Incidental Mutation 'R6153:Ache'
ID 489377
Institutional Source Beutler Lab
Gene Symbol Ache
Ensembl Gene ENSMUSG00000023328
Gene Name acetylcholinesterase
Synonyms
MMRRC Submission 044300-MU
Accession Numbers
Essential gene? Possibly essential (E-score: 0.683) question?
Stock # R6153 (G1)
Quality Score 225.009
Status Validated
Chromosome 5
Chromosomal Location 137286516-137292728 bp(+) (GRCm39)
Type of Mutation missense
DNA Base Change (assembly) T to C at 137290117 bp (GRCm39)
Zygosity Heterozygous
Amino Acid Change Isoleucine to Threonine at position 394 (I394T)
Ref Sequence ENSEMBL: ENSMUSP00000142427 (fasta)
Gene Model predicted gene model for transcript(s): [ENSMUST00000024099] [ENSMUST00000040873] [ENSMUST00000052825] [ENSMUST00000085934] [ENSMUST00000125195] [ENSMUST00000132191] [ENSMUST00000196208] [ENSMUST00000196109] [ENSMUST00000138591] [ENSMUST00000137126] [ENSMUST00000141123] [ENSMUST00000199243] [ENSMUST00000197466] [ENSMUST00000198526]
AlphaFold P21836
Predicted Effect probably damaging
Transcript: ENSMUST00000024099
AA Change: I482T

PolyPhen 2 Score 0.989 (Sensitivity: 0.72; Specificity: 0.97)
SMART Domains Protein: ENSMUSP00000024099
Gene: ENSMUSG00000023328
AA Change: I482T

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 damaging
Transcript: ENSMUST00000085934
AA Change: I482T

PolyPhen 2 Score 0.989 (Sensitivity: 0.72; Specificity: 0.97)
SMART Domains Protein: ENSMUSP00000083097
Gene: ENSMUSG00000023328
AA Change: I482T

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 probably damaging
Transcript: ENSMUST00000196208
AA Change: I394T

PolyPhen 2 Score 0.997 (Sensitivity: 0.41; Specificity: 0.98)
SMART Domains Protein: ENSMUSP00000142427
Gene: ENSMUSG00000023328
AA Change: I394T

