CHRNB2

Summary

CHRNB2 (cholinergic receptor nicotinic beta 2 subunit, HGNC:1962) is a protein-coding gene on chromosome 1q21.3, encoding Neuronal acetylcholine receptor subunit beta-2 (P17787). 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….

Neuronal acetylcholine receptors are homo- or heteropentameric complexes composed of homologous alpha and beta subunits. They belong to a superfamily of ligand-gated ion channels which allow the flow of sodium and potassium across the plasma membrane in response to ligands such as acetylcholine and nicotine. This gene encodes one of several beta subunits. Mutations in this gene are associated with autosomal dominant nocturnal frontal lobe epilepsy.

Source: NCBI Gene 1141 — RefSeq curated summary.

At a glance

• Gene–disease (curated): familial sleep-related hypermotor epilepsy (Definitive, ClinGen) — +2 more curated relationships
• GWAS associations: 3
• Clinical variants (ClinVar): 687 total — 2 pathogenic, 3 likely-pathogenic
• Phenotypes (HPO): 23
• Druggable target: yes — 26 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_000748

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:1962
Approved symbol	CHRNB2
Name	cholinergic receptor nicotinic beta 2 subunit
Location	1q21.3
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000160716
Ensembl biotype	protein_coding
OMIM	118507
Entrez	1141

Gene structure

Transcript identifiers

Ensembl transcripts: 5 — 2 protein_coding, 2 protein_coding_CDS_not_defined, 1 nonsense_mediated_decay

ENST00000368476, ENST00000635876, ENST00000636034, ENST00000636695, ENST00000637900

RefSeq mRNA: 1 — MANE Select: NM_000748 NM_000748

CCDS: CCDS1070

Canonical transcript exons

ENST00000368476 — 6 exons

Exon	Start	End
ENSE00001053945	154569462	154569607
ENSE00001053946	154569792	154569836
ENSE00001053947	154571189	154572161
ENSE00001053948	154570258	154570367
ENSE00001447217	154575762	154580013
ENSE00001447218	154567778	154568108

Expression profiles

Bgee: expression breadth ubiquitous, 208 present calls, max score 94.34.

FANTOM5 (CAGE): breadth broad, TPM avg 2.6077 / max 112.4383, expressed in 240 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
5526	1.2671	218
5525	0.9423	146
5524	0.3770	114
5523	0.0214	6

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
tongue squamous epithelium	UBERON:0006919	94.34	silver quality
cervix squamous epithelium	UBERON:0006922	92.31	silver quality
type B pancreatic cell	CL:0000169	92.16	silver quality
olfactory bulb	UBERON:0002264	91.07	silver quality
vena cava	UBERON:0004087	89.75	silver quality
lateral nuclear group of thalamus	UBERON:0002736	89.74	gold quality
substantia nigra pars reticulata	UBERON:0001966	88.23	gold quality
lateral globus pallidus	UBERON:0002476	87.95	gold quality
subthalamic nucleus	UBERON:0001906	87.42	silver quality
cervix epithelium	UBERON:0004801	87.41	silver quality
pharyngeal mucosa	UBERON:0000355	87.14	silver quality
ventral tegmental area	UBERON:0002691	86.99	silver quality
body of tongue	UBERON:0011876	86.90	silver quality
substantia nigra pars compacta	UBERON:0001965	86.89	gold quality
cardia of stomach	UBERON:0001162	86.88	silver quality
periodontal ligament	UBERON:0008266	86.88	gold quality
upper arm skin	UBERON:0004263	86.80	silver quality
cortical plate	UBERON:0005343	86.75	gold quality
dorsal plus ventral thalamus	UBERON:0001897	86.56	gold quality
inferior vagus X ganglion	UBERON:0005363	86.56	silver quality
tongue	UBERON:0001723	86.53	silver quality
gluteal muscle	UBERON:0002000	86.51	silver quality
right frontal lobe	UBERON:0002810	86.45	gold quality
pylorus	UBERON:0001166	86.28	silver quality
gingival epithelium	UBERON:0001949	86.25	gold quality
buccal mucosa cell	CL:0002336	85.96	silver quality
pericardium	UBERON:0002407	85.86	silver quality
pons	UBERON:0000988	85.47	gold quality
prefrontal cortex	UBERON:0000451	85.43	gold quality
superior surface of tongue	UBERON:0007371	85.32	silver quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	2.61

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): REST

miRNA regulators (miRDB)

119 targeting CHRNB2, 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-4533	100.00	69.48	2758
HSA-MIR-29A-3P	100.00	73.11	1835
HSA-MIR-29B-3P	100.00	73.18	1833
HSA-MIR-29C-3P	100.00	73.15	1833
HSA-MIR-4476	100.00	68.18	2030
HSA-MIR-6876-5P	100.00	67.68	2126
HSA-MIR-4534	99.99	66.58	1907
HSA-MIR-6077	99.99	68.04	2299
HSA-MIR-150-5P	99.99	66.69	1976
HSA-MIR-3667-3P	99.99	67.17	1636
HSA-MIR-10401-5P	99.99	65.79	948
HSA-MIR-4650-5P	99.98	64.69	999
HSA-MIR-4725-3P	99.96	69.53	2520
HSA-MIR-6780B-5P	99.96	69.60	2562
HSA-MIR-4267	99.96	66.53	2368
HSA-MIR-2110	99.96	66.68	1930
HSA-MIR-8082	99.95	67.27	1170
HSA-MIR-1236-3P	99.94	68.04	1695
HSA-MIR-497-5P	99.92	71.83	2674
HSA-MIR-1297	99.91	73.41	3162
HSA-MIR-15A-5P	99.90	72.80	2787
HSA-MIR-15B-5P	99.90	72.78	2798
HSA-MIR-16-5P	99.90	72.80	2780
HSA-MIR-195-5P	99.90	72.81	2805
HSA-MIR-424-5P	99.89	71.90	2641
HSA-MIR-6838-5P	99.89	71.94	2690
HSA-MIR-4271	99.88	68.32	2244
HSA-MIR-7845-5P	99.88	64.88	771
HSA-MIR-4492	99.87	68.25	3611
HSA-MIR-3151-5P	99.86	63.83	1069

