ACHE

Summary

ACHE (acetylcholinesterase (Yt blood group), HGNC:108) is a protein-coding gene on chromosome 7q22.1, encoding Acetylcholinesterase (P22303). Hydrolyzes rapidly the acetylcholine neurotransmitter released into the synaptic cleft allowing to terminate the signal transduction at the neuromuscular junction.

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. AChE activity may constitute a sensitive biomarker of RBC ageing in vivo, and thus, may be of aid in understanding the effects of transfusion

Source: NCBI Gene 43 — RefSeq curated summary.

At a glance

• GWAS associations: 35 (top 3% of genes corpus-wide)
• Clinical variants (ClinVar): 86 total — 7 pathogenic, 1 likely-pathogenic
• GTEx eGene: eQTL in 32 tissues, sQTL in 12 (q < 0.05)
• Drug target: yes — 20 curated mechanism-of-action drugs, 2 via a complex or family; 153 molecules with ChEMBL bioactivity (top 1% of genes corpus-wide)
• Approved drugs (ChEMBL mechanism of action): 17 — Ambenonium Chloride, Benzgalantamine Gluconate, Demecarium Bromide, +14 more
• Approved drugs acting on a complex or family including it: 2 — Rivastigmine, Tacrine Hydrochloride (Cholinesterases; ACHE & BCHE)
• Constraint (gnomAD): pLI 0.81 (intermediate), LOEUF 0.55 (moderately constrained)
• MANE Select transcript: NM_000665
• Interaction hub: 1,838 STRING partners (top 9% of genes corpus-wide)
• Notable: 86 clinical variants but no curated precision-oncology (CIViC) evidence yet

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:108
Approved symbol	ACHE
Name	acetylcholinesterase (Yt blood group)
Location	7q22.1
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000087085
Ensembl biotype	protein_coding
OMIM	100740
Entrez	43

Gene structure

Transcript identifiers

Ensembl transcripts: 41 — 32 protein_coding, 8 nonsense_mediated_decay, 1 retained_intron

MANE Select: ENST00000241069

Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 1: 7, TSL 3: 5, TSL 4: 1

ENST00000241069, ENST00000302913, ENST00000411582, ENST00000412389, ENST00000419336, ENST00000426415, ENST00000428317, ENST00000430554, ENST00000440755, ENST00000441605, ENST00000442452, ENST00000445236, ENST00000454485, ENST00000651875, ENST00000894903, ENST00000894904, ENST00000894905, ENST00000894906, ENST00000894907, ENST00000894908, ENST00000894909, ENST00000894910, ENST00000894911, ENST00000932266, ENST00000932267, ENST00000956361, ENST00000956362, ENST00000956363, ENST00000985930, ENST00000985931, ENST00000985932, ENST00001022760, ENST00001022761, ENST00001022762, ENST00001022763, ENST00001022764, ENST00001061738, ENST00001061739, ENST00001061740, ENST00001061741, ENST00001112842

RefSeq mRNA: 8 — MANE Select: NM_000665 NM_000665, NM_001282449, NM_001302621, NM_001302622, NM_001367915, NM_001367917, NM_001367918, NM_001367919

CCDS: CCDS5709, CCDS5710, CCDS64736

Canonical transcript exons

ENST00000241069 — 5 exons

Exon	Start	End
ENSE00001639836	100889994	100890335
ENSE00001873556	100895802	100895888
ENSE00002523632	100893165	100894252
ENSE00002524107	100892334	100892818
ENSE00003568040	100891169	100891338

Expression profiles

Bgee: expression breadth ubiquitous, 202 present calls, max score 95.68.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 7.4021 / max 182.5674, expressed in 916 samples.

Highest expression (Bgee): hindlimb stylopod muscle, hemisphere of cerebellum, cerebellar hemisphere, cerebellar cortex, hypothalamus.

Genetic regulation across tissues (GTEx eQTL / sQTL)

ACHE is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 32 tissues and its splicing (sQTL) in 12 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

showing 20 of 44 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Artery Aorta	eqtl	5.3e-50	+1.07	7:100873422:C:T
Testis	sqtl	6.4e-49	-1.06	7:100896377:T:G
Nerve Tibial	eqtl	1.1e-45	+0.81	7:100901695:G:A
Brain Cerebellar Hemisphere	sqtl	7.1e-44	-1.22	7:100902485:C:T
Artery Tibial	eqtl	1.3e-43	+0.69	7:100895738:G:A
Thyroid	eqtl	3.7e-41	+0.77	7:100895738:G:A
Brain Cerebellum	sqtl	8.5e-35	-1.08	7:100896377:T:G
Adipose Subcutaneous	eqtl	6.9e-24	+0.58	7:100873422:C:T
Heart Atrial Appendage	eqtl	3.1e-20	+0.68	7:100895738:G:A
Skin Sun Exposed Lower leg	eqtl	1.8e-19	+0.36	7:100855586:T:C
Brain Frontal Cortex BA9	sqtl	4.0e-19	-1.01	7:100896377:T:G
Brain Cortex	sqtl	1.6e-18	-0.90	7:100902485:C:T
Liver	eqtl	1.4e-14	+0.58	7:100914499:C:T
Skin Not Sun Exposed Suprapubic	eqtl	2.1e-14	+0.36	7:100855586:T:C
Artery Coronary	eqtl	4.2e-14	+0.75	7:100873422:C:T
Breast Mammary Tissue	eqtl	1.6e-13	+0.50	7:100855586:T:C
Brain Nucleus accumbens basal ganglia	sqtl	2.5e-13	-0.86	7:100896377:T:G
Pancreas	eqtl	1.6e-10	+0.43	7:100873422:C:T
Adrenal Gland	eqtl	1.7e-09	+0.47	7:100873422:C:T
Esophagus Muscularis	eqtl	4.4e-09	+0.23	7:100873422:C:T

FANTOM5 promoters

5 alternative TSS:

Promoter ID	TPM avg	Samples expressed
85253	6.1941	887
85257	0.5404	109
85254	0.3379	127
85252	0.1949	78
85255	0.1348	72

Top tissues by expression

showing 100 of 293 tissues by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
hindlimb stylopod muscle	UBERON:0004252	95.68	gold quality
right hemisphere of cerebellum	UBERON:0014890	95.30	gold quality
cerebellar hemisphere	UBERON:0002245	94.16	gold quality
cerebellar cortex	UBERON:0002129	93.98	gold quality
hypothalamus	UBERON:0001898	92.58	gold quality
cerebellum	UBERON:0002037	91.78	gold quality
gastrocnemius	UBERON:0001388	89.72	gold quality
nucleus accumbens	UBERON:0001882	89.30	gold quality
muscle of leg	UBERON:0001383	88.94	gold quality
triceps brachii	UBERON:0001509	88.68	gold quality
muscle organ	UBERON:0001630	88.22	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	87.97	gold quality
right frontal lobe	UBERON:0002810	87.87	gold quality
skeletal muscle tissue	UBERON:0001134	87.49	gold quality
putamen	UBERON:0001874	87.18	gold quality
caudate nucleus	UBERON:0001873	87.15	gold quality
biceps brachii	UBERON:0001507	86.41	gold quality
prefrontal cortex	UBERON:0000451	86.15	gold quality
cingulate cortex	UBERON:0003027	85.85	gold quality
anterior cingulate cortex	UBERON:0009835	85.75	gold quality
pons	UBERON:0000988	85.54	gold quality
substantia nigra pars compacta	UBERON:0001965	85.39	gold quality
substantia nigra	UBERON:0002038	85.37	gold quality
quadriceps femoris	UBERON:0001377	85.18	silver quality
vastus lateralis	UBERON:0001379	85.13	silver quality
midbrain	UBERON:0001891	84.60	gold quality
substantia nigra pars reticulata	UBERON:0001966	84.50	gold quality
Brodmann (1909) area 9	UBERON:0013540	84.09	gold quality
muscle tissue	UBERON:0002385	83.93	gold quality
superior vestibular nucleus	UBERON:0007227	83.89	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	83.45	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	82.94	gold quality
dorsal root ganglion	UBERON:0000044	82.56	gold quality
frontal cortex	UBERON:0001870	82.31	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	82.10	gold quality
neocortex	UBERON:0001950	81.98	gold quality
brain	UBERON:0000955	81.71	gold quality
amygdala	UBERON:0001876	81.67	gold quality
central nervous system	UBERON:0001017	81.63	gold quality
Brodmann (1909) area 10	UBERON:0013541	81.48	silver quality
forebrain	UBERON:0001890	80.71	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	80.70	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	80.57	gold quality
telencephalon	UBERON:0001893	80.38	gold quality
right atrium auricular region	UBERON:0006631	79.73	gold quality
spinal cord	UBERON:0002240	79.43	gold quality
cortical plate	UBERON:0005343	79.20	gold quality
cerebral cortex	UBERON:0000956	78.95	gold quality
cardiac atrium	UBERON:0002081	78.35	gold quality
mucosa of transverse colon	UBERON:0004991	78.19	gold quality
small intestine Peyer’s patch	UBERON:0003454	77.87	gold quality
diaphragm	UBERON:0001103	77.81	silver quality
adenohypophysis	UBERON:0002196	77.66	gold quality
transverse colon	UBERON:0001157	77.46	gold quality
pituitary gland	UBERON:0000007	76.90	gold quality
small intestine	UBERON:0002108	76.64	gold quality
medulla oblongata	UBERON:0001896	76.46	gold quality
deltoid	UBERON:0001476	75.83	silver quality
ventral tegmental area	UBERON:0002691	75.82	gold quality
Ammon’s horn	UBERON:0001954	75.22	gold quality
muscle layer of sigmoid colon	UBERON:0035805	75.13	gold quality
paraflocculus	UBERON:0005351	74.45	silver quality
lymph node	UBERON:0000029	74.37	gold quality
minor salivary gland	UBERON:0001830	74.25	gold quality
metanephros cortex	UBERON:0010533	74.05	gold quality
body of tongue	UBERON:0011876	73.10	gold quality
temporal lobe	UBERON:0001871	73.05	gold quality
tibialis anterior	UBERON:0001385	72.52	silver quality
colon	UBERON:0001155	72.42	gold quality
trigeminal ganglion	UBERON:0001675	72.35	gold quality
intestine	UBERON:0000160	72.33	gold quality
saliva-secreting gland	UBERON:0001044	72.09	gold quality
inferior vagus X ganglion	UBERON:0005363	71.72	gold quality
lower esophagus mucosa	UBERON:0035834	71.58	gold quality
rectum	UBERON:0001052	71.50	gold quality
large intestine	UBERON:0000059	71.41	gold quality
mouth mucosa	UBERON:0003729	71.41	gold quality
left ovary	UBERON:0002119	71.20	gold quality
prostate gland	UBERON:0002367	71.16	gold quality
sigmoid colon	UBERON:0001159	71.10	gold quality
gluteal muscle	UBERON:0002000	70.92	gold quality
lateral globus pallidus	UBERON:0002476	70.87	silver quality
left uterine tube	UBERON:0001303	70.83	gold quality
endocervix	UBERON:0000458	70.72	gold quality
duodenum	UBERON:0002114	70.69	gold quality
inferior olivary complex	UBERON:0002127	70.62	gold quality
dorsal motor nucleus of vagus nerve	UBERON:0002870	70.49	silver quality
gall bladder	UBERON:0002110	70.42	gold quality
apex of heart	UBERON:0002098	70.40	gold quality
body of uterus	UBERON:0009853	70.39	gold quality
right ovary	UBERON:0002118	70.33	gold quality
right testis	UBERON:0004534	70.31	gold quality
frontal pole	UBERON:0002795	70.30	gold quality
jejunum	UBERON:0002115	69.85	silver quality
cerebellar vermis	UBERON:0004720	69.18	silver quality
endometrium epithelium	UBERON:0004811	69.16	gold quality
body of pancreas	UBERON:0001150	69.09	gold quality
upper lobe of left lung	UBERON:0008952	68.95	gold quality
tongue	UBERON:0001723	68.81	silver quality
superior frontal gyrus	UBERON:0002661	68.77	gold quality

Single-cell (SCXA)

Detected in 4 experiment(s), a significant marker in 3.

