properties, but differ in their oligomeric assembly and mode of cell attachment to the cell surface. It is encoded by the single ACHE gene, and the structural diversity in the gene products arises from alternative mRNA splicing, and post-translational associations of catalytic and structural subunits. The major form of acetylcholinesterase found in brain, muscle and other tissues is the hydrophilic species, which forms disulfide-linked oligomers with collagenous, or lipid-containing structural subunits. The other, alternatively spliced form, expressed primarily in the erythroid tissues, differs at the C-terminal end, and contains a cleavable hydrophobic peptide with a GPI-anchor site. It associates with the membranes through the phosphoinositide (PI) moieties added post-translationally. [provided by RefSeq, Jul 2008]
PHENOTYPE: Homozygous mutants show retarded postnatal development, tremors, impaired righting response, delayed maturation of external ear, failure of eyelids to open, and die by 3-wk. of age. Mutants are highly sensitive to butyrylcholinesterase inhibitor toxicity. [provided by MGI curators]
|
| Allele List at MGI |
|
| Other mutations in this stock |
Total: 43 list
| Gene | Ref | Var | Chr/Loc | Mutation | Predicted Effect | Zygosity |
|---|
| 2210408I21Rik |
T |
A |
13: 77,464,646 (GRCm39) |
W948R |
possibly damaging |
Het |
| Adgrb2 |
A |
T |
4: 129,886,454 (GRCm39) |
E198V |
probably damaging |
Het |
| Adgrl4 |
A |
G |
3: 151,216,422 (GRCm39) |
N535S |
possibly damaging |
Het |
| Agbl3 |
T |
C |
6: 34,834,533 (GRCm39) |
S906P |
probably benign |
Het |
| Akna |
T |
C |
4: 63,313,278 (GRCm39) |
T282A |
probably benign |
Het |
| Arfgef2 |
G |
A |
2: 166,727,734 (GRCm39) |
V1561M |
probably damaging |
Het |
| Arfgef3 |
T |
C |
10: 18,484,091 (GRCm39) |
D1388G |
possibly damaging |
Het |
| Asnsd1 |
A |
G |
1: 53,387,129 (GRCm39) |
V166A |
probably benign |
Het |
| Bank1 |
T |
C |
3: 135,990,004 (GRCm39) |
I29V |
probably benign |
Het |
| Bpifb5 |
A |
T |
2: 154,082,678 (GRCm39) |
I484F |
possibly damaging |
Het |
| Camta2 |
T |
C |
11: 70,565,512 (GRCm39) |
E788G |
probably damaging |
Het |
| Ccdc18 |
T |
G |
5: 108,376,826 (GRCm39) |
S1422R |
possibly damaging |
Het |
| Cdc42bpg |
C |
T |
19: 6,370,585 (GRCm39) |
P1226L |
possibly damaging |
Het |
| Cep126 |
T |
C |
9: 8,101,589 (GRCm39) |
N315S |
possibly damaging |
Het |
| Dcaf4 |
T |
A |
12: 83,586,134 (GRCm39) |
L367Q |
probably damaging |
Het |
| Dcc |
A |
T |
18: 71,680,388 (GRCm39) |
V616D |
probably benign |
Het |
| Dennd4a |
G |
A |
9: 64,817,405 (GRCm39) |
D1680N |
possibly damaging |
Het |
| Dgkq |
C |
G |
5: 108,797,527 (GRCm39) |
E788D |
possibly damaging |
Het |
| Dpep2 |
T |
C |
8: 106,712,114 (GRCm39) |
E282G |
probably benign |
Het |
| Gm8221 |
T |
A |
15: 77,510,245 (GRCm39) |
|
noncoding transcript |
Het |
| Ice1 |
T |
C |
13: 70,757,146 (GRCm39) |
S280G |
possibly damaging |
Het |
| Lrrc2 |
A |
T |
9: 110,791,713 (GRCm39) |
Q155L |
probably benign |
Het |
| Mesd |
G |
A |
7: 83,547,185 (GRCm39) |
R216Q |
probably benign |
Het |
| Msh6 |
T |
A |
17: 88,287,697 (GRCm39) |
N112K |
probably damaging |
Het |
| Myo15b |
A |
G |
11: 115,781,778 (GRCm39) |
E307G |
probably benign |
Het |
| Nod1 |
T |
A |
6: 54,920,981 (GRCm39) |
N446Y |
probably damaging |
Het |
| Nrap |
G |
A |
19: 56,339,913 (GRCm39) |
T787I |
probably damaging |
Het |
| P2ry12 |
A |
G |
3: 59,125,078 (GRCm39) |
I199T |
probably damaging |
Het |
| Prr11 |
T |
G |
11: 86,989,533 (GRCm39) |
K279N |
possibly damaging |
Het |
| Psg25 |
C |
T |
7: 18,258,816 (GRCm39) |
E287K |
possibly damaging |
Het |
| Rusc1 |
T |
C |
3: 88,999,615 (GRCm39) |
S56G |
probably benign |
Het |
| Slc16a7 |
T |
C |
10: 125,064,056 (GRCm39) |