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)
• CHRNB2 is a logical candidate for influencing smoking behavior and nicotine dependence (PMID:11906688)
• autosomal dominant nocturnal frontal lobe epilepsy probands were analyzed for the presence of V287L and V287M mutations in the CHRNB2 gene. No mutations in the analyzed region of CHRNB2 found. (PMID:11952766)
• Mutations of the gene encoding CHRNB2 may be linked to nocturnal frontal lobe epilepsy. (PMID:12185808)
• CHRNB2 subunit is expressed in the soma of the majority of pyramidal cells, with the most beta 2 immunoreactivity observed in CA2-4 and entorhinal cortex and relatively less in CA1 and subicular pyramidal cell soma. (PMID:12663058)
• Mutations in genes coding for the alpha 4 and beta 2 subunits of the neuronal nicotinic acetylcholine receptor receptor (CHRN) are known to cause autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE). (PMID:12681012)
• A significant association for Alzheimer’s disease is observed for a non-coding polymorphism in CHRNB2 subunit. (PMID:15026168)
• Nicotinic acetylcholine receptor beta 2 subunit polymorphisms are not a useful marker for prediction of the susceptibility.to febrile seizures. (PMID:15033200)
• 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)
• A common haplotype of the nicotine acetylcholine receptor alpha 4 subunit gene is associated with vulnerability to nicotine addiction in men (PMID:15154117)
• alpha3beta2 nicotinic receptor has a role in regulating gene expression after tobacco exposure in oral epithelial cells (PMID:15681842)
• Here, we report a new CHRNB2 mutation located in transmembrane region 3 (M3), outside the known ADNFLE mutation cluster. The CHRNB2 mutation I312M, which occurred de novo in twins, markedly increases the receptor’s sensitivity to acetylcholine. (PMID:15964197)
• nicotinic modulation of thalamo-cortical circuitry as a key component in the control of conscious awareness in dementia with Lewy bodies (PMID:16023355)
• M1 domains on both alpha4 and beta2 play an important role for efficient expression of extracellular domain alpha4beta2 nAChRs that are high fidelity structural models of full-length alpha4beta2 nAChR (PMID:16174636)
• nicotine-induced up-regulation of alpha4beta2 acetylcholine receptors resulted primarily from an increase in assembly from large pools of unassembled subunits, but up-regulation also resulted from a 5-fold increase in the lifetime in the surface membrane (PMID:16183856)
• analysis of single channel conductance within the large cytoplasmic loop of 5-hydroxytryptamine type 3 and alpha4beta2 nicotinic acetylcholine receptors (PMID:16407231)
• Our present study provided the first line of direct evidence suggesting that the CHRNA4 gene combined with CHRNB2 receptor gene may be linked to schizophrenia. (PMID:16636791)
• Greater beta2*-nAChR availability during early abstinence may impact the ability of smokers to maintain abstinence. (PMID:16928859)
• This study provides the first evidence for association between the CHRNB2 gene and nicotine- and alcohol-related phenotypes, and suggests that polymorphisms in CHRNB2 may be important in mediating early responses to nicotine and alcohol. (PMID:17226798)
• To our knowledge, this is the third family reported presenting a mutation in CHRNB2 in nocturnal frontal lobe epilepsy. (PMID:17900292)
• results do not demonstrate a significant genetic difference in 7 markers from the CHRNA4 and CHRNB2 genes between schizophrenia patients who smoke and those who do not (PMID:18043764)
• These results in living human subjects corroborate postmortem reports of decline in high affinity nicotine binding with age and may aid in elucidating the role of beta(2)-nAChRs in cognitive aging. (PMID:18242781)
• Genetic testing revealed the CHRNB2 mutation I312M in transmembrane region 3 (M3) of the neuronal nicotinic acetylcholine receptor. (PMID:18534914)
• An SNP (rs2072661) in the 3’ UTR region of the CHRNB2 has an impact on abstinence rates at the end of treatment and after a 6-month follow-up period. (PMID:18593715)
• CHRNA4 and CHRNB2 do not play a major role in Japanese schizophrenia. (PMID:18762859)
• Results suggest that neither CHRNA4 nor CHRNB2 plays a major role in Japanese methamphetamine-use disorder. (PMID:18991851)
• Results report that overexpression of VILIP-1 enhances ACh responsiveness, whereas siRNA against VILIP-1 reduces alpha4beta2 nAChR currents of hippocampal neurons. (PMID:19063970)
• results indicate activation of protein kinase A & protein kinase C leads to phosphorylation of alpha4beta2 receptors at different stages of receptor formation & maturation & has different effects on expression & function of alpha4beta2 receptors (PMID:19101612)
• Extracellular beta1-beta2 and cysteine-loops bridge the pre-M1 transmembrane domain and M2-M3 linker to transduce agonist binding into channel gating. (PMID:19279256)
• There was no evidence of association of any of the SNPs in CHRNAB2 (rs2072661, rs4845378) or CHRNAB3 (rs4953, rs6474413) with smoking status (p=0.30) or, among daily smokers, of association with cotinine levels (p=0.08). (PMID:19482438)
• analysis of the agonist bindnig site of alpha4beta2 nicotinic acetylcholine receptors (PMID:19620239)
• association of a 3’ untranslated region polymorphism (rs2072661) in the nicotinic acetylcholine receptor beta2 subunit (CHRNB2) gene with quitting success in response to nicotine versus placebo patch during a short-term test of patch effects. (PMID:19755656)
• Data suggests that beta(2)*-nAChRs play a role in pain sensitivity but not pain tolerance during tobacco smoking withdrawal. (PMID:20371741)
• Using high-resolution NMR spectroscopy, we solved the structure of the entire transmembrane domain (TM1234) of the beta2 subunit. We found that TM1234 formed a four-helix bundle in the absence of the extracellular and intracellular domains. (PMID:20441771)
• A novel mutant mouse harboring the human ADNFLE mutation in the Chrnb2 gene was generated and used to study the roles of beta2* nicotinic receptors in complex biological processes including the activity-rest cycle, natural reward and anxiety. (PMID:20603624)
• Used analysis of non-stationary noise to estimate the maximal probability the nicotinic alpha4beta2 receptor is open. (PMID:20649589)
• variation in the promoter region of CHRNB2 gene may be important in mediating levels of expression of the beta2 nicotinic receptor subunit, which may be associated with variation in subjective response to nicotine (PMID:20854418)
• The high sensitivity to activation and desensitization of (alpha4beta2)alpha5 nAChRbeta2 by nicotine results in a narrow concentration range in which activation and desensitization curves overlap. (PMID:20881005)
• Concatameric pentamers and pentamers formed from combinations of trimers, dimers, and monomers of alpha6beta2beta3* acetylcholine receptors exhibit similar properties, indicating that the linkers between subunits do not alter their functional properties. (PMID:20923852)
• A signaling cascade involving Janus kinase-2 and signal transducer and activator of transcription 3 mediates anti-inflammatory effects through alpha4beta2 nicotinic receptors. (PMID:20943775)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	chrnb2	ENSDARG00000017790
danio_rerio	chrnb5b	ENSDARG00000021392
mus_musculus	Chrnb2	ENSMUSG00000027950
rattus_norvegicus	Chrnb2	ENSRNOG00000020778

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), GABRG1 (ENSG00000163285), GABRB1 (ENSG00000163288), GABRB3 (ENSG00000166206), CHRFAM7A (ENSG00000166664), HTR3A (ENSG00000166736), CHRNA5 (ENSG00000169684), CHRNB1 (ENSG00000170175), CHRNA9 (ENSG00000174343), CHRNA7 (ENSG00000175344), HTR3C (ENSG00000178084), GABRG3 (ENSG00000182256), GABRR3 (ENSG00000183185), HTR3E (ENSG00000186038), HTR3D (ENSG00000186090)

Protein

Protein identifiers

Neuronal acetylcholine receptor subunit beta-2 — P17787 (reviewed: P17787)

All UniProt accessions (4): P17787, A0A1B0GTH5, A0A1B0GVD7, Q5SXY3

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. CHRNB2 forms heteropentameric neuronal acetylcholine receptors with CHRNA2, CHRNA3, CHRNA4 and CHRNA6, as well as CHRNA5 and CHRNB3 as accesory subunits. Found in two major stoichiometric forms,(CHRNA4)3:(CHRNB2)2 and (CHRNA4)2:(CHRNB2)3, the two stoichiometric forms differ in their unitary conductance, calcium permeability, ACh sensitivity and potentiation by divalent cation. Heteropentameric channels with CHRNA6 and CHRNA4 exhibit high sensitivity to ACh and nicotine and are predominantly expressed in only a few brain areas, including dopaminergic neurons, norepirephrine neurons and cells of the visual system. nAChrs containing CHRNA6 subunits mediate endogenous cholinergic modulation of dopamine and gamma-aminobutyric acid (GABA) release in response to nicotine at nerve terminals. Also forms functional nAChRs with other subunits such as CHRNA7:CHRNB2, mainly expressed in basal forebrain cholinergic neurons.

Subunit / interactions. Neuronal AChR is a heteropentamer composed of two different types of subunits: alpha and beta. CHRNB2/Beta-2 subunit can be combined to CHRNA2/alpha-2, CHRNA3/alpha-3 or CHRNA4/alpha-4, CHRNA5/alpha-5, CHRNA6/alpha-6 and CHRNB3/beta-3 to give rise to functional receptors. CHRNA2:CHRNB2 and CHRNA4:CHRNB2 nAChR complexes exist in two subtypes: LS (low agonist sensitivity) with a (CHRNA2/4)3:(CHRNB2)2 and HS (high agonist sensitivity) with a (CHRNA2/4)2:(CHRNB2)3 stoichiometry; the subtypes differ in their subunit binding interfaces which are involved in ligand binding. Cells produce predominantly an (CHRNA4)3:(CHRNB2)2 nAChR. The stoichiometric form (CHRNA4)2:(CHRNB2)3 expression is selectively up-regulated by nicotine and has lower single channel conductance and calcium permeability. Also part of the stoichiometric forms: (CHRNA4:CHRNB2)2:CHRNB3 or (CHRNA6:CHRNB2)2:CHRNB3. Can form heteropentamers with CHRNA7, mainly found in basal forebrain cholinergic neurons. Interacts with RIC3; which is required for proper folding and assembly. Interacts with LYPD6.

Subcellular location. Synaptic cell membrane. Cell membrane.

Disease relevance. Epilepsy, nocturnal frontal lobe, 3 (ENFL3) [MIM:605375] An autosomal dominant focal epilepsy characterized by nocturnal seizures with hyperkinetic automatisms and poorly organized stereotyped movements. The disease is caused by variants affecting the gene represented in this entry.

Activity regulation. Activated by a myriad of ligands such as acetylcholine, cytisine, nicotine, choline and epibatidine. Channel potentiation by calcium is stoichiometry-selective, CHRNA4:CHRNB2 nACh receptor is achieved by calcium association with topographically distinct sites framed by anionic residues within the CHRNA4 subunit and between the CHRNA4 and CHRNB2 subunits. Oligomeric amyloid-beta protein 42 activates specifially CHRNA7:CHRNB2 nAchRs. nAChR activity is inhibited by the antagonist alpha-conotoxins BuIA, PnIA, PnIC, GID and MII, small disulfide-constrained peptides from cone snails.

Similarity. Belongs to the ligand-gated ion channel (TC 1.A.9) family. Acetylcholine receptor (TC 1.A.9.1) subfamily. Beta-2/CHRNB2 sub-subfamily.

RefSeq proteins (1): NP_000739* (*=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), 3 shown:

• K(+)(in) = K(+)(out) (RHEA:29463)
• Ca(2+)(in) = Ca(2+)(out) (RHEA:29671)
• Na(+)(in) = Na(+)(out) (RHEA:34963)

UniProt features (65 total): helix 14, strand 14, mutagenesis site 7, turn 7, topological domain 4, transmembrane region 4, site 3, glycosylation site 3, sequence variant 3, sequence conflict 3, signal peptide 1, chain 1, disulfide bond 1

Structure

Experimental structures (PDB)

15 structures.

