CHRNA7

Summary

CHRNA7 (cholinergic receptor nicotinic alpha 7 subunit, HGNC:1960) is a protein-coding gene on chromosome 15q13.3, encoding Neuronal acetylcholine receptor subunit alpha-7 (P36544). Component of neuronal acetylcholine receptors (nAChRs) that function as pentameric, ligand-gated cation channels with high calcium permeability among other activities. nAChRs are excitatory neurotrasnmitter receptors formed by a collection of nAChR subunits known to mediate syna….

The nicotinic acetylcholine receptors (nAChRs) are members of a superfamily of ligand-gated ion channels that mediate fast signal transmission at synapses. The nAChRs are thought to be hetero-pentamers composed of homologous subunits. The proposed structure for each subunit is a conserved N-terminal extracellular domain followed by three conserved transmembrane domains, a variable cytoplasmic loop, a fourth conserved transmembrane domain, and a short C-terminal extracellular region. The protein encoded by this gene forms a homo-oligomeric channel, displays marked permeability to calcium ions and is a major component of brain nicotinic receptors that are blocked by, and highly sensitive to, alpha-bungarotoxin. Once this receptor binds acetylcholine, it undergoes an extensive change in conformation that affects all subunits and leads to opening of an ion-conducting channel across the plasma membrane. This gene is located in a region identified as a major susceptibility locus for juvenile myoclonic epilepsy and a chromosomal location involved in the genetic transmission of schizophrenia. An evolutionarily recent partial duplication event in this region results in a hybrid containing sequence from this gene and a novel FAM7A gene. Alternative splicing results in multiple transcript variants.

Source: NCBI Gene 1139 — RefSeq curated summary.

At a glance

• Gene–disease (curated): complex neurodevelopmental disorder (Limited, GenCC) — +1 more curated relationship
• GWAS associations: 1
• Clinical variants (ClinVar): 275 total — 56 pathogenic, 6 likely-pathogenic
• Phenotypes (HPO): 34
• Druggable target: yes — 30 molecules with ChEMBL bioactivity
• Dosage sensitivity (ClinGen): haploinsufficiency no evidence, triplosensitivity no evidence
• MANE Select transcript: NM_000746

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:1960
Approved symbol	CHRNA7
Name	cholinergic receptor nicotinic alpha 7 subunit
Location	15q13.3
Locus type	gene with protein product
Status	Approved
Aliases	a7nAChR
Ensembl gene	ENSG00000175344
Ensembl biotype	protein_coding
OMIM	118511
Entrez	1139

Gene structure

Transcript identifiers

Ensembl transcripts: 38 — 15 protein_coding, 11 nonsense_mediated_decay, 9 retained_intron, 3 protein_coding_CDS_not_defined

ENST00000306901, ENST00000437966, ENST00000454250, ENST00000635722, ENST00000635759, ENST00000635883, ENST00000635884, ENST00000635978, ENST00000636044, ENST00000636184, ENST00000636245, ENST00000636271, ENST00000636292, ENST00000636295, ENST00000636440, ENST00000636521, ENST00000636603, ENST00000636647, ENST00000636709, ENST00000636850, ENST00000636898, ENST00000636957, ENST00000637033, ENST00000637183, ENST00000637189, ENST00000637348, ENST00000637350, ENST00000637519, ENST00000637552, ENST00000637649, ENST00000637786, ENST00000637971, ENST00000638031, ENST00000638081, ENST00000638106, ENST00000675428, ENST00000676380, ENST00000965369

RefSeq mRNA: 2 — MANE Select: NM_000746 NM_000746, NM_001190455

CCDS: CCDS10027, CCDS53924

Canonical transcript exons

ENST00000306901 — 10 exons

Exon	Start	End
ENSE00000941817	32111790	32111899
ENSE00001687700	32153907	32153986
ENSE00001953288	32167940	32173018
ENSE00003476235	32159569	32159655
ENSE00003487368	32030898	32031037
ENSE00003497165	32157608	32157775
ENSE00003629830	32101303	32101347
ENSE00003656444	32158412	32158606
ENSE00003686247	32163226	32163335
ENSE00003797685	32030515	32030649

Expression profiles

Bgee: expression breadth ubiquitous, 186 present calls, max score 93.29.

FANTOM5 (CAGE): breadth broad, TPM avg 2.4504 / max 363.9228, expressed in 501 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
145690	2.1128	464
145689	0.3177	186
145688	0.0199	5

Top tissues by expression

250 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
adrenal tissue	UBERON:0018303	93.29	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	86.69	gold quality
oocyte	CL:0000023	84.74	gold quality
secondary oocyte	CL:0000655	83.83	gold quality
ganglionic eminence	UBERON:0004023	81.98	gold quality
embryo	UBERON:0000922	81.97	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	81.78	gold quality
ventricular zone	UBERON:0003053	79.29	gold quality
jejunal mucosa	UBERON:0000399	77.97	gold quality
pigmented layer of retina	UBERON:0001782	77.65	gold quality
ileal mucosa	UBERON:0000331	77.03	gold quality
prefrontal cortex	UBERON:0000451	76.51	gold quality
left lobe of thyroid gland	UBERON:0001120	74.65	gold quality
thyroid gland	UBERON:0002046	74.39	gold quality
left ovary	UBERON:0002119	74.39	gold quality
right lobe of thyroid gland	UBERON:0001119	74.36	gold quality
cortical plate	UBERON:0005343	74.31	gold quality
right ovary	UBERON:0002118	73.42	gold quality
rectum	UBERON:0001052	72.68	gold quality
body of pancreas	UBERON:0001150	72.02	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	71.96	gold quality
frontal cortex	UBERON:0001870	71.61	gold quality
Brodmann (1909) area 9	UBERON:0013540	71.60	gold quality
body of stomach	UBERON:0001161	71.51	gold quality
neocortex	UBERON:0001950	71.51	gold quality
primary visual cortex	UBERON:0002436	71.38	gold quality
right frontal lobe	UBERON:0002810	71.26	gold quality
stomach	UBERON:0000945	71.08	gold quality
anterior cingulate cortex	UBERON:0009835	70.77	gold quality
duodenum	UBERON:0002114	70.69	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-GEOD-137537	yes	6.33
E-HCAD-10	yes	4.46
E-ANND-3	no	2.55

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): EGR1, GLI2, HR, IRF6, MYC, NFKB, NKX2-1, NR3C1, TFAP2A, USF1

miRNA regulators (miRDB)

85 targeting CHRNA7, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-4692	100.00	67.32	2066
HSA-MIR-6873-3P	100.00	71.42	2626
HSA-MIR-4673	100.00	66.64	1490
HSA-MIR-4283	100.00	66.42	2097
HSA-MIR-6833-3P	100.00	70.63	3197
HSA-MIR-4768-5P	100.00	69.49	2861
HSA-MIR-3925-3P	100.00	69.95	1237
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-4514	99.99	67.10	1870
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-1184	99.99	68.19	1458
HSA-MIR-4645-5P	99.98	65.81	1284
HSA-MIR-1468-3P	99.96	72.74	3797
HSA-MIR-548AB	99.95	71.31	3488
HSA-MIR-559	99.95	72.28	3609
HSA-MIR-548A-5P	99.94	71.27	3482
HSA-MIR-548AD-5P	99.94	71.23	3502
HSA-MIR-548AE-5P	99.94	71.23	3502
HSA-MIR-548AK	99.94	71.24	3488
HSA-MIR-548AM-5P	99.94	71.24	3488
HSA-MIR-548AP-5P	99.94	71.14	3489
HSA-MIR-548AQ-5P	99.94	71.34	3426
HSA-MIR-548AR-5P	99.94	71.28	3515
HSA-MIR-548AS-5P	99.94	71.22	3482
HSA-MIR-548AU-5P	99.94	71.24	3488
HSA-MIR-548AY-5P	99.94	71.23	3502
HSA-MIR-548B-5P	99.94	71.23	3502
HSA-MIR-548BB-5P	99.94	71.27	3509
HSA-MIR-548C-5P	99.94	71.24	3488
HSA-MIR-548D-5P	99.94	71.23	3502

Functional genomics

ClinGen dosage: haploinsufficiency 0 (no evidence), triplosensitivity 0 (no evidence). ClinGen Gene Dosage Map

Literature-anchored findings (GeneRIF, showing 40)

