Mutagenetix > Incidental Mutation

Incidental Mutation 'R6526:Ache'

521835

Institutional Source

Beutler Lab

Gene Symbol

Ache

Ensembl Gene

ENSMUSG00000023328

Gene Name

acetylcholinesterase

Synonyms

MMRRC Submission

044652-MU

Accession Numbers

Essential gene?

Possibly essential (E-score: 0.685) question?

Stock #

R6526 (G1)

Quality Score

225.009

Status

Validated

Chromosome

Chromosomal Location

137286516-137292728 bp(+) (GRCm39)

Type of Mutation

missense

DNA Base Change (assembly)

T to A at 137288906 bp (GRCm39)

Zygosity

Heterozygous

Amino Acid Change

Leucine to Glutamine at position 204 (L204Q)

Ref Sequence

ENSEMBL: ENSMUSP00000083097 (fasta)

Gene Model

predicted gene model for transcript(s): [ENSMUST00000024099] [ENSMUST00000052825] [ENSMUST00000085934] [ENSMUST00000125195] [ENSMUST00000132191] [ENSMUST00000137126] [ENSMUST00000138591] [ENSMUST00000196208] [ENSMUST00000141123]

AlphaFold

P21836

Predicted Effect

probably damaging
Transcript: ENSMUST00000024099
AA Change: L204Q

PolyPhen 2 Score 1.000 (Sensitivity: 0.00; Specificity: 1.00)

SMART Domains

Protein: ENSMUSP00000024099
Gene: ENSMUSG00000023328
AA Change: L204Q

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: 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: L204Q

PolyPhen 2 Score 1.000 (Sensitivity: 0.00; Specificity: 1.00)

SMART Domains

Protein: ENSMUSP00000083097
Gene: ENSMUSG00000023328
AA Change: L204Q

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

probably benign
Transcript: ENSMUST00000138591

Predicted Effect

probably damaging
Transcript: ENSMUST00000196208
AA Change: L204Q

PolyPhen 2 Score 0.994 (Sensitivity: 0.69; Specificity: 0.97)

SMART Domains

Protein: ENSMUSP00000142427
Gene: ENSMUSG00000023328
AA Change: L204Q

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: ENSMUST00000150983

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000196840

Predicted Effect

probably benign
Transcript: ENSMUST00000141123

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000184134

Meta Mutation Damage Score

0.6467

Coding Region Coverage

1x: 99.9%
3x: 99.5%
10x: 97.4%
20x: 91.5%

Validation Efficiency

100% (72/72)

