Atlas of Genetics and Cytogenetics in Oncology and Haematology

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ACHE (acetylcholinesterase)

Written2012-05Hermona Soreq, David S Greenberg
Department of Biological Chemistry, the Edmond, Lily Safra Center of Neuroscience, The Hebrew University of Jerusalem, 91904 Jerusalem, Israel

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HGNC Alias nameYt blood group
HGNC Previous nameYT
HGNC Previous nameacetylcholinesterase (YT blood group)
 acetylcholinesterase (Yt blood group)
LocusID (NCBI) 43
Atlas_Id 44317
Location 7q22.1  [Link to chromosome band 7q22]
Location_base_pair Starts at 100889994 and ends at 100896994 bp from pter ( according to GRCh38/hg38-Dec_2013)  [Mapping ACHE.png]
Fusion genes
(updated 2017)
Data from Atlas, Mitelman, Cosmic Fusion, Fusion Cancer, TCGA fusion databases with official HUGO symbols (see references in chromosomal bands)
CDK6 (7q21.2)::ACHE (7q22.1)CUX1 (7q22.1)::ACHE (7q22.1)


  The human AChE gene is located at q22 of the long arm of chromosome 7. The AChE mRNA has multiple isoforms which arise from both alternative promoter usage in the 5' of the gene and alternative splicing of exons 4, 5 and 6.
Description The ACHE gene spans about 6 kilobases on chromosome 7q22.
Transcription The gene gives rise to multiple alternatively spliced transcripts. These include AChE-Synaptic (AChE-S), AChE-Erythrocyte (AChE-E) and AChE-Read through (AChE-R). AChE-S is the major neuronal transcript. Alternative 3' splicing gives rise to AChE-E, a dimeric glycophosphatidylinositol (GPI)-anchored isoform expressed primarily in erythrocytes. The third variant AChE-R is produced by the inclusion of the normally spliced out intron 4 and is reported to be elevated during stress. In addition, the existence of multiple promoters leads to the production of several variants with extended N-terminal sequences which are transcribed from the alternative promoters although their expression patterns have not yet been well characterized (Soreq and Seidman, 2001; Meshorer and Soreq, 2006).
Pseudogene None.


Description Acetylcholinesterase (AChE) is a 57 kDa protein. AChE can be monomeric (AChE-R), dimeric (AChE-E) or tetrameric (AChE-S). Tetrameric AChE-S can further interact with collagen Q (ColQ), enabling anchorage to neuromuscular junctions (NMJs), and a proline-rich membrane anchor protein (PRiMA) is responsible for the synaptic docking of AChE-S in the brain. AChE-R is a soluble monomer with a unique naturally unfolded C-terminal peptide. Because AChE-E and AChE-R are incapable of anchorage to the NMJ or to synaptic membranes through ColQ or PRiMA, only the AChE-S form of the enzyme is regarded as truly "synaptic" (Massoulié et al., 1993; Taylor et al., 1993; Silman and Sussman, 2008).
Expression Functional heterogeneity in AChE activity is regulated at the transcriptional, post-transcriptional and post-translational levels, leading to complex expression patterns that reflect tissue and cell-type specificity, differentiation state, physiological condition and response to external stimuli. Recent studies have also looked at regulation of AChE expression by microRNA (Hanin and Soreq, 2011).
Localisation Intracellular, extracellular, plasma, cerebrospinal fluid.
Function Acetylcholinesterase is a type B hydrolase that rapidly and selectively hydrolyzes the neurotransmitter acetylcholine (ACh) at cholinergic synapses, as well as at neuromuscular junctions (Soreq and Seidman, 2001). In addition to its catalytic function of the hydrolysis of acetylcholine, AChE has been shown to be involved in many non-cholinergic functions, such as cell growth, stem cell differentiation (Sperling et al., 2008; Falugi and Aluigi, 2012), neuritogenesis, cell adhesion (Paraoanu and Layer, 2008), synaptogenesis, activation of dopaminergic neurons, tumorigenesis, amyloid fibril assembly (Inestrosa et al., 1996; Alvarez et al., 1997), haematopoiesis and thrombopoiesis (Greenfield, 1996; Layer, 1996; Small et al., 1996). The role of acetylcholinesterase in modulating the regulation of cholinergic function is still being investigated (Shaked et al., 2009; Schliebs and Arendt, 2011). The role of AChE inhibitors in many neurodegenerative and neurodevelopmental pathologies is also being studied (Hargreaves, 2012; Li et al., 2012).
Homology AChE is widely conserved in the animal kingdom and is found in mammals, Drosophila, C. elegans and Torpedo californica, among others.