• Changes in nicotinic acetylcholine receptor subunits expression in brain of patients with Down syndrome and Alzheimer’s disease. (PMID:11771745)
• Results suggest that the CHRNA7 may play a role in schizophrenia in these families. (PMID:11803513)
• 3-Mb map of 15q13-q14 showing that CHRFAM7A is part of a large segmental duplication in the opposite orientation to CHRNA7 and revealing several other duplications (PMID:11829490)
• Some properties of human neuronal alpha 7 nicotinic acetylcholine receptors fused to the green fluorescent protein (PMID:11891308)
• single-channel properties of human acetylcholine alpha 7 receptors are altered by fusing alpha 7 to the green fluorescent protein (PMID:11891309)
• The increasing levels of the alpha7 nicotinic acetylcholine receptor during the first trimester support the important role of nAChRs for the development of the central nervous system. (PMID:11905992)
• Expression of an alpha7 duplicate nicotinic acetylcholine receptor-related protein in human leukocytes. (PMID:12020960)
• The positional candidate gene CHRNA7 at the juvenile myoclonic epilepsy locus (EJM2) on chromosome 15q13-14. (PMID:12049804)
• results strongly suggest that a human sperm alpha7 subunit-containing nicotinic acetylcholine receptor plays a role in the recombinant human ZP3-initiated acrosome reaction (PMID:12193385)
• ACh signaling through alpha7 nAChR channels controls late stages of keratinocyte development in the epidermis by regulating expression of the cell cycle progression, apoptosis, and terminal differentiation genes and mediated, by transmembrane Ca2+ influx. (PMID:12391028)
• the -2 bp deletion within the CHRNA7-like gene is a risk factor for P50 sensory gating deficit in auditory evoked potentials (PMID:12399955)
• the G23-N46 portion of the alpha7 N-terminal region may contribute to receptor homooligomerizations (PMID:12431773)
• In the developing human spinal cord, neuronal nicotinic receptors are expressed during important embryonic periods. (PMID:12454998)
• An increase in the number of astrocytes expressing alpha7 immunoreactivity was observed in Alzheimer Disease compared with age-matched controls. A similar increase was not evident in Lewy Body Dementia. (PMID:12509811)
• An extra cysteine residue in the N-terminal extracellular domain, a unique feature of the alpha7 subunit, appears to have neither positive nor negative consequences in the formation of functional cell surface receptors. (PMID:12549904)
• alpha 7-Nicotinic acetylcholine receptors alpha 7-nAChRs play important roles in chemical and electrical signaling, and perhaps in neurite outgrowth, synaptic plasticity, and neuronal death/survival. (PMID:12626641)
• CHRNA7 subunit is expressed in the soma of the majority of pyramidal cells, with fairly consistent immunoreactivity observed throughout the different regions of the hippocampus. (PMID:12663058)
• significant decrease of the alpha4 and the alpha7 nicotinic acetylcholine receptor subunit in cortices of Parkinson patients which turns out to be similar to recent findings in Alzheimer patients. (PMID:12781587)
• Promoter region of the CHRNA7 gene as risk factors for the P50 inhibitory deficit in sschizophrenia. (PMID:14569275)
• expression of CHRNA7 is decreased in schizophrenia (PMID:14582144)
• The -2 bp polymorphism or a nearby polymorphism of the NACHR alpha7 subunit may play a role in the pathogenesis of Bipolar Disorder. (PMID:14729237)
• Reduced gene expression of the alpha4beta2 nicotinic receptor in the cerebral cortex is a major feature of the neurochemical pathology of autism, whilst post-transcriptional abnormalities of both this and the alpha7 subtype are apparent in the cerebellum (PMID:15046869)
• an association between the homozygous 113 bp allele of the alpha-7-nicotinic receptor and smoking risk in schizophrenics (PMID:15100704)
• shows that the most important interactions occur between the residues V12-K28 from the peptide and the loop C of the receptor (PMID:15219869)
• kinetic and solubility studies on human alpha7 acetylcholine receptor expressed in yeast (PMID:15226316)
• direct evidence suggesting that the M5 muscarinic receptor gene combined with the alpha7-nicotinic receptor gene may be linked to schizophrenia (PMID:15292665)
• The number of astrocytes labeled alpha7 antibodies was increased in most areas of the hippocampus and entorhinal cortex in Alzheimer’s disease. (PMID:15465084)
• alpha3 and alpha7 nicotinic acetylcholine receptors regulate keratinocyte chemokinesis and chemotaxis (PMID:15494367)
• ric-3 appears to be necessary for proper folding and/or assembly of alpha7 receptors in HEK293 cells (PMID:15504725)
• Mutations in the human alpha 7 neuronal nicotinic receptor subunit gene promoter that are associated with schizophrenia were not found in a population of 249 unrelated Han Chinese schizophrenic patients. (PMID:15531077)
• The alpha7 nicotinic receptor protein is expressed in fewer cell lines, and the tobacco carcinogen NNK increases alpha7 nicotinic receptor protein levels. (PMID:15807899)
• biophysical analysis of the gating mechanism of human alpha7 nicotinic acetylcholine receptor (PMID:15857954)
• Results indicate that the alpha7 nicotinic receptor subunit may mediate some aspects of nicotine dependence. (PMID:15896732)
• hRIC-3 can act as a specific regulator of alpha7 and 5-HT3 expression at different levels by increasing the number of mature receptors and facilitating its transport to the membrane (PMID:15927954)
• The gating motion of the human nicotinic acetylcholine receptor (nAChR) alpha7 was investigated with normal mode analysis (NMA) of two homology models. (PMID:16307758)
• Two alleles showed both familial transmission disequilibrium and population-wide association with schizophrenia. Variations in the frequency of SNPs in CHRNA7, the alpha-7-nicotinic acetylcholine receptor subunit gene at 15q14, were found in each group. (PMID:16417613)
• Review cites the role of nAChR alpha 7 as an essential component of the cholinergic anti-inflammatory pathway, because activation of the receptor prevents cytokine release. (PMID:16461803)
• Incorporation of beta3 into neuronal nicotinic receptors other than alpha3beta4 has a powerful dominant-negative effect. This raises the possibility of a novel regulatory role for the beta3 subunit on neuronal nicotinic signaling in CNS. (PMID:16822928)
• Placental expression of alpha7 nAChR is increased in severe preeclampsia placentas when compared with normal placentas. (PMID:16837119)
• The Ras/Raf-1/MEK1/ERK cascade culminates in nicotine up-regulated expression of the gene encoding STAT-3, whereas recruitment and activation of tyrosine kinase JAK-2 phosphorylates it. (PMID:17012261)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio		ENSDARG00000101522
danio_rerio	chrna7a	ENSDARG00000101702
mus_musculus	Chrna7	ENSMUSG00000030525
rattus_norvegicus	Chrna7	ENSRNOG00000010853

Paralogs (45): GABRA3 (ENSG00000011677), GABRA1 (ENSG00000022355), CHRNA3 (ENSG00000080644), GABRP (ENSG00000094755), CHRNA4 (ENSG00000101204), GLRA2 (ENSG00000101958), GABRE (ENSG00000102287), CHRNE (ENSG00000108556), GABRA4 (ENSG00000109158), GLRB (ENSG00000109738), GABRR2 (ENSG00000111886), GABRG2 (ENSG00000113327), CHRNB4 (ENSG00000117971), CHRNA2 (ENSG00000120903), CHRNA10 (ENSG00000129749), CHRND (ENSG00000135902), CHRNA1 (ENSG00000138435), GLRA3 (ENSG00000145451), GABRA6 (ENSG00000145863), GABRB2 (ENSG00000145864), GLRA1 (ENSG00000145888), GABRR1 (ENSG00000146276), CHRNB3 (ENSG00000147432), CHRNA6 (ENSG00000147434), HTR3B (ENSG00000149305), GABRA2 (ENSG00000151834), CHRNB2 (ENSG00000160716), GABRG1 (ENSG00000163285), GABRB1 (ENSG00000163288), GABRB3 (ENSG00000166206), CHRFAM7A (ENSG00000166664), HTR3A (ENSG00000166736), CHRNA5 (ENSG00000169684), CHRNB1 (ENSG00000170175), CHRNA9 (ENSG00000174343), HTR3C (ENSG00000178084), GABRG3 (ENSG00000182256), GABRR3 (ENSG00000183185), HTR3E (ENSG00000186038), HTR3D (ENSG00000186090)

Protein

Protein identifiers

Neuronal acetylcholine receptor subunit alpha-7 — P36544 (reviewed: P36544)

Alternative names: Nicotinic acetylcholine receptor subunit alpha-7

All UniProt accessions (20): A0A1B0GTE0, A0A1B0GTT0, A0A1B0GTT9, A0A1B0GU04, A0A1B0GU11, A0A1B0GU56, A0A1B0GU93, A0A1B0GUR5, A0A1B0GV25, A0A1B0GV43, A0A1B0GV44, A0A1B0GV86, P36544, A0A1B0GVH2, A0A1B0GVI5, A0A1B0GVN6, A0A1B0GVP9, A0A1B0GW47, A0A1B0GW52, A0A1B0GWH1

UniProt curated annotations — full annotation on UniProt →

Function. Component of neuronal acetylcholine receptors (nAChRs) that function as pentameric, ligand-gated cation channels with high calcium permeability among other activities. nAChRs are excitatory neurotrasnmitter receptors formed by a collection of nAChR subunits known to mediate synaptic transmission in the nervous system and the neuromuscular junction. Each nAchR subunit confers differential attributes to channel properties, including activation, deactivation and desensitization kinetics, pH sensitivity, cation permeability, and binding to allosteric modulators. CHRNA7 forms homopentameric neuronal acetylcholine receptors abundantly expressed in the central nervous system, characterized by fast desensitization and high calcium permeability. Also forms heteropentamers with CHRNB2, mainly expressed in basal forebrain cholinergic neurons. Involved in the modulation of calcium-dependent signaling pathways and influences the release of neurotransmitters, including dopamine, glutamate and GABA. Also expressed in non-neuronal cells such as immune cells like lymphocytes, monocytes and macrophages. In T cells, activation induces metabotropic signaling that results in an increase of intracellular Ca2+ concentrations, independent of ionotropic receptor functions. In macrophages, required for acetylcholine-mediated inhibition of TNF and other inflammatory cytokine release. Once activated by acetylcholine, nicotine or other agonists, selectively inhibits production of pro-inflammatory cytokines while leaving anti-inflammatory cytokines undisturbed. Stimulates the cholinergic anti-inflammatory pathway, controlling inflammation by inhibiting NFKB nuclear translocation and activating the JAK2-STAT3 pathway, independently of ion channel activity. Also expressed in the urothelium where it modulates reflex bladder activity by increasing intracellular calcium through internal stores and decreasing basal ATP release.

Subunit / interactions. Homopentamer. Can also form heteropentamers with CHRNB2, mainly found in basal forebrain cholinergic neurons. Interacts with RIC3; which is required for proper folding and assembly. Interacts with LYPD6. Interacts with CANX.

Subcellular location. Postsynaptic cell membrane. Cell membrane.

Tissue specificity. Expressed in neuronal cells. Expressed in macrophages (at protein level).

Post-translational modifications. Glycosylations at Asn-46, Asn-90 and Asn-133 are essential for TMEM35A/NACHO-mediated proper subunit assembly and trafficking to the cell membrane.

Activity regulation. Activated by a myriad of ligands such as acetylcholine, cytisine, nicotine, choline and epibatidine. Oligomeric amyloid-beta protein 42 activates specifially CHRNA7:CHRNB2 nAchRs. Activity is modulated by positive allosteric modulators (PAMs), such as flavonoids, with a wide range of chemical diversity, pharmacological sensitivity and efficacy. AChR activity is inhibited by the antagonists alpha-conotoxons RgIA, ImI and ImII, small disulfide-constrained peptides from cone snails. Alpha-conotoxin PnIC selectively inhibits CHRNA7:CHRNB2 over CHRNA7 homopentamer.

Miscellaneous. May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay.

Similarity. Belongs to the ligand-gated ion channel (TC 1.A.9) family. Acetylcholine receptor (TC 1.A.9.1) subfamily. Alpha-7/CHRNA7 sub-subfamily.

Isoforms (3)

UniProt ID	Names	Canonical?
P36544-1	1	yes
P36544-2	2
P36544-3	3

RefSeq proteins (2): NP_000737, NP_001177384 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR002394	Nicotinic_acetylcholine_rcpt	Family
IPR006029	Neurotrans-gated_channel_TM	Domain
IPR006201	Neur_channel	Family
IPR006202	Neur_chan_lig-bd	Domain
IPR018000	Neurotransmitter_ion_chnl_CS	Conserved_site
IPR036719	Neuro-gated_channel_TM_sf	Homologous_superfamily
IPR036734	Neur_chan_lig-bd_sf	Homologous_superfamily
IPR038050	Neuro_actylchol_rec	Homologous_superfamily

Pfam: PF02931, PF02932

Catalyzed reactions (Rhea), 7 shown:

• NH4(+)(in) = NH4(+)(out) (RHEA:28747)
• K(+)(in) = K(+)(out) (RHEA:29463)
• Ca(2+)(in) = Ca(2+)(out) (RHEA:29671)
• L-arginine(in) = L-arginine(out) (RHEA:32143)
• choline(out) = choline(in) (RHEA:32751)
• Na(+)(in) = Na(+)(out) (RHEA:34963)
• guanidine(out) = guanidine(in) (RHEA:73883)

UniProt features (83 total): strand 22, helix 14, turn 13, mutagenesis site 7, sequence conflict 6, binding site 4, transmembrane region 4, glycosylation site 3, splice variant 3, disulfide bond 2, topological domain 2, signal peptide 1, chain 1, region of interest 1

Structure

Experimental structures (PDB)

51 structures, top 30 by resolution.