N427S |
probably damaging |
Het |
| Slc47a1 |
T |
A |
11: 61,250,355 (GRCm39) |
I341L |
probably benign |
Het |
| Slc9a8 |
T |
A |
2: 167,266,113 (GRCm39) |
L30Q |
probably benign |
Het |
| Ssh2 |
T |
A |
11: 77,283,893 (GRCm39) |
L49* |
probably null |
Het |
| Stard9 |
T |
A |
2: 120,530,722 (GRCm39) |
D2326E |
probably benign |
Het |
| Thbs1 |
T |
C |
2: 117,950,431 (GRCm39) |
I688T |
possibly damaging |
Het |
| Ttn |
T |
A |
2: 76,746,822 (GRCm39) |
E4742D |
probably benign |
Het |
| Vps37b |
T |
C |
5: 124,145,689 (GRCm39) |
I117V |
probably damaging |
Het |
| Xirp2 |
A |
T |
2: 67,343,782 (GRCm39) |
M2008L |
probably benign |
Het |
| Zfp1005 |
T |
G |
2: 150,111,362 (GRCm39) |
V684G |
possibly damaging |
Het |
| Zfp53 |
A |
G |
17: 21,729,497 (GRCm39) |
E510G |
probably damaging |
Het |
| Zswim8 |
T |
A |
14: 20,764,365 (GRCm39) |
S578R |
probably benign |
Het |
|
| Other mutations in Ache |
| Allele | Source | Chr | Coord | Type | Predicted Effect | PPH Score |
|---|
|
IGL02323:Ache
|
APN |
5 |
137,289,326 (GRCm39) |
missense |
probably damaging |
1.00 |
|
IGL02833:Ache
|
APN |
5 |
137,289,371 (GRCm39) |
unclassified |
probably benign |
|
|
R0058:Ache
|
UTSW |
5 |
137,289,104 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R0358:Ache
|
UTSW |
5 |
137,288,635 (GRCm39) |
missense |
probably benign |
0.21 |
|
R0377:Ache
|
UTSW |
5 |
137,289,190 (GRCm39) |
missense |
possibly damaging |
0.54 |
|
R0780:Ache
|
UTSW |
5 |
137,288,794 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R1233:Ache
|
UTSW |
5 |
137,288,419 (GRCm39) |
splice site |
probably null |
|
|
R1702:Ache
|
UTSW |
5 |
137,289,251 (GRCm39) |
missense |
possibly damaging |
0.94 |
|
R1762:Ache
|
UTSW |
5 |
137,288,837 (GRCm39) |
missense |
possibly damaging |
0.91 |
|
R4191:Ache
|
UTSW |
5 |
137,289,334 (GRCm39) |
missense |
probably damaging |
0.98 |
|
R4226:Ache
|
UTSW |
5 |
137,289,152 (GRCm39) |
missense |
possibly damaging |
0.83 |
|
R4931:Ache
|
UTSW |
5 |
137,290,176 (GRCm39) |
missense |
probably benign |
0.00 |
|
R5411:Ache
|
UTSW |
5 |
137,288,692 (GRCm39) |
splice site |
probably null |
|
|
R5411:Ache
|
UTSW |
5 |
137,288,326 (GRCm39) |
missense |
possibly damaging |
0.93 |
|
R5698:Ache
|
UTSW |
5 |
137,288,821 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R6153:Ache
|
UTSW |
5 |
137,290,117 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R6526:Ache
|
UTSW |
5 |
137,288,906 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R6896:Ache
|
UTSW |
5 |
137,289,996 (GRCm39) |
missense |
probably damaging |
0.98 |
|
R6981:Ache
|
UTSW |
5 |
137,289,940 (GRCm39) |
missense |
probably benign |
|
|
R7199:Ache
|
UTSW |
5 |
137,288,504 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R7208:Ache
|
UTSW |
5 |
137,289,751 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R8200:Ache
|
UTSW |
5 |
137,292,457 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R8338:Ache
|
UTSW |
5 |
137,290,006 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R8461:Ache
|
UTSW |
5 |
137,288,582 (GRCm39) |
missense |
probably damaging |
0.96 |
|
R8933:Ache
|
UTSW |
5 |
137,288,449 (GRCm39) |
missense |
possibly damaging |
0.56 |
|
R9146:Ache
|
UTSW |
5 |
137,289,077 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R9376:Ache
|
UTSW |
5 |
137,289,025 (GRCm39) |
missense |
probably benign |
|
|
R9439:Ache
|
UTSW |
5 |
137,289,185 (GRCm39) |
missense |
probably damaging |
0.97 |
|
X0061:Ache
|
UTSW |
5 |
137,288,357 (GRCm39) |
missense |
probably damaging |
1.00 |
|
| Predicted Primers |
PCR Primer
(F):5'- GAGATGCCATGAGTGCAGTG -3'
(R):5'- TAAGGACTCCCTGTTCTGCCTG -3'
Sequencing Primer
(F):5'- ACAACGTTGTGTGCCCTG -3'
(R):5'- GCCTTGTTCTCCGGCATCAC -3'
|
| Posted On |
2015-07-21 |
Incidental Mutation