Note No natural disease-causing mutations have been reported but a number of single nucleotide polymorphisms (SNPs) are known which may affect transcriptional activity and immune properties.

Implicated in

Entity Primary ovarian carcinomas
Note Significant amplification and mutagenesis of both the ache and the highly homologous BChE gene were identified in malignant tumors. The frequent co-amplification in ovarian carcinomas of ACHE implicates cholinesterases in neoplastic growth and/or proliferation (Zakut et al., 1990).
Entity Glioblastoma multiforme
Note AChE mRNA accumulates in primary human astrocytomas in a manner associated with these tumors' grade of aggressiveness (Perry et al., 2002). CREB regulation allows AChE-R-induced, PKA-mediated proliferation of glioblastoma tumors (Perry et al., 2004).
Entity Leukemia
Note AChE-S may be a regulator of hematopoiesis, affecting cell fate decisions downstream to the GEMM progenitor cells (Perry et al., 2007). Deletion of the acetylcholinesterase locus at 7q22 is associated with myelodysplastic syndromes (MDS) and acute myeloid leukaemia (AML) (Stephenson et al., 1996).
Entity Breast cancer
Note In a recent study, amplifications and deletions in the AChE and BChE genes were investigated in sporadic breast tumors using real-time polymerase chain reaction and the relative quantification method and the majority of the tumor tissues showed a notable number of both deletions and amplifications of both the AChE and BChE genes (Bernardi et al., 2010).
Entity Alzheimer's disease
Note The loss of cholinergic neurons has long been believed to be an important aspect of Alzheimer's pathology (Oddo and LaFerla, 2006; Schliebs and Arendt, 2011) and increasing the level of acetylcholine by the use of cholinesterase inhibitors is one of the few pharmacological interventions available for the treatment of Alzheimer's disease (Birks, 2006; Shanks et al., 2009). AChE has been identified in the amyloid plaques found in Alzheimers disease and the isoforms of AChE have different effects on the extent of plaque development (Berson et al., 2008).
Entity Inflammation
Note Being a major regulator of acetylcholine levels, AChE may relieve the cholinergic blockade of inflammation (Shaked et al., 2009). Correspondingly, increasing levels of the AChE-targeted microRNA-132, and presumably other AChE-targeted microRNAs can potentiate this blockade (Hanin and Soreq, 2011).