PDB	Method	Resolution (Å)
8ST4	ELECTRON MICROSCOPY	2.35
8ST0	ELECTRON MICROSCOPY	2.4
8SSZ	ELECTRON MICROSCOPY	2.64
8ST3	ELECTRON MICROSCOPY	2.93
8ST2	ELECTRON MICROSCOPY	2.94
8ST1	ELECTRON MICROSCOPY	3.41
6CNJ	ELECTRON MICROSCOPY	3.7
6UR8	ELECTRON MICROSCOPY	3.71
6USF	ELECTRON MICROSCOPY	3.87
6CNK	ELECTRON MICROSCOPY	3.9
5KXI	X-RAY DIFFRACTION	3.94
2K58	SOLUTION NMR
2K59	SOLUTION NMR
2KSR	SOLUTION NMR
2LM2	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P17787-F1	81.16	0.51

Antibody-complex structures (SAbDab): 9 — 6CNJ, 6CNK, 6USF, 8SSZ, 8ST0, 8ST1, 8ST2, 8ST3, 8ST4

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): 84 (key residue that may interfere with effective access of the conotoxin buia to the channel binding site); 136 (key residue for a rapid dissociation (k(off)) from the conotoxin buia); 144 (key residue for a rapid dissociation (k(off)) from the conotoxin buia)

Disulfide bonds (1): 155–169

Glycosylation sites (3): 51, 168, 485

Mutagenesis-validated functional residues (7):

Position	Phenotype
72	reduces chrna4:chrnb2 channel opening potentiation by divalent cations.
74	reduces chrna4:chrnb2 channel opening potentiation by divalent cations.
196	loss of chrna4:chrnb2 channel opening potentiation by divalent cations.
197	increases ligand activation in ls and hs nachr subtypes.
202	reduces chrna4:chrnb2 channel opening potentiation by divalent cations.
218	reduces chrna4:chrnb2 channel opening potentiation by divalent cations.
285	increases ca(2+) permeability.

Function

Pathways and Gene Ontology

Reactome pathways

9 pathways

ID	Pathway
R-HSA-629587	Highly sodium permeable postsynaptic acetylcholine nicotinic receptors
R-HSA-629594	Highly calcium permeable postsynaptic nicotinic acetylcholine receptors
R-HSA-629597	Highly calcium permeable 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-622323	Presynaptic nicotinic acetylcholine receptors
R-HSA-622327	Postsynaptic nicotinic acetylcholine receptors

MSigDB gene sets: 325 (showing top): GSE45365_CD8A_DC_VS_CD11B_DC_IFNAR_KO_MCMV_INFECTION_DN, GOBP_CIRCADIAN_RHYTHM, GOBP_DENDRITE_DEVELOPMENT, GOBP_MEMORY, GOBP_REGULATION_OF_CELL_ACTIVATION, RNGTGGGC_UNKNOWN, GOBP_PHENOL_CONTAINING_COMPOUND_METABOLIC_PROCESS, GOBP_EXCRETION, GOBP_MEMBRANE_DEPOLARIZATION, GOBP_RESPONSE_TO_NITROGEN_COMPOUND, GOBP_REGULATION_OF_LEUKOCYTE_PROLIFERATION, GOBP_RESPONSE_TO_ETHANOL, GOBP_COGNITION, MODULE_274, GOBP_BEHAVIOR

GO Biological Process (43): response to hypoxia (GO:0001666), monoatomic ion transport (GO:0006811), calcium ion transport (GO:0006816), smooth muscle contraction (GO:0006939), signal transduction (GO:0007165), chemical synaptic transmission (GO:0007268), synaptic transmission, cholinergic (GO:0007271), visual perception (GO:0007601), sensory perception of sound (GO:0007605), learning (GO:0007612), memory (GO:0007613), locomotory behavior (GO:0007626), associative learning (GO:0008306), visual learning (GO:0008542), regulation of dopamine secretion (GO:0014059), sensory perception of pain (GO:0019233), vestibulocochlear nerve development (GO:0021562), optic nerve morphogenesis (GO:0021631), lateral geniculate nucleus development (GO:0021771), central nervous system projection neuron axonogenesis (GO:0021952), positive regulation of B cell proliferation (GO:0030890), regulation of synaptic transmission, dopaminergic (GO:0032225), positive regulation of dopamine secretion (GO:0033603), monoatomic ion transmembrane transport (GO:0034220), response to nicotine (GO:0035094), behavioral response to nicotine (GO:0035095), social behavior (GO:0035176), regulation of dopamine metabolic process (GO:0042053), B cell activation (GO:0042113), response to cocaine (GO:0042220), regulation of circadian sleep/wake cycle, REM sleep (GO:0042320), response to ethanol (GO:0045471), negative regulation of action potential (GO:0045759), regulation of dendrite morphogenesis (GO:0048814), nervous system process (GO:0050877), cognition (GO:0050890), membrane depolarization (GO:0051899), regulation of synapse assembly (GO:0051963), synaptic transmission involved in micturition (GO:0060084), acetylcholine receptor signaling pathway (GO:0095500)

GO Molecular Function (8): ligand-gated monoatomic ion channel activity (GO:0015276), acetylcholine receptor activity (GO:0015464), acetylcholine-gated monoatomic cation-selective channel activity (GO:0022848), acetylcholine binding (GO:0042166), transmembrane signaling receptor activity (GO:0004888), monoatomic ion channel activity (GO:0005216), extracellular ligand-gated monoatomic ion channel activity (GO:0005230), protein binding (GO:0005515)

GO Cellular Component (11): plasma membrane (GO:0005886), acetylcholine-gated channel complex (GO:0005892), external side of plasma membrane (GO:0009897), membrane (GO:0016020), neuron projection (GO:0043005), plasma membrane raft (GO:0044853), synapse (GO:0045202), postsynaptic membrane (GO:0045211), neurotransmitter receptor complex (GO:0098878), cation channel complex (GO:0034703), synaptic membrane (GO:0097060)

Reactome top-level categories

Rollup of top-6 pathways:

Category	Pathways
Presynaptic nicotinic acetylcholine receptors	2
Postsynaptic nicotinic acetylcholine receptors	2
Acetylcholine binding and downstream events	2
Transmission across Chemical Synapses	1
Neuronal System	1
Neurotransmitter receptors and postsynaptic signal transmission	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
learning or memory	2
postsynaptic neurotransmitter receptor activity	2
monoatomic ion channel complex	2
plasma membrane signaling receptor complex	2
plasma membrane	2
plasma membrane region	2
response to stress	1
response to decreased oxygen levels	1
transport	1
metal ion transport	1
muscle contraction	1
cell communication	1
cellular process	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
anterograde trans-synaptic signaling	1
chemical synaptic transmission	1
sensory perception of light stimulus	1
sensory perception of mechanical stimulus	1
behavior	1
learning	1
visual behavior	1
associative learning	1
dopamine secretion	1
regulation of catecholamine secretion	1
sensory perception	1
cranial nerve development	1
optic nerve development	1
cranial nerve morphogenesis	1
thalamus development	1
neural nucleus development	1
central nervous system neuron axonogenesis	1
monoatomic ion channel activity	1
ligand-gated channel activity	1
transmembrane signaling receptor activity	1
synaptic transmission, cholinergic	1
acetylcholine binding	1
excitatory extracellular ligand-gated monoatomic ion channel activity	1
ligand-gated monoatomic cation channel activity	1

Protein interactions and networks

STRING

1424 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CHRNB2	CHRM2	P08172	710
CHRNB2	CHRNA4	P43681	683
CHRNB2	IGBP1	P78318	677
CHRNB2	KCNT1	Q5JUK3	669
CHRNB2	GABBR2	O75899	662
CHRNB2	CHRM5	P08912	660
CHRNB2	SLC17A6	Q9P2U8	650
CHRNB2	DRD2	P14416	618
CHRNB2	GRIN2A	Q12879	601
CHRNB2	SLC6A3	Q01959	599
CHRNB2	GRIN2B	Q13224	591
CHRNB2	DEPDC5	O75140	585
CHRNB2	PURA	Q00577	575
CHRNB2	DRD1	P21728	572
CHRNB2	ACHE	P22303	560

IntAct

18 interactions, top by confidence:

A	B	Type	Score
CHRNB2	CHRNA5	psi-mi:“MI:0915”(physical association)	0.660
CHRNA5	CHRNB2	psi-mi:“MI:0914”(association)	0.660
CHRNB2	CHRNA5	psi-mi:“MI:0914”(association)	0.660
CHRNA4	CHRNB2	psi-mi:“MI:0915”(physical association)	0.490
CHRNB2	CRELD2	psi-mi:“MI:0915”(physical association)	0.440
CRELD2	CHRNB2	psi-mi:“MI:0403”(colocalization)	0.440
CHRNA4	CHRNB2	psi-mi:“MI:0915”(physical association)	0.400
LYPD6	CHRNB2	psi-mi:“MI:0914”(association)	0.350
LYNX1	CHRNB2	psi-mi:“MI:0914”(association)	0.350
CHRNB2	TMEM131L	psi-mi:“MI:0914”(association)	0.350
CHRNB2	SNX2	psi-mi:“MI:0914”(association)	0.350
IL5RA	LETM1	psi-mi:“MI:0914”(association)	0.350
STRIP2	OXSR1	psi-mi:“MI:0914”(association)	0.350