Experiment	Marker?	Max mean expression
E-MTAB-7381	yes	371.79
E-MTAB-8498	yes	112.33
E-HCAD-25	yes	9.38
E-ANND-3	no	1.51

HPA expression

RNA tissue specificity: Group enriched

showing 60 of 76 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM
Locus coeruleus	tissue	180.2
Skeletal muscle	tissue	152.9
Pons	tissue	88.8
Postcentral gyrus	tissue	82.4
Thalamus	tissue	68.5
Caudate putamen	tissue	67.9
Hypothalamus	tissue	66.4
Substantia nigra	tissue	65.1
Nucleus accumbens	tissue	58.4
Midbrain	tissue	57.3
Septum	tissue	54.2
Ventral forebrain	tissue	46.1
Tongue	tissue	44.9
Basal ganglia	tissue	42.1
Periaqueductal gray	tissue	40.7
Superior colliculi	tissue	40.4
Medulla oblongata	tissue	39.6
Hippocampus	tissue	36.3
Frontal cortex	tissue	35.8
Spinal cord	tissue	34.6
Putamen	tissue	32.8
Cerebellum	tissue	30.4
Prefrontal cortex	tissue	28.1
Cerebral cortex	tissue	28.1
Hippocampal formation	tissue	28.0
Amygdala	tissue	25.3
Motor cortex	tissue	25.0
Insular cortex	tissue	24.2
Retrosplenial and cingulate cortex	tissue	24.1
Entorhinal cortex	tissue	24.0
Retrosplenial cortex	tissue	23.1
Temporal cortex	tissue	21.2
Somatosensory cortex	tissue	19.3
Occipital cortex	tissue	17.6
Olfactory bulb	tissue	14.1
Bone marrow	tissue	7.4
Pituitary gland	tissue	6.4
Small intestine	tissue	5.8
Retina	tissue	5.3
Duodenum	tissue	4.6
Salivary gland	tissue	4.5
Parathyroid gland	tissue	4.4
Adrenal gland	tissue	4.4
Corpus callosum	tissue	4.0
Heart muscle	tissue	3.5
Lymph node	tissue	3.3
Thymus	tissue	3.3
Colon	tissue	3.0
Choroid plexus	tissue	3.0
Vagina	tissue	2.8
Prostate	tissue	2.3
Esophagus	tissue	2.2
Appendix	tissue	2.1
Rectum	tissue	1.7
Seminal vesicle	tissue	1.5
Tonsil	tissue	1.4
Gallbladder	tissue	1.2
Testis	tissue	1.1
Stomach 1	tissue	1.1
Spleen	tissue	1.0

Brain sub-regions (HPA Brain Atlas): detected in 189; highest nTPM — Lateral hypothalamic area (234.8), Arcuate nucleus (192.1), Nucleus ambiguus (162.3), Ventromedial nucleus (144.3), Pontine raphe nucleus (141.8).

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): AHR, AP1, AR, ASCL1, ATF1, ATF2, CEBPB, CREB1, CTBP2, DIDO1, DLX4, E4F1, EBF1, EGR1, ELK3, ESR1, FOS, FOXC1, GABPA, GRHL3, HR, IRF1, JUN, KLF12, LITAF, MYC, MYOD1, MYOG, MYT1, NCOR1, NCOR2, NFATC1, NFATC3, NFATC4, NFE2L2, NFKB1, NKX3-1, RARB, SMAD3, SOX17

Functional genomics

gnomAD constraint: pLI 0.814, LOEUF 0.546, missense Z 2.75 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD)

ENST00000241069 splits into 4 regions with different missense tolerance; 0 are missense-constrained. Missense variants in a constrained region (low observed/expected) are more likely to be pathogenic. gnomAD

Region (GRCh38)	Missense obs / exp	o/e	Constrained
7:100,890,217–100,891,170	28 / 54.8	0.51	no
7:100,891,171–100,892,341	91 / 83.2	1.09	no
7:100,892,342–100,894,055	397 / 632.5	0.63	no
7:100,894,056–100,894,232	89 / 78.9	1.13	no

Literature-anchored findings (GeneRIF, showing 40)

• Generation of a gp43-gp59-DNA ternary complex is absolutely required for recombination-dependent replication in the bacteriophage T4 system. (PMID:15909989)
• the primer strand is not stably bound within the exonuclease active site in the absence of the beta hairpin loop (PMID:17098747)
• The authors propose that their beta loops facilitate strand separation, while the residues that form the loop have low structural constraints. (PMID:19409904)
• Amino acid substitutions that confer decreased ability to replicate DNA under low-dGTP conditions or drug sensitivity were identified in the new motif, which suggests that the motif functions in regulating the stability of polymerase complexes. (PMID:20493878)
• Data describe the crystal structures of the pol alpha family RB69 DNA polymerase with DNA containing the two most prevalent, spontaneously generated premutagenic lesions (PMID:15057282)
• Results describe the structure of the bacteriophage RB69 replicative DNA polymerase attempting to process an abasic site analog. (PMID:15057283)
• the primer strand is not stably bound within the exonuclease active site in the absence of the beta hairpin loop (PMID:17098747)
• The Y619F substitution would disrupt the hydrogen bond network at the primer terminus and may affect the alignment of the 3’ primer terminus at the polymerase active site, slowing chemistry and overall DNA synthesis. (PMID:17321543)
• Binding of a metal ion to the A site is required for the nucleotidyl transfer reaction, but is insufficient to initiate the enzyme isomerization. Binding of a dNTP, in the absence of a metal ion, is sufficient to induce this conformational change. (PMID:19228036)
• The effect of A and B metal ion site occupancy on the rates of Fingers closing and on the affinity of Rh.dTTP for the E.D binary complex of the catalytic site of RB69 DNA polymerase was studied. (PMID:19228037)
• The authors propose that their beta loops facilitate strand separation, while the residues that form the loop have low structural constraints. (PMID:19409904)
• When Y567A and S565G replacements were combined, mutator activity was strongly decreased compared to that with Y567A replacement alone. (PMID:20950625)
• The structure of an RB69 pol ternary complex at 1.8 A is reported. A network of five highly ordered, buried water molecules can be seen to interact with the N3 and O2 atoms in the minor groove of the DNA duplex. (PMID:21158418)
• The authors show that the S565G/Y567A mutant generally had greater base selectivity than the Y567A mutant and that the kinetic parameters for dNMP insertion, excision of the 3’-terminal nucleotide residue, and primer extension beyond a mispair differed. (PMID:21216248)
• The miscoding potential of 5-hydroxycytosine arises due to template instability in the DNA polymerase active site. (PMID:22026756)
• evaluated the contribution of minor groove hydrogen bonding interactions with RB69pol (PMID:22571765)
• Determined is the crystal structure of the dATP/tC(o)-containing ternary complex of the RB69 DNA polymerase Y567A mutant at 1.9 A resolution; the incoming dATP formed two hydrogen bonds with an imino-tautomerized form of tC(o). (PMID:22616982)
• Data indicate that alanine replacement of residues distant from the active site of the replicative RB69 DNA polymerase renders the enzyme incapable of sustaining phage replication in vivo. (PMID:24116139)
• structures of the various RB69pol ternary complexes can be used to rationalize the results obtained from pre-steady-state kinetic assays[review] (PMID:24720884)
• Co(2+) and Mn(2+) enhanced ground-state binding of both correct and incorrect dNTPs to RB69pol:dideoxy-terminated primer-template complexes. (PMID:27096230)
• The control of the discrimination between dNTP and rNTP in DNA and RNA polymerases has been described. (PMID:27480935)
• serum and erythrocyte membrane enzyme inhibited by antidepressants, fluoxetine, sertraline and amitriptyline, in a dose related manner (PMID:12009429)
• REVIEW: Simulations show how breathing motions in the enzyme facilitate the displacement of substrate from the surface of the enzyme to the buried active site; such motions suggest possible modes of regulation of the activity of the enzyme. (PMID:12069617)
• The aromatic “trapping” of the catalytic histidine is essential for efficient catalysis (PMID:12081473)
• regulation of ACHE expression in developing muscle cells (PMID:12140295)
• complex regulation of its gene expression in brain tumors (PMID:12466963)
• AChE activity in the CSF of Alzeimer’s disease patients is affected differentially by different AChE inhibitors. (AChE) (PMID:12548360)
• AChE was predominantly expressed in neurons of the anterodorsal, midline, ventral, intralaminar, and reticular nuclei. (PMID:12811800)
• analysis of acetylcholinesterase active site (PMID:12851386)
• muscle-induced neuronal AChE expression in co-culture is mediated by a cAMP-dependent signaling (PMID:12963741)
• oxidation of AchE by hydrogen peroxide contributes significantly to the well-established oxidative stress in vitiligo (PMID:14766237)
• analysis of acetylcholinesterase near the active center gorge (PMID:15078872)
• Data suggest that alternative promoter usage combined with alternative splicing may lead to stress-dependent combinatorial complexity of acetylcholinesterase mRNA transcripts and their protein products. (PMID:15123727)
• complexed with abeta protein, is toxic to rat brain beta-amyloid aggregation, laminin expression, reactive astrocytosis, and neuronal cell loss. (PMID:15161650)
• AChE is involved in regulating cell-matrix interactions in bone (PMID:15454088)
• A total of 13 ACHE SNPs were identified, 10 of which are newly described, and five that should produce amino acid substitutions (PMID:15459952)
• This study found a layer 3 magnopyramidal AChERN left-right size asymmetry restricted to Brodmann’s area 45, a component of Broca’s language area. (PMID:15488495)
• findings suggest that inherited interactive weakness of acetylcholinesterase and paraoxonase 1 expression increases the insecticide-induced occurrence of Parkinson’s disease (PMID:15629887)
• Variations were observed in expression of mRNA for presenilin-1, which was highest in singly transgenic hAChE mice, and the stress-inducible form of AChE, which was elevated when both transgenes were present. (PMID:15974894)
• Human plasma contains four esterases: butyrylcholinesterase, paraoxonase, acetylcholinesterase, and albumin. (PMID:16213467)

