CHRNA2

Summary

CHRNA2 (cholinergic receptor nicotinic alpha 2 subunit, HGNC:1956) is a protein-coding gene on chromosome 8p21.2, encoding Neuronal acetylcholine receptor subunit alpha-2 (Q15822). 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….

Nicotinic acetylcholine receptors (nAChRs) are ligand-gated ion channels formed by a pentameric arrangement of alpha and beta subunits to create distinct muscle and neuronal receptors. Neuronal receptors are found throughout the peripheral and central nervous system where they are involved in fast synaptic transmission. This gene encodes an alpha subunit that is widely expressed in the brain. The proposed structure for nAChR subunits 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. Mutations in this gene cause autosomal dominant nocturnal frontal lobe epilepsy type 4. Single nucleotide polymorphisms (SNPs) in this gene have been associated with nicotine dependence.

Source: NCBI Gene 1135 — RefSeq curated summary.

At a glance

• Gene–disease (curated): autosomal dominant nocturnal frontal lobe epilepsy 4 (Strong, GenCC) — +3 more curated relationships
• GWAS associations: 10
• Clinical variants (ClinVar): 853 total — 2 pathogenic, 2 likely-pathogenic
• Phenotypes (HPO): 30
• Druggable target: yes — 4 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_000742

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:1956
Approved symbol	CHRNA2
Name	cholinergic receptor nicotinic alpha 2 subunit
Location	8p21.2
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000120903
Ensembl biotype	protein_coding
OMIM	118502
Entrez	1135

Gene structure

Transcript identifiers

Ensembl transcripts: 13 — 7 protein_coding, 2 retained_intron, 2 protein_coding_CDS_not_defined, 2 nonsense_mediated_decay

ENST00000240132, ENST00000407991, ENST00000518712, ENST00000520208, ENST00000520600, ENST00000520650, ENST00000520933, ENST00000521921, ENST00000522008, ENST00000523695, ENST00000524096, ENST00000637241, ENST00000637361

RefSeq mRNA: 6 — MANE Select: NM_000742 NM_000742, NM_001282455, NM_001347705, NM_001347706, NM_001347707, NM_001347708

CCDS: CCDS6059, CCDS64856

Canonical transcript exons

ENST00000407991 — 7 exons

Exon	Start	End
ENSE00000818650	27469761	27469981
ENSE00001550811	27459756	27461754
ENSE00003526614	27467229	27467338
ENSE00003576758	27469335	27469379
ENSE00003595875	27470986	27471194
ENSE00003657680	27462979	27463993
ENSE00003795847	27478824	27479261

Expression profiles

Bgee: expression breadth ubiquitous, 143 present calls, max score 84.38.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.4308 / max 195.5315, expressed in 82 samples.

FANTOM5 promoters (9 alternative TSS)

Promoter ID	TPM avg	Samples expressed
92454	0.1943	60
92451	0.0910	21
92453	0.0701	30
92450	0.0217	7
92452	0.0188	7
92447	0.0126	4
92449	0.0103	3
92448	0.0070	3
92446	0.0050	3

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
cervix squamous epithelium	UBERON:0006922	84.38	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	82.27	gold quality
gingival epithelium	UBERON:0001949	78.73	gold quality
endometrium epithelium	UBERON:0004811	77.11	gold quality
vastus lateralis	UBERON:0001379	76.83	gold quality
quadriceps femoris	UBERON:0001377	76.20	gold quality
triceps brachii	UBERON:0001509	75.45	gold quality
gluteal muscle	UBERON:0002000	75.32	silver quality
lateral nuclear group of thalamus	UBERON:0002736	75.32	gold quality
squamous epithelium	UBERON:0006914	75.08	gold quality
diaphragm	UBERON:0001103	74.97	gold quality
gingiva	UBERON:0001828	74.78	gold quality
germinal epithelium of ovary	UBERON:0001304	74.15	gold quality
secondary oocyte	CL:0000655	74.04	silver quality
myocardium	UBERON:0002349	73.44	gold quality
epithelial cell of pancreas	CL:0000083	73.24	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	73.19	gold quality
prostate gland	UBERON:0002367	73.17	gold quality
superficial temporal artery	UBERON:0001614	72.21	gold quality
frontal pole	UBERON:0002795	72.04	gold quality
epithelium of esophagus	UBERON:0001976	71.92	gold quality
epithelium of nasopharynx	UBERON:0001951	71.84	gold quality
dorsal plus ventral thalamus	UBERON:0001897	71.81	silver quality
paraflocculus	UBERON:0005351	71.81	gold quality
trachea	UBERON:0003126	71.55	gold quality
prefrontal cortex	UBERON:0000451	71.54	gold quality
middle frontal gyrus	UBERON:0002702	71.50	gold quality
saphenous vein	UBERON:0007318	71.30	gold quality
esophagus squamous epithelium	UBERON:0006920	71.15	gold quality
trabecular bone tissue	UBERON:0002483	71.13	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	2.11