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: ENSMUST00000197144
Predicted Effect noncoding transcript
Transcript: ENSMUST00000197409
Predicted Effect noncoding transcript
Transcript: ENSMUST00000184134
Predicted Effect noncoding transcript
Transcript: ENSMUST00000196960
Predicted Effect noncoding transcript
Transcript: ENSMUST00000196840
Predicted Effect noncoding transcript
Transcript: ENSMUST00000184197
Predicted Effect noncoding transcript
Transcript: ENSMUST00000150983
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: ENSMUST00000138591
Predicted Effect probably benign
Transcript: ENSMUST00000137126
Predicted Effect probably benign
Transcript: ENSMUST00000141123
Predicted Effect noncoding transcript
Transcript: ENSMUST00000200643
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: 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: ENSMUST00000199756
Meta Mutation Damage Score 0.6338 question?
Coding Region Coverage
  • 1x: 99.9%
  • 3x: 99.6%
  • 10x: 98.0%
  • 20x: 94.3%
Validation Efficiency 99% (66/67)
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: 63 list
GeneRefVarChr/LocMutationPredicted EffectZygosity
Abca13 G T 11: 9,251,259 (GRCm39) probably null Het
Acsm1 G A 7: 119,232,289 (GRCm39) G62D probably damaging Het
Actrt3 T A 3: 30,653,899 (GRCm39) I34F probably damaging Het
Adgrf5 T C 17: 43,761,974 (GRCm39) I1223T possibly damaging Het
Adora2a T C 10: 75,161,981 (GRCm39) F40S possibly damaging Het
Ano8 T C 8: 71,933,441 (GRCm39) probably benign Het
Arid1b T A 17: 5,293,107 (GRCm39) L675Q probably damaging Het
Atg2b T C 12: 105,589,741 (GRCm39) I1837V possibly damaging Het
Atp10b A G 11: 43,145,109 (GRCm39) Y1284C probably damaging Het
B3gnt7 G T 1: 86,233,237 (GRCm39) G44V probably damaging Het
Chrna1 G T 2: 73,403,653 (GRCm39) H99N probably benign Het
Cnksr1 T C 4: 133,961,204 (GRCm39) H220R probably damaging Het
Cpsf2 T A 12: 101,965,619 (GRCm39) probably null Het
Daglb T C 5: 143,489,096 (GRCm39) L651P probably benign Het
Ddx60 A G 8: 62,398,974 (GRCm39) D231G possibly damaging Het
Ehd4 A C 2: 119,932,904 (GRCm39) F174C probably damaging Het
Emsy G T 7: 98,260,060 (GRCm39) P9T probably damaging Het
Fnbp1l T C 3: 122,352,805 (GRCm39) E217G probably benign Het
Gm11596 A T 11: 99,683,524 (GRCm39) C199S unknown Het
Gmps T G 3: 63,908,964 (GRCm39) C489G probably benign Het
Gpsm1 T C 2: 26,215,425 (GRCm39) Y296H probably benign Het
Heatr5b T C 17: 79,138,870 (GRCm39) T91A possibly damaging Het
Hs3st3b1 A T 11: 63,780,324 (GRCm39) W268R probably damaging Het
Il27ra T C 8: 84,758,773 (GRCm39) probably null Het
Itga5 T A 15: 103,265,880 (GRCm39) I156F probably damaging Het
Kcnmb3 T A 3: 32,527,976 (GRCm39) D96V probably damaging Het
Khdrbs1 T A 4: 129,609,965 (GRCm39) N417Y probably damaging Het
Loxhd1 A G 18: 77,383,454 (GRCm39) N118D possibly damaging Het
Mdm4 A G 1: 132,919,845 (GRCm39) L341P probably damaging Het
Mecom T C 3: 30,047,797 (GRCm39) E225G possibly damaging Het
Megf8 G A 7: 25,046,796 (GRCm39) G1560S possibly damaging Het
Mfsd13a A T 19: 46,356,321 (GRCm39) D142V probably damaging Het
Muc5b A T 7: 141,415,181 (GRCm39) Y2709F possibly damaging Het
Nelfa A T 5: 34,056,223 (GRCm39) I480N probably damaging Het
Or10ak8 G A 4: 118,773,944 (GRCm39) S240F probably damaging Het
Or8b36 ATTGCTGTTT ATTGCTGTTTGCTGTTT 9: 37,937,836 (GRCm39) probably null Het
Palld G T 8: 62,003,186 (GRCm39) N304K probably damaging Het
Pcsk5 A G 19: 17,488,856 (GRCm39) L988P probably damaging Het
Prmt1 A T 7: 44,631,251 (GRCm39) F34I probably damaging Het
Pzp A G 6: 128,465,979 (GRCm39) S1234P probably benign Het
Ralb A T 1: 119,405,870 (GRCm39) probably null Het
Robo2 T A 16: 73,717,617 (GRCm39) D141V probably damaging Het
Rsrc1 T C 3: 67,262,895 (GRCm39) I283T probably benign Het
Sec62 A T 3: 30,864,631 (GRCm39) K165M unknown Het
Sez6 A G 11: 77,868,648 (GRCm39) D974G probably damaging Het
Shc2 T A 10: 79,465,752 (GRCm39) I187F possibly damaging Het
Shroom3 G A 5: 93,112,267 (GRCm39) R1876Q probably damaging Het
Siglecg C A 7: 43,061,441 (GRCm39) N481K possibly damaging Het
Skil T A 3: 31,152,002 (GRCm39) F175I probably damaging Het
Slc1a1 T C 19: 28,886,935 (GRCm39) V432A probably damaging Het
Slit3 G T 11: 35,591,310 (GRCm39) G1374V possibly damaging Het
Snx14 T C 9: 88,273,859 (GRCm39) Y644C probably damaging Het
Snx33 T A 9: 56,833,983 (GRCm39) I29F possibly damaging Het
Sos1 T A 17: 80,756,764 (GRCm39) I263L probably benign Het
Susd2 C T 10: 75,473,853 (GRCm39) A581T probably damaging Het
Tbpl2 C A 2: 23,966,028 (GRCm39) V320F probably damaging Het
Tmem209 A G 6: 30,505,794 (GRCm39) S171P probably benign Het
Tprkb T A 6: 85,893,172 (GRCm39) probably null Het
Tspan11 G A 6: 127,916,061 (GRCm39) S119N probably benign Het
Ulk2 A T 11: 61,672,572 (GRCm39) V922D probably damaging Het
Zfp267 A G 3: 36,219,303 (GRCm39) H442R possibly damaging Het
Zfp976 A C 7: 42,263,610 (GRCm39) Y76D probably damaging Het
Zkscan2 G A 7: 123,088,993 (GRCm39) T426I 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
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
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
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'- CTGAGAGATGCCATGAGTGC -3'
(R):5'- CGGCATCACCTGAGACTTTCTC -3'

Sequencing Primer
(F):5'- CCATGAGTGCAGTGGTAGGC -3'
(R):5'- TCACCCCTTAACTTTGTGAAGG -3'
Posted On 2017-10-10