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: 72 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
Aamp	A	G	1: 74,323,331 (GRCm39)		probably null	Het
Abcc3	C	T	11: 94,250,198 (GRCm39)	G975D	probably benign	Het
Abhd13	G	A	8: 10,037,777 (GRCm39)	G125S	probably damaging	Het
Acnat2	A	G	4: 49,383,497 (GRCm39)	S19P	probably benign	Het
Adprh	A	G	16: 38,267,638 (GRCm39)	Y216H	probably benign	Het
Anapc1	T	A	2: 128,514,055 (GRCm39)	K429*	probably null	Het
Anxa13	T	C	15: 58,208,353 (GRCm39)		noncoding transcript	Het
Aprt	A	C	8: 123,303,555 (GRCm39)	L6W	probably damaging	Het
Arhgef15	T	C	11: 68,840,820 (GRCm39)	T569A	probably damaging	Het
Atp11a	T	C	8: 12,914,999 (GRCm39)	L1139P	probably benign	Het
Atp2b4	A	G	1: 133,639,467 (GRCm39)	S1136P	probably damaging	Het
B9d1	T	A	11: 61,399,923 (GRCm39)	Y90*	probably null	Het
Btla	G	A	16: 45,059,457 (GRCm39)	A54T	probably damaging	Het
Cd63	T	C	10: 128,747,358 (GRCm39)	V35A	probably benign	Het
Chek2	T	C	5: 110,996,556 (GRCm39)	F173L	probably damaging	Het
Cntnap3	T	A	13: 64,929,702 (GRCm39)	N499I	possibly damaging	Het
Cog4	T	C	8: 111,608,418 (GRCm39)	L738P	probably damaging	Het
Cops6	T	C	5: 138,162,162 (GRCm39)		probably null	Het
Cpeb1	T	A	7: 81,011,417 (GRCm39)	I175F	probably benign	Het
Cyp3a16	C	T	5: 145,392,705 (GRCm39)	D174N	probably benign	Het
Dnah6	T	G	6: 73,051,687 (GRCm39)	I2984L	probably benign	Het
Dock10	A	T	1: 80,564,068 (GRCm39)	I540N	probably damaging	Het
Elf5	A	G	2: 103,269,578 (GRCm39)	Y53C	probably damaging	Het
Elmod2	T	C	8: 84,046,086 (GRCm39)	T164A	probably damaging	Het
Elp1	T	C	4: 56,798,812 (GRCm39)		probably null	Het
Epn3	A	G	11: 94,385,758 (GRCm39)		probably null	Het
Fam151a	A	T	4: 106,591,201 (GRCm39)	I15F	possibly damaging	Het
Gm11115	T	A	5: 88,301,909 (GRCm39)		probably null	Het
Golga3	T	A	5: 110,352,761 (GRCm39)	I884N	probably damaging	Het
Gria2	A	T	3: 80,599,776 (GRCm39)	F703I	probably damaging	Het
Gtf2h3	C	T	5: 124,722,360 (GRCm39)	T121I	probably benign	Het
Gtpbp2	A	T	17: 46,475,037 (GRCm39)		probably null	Het
Herc2	T	C	7: 55,807,078 (GRCm39)	S2419P	probably damaging	Het
Inpp5d	T	C	1: 87,603,972 (GRCm39)		probably benign	Het
Kdm2b	C	A	5: 123,099,532 (GRCm39)	V136F	probably damaging	Het
Klra2	T	A	6: 131,198,839 (GRCm39)	D234V	probably benign	Het
Lct	A	T	1: 128,228,215 (GRCm39)	S1093T	probably benign	Het
Marchf9	A	G	10: 126,892,558 (GRCm39)	L310P	probably benign	Het
Morc1	G	T	16: 48,407,487 (GRCm39)	E668*	probably null	Het
Nbas	A	T	12: 13,455,426 (GRCm39)	L1213F	probably damaging	Het
Neto1	A	G	18: 86,516,873 (GRCm39)	T397A	possibly damaging	Het
Oit3	A	G	10: 59,265,462 (GRCm39)	C268R	probably damaging	Het
Or5p55	A	G	7: 107,566,669 (GRCm39)	T22A	probably benign	Het
Pcx	T	C	19: 4,654,523 (GRCm39)	F312L	probably benign	Het
Pitx2	T	C	3: 129,008,432 (GRCm39)		probably null	Het
Pkhd1l1	G	A	15: 44,361,485 (GRCm39)		probably null	Het
Polr1a	C	A	6: 71,906,427 (GRCm39)	D414E	possibly damaging	Het
Pramel27	A	G	4: 143,579,384 (GRCm39)	D323G	probably damaging	Het
Prkch	T	C	12: 73,749,549 (GRCm39)	Y381H	probably damaging	Het
Ptger3	T	A	3: 157,273,139 (GRCm39)	V162E	probably damaging	Het
Ptgr2	T	G	12: 84,360,726 (GRCm39)	M332R	probably damaging	Het
Ptprq	G	T	10: 107,378,514 (GRCm39)	S2009*	probably null	Het
Pwwp3a	A	G	10: 80,068,113 (GRCm39)	T86A	probably benign	Het
Rangrf	C	T	11: 68,864,514 (GRCm39)	G11R	probably damaging	Het
Rbl2	A	T	8: 91,823,467 (GRCm39)	Q465L	probably benign	Het
Rhbdd1	A	T	1: 82,318,380 (GRCm39)	M88L	probably benign	Het
Setd2	G	A	9: 110,361,785 (GRCm39)	M13I	probably benign	Het
Sirpb1a	T	C	3: 15,444,080 (GRCm39)	Y384C	probably damaging	Het
Slc13a1	C	T	6: 24,097,611 (GRCm39)	G439S	probably damaging	Het
Slc41a1	T	A	1: 131,768,887 (GRCm39)	I239N	probably damaging	Het
Slit2	T	A	5: 48,461,509 (GRCm39)	C1502S	probably damaging	Het
Slit3	G	A	11: 35,552,119 (GRCm39)	E888K	probably benign	Het
Srrm3	G	T	5: 135,864,088 (GRCm39)	R62L	probably damaging	Het
Synm	A	G	7: 67,385,331 (GRCm39)	V777A	possibly damaging	Het
Trmt13	T	A	3: 116,385,864 (GRCm39)	N31I	probably damaging	Het
Trpm8	G	A	1: 88,289,720 (GRCm39)	E893K	probably damaging	Het
Uqcc1	A	G	2: 155,693,343 (GRCm39)	F197S	probably damaging	Het
Vmn1r67	T	A	7: 10,181,598 (GRCm39)	N287K	probably benign	Het
Vmn2r44	A	T	7: 8,381,098 (GRCm39)	M265K	probably benign	Het
Wwc1	C	T	11: 35,744,264 (GRCm39)	E853K	probably benign	Het
Xdh	C	A	17: 74,207,546 (GRCm39)	C937F	probably damaging	Het
Zfp846	T	A	9: 20,505,167 (GRCm39)	N342K	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
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
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'- CTGTCCTCATCTGGATCTATGG -3'
(R):5'- CTATCAGCTCGGTGTCATTGC -3'

Sequencing Primer
(F):5'- CCTCATCTGGATCTATGGGGGTG -3'
(R):5'- CCATTGGGTGTGCCACTCTG -3'

Posted On

2018-06-06