Cross-species orthologs

45 orthologs

Organism	Symbol	Gene ID
danio_rerio	ache	ENSDARG00000031796
mus_musculus	Ache	ENSMUSG00000023328
rattus_norvegicus	Ache	ENSRNOG00000050841
drosophila_melanogaster	Est-6	FBGN0000592
drosophila_melanogaster	Est-P	FBGN0000594
drosophila_melanogaster	Glt	FBGN0001114
drosophila_melanogaster	Jhe	FBGN0010052
drosophila_melanogaster	alpha-Est1	FBGN0015568
drosophila_melanogaster	alpha-Est10	FBGN0015569
drosophila_melanogaster	alpha-Est2	FBGN0015570
drosophila_melanogaster	alpha-Est3	FBGN0015571
drosophila_melanogaster	alpha-Est4	FBGN0015572
drosophila_melanogaster	alpha-Est6	FBGN0015574
drosophila_melanogaster	alpha-Est7	FBGN0015575
drosophila_melanogaster	alpha-Est8	FBGN0015576
drosophila_melanogaster	alpha-Est9	FBGN0015577
drosophila_melanogaster	CG4757	FBGN0027584
drosophila_melanogaster	CG9287	FBGN0032057
drosophila_melanogaster	CG9289	FBGN0032058
drosophila_melanogaster	CG3841	FBGN0032131
drosophila_melanogaster	CG4382	FBGN0032132
drosophila_melanogaster	Jhedup	FBGN0034076
drosophila_melanogaster	gas	FBGN0034736
drosophila_melanogaster	alpha-Est5	FBGN0261393
caenorhabditis_elegans		WBGENE00000037
caenorhabditis_elegans		WBGENE00000038
caenorhabditis_elegans		WBGENE00007691
caenorhabditis_elegans		WBGENE00007692
caenorhabditis_elegans		WBGENE00007693
caenorhabditis_elegans		WBGENE00007695
caenorhabditis_elegans		WBGENE00008451
caenorhabditis_elegans		WBGENE00011362
caenorhabditis_elegans		WBGENE00011364
caenorhabditis_elegans		WBGENE00013873
caenorhabditis_elegans		WBGENE00013874
caenorhabditis_elegans		WBGENE00013875
caenorhabditis_elegans		WBGENE00015067
caenorhabditis_elegans		WBGENE00015071
caenorhabditis_elegans		WBGENE00015279
caenorhabditis_elegans		WBGENE00015284
caenorhabditis_elegans		WBGENE00016595
caenorhabditis_elegans		WBGENE00016862
caenorhabditis_elegans		WBGENE00016863
caenorhabditis_elegans	cest-27	WBGENE00018958
caenorhabditis_elegans		WBGENE00020688

Paralogs (13): TG (ENSG00000042832), BCHE (ENSG00000114200), NLGN4X (ENSG00000146938), CES5A (ENSG00000159398), NLGN4Y (ENSG00000165246), NLGN1 (ENSG00000169760), NLGN2 (ENSG00000169992), CEL (ENSG00000170835), CES4A (ENSG00000172824), CES3 (ENSG00000172828), CES2 (ENSG00000172831), NLGN3 (ENSG00000196338), CES1 (ENSG00000198848)

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:87876) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 43 distinct phenotype terms.

Mouse phenotype (MP)	Records
tremors	3
decreased body weight	3
muscle weakness	2
decreased body size	2
abnormal posture	2
abnormal vocalization	2
infertility	2
decreased body temperature	2
increased physiological sensitivity to xenobiotic	2
decreased grip strength	2
delayed ear emergence	1
increased neutrophil cell number	1
abnormal heart morphology	1
weakness	1
circling	1
abnormal gait	1
hunched posture	1
impaired righting response	1
abnormal body temperature homeostasis	1
decreased white adipose tissue amount	1
hemorrhage	1
abnormal respiration	1
seizures	1
premature death	1
small heart	1

+18 more (showing top 25).

Additional cross-species homologs

Sequence homologs in species beyond Ensembl Compara’s model organisms, by Diamond local protein alignment (% sequence identity; best hit per species). Lower-identity rows are more distant homologs. The matched accessions’ gene symbols aren’t in biobtree yet, so each row shows the UniProt accession.

Organism	UniProt	Identity	Method
Bos taurus	P32749	100.0%	Diamond
Macaca mulatta	P32751	100.0%	Diamond
Ovis aries	P32753	100.0%	Diamond
Culex quinquefasciatus	Q867X2	100.0%	Diamond
Culex pipiens pipiens	Q867X3	100.0%	Diamond
Culex pipiens	Q86GC8	100.0%	Diamond
Culex torrentium	Q86GC9	100.0%	Diamond
Thermobifida fusca	P86325	99.6%	Diamond
Thermobifida fusca YX	Q47M62	99.6%	Diamond
Felis catus	O62760	99.5%	Diamond
Panthera tigris tigris	O62761	99.5%	Diamond
Geotrichum candidum	P22394	99.5%	Diamond
Geotrichum fermentans	P79066	99.5%	Diamond
Drosophila persimilis	O16171	99.3%	Diamond
Drosophila pseudoobscura pseudoobscura	P25725	99.3%	Diamond
Drosophila miranda	O16169	98.9%	Diamond
Myzus persicae	P35501	98.4%	Diamond
Drosophila mauritiana	P47982	98.3%	Diamond
Drosophila simulans	Q08662	98.3%	Diamond
Tetronarce californica	P04058	97.6%	Diamond
Torpedo marmorata	P07692	97.6%	Diamond
Oryctolagus cuniculus	P21927	97.2%	Diamond
Canis lupus familiaris	P32750	96.5%	Diamond
Sus scrofa	P32752	95.7%	Diamond
Equus caballus	P81908	95.0%	Diamond
Caenorhabditis briggsae	Q27459	94.8%	Diamond
Anopheles gambiae	Q869C3	93.9%	Diamond
Pongo abelii	Q5RCL7	93.4%	Diamond
Macaca fascicularis	O46421	92.9%	Diamond
Diutina rugosa	P20261	88.3%	Diamond
Arabidopsis thaliana	Q1PET6	80.6%	Diamond
Electrophorus electricus	O42275	80.4%	Diamond
Mesocricetus auratus	Q64419	78.4%	Diamond

Genomic neighbors (locus context)

Genes flanking this one on the chromosome (NCBI/Entrez gene neighborhood). Positional context only — some neighbors share regulatory elements (bidirectional promoters, antisense/overlapping transcripts), but chromosomal adjacency is not itself a functional relationship (see Interactions for that).

Symbol	Type	Entrez
MUC3A	protein-coding	4584
UFSP1	protein-coding	402682
MIR6875	ncRNA	102466755
SLC12A9-AS1	ncRNA	105375430
SRRT	protein-coding	51593
SLC12A9	protein-coding	56996
TRIP6	protein-coding	7205

Protein

Protein identifiers

Acetylcholinesterase — P22303 (reviewed: P22303)

All UniProt accessions (8): A0A498U6H7, C9J2S3, C9JD78, C9JZL6, P22303, F8WAR7, F8WD34, F8WD68

UniProt curated annotations — full annotation on UniProt →

Function. Hydrolyzes rapidly the acetylcholine neurotransmitter released into the synaptic cleft allowing to terminate the signal transduction at the neuromuscular junction. Role in neuronal apoptosis.

Subunit / interactions. Interacts with PRIMA1. The interaction with PRIMA1 is required to anchor it to the basal lamina of cells and organize into tetramers. Isoform H generates GPI-anchored dimers; disulfide linked. Isoform T generates multiple structures, ranging from monomers and dimers to collagen-tailed and hydrophobic-tailed forms, in which catalytic tetramers are associated with anchoring proteins that attach them to the basal lamina or to cell membranes. In the collagen-tailed forms, isoform T subunits are associated with a specific collagen, COLQ, which triggers the formation of isoform T tetramers, from monomers and dimers. Isoform R may be monomeric.

Subcellular location. Synapse. Secreted. Cell membrane Nucleus Cell membrane.

Tissue specificity. Isoform H is highly expressed in erythrocytes.

Polymorphism. ACHE is responsible for the Yt blood group system [MIM:112100]. The molecular basis of the Yt(a)=Yt1/Yt(b)=Yt2 blood group antigens is a single variation in position 353; His-353 corresponds to Yt(a) and the rare variant with Asn-353 to Yt(b).

Similarity. Belongs to the type-B carboxylesterase/lipase family.

Isoforms (4)

UniProt ID	Names	Canonical?
P22303-1	T, ACHE-S, synaptic	yes
P22303-2	H, ACHE-E, erythrocytic, E4-E5
P22303-4	R, ACHE-R, readthrough
P22303-3	4

RefSeq proteins (8): NP_000656, NP_001269378, NP_001289550, NP_001289551, NP_001354844, NP_001354846, NP_001354847, NP_001354848 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000997	Cholinesterase	Family
IPR002018	CarbesteraseB	Domain
IPR014788	AChE_tetra	Domain
IPR019819	Carboxylesterase_B_CS	Conserved_site
IPR019826	Carboxylesterase_B_AS	Active_site
IPR029058	AB_hydrolase_fold	Homologous_superfamily
IPR050654	AChE-related_enzymes	Family

Pfam: PF00135, PF08674

Enzyme classification (BRENDA)

• EC 3.1.1.7 — acetylcholinesterase (BRENDA: 125 organisms, 230 substrates, 2038 inhibitors, 343 Km, 72 kcat entries)
• EC 3.1.1.8 — cholinesterase (BRENDA: 97 organisms, 292 substrates, 1528 inhibitors, 221 Km, 106 kcat entries)
• EC 3.5.1.13 — aryl-acylamidase (BRENDA: 52 organisms, 138 substrates, 181 inhibitors, 55 Km, 24 kcat entries)

Substrate kinetics (BRENDA)

101 substrates with measured Km, best-characterized 15. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
ACETYLTHIOCHOLINE	0.0062–34	131
BUTYRYLTHIOCHOLINE	0.0001–6	47
ACETYLTHIOCHOLINE IODIDE	0.0002–5.8	42
ACETYLCHOLINE	0.0001–2.36	38
PROPIONYLTHIOCHOLINE	0.006–27.912	37
BUTYRYLTHIOCHOLINE	0.0029–5.14	33
ACETYLTHIOCHOLINE	0.019–4.8	30
PROPIONYLTHIOCHOLINE	0.006–5.4	26
BUTYRYLTHIOCHOLINE IODIDE	0.03–3.9	17
3’,4’-DICHLOROPROPIONANILIDE	0.02–25	14
BUTANOYLTHIOCHOLINE	0.0051–0.34	11
BENZOYLCHOLINE	0.003–0.047	10
(-)-COCAINE	0.0031–0.065	6
BENZOYLTHIOCHOLINE	0.0029–0.135	6
BUTYRYLTHIOCHOLINE IODIDE	0.0004–0.59	5

Catalyzed reactions (Rhea)

• acetylcholine + H2O = choline + acetate + H(+) (RHEA:17561)

UniProt features (109 total): helix 36, strand 25, binding site 10, turn 7, mutagenesis site 6, sequence conflict 4, disulfide bond 4, splice variant 4, sequence variant 4, glycosylation site 3, active site 3, signal peptide 1, chain 1, lipid moiety-binding region 1

Structure

Experimental structures (PDB)

showing 30 of 81 structures by resolution:

PDB	Title	Method	Resolution (Å)
4M0E	Structure of human acetylcholinesterase in complex with dihydrotanshinone I	X-RAY DIFFRACTION	2
6NTO	Crystal Structure of Recombinant Human Acetylcholinesterase Inhibited by A-230	X-RAY DIFFRACTION	2.05
6O69	Crystal Structure of Double Mutant L380R/F535K of Human Acetylcholinesterase	X-RAY DIFFRACTION	2.08
5HF5	Crystal structure of human acetylcholinesterase in complex with paraoxon in the unaged …	X-RAY DIFFRACTION	2.15
6O5V	Binary complex of native hAChE with oxime reactivator RS-170B	X-RAY DIFFRACTION	2.15
4EY4	Crystal Structure of Recombinant Human Acetylcholinesterase in the Apo state	X-RAY DIFFRACTION	2.16
6WVO	Crystal Structure of Recombinant Human Acetylcholinesterase In Complex with GD and HI-6	X-RAY DIFFRACTION	2.19
5HF9	Crystal structure of human acetylcholinesterase in complex with paraoxon and HI6	X-RAY DIFFRACTION	2.2
5HFA	Crystal structure of human acetylcholinesterase in complex with paraoxon and 2-PAM	X-RAY DIFFRACTION	2.2
8DT7	X-ray structure of human acetylcholinesterase in complex with oxime MMB4 (hAChE-MMB4)	X-RAY DIFFRACTION	2.21
6CQZ	Crystal Structure of Recombinant Human Acetylcholinesterase Inhibited by VX	X-RAY DIFFRACTION	2.22
6NTL	Crystal Structure of Recombinant Human Acetylcholinesterase Inhibited by A-234	X-RAY DIFFRACTION	2.25
6U37	Structure of VX-phosphonylated hAChE in complex with oxime reactivator RS194B	X-RAY DIFFRACTION	2.25
6WUZ	Crystal Structure of Recombinant Human Acetylcholinesterase Inhibited by GB	X-RAY DIFFRACTION	2.25
6CQT	Crystal Structure of Recombinant Human Acetylcholinesterase Inhibited by (-) Stereoisomer …	X-RAY DIFFRACTION	2.27
6CQW	Crystal Structure of Recombinant Human Acetylcholinesterase in Complex with VX(-) and HI-6	X-RAY DIFFRACTION	2.28
6WVQ	Crystal Structure of Recombinant Human Acetylcholinesterase Inhibited by GP	X-RAY DIFFRACTION	2.29
5HF6	Crystal structure of human acetylcholinesterase in complex with paraoxon in the aged state	X-RAY DIFFRACTION	2.3
6O4X	Binary complex of native hAChE with 9-aminoacridine	X-RAY DIFFRACTION	2.3
5FOQ	Acetylcholinesterase in complex with C7653	X-RAY DIFFRACTION	2.3
4EY5	Crystal Structure of Recombinant Human Acetylcholinesterase in Complex with (-)-huperzine …	X-RAY DIFFRACTION	2.3
4M0F	Structure of human acetylcholinesterase in complex with territrem B	X-RAY DIFFRACTION	2.3
6CQU	Crystal Structure of Recombinant Human Acetylcholinesterase with Reactivator HI-6	X-RAY DIFFRACTION	2.31
6WVP	Crystal Structure of Recombinant Human Acetylcholinesterase Inhibited by GF	X-RAY DIFFRACTION	2.31
1VZJ	Structure of the tetramerization domain of acetylcholinesterase: four-fold interaction of …	X-RAY DIFFRACTION	2.35
6O4W	Binary complex of native hAChE with Donepezil	X-RAY DIFFRACTION	2.35
4EY7	Crystal Structure of Recombinant Human Acetylcholinesterase in Complex with Donepezil	X-RAY DIFFRACTION	2.35
6O50	Binary complex of native hAChE with BW284c51	X-RAY DIFFRACTION	2.35
6WV1	Crystal Structure of Recombinant Human Acetylcholinesterase In Complex with GB and HI-6	X-RAY DIFFRACTION	2.37
4EY6	Crystal Structure of Recombinant Human Acetylcholinesterase in Complex with …	X-RAY DIFFRACTION	2.4

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P22303-F1	93.04	0.85

Human Protein Atlas

Protein class: Enzymes, ENZYME proteins, Hydrolases, Metabolic proteins, Blood group antigen proteins, Predicted membrane proteins, Predicted intracellular proteins, FDA approved drug targets, Small molecule drugs

Protein evidence: Evidence at protein level

Subcellular location (HPA, imaging): golgi apparatus; vesicles

Antibody reliability (HPA): IF approved

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Catalytic / active sites (3)

Position	Role
234	acyl-ester intermediate
365	charge relay system
478	charge relay system

Ligand- & substrate-binding residues (10)

Position	Role
234	huprine W
368	galanthamine
368	huperzine A
470	huprine W
478	huprine W
117	galanthamine
117	huperzine A
153	huprine W
164	huperzine A
233–234	galanthamine

Post-translational modifications (1)

Type	Positions
Gpi-anchor amidated glycine	588

Disulfide bonds (4)

Type	Positions
Disulfide bond	100–127, 288–303, 440–560
Interchain	611

Glycosylation sites (3)

Type	Positions
N-linked (glcnac…) asparagine	296, 381, 495

Mutagenesis-validated functional residues (6)

Position	Phenotype
206	misfolding, absence of secretion.
234	loss of activity.
365	loss of activity.
435	misfolding, absence of secretion.
478	loss of activity.
611	impairment of interchain disulfide bridge formation.

Function

Pathways and Gene Ontology

Reactome pathways

3 curated (TAS) of 11; 0 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

11 pathways:

ID	Pathway	Evidence
R-HSA-112311	Neurotransmitter clearance	curated
R-HSA-1483191	Synthesis of PC	curated
R-HSA-422085	Synthesis, secretion, and deacylation of Ghrelin	curated
R-HSA-1483206	Glycerophospholipid biosynthesis	—
R-HSA-1430728	Metabolism	—
R-HSA-556833	Metabolism of lipids	—
R-HSA-392499	Metabolism of proteins	—
R-HSA-112316	Neuronal System	—
R-HSA-2980736	Peptide hormone metabolism	—
R-HSA-1483257	Phospholipid metabolism	—
R-HSA-112315	Transmission across Chemical Synapses	—

MSigDB gene sets: 0 (showing top):

GO Biological Process (10): acetylcholine catabolic process in synaptic cleft (GO:0001507), osteoblast development (GO:0002076), acetylcholine catabolic process (GO:0006581), cell adhesion (GO:0007155), nervous system development (GO:0007399), synapse assembly (GO:0007416), negative regulation of synaptic transmission, cholinergic (GO:0032223), amyloid precursor protein metabolic process (GO:0042982), positive regulation of protein secretion (GO:0050714), positive regulation of cold-induced thermogenesis (GO:0120162)

GO Molecular Function (12): amyloid-beta binding (GO:0001540), acetylcholinesterase activity (GO:0003990), cholinesterase activity (GO:0004104), collagen binding (GO:0005518), hydrolase activity (GO:0016787), serine hydrolase activity (GO:0017171), acetylcholine binding (GO:0042166), protein homodimerization activity (GO:0042803), laminin binding (GO:0043236), protein binding (GO:0005515), identical protein binding (GO:0042802), carboxylic ester hydrolase activity (GO:0052689)

GO Cellular Component (12): extracellular region (GO:0005576), basement membrane (GO:0005604), nucleus (GO:0005634), Golgi apparatus (GO:0005794), plasma membrane (GO:0005886), cell surface (GO:0009986), membrane (GO:0016020), neuromuscular junction (GO:0031594), synaptic cleft (GO:0043083), synapse (GO:0045202), perinuclear region of cytoplasm (GO:0048471), side of membrane (GO:0098552)

Reactome top-level categories

8 top-level categories:

Category	Pathways
Transmission across Chemical Synapses	1
Glycerophospholipid biosynthesis	1
Peptide hormone metabolism	1
Neuronal System	1
Phospholipid metabolism	1
Metabolism of lipids	1
Metabolism of proteins	1
Metabolism	1

GO top-level categories

47 GO namespaces:

Category	Terms
cellular anatomical structure	6
synaptic transmission, cholinergic	2
protein binding	2
intracellular membrane-bounded organelle	2
cytoplasm	2
membrane	2
acetylcholine catabolic process	1
synaptic cleft	1
osteoblast differentiation	1
cell development	1
acetylcholine metabolic process	1
catabolic process	1
cellular process	1
system development	1
animal gross anatomical part developmental process	1
nervous system development	1
cell junction assembly	1
synapse organization	1
regulation of synaptic transmission, cholinergic	1
negative regulation of synaptic transmission	1
protein metabolic process	1
protein secretion	1
regulation of protein secretion	1
positive regulation of protein transport	1
positive regulation of secretion by cell	1
positive regulation of multicellular organismal process	1
cold-induced thermogenesis	1
regulation of cold-induced thermogenesis	1
peptide binding	1
cholinesterase activity	1
carboxylic ester hydrolase activity	1
protein-containing complex binding	1
catalytic activity	1
hydrolase activity	1
cation binding	1
identical protein binding	1
protein dimerization activity	1
extracellular matrix binding	1
binding	1
hydrolase activity, acting on ester bonds	1
extracellular matrix	1
endomembrane system	1
cell periphery	1
synapse	1
extracellular region	1
cell junction	1
leaflet of membrane bilayer	1

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 17 of 35 annotations. The rest are phylogenetic / computational / electronic (IEA).

17 experimentally-supported GO terms:

GO term	NS	Evidence
acetylcholine catabolic process	BP	direct assay
cell adhesion	BP	direct assay
osteoblast development	BP	expression pattern
Golgi apparatus	CC	direct assay
extracellular region	CC	direct assay
membrane	CC	direct assay
neuromuscular junction	CC	direct assay
perinuclear region of cytoplasm	CC	direct assay
synapse	CC	direct assay
acetylcholine binding	MF	direct assay
acetylcholinesterase activity	MF	direct assay
cholinesterase activity	MF	direct assay
collagen binding	MF	direct assay
hydrolase activity	MF	direct assay
laminin binding	MF	direct assay
protein homodimerization activity	MF	physical interaction
serine hydrolase activity	MF	direct assay

Protein interactions and networks

STRING

showing 15 of 1,838 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ACHE	COLQ	Q9Y215	950
ACHE	CHAT	P28329	882
ACHE	DOK7	Q18PE1	851
ACHE	PNPLA6	Q8IY17	832
ACHE	MAOB	P27338	769
ACHE	F5H3C5	F5H3C5	763
ACHE	SLC18A3	Q16572	763
ACHE	APP	P05067	759
ACHE	BACE1	P56817	749
ACHE	MAOA	P21397	746
ACHE	NGF	P01138	723
ACHE	RAPSN	Q13702	722
ACHE	TH	P07101	713
ACHE	MUSK	O15146	712
ACHE	AGRN	O00468	705

IntAct

Human interaction partners of ACHE in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

4 partners by confidence:

Partner	Interaction type	MIscore	Records
COLQ	direct interaction	0.560	2
ENO1	physical association	0.530	2
RACK1	physical association	0.530	2
ATF7	physical association	0.000	1

BioGRID (4 interactions; top human partners by supporting records): APP (Reconstituted Complex), COL4A1 (Reconstituted Complex), DDX39A (Affinity Capture-RNA), PARP2 (Proximity Label-MS)

SIGNOR signaling

10 signaling interactions:

A	Effect	B	Mechanism
“Galanthamine hydrobromide”	down-regulates	ACHE	“chemical inhibition”
neostigmine	“down-regulates activity”	ACHE	“chemical inhibition”
4’-((2-Butyl-4-oxo-1,3-diazaspiro[4.4]non-1-en-3-yl)methyl)-[1,1’-biphenyl]-2-carbonitrile	“down-regulates activity”	ACHE	“chemical inhibition”
3-[(2-Bromo-4,5-dimethoxyphenyl)methyl]-2-butyl-1,3-diazaspiro[4.4]non-1-en-4-one	“down-regulates activity”	ACHE	“chemical inhibition”
3-[(4-Bromophenyl)methyl]-2-butyl-1,3-diazaspiro[4.4]non-1-en-4-one	“down-regulates activity”	ACHE	“chemical inhibition”
ACHE	“down-regulates quantity”	acetylcholine	“chemical modification”
Pyridostigmine	“down-regulates activity”	ACHE	“chemical inhibition”
pralidoxime	“up-regulates activity”	ACHE	“chemical activation”
edrophonium	“down-regulates activity”	ACHE	“chemical inhibition”
procainamide	“down-regulates activity”	ACHE	“chemical inhibition”

Protein complexes (CORUM) (8)

Experimentally-characterized complexes this protein is a subunit of (★ = the complex contains a known drug target).