PDB	Method	Resolution (Å)
8P1H	X-RAY DIFFRACTION	1.95
5AFN	X-RAY DIFFRACTION	2.15
9QTO	ELECTRON MICROSCOPY	2.16
8V8A	ELECTRON MICROSCOPY	2.19
5AFJ	X-RAY DIFFRACTION	2.2
9QTN	ELECTRON MICROSCOPY	2.28
8C9X	ELECTRON MICROSCOPY	2.3
8UT1	ELECTRON MICROSCOPY	2.3
8UTB	ELECTRON MICROSCOPY	2.3
8UZJ	ELECTRON MICROSCOPY	2.3
8V88	ELECTRON MICROSCOPY	2.3
8V80	ELECTRON MICROSCOPY	2.34
5AFK	X-RAY DIFFRACTION	2.38
5AFL	X-RAY DIFFRACTION	2.38
5AFH	X-RAY DIFFRACTION	2.4
8V86	ELECTRON MICROSCOPY	2.47
8V89	ELECTRON MICROSCOPY	2.53
8V82	ELECTRON MICROSCOPY	2.61
9LH5	ELECTRON MICROSCOPY	2.61
9LH6	ELECTRON MICROSCOPY	2.69
7KOX	ELECTRON MICROSCOPY	2.7
8CE4	ELECTRON MICROSCOPY	2.7
9LH8	ELECTRON MICROSCOPY	2.74
8CI1	ELECTRON MICROSCOPY	2.8
5AFM	X-RAY DIFFRACTION	2.85
7EKP	ELECTRON MICROSCOPY	2.85
9IIV	ELECTRON MICROSCOPY	2.89
9IIR	ELECTRON MICROSCOPY	2.93
9LN7	ELECTRON MICROSCOPY	2.94
9LHA	ELECTRON MICROSCOPY	2.96

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P36544-F1	79.16	0.40

Antibody-complex structures (SAbDab): 5 — 8C9X, 8CAU, 8CE4, 8CI1, 8CI2

Functional residue map

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

Ligand- & substrate-binding residues (4): 44; 172; 210; 42

Disulfide bonds (2): 150–164, 212–213

Glycosylation sites (3): 46, 90, 133

Mutagenesis-validated functional residues (7):

Position	Phenotype
120	decreases permeability to ca(2+). no effect on permeability to k(+).
139	115-fold more potently inhibited by the alpha-conotoxin imi; but no change in inhibition by the alpha-conotoxin imii.
156	no effect on ligand-gated cation channel activity.
227	no effect on ligand-gated cation channel activity.
490	loss of ligand-gated cation channel activity.
491	loss of ligand-gated cation channel activity.
500	no effect on ligand-gated cation channel activity.

Function

Pathways and Gene Ontology

Reactome pathways

6 pathways

ID	Pathway
R-HSA-629594	Highly calcium permeable postsynaptic nicotinic acetylcholine receptors
R-HSA-112314	Neurotransmitter receptors and postsynaptic signal transmission
R-HSA-112315	Transmission across Chemical Synapses
R-HSA-112316	Neuronal System
R-HSA-181431	Acetylcholine binding and downstream events
R-HSA-622327	Postsynaptic nicotinic acetylcholine receptors

MSigDB gene sets: 332 (showing top): VALK_AML_WITH_FLT3_ITD, GOBP_DENDRITE_DEVELOPMENT, GOBP_MEMORY, GOBP_EXCRETION, GOBP_MEMBRANE_DEPOLARIZATION, GOBP_RESPONSE_TO_NITROGEN_COMPOUND, MODULE_328, GOBP_COGNITION, MODULE_274, GRUETZMANN_PANCREATIC_CANCER_DN, GOBP_BEHAVIOR, GOBP_INFLAMMATORY_RESPONSE, GOBP_POSITIVE_REGULATION_OF_AMIDE_METABOLIC_PROCESS, MODULE_64, GOBP_CANONICAL_NF_KAPPAB_SIGNAL_TRANSDUCTION

GO Biological Process (44): response to hypoxia (GO:0001666), monoatomic ion transport (GO:0006811), calcium ion transport (GO:0006816), intracellular calcium ion homeostasis (GO:0006874), signal transduction (GO:0007165), chemical synaptic transmission (GO:0007268), learning or memory (GO:0007611), memory (GO:0007613), short-term memory (GO:0007614), positive regulation of cell population proliferation (GO:0008284), negative regulation of tumor necrosis factor production (GO:0032720), monoatomic ion transmembrane transport (GO:0034220), response to nicotine (GO:0035094), regulation of membrane potential (GO:0042391), negative regulation of canonical NF-kappaB signal transduction (GO:0043124), positive regulation of MAPK cascade (GO:0043410), positive regulation of angiogenesis (GO:0045766), synapse organization (GO:0050808), cognition (GO:0050890), sensory processing (GO:0050893), positive regulation of protein metabolic process (GO:0051247), excitatory postsynaptic potential (GO:0060079), synaptic transmission involved in micturition (GO:0060084), positive regulation of ERK1 and ERK2 cascade (GO:0070374), acetylcholine receptor signaling pathway (GO:0095500), dendritic spine organization (GO:0097061), modulation of excitatory postsynaptic potential (GO:0098815), dendrite arborization (GO:0140059), negative regulation of cytokine production involved in inflammatory response (GO:1900016), positive regulation of long-term synaptic potentiation (GO:1900273), positive regulation of amyloid-beta formation (GO:1902004), negative regulation of amyloid-beta formation (GO:1902430), regulation of amyloid precursor protein catabolic process (GO:1902991), response to amyloid-beta (GO:1904645), response to acetylcholine (GO:1905144), regulation of amyloid fibril formation (GO:1905906), positive regulation of excitatory postsynaptic potential (GO:2000463), canonical NF-kappaB signal transduction (GO:0007249), synaptic transmission, cholinergic (GO:0007271), signal transduction involved in regulation of gene expression (GO:0023019)

GO Molecular Function (12): amyloid-beta binding (GO:0001540), transmembrane signaling receptor activity (GO:0004888), monoatomic ion channel activity (GO:0005216), calcium channel activity (GO:0005262), acetylcholine receptor activity (GO:0015464), toxic substance binding (GO:0015643), chloride channel regulator activity (GO:0017081), acetylcholine-gated monoatomic cation-selective channel activity (GO:0022848), acetylcholine binding (GO:0042166), protein homodimerization activity (GO:0042803), extracellular ligand-gated monoatomic ion channel activity (GO:0005230), protein binding (GO:0005515)

GO Cellular Component (13): endoplasmic reticulum membrane (GO:0005789), plasma membrane (GO:0005886), acetylcholine-gated channel complex (GO:0005892), membrane (GO:0016020), dendrite (GO:0030425), neuron projection (GO:0043005), plasma membrane raft (GO:0044853), synapse (GO:0045202), postsynaptic membrane (GO:0045211), postsynapse (GO:0098794), cation channel complex (GO:0034703), synaptic membrane (GO:0097060), neurotransmitter receptor complex (GO:0098878)

Reactome top-level categories

Rollup of top-5 pathways:

Category	Pathways
Postsynaptic nicotinic acetylcholine receptors	1
Transmission across Chemical Synapses	1
Neuronal System	1
Neurotransmitter receptors and postsynaptic signal transmission	1
Acetylcholine binding and downstream events	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cognition	2
postsynaptic neurotransmitter receptor activity	2
binding	2
monoatomic ion channel complex	2
plasma membrane signaling receptor complex	2
cellular anatomical structure	2
plasma membrane region	2
synapse	2
response to stress	1
response to decreased oxygen levels	1
transport	1
metal ion transport	1
intracellular monoatomic cation homeostasis	1
calcium ion homeostasis	1
cell communication	1
cellular process	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
anterograde trans-synaptic signaling	1
behavior	1
learning or memory	1
memory	1
cell population proliferation	1
regulation of cell population proliferation	1
positive regulation of cellular process	1
tumor necrosis factor production	1
regulation of tumor necrosis factor production	1
negative regulation of tumor necrosis factor superfamily cytokine production	1
monoatomic ion transport	1
transmembrane transport	1
response to chemical	1
monoatomic ion transmembrane transport	1
regulation of biological quality	1
canonical NF-kappaB signal transduction	1
regulation of canonical NF-kappaB signal transduction	1
negative regulation of intracellular signal transduction	1
MAPK cascade	1
regulation of MAPK cascade	1
positive regulation of intracellular signal transduction	1

Protein interactions and networks

STRING

492 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CHRNA7	SLURP1	P55000	485
CHRNA7	GRIN1	P35437	456
CHRNA7	ACHE	P22303	423
CHRNA7	APP	P05067	420
CHRNA7	CHRM1	P11229	418
CHRNA7	RASL12	Q9NYN1	404
CHRNA7	CHRM2	P08172	374
CHRNA7	RIC3	Q7Z5B4	366
CHRNA7	OTUD7A	Q8TE49	357
CHRNA7	MTMR10	Q9NXD2	354
CHRNA7	BHLHE23	Q8NDY6	353
CHRNA7	MSL3	Q8N5Y2	350
CHRNA7	CCDC66	A2RUB6	350
CHRNA7	CHAT	P28329	340
CHRNA7	SLC18A3	Q16572	340

IntAct

43 interactions, top by confidence:

A	B	Type	Score
CHRNA7	APP	psi-mi:“MI:0915”(physical association)	0.700
APP	CHRNA7	psi-mi:“MI:0407”(direct interaction)	0.700
APP	CHRNA7	psi-mi:“MI:0915”(physical association)	0.700
APP	CHRNA7	psi-mi:“MI:0915”(physical association)	0.650
CHRNA7	APP	psi-mi:“MI:0403”(colocalization)	0.650
RBBP4	CHRNA7	psi-mi:“MI:0915”(physical association)	0.560
DBF4	CHRNA7	psi-mi:“MI:0915”(physical association)	0.560
SNW1	CHRNA7	psi-mi:“MI:0915”(physical association)	0.560
BRWD1	CHRNA7	psi-mi:“MI:0915”(physical association)	0.560
MINDY1	CHRNA7	psi-mi:“MI:0915”(physical association)	0.560
SLURP1	CHRNA7	psi-mi:“MI:0915”(physical association)	0.400
CHRNA7	SLURP2	psi-mi:“MI:0915”(physical association)	0.400
	CHRNA7	psi-mi:“MI:0915”(physical association)	0.400
CHRNA7	APOE	psi-mi:“MI:0915”(physical association)	0.400

BioGRID (33): PPP1CC (Affinity Capture-Western), CHRNA7 (Affinity Capture-Western), CHRNA7 (Co-localization), CHRNA7 (Affinity Capture-Western), PRNP (Affinity Capture-Western), FYN (Affinity Capture-Western), CHRNA7 (Affinity Capture-Western), CHRFAM7A (Negative Genetic), SNX14 (Affinity Capture-MS), SLC12A4 (Affinity Capture-MS), OSBPL8 (Affinity Capture-MS), PKMYT1 (Affinity Capture-MS), SREBF1 (Affinity Capture-MS), FNDC3A (Affinity Capture-MS), TAP2 (Affinity Capture-MS)

ESM2 similar proteins: A8MPY1, P02713, P02714, P02715, P02716, P02717, P02718, P04758, P04759, P04760, P05376, P07510, P09484, P09628, P09660, P09690, P11230, P12390, P13536, P17787, P18916, P20782, P22770, P25109, P25110, P26153, P26714, P36544, P43144, P47742, P49579, P49580, P49582, P50573, P54131, P56476, P78334, Q04844, Q05941, Q07001

Diamond homologs: A5X5Y0, O70212, O95264, P04757, P05376, P18845, P19370, P22770, P23979, P26153, P32297, P35563, P36544, P43143, P43679, P46098, P48182, P49581, P49582, P54131, Q05941, Q07263, Q15825, Q494W8, Q5IS76, Q68RJ7, Q70Z44, Q866A2, Q8R4G9, Q8WXA8, Q9I8C7, Q9JHJ5, Q9JJ16, A8WQK3, O16926, O70174, P02708, P02709, P02710, P02711

SIGNOR signaling

5 interactions.