BioGRID (105): CHRNA3 (Affinity Capture-Western), CHRNA4 (Affinity Capture-Western), P2RX2 (Affinity Capture-Western), CHRNB2 (Affinity Capture-Western), CHRNB2 (Affinity Capture-Western), CHRNB2 (Affinity Capture-Western), WNT5A (Affinity Capture-MS), CYB5R1 (Affinity Capture-MS), EIF2AK3 (Affinity Capture-MS), ASPHD2 (Affinity Capture-MS), B4GALT7 (Affinity Capture-MS), B4GALT1 (Affinity Capture-MS), ST3GAL6 (Affinity Capture-MS), ENTPD6 (Affinity Capture-MS), TTC17 (Affinity Capture-MS)

ESM2 similar proteins: F1R8P4, G5EBR3, O00591, O09028, O14764, O18276, O75311, O93430, P02712, P07727, P09478, P09484, P12389, P12390, P12392, P17644, P17787, P18506, P20781, P22771, P22933, P23414, P23415, P23416, P24524, P30926, P32297, P48167, P48168, P57695, P91730, P91766, Q09453, Q15822, Q17328, Q21005, Q5EA06, Q61603, Q64018, Q75NA5

Diamond homologs: A8WQK3, O16926, O70174, P02708, P02709, P02710, P02711, P02712, P02713, P02716, P02717, P04755, P04756, P04757, P04758, P04759, P05377, P09478, P09479, P09480, P09481, P09482, P09483, P09484, P09628, P09690, P11230, P12389, P12390, P12391, P12392, P13908, P17644, P17787, P18257, P18845, P19370, P20420, P22456, P22770

SIGNOR signaling

5 interactions.

A	Effect	B	Mechanism
CHRNB2	“form complex”	“Neuronal nicotinic acetylcholine receptor complex, 3xalpha4-2xbeta2”	binding
CHRNB2	“form complex”	“Neuronal nicotinic acetylcholine receptor complex, alpha3-alpha5-beta2”	binding
CHRNB2	“form complex”	“Neuronal nicotinic acetylcholine receptor complex, alpha4-alpha5-beta2”	binding
CHRNB2	“form complex”	“Neuronal nicotinic acetylcholine receptor complex, alpha7-beta2”	binding
CHRNB2	“form complex”	“Neuronal nicotinic acetylcholine receptor complex, alpha3-alpha6-beta2-beta3”	binding

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	2
Likely pathogenic	3
Uncertain significance	372
Likely benign	242
Benign	18

Top pathogenic / likely-pathogenic (5)

Variant ID	HGVS	Classification
17495	NM_000748.3(CHRNB2):c.859G>C (p.Val287Leu)	Pathogenic
17496	NM_000748.3(CHRNB2):c.859G>A (p.Val287Met)	Pathogenic
1030889	NM_000748.3(CHRNB2):c.845T>A (p.Leu282His)	Likely pathogenic
3061958	NM_000748.3(CHRNB2):c.256-1G>A	Likely pathogenic
3391473	NM_000748.3(CHRNB2):c.1010T>G (p.Val337Gly)	Likely pathogenic

SpliceAI

996 predictions. Top by Δscore:

Variant	Effect	Δscore
1:154568106:CAGGT:C	donor_loss	1.0000
1:154568107:AGGTA:A	donor_loss	1.0000
1:154568109:G:GA	donor_loss	1.0000
1:154568110:T:G	donor_loss	1.0000
1:154569455:T:A	acceptor_gain	1.0000
1:154569458:CCA:C	acceptor_loss	1.0000
1:154569459:CA:C	acceptor_loss	1.0000
1:154569460:A:AG	acceptor_gain	1.0000
1:154569460:AG:A	acceptor_gain	1.0000
1:154569460:AGG:A	acceptor_gain	1.0000
1:154569460:AGGG:A	acceptor_gain	1.0000
1:154569461:G:A	acceptor_gain	1.0000
1:154569461:G:GA	acceptor_gain	1.0000
1:154569461:GGG:G	acceptor_gain	1.0000
1:154569461:GGGG:G	acceptor_gain	1.0000
1:154569461:GGGGT:G	acceptor_gain	1.0000
1:154569565:GAC:G	donor_gain	1.0000
1:154569566:ACA:A	donor_gain	1.0000
1:154569603:GTGTG:G	donor_gain	1.0000
1:154569605:GTG:G	donor_gain	1.0000
1:154569606:TG:T	donor_gain	1.0000
1:154569607:GG:G	donor_gain	1.0000
1:154569608:G:GC	donor_loss	1.0000
1:154569608:G:GG	donor_gain	1.0000
1:154570249:A:AG	acceptor_gain	1.0000
1:154570250:T:G	acceptor_gain	1.0000
1:154570254:CCAG:C	acceptor_loss	1.0000
1:154570255:CAG:C	acceptor_loss	1.0000
1:154570256:A:AG	acceptor_gain	1.0000
1:154570256:AG:A	acceptor_gain	1.0000

AlphaMissense

3287 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:154569540:C:A	P48Q	1.000
1:154569825:T:A	W82R	1.000
1:154569825:T:C	W82R	1.000
1:154570261:T:A	W87R	1.000
1:154570261:T:C	W87R	1.000
1:154570263:G:C	W87C	1.000
1:154570263:G:T	W87C	1.000
1:154570267:G:C	D89H	1.000
1:154570274:G:C	R91P	1.000
1:154570277:T:C	L92P	1.000
1:154570282:T:A	W94R	1.000
1:154570282:T:C	W94R	1.000
1:154570284:G:C	W94C	1.000
1:154570284:G:T	W94C	1.000
1:154570339:T:A	W113R	1.000
1:154570339:T:C	W113R	1.000
1:154570341:G:C	W113C	1.000
1:154570341:G:T	W113C	1.000
1:154570346:C:A	P115Q	1.000
1:154571256:T:A	W145R	1.000
1:154571256:T:C	W145R	1.000
1:154571280:A:C	S153R	1.000
1:154571282:C:A	S153R	1.000
1:154571282:C:G	S153R	1.000
1:154571286:T:A	C155S	1.000
1:154571286:T:C	C155R	1.000
1:154571287:G:A	C155Y	1.000
1:154571287:G:C	C155S	1.000
1:154571288:C:G	C155W	1.000
1:154571307:T:C	F162L	1.000

dbSNP variants (sampled 300 via entrez): RS1000867963 (1:154568532 C>T), RS1001642557 (1:154570998 T>A,G), RS1001854931 (1:154575684 G>A,C,T), RS1001916378 (1:154576724 C>G), RS1001976248 (1:154569009 AC>A), RS1002883487 (1:154569393 T>C,G), RS1003043795 (1:154573061 C>T), RS1003490551 (1:154571081 C>T), RS1003550319 (1:154578184 G>A), RS1003915084 (1:154579095 G>C), RS1003950436 (1:154571519 C>A), RS1004366641 (1:154566419 G>A), RS1004807893 (1:154577578 T>C), RS1004901701 (1:154578685 A>G), RS1004998847 (1:154571604 G>A,T)

Disease associations

OMIM: gene MIM:118507 | disease phenotypes: MIM:600513, MIM:605375

GenCC curated gene-disease

Disease	Classification	Inheritance
autosomal dominant nocturnal frontal lobe epilepsy 3	Strong	Autosomal dominant
autosomal dominant nocturnal frontal lobe epilepsy	Supportive	Autosomal dominant

ClinGen Gene-Disease Validity (1)

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

Disease	Classification	Inheritance
familial sleep-related hypermotor epilepsy	Definitive	AD

Mondo (7): familial sleep-related hypermotor epilepsy (MONDO:0000030), autosomal dominant nocturnal frontal lobe epilepsy 3 (MONDO:0011545), autosomal dominant nocturnal frontal lobe epilepsy 1 (MONDO:0010899), intellectual disability (MONDO:0001071), microcephaly (MONDO:0001149), enophthalmos (MONDO:0001210), (MONDO:0020300)

Orphanet (2): Sleep-related hypermotor epilepsy (Orphanet:98784), NON RARE IN EUROPE: Unexplained intellectual disability (Orphanet:319658)