8 complexes by size:

Complex	Subunits	Members
★ ACHE(G2)-BCHE(G2) heterotetramer	2	ACHE, BCHE
★ ACHE-NRXN1 complex	2	ACHE, NRXN1
★ ACHE (A12)-COLQ complex	2	COLQ, ACHE
★ ACHE (A8)-COLQ complex	2	ACHE, COLQ
★ ACHE (A4)-COLQ complex	2	ACHE, COLQ
★ Abeta-ACHE complex	2	ACHE, APP
★ ACHE (G4) homotetramer	1	ACHE
★ ACHE (G2) homodimer	1	ACHE

Disease & clinical

Genetic variants

Variant evidence for ACHE: 86 ClinVar records (8 pathogenic / likely pathogenic); 1 PharmGKB clinical annotation; 35 GWAS associations. Per-variant detail is on Sugi Variant.

ClinVar

86 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	7
Likely pathogenic	1
Uncertain significance	56
Likely benign	9
Benign	3

Top pathogenic / likely-pathogenic (8)

Showing all 8 pathogenic / likely-pathogenic ClinVar records, ranked by ClinVar review status (expert panel → multiple submitters → single submitter), then by number of submitting labs.

Variant ID	HGVS	Classification	Review	Submitters
59713	GRCh38/hg38 7q21.3-22.1(chr7:98288474-101259804)x3	Pathogenic	criteria provided, single submitter	1
60280	GRCh38/hg38 7q22.1(chr7:99219420-100902269)x1	Pathogenic	criteria provided, single submitter	1
60281	GRCh38/hg38 7q22.1(chr7:100419914-102482826)x1	Pathogenic	criteria provided, single submitter	1
1527379	GRCh37/hg19 7q22.1-31.1(chr7:99417471-111586308)x1	Pathogenic	criteria provided, single submitter	1
3062968	GRCh37/hg19 7q22.1(chr7:100454649-101886704)x1	Pathogenic	criteria provided, single submitter	1
4820055	NC_000007.14:g.99487704_102394107del	Pathogenic	criteria provided, single submitter	1
3062972	GRCh37/hg19 7q22.1(chr7:98396469-102108193)x1	Likely pathogenic	criteria provided, single submitter	1
146501	GRCh38/hg38 7q22.1(chr7:99195836-102258175)x1	Pathogenic	no assertion criteria provided	1

Per-variant reference — Sugi Variant

Explore ACHE’s pathogenic and likely-pathogenic variants individually — each with its ClinVar classification and conditions, applied ACMG criteria (ClinGen expert panel, where curated), the calibrated in-silico predictors (AlphaMissense, REVEL, SaProt, conservation), gnomAD frequency, and the predictor-disagreement QC signal — on Sugi Variant.

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 31 predictions of 504):

Position(s)	Effect	Δscore	Sites
7:100891339–100891340	acceptor_loss	1.0000	5
7:100892770	acceptor_gain	1.0000
7:100893163–100893164	donor_loss	1.0000	5
7:100891167–100891168	donor_loss	0.9900	4
7:100891343	acceptor_gain	0.9900
7:100892819–100892820	acceptor_loss	0.9900	6
7:100895800–100895801	donor_loss	0.9900	5
7:100890353	acceptor_gain	0.9800
7:100890361	acceptor_gain	0.9800
7:100890493–100890495	acceptor_gain	0.9800	2

HPA cancer prognostics

RNA cancer specificity: Low cancer specificity

Human Protein Atlas survival analysis — favorable = higher expression predicts better survival.

4 prognostic cancer types:

Cancer	Prognostic	p-value
Glioblastoma Multiforme (TCGA)	unfavorable	2.24e-05
Liver Hepatocellular Carcinoma (validation)	unfavorable	2.58e-05
Kidney Renal Clear Cell Carcinoma (TCGA)	unfavorable	5.51e-05
Lung Adenocarcinoma (TCGA)	favorable	0.000501

Disease associations

OMIM: gene MIM:100740 | disease phenotypes:

GWAS associations

showing 30 of 35 associations:

Study	Trait	p-value
GCST003818_67	Resting heart rate	1e-41
GCST001969_9	Heart rate	8e-27
GCST005849_14	Heart rate response to recovery post exercise (40 sec)	6e-24
GCST005848_8	Heart rate response to recovery post exercise (50 sec)	4e-23
GCST005850_6	Heart rate response to recovery post exercise (30 sec)	8e-23
GCST005847_6	Heart rate response to recovery post exercise (20 sec)	3e-21
GCST005846_7	Heart rate response to recovery post exercise (10 sec)	6e-21
GCST005845_4	Heart rate increase in response to exercise	3e-16
GCST001684_4	Plasminogen activator inhibitor type 1 levels (PAI-1)	6e-13
GCST006979_419	Heel bone mineral density	3e-12
GCST005788_23	Heart rate response to recovery post exercise	7e-11
GCST007268_34	Diastolic blood pressure	1e-10
GCST008129_40	Body mass index	3e-10
GCST007096_237	Pulse pressure	4e-10
GCST010796_2770	Electrocardiogram morphology (amplitude at temporal datapoints)	8e-10
GCST010796_2945	Electrocardiogram morphology (amplitude at temporal datapoints)	8e-10
GCST010083_137	Hemoglobin levels	1e-9
GCST010796_2784	Electrocardiogram morphology (amplitude at temporal datapoints)	1e-9
GCST010796_2936	Electrocardiogram morphology (amplitude at temporal datapoints)	1e-9
GCST010796_2937	Electrocardiogram morphology (amplitude at temporal datapoints)	1e-9
GCST010796_2781	Electrocardiogram morphology (amplitude at temporal datapoints)	2e-9
GCST010796_2782	Electrocardiogram morphology (amplitude at temporal datapoints)	3e-9
GCST010796_2783	Electrocardiogram morphology (amplitude at temporal datapoints)	3e-9
GCST010796_2944	Electrocardiogram morphology (amplitude at temporal datapoints)	6e-9
GCST010796_2938	Electrocardiogram morphology (amplitude at temporal datapoints)	9e-9
GCST010796_2780	Electrocardiogram morphology (amplitude at temporal datapoints)	1e-8
GCST010796_2935	Electrocardiogram morphology (amplitude at temporal datapoints)	1e-8
GCST010796_2941	Electrocardiogram morphology (amplitude at temporal datapoints)	2e-8
GCST010796_2943	Electrocardiogram morphology (amplitude at temporal datapoints)	2e-8
GCST010796_2939	Electrocardiogram morphology (amplitude at temporal datapoints)	3e-8

EFO canonical traits (from GWAS)

10 canonical traits:

EFO ID	Trait name
EFO:0004792	plasminogen activator inhibitor 1 measurement
EFO:0009185	heart rate response to recovery post exercise
EFO:0009184	heart rate response to exercise
EFO:0009270	heel bone mineral density
EFO:0005763	pulse pressure measurement
EFO:0009707	fractures, ununited
EFO:0006336	diastolic blood pressure
EFO:0004340	body mass index
EFO:0004509	hemoglobin measurement
EFO:0004327	electrocardiography

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (2): CHEMBL2095233 (SELECTIVITY GROUP), CHEMBL220 (SINGLE PROTEIN)

Drugs by curated mechanism of action (ChEMBL)

Drugs whose curated ChEMBL mechanism of action targets the ACHE protein itself — single-protein targets only (drugs acting on a protein family or complex that merely includes it are excluded). Includes antibodies and oligonucleotides that bioactivity screening does not capture.

20 curated-mechanism drugs:

Drug	Modality	Max phase
AMBENONIUM CHLORIDE	Small molecule	4
BENZGALANTAMINE GLUCONATE	Small molecule	4
DEMECARIUM BROMIDE	Small molecule	4
DISTIGMINE	Small molecule	4
DONEPEZIL HYDROCHLORIDE	Small molecule	4
ECHOTHIOPHATE	Small molecule	4
ECHOTHIOPHATE IODIDE	Small molecule	4
EDROPHONIUM CHLORIDE	Small molecule	4
GALANTAMINE HYDROBROMIDE	Small molecule	4
HEXAFLUORENIUM BROMIDE	Small molecule	4
ISOFLUROPHATE	Small molecule	4
MINAPRINE	Small molecule	4
NEOSTIGMINE METHYLSULFATE	Small molecule	4
PHYSOSTIGMINE SALICYLATE	Small molecule	4
PRALIDOXIME CHLORIDE	Small molecule	4
PROPANIDID	Small molecule	4
PYRIDOSTIGMINE BROMIDE	Small molecule	4
ACOTIAMIDE HYDROCHLORIDE	Small molecule	3
ITOPRIDE	Small molecule	3
HUPERZINE A	Small molecule	2

Drugs acting on a complex or family that includes this protein

Curated ChEMBL mechanism-of-action drugs whose target is a protein complex or family of ≤10 members that includes ACHE — the drug acts on the assembly or class, not necessarily on this subunit alone.