A	Effect	B	Mechanism
SRC	down-regulates	CHRNA7	phosphorylation
CHRNA7	“form complex”	“Neuronal nicotinic acetylcholine receptor complex, alpha7-beta2”	binding
acetylcholine	“up-regulates activity”	CHRNA7	“chemical activation”
CHRNA7	“up-regulates activity”	RHOA	binding

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	56
Likely pathogenic	6
Uncertain significance	123
Likely benign	33
Benign	37

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1180504	GRCh37/hg19 15q13.2-13.3(chr15:30935243-32445105)x1	Pathogenic
145454	GRCh38/hg38 15q13.2-13.3(chr15:30662521-32217731)x1	Pathogenic
146004	GRCh38/hg38 15q13.2-13.3(chr15:30797731-32150818)x3	Pathogenic
146926	GRCh38/hg38 15q13.3(chr15:31738809-32343758)x3	Pathogenic
148887	GRCh38/hg38 15q13.3(chr15:31772797-32153051)x1	Pathogenic
148888	GRCh38/hg38 15q13.3(chr15:31772797-32153051)x0	Pathogenic
148963	GRCh38/hg38 15q13.3(chr15:31772797-32247465)x1	Pathogenic
149560	GRCh38/hg38 15q13.3(chr15:31772797-32222779)x1	Pathogenic
150474	GRCh38/hg38 15q13.2-13.3(chr15:30662521-32150923)x1	Pathogenic
150479	GRCh38/hg38 15q13.2-13.3(chr15:30662521-32569411)x1	Pathogenic
152611	GRCh38/hg38 15q13.2-13.3(chr15:30797731-32170441)x1	Pathogenic
153886	GRCh38/hg38 15q13.3(chr15:31711334-32154629)x1	Pathogenic
154195	GRCh38/hg38 15q13.2-13.3(chr15:30781532-32154629)x1	Pathogenic
154609	GRCh38/hg38 15q13.3(chr15:31680443-32217725)x1	Pathogenic
155680	GRCh38/hg38 15q13.2-13.3(chr15:30781465-32154629)x1	Pathogenic
160946	GRCh38/hg38 15q13.3(chr15:31738809-32217725)x1	Pathogenic
1703648	GRCh37/hg19 15q13.2-13.3(chr15:31088442-32446830)	Pathogenic
1703658	GRCh37/hg19 15q13.2-13.3(chr15:31073668-32446830)	Pathogenic
1710519	GRCh37/hg19 15q13.3(chr15:31955021-32444857)x1	Pathogenic
1711871	GRCh37/hg19 15q13.2-13.3(chr15:31098690-32444044)x1	Pathogenic
1807711	GRCh37/hg19 15q13.3(chr15:32011476-32446830)x1	Pathogenic
1808694	GRCh37/hg19 15q13.3(chr15:32003538-32446830)x1	Pathogenic
236369	Single allele	Pathogenic
2423387	NC_000015.9:g.(?32322798)(32404100_?)del	Pathogenic
253378	GRCh37/hg19 15q13.2-13.3(chr15:31115047-32418279)x1	Pathogenic
2574687	GRCh37/hg19 15q13.2-13.3(chr15:31073735-32446830)	Pathogenic
2685505	GRCh37/hg19 15q13.3(chr15:31223642-32446830)x1	Pathogenic
3242303	GRCh37/hg19 15q13.2-13.3(chr15:30935396-32444881)x3	Pathogenic
32642	GRCh38/hg38 15q13.2-13.3(chr15:30662523-32217725)x1	Pathogenic
395453	GRCh37/hg19 15q13.2-13.3(chr15:31115047-32418220)x1	Pathogenic

SpliceAI

2242 predictions. Top by Δscore:

Variant	Effect	Δscore
15:32030645:GCACG:G	donor_gain	1.0000
15:32030647:ACGG:A	donor_loss	1.0000
15:32030650:G:GG	donor_gain	1.0000
15:32030650:GTA:G	donor_loss	1.0000
15:32030651:T:A	donor_loss	1.0000
15:32030895:A:AG	acceptor_gain	1.0000
15:32030895:AAGT:A	acceptor_gain	1.0000
15:32030896:A:AG	acceptor_gain	1.0000
15:32030897:G:GG	acceptor_gain	1.0000
15:32030897:GT:G	acceptor_gain	1.0000
15:32031032:G:GT	donor_gain	1.0000
15:32031035:GTG:G	donor_gain	1.0000
15:32153905:A:AG	acceptor_gain	1.0000
15:32153906:G:GT	acceptor_gain	1.0000
15:32153906:GT:G	acceptor_gain	1.0000
15:32158406:A:AG	acceptor_gain	1.0000
15:32158406:AT:A	acceptor_gain	1.0000
15:32158406:ATG:A	acceptor_gain	1.0000
15:32158407:T:A	acceptor_gain	1.0000
15:32158407:T:G	acceptor_gain	1.0000
15:32158408:G:A	acceptor_gain	1.0000
15:32158409:GAGG:G	acceptor_loss	1.0000
15:32158411:G:A	acceptor_gain	1.0000
15:32158411:GG:G	acceptor_loss	1.0000
15:32163224:A:AG	acceptor_gain	1.0000
15:32163225:G:GG	acceptor_gain	1.0000
15:32163332:GTGG:G	donor_gain	1.0000
15:32163334:GG:G	donor_gain	1.0000
15:32163335:GG:G	donor_gain	1.0000
15:32030896:A:AC	acceptor_loss	0.9900

AlphaMissense

3300 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
15:32111793:T:A	W82R	1.000
15:32111793:T:C	W82R	1.000
15:32111795:G:C	W82C	1.000
15:32111795:G:T	W82C	1.000
15:32111814:T:A	W89R	1.000
15:32111814:T:C	W89R	1.000
15:32111816:G:C	W89C	1.000
15:32111816:G:T	W89C	1.000
15:32111871:T:A	W108R	1.000
15:32111871:T:C	W108R	1.000
15:32111873:G:C	W108C	1.000
15:32111873:G:T	W108C	1.000
15:32157625:T:C	C150R	1.000
15:32157626:G:A	C150Y	1.000
15:32157627:C:G	C150W	1.000
15:32157646:T:C	F157L	1.000
15:32157647:T:C	F157S	1.000
15:32157647:T:G	F157C	1.000
15:32157648:T:A	F157L	1.000
15:32157648:T:G	F157L	1.000
15:32157649:C:T	P158S	1.000
15:32157650:C:A	P158H	1.000
15:32157667:T:A	C164S	1.000
15:32157667:T:C	C164R	1.000
15:32157668:G:A	C164Y	1.000
15:32157668:G:C	C164S	1.000
15:32157669:C:G	C164W	1.000
15:32157763:T:A	W196R	1.000
15:32157763:T:C	W196R	1.000
15:32157765:G:C	W196C	1.000

dbSNP variants (sampled 300 via entrez): RS1000024280 (15:32053797 G>A,T), RS1000028368 (15:32136514 A>C,G), RS1000036085 (15:32138706 A>C,G), RS1000110150 (15:32098032 G>C,T), RS1000129737 (15:32058078 C>T), RS1000153691 (15:32076322 G>A,T), RS1000187178 (15:32036002 T>G), RS1000236576 (15:32033210 T>TA), RS1000239568 (15:32036263 C>T), RS1000254558 (15:32142117 T>C), RS1000260240 (15:32104195 C>G), RS1000284793 (15:32147902 C>T), RS1000295527 (15:32092530 T>C), RS1000353452 (15:32114588 G>A), RS1000355704 (15:32051701 G>A,C)

Disease associations

OMIM: gene MIM:118511 | disease phenotypes: MIM:608636, MIM:612001, MIM:604827

GenCC curated gene-disease

Disease	Classification	Inheritance
complex neurodevelopmental disorder	Limited	Autosomal dominant

ClinGen Gene-Disease Validity (1)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
epilepsy	Refuted	UD

Mondo (8): 15q11q13 microduplication syndrome (MONDO:0012081), chromosome 15q13.3 microdeletion syndrome (MONDO:0012774), primary ovarian failure (MONDO:0005387), epilepsy (MONDO:0005027), autism spectrum disorder (MONDO:0005258), epilepsy, idiopathic generalized, susceptibility to, 7 (MONDO:0011491), intellectual disability (MONDO:0001071), complex neurodevelopmental disorder (MONDO:0100038)

Orphanet (6): 15q11q13 microduplication syndrome (Orphanet:238446), 15q13.3 microdeletion syndrome (Orphanet:199318), Juvenile myoclonic epilepsy (Orphanet:307), NON RARE IN EUROPE: Primary ovarian failure (Orphanet:619), NON RARE IN EUROPE: Autism (Orphanet:106), NON RARE IN EUROPE: Unexplained intellectual disability (Orphanet:319658)

HPO phenotypes

34 total (30 of 34 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000252	Microcephaly
HP:0000256	Macrocephaly
HP:0000286	Epicanthus
HP:0000316	Hypertelorism
HP:0000377	Abnormal pinna morphology
HP:0000400	Macrotia
HP:0000411	Protruding ear
HP:0000486	Strabismus
HP:0000494	Downslanted palpebral fissures
HP:0000664	Synophrys
HP:0000708	Atypical behavior
HP:0000717	Autism
HP:0000995	Melanocytic nevus
HP:0001156	Brachydactyly
HP:0001249	Intellectual disability
HP:0001250	Seizure
HP:0001252	Hypotonia
HP:0001256	Mild intellectual disability
HP:0001263	Global developmental delay
HP:0001328	Specific learning disability
HP:0001999	Abnormal facial shape
HP:0002007	Frontal bossing
HP:0002342	Moderate intellectual disability
HP:0003829	Typified by incomplete penetrance
HP:0004209	Clinodactyly of the 5th finger
HP:0004322	Short stature
HP:0005274	Prominent nasal tip
HP:0007018	Attention deficit hyperactivity disorder
HP:0007302	Bipolar affective disorder

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST010461_7	Hepatocyte growth factor levels	1.000000e-06

MeSH disease descriptors (4)

Descriptor	Name	Tree numbers
D004827	Epilepsy	C10.228.140.490
D008607	Intellectual Disability	C10.597.606.360; C23.888.592.604.646; F01.700.687; F03.625.539
D016649	Primary Ovarian Insufficiency	C12.050.351.500.056.630.750; C12.100.250.056.630.750; C19.391.630.750
C567439	Chromosome 15q13.3 Microdeletion Syndrome (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (3): CHEMBL2492 (SINGLE PROTEIN), CHEMBL4524133 (PROTEIN COMPLEX GROUP), CHEMBL4804182 (PROTEIN COMPLEX GROUP)

Molecules with ChEMBL bioactivity

30 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 473,115 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL1076903	VARENICLINE	4	5,807
CHEMBL19019	NALTREXONE	4	34,647
CHEMBL267936	MECAMYLAMINE	4	5,623
CHEMBL3	NICOTINE	4	184,969
CHEMBL56564	TROPISETRON	4	19,312
CHEMBL667	ACETYLCHOLINE	4	124,626
CHEMBL894	BUPROPION	4	36,982
CHEMBL965	CARBAMOYLCHOLINE	4	22,580
CHEMBL2103881	DEXMECAMYLAMINE	3	18
CHEMBL2151572	ENCENICLINE	3	116
CHEMBL497939	CYTISINICLINE	3	2,766
CHEMBL1096927	LEVOMENOL	2	31,030
CHEMBL122270	LOBELINE	2	2,266
CHEMBL1257065	STILONIUM IODIDE	2	751
CHEMBL1258006	BRADANICLINE	2	208
CHEMBL132966	RIVANICLINE	2	911
CHEMBL134713	GTS-21	2	269
CHEMBL191491	STILONIUM	2	8
CHEMBL2151437	AZD0328	2	160
CHEMBL2151439	FACINICLINE	2	66
CHEMBL2179529	AZD1446	2
CHEMBL430497	TEBANICLINE	2
CHEMBL47298	TILORONE	2
CHEMBL559478	SSR180711	2
CHEMBL214268	PHA-543613	1
CHEMBL2151570	ABT-107	1
CHEMBL299155	TRANSTORINE	1
CHEMBL429317	AVL-3288	1
CHEMBL504652	TC-2216	1
CHEMBL6200	NORNICOTINE	1

PharmGKB: 1 entry (VIP=true, CPIC=false)

PharmGKB clinical annotations

2 annotations.