HPO phenotypes

23 total (25 of 23 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000020	Urinary incontinence
HP:0000708	Atypical behavior
HP:0000716	Depression
HP:0000733	Motor stereotypy
HP:0000739	Anxiety
HP:0001250	Seizure
HP:0001256	Mild intellectual disability
HP:0001345	Psychotic mentation
HP:0002069	Bilateral tonic-clonic seizure
HP:0002268	Paroxysmal dystonia
HP:0002883	Hyperventilation
HP:0004305	Involuntary movements
HP:0007018	Attention deficit hyperactivity disorder
HP:0011174	Focal hyperkinetic seizure
HP:0011182	Interictal epileptiform activity
HP:0011193	EEG with focal spikes
HP:0025235	NREM parasomnia
HP:0025236	Sleep walking
HP:0031535	Increased theta frequency activity in EEG
HP:0031589	Suicidal ideation
HP:0031951	Nocturnal seizures
HP:0100543	Cognitive impairment
HP:0000252	Microcephaly
HP:0000490	Deeply set eye

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST004294_8	Nicotine dependence	4.000000e-06
GCST008809_1	Smoking behaviour (cigarettes smoked per day)	4.000000e-08
GCST012497_2	Lung function (FEV1)	4.000000e-07

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0006525	cigarettes per day measurement
EFO:0004314	forced expiratory volume

MeSH disease descriptors (6)

Descriptor	Name	Tree numbers
D015841	Enophthalmos	C11.675.319
D008607	Intellectual Disability	C10.597.606.360; C23.888.592.604.646; F01.700.687; F03.625.539
D008831	Microcephaly	C05.660.207.620; C10.500.507.400.500; C16.131.621.207.620; C16.131.666.507.400.500
C579932	Autosomal Dominant Nocturnal Frontal Lobe Epilepsy (supp.)
C563930	Epilepsy, Nocturnal Frontal Lobe, Type 1 (supp.)
C565334	Epilepsy, Nocturnal Frontal Lobe, Type 3 (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (14): CHEMBL1883 (SINGLE PROTEIN), CHEMBL1907589 (PROTEIN COMPLEX), CHEMBL2109233 (PROTEIN COMPLEX), CHEMBL2109234 (PROTEIN COMPLEX), CHEMBL2109236 (PROTEIN COMPLEX), CHEMBL2109237 (PROTEIN COMPLEX), CHEMBL2111384 (PROTEIN COMPLEX GROUP), CHEMBL2221346 (PROTEIN COMPLEX GROUP), CHEMBL3038458 (PROTEIN COMPLEX), CHEMBL3038461 (PROTEIN COMPLEX)

Molecules with ChEMBL bioactivity

26 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 450,937 (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
CHEMBL267936	MECAMYLAMINE	4	5,623
CHEMBL289469	GRANISETRON	4	431
CHEMBL3	NICOTINE	4	184,969
CHEMBL46	ONDANSETRON	4	41,386
CHEMBL56564	TROPISETRON	4	19,312
CHEMBL667	ACETYLCHOLINE	4	124,626
CHEMBL894	BUPROPION	4	36,982
CHEMBL965	CARBAMOYLCHOLINE	4	22,580
CHEMBL2103881	DEXMECAMYLAMINE	3	18
CHEMBL497939	CYTISINICLINE	3	2,766
CHEMBL111659	ALTINICLINE	2	129
CHEMBL1172928	RADAFAXINE	2	1,079
CHEMBL122270	LOBELINE	2	2,266
CHEMBL1257065	STILONIUM IODIDE	2	751
CHEMBL1258006	BRADANICLINE	2	208
CHEMBL127071	POZANICLINE	2	360
CHEMBL132966	RIVANICLINE	2	911
CHEMBL134713	GTS-21	2	269
CHEMBL188462	ISPRONICLINE	2	464
CHEMBL2151437	AZD0328	2
CHEMBL2179529	AZD1446	2
CHEMBL238465	SOFINICLINE	2
CHEMBL430497	TEBANICLINE	2
CHEMBL504652	TC-2216	1
CHEMBL6200	NORNICOTINE	1

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

PharmGKB clinical annotations

3 annotations.

Variant	Type	Level	Drugs	Phenotypes
rs2072658	Other	3	nicotine	Tobacco Use Disorder
rs2072660	Toxicity	3	nicotine	Tobacco Use Disorder
rs2072661	Efficacy,Toxicity	3	nicotine	Tobacco Use Disorder

PharmGKB variants

5 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs2072658	CHRNB2	3	1.25	1	nicotine
rs2072660	CHRNB2	3	1.75	1	nicotine
rs2072661	CHRNB2	3	3.00	1	nicotine
rs4292956	CHRNB2		0.00	0
rs12072348	CHRNB2		0.00	0

GtoPdb / IUPHAR curated pharmacology

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

Target class: lgic — Nicotinic acetylcholine receptors (nACh)

Binding affinities (BindingDB)

78 measured of 87 human assays (101 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
(S)-2-(6-Chloro-pyridin-3-yl)-7-aza-bicyclo[2.2.1]heptane	KI	0.05 nM
syn-7-(6-chloro-pyridin-3-yl)-2-azabicyclo[2.2.1]heptane	KI	0.0785 nM
5-[5-(azetidin-2-ylmethoxy)-6-methyl-3-pyridinyl]pent-4-yn-1-ol	KI	0.087 nM	US-9993465: 2,5-disubstituted-pyridyl nicotinic ligands, and methods of use thereof
6-[5-(7-Aza-bicyclo[2.2.1]hept-2-yl)-pyridin-3-yl]-hex-5-yn-1-ol	KI	0.23 nM
3-(4-Methyl-isoxazol-5-ylmethyl)-1-aza-bicyclo[2.2.1]heptane	KI	0.3 nM
CHEMBL4740159	KI	0.32 nM
6-(6-Chloro-pyridin-3-yl)-8-aza-bicyclo[3.2.1]octane	KI	0.343 nM
VARENICLINE	KI	0.48 nM	US-9993465: 2,5-disubstituted-pyridyl nicotinic ligands, and methods of use thereof
7-(3-methylisoxazol-5-yl)-6-aza-bicyclo[2.2.1]heptane	KI	0.763 nM
11-Bromo-1,2,3,4,5,6-hexahydro-1,5-methano-pyrido[1,2-a][1,5]diazocin-8-one	EC50	1.1 nM
CHEMBL3329537	KI	1.1 nM
CHEMBL4791046	KI	1.3 nM
CHEMBL4793576	KI	1.6 nM
(1S,4S)-2-(6-fluoro-3-pyridinyl)-2,5-diazabicyclo[2.2.1]-heptane	EC50	1.62 nM
CHEMBL2177548	KI	1.7 nM
CHEMBL3329538	KI	1.7 nM
4-[[(2-oxo-1-piperidin-3-yl-4-pyridinyl)methylamino]methyl]-7,11-diazatricyclo[7.3.1.02,7]trideca-2,4-dien-6-one	KI	3.5 nM	US-11667638: 4-substitued cytisine analogues
CHEMBL2177550	KI	4.4 nM
6-[5-(azetidin-2-ylmethoxy)-6-methyl-3-pyridinyl]hex-5-yn-1-ol	KI	5.3 nM	US-9993465: 2,5-disubstituted-pyridyl nicotinic ligands, and methods of use thereof
CHEMBL3329539	KI	5.4 nM
CHEMBL3329542	KI	7 nM
6-(6-Chloro-pyridin-3-yl)-8-aza-bicyclo[3.2.1]octan-3-ol	KI	7.4 nM
3-(azetidin-2-ylmethoxy)-5-(6-chlorohex-1-ynyl)-2-methylpyridine	KI	8.6 nM	US-9993465: 2,5-disubstituted-pyridyl nicotinic ligands, and methods of use thereof
3-(azetidin-2-ylmethoxy)-5-(6-fluorohex-1-ynyl)-2-methylpyridine	KI	8.7 nM	US-9993465: 2,5-disubstituted-pyridyl nicotinic ligands, and methods of use thereof
CHEMBL2178154	KI	9.6 nM
CHEMBL2057714	KI	10 nM
3-(azetidin-2-ylmethoxy)-5-(2-cyclopropylethynyl)-2-methylpyridine	KI	13 nM	US-9993465: 2,5-disubstituted-pyridyl nicotinic ligands, and methods of use thereof
CHEMBL2177554	KI	13 nM
3-(3-Methyl-isoxazol-5-ylmethylene)-1-aza-bicyclo[2.2.1]heptane	IC50	14 nM
3-[1-(3-Methyl-isoxazol-5-yl)-meth-(Z)-ylidene]-1-aza-bicyclo[2.2.1]heptane	IC50	15 nM
3-(azetidin-2-ylmethoxy)-5-hex-1-ynyl-2-methylpyridine	KI	16 nM	US-9993465: 2,5-disubstituted-pyridyl nicotinic ligands, and methods of use thereof
CHEMBL2177525	KI	22 nM
CHEMBL3329541	KI	22 nM
CHEMBL2177534	KI	24 nM
CHEMBL2057712	KI	29 nM
11,11-dimethyl-6-oxo-7-aza-11-azoniatricyclo[7.3.1.02,7]trideca-2,4-diene iodide	EC50	41 nM
CHEMBL3329540	EC50	53 nM
2-(6-chloropyridin-3-yl)-1,2,3,4-tetrahydro-1,4-epiminonaphthalene	KI	65.2 nM
CHEMBL4798114	KI	88 nM
CHEMBL2296158	IC50	90 nM
2-(6-fluoro-5-phenylpyridin-3-yl)-1,2,3,4-tetrahydro-1,4-epiminonaphthalene	KI	128 nM
5-hex-1-ynyl-2-methyl-3-(pyrrolidin-2-ylmethoxy)pyridine	KI	130 nM	US-9993465: 2,5-disubstituted-pyridyl nicotinic ligands, and methods of use thereof
CHEMBL3329544	KI	310 nM
CHEMBL4438684	KI	519 nM
CHEMBL3329545	EC50	540 nM
CHEMBL4472617	KI	627 nM
3-[1-(3-Methyl-isoxazol-5-yl)-meth-(E)-ylidene]-1-aza-bicyclo[2.2.2]octane	IC50	854 nM
(1R,4R)-2-(5-cyano-3-pyridinyl)-2,5-diazabicyclo[2.2.1]-heptane	EC50	980 nM
CHEMBL3329546	EC50	1000 nM
CHEMBL4557590	KI	1010 nM