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): FOS, NKX2-1, POU3F1, SOX10, SP1

miRNA regulators (miRDB)

66 targeting CHRNA2, 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-1193	100.00	65.93	529
HSA-MIR-4476	100.00	68.18	2030
HSA-MIR-6876-5P	100.00	67.68	2126
HSA-MIR-4533	100.00	69.48	2758
HSA-MIR-4267	99.96	66.53	2368
HSA-MIR-23A-3P	99.95	74.24	3163
HSA-MIR-23B-3P	99.95	74.24	3163
HSA-MIR-23C	99.95	73.92	3192
HSA-MIR-22-3P	99.93	68.13	917
HSA-MIR-515-5P	99.92	69.82	2343
HSA-MIR-519E-5P	99.92	69.62	2358
HSA-MIR-4753-3P	99.90	71.03	3786
HSA-MIR-6783-3P	99.89	67.92	2059
HSA-MIR-1343-3P	99.89	66.78	1815
HSA-MIR-4731-5P	99.89	67.23	2537
HSA-MIR-7845-5P	99.88	64.88	771
HSA-MIR-4668-5P	99.79	70.58	3782
HSA-MIR-4306	99.72	70.50	3630
HSA-MIR-149-3P	99.72	68.22	3963
HSA-MIR-1827	99.63	68.57	3265
HSA-MIR-7106-5P	99.53	67.47	3574
HSA-MIR-4441	99.49	66.56	3216
HSA-MIR-4316	99.37	65.75	1360
HSA-MIR-185-5P	99.35	68.60	2497
HSA-MIR-4644	99.35	69.12	2514
HSA-MIR-6731-5P	99.28	67.42	2375
HSA-MIR-8085	99.28	67.56	2362
HSA-MIR-4426	99.17	66.74	1949
HSA-MIR-6852-5P	99.17	66.69	2073
HSA-MIR-6791-5P	99.16	65.92	1844

Literature-anchored findings (GeneRIF, showing 19)

• How mutations in the nAChRs can cause autosomal dominant nocturnal frontal lobe epilepsy (PMID:12121305)
• A new CHRNA2 mutation markedly increases the receptor sensitivity to acetylcholine, indicating that the nicotinic alpha 2 subunit alteration is the underlying cause. (PMID:16826524)
• From a panel of 59 single-nucleotide polymorphisms (SNPs) located on 11 candidate genes, we identify four SNPs (one each on CHRNA5 and CHRNA2 and two on CHAT) that appear to have pharmacogenetic relevance in smokin cessation therapy. (PMID:18165968)
• data demonstrate the rarity of the identified CHRNA2 mutations in nocturnal frontal lobe epilepsy patients, supporting the recently reported hypothesis of a restricted role for this gene in the disease (PMID:18226955)
• The CHRNA2 rs2043063 SNP might be a risk factor for overweight/obesity in Koreans (PMID:18588430)
• Results suggest that neither CHRNA4 nor CHRNB2 plays a major role in Japanese methamphetamine-use disorder. (PMID:18991851)
• Pleiotropic functional effects of the first epilepsy-associated mutation in the human CHRNA2 gene (PMID:19383498)
• mutations of CHRNB2 and CHRNA2 genes may be rare in Chinese autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE) population. (PMID:21287502)
• Level of cigarettes per day during adolescence and young adulthood is associated with CHRNB3A6, CHRNA5A3B4, and CHRNA2 (PMID:23943838)
• findings indicate that both CHRNA2 and CHRNA6 play a significant role in the etiology of ND in AA and EA smokers (PMID:24253422)
• Results indicate that the CHRNA2 signal peptide mutation T22I modulates the function of both alpha2beta2- and alpha2beta4-nAChR and decreases sensitivities to nicotine and acetylcholine, and quite possibly increasing susceptibility to nicotine dependence (PMID:24467848)
• Results show that D478E variation in nAChR alpha2 subunit increases the peak current responses of both alpha2beta2- and alpha2beta4-nAChRs; but the D478N variation in nAChR alpha2 subunit only increases the peak current responses of alpha2beta2-nAChRs (PMID:24950454)
• The rare variants in CHRNA2 were significantly associated with smoking status. (PMID:25450229)
• CHRNA2 mutations play a causative role in autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE). (PMID:25770198)
• a heterozygous single-nucleotide substitution in CHRNA2 gene (c.1126 C>T; p. Arg376Trp) in subjects with benign familial infantile seizures (PMID:25847220)
• A crystal structure of a human neuronal CHRNA2 extracellular domain in pentameric assembly has been reported. (PMID:27493220)
• In our analysis, we found one pair of SNPs in CHRNA1 and CHRNA7, plus one pair of SNPs in CHRNA2 and CHRNA3 reached corrected significance in tests for GxG interaction. Our study suggested evidence of interactions between CHRNs in controlling the risk of NSCL/P. (PMID:29688589)
• These results reveal a beige-selective immune-adipose interaction mediated through CHRNA2 and identify a novel function of nicotinic acetylcholine receptors in energy metabolism. (PMID:29785025)
• The index variant (rs56372821) is a strong expression quantitative trait locus for CHRNA2; analyses of the genetically regulated gene expression identified a significant association of CHRNA2 expression with cannabis use disorder (CUD) in brain tissue. At the polygenic level, analyses revealed a significant decrease in the risk of CUD with increased load of variants associated with cognitive performance. (PMID:31209380)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	chrna2a	ENSDARG00000006602
danio_rerio	chrna2b	ENSDARG00000057025
mus_musculus	Chrna2	ENSMUSG00000022041
rattus_norvegicus	Chrna2	ENSRNOG00000017424