Variant	Type	Level	Drugs	Phenotypes
rs2337980	Efficacy	3	nicotine
rs6494223	Efficacy	3	donepezil;galantamine;rivastigmine	Alzheimer Disease

PharmGKB variants

3 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs6494223	CHRNA7	3	2.00	1	donepezil;galantamine;rivastigmine
rs2337980	CHRNA7	3	1.50	1	nicotine
rs883473	CHRNA7		0.00	0

GtoPdb / IUPHAR curated pharmacology

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

Target class: lgic — Nicotinic acetylcholine receptors (nACh)

Most potent curated ligand interactions (18 total), top 18:

Ligand	Action	Affinity	Parameter
[3H]epibatidine	Full agonist	12.22	pKd
[3H]A-585539	Full agonist	10.15	pKd
[3H]AZ11637326	Full agonist	9.64	pKd
[125I]α-bungarotoxin	Antagonist	9.15	pKd
[3H]α-bungarotoxin	Antagonist	9.15	pKd
NS6740	Agonist	8.96	pKi
[3H]methyllycaconitine	Antagonist	8.72	pKd
AZD0328	Full agonist	8.52	pKi
encenicline	Partial agonist	8.37	pKi
atracurium	Antagonist	8.25	pIC50
AQW051	Agonist	7.57	pKi
GTS-21	Agonist	6.66	pKi
4OH-GTS-21	Agonist	6.38	pKi
soclenicant	Negative	5.82	pIC50
PSAB-OFP	Full agonist	5.7	pEC50
BNC375	Positive	5.58	pEC50
ivermectin	Positive	5.1	pEC50
mecamylamine	Channel blocker	4.81	pIC50

Binding affinities (BindingDB)

350 measured of 476 human assays (499 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
N-[(3R)-1-azabicyclo[2.2.2]oct-3-yl]-5-pyridin-2-ylthiophene-2-carboxamide	KI	1.3 nM
N-[(3R)-1-azabicyclo[2.2.2]oct-3-yl]-5-phenylthiophene-2-carboxamide acetate	KI	1.8 nM
7-amino-N-[(3R)-1-azabicyclo[2.2.2]octan-3-yl]-1-benzothiophene-2-carboxamide	KI	2 nM	US-8884017: 2-heteroarylcarboxylic acid amides
6-amino-N-[(3R)-1-azabicyclo[2.2.2]octan-3-yl]-1-benzothiophene-2-carboxamide	KI	2.8 nM	US-8884017: 2-heteroarylcarboxylic acid amides
N-[(3R)-1-azabicyclo[2.2.2]octan-3-yl]-7-fluoro-1-benzothiophene-2-carboxamide	KI	3.1 nM	US-8884017: 2-heteroarylcarboxylic acid amides
6-amino-N-[(3R)-1-azabicyclo[2.2.2]octan-3-yl]-1-benzofuran-2-carboxamide	KI	3.7 nM	US-8884017: 2-heteroarylcarboxylic acid amides
N-[(3R)-1-azabicyclo[2.2.2]octan-3-yl]-1-benzothiophene-2-carboxamide	KI	3.9 nM	US-8884017: 2-heteroarylcarboxylic acid amides
PHA-543613	EC50	4.2 nM
[2-(pyridin-3-ylmethyl)-1-azabicyclo[2.2.2]octan-3-yl] N-(4-bromophenyl)carbamate	KI	5 nM	US-8541447: 3-substituted-2-(arlyalkyl)-1-azabicycloalkanes and methods of use thereof
N-[(3R)-1-azabicyclo[2.2.2]octan-3-yl]-7-methoxy-1-benzothiophene-2-carboxamide	KI	6.7 nM	US-8884017: 2-heteroarylcarboxylic acid amides
5-Pyridin-2-yl-thiophene-2-carboxylic acid (1-aza-bicyclo[2.2.2]oct-3-yl)-amide	KI	6.9 nM
[2-(pyridin-3-ylmethyl)-1-azabicyclo[2.2.2]octan-3-yl] N-phenylcarbamate	KI	7 nM	US-8541447: 3-substituted-2-(arlyalkyl)-1-azabicycloalkanes and methods of use thereof
5’N-(3-pyridylmethyl)-(2’R)-spiro[4-azabicyclo[2.2.2]octane-2,2’-furo[2,3-b]pyridine]-5’-amine	KI	8.3 nM
4-phenylsulfanyl-N-[2-(pyridin-3-ylmethyl)-1-azabicyclo[2.2.2]octan-3-yl]benzamide	KI	9 nM	US-8541447: 3-substituted-2-(arlyalkyl)-1-azabicycloalkanes and methods of use thereof
azidoepibatidine	KI	9.7 nM
Benzo[b]thiophene-2-carboxylic acid (1-aza-bicyclo[2.2.2]oct-3-yl)-amide	KI	14.6 nM
CHEMBL3963469	EC50	18 nM
N-[(3S)-1-azabicyclo[2.2.2]octan-3-yl]-7-fluoro-1-benzothiophene-2-carboxamide	KI	20 nM	US-8884017: 2-heteroarylcarboxylic acid amides
N-[(3R)-1-azabicyclo[2.2.2]octan-3-yl]-7-(trifluoromethyl)-1-benzothiophene-2-carboxamide	KI	20 nM	US-8884017: 2-heteroarylcarboxylic acid amides
N-[(3S)-1-azabicyclo[2.2.2]octan-3-yl]-7-methoxy-1-benzothiophene-2-carboxamide	KI	20 nM	US-8884017: 2-heteroarylcarboxylic acid amides
N-[(3R)-1-azabicyclo[2.2.2]octan-3-yl]-5-fluoro-1-benzothiophene-2-carboxamide	KI	22 nM	US-8884017: 2-heteroarylcarboxylic acid amides
CHEMBL4582201	EC50	24 nM
N-[(3S)-1-azabicyclo[2.2.2]oct-3-yl]-5-phenylthiophene-2-carboxamide acetate	KI	26.9 nM
6-acetamido-N-[(3R)-1-azabicyclo[2.2.2]octan-3-yl]-1-benzothiophene-2-carboxamide	KI	28 nM	US-8884017: 2-heteroarylcarboxylic acid amides
CHEMBL2113232	KI	28 nM
(R)-7-phenyl-N-(1’-azaspiro[cyclopropane-1,2’-bicyclo[2.2.2]octan]-3’-yl)benzo[b]thiophene-2-carboxamide	KI	30 nM	US-10183938: Geminal substituted quinuclidine amide compounds as agonists of α-7 nicotonic acetylcholine receptors
N-[(3R)-1-azabicyclo[2.2.2]octan-3-yl]-5,7-difluoro-1-benzothiophene-2-carboxamide	KI	31 nM	US-8884017: 2-heteroarylcarboxylic acid amides
CHEMBL3891441	EC50	31 nM
N-(1-azabicyclo[2.2.2]octan-3-yl)-6-chloro-1,2-benzoxazol-3-amine	KI	32 nM	US-10370370: Aminobenzisoxazole compounds as agonists of α7-nicotinic acetylcholine receptors
N-[(3S)-1-azabicyclo[2.2.2]octan-3-yl]-6-methoxy-1,2-benzoxazol-3-amine	KI	32 nM	US-10370370: Aminobenzisoxazole compounds as agonists of α7-nicotinic acetylcholine receptors
N-[(3R)-1-azabicyclo[2.2.2]octan-3-yl]-5-fluoro-1-benzofuran-2-carboxamide	KI	37 nM	US-8884017: 2-heteroarylcarboxylic acid amides
CHEMBL1255908	KI	38.9 nM
(R)-4-chloro-N-(quinuclidin-3-yl)benzamide	EC50	40 nM
1-azabicyclo[2.2.2]octan-3-yl N-(4-bromophenyl)carbamate	KI	40 nM	US-8541447: 3-substituted-2-(arlyalkyl)-1-azabicycloalkanes and methods of use thereof
CHEMBL3928422	EC50	40 nM
N-[(3R)-1-azabicyclo[2.2.2]octan-3-yl]-7-methoxy-1-benzofuran-2-carboxamide	KI	42 nM	US-8884017: 2-heteroarylcarboxylic acid amides
N-[(3R)-1-azabicyclo[2.2.2]octan-3-yl]-6,7-dichloro-1,2-benzoxazol-3-amine	KI	43.5 nM	US-10370370: Aminobenzisoxazole compounds as agonists of α7-nicotinic acetylcholine receptors
CHEMBL1258125	KI	43.6 nM
N-[(3R)-1-azabicyclo[2.2.2]octan-3-yl]-6-bromo-1,2-benzoxazol-3-amine	KI	44 nM	US-10370370: Aminobenzisoxazole compounds as agonists of α7-nicotinic acetylcholine receptors
N-[(3R)-1-azabicyclo[2.2.2]octan-3-yl]-6-chloro-7-fluoro-1,2-benzoxazol-3-amine	KI	46 nM	US-10370370: Aminobenzisoxazole compounds as agonists of α7-nicotinic acetylcholine receptors
7-chloro-N-(1’-azaspiro[cyclopropane-1,2’-bicyclo[2.2.2]octan]-3’-yl)benzo[b]thiophene-2-carboxamide	KI	48 nM	US-10183938: Geminal substituted quinuclidine amide compounds as agonists of α-7 nicotonic acetylcholine receptors
5-amino-N-[(3R)-1-azabicyclo[2.2.2]octan-3-yl]-1-benzothiophene-2-carboxamide	KI	50 nM	US-8884017: 2-heteroarylcarboxylic acid amides
N-(1-azabicyclo[2.2.2]octan-3-yl)-4-phenylsulfanylbenzamide	KI	53 nM	US-8541447: 3-substituted-2-(arlyalkyl)-1-azabicycloalkanes and methods of use thereof
CHEMBL4104136	EC50	53 nM
N-[(3S)-1-azabicyclo[2.2.2]octan-3-yl]-7-(trifluoromethyl)-1-benzothiophene-2-carboxamide	KI	55 nM	US-8884017: 2-heteroarylcarboxylic acid amides
N-[(3R)-1-azabicyclo[2.2.2]octan-3-yl]-7-bromo-1-benzofuran-2-carboxamide	KI	58 nM	US-8884017: 2-heteroarylcarboxylic acid amides
N-[(3R)-1-azabicyclo[2.2.2]octan-3-yl]-7-nitro-1-benzofuran-2-carboxamide	KI	63 nM	US-8884017: 2-heteroarylcarboxylic acid amides
CHEMBL3937435	EC50	63 nM
CHEMBL3946303	EC50	70 nM
3-[[(3R)-1-azabicyclo[2.2.2]octan-3-yl]amino]-6-chloro-1,2-benzoxazol-7-ol	KI	71 nM	US-10370370: Aminobenzisoxazole compounds as agonists of α7-nicotinic acetylcholine receptors