ChEMBL bioactivities

2055 potent at pChembl≥5 of 2326 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
11.00	Ki	0.01	nM	EPIBATIDINE
11.00	Kd	0.01	nM	EPIBATIDINE
11.00	Kd	0.0101	nM	EPIBATIDINE
10.77	Ki	0.017	nM	CHEMBL2024096
10.77	Ki	0.01698	nM	CHEMBL2024096
10.74	Ki	0.018	nM	CHEMBL245243
10.70	EC50	0.02	nM	EPIBATIDINE
10.70	Ki	0.02	nM	CHEMBL4168511
10.68	Ki	0.021	nM	CHEMBL361465
10.66	Ki	0.022	nM	CHEMBL361465
10.59	Ki	0.026	nM	(+)-EPIBATIDINE
10.57	Ki	0.027	nM	AZIDOEPIBATIDINE
10.52	Kd	0.03	nM	EPIBATIDINE
10.52	Kd	0.03	nM	(-)-EPIBATIDINE
10.52	Ki	0.03	nM	CHEMBL2164666
10.51	Ki	0.031	nM	CHEMBL3086984
10.49	Ki	0.032	nM	CHEMBL3086994
10.48	Ki	0.033	nM	EPIBATIDINE
10.47	Ki	0.034	nM	TEBANICLINE
10.46	Ki	0.035	nM	EPIBATIDINE
10.44	EC50	0.036	nM	CHEMBL62858
10.42	Ki	0.038	nM	CHEMBL291498
10.40	Ki	0.04	nM	CHEMBL59986
10.40	Ki	0.04	nM	VARENICLINE
10.40	Ki	0.04	nM	CHEMBL63102
10.37	Ki	0.043	nM	CHEMBL3086985
10.35	Ki	0.045	nM	(+)-EPIBATIDINE
10.35	Ki	0.045	nM	NICOTINE
10.34	Ki	0.046	nM	CHEMBL3086982
10.34	Ki	0.046	nM	EPIBATIDINE
10.31	Ki	0.049	nM	CHEMBL3086991
10.30	Ki	0.05	nM	EPIBATIDINE
10.30	Ki	0.05	nM	CHEMBL3086995
10.30	EC50	0.05	nM	CHEMBL305106
10.30	Ki	0.05	nM	CHEMBL59986
10.30	Ki	0.05	nM	CHEMBL54902
10.28	Ki	0.052	nM	CHEMBL59986
10.26	Ki	0.055	nM	TEBANICLINE
10.25	Ki	0.0558	nM	EPIBATIDINE
10.22	EC50	0.06	nM	VARENICLINE
10.22	Ki	0.06	nM	VARENICLINE
10.22	Ki	0.06	nM	EPIBATIDINE
10.22	Ki	0.06	nM	CHEMBL5412811
10.21	Ki	0.062	nM	CHEMBL2024096
10.15	Ki	0.07	nM	EPIBATIDINE
10.14	Ki	0.072	nM	CHEMBL3086993
10.14	Ki	0.073	nM	CHEMBL185061
10.12	Ki	0.076	nM	CHEMBL3086986
10.11	Ki	0.0785	nM	CHEMBL220476
10.11	Ki	0.077	nM	CHEMBL5404069