Acetylcholinesterase promotes the aggregation of amyloid-beta-peptide fragments by forming a complex with the growing fibrils.
Alvarez A, Opazo C, Alarcon R, Garrido J, Inestrosa NC.
J Mol Biol. 1997 Sep 26;272(3):348-61.
PMID 9325095
Amplification and deletion of the ACHE and BCHE cholinesterase genes in sporadic breast cancer.
Bernardi CC, Ribeiro Ede S, Cavalli IJ, Chautard-Freire-Maia EA, Souza RL.
Cancer Genet Cytogenet. 2010 Mar;197(2):158-65.
PMID 20193849
Changes in readthrough acetylcholinesterase expression modulate amyloid-beta pathology.
Berson A, Knobloch M, Hanan M, Diamant S, Sharoni M, Schuppli D, Geyer BC, Ravid R, Mor TS, Nitsch RM, Soreq H.
Brain. 2008 Jan;131(Pt 1):109-19. Epub 2007 Dec 3.
PMID 18056160
Cholinesterase inhibitors for Alzheimer's disease.
Birks J.
Cochrane Database Syst Rev. 2006 Jan 25;(1):CD005593. (REVIEW)
PMID 16437532
Early appearance and possible functions of non-neuromuscular cholinesterase activities.
Falugi C, Aluigi MG.
Front Mol Neurosci. 2012;5:54. Epub 2012 Apr 20.
PMID 22529777
Non-classical actions of cholinesterases: role in cellular differentiation, tumorigenesis and Alzheimer's disease.
Greenfield S.
Neurochem Int. 1996 May-Jun;28(5-6):485-90. (REVIEW)
PMID 8792328
Cholinesterase-Targeting microRNAs Identified in silico Affect Specific Biological Processes.
Hanin G, Soreq H.
Front Mol Neurosci. 2011;4:28. Epub 2011 Oct 5.
PMID 22007158
Neurodegenerations induced by organophosphorous compounds.
Hargreaves AJ.
Adv Exp Med Biol. 2012;724:189-204. (REVIEW)
PMID 22411244
Acetylcholinesterase accelerates assembly of amyloid-beta-peptides into Alzheimer's fibrils: possible role of the peripheral site of the enzyme.
Inestrosa NC, Alvarez A, Perez CA, Moreno RD, Vicente M, Linker C, Casanueva OI, Soto C, Garrido J.
Neuron. 1996 Apr;16(4):881-91.
PMID 8608006
Non-classical actions of cholinesterases: role in cellular differentiation, tumorigenesis and Alzheimer's disease.
Layer PG.
Neurochem Int. 1996 May-Jun;28(5-6):491-5. (REVIEW)
PMID 8792329
Evaluation of epidemiology and animal data for risk assessment: chlorpyrifos developmental neurobehavioral outcomes.
Li AA, Lowe KA, McIntosh LJ, Mink PJ.
J Toxicol Environ Health B Crit Rev. 2012;15(2):109-84. (REVIEW)
PMID 22401178
Structure and functions of acetylcholinesterase and butyrylcholinesterase.
Massoulie J, Sussman J, Bon S, Silman I.
Prog Brain Res. 1993;98:139-46. (REVIEW)
PMID 8248501
Virtues and woes of AChE alternative splicing in stress-related neuropathologies.
Meshorer E, Soreq H.
Trends Neurosci. 2006 Apr;29(4):216-24. Epub 2006 Mar 3. (REVIEW)
PMID 16516310
The role of nicotinic acetylcholine receptors in Alzheimer's disease.
Oddo S, LaFerla FM.
J Physiol Paris. 2006 Mar-May;99(2-3):172-9. Epub 2006 Jan 30. (REVIEW)
PMID 16448808
Acetylcholinesterase in cell adhesion, neurite growth and network formation.
Paraoanu LE, Layer PG.
FEBS J. 2008 Feb;275(4):618-24. Epub 2008 Jan 17. (REVIEW)
PMID 18205832
Acetylcholinesterase/C terminal binding protein interactions modify Ikaros functions, causing T lymphopenia.
Perry C, Pick M, Podoly E, Gilboa-Geffen A, Zimmerman G, Sklan EH, Ben-Shaul Y, Diamant S, Soreq H.
Leukemia. 2007 Jul;21(7):1472-80. Epub 2007 May 3.
PMID 17476278
CREB regulates AChE-R-induced proliferation of human glioblastoma cells.
Perry C, Sklan EH, Soreq H.
Neoplasia. 2004 May-Jun;6(3):279-86.
PMID 15153340
The cholinergic system in aging and neuronal degeneration.
Schliebs R, Arendt T.
Behav Brain Res. 2011 Aug 10;221(2):555-63. Epub 2010 Dec 9. (REVIEW)
PMID 21145918
MicroRNA-132 potentiates cholinergic anti-inflammatory signaling by targeting acetylcholinesterase.
Shaked I, Meerson A, Wolf Y, Avni R, Greenberg D, Gilboa-Geffen A, Soreq H.
Immunity. 2009 Dec 18;31(6):965-73. Epub 2009 Dec 10.
PMID 20005135
Cholinesterase inhibition: is there evidence for disease-modifying effects?
Shanks M, Kivipelto M, Bullock R, Lane R.
Curr Med Res Opin. 2009 Oct;25(10):2439-46. (REVIEW)
PMID 19678754
Acetylcholinesterase: how is structure related to function?
Silman I, Sussman JL.
Chem Biol Interact. 2008 Sep 25;175(1-3):3-10. Epub 2008 Jun 6. (REVIEW)
PMID 18586019
Non-classical actions of cholinesterases: role in cellular differentiation, tumorigenesis and Alzheimer's disease.
Small DH, Michaelson S, Sberna G.
Neurochem Int. 1996 May-Jun;28(5-6):453-83. (REVIEW)
PMID 8792327
Acetylcholinesterase--new roles for an old actor.
Soreq H, Seidman S.
Nat Rev Neurosci. 2001 Apr;2(4):294-302. (REVIEW)
PMID 11283752
Characterisation of cholinesterase expression during murine embryonic stem cell differentiation.
Sperling LE, Steinert G, Boutter J, Landgraf D, Hescheler J, Pollet D, Layer PG.
Chem Biol Interact. 2008 Sep 25;175(1-3):156-60. Epub 2008 Jun 6.
PMID 18588865
Deletion of the acetylcholinesterase locus at 7q22 associated with myelodysplastic syndromes (MDS) and acute myeloid leukaemia (AML).
Stephenson J, Czepulkowski B, Hirst W, Mufti GJ.
Leuk Res. 1996 Mar;20(3):235-41.
PMID 8637218
Structure and regulation of expression of the acetylcholinesterase gene.
Taylor P, Li Y, Camp S, Rachinsky TL, Ekstrom T, Getman D, Fuentes ME, Vellom DC, Radic Z.
Chem Biol Interact. 1993 Jun;87(1-3):199-207. (REVIEW)
PMID 8343976
Acetylcholinesterase and butyrylcholinesterase genes coamplify in primary ovarian carcinomas.
Zakut H, Ehrlich G, Ayalon A, Prody CA, Malinger G, Seidman S, Ginzberg D, Kehlenbach R, Soreq H.
J Clin Invest. 1990 Sep;86(3):900-8.
PMID 2394839