ChEMBL bioactivities

1784 potent at pChembl≥5 of 2020 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
10.52	Ki	0.03	nM	CHEMBL2151438
10.04	Ki	0.092	nM	CHEMBL3235498
9.70	Ki	0.2	nM	ABT-107
9.66	Ki	0.22	nM	ABT-107
9.62	Ki	0.24	nM	CHEMBL2151569
9.62	Ki	0.24	nM	CHEMBL3235495
9.52	IC50	0.3	nM	CHEMBL412032
9.29	Ki	0.51	nM	CHEMBL2179874
9.12	IC50	0.75	nM	CHEMBL429557
9.10	Ki	0.8	nM	CHEMBL2179875
9.05	Ki	0.9	nM	CHEMBL2179877
9.00	Ki	1	nM	BRADANICLINE
9.00	Ki	1	nM	CHEMBL597241
9.00	Ki	1	nM	METHYLLYCACONITINE
9.00	Ki	1	nM	CHEMBL5276123
9.00	Ki	1	nM	CHEMBL5393773
8.97	Kd	1.06	nM	R-NICOTINE
8.97	Kd	1.06	nM	NORNICOTINE
8.97	Kd	1.06	nM	EPIBATIDINE
8.97	Kd	1.06	nM	CHEMBL149667
8.97	Kd	1.06	nM	CHEMBL366923
8.96	IC50	1.09	nM	CHEMBL2151573
8.96	Ki	1.1	nM	CHEMBL2179873
8.96	IC50	1.1	nM	CHEMBL437423
8.96	Ki	1.1	nM	CHEMBL195190
8.96	Ki	1.1	nM	METHYLLYCACONITINE
8.92	Ki	1.2	nM	CHEMBL2177538
8.92	Ki	1.2	nM	CHEMBL2179878
8.89	Ki	1.3	nM	CHEMBL2177537
8.89	Ki	1.3	nM	CHEMBL364069
8.89	Ki	1.3	nM	CHEMBL3918431
8.85	Ki	1.4	nM	CHEMBL5276123
8.83	IC50	1.48	nM	CHEMBL5201239
8.83	IC50	1.49	nM	CHEMBL5178473
8.82	IC50	1.5	nM	CHEMBL411146
8.80	Ki	1.6	nM	CHEMBL378471
8.80	Ki	1.6	nM	CHEMBL2177512
8.80	Ki	1.6	nM	CHEMBL2177553
8.80	Ki	1.6	nM	METHYLLYCACONITINE
8.79	Ki	1.622	nM	METHYLLYCACONITINE
8.74	Ki	1.8	nM	CHEMBL2180253
8.74	Ki	1.8	nM	CHEMBL370535
8.70	Ki	2	nM	CHEMBL3699100
8.70	Ki	2	nM	CHEMBL195345
8.70	IC50	1.99	nM	STILONIUM IODIDE
8.70	EC50	1.995	nM	CHEMBL1210516
8.70	EC50	1.995	nM	CHEMBL1210515
8.69	IC50	2.04	nM	CHEMBL5190813
8.68	Ki	2.1	nM	CHEMBL378349
8.68	Ki	2.1	nM	CHEMBL2179881