PubChem BioAssay actives

1865 with measured affinity, of 4461 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
2-(6-chloro-3-pyridinyl)-7-methyl-7-azabicyclo[2.2.1]heptane	304128: Displacement of [3H]epibatidine from alpha-4-beta-2 nAChR	ki	<0.0001	uM
2-(6-chloro-3-pyridinyl)-7-azabicyclo[2.2.1]heptane	1410535: Displacement of [3H]epibatidine from alpha4beta2 nAChR (unknown origin) expressed in HEK cell membranes after 4 hrs by liquid scintillation counting method	ki	<0.0001	uM
(1R,4R)-2-pyridin-3-yl-2,5-diazabicyclo[2.2.1]heptane	1359521: Agonist activity at alpha4beta2 nAChR (unknown origin)	ki	<0.0001	uM
(1S,2S,4R)-2-(6-chloro-3-pyridinyl)-7-azabicyclo[2.2.1]heptane	1252856: Binding affinity to alpha4beta2 nAChR (unknown origin)	ki	<0.0001	uM
5-[[(2R)-azetidin-2-yl]methoxy]-2-chloropyridine	146301: Compound was evaluated for its ability to displace [3H]cytisine from K177 cells expressing human Nicotinic acetylcholine receptor alpha4-beta2	ki	<0.0001	uM
2-(5-azido-6-chloro-3-pyridinyl)-7-azabicyclo[2.2.1]heptane	146309: Binding affinity to alpha4 beta-2 receptor subtype from mouse fibroblast M10 cells was measured using [3 H]nicotine	ki	<0.0001	uM
2-(6-chloro-3-pyridinyl)-9-azabicyclo[4.2.1]non-2-ene	640183: Displacement of [3H]epibatidine from nAChR alpha4beta2 receptor	ki	<0.0001	uM
Varenicline	1647833: Displacement of [3H]cytisine from human alpha4beta2 nAChR expressed in CHOK1 cell membrane by microbeta scintillation counting method	ki	<0.0001	uM
3-[[(2S)-azetidin-2-yl]methoxy]pyridine	146301: Compound was evaluated for its ability to displace [3H]cytisine from K177 cells expressing human Nicotinic acetylcholine receptor alpha4-beta2	ki	<0.0001	uM
3-[[(2S)-azetidin-2-yl]methoxy]-5-(2-phenylethynyl)pyridine	1053303: Displacement of [3H]epibatidine from human alpha4beta2 nAChR after 4 hrs by cell-based assay	ki	<0.0001	uM
3-[[(2S)-azetidin-2-yl]methoxy]-5-[2-(3-fluorophenyl)ethynyl]pyridine	1053303: Displacement of [3H]epibatidine from human alpha4beta2 nAChR after 4 hrs by cell-based assay	ki	<0.0001	uM
3-[[(2S)-azetidin-2-yl]methoxy]-5-[2-(3-fluoro-5-methylphenyl)ethynyl]pyridine	1053303: Displacement of [3H]epibatidine from human alpha4beta2 nAChR after 4 hrs by cell-based assay	ki	<0.0001	uM
3-[2-[5-[[(2S)-azetidin-2-yl]methoxy]-3-pyridinyl]ethynyl]-5-fluoro-N,N-dimethylaniline	1053303: Displacement of [3H]epibatidine from human alpha4beta2 nAChR after 4 hrs by cell-based assay	ki	<0.0001	uM
3-[[(2S)-azetidin-2-yl]methoxy]-5-[2-(3-methylphenyl)ethynyl]pyridine	1053303: Displacement of [3H]epibatidine from human alpha4beta2 nAChR after 4 hrs by cell-based assay	ki	<0.0001	uM
(1R,2R,4S)-2-(6-chloro-3-pyridinyl)-7-azabicyclo[2.2.1]heptane	1275134: Binding affinity to alpha4beta2 nACh receptor (unknown origin) expressed in Xenopus oocytes	kd	<0.0001	uM
Nicotine	1359521: Agonist activity at alpha4beta2 nAChR (unknown origin)	ki	<0.0001	uM
5-iodo-7,11-diazatricyclo[7.3.1.02,7]trideca-2,4-dien-6-one	246575: Change in membrane potential in K-177 cells expressing acetylcholine central neuronal receptor alpha4-beta2 subunits	ec50	<0.0001	uM
2-(6-chloro-3-pyridinyl)-2,5-diazabicyclo[2.2.1]heptane	1359521: Agonist activity at alpha4beta2 nAChR (unknown origin)	ki	<0.0001	uM
1-decyl-3-[(2S)-1-methylpyrrolidin-2-yl]pyridin-1-ium iodide	1243907: Binding affinity to alpha4beta2 nAChR (unknown origin)	ki	0.0001	uM
6-methyl-5,7,13-triazatetracyclo[9.3.1.02,10.04,8]pentadeca-2,4(8),5,9-tetraene	254476: Binding affinity for human Nicotinic acetylcholine receptor alpha4-beta2 expressed in HEK 293 cells using [3H]nicotine	ki	0.0001	uM
1-dodecyl-3-[(2S)-1-methylpyrrolidin-2-yl]pyridin-1-ium iodide	1243907: Binding affinity to alpha4beta2 nAChR (unknown origin)	ki	0.0001	uM
6-[5-[[(2S)-azetidin-2-yl]methoxy]-3-pyridinyl]hex-5-yn-1-ol	1053303: Displacement of [3H]epibatidine from human alpha4beta2 nAChR after 4 hrs by cell-based assay	ki	0.0001	uM
(1S,2S,5R)-2-(pyridin-3-yloxymethyl)-3-azabicyclo[3.1.0]hexane;hydrochloride	1647833: Displacement of [3H]cytisine from human alpha4beta2 nAChR expressed in CHOK1 cell membrane by microbeta scintillation counting method	ki	0.0001	uM
(1S,4S)-2-pyridin-3-yl-2,5-diazabicyclo[2.2.1]heptane	1359521: Agonist activity at alpha4beta2 nAChR (unknown origin)	ki	0.0001	uM
2-chloro-5-[(3S)-3-methyl(511C)pentyl]-3-[(E)-2-pyridin-4-ylethenyl]pyridine	1988843: Binding affinity to nACh alpha6beta2 receptor (unknown origin) assessed as inhibition constant	ki	0.0001	uM
6-[5-(2-(18F)fluoro-3-pyridinyl)-3-pyridinyl]-8-methyl-8-azabicyclo[3.2.1]octane	1988843: Binding affinity to nACh alpha6beta2 receptor (unknown origin) assessed as inhibition constant	ki	0.0001	uM
3-[[(2S)-azetidin-2-yl]methoxy]-5-phenylpyridine	1053303: Displacement of [3H]epibatidine from human alpha4beta2 nAChR after 4 hrs by cell-based assay	ki	0.0001	uM
(4S)-2-(6-chloro-3-pyridinyl)-7-azabicyclo[2.2.1]heptane	146639: Binding affinity towards nicotinic acetylcholine receptor alpha4-beta2	ki	0.0001	uM
6-(6-chloro-3-pyridinyl)-8-azabicyclo[3.2.1]octane	276249: Displacement of [3H]epibatidine from human recombinant alpha4beta2 nAChR in HEK293 cells by SPA assay	ki	0.0001	uM
7-(6-chloro-3-pyridinyl)-2-azabicyclo[2.2.1]heptane	276249: Displacement of [3H]epibatidine from human recombinant alpha4beta2 nAChR in HEK293 cells by SPA assay	ki	0.0001	uM
(1R,5S)-7-pyridin-3-yl-3-azabicyclo[3.3.1]non-6-ene	705817: Displacement of [3H]nicotine from human alpha4beta2 nAChR expressed in human SH-EP1 cells	ki	0.0001	uM
3-[[(2S)-azetidin-2-yl]methoxy]-5-[2-(3-fluoro-5-methoxyphenyl)ethynyl]pyridine	1053303: Displacement of [3H]epibatidine from human alpha4beta2 nAChR after 4 hrs by cell-based assay	ki	0.0001	uM
3-[[(2S)-azetidin-2-yl]methoxy]-5-[2-(3-chlorophenyl)ethynyl]pyridine	1053303: Displacement of [3H]epibatidine from human alpha4beta2 nAChR after 4 hrs by cell-based assay	ki	0.0001	uM
3-[[(2S)-azetidin-2-yl]methoxy]-5-[2-(4-fluorophenyl)ethynyl]pyridine	1053303: Displacement of [3H]epibatidine from human alpha4beta2 nAChR after 4 hrs by cell-based assay	ki	0.0001	uM
3-[[(2S)-azetidin-2-yl]methoxy]-5-[2-(3,5-difluorophenyl)ethynyl]pyridine	1053303: Displacement of [3H]epibatidine from human alpha4beta2 nAChR after 4 hrs by cell-based assay	ki	0.0001	uM
3-[[(2S)-azetidin-2-yl]methoxy]-5-[2-(2-fluorophenyl)ethynyl]pyridine	1053303: Displacement of [3H]epibatidine from human alpha4beta2 nAChR after 4 hrs by cell-based assay	ki	0.0001	uM
3-[[(2R)-azetidin-2-yl]methoxy]-5-(2-phenylethynyl)pyridine	1053303: Displacement of [3H]epibatidine from human alpha4beta2 nAChR after 4 hrs by cell-based assay	ki	0.0001	uM
6-methyl-5-oxa-7,13-diazatetracyclo[9.3.1.02,10.04,8]pentadeca-2,4(8),6,9-tetraene	254476: Binding affinity for human Nicotinic acetylcholine receptor alpha4-beta2 expressed in HEK 293 cells using [3H]nicotine	ki	0.0001	uM
7-methyl-5-oxa-6,13-diazatetracyclo[9.3.1.02,10.04,8]pentadeca-2(10),3,6,8-tetraene	254476: Binding affinity for human Nicotinic acetylcholine receptor alpha4-beta2 expressed in HEK 293 cells using [3H]nicotine	ki	0.0001	uM
5-bromo-7,11-diazatricyclo[7.3.1.02,7]trideca-2,4-dien-6-one	246575: Change in membrane potential in K-177 cells expressing acetylcholine central neuronal receptor alpha4-beta2 subunits	ec50	0.0001	uM
5-chloro-7,11-diazatricyclo[7.3.1.02,7]trideca-2,4-dien-6-one	246575: Change in membrane potential in K-177 cells expressing acetylcholine central neuronal receptor alpha4-beta2 subunits	ec50	0.0001	uM
4,5-dichloro-10-azatricyclo[6.3.1.02,7]dodeca-2,4,6-triene	254476: Binding affinity for human Nicotinic acetylcholine receptor alpha4-beta2 expressed in HEK 293 cells using [3H]nicotine	ki	0.0001	uM
6-methyl-5-thia-7,13-diazatetracyclo[9.3.1.02,10.04,8]pentadeca-2,4(8),6,9-tetraene	254476: Binding affinity for human Nicotinic acetylcholine receptor alpha4-beta2 expressed in HEK 293 cells using [3H]nicotine	ki	0.0001	uM
5,7,13-triazatetracyclo[9.3.1.02,10.04,8]pentadeca-2,4(8),5,9-tetraene	254476: Binding affinity for human Nicotinic acetylcholine receptor alpha4-beta2 expressed in HEK 293 cells using [3H]nicotine	ki	0.0001	uM
3-pyridin-3-yl-3,7-diazabicyclo[3.3.1]nonane	705817: Displacement of [3H]nicotine from human alpha4beta2 nAChR expressed in human SH-EP1 cells	ki	0.0001	uM
7-phenyl-5,7,13-triazatetracyclo[9.3.1.02,10.04,8]pentadeca-2,4(8),5,9-tetraene	254476: Binding affinity for human Nicotinic acetylcholine receptor alpha4-beta2 expressed in HEK 293 cells using [3H]nicotine	ki	0.0001	uM
1-(10-azatricyclo[6.3.1.02,7]dodeca-2(7),3,5-trien-4-yl)ethanone	254476: Binding affinity for human Nicotinic acetylcholine receptor alpha4-beta2 expressed in HEK 293 cells using [3H]nicotine	ki	0.0002	uM
5-(6-chloro-3-pyridinyl)-2-azabicyclo[2.2.1]heptane	276249: Displacement of [3H]epibatidine from human recombinant alpha4beta2 nAChR in HEK293 cells by SPA assay	ki	0.0002	uM
cytisinicline	239394: Binding affinity against nicotinic acetylcholine receptor alpha4-beta2 in human HEK293 cells using [3H]- nicotine as radioligand	ki	0.0002	uM
(1R,3S,5R)-3-[(5-chloro-3-pyridinyl)oxymethyl]-2-azabicyclo[3.1.0]hexane;hydrochloride	1647833: Displacement of [3H]cytisine from human alpha4beta2 nAChR expressed in CHOK1 cell membrane by microbeta scintillation counting method	ki	0.0002	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Acetylcholine	affects binding, affects reaction, decreases reaction, increases reaction, decreases activity (+3 more)	15
Nicotine	increases phosphorylation, increases activity, increases expression, affects binding, increases response to substance (+2 more)	6
Varenicline	affects binding, increases activity	4
Mecamylamine	affects binding, decreases activity, decreases reaction, increases activity, decreases uptake	4
cytisine	increases activity, decreases reaction, affects binding	3
Dihydro-beta-Erythroidine	affects binding, decreases activity, decreases reaction, increases activity, decreases uptake	3
Tubocurarine	affects activity, affects binding, decreases reaction, increases activity, increases reaction (+1 more)	3
tetrabromobisphenol A	affects binding, decreases reaction, increases activity, affects cotreatment	2
imidacloprid	increases activity, affects binding, decreases reaction	2
epibatidine	affects binding, decreases reaction, increases activity	2
Estradiol	affects binding, affects cotreatment, increases activity, increases expression	2
Ethinyl Estradiol	affects binding, affects cotreatment, increases activity, affects activity, increases reaction (+1 more)	2
Flame Retardants	affects binding, decreases reaction, increases activity, affects cotreatment	2
Lobeline	affects binding, decreases activity, decreases reaction, increases phosphorylation	2
Pancuronium	decreases activity, affects binding, decreases reaction, increases activity	2
Physostigmine	affects binding, decreases activity, decreases reaction, affects activity, increases reaction	2
Vecuronium Bromide	affects binding, decreases reaction, increases activity, decreases activity	2
Cyclosporine	increases methylation, decreases expression	2
triptolide	affects binding, decreases reaction, increases activity	1
triphenyl phosphate	decreases reaction, increases activity, affects cotreatment	1
bisphenol A	affects binding, decreases reaction, affects activity	1
subecholine	decreases activity, increases activity, affects binding, decreases reaction	1
decabromobiphenyl ether	affects cotreatment, decreases reaction, increases activity	1
decamethonium	decreases activity, decreases reaction, affects binding	1
2,4,2’,4’-tetrachlorobiphenyl	affects binding, decreases reaction, increases activity, affects cotreatment	1
antimony trioxide	affects cotreatment, decreases reaction, increases activity	1
4-nonylphenol	affects activity, affects binding, decreases reaction	1
celastrol	affects binding, decreases reaction, increases activity	1
methyllycaconitine	decreases reaction, affects binding, decreases activity	1
4-octylphenol	affects binding, decreases reaction, affects activity	1

