Incidental Mutation 'R0377:Ache'
ID 30798
Institutional Source Beutler Lab
Gene Symbol Ache
Ensembl Gene ENSMUSG00000023328
Gene Name acetylcholinesterase
Synonyms
MMRRC Submission 038583-MU
Accession Numbers
Essential gene? Possibly essential (E-score: 0.683) question?
Stock # R0377 (G1)
Quality Score 225
Status Validated
Chromosome 5
Chromosomal Location 137286516-137292728 bp(+) (GRCm39)
Type of Mutation missense
DNA Base Change (assembly) G to A at 137289190 bp (GRCm39)
Zygosity Heterozygous
Amino Acid Change Glutamic Acid to Lysine at position 299 (E299K)
Ref Sequence ENSEMBL: ENSMUSP00000142427 (fasta)
Gene Model predicted gene model for transcript(s): [ENSMUST00000024099] [ENSMUST00000040873] [ENSMUST00000052825] [ENSMUST00000085934] [ENSMUST00000125195] [ENSMUST00000132191] [ENSMUST00000196208] [ENSMUST00000199243] [ENSMUST00000197466] [ENSMUST00000196109] [ENSMUST00000141123] [ENSMUST00000198526] [ENSMUST00000137126] [ENSMUST00000138591]
AlphaFold P21836
Predicted Effect probably benign
Transcript: ENSMUST00000024099
AA Change: E299K

PolyPhen 2 Score 0.426 (Sensitivity: 0.89; Specificity: 0.90)
SMART Domains Protein: ENSMUSP00000024099
Gene: ENSMUSG00000023328
AA Change: E299K

DomainStartEndE-ValueType
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

DomainStartEndE-ValueType
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

DomainStartEndE-ValueType
Pfam:Peptidase_C78 27 212 5.4e-37 PFAM
Predicted Effect probably benign
Transcript: ENSMUST00000085934
AA Change: E299K

PolyPhen 2 Score 0.426 (Sensitivity: 0.89; Specificity: 0.90)
SMART Domains Protein: ENSMUSP00000083097
Gene: ENSMUSG00000023328
AA Change: E299K

DomainStartEndE-ValueType
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 possibly damaging
Transcript: ENSMUST00000196208
AA Change: E299K

PolyPhen 2 Score 0.544 (Sensitivity: 0.88; Specificity: 0.91)
SMART Domains Protein: ENSMUSP00000142427
Gene: ENSMUSG00000023328
AA Change: E299K

DomainStartEndE-ValueType
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: ENSMUST00000184134
Predicted Effect noncoding transcript
Transcript: ENSMUST00000196840
Predicted Effect noncoding transcript
Transcript: ENSMUST00000150983
Predicted Effect probably benign
Transcript: ENSMUST00000199243
SMART Domains Protein: ENSMUSP00000143232
Gene: ENSMUSG00000037364

DomainStartEndE-ValueType
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: ENSMUST00000197466
SMART Domains Protein: ENSMUSP00000142564
Gene: ENSMUSG00000037364

DomainStartEndE-ValueType
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: ENSMUST00000196109
SMART Domains Protein: ENSMUSP00000142351
Gene: ENSMUSG00000037364

DomainStartEndE-ValueType
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: ENSMUST00000141123
Predicted Effect probably benign
Transcript: ENSMUST00000198526
SMART Domains Protein: ENSMUSP00000142435
Gene: ENSMUSG00000037364