PubChem BioAssay actives

1432 with measured affinity, of 3884 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
(3R)-5’-(furan-3-yl)spiro[1-azabicyclo[2.2.2]octane-3,2’-3H-furo[2,3-b]pyridine]	690414: Binding affinity to human alpha7 nAchR	ki	<0.0001	uM
2-[(1S,5S)-6-(111C)methyl-3,6-diazabicyclo[3.2.0]heptan-3-yl]-7-[(1S,5S)-6-methyl-3,6-diazabicyclo[3.2.0]heptan-3-yl]fluoren-9-one	1127765: Binding affinity to alpha7 nAChR (unknown origin)	ki	0.0001	uM
5-[6-[[(3R)-1-azabicyclo[2.2.2]octan-3-yl]oxy]pyridazin-3-yl]-1H-indole	1631152: Displacement of [3H]A-585539 from alpha7 nAChR in human cerebral cortex membranes after 75 mins by scintillation counting	ki	0.0002	uM
5-[6-(2-methyl-1,3,3a,4,6,6a-hexahydropyrrolo[3,4-c]pyrrol-5-yl)pyridazin-3-yl]-1H-indole	690406: Binding affinity to alpha7 nAChR	ki	0.0002	uM
5-[6-(2-(111C)methyl-1,3,3a,4,6,6a-hexahydropyrrolo[3,4-c]pyrrol-5-yl)pyridazin-3-yl]-1H-indole	1127765: Binding affinity to alpha7 nAChR (unknown origin)	ki	0.0002	uM
(3S)-3-[[(2S)-5-amino-2-[[(2S)-4-amino-2-[[(2S)-4-amino-2-[[(2S)-2-[[(2S)-2-[[(2R)-2-[[(2S)-2-[[(2S)-1-[(2S)-2-[[(2S)-2-[[(2R)-2-[[(2R)-2-[[2-[(2-aminoacetyl)amino]acetyl]amino]-3-sulfanylpropanoyl]amino]-3-sulfanylpropanoyl]amino]-3-hydroxypropanoyl]amino]-3-(1H-imidazol-4-yl)propanoyl]pyrrolidine-2-carbonyl]amino]propanoyl]amino]-3-sulfanylpropanoyl]amino]propanoyl]amino]propanoyl]amino]-4-oxobutanoyl]amino]-4-oxobutanoyl]amino]-5-oxopentanoyl]amino]-4-[[(2S)-1-[[(2R)-1-amino-1-oxo-3-sulfanylpropan-2-yl]amino]-3-(4-hydroxyphenyl)-1-oxopropan-2-yl]amino]-4-oxobutanoic acid	241410: Inhibitory concentration against Nicotinic acetylcholine receptor alpha 7	ic50	0.0003	uM
5-iodo-N-[(2S,3R)-2-(pyridin-3-ylmethyl)-1-azabicyclo[2.2.2]octan-3-yl]thiophene-2-carboxamide	709627: Displacement of [3H]epibatidine form human alpha7 nAchR expressed in HEK293 cells	ki	0.0005	uM
(3S)-3-[[(2S)-1-[(2S)-4-amino-2-[[(2S,3R)-2-[[(2S)-2-[[(2S)-2-[[(2R)-2-[[(2S)-1-[(2S)-1-[(2S)-2-[[(2S)-2-[[(2R)-2-[[(2R)-2-[(2-aminoacetyl)amino]-3-sulfanylpropanoyl]amino]-3-sulfanylpropanoyl]amino]-3-hydroxypropanoyl]amino]-3-(4-hydroxyphenyl)propanoyl]pyrrolidine-2-carbonyl]pyrrolidine-2-carbonyl]amino]-3-sulfanylpropanoyl]amino]-3-phenylpropanoyl]amino]propanoyl]amino]-3-hydroxybutanoyl]amino]-4-oxobutanoyl]pyrrolidine-2-carbonyl]amino]-4-oxo-4-[[(2R)-1-oxo-3-sulfanylpropan-2-yl]amino]butanoic acid	242049: Inhibitory concentration against Nicotinic acetylcholine receptor alpha7; Range is 0.3-1.5 nM	ic50	0.0008	uM
5-phenyl-N-[(2S,3R)-2-(pyridin-3-ylmethyl)-1-azabicyclo[2.2.2]octan-3-yl]thiophene-2-carboxamide	709627: Displacement of [3H]epibatidine form human alpha7 nAchR expressed in HEK293 cells	ki	0.0008	uM
5-pyridin-2-yl-N-[(2S,3R)-2-(pyridin-3-ylmethyl)-1-azabicyclo[2.2.2]octan-3-yl]thiophene-2-carboxamide	709627: Displacement of [3H]epibatidine form human alpha7 nAchR expressed in HEK293 cells	ki	0.0009	uM
6-chloro-2-(1,4-diazabicyclo[3.2.2]nonan-4-yl)-[1,3]oxazolo[4,5-b]pyridine	690406: Binding affinity to alpha7 nAChR	ki	0.0010	uM
5-[6-[[(2S,3R)-2-(pyridin-3-ylmethyl)-1-azabicyclo[2.2.2]octan-3-yl]oxy]pyridazin-3-yl]-1H-indole	1935055: Binding affinity to alpha7 nAChR (unknown origin) assessed as dissociation constant	ki	0.0010	uM
5-[4-[(3R)-1,1-dimethylpyrrolidin-1-ium-3-yl]oxyphenyl]-1H-indole iodide	1964366: Displacement of [125I]alpha-Bungarotoxin from human alpha7 nAChR expressed in human SH-SY5Y cell membrane assessed as inhibition constant by direct gamma counting method	ki	0.0010	uM
N-[(2S,3R)-2-(pyridin-3-ylmethyl)-1-azabicyclo[2.2.2]octan-3-yl]-1-benzofuran-2-carboxamide	690445: Binding affinity to human alpha7 nAChR expressed in HEK293 cells co-expressing RIC3 cDNA	ki	0.0010	uM
[(1S,2R,3R,4S,5R,6S,8R,9R,10S,13S,16S,17R,18S)-11-ethyl-8,9-dihydroxy-4,6,16,18-tetramethoxy-11-azahexacyclo[7.7.2.12,5.01,10.03,8.013,17]nonadecan-13-yl]methyl 2-[(3S)-3-methyl-2,5-dioxopyrrolidin-1-yl]benzoate	297964: Displacement of [3H]methyllycaconitine from human alpha-7 in tsA201 cells coexpressed with 5HT3A receptor	ki	0.0010	uM
2-(6-chloro-3-pyridinyl)-7-azabicyclo[2.2.1]heptane	238082: Dissociation constant for nicotinic acetylcholine receptor alpha 7 from human neuroblastoma SH-SY5Y cells; n=3	kd	0.0011	uM
4,13-diazatricyclo[8.2.1.02,7]trideca-2(7),3,5-triene	238082: Dissociation constant for nicotinic acetylcholine receptor alpha 7 from human neuroblastoma SH-SY5Y cells; n=3	kd	0.0011	uM
3-[(2R)-1-methylpyrrolidin-2-yl]pyridine	238082: Dissociation constant for nicotinic acetylcholine receptor alpha 7 from human neuroblastoma SH-SY5Y cells; n=3	kd	0.0011	uM
(2S)-2-[[(2S)-4-amino-2-[[(2S)-4-amino-2-[[2-[[(2S)-2-[[(2R)-2-[[(2S)-2-[[(2S)-1-[(2S)-2-[[(2S)-2-[[(2R)-2-[[(2R)-2-[(2-aminoacetyl)amino]-3-sulfanylpropanoyl]amino]-3-sulfanylpropanoyl]amino]-3-hydroxypropanoyl]amino]-3-(1H-imidazol-5-yl)propanoyl]pyrrolidine-2-carbonyl]amino]propanoyl]amino]-3-sulfanylpropanoyl]amino]propanoyl]amino]acetyl]amino]-4-oxobutanoyl]amino]-4-oxobutanoyl]amino]-N-[(2S)-1-[[(2S,3S)-1-[[(2R)-1-amino-1-oxo-3-sulfanylpropan-2-yl]amino]-3-methyl-1-oxopentan-2-yl]amino]-3-(1H-imidazol-5-yl)-1-oxopropan-2-yl]pentanediamide	241410: Inhibitory concentration against Nicotinic acetylcholine receptor alpha 7	ic50	0.0011	uM
5-methyl-4,13-diazatricyclo[8.2.1.02,7]trideca-2(7),3,5-triene	238082: Dissociation constant for nicotinic acetylcholine receptor alpha 7 from human neuroblastoma SH-SY5Y cells; n=3	kd	0.0011	uM
N-(1-azabicyclo[2.2.2]octan-3-yl)-5-thiophen-2-ylthiophene-2-carboxamide	254538: Binding affinity towards human nicotinic acetylcholine receptor alpha 7 expressed in GH4C1 cell using [3H]methyllycaconitine	ki	0.0011	uM
(4S)-4-[[(2S)-2-amino-3-carboxypropanoyl]amino]-5-oxo-5-[[(1R,6R,9S,12S,15S,21S,24S,27S,30S,33R,36S,39S,45S,48S,53R)-21,24,45-tris(2-amino-2-oxoethyl)-6-[[(2S)-5-carbamimidamido-1-[[(2S)-5-carbamimidamido-1-[[(1S)-4-carbamimidamido-1-carboxybutyl]amino]-1-oxopentan-2-yl]amino]-1-oxopentan-2-yl]carbamoyl]-30-(3-carbamimidamidopropyl)-9-(carboxymethyl)-48-(hydroxymethyl)-12-(1H-imidazol-5-ylmethyl)-36-methyl-27-(2-methylpropyl)-8,11,14,20,23,26,29,32,35,38,44,47,50,52-tetradecaoxo-3,4,55,56-tetrathia-7,10,13,19,22,25,28,31,34,37,43,46,49,51-tetradecazatetracyclo[31.17.7.015,19.039,43]heptapentacontan-53-yl]amino]pentanoic acid	690451: Antagonist activity at human alpha7 nAChR expressed in Xenopus oocyte	ic50	0.0011	uM
5-bromo-N-[(2S,3R)-2-(pyridin-3-ylmethyl)-1-azabicyclo[2.2.2]octan-3-yl]thiophene-2-carboxamide	709627: Displacement of [3H]epibatidine form human alpha7 nAchR expressed in HEK293 cells	ki	0.0011	uM
3-[(2S)-pyrrolidin-2-yl]pyridine	238082: Dissociation constant for nicotinic acetylcholine receptor alpha 7 from human neuroblastoma SH-SY5Y cells; n=3	kd	0.0011	uM
(1S,5R)-7-pyridin-3-yl-3-azabicyclo[3.3.1]non-6-ene	705816: Displacement of [3H]epibatidine from human alpha7 nAChR expressed in human HEK/RIC3 cells	ki	0.0012	uM
N-[(2S,3R)-2-(pyridin-3-ylmethyl)-1-azabicyclo[2.2.2]octan-3-yl]-5-thiophen-2-ylthiophene-2-carboxamide	709627: Displacement of [3H]epibatidine form human alpha7 nAchR expressed in HEK293 cells	ki	0.0012	uM
N-[(3R)-1-azabicyclo[2.2.2]octan-3-yl]-5-pyridin-2-ylthiophene-2-carboxamide	254538: Binding affinity towards human nicotinic acetylcholine receptor alpha 7 expressed in GH4C1 cell using [3H]methyllycaconitine	ki	0.0013	uM
(3R)-N-isoquinolin-3-ylspiro[1-azabicyclo[2.2.2]octane-3,5’-4H-1,3-oxazole]-2’-amine	1437368: Displacement of [125I]alpha-bungarotoxin from human alpha7 nAChR expressed in HEK293 cell membranes incubated for 2 hrs and measured by gamma counting method	ki	0.0013	uM
(1R,5S)-7-pyridin-3-yl-3-azabicyclo[3.3.1]non-6-ene	705816: Displacement of [3H]epibatidine from human alpha7 nAChR expressed in human HEK/RIC3 cells	ki	0.0013	uM
(3R)-1,1-dimethyl-3-[4-[(E)-2-phenylethenyl]phenoxy]pyrrolidin-1-ium iodide	1881222: Antagonist activity at human alpha7 nAChR expressed in Xenopus laevis oocytes assessed as inhibition of acetylcholine-induced current response treated for 1 sec in presence of acetylcholine at holding potential of -70 mV by two electrode voltage-clamp assay	ic50	0.0015	uM
(3S)-1,1-dimethyl-3-[4-[(E)-2-phenylethenyl]phenoxy]pyrrolidin-1-ium iodide	1881222: Antagonist activity at human alpha7 nAChR expressed in Xenopus laevis oocytes assessed as inhibition of acetylcholine-induced current response treated for 1 sec in presence of acetylcholine at holding potential of -70 mV by two electrode voltage-clamp assay	ic50	0.0015	uM
(2S)-1-[(2S)-1-[(2S,3R)-2-[[(2S)-2-[[(2R)-2-[[(2R)-2-[(2-aminoacetyl)amino]-3-sulfanylpropanoyl]amino]-3-sulfanylpropanoyl]amino]-3-hydroxypropanoyl]amino]-3-hydroxybutanoyl]pyrrolidine-2-carbonyl]-N-[(2R)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2R)-1-[[2-[[(2S)-5-(diaminomethylideneamino)-1-[[(2S)-5-(diaminomethylideneamino)-1-[[(2S)-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-1-oxopentan-2-yl]amino]-1-oxopentan-2-yl]amino]-2-oxoethyl]amino]-1-oxo-3-sulfanylpropan-2-yl]amino]-3-(4-hydroxyphenyl)-1-oxopropan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-3-methyl-1-oxobutan-2-yl]amino]-1-oxopropan-2-yl]amino]-1-oxo-3-sulfanylpropan-2-yl]pyrrolidine-2-carboxamide	242032: Inhibitory concentration against Nicotinic acetylcholine receptor alpha7; Range is 0.3-1.5 nM	ic50	0.0015	uM
(1S,5R)-7-(5-fluoro-3-pyridinyl)-3-azabicyclo[3.3.1]non-6-ene	705816: Displacement of [3H]epibatidine from human alpha7 nAChR expressed in human HEK/RIC3 cells	ki	0.0016	uM
3-pyridin-3-yl-3,7-diazabicyclo[3.3.1]nonane	705816: Displacement of [3H]epibatidine from human alpha7 nAChR expressed in human HEK/RIC3 cells	ki	0.0016	uM
N-[(3R)-1-azabicyclo[2.2.2]octan-3-yl]-1-benzofuran-5-carboxamide	690406: Binding affinity to alpha7 nAChR	ki	0.0016	uM
acetic acid;N-[(3R)-1-azabicyclo[2.2.2]octan-3-yl]-5-phenylthiophene-2-carboxamide	254538: Binding affinity towards human nicotinic acetylcholine receptor alpha 7 expressed in GH4C1 cell using [3H]methyllycaconitine	ki	0.0018	uM
5-hydroxy-N-[(2S,3R)-2-(pyridin-3-ylmethyl)-1-azabicyclo[2.2.2]octan-3-yl]-1-benzofuran-2-carboxamide	709627: Displacement of [3H]epibatidine form human alpha7 nAchR expressed in HEK293 cells	ki	0.0018	uM
(3R)-5’-phenylspiro[1-azabicyclo[2.2.2]octane-3,2’-3H-furo[2,3-b]pyridine]	1366574: Binding affinity to human alpha7 nAChR	ki	0.0020	uM
1-methyl-1-[2-[4-[(E)-2-phenylethenyl]phenoxy]ethyl]pyrrolidin-1-ium iodide	1881222: Antagonist activity at human alpha7 nAChR expressed in Xenopus laevis oocytes assessed as inhibition of acetylcholine-induced current response treated for 1 sec in presence of acetylcholine at holding potential of -70 mV by two electrode voltage-clamp assay	ic50	0.0020	uM
2-[3-cyclohexyl-5-(furan-2-ylmethyl)-6-oxopyridazin-1-yl]-N-(2,3-dihydro-1H-inden-2-yl)acetamide	493527: Positive allosteric modulator activity at human alpha7 nAChR expressed in rat GH4C1 assessed as calcium mobilization by FLIPR assay	ec50	0.0020	uM
2-[3-cyclohexyl-5-(furan-2-ylmethyl)-6-oxopyridazin-1-yl]-N-[2-(3-fluorophenyl)ethyl]acetamide	493527: Positive allosteric modulator activity at human alpha7 nAChR expressed in rat GH4C1 assessed as calcium mobilization by FLIPR assay	ec50	0.0020	uM
triethyl-[2-[4-[(E)-2-phenylethenyl]phenoxy]ethyl]azanium iodide	1881222: Antagonist activity at human alpha7 nAChR expressed in Xenopus laevis oocytes assessed as inhibition of acetylcholine-induced current response treated for 1 sec in presence of acetylcholine at holding potential of -70 mV by two electrode voltage-clamp assay	ic50	0.0020	uM
N-[(3R)-1-azabicyclo[2.2.2]octan-3-yl]-1-benzothiophene-6-carboxamide	690406: Binding affinity to alpha7 nAChR	ki	0.0021	uM
5-methoxy-N-[(2S,3R)-2-(pyridin-3-ylmethyl)-1-azabicyclo[2.2.2]octan-3-yl]-1-benzofuran-2-carboxamide	709627: Displacement of [3H]epibatidine form human alpha7 nAchR expressed in HEK293 cells	ki	0.0021	uM
3-methyl-N-[(2S,3R)-2-(pyridin-3-ylmethyl)-1-azabicyclo[2.2.2]octan-3-yl]-1-benzofuran-2-carboxamide	709627: Displacement of [3H]epibatidine form human alpha7 nAchR expressed in HEK293 cells	ki	0.0022	uM
1-methyl-1-[2-[4-[(E)-2-phenylethenyl]phenoxy]ethyl]piperidin-1-ium iodide	1881222: Antagonist activity at human alpha7 nAChR expressed in Xenopus laevis oocytes assessed as inhibition of acetylcholine-induced current response treated for 1 sec in presence of acetylcholine at holding potential of -70 mV by two electrode voltage-clamp assay	ic50	0.0023	uM
1-methyl-1-[2-[4-[(E)-2-phenylethenyl]phenoxy]ethyl]azetidin-1-ium iodide	1881222: Antagonist activity at human alpha7 nAChR expressed in Xenopus laevis oocytes assessed as inhibition of acetylcholine-induced current response treated for 1 sec in presence of acetylcholine at holding potential of -70 mV by two electrode voltage-clamp assay	ic50	0.0024	uM
2-(1,4-diazabicyclo[3.2.2]nonan-4-yl)-5-[1-(2-fluoroethyl)indol-6-yl]-1,3,4-oxadiazole	746176: Displacement of [3H]-methyllycaconitine from human alpha7 nAChR transfected in human SH-SY5Y cells after 240 mins by liquid scintillation counting analysis	ki	0.0025	uM
1-[2-[4-[(E)-2-phenylethenyl]phenoxy]ethyl]-1-azoniabicyclo[2.2.2]octane iodide	1881222: Antagonist activity at human alpha7 nAChR expressed in Xenopus laevis oocytes assessed as inhibition of acetylcholine-induced current response treated for 1 sec in presence of acetylcholine at holding potential of -70 mV by two electrode voltage-clamp assay	ic50	0.0027	uM
[(2S,3R)-2-(pyridin-3-ylmethyl)-1-azabicyclo[2.2.2]octan-3-yl] N-(4-bromophenyl)carbamate	517472: Displacement of [3H]-MLA from human alpha7 nAChR expressed in human SH-SY5Y cells	ki	0.0027	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Nicotine	decreases expression, increases response to substance, decreases activity, increases abundance, affects activity (+9 more)	19
methyllycaconitine	increases abundance, increases phosphorylation, decreases expression, affects activity, decreases reaction (+8 more)	13
Acetylcholine	increases activity, increases reaction, affects binding, increases uptake, decreases reaction (+1 more)	11
Bungarotoxins	increases activity, increases transport, affects activity, increases uptake, affects binding (+3 more)	11
1-(5-chloro-2,4-dimethoxyphenyl)-3-(5-methylisoxazol-3-yl)urea	affects binding, decreases response to substance, increases reaction, affects activity, affects cotreatment (+4 more)	4
Choline	affects binding, decreases reaction, increases activity, increases response to substance	4
4-(N-methyl-N-nitrosamino)-1-(3-pyridyl)-1-butanone	affects binding, increases activity, increases expression	3
PNU-282987	affects binding, increases uptake, increases phosphorylation, decreases response to substance, increases expression (+5 more)	3
Calcium	affects binding, affects cotreatment, increases activity, increases uptake, decreases response to substance (+4 more)	3
Carbachol	affects activity, increases reaction, affects binding, decreases reaction	3
Tubocurarine	affects binding, decreases activity, decreases reaction, increases activity	3
sodium arsenite	affects methylation, increases expression	2
imidacloprid	increases activity	2
epibatidine	affects activity, increases reaction, affects binding, decreases reaction	2
pozanicline	increases response to substance, affects binding, decreases reaction, increases activity	2
MB327	affects activity, increases reaction, increases activity	2
Dimethylphenylpiperazinium Iodide	affects binding, decreases reaction, increases activity, increases response to substance	2
Mecamylamine	decreases activity, affects activity, affects cotreatment, decreases reaction, increases activity (+2 more)	2
Tobacco Smoke Pollution	decreases reaction, increases expression, affects reaction	2
Okadaic Acid	increases phosphorylation, affects activity, decreases reaction, decreases response to substance, increases uptake (+4 more)	2
flupyradifurone	increases activity	1
cytisine	affects binding, decreases reaction	1
methylmercuric chloride	decreases expression	1
propionaldehyde	increases expression	1
beta-thujone	decreases reaction, increases activity	1
bisphenol A	decreases expression	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
SAD-128	affects binding, decreases reaction	1
butyraldehyde	increases expression	1
dinophysistoxin 1	increases expression	1