ChEMBL screening assays

696 unique, capped per target: 567 binding, 127 functional, 1 toxicity, 1 admet

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1669854	Binding	Binding affinity to beta2 nAChR	Synthesis and structure-analgesic activity relationships of a novel series of monospirocyclopiperazinium salts (MSPZ). — Bioorg Med Chem Lett
CHEMBL1022415	Functional	Agonist activity at human alpha4beta2 nAChR expressed in HEK293 cells assessed as intracellular calcium level by FLIPR assay	Complementary three-dimensional quantitative structure-activity relationship modeling of binding affinity and functional potency: a study on alpha4beta2 nicotinic ligands. — J Med Chem
CHEMBL5166939	Toxicity	Inhibition of human recombinant nAChRalpha4/beta2 incubated for 120 mins by radiometric scintillation counting method	Design of a Potent, Selective, and Brain-Penetrant Inhibitor of Wnt-Deactivating Enzyme Notum by Optimization of a Crystallographic Fragment Hit. — J Med Chem

Cellosaurus cell lines

7 cell lines: 4 cancer cell line, 3 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_5I63	K177	Transformed cell line	Female
CVCL_C7NI	MKN1 CHRNB2 KO-1	Cancer cell line	Male
CVCL_C7NJ	MKN1 CHRNB2 KO-2	Cancer cell line	Male
CVCL_D1KG	PrecisION hnAChR alpha4/alpha6/beta2-HEK	Transformed cell line	Female
CVCL_D1KH	PrecisION hnAChR alpha4/beta2-HEK	Transformed cell line	Female
CVCL_SJ01	HAP1 CHRNB2 (-) 1	Cancer cell line	Male
CVCL_SJ02	HAP1 CHRNB2 (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT05657860	PHASE4	COMPLETED	Guanfacine Extended Release for the Reduction of Aggression and Self-injurious Behavior Associated With Prader-Willi Syndrome
NCT05744479	PHASE4	RECRUITING	Metformin for Antipsychotic-induced Weight Gain in Adults With Intellectual Disability
NCT06107829	PHASE4	WITHDRAWN	Valbenazine Treatment of Tardive Dyskinesia in Adults With Intellectual/Developmental Disabilities
NCT06997198	PHASE4	NOT_YET_RECRUITING	Deutetrabenazine Treatment for Tardive Dyskinesia in Intellectual/Developmental Disabilities
NCT02270736	PHASE3	COMPLETED	Clinical Study to Investigate the Efficacy and Safety of NT 201 Compared to Placebo in the Treatment of Chronic Troublesome Drooling Associated With Neurological Disorders and/or Intellectual Disability
NCT02304302	PHASE2	COMPLETED	Down Syndrome Memantine Follow-up Study
NCT03862950	PHASE2	COMPLETED	A Trial of Metformin in Individuals With Fragile X Syndrome (Met)
NCT04529226	PHASE2	UNKNOWN	Study to Compare Clozapine vs Treatment as Usual in People With Intellectual Disability & Treatment-resistant Psychosis
NCT04821856	PHASE2	COMPLETED	Evaluation of the Effectiveness of Cannabidiol in Treating Severe Behavioural Problems in Children and Adolescents With Intellectual Disability
NCT01119144	PHASE2	UNKNOWN	Polycaprolactone / Tricalcium Phosphate (PCL/TCP) v Titanium Orbital Implant : Randomised Trial
NCT05273320	PHASE1	COMPLETED	Clinical Trial of Nabilone for Aggression in Adults With Intellectual and Developmental Disabilities
NCT05301361	PHASE1	ENROLLING_BY_INVITATION	Sensitivity of the NIH Toolbox to Stimulant Treatment in Intellectual Disabilities
NCT06016764	PHASE1	COMPLETED	Use of MRI and cTBS for Catatonia in Autism
NCT06586827	PHASE1	COMPLETED	Impact of Competency-Based Training and Technical Assistance Employment Outcomes of Individuals With ID/DD
NCT07531940	PHASE1	NOT_YET_RECRUITING	Escalating Doses of Memantine in Down Syndrome (MEDS-123)
NCT03479476	PHASE2/PHASE3	COMPLETED	A Trial of Metformin in Individuals With Fragile X Syndrome
NCT02616796	PHASE1/PHASE2	COMPLETED	Effects of Social Gaze Training on Brain and Behavior in Fragile X Syndrome
NCT06860672	EARLY_PHASE1	RECRUITING	Clinical Trial of the Dual Vector Base Editor for the Treatment of the CHD3-R1025W Mutation
NCT00597948	Not specified	COMPLETED	Healthy Lifestyles for People With Intellectual Disabilities
NCT01087320	Not specified	RECRUITING	Genome Medical Sequencing for Gene Discovery
NCT01652963	Not specified	UNKNOWN	Picture-based Computerised Assessment and Training of Cognitive Behaviour Therapy Skills
NCT01695395	Not specified	COMPLETED	Mental Health Care Provision for Adults With Intellectual Disability and a Mental Disorder
NCT01867554	Not specified	COMPLETED	Research and Characterization of New Genes Involved in Intellectual Disability
NCT01915381	Not specified	COMPLETED	Improving Adherence Healthy Lifestyle With a Smartphone Application Based on Adults With Intellectual Disabilities
NCT01988623	Not specified	COMPLETED	Pivotal Response Treatment for Individuals With Intellectual Disabilities
NCT02099773	Not specified	COMPLETED	Support Staff-client Interactions With Augmentative and Alternative Communication
NCT02136849	Not specified	COMPLETED	Inter-regional Project of the Great Western Exploration Approach for Exome Molecular Causes Severe Intellectual Disability Isolated or Syndromic
NCT02225041	Not specified	COMPLETED	Sedation Strategy and Cognitive Outcome After Critical Illness in Early Childhood
NCT02414438	Not specified	COMPLETED	Establishing the Clinical Utility of First StepDx PLUS and NextStepDx PLUS Study
NCT02451761	Not specified	COMPLETED	Apparently Balanced Chromosomal Translocation/ Next-generation Sequencing/ Intellectual Disability
NCT02461420	Not specified	ACTIVE_NOT_RECRUITING	Mapping the Genotype, Phenotype, and Natural History of Phelan-McDermid Syndrome
NCT02461459	Not specified	ACTIVE_NOT_RECRUITING	Autism Spectrum Disorder (ASD) and Intellectual Disability (ID) Determinants in Tuberous Sclerosis Complex (TSC)
NCT02486081	Not specified	COMPLETED	Development and Application-Smart Football for Movement Evaluation and Training in the Special Education Population
NCT02504502	Not specified	COMPLETED	Enhancing Genomic Laboratory Reports to Enhance Communication and Empower Patients
NCT02513277	Not specified	COMPLETED	Diabetes Screening & Prevention for People With Learning (Intellectual) Disabilities:STOP Diabetes Study
NCT02561754	Not specified	COMPLETED	Weight Management for Adolescents With IDD
NCT02591446	Not specified	COMPLETED	Transcranial Magnetic Stimulation Studies in Autism Spectrum Disorders
NCT02714868	Not specified	COMPLETED	Evaluation of Project TEAM (Teens Making Environmental and Activity Modifications)
NCT02721394	Not specified	UNKNOWN	FCT With Young Children With ID in the UK: A Feasibility Project V.1
NCT02746614	Not specified	COMPLETED	Psychomotor Therapy Effects in Adaptive Behavior and Motor Proficiency in Intellectual Disability