2 drugs via a complex or family:

Drug	Target (ChEMBL)	Members	Max phase
RIVASTIGMINE	Cholinesterases; ACHE & BCHE	2	4
TACRINE HYDROCHLORIDE	Cholinesterases; ACHE & BCHE	2	4

Molecules with ChEMBL bioactivity

Phase ≥1, by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 306,967 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

showing 60 of 153 molecules by phase:

Molecule	Name	Phase	Patents
CHEMBL502	DONEPEZIL	4	43,884
CHEMBL1678	DONEPEZIL HYDROCHLORIDE	4	22,788
CHEMBL1104	EDROPHONIUM	4	17,780
CHEMBL1128	EDROPHONIUM CHLORIDE	4	20,295
CHEMBL659	GALANTAMINE	4	31,160
CHEMBL1555	GALANTAMINE HYDROBROMIDE	4	2,215
CHEMBL1201349	HEXAFLUORENIUM	4	669
CHEMBL1025	ISOFLUROPHATE	4	13,214
CHEMBL278819	MINAPRINE	4	3,340
CHEMBL211471	NEOSTIGMINE METHYLSULFATE	4	2,210
CHEMBL338975	PHYSOSTIGMINE SALICYLATE	4	2,662
CHEMBL748	PRALIDOXIME CHLORIDE	4	4,155
CHEMBL1115	PYRIDOSTIGMINE	4	13,767
CHEMBL812	PYRIDOSTIGMINE BROMIDE	4	2,920
CHEMBL709	ALFUZOSIN	4	6,651
CHEMBL1112	ARIPIPRAZOLE	4	24,497
CHEMBL295124	BERBERINE	4	27,107
CHEMBL288441	BOSUTINIB	4	12,869
CHEMBL493	BROMOCRIPTINE	4	44,193
CHEMBL990	BUTENAFINE	4	10,591
CHEMBL1201087	CABERGOLINE	4
CHEMBL113	CAFFEINE	4
CHEMBL190461	CANNABIDIOL	4
CHEMBL549	CITALOPRAM	4
CHEMBL104	CLOTRIMAZOLE	4
CHEMBL1190	DECAMETHONIUM	4
CHEMBL1134	DECAMETHONIUM BROMIDE	4
CHEMBL333826	DEQUALINIUM	4
CHEMBL411	DIETHYLSTILBESTROL	4
CHEMBL964	DISULFIRAM	4
CHEMBL473	DOFETILIDE	4
CHEMBL1201217	DYCLONINE	4
CHEMBL305660	EBASTINE	4
CHEMBL808	ECONAZOLE	4
CHEMBL417	EPIRUBICIN	4
CHEMBL1206	ETHOPROPAZINE	4
CHEMBL1200970	ETHOPROPAZINE HYDROCHLORIDE	4
CHEMBL1200623	ETHYLESTRENOL	4
CHEMBL672	FENOFIBRATE	4
CHEMBL1493	FLAVOXATE	4
CHEMBL41	FLUOXETINE	4
CHEMBL360055	GALLAMINE	4
CHEMBL64894	GENTIAN VIOLET	4
CHEMBL496	HEXACHLOROPHENE	4
CHEMBL14376	ILOPERIDONE	4
CHEMBL481	IRINOTECAN	4
CHEMBL1254682	LEVALLORPHAN	4
CHEMBL3286830	LORLATINIB	4
CHEMBL1237021	LURASIDONE	4
CHEMBL852	MELPHALAN	4
CHEMBL807	MEMANTINE	4
CHEMBL314437	MEPTAZINOL	4
CHEMBL416	METHOXSALEN	4
CHEMBL91	MICONAZOLE	4
CHEMBL142635	NAFTOPIDIL	4
CHEMBL623	NEFAZODONE	4
CHEMBL278020	NEOSTIGMINE	4
CHEMBL1372950	NICERGOLINE	4
CHEMBL3183075	NIZATIDINE	4
CHEMBL175247	ORLISTAT	4

PharmGKB: 1 entry (CPIC guideline: no)

PharmGKB clinical annotations

1 annotations by evidence level (1 strongest → 4):

Variant	Association	Level	Drugs	Phenotypes
rs2571598	Efficacy	3	rivastigmine	Alzheimer Disease

PharmGKB variants

1 variants:

Variant	Genes	Level	Score	#Clin annots	Drugs
rs2571598	ACHE	3	1.75	1	rivastigmine

PharmGKB variant annotations

Per-publication pharmacogenomic findings for this gene (significant associations).

1 published findings:

Variant	Drug(s)	Category	Finding	PMID
rs2571598	rivastigmine	Efficacy	Genotype TT is associated with increased response to rivastigmine in people with Alzheimer Disease as compared to genotypes CC + CT.	PMID:18780301

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: enzyme — Acetylcholine turnover

Most potent curated ligand interactions (17 total), top 17:

Ligand	Action	Affinity	Parameter
donepezil	Inhibition	8.3	pIC50
compound 2f [Jiang et al., 2018]	Inhibition	8.19	pIC50
apigenin	Inhibition	7.92	pIC50
donecopride	Inhibition	7.8	pIC50
physostigmine	Inhibition	7.8	pIC50
huperzine A	Inhibition	7.77	pKd
BW284C51	Inhibition	7.7	pIC50
tacrine	Inhibition	7.5	pKi
neostigmine	Inhibition	7.35	pIC50
edrophonium	Inhibition	6.7	pKi
anivecrine	Inhibition	6.44	pIC50
pyridostigmine	Inhibition	6.44	pIC50
galantamine	Inhibition	6.3	pIC50
(-)-isatispironeol A	Inhibition	6.17	pIC50
AChE reactivator 2		5.64	pIC50
rivastigmine	Inhibition	5.4	pIC50
pralidoxime	Inhibition	3.1	pIC50

Binding affinities (BindingDB)

4193 measured of 5119 human assays (6100 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value
CHEMBL3322232	IC50	0.006 nM
CHEMBL4589980	IC50	0.008 nM
CHEMBL4205425	IC50	0.011 nM
N-Methyl-N-(1,2,3,4-tetrahydroacridin-9-yl)-N-{3-[(1,2,3,4-tetrahydroacridin-9-yl)amino]propyl}-1,4-butanediamine	KI	0.012 nM
CHEMBL4205954	IC50	0.013 nM
CHEMBL4217663	IC50	0.014 nM
CHEMBL4210316	IC50	0.014 nM
CHEMBL4209803	IC50	0.014 nM
CHEMBL4214430	IC50	0.017 nM
CHEMBL4213253	IC50	0.019 nM
3-(1H-indol-3-yl)-N-(6-(1,2,3,4-tetrahydroacridin-9-ylamino)hexyl)propanamide	IC50	0.02 nM
CHEMBL4214707	IC50	0.021 nM
CHEMBL4210041	IC50	0.022 nM
CHEMBL4218191	IC50	0.026 nM
CHEMBL4205144	IC50	0.026 nM
CHEMBL3585783	IC50	0.027 nM
CHEMBL3585782	IC50	0.027 nM
CHEMBL3585781	IC50	0.027 nM
CHEMBL3585780	IC50	0.027 nM
CHEMBL3585779	IC50	0.027 nM
CHEMBL3585778	IC50	0.027 nM
CHEMBL3585777	IC50	0.027 nM
CHEMBL3585776	IC50	0.027 nM
CHEMBL3585775	IC50	0.027 nM
CHEMBL3585784	IC50	0.027 nM
CHEMBL4208866	IC50	0.028 nM
CHEMBL4209518	IC50	0.029 nM
3-(1H-indol-3-yl)-N-(7-(1,2,3,4-tetrahydroacridin-9-ylamino)heptyl)propanamide	IC50	0.06 nM
N-Allyl-N-(1,2,3,4-tetrahydroacridin-9-yl)-N-{3-[(1,2,3,4-tetrahydroacridin-9-yl)amino]propyl}-1,4-butanediamine	KI	0.085 nM
N-(2-Hydroxyethyl)-N-(1,2,3,4-tetrahydroacridin-9-yl)-N-{3-[(1,2,3,4-tetrahydroacridin-9-yl)amino]propyl}-1,4-butanediamine	KI	0.119 nM
1,4-bis[3-(1,2,3,4-Tetrahydroacridin-9-yl)aminopropyl]piperazine	KI	0.136 nM
N-Ethyl-N-(1,2,3,4-tetrahydroacridin-9-yl)-N-{3-[(1,2,3,4-tetrahydroacridin-9-yl)amino]propyl}-1,4-butanediamine	KI	0.162 nM
N-{4-[(1,2,3,4-Tetrahydroacridin-9-yl)amino]butyl}-N{3-[(1,2,3,4-tetrahydroacridin-9-yl)amino]propyl}acetamide	KI	0.223 nM
CHEMBL3099497	KI	0.23 nM
CHEMBL1912059	IC50	0.23 nM
CHEMBL1940738	IC50	0.236 nM
N-{3-[(6-chloro-1,2,3,4-tetrahydroacridin-9-yl)amino]propyl}-5-(1,2-dithiolan-3-yl)pentanamide	IC50	0.25 nM
CHEMBL4785201	IC50	0.27 nM
{3-[(6-chloro-1,2,3,4-tetrahydroacridin-9-yl)amino]propyl}[3-({7-chloro-15-methyl-10-azatetracyclo[11.3.1.0^{2,11}.0^{4,9}]heptadeca-2(11),3,5,7,9,14-hexaen-3-yl}amino)propyl]methylamine trihydrochloride	IC50	0.29 nM
3-{[methyl({3-[(9-oxo-9H-xanthen-3-yl)oxy]propyl})amino]methyl}phenyl N-methylcarbamate	IC50	0.3 nM
1-(3-(4-(piperidin-1-ylmethyl)phenoxy)propyl)piperidine	KI	0.3 nM
CHEMBL4471659	IC50	0.3 nM
3-({7-chloro-15-methyl-10-azatetracyclo[11.3.1.0^{2,11}.0^{4,9}]heptadeca-2(11),3,5,7,9,14-hexaen-3-yl}amino)propyl[3-(1,2,3,4-tetrahydroacridin-9-ylamino)propyl]amine trihydrochloride	IC50	0.32 nM
CHEMBL2236393	IC50	0.32 nM
3-Chloro-6,7,10,11-tetrahydro-9-methyl-12-{{7-[(6-chloro-1,2,3,4-tetrahydroacridin-9-yl)amino]heptyl}amino}-7,11-methanocycloocta[b]quinoline dihydrochloride	IC50	0.33 nM
3-[2-(1-Benzyl-piperidin-4-yl)-ethyl]-5,7-dihydro-isoxazolo[4,5-f]indol-6-one; compound with (Z)-but-2-enedioic acid	IC50	0.33 nM
N-(4-(3-(piperidin-1-yl)propoxy)phenethyl)-5,6,7,8-tetrahydroacridin-9-amine	KI	0.33 nM
7-chloro-15-methyl-N-[7-(1,2,3,4-tetrahydroacridin-9-ylamino)heptyl]-10-azatetracyclo[11.3.1.0^{2,11}.0^{4,9}]heptadeca-2(11),3,5,7,9,14-hexaen-3-amine dihydrochloride	IC50	0.34 nM
2-(6-(ethyl((R)-1-(2-methoxyphenyl)ethyl)amino)hexylamino)-5-(6-(ethyl((S)-1-(2-methoxyphenyl)ethyl)amino)hexylamino)cyclohexa-2,5-diene-1,4-dione	IC50	0.36 nM
2,7-bis(6-(ethyl(2-methoxybenzyl)amino)hexyl)benzo[lmn][3,8]phenanthroline-1,3,6,8(2H,7H)-tetraone	IC50	0.37 nM