DomainStartEndE-ValueType
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: ENSMUST00000137126
Predicted Effect probably benign
Transcript: ENSMUST00000138591
Meta Mutation Damage Score 0.1939 question?
Coding Region Coverage
  • 1x: 99.1%
  • 3x: 98.1%
  • 10x: 95.7%
  • 20x: 90.8%
Validation Efficiency 97% (67/69)
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: 64 list
GeneRefVarChr/LocMutationPredicted EffectZygosity
Abcc3 C A 11: 94,265,922 (GRCm39) V107F possibly damaging Het
Acad11 T A 9: 103,958,891 (GRCm39) probably benign Het
Adam5 T C 8: 25,237,557 (GRCm39) T618A probably benign Het
Amigo2 T A 15: 97,144,261 (GRCm39) T54S possibly damaging Het
Anapc1 A G 2: 128,483,260 (GRCm39) probably null Het
Btaf1 A G 19: 36,966,402 (GRCm39) K1057E probably benign Het
Cep55 T A 19: 38,060,337 (GRCm39) L396* probably null Het
Cic C A 7: 24,985,224 (GRCm39) H1157N probably damaging Het
Cntnap5a A T 1: 116,220,259 (GRCm39) T690S probably benign Het
D5Ertd579e A T 5: 36,761,911 (GRCm39) C1319S probably benign Het
Dnah6 A G 6: 73,098,975 (GRCm39) S2027P possibly damaging Het
Dnai4 A G 4: 102,905,456 (GRCm39) V775A probably damaging Het
Dntt G A 19: 41,036,066 (GRCm39) W369* probably null Het
Esp18 T A 17: 39,720,835 (GRCm39) W27R probably benign Het
Fam227b A T 2: 125,966,920 (GRCm39) probably benign Het
Fbxo31 G A 8: 122,285,841 (GRCm39) probably benign Het
Gm13547 G A 2: 29,651,803 (GRCm39) probably null Het
Gnl2 T A 4: 124,940,175 (GRCm39) probably benign Het
Gpx2 G A 12: 76,841,930 (GRCm39) Q74* probably null Het
Gucy2c A G 6: 136,727,915 (GRCm39) probably null Het
Hoxa5 A T 6: 52,179,626 (GRCm39) W250R probably damaging Het
Izumo4 G A 10: 80,538,674 (GRCm39) R42H probably damaging Het
Kcnj12 G A 11: 60,960,222 (GRCm39) M71I probably benign Het
Kmt2b A T 7: 30,273,618 (GRCm39) L2333Q probably damaging Het
Mak T C 13: 41,202,824 (GRCm39) E177G probably damaging Het
Map3k7 T A 4: 31,985,731 (GRCm39) I218N probably damaging Het
Mark3 T C 12: 111,595,463 (GRCm39) L393P probably damaging Het
Msh4 A G 3: 153,602,527 (GRCm39) S234P probably benign Het
Mug1 A G 6: 121,834,320 (GRCm39) D367G probably benign Het
Mypn A G 10: 62,963,401 (GRCm39) probably benign Het
Ncapg T C 5: 45,851,159 (GRCm39) V784A probably benign Het
Nutf2 T A 8: 106,605,504 (GRCm39) V113D probably damaging Het
Odad2 G A 18: 7,127,415 (GRCm39) R933C probably benign Het
Opn3 T C 1: 175,491,260 (GRCm39) M258V probably damaging Het
Or8k33 A T 2: 86,383,927 (GRCm39) D180E probably damaging Het
Osbpl7 A G 11: 96,946,760 (GRCm39) D211G probably damaging Het
Pcnx1 C T 12: 82,021,353 (GRCm39) probably benign Het
Plekhd1 G A 12: 80,753,210 (GRCm39) probably benign Het
Pnpla6 A G 8: 3,591,501 (GRCm39) E1165G probably damaging Het
Prkab2 T A 3: 97,569,633 (GRCm39) D66E probably benign Het
Prpsap2 A G 11: 61,631,826 (GRCm39) I177T possibly damaging Het
Ptpn23 A T 9: 110,217,200 (GRCm39) S885R possibly damaging Het
Rab26 A T 17: 24,749,019 (GRCm39) probably benign Het
Rab5a G A 17: 53,807,490 (GRCm39) M175I probably benign Het
Rassf9 T A 10: 102,381,510 (GRCm39) D297E probably benign Het
Rimbp2 C T 5: 128,880,925 (GRCm39) R161Q probably damaging Het
Rtp1 A G 16: 23,250,034 (GRCm39) Y133C probably damaging Het
Sdr16c5 G A 4: 4,005,546 (GRCm39) L263F probably benign Het
Sec14l1 T G 11: 117,039,966 (GRCm39) probably benign Het
Snrnp40 C G 4: 130,271,836 (GRCm39) probably null Het
Spaca1 T C 4: 34,044,267 (GRCm39) probably null Het
Stk36 C T 1: 74,651,889 (GRCm39) P394L probably benign Het
Stk4 T C 2: 163,938,720 (GRCm39) I196T probably damaging Het
Sult1b1 A T 5: 87,665,235 (GRCm39) M233K probably damaging Het
Tmem8b C T 4: 43,674,005 (GRCm39) T212M probably damaging Het
Tmprss11g A T 5: 86,638,610 (GRCm39) F293I probably damaging Het
Tnfsf11 T G 14: 78,537,352 (GRCm39) T104P probably benign Het
Trmt2a G A 16: 18,067,567 (GRCm39) R80Q possibly damaging Het
Trps1 C A 15: 50,695,174 (GRCm39) E324* probably null Het
U2surp C T 9: 95,366,496 (GRCm39) V470I probably benign Het
Wdr18 G A 10: 79,803,336 (GRCm39) R400H probably benign Het
Zfp119b T A 17: 56,245,671 (GRCm39) H505L probably damaging Het
Zfp619 T A 7: 39,186,221 (GRCm39) C750* probably null Het
Zfr T C 15: 12,160,677 (GRCm39) I750T probably benign Het
Other mutations in Ache
AlleleSourceChrCoordTypePredicted EffectPPH 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
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
R4499:Ache UTSW 5 137,290,194 (GRCm39) missense probably damaging 0.98
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'- ATCAACGGCTTGCCTTGCAATG -3'
(R):5'- AGGACTGATTTTGGGACCCACAAAC -3'

Sequencing Primer
(F):5'- ACCCGATGTCAGTGACTCTG -3'
(R):5'- GGATCTGTAGTAAGCCCTCATGC -3'
Posted On 2013-04-24