ChEMBL screening assays

562 unique, capped per target: 474 binding, 84 functional, 3 admet, 1 toxicity

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1020769	Binding	Displacement of [3H]MLA from alpha7 nAChR/5HT3A receptor expressed in HEK293 cells	Carbamoylcholine analogs as nicotinic acetylcholine receptor agonists–structural modifications of 3-(dimethylamino)butyl dimethylcarbamate (DMABC). — Bioorg Med Chem Lett
CHEMBL1023871	Functional	Agonist activity to alpha7 nAChR expressed in Xenopus oocytes assessed as response current at 1mM by two-electrode voltage clamp relative to acetylcholine	Synthesis of H-bonding probes of alpha7 nAChR agonist selectivity. — Bioorg Med Chem Lett
CHEMBL4679972	ADMET	Inhibition of alpha7 nAChR (unknown origin)	Discovery and Preclinical Evaluation of BMS-986242, a Potent, Selective Inhibitor of Indoleamine-2,3-dioxygenase 1. — ACS Med Chem Lett

Cellosaurus cell lines

9 cell lines: 5 cancer cell line, 3 transformed cell line, 1 induced pluripotent stem cell

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

Cellosaurus	Name	Category	Sex
CVCL_D1KI	PrecisION hnAChR alpha7/ric3-HEK	Transformed cell line	Female
CVCL_D7MH	Ubigene A-549 CHRNA7 KO	Cancer cell line	Male
CVCL_D8IZ	Ubigene HCT 116 CHRNA7 KO	Cancer cell line	Male
CVCL_D9BZ	Ubigene HEK293 CHRNA7 KO	Transformed cell line	Female
CVCL_F0SI	GH3-ha7-22	Cancer cell line	Female
CVCL_F0SQ	K28	Transformed cell line	Female
CVCL_F0SS	SH-EP1-pCEP4-ha7	Cancer cell line	Female
CVCL_SJ00	HAP1 CHRNA7 (-)	Cancer cell line	Male
CVCL_VD32	CSSi005-A	Induced pluripotent stem cell	Female

Clinical trials (associated diseases)

302 trials via MONDO — disease-level, not drug-specific.

Trial	Phase	Status	Title
NCT00417066	PHASE4	COMPLETED	Flexible GnRH Antagonist vs Flare up GnRH Agonist Protocol in Poor Responders
NCT00732693	PHASE4	COMPLETED	Evaluation of Physiologic and Standard Sex Steroid Replacement Regimens in Women With Premature Ovarian Failure
NCT00837616	PHASE4	COMPLETED	Estrogen Dosing in Turner Syndrome: Pharmacology and Metabolism
NCT01853501	PHASE4	UNKNOWN	Effects of ADSC Therapy in Women With POF
NCT02783937	PHASE4	COMPLETED	Filgrastim for Premature Ovarian Insufficiency
NCT03535480	PHASE4	UNKNOWN	Autologous Bone Marrow Stem Cell Ovarian Transplantation to Restore Ovarian Function in Premature Ovarian Failure
NCT00004637	PHASE4	COMPLETED	Double-Blind, Placebo-Controlled Trial of Vitamin E as Add-on Therapy for Children With Epilepsy
NCT00043914	PHASE4	COMPLETED	Measurement Of Serum Levels Of Two Antiepileptic Drugs During Conversion In Patients With Epilepsy
NCT00132223	PHASE4	UNKNOWN	Effects on the Diagnostic Accuracy of Magnetic Imaging Angiographies of the Supra-Aortic Vessels by Three Different Magnetic Resonance Contrast Agents in Patients
NCT00133081	PHASE4	UNKNOWN	Study to Improve the Treatment of Epilepsy (SITE)
NCT00137709	PHASE4	UNKNOWN	Hormone Profiles in Adults With Newly Diagnosed Epilepsy
NCT00154076	PHASE4	COMPLETED	A Multicenter Comparative Trial of Zonisamide and Topiramate as Initial Monotherapy in Untreated Epilepsies
NCT00165828	PHASE4	TERMINATED	Efficacy and Safety of an add-on Treatment With Zonisamide in Adults With Focal Epileptic Seizures With or Without Secondary Generalization
NCT00181116	PHASE4	COMPLETED	Levetiracetam for Benign Rolandic Epilepsy
NCT00207935	PHASE4	COMPLETED	Use of Sustained Release Antiepileptic Medication (Depakote® ER) for Pediatric Epilepsy in a Mental Retardation/Developmental Disorder Population
NCT00215592	PHASE4	COMPLETED	Open Label, Zonegran (Zonisamide) In Partial Onset Seizures
NCT00266604	PHASE4	COMPLETED	A Study to Evaluate the Dosing, Effectiveness and Safety of Topiramate for the Treatment of Epilepsy
NCT00288639	PHASE4	COMPLETED	Lyrica (Pregabalin) Administered as an Add-on Therapy for Partial Seizures (LEADER).
NCT00312676	PHASE4	UNKNOWN	Compare Tolerability of an Overnight Switch to Gradual Switch Between Two Different Forms of Depakote
NCT00323947	PHASE4	COMPLETED	Methylphenidate for Treating Attention Deficit Hyperactivity Disorder in Children With Both ADHD and Epilepsy
NCT00385411	PHASE4	COMPLETED	Study of Valproate in Young Patients Suffering From Epilepsy
NCT00522418	PHASE4	TERMINATED	Study Comparing Best Medical Practice With or Without VNS Therapy in Pharmacoresistant Partial Epilepsy Patients
NCT00537940	PHASE4	COMPLETED	Comparative Study Of Pregabalin And Gabapentin As Adjunctive Therapy In Subjects With Partial Seizures
NCT00552526	PHASE4	UNKNOWN	Ketogenic Diet vs.Antiepileptic Drug Treatment in Drug Resistant Epilepsy
NCT00564915	PHASE4	COMPLETED	RCT of the Efficacy of the Ketogenic Diet in the Treatment of Epilepsy
NCT00571155	PHASE4	COMPLETED	Trial of Levetiracetam in Patients With Primary Brain Tumors and Symptomatic Seizures Who Undergo Surgery
NCT00572195	PHASE4	COMPLETED	RNS® System LTT Study
NCT00610532	PHASE4	TERMINATED	Evaluating the Transporter Protein Inhibitor Probenecid In Patients With Epilepsy
NCT00630357	PHASE4	COMPLETED	Trial to Evaluate the Safety and Efficacy of Keppra After Conversion to Mono-therapy in Subjects With Partial Epilepsy
NCT00630630	PHASE4	COMPLETED	Study on Safety and Efficacy of Levetiracetam in the Adjunctive Treatment of Female Subjects With C1 Catamenial Epilepsy
NCT00630968	PHASE4	COMPLETED	S.K.A.T.E.: Safety of Keppra as Adjunctive Therapy in Epilepsy
NCT00631150	PHASE4	COMPLETED	A Phase IV-Pharmacovigilance Study of Keppra Greece - S.K.A.T.E.: Safety of Keppra as Adjunctive Therapy in Epilepsy
NCT00659958	PHASE4	COMPLETED	ZAGAL Study: Evaluating Effectiveness and Tolerability of Zonisamide as Adjunctive Therapy in Patients With Partial Onset Seizures Treated With Two Antiepileptic Drugs
NCT00713622	PHASE4	COMPLETED	Comparing The Effect On Cognition Of Adjunctive Therapy With Zonisamide Versus Sodium Valproate
NCT00807989	PHASE4	COMPLETED	The Efficacy and Safety of Low Dose Combination of LTG and VPA Compared to CBZ Monotherapy
NCT00832884	PHASE4	COMPLETED	The Safety of Intravenous Lacosamide
NCT00869622	PHASE4	COMPLETED	Antiepileptic Drugs and Osteoporotic Prevention Trial
NCT00896987	PHASE4	COMPLETED	Lamotrigine Cognitive Function Study in Adult Untreated Epilepsies
NCT00952081	PHASE4	COMPLETED	A Pilot Study to Evaluate Efficacy and Safety of Clevidipine in Neurosurgical Patients
NCT01118455	PHASE4	TERMINATED	Trial to Assess Vagus Nerve Stimulation Therapy vs. Anti-Epileptic Drug (AED) Treatment in Children With Refractory Seizures