ChEMBL bioactivities

6100 potent at pChembl≥5 of 6100 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
10.98	Ki	0.0105	nM	CHEMBL3585779
10.96	IC50	0.01095	nM	CHEMBL4205425
10.93	Ki	0.0118	nM	CHEMBL489454
10.92	Ki	0.012	nM	CHEMBL489454
10.88	IC50	0.01323	nM	CHEMBL4205954
10.87	IC50	0.01352	nM	CHEMBL4209803
10.85	Ki	0.014	nM	CHEMBL225567
10.85	IC50	0.01415	nM	CHEMBL4217663
10.84	IC50	0.01441	nM	CHEMBL4210316
10.82	Ki	0.015	nM	CHEMBL223443
10.78	IC50	0.01672	nM	CHEMBL4214430
10.72	IC50	0.01893	nM	CHEMBL4213253
10.70	IC50	0.02	nM	CHEMBL225198
10.70	Ki	0.02	nM	CHEMBL225326
10.70	IC50	0.02	nM	CHEMBL225567
10.70	IC50	0.02	nM	CHEMBL1083983
10.68	IC50	0.02094	nM	CHEMBL4214707
10.67	IC50	0.02158	nM	CHEMBL4210041
10.66	Ki	0.022	nM	CHEMBL5433692
10.64	Ki	0.0229	nM	CHEMBL3585778
10.59	Ki	0.026	nM	HUPRINE X
10.59	IC50	0.02592	nM	CHEMBL4205144
10.58	IC50	0.02621	nM	CHEMBL4218191
10.57	IC50	0.02685	nM	CHEMBL3585777
10.57	IC50	0.02685	nM	CHEMBL3585776
10.57	IC50	0.02685	nM	CHEMBL3585775
10.57	IC50	0.02685	nM	CHEMBL3585778
10.57	IC50	0.02685	nM	CHEMBL3585779
10.57	IC50	0.02685	nM	CHEMBL3585780
10.57	IC50	0.02685	nM	CHEMBL3585781
10.57	IC50	0.02685	nM	CHEMBL3585782
10.57	IC50	0.02685	nM	CHEMBL3585783
10.57	IC50	0.02685	nM	CHEMBL3585784
10.55	IC50	0.02836	nM	CHEMBL4208866
10.53	IC50	0.02938	nM	CHEMBL4209518
10.48	Ki	0.033	nM	CHEMBL536047
10.46	IC50	0.035	nM	CHEMBL2019048
10.42	Ki	0.0382	nM	CHEMBL3585780
10.40	IC50	0.04	nM	CHEMBL372202
10.37	IC50	0.043	nM	NEOSTIGMINE BROMIDE
10.33	Ki	0.047	nM	CHEMBL3137700
10.22	IC50	0.06	nM	CHEMBL225198
10.22	IC50	0.06	nM	CHEMBL1083984
10.19	IC50	0.065	nM	CHEMBL2019049
10.17	IC50	0.068	nM	CHEMBL5190569
10.15	IC50	0.07	nM	CHEMBL225567
10.15	IC50	0.07	nM	CHEMBL307004
10.10	Ki	0.08	nM	CHEMBL3621322
10.07	Ki	0.0847	nM	CHEMBL507174
10.05	IC50	0.09	nM	CHEMBL2019053

PubChem BioAssay actives

1952 with measured affinity, of 6100 total; 50 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
N-[7-[(6-chloro-1,2,3,4-tetrahydroacridin-9-yl)amino]heptyl]-3-(1H-indol-3-yl)propanamide	282827: Inhibition of human brain AchE	ic50	<0.0001	uM
N-[6-[(6-chloro-1,2,3,4-tetrahydroacridin-9-yl)amino]hexyl]-3-(1H-indol-3-yl)propanamide	282827: Inhibition of human brain AchE	ki	<0.0001	uM
1-methoxy-2-[1-(sulfamoylamino)ethyl]benzene	1231568: Inhibition of acetylcholinesterase (unknown origin) assessed as AChI hydrolysis using AChI and DTNB as substrate by Ellman’s method	ic50	<0.0001	uM
1,2-dimethoxy-4-[1-(sulfamoylamino)ethyl]benzene	1231568: Inhibition of acetylcholinesterase (unknown origin) assessed as AChI hydrolysis using AChI and DTNB as substrate by Ellman’s method	ic50	<0.0001	uM
1-methoxy-4-[1-(sulfamoylamino)ethyl]benzene	1231568: Inhibition of acetylcholinesterase (unknown origin) assessed as AChI hydrolysis using AChI and DTNB as substrate by Ellman’s method	ic50	<0.0001	uM
N-[7-[(6-chloro-1,2,3,4-tetrahydroacridin-9-yl)amino]heptyl]-2-(1H-indol-3-yl)acetamide	282827: Inhibition of human brain AchE	ki	<0.0001	uM
N-[2-[5-[6-[(1R)-6,7-dimethoxy-1-phenyl-3,4-dihydro-1H-isoquinolin-2-yl]hexyl]triazol-1-yl]ethyl]-1,2,3,4-tetrahydroacridin-9-amine	1178308: Binding affinity to acetylcholine esterase (unknown origin)	kd	<0.0001	uM
N-[2-[5-[6-[(1S)-6,7-dimethoxy-1-phenyl-3,4-dihydro-1H-isoquinolin-2-yl]hexyl]triazol-1-yl]ethyl]-1,2,3,4-tetrahydroacridin-9-amine	1178308: Binding affinity to acetylcholine esterase (unknown origin)	kd	<0.0001	uM
N-[5-[(6-chloro-1,2,3,4-tetrahydroacridin-9-yl)amino]pentyl]-4-(1H-indol-3-yl)butanamide	282827: Inhibition of human brain AchE	ki	<0.0001	uM
2-(5-bromo-1H-indol-3-yl)-N-[7-[(6-chloro-1,2,3,4-tetrahydroacridin-9-yl)amino]heptyl]acetamide	282827: Inhibition of human brain AchE	ki	<0.0001	uM
N-[2-(5-methoxy-1H-indol-3-yl)ethyl]-7-(1,2,3,4-tetrahydroacridin-9-ylamino)heptanamide	1545307: Inhibition of human erythrocyte acetylcholinesterase using acetylthiocholine as substrate by Ellman’s method	ic50	<0.0001	uM
6-[(6-chloro-1,2,3,4-tetrahydroacridin-9-yl)amino]-N-[2-(5-methoxy-1H-indol-3-yl)ethyl]hexanamide	1545307: Inhibition of human erythrocyte acetylcholinesterase using acetylthiocholine as substrate by Ellman’s method	ic50	<0.0001	uM
6-[(8-chloro-1,2,3,4-tetrahydroacridin-9-yl)amino]-N-[2-(5-methoxy-1H-indol-3-yl)ethyl]hexanamide	1545307: Inhibition of human erythrocyte acetylcholinesterase using acetylthiocholine as substrate by Ellman’s method	ic50	<0.0001	uM
6-[(6,8-dichloro-1,2,3,4-tetrahydroacridin-9-yl)amino]-N-[2-(1H-indol-3-yl)ethyl]hexanamide	1545307: Inhibition of human erythrocyte acetylcholinesterase using acetylthiocholine as substrate by Ellman’s method	ic50	<0.0001	uM
6-[(6-chloro-1,2,3,4-tetrahydroacridin-9-yl)amino]-N-[2-(1H-indol-3-yl)ethyl]hexanamide	1545307: Inhibition of human erythrocyte acetylcholinesterase using acetylthiocholine as substrate by Ellman’s method	ic50	<0.0001	uM
7-[(6,8-dichloro-1,2,3,4-tetrahydroacridin-9-yl)amino]-N-[2-(5-methoxy-1H-indol-3-yl)ethyl]heptanamide	1545307: Inhibition of human erythrocyte acetylcholinesterase using acetylthiocholine as substrate by Ellman’s method	ic50	<0.0001	uM
N-[2-(5-methoxy-1H-indol-3-yl)ethyl]-6-(1,2,3,4-tetrahydroacridin-9-ylamino)hexanamide	1545307: Inhibition of human erythrocyte acetylcholinesterase using acetylthiocholine as substrate by Ellman’s method	ic50	<0.0001	uM
N-[2-(1H-indol-3-yl)ethyl]-6-(1,2,3,4-tetrahydroacridin-9-ylamino)hexanamide	1545307: Inhibition of human erythrocyte acetylcholinesterase using acetylthiocholine as substrate by Ellman’s method	ic50	<0.0001	uM
7-[(6-chloro-1,2,3,4-tetrahydroacridin-9-yl)amino]-N-[2-(1H-indol-3-yl)ethyl]heptanamide	1545307: Inhibition of human erythrocyte acetylcholinesterase using acetylthiocholine as substrate by Ellman’s method	ic50	<0.0001	uM
N-[2-(1H-indol-3-yl)ethyl]-7-(1,2,3,4-tetrahydroacridin-9-ylamino)heptanamide	1545307: Inhibition of human erythrocyte acetylcholinesterase using acetylthiocholine as substrate by Ellman’s method	ic50	<0.0001	uM
7-[(6,8-dichloro-1,2,3,4-tetrahydroacridin-9-yl)amino]-N-[2-(1H-indol-3-yl)ethyl]heptanamide	1545307: Inhibition of human erythrocyte acetylcholinesterase using acetylthiocholine as substrate by Ellman’s method	ic50	<0.0001	uM
N-[2-(5-hydroxy-1H-indol-3-yl)ethyl]-6-(1,2,3,4-tetrahydroacridin-9-ylamino)hexanamide	1545307: Inhibition of human erythrocyte acetylcholinesterase using acetylthiocholine as substrate by Ellman’s method	ic50	<0.0001	uM
5-(4-chlorophenyl)-N-[3-[(6-chloro-1,2,3,4-tetrahydroacridin-9-yl)amino]propyl]-1,2,3,4-tetrahydrobenzo[h][1,6]naphthyridine-9-carboxamide;hydrochloride	1183274: Inhibition of human recombinant AChE using acetylthiocholine iodide as substrate by spectrophotometric analysis	ic50	<0.0001	uM
benzyl N-[1-(2-methoxyphenyl)ethylsulfamoyl]carbamate	1231568: Inhibition of acetylcholinesterase (unknown origin) assessed as AChI hydrolysis using AChI and DTNB as substrate by Ellman’s method	ic50	<0.0001	uM
benzyl N-[1-(4-methoxyphenyl)ethylsulfamoyl]carbamate	1231568: Inhibition of acetylcholinesterase (unknown origin) assessed as AChI hydrolysis using AChI and DTNB as substrate by Ellman’s method	ic50	<0.0001	uM
benzyl N-[1-(3,4-dimethoxyphenyl)ethylsulfamoyl]carbamate	1231568: Inhibition of acetylcholinesterase (unknown origin) assessed as AChI hydrolysis using AChI and DTNB as substrate by Ellman’s method	ic50	<0.0001	uM
benzyl N-[1-(2,5-dimethoxyphenyl)ethylsulfamoyl]carbamate	1231568: Inhibition of acetylcholinesterase (unknown origin) assessed as AChI hydrolysis using AChI and DTNB as substrate by Ellman’s method	ic50	<0.0001	uM
benzyl N-[1-(2,6-dimethoxyphenyl)ethylsulfamoyl]carbamate	1231568: Inhibition of acetylcholinesterase (unknown origin) assessed as AChI hydrolysis using AChI and DTNB as substrate by Ellman’s method	ic50	<0.0001	uM
1,3-dimethoxy-2-[1-(sulfamoylamino)ethyl]benzene	1231568: Inhibition of acetylcholinesterase (unknown origin) assessed as AChI hydrolysis using AChI and DTNB as substrate by Ellman’s method	ic50	<0.0001	uM
6-[(2-methoxyphenyl)methyl-methylamino]-N-[8-[6-[(2-methoxyphenyl)methyl-methylamino]hexanoyl-methylamino]octyl]-N-methylhexanamide	31618: Inhibition constant determined against Acetylcholinesterase (AChE) receptor.	ki	0.0001	uM
N’-methyl-N-(1,2,3,4-tetrahydroacridin-9-yl)-N’-[3-(1,2,3,4-tetrahydroacridin-9-ylamino)propyl]propane-1,3-diamine	1796269: Measurement of FBSAChE/EqBuChE Inhibitory Activity from Article 10.1021/jm049510k: “Development of molecular probes for the identification of extra interaction sites in the mid-gorge and peripheral sites of butyrylcholinesterase (BuChE). Rational design of novel, selective, and highly potent BuChE inhibitors.”	ki	0.0001	uM
N-[3-[(6-chloro-1,2,3,4-tetrahydroacridin-9-yl)amino]propyl]-5-[(3R)-dithiolan-3-yl]pentanamide	625546: Inhibition of human serum recombinant AChE after 20 mins using acetylthiocholine iodide as a substrate by Ellman’s assay	ic50	0.0002	uM
7-chloro-15-methyl-10-azatetracyclo[11.3.1.02,11.04,9]heptadeca-2,4(9),5,7,10,14-hexaen-3-amine	1545298: Inhibition of human Acetylcholinesterase using acetylthiocholine as substrate incubated for 15 mins by Ellman’s method	ic50	0.0003	uM
[3-[[methyl-[3-(9-oxoxanthen-3-yl)oxypropyl]amino]methyl]phenyl] N-methylcarbamate	1796503: Cholinesterase Inhibition Assay from Article 10.1021/jm049515h: “Cholinesterase inhibitors: xanthostigmine derivatives blocking the acetylcholinesterase-induced beta-amyloid aggregation.”	ic50	0.0003	uM
[3-[[methyl-[7-(9-oxoxanthen-3-yl)oxyheptyl]amino]methyl]phenyl] N-methylcarbamate	1796503: Cholinesterase Inhibition Assay from Article 10.1021/jm049515h: “Cholinesterase inhibitors: xanthostigmine derivatives blocking the acetylcholinesterase-induced beta-amyloid aggregation.”	ic50	0.0003	uM
N-[3-[(6-chloro-1,2,3,4-tetrahydroacridin-9-yl)amino]propyl]-5-(dithiolan-3-yl)pentanamide	1127774: Inhibition of AChE (unknown origin)	ic50	0.0003	uM
2-methyl-5-[9-(2-methylpyrido[4,3-b]indol-2-ium-5-yl)nonyl]pyrido[4,3-b]indol-2-ium diiodide	1766053: Inhibition of recombinant human AChE expressed in HEK293 cells by Ellman’s method	ic50	0.0003	uM
3-[2-(1-benzylpiperidin-4-yl)ethyl]-5,7-dihydropyrrolo[3,2-f][1,2]benzoxazol-6-one;(Z)-but-2-enedioic acid	31169: In vitro inhibition of Acetylcholinesterase from human erythrocytes	ic50	0.0003	uM
2-[(1-benzyl-3-bromopyridin-1-ium-4-yl)methyl]-5,6-dimethoxy-2,3-dihydroinden-1-one bromide	1351939: Inhibition of human erythrocyte AChE using acetylthiocholine iodide as substrate preincubated for 5 mins followed by substrate addition measured every minute for 10 mins by Ellman’s method	ic50	0.0004	uM
2-(dimethylsulfamoylamino)-5-methoxy-1,2,3,4-tetrahydronaphthalene	1292255: Inhibition of AChE (unknown origin) using acetylcholine iodate as substrate preincubated for 10 mins followed by substrate addition by Lineweaver-Burk plot analysis	ki	0.0004	uM
3-[2-(1-benzylpiperidin-4-yl)ethyl]-7-methyl-5H-pyrrolo[3,2-f][1,2]benzoxazol-6-one	566585: Inhibition of human acetylcholinesterase	ic50	0.0005	uM
N-[8-[(6-chloro-1,2,3,4-tetrahydroacridin-9-yl)amino]octyl]-3-(1H-indol-3-yl)propanamide	482894: Inhibition of AChE	ic50	0.0005	uM
N-[6-[(6-chloro-1,2,3,4-tetrahydroacridin-9-yl)amino]hexyl]-4-(1H-indol-3-yl)butanamide	482894: Inhibition of AChE	ic50	0.0005	uM
[3-[[methyl-[7-[[(2Z)-3-oxo-2-[(3,4,5-trimethoxyphenyl)methylidene]-1-benzofuran-6-yl]oxy]heptyl]amino]methyl]phenyl] N-methylcarbamate	1796503: Cholinesterase Inhibition Assay from Article 10.1021/jm049515h: “Cholinesterase inhibitors: xanthostigmine derivatives blocking the acetylcholinesterase-induced beta-amyloid aggregation.”	ic50	0.0005	uM
3-[2-(1-benzylpiperidin-4-yl)ethyl]-7,8-dihydro-5H-[1,2]oxazolo[4,5-g]quinolin-6-one	482894: Inhibition of AChE	ic50	0.0005	uM
[3-[[ethyl-[3-(9-oxoxanthen-3-yl)oxypropyl]amino]methyl]phenyl] N-methylcarbamate	1796566: Cholinesterase Inhibition Assay from Article 10.1021/jm9810046: “Acetylcholinesterase inhibitors: synthesis and structure-activity relationships of omega-[N-methyl-N-(3-alkylcarbamoyloxyphenyl)- methyl]aminoalkoxyheteroaryl derivatives.”	ic50	0.0006	uM
2-[bis[3-(1,2,3,4-tetrahydroacridin-9-ylamino)propyl]amino]ethanol	1796269: Measurement of FBSAChE/EqBuChE Inhibitory Activity from Article 10.1021/jm049510k: “Development of molecular probes for the identification of extra interaction sites in the mid-gorge and peripheral sites of butyrylcholinesterase (BuChE). Rational design of novel, selective, and highly potent BuChE inhibitors.”	ki	0.0006	uM
3-[2-(1-benzylpiperidin-4-yl)ethyl]-6,8-dihydro-5H-[1,2]oxazolo[4,5-g]quinolin-7-one	239914: Binding affinity towards Acetylcholinesterase	ki	0.0006	uM
[3-[[3-(9-oxoxanthen-3-yl)oxypropyl-propan-2-ylamino]methyl]phenyl] N-methylcarbamate	1796566: Cholinesterase Inhibition Assay from Article 10.1021/jm9810046: “Acetylcholinesterase inhibitors: synthesis and structure-activity relationships of omega-[N-methyl-N-(3-alkylcarbamoyloxyphenyl)- methyl]aminoalkoxyheteroaryl derivatives.”	ic50	0.0007	uM
N-[6-[(6-chloro-1,2,3,4-tetrahydroacridin-9-yl)amino]hexyl]-3-(5-cyano-1H-indol-3-yl)propanamide	482894: Inhibition of AChE	ic50	0.0007	uM