This paper should be referenced as such :
Soreq, H ; Greenberg, DS
ACHE (acetylcholinesterase)
Atlas Genet Cytogenet Oncol Haematol. 2012;16(10):710-713.
Free journal version : [ pdf ]   [ DOI ]

External links

HGNC (Hugo)ACHE   108
LRG (Locus Reference Genomic)LRG_804
Entrez_Gene (NCBI)ACHE    acetylcholinesterase (Cartwright blood group)
GeneCards (Weizmann)ACHE
Ensembl hg19 (Hinxton)ENSG00000087085 [Gene_View]
Ensembl hg38 (Hinxton)ENSG00000087085 [Gene_View]  ENSG00000087085 [Sequence]  chr7:100889994-100896994 [Contig_View]  ACHE [Vega]
ICGC DataPortalENSG00000087085
Genatlas (Paris)ACHE
SOURCE (Princeton)ACHE
Genetics Home Reference (NIH)ACHE
Genomic and cartography
GoldenPath hg38 (UCSC)ACHE  -     chr7:100889994-100896994 -  7q22.1   [Description]    (hg38-Dec_2013)
GoldenPath hg19 (UCSC)ACHE  -     7q22.1   [Description]    (hg19-Feb_2009)
GoldenPathACHE - 7q22.1 [CytoView hg19]  ACHE - 7q22.1 [CytoView hg38]
Genome Data Viewer NCBIACHE [Mapview hg19]  
OMIM100740   112100   
Gene and transcription
Genbank (Entrez)AF334270 AI831696 AK223443 AK291321 AY389977
RefSeq transcript (Entrez)NM_000665 NM_001282449 NM_001302621 NM_001302622 NM_001367915 NM_001367917 NM_001367918 NM_001367919 NM_015831
Consensus coding sequences : CCDS (NCBI)ACHE
Gene ExpressionACHE [ NCBI-GEO ]   ACHE [ EBI - ARRAY_EXPRESS ]   ACHE [ SEEK ]   ACHE [ MEM ]
Gene Expression Viewer (FireBrowse)ACHE [ Firebrowse - Broad ]
GenevisibleExpression of ACHE in : [tissues]  [cell-lines]  [cancer]  [perturbations]  
BioGPS (Tissue expression)43
GTEX Portal (Tissue expression)ACHE
Human Protein AtlasENSG00000087085-ACHE [pathology]   [cell]   [tissue]
Protein : pattern, domain, 3D structure
Domain families : Pfam (Sanger)
Domain families : Pfam (NCBI)
Conserved Domain (NCBI)ACHE
Human Protein Atlas [tissue]ENSG00000087085-ACHE [tissue]
Protein Interaction databases
Ontologies - Pathways
PubMed217 Pubmed reference(s) in Entrez
GeneRIFsGene References Into Functions (Entrez)
REVIEW articlesautomatic search in PubMed
Last year publicationsautomatic search in PubMed

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indexed on : Fri Oct 8 21:11:42 CEST 2021

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