CTD chemical–gene interactions

321 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Paraoxon	increases reaction, decreases expression, decreases activity, affects cotreatment, affects reaction (+4 more)	39
Sarin	affects binding, increases reaction, increases metabolic processing, increases phosphorylation, decreases activity (+5 more)	37
pralidoxime	decreases activity, affects binding, decreases reaction, increases reaction, affects reaction	36
asoxime chloride	decreases response to substance, affects reaction, affects cotreatment, increases reaction, decreases activity (+3 more)	35
Obidoxime Chloride	affects cotreatment, affects reaction, decreases activity, decreases reaction, increases reaction (+1 more)	34
tabun	decreases reaction, affects binding, affects cotreatment, affects reaction, increases phosphorylation (+1 more)	31
VX-agent	decreases activity, decreases reaction, decreases response to substance, increases reaction, affects reaction (+2 more)	30
methamidophos	increases reaction, decreases activity, decreases reaction, affects binding, increases phosphorylation (+1 more)	20
cyclohexyl methylphosphonofluoridate	decreases activity, decreases reaction, affects reaction, affects binding, increases metabolic processing (+1 more)	19
Dichlorvos	decreases reaction, affects cotreatment, increases reaction, increases phosphorylation, affects binding (+1 more)	19
O,O-diethyl O-3,5,6-trichloro-2-pyridyl phosphate	affects reaction, decreases activity, affects binding, increases phosphorylation, decreases reaction	16
Soman	increases response to substance, affects binding, decreases activity, decreases reaction, decreases carbamoylation (+1 more)	15
N,N’-monomethylenebis(pyridiniumaldoxime)	decreases reaction, affects reaction, decreases activity, affects binding	14
Trichlorfon	decreases activity, decreases reaction, affects cotreatment	14
Chlorpyrifos	decreases activity, decreases reaction, affects cotreatment, increases expression, affects reaction	13
Organophosphorus Compounds	decreases response to substance, increases metabolic processing, decreases activity, decreases reaction, increases abundance	11
Pesticides	affects response to substance, affects activity, decreases activity, decreases expression, decreases abundance (+1 more)	10
malaoxon	decreases activity, decreases reaction, affects cotreatment	9
Diazinon	affects cotreatment, decreases activity, increases abundance, decreases reaction	9
mipafox	affects binding, decreases activity, decreases reaction	8
Isoflurophate	decreases activity, decreases reaction	8
Oximes	decreases activity, decreases reaction, affects binding	8
Tacrine	affects reaction, decreases activity	8
Acetylthiocholine	decreases reaction, increases hydrolysis, increases metabolic processing, affects binding	7
2-(2-cresyl)-4H-1-3-2-benzodioxaphosphorin-2-oxide	affects binding, decreases activity, increases reaction	6
HLo 7	affects reaction, decreases activity, decreases reaction	6
S-(N,N-diethylaminoethyl) isobutyl methylphosphothiolate	affects reaction, decreases activity, decreases reaction	6
Donepezil	affects reaction, decreases activity, affects binding, decreases reaction, increases reaction	6
Aldicarb	decreases activity	6
Galantamine	decreases activity, decreases reaction, increases reaction, affects binding	6

ChEMBL screening assays

2563 unique, capped per target: 2513 binding, 27 admet, 22 functional, 1 toxicity

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1004516	Binding	Selectivity ratio of IC50 for human serum BChE to IC50 for human serum AChE	Tacripyrines, the first tacrine-dihydropyridine hybrids, as multitarget-directed ligands for the treatment of Alzheimer’s disease. — *J Med Chem*
CHEMBL1648945	Functional	Antagonist activity at human nAChR in human SH-SY5Y cells assessed as inhibition of acetylcholine-induced cytosolic Ca2+ signal at 0.3 to 100 uM	Cholinergic and neuroprotective drugs for the treatment of Alzheimer and neuronal vascular diseases. II. Synthesis, biological assessment, and molecular modelling of new tacrine analogues from highly substituted 2-aminopyridine-3-carbonitriles. — *Bioorg Med Chem*
CHEMBL3283247	ADMET	Stability of the compound assessed as acetylcholinesterase (unknown origin)-mediated hydrolysis at 5 X 10’-3 M	Chemistry and biological activities of N,N-dimethylaminoethyl acrylate, a choline acetyltransferase inhibitor. — *J Med Chem*

Cellosaurus cell lines

4 cell lines: 4 cancer cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_B1IS	Abcam HeLa ACHE KO	Cancer cell line	Female
CVCL_F5HP	EDITGENE ACHE Knockout HAP1 Cell Line	Cancer cell line	Male
CVCL_SB21	HAP1 ACHE (-) 1	Cancer cell line	Male
CVCL_SB22	HAP1 ACHE (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

Via MONDO — disease-level, not drug-specific.

Predicted chemistry — Sugi Predict

The predicted patent-compound landscape for ACHE across ~30M SureChEMBL compounds — explore on Sugi Predict.