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), 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), CHRNA7 (ENSG00000175344), HTR3C (ENSG00000178084), GABRG3 (ENSG00000182256), GABRR3 (ENSG00000183185), HTR3E (ENSG00000186038), HTR3D (ENSG00000186090)

Protein

Protein identifiers

Neuronal acetylcholine receptor subunit alpha-2 — Q15822 (reviewed: Q15822)

Alternative names: Nicotinic acetylcholine receptor subunit alpha-2

All UniProt accessions (8): A0A0X1KG79, A0A1B0GVX5, E5RGP6, E5RGT4, E5RHQ4, E5RJ54, E5RK67, Q15822

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. CHRNA2 forms heteropentameric neuronal acetylcholine receptors with CHRNB2 and CHRNB4 and plays a role in nicotine dependence.

Subunit / interactions. Neuronal AChR is composed of two different types of subunits: alpha and non-alpha (beta). CHRNA2/alpha-2 subunit can be combined to CHRNB2/beta-2 or CHRNB4/beta-4 to give rise to functional receptors. Both CHRNA2:CHRNB2 and CHRNA2:CHRNB4 nAChR complexes are heteropentamers with two subtypes: LS (low agonist sensitivity) with a (CHRNA2)3:(CHRNB2/4)2 and HS (high agonist sensitivity) with a (CHRNA2)2:(CHRNB2/4)3 stoichiometries; the subtypes differ in their subunit binding interfaces which are involved in ligand binding.

Subcellular location. Synaptic cell membrane. Cell membrane.

Disease relevance. Epilepsy, nocturnal frontal lobe, 4 (ENFL4) [MIM:610353] An autosomal dominant focal epilepsy characterized by nocturnal seizures associated with fear sensation, tongue movements, and nocturnal wandering, closely resembling nightmares and sleep walking. The disease is caused by variants affecting the gene represented in this entry. Seizures, benign familial infantile, 6 (BFIS6) [MIM:610353] A form of benign familial infantile epilepsy, a neurologic disorder characterized by afebrile seizures occurring in clusters during the first year of life, without neurologic sequelae. BFIS6 inheritance is autosomal dominant. The disease may be caused by variants affecting the gene represented in this entry.

Similarity. Belongs to the ligand-gated ion channel (TC 1.A.9) family. Acetylcholine receptor (TC 1.A.9.1) subfamily. Alpha-2/CHRNA2 sub-subfamily.

Isoforms (2)

UniProt ID	Names	Canonical?
Q15822-1	1	yes
Q15822-2	2

RefSeq proteins (6): NP_000733, NP_001269384, NP_001334634, NP_001334635, NP_001334636, NP_001334637 (=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 (44 total): strand 14, turn 7, sequence variant 4, transmembrane region 4, glycosylation site 3, disulfide bond 2, mutagenesis site 2, topological domain 2, helix 2, signal peptide 1, chain 1, splice variant 1, region of interest 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
5FJV	X-RAY DIFFRACTION	3.2

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q15822-F1	77.88	0.50

Functional residue map

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

Disulfide bonds (2): 183–197, 247–248

Glycosylation sites (3): 129, 235, 79

Mutagenesis-validated functional residues (2):

Position	Phenotype
115	changes ligand activation kinetics in a alpha-2(+):alpha-2(-) subunit interface (in ls nachr subtype).
225	decreases ligand activation in ls nachr subtype; no effect in hs nachr subtype.

Function

Pathways and Gene Ontology

Reactome pathways

8 pathways

ID	Pathway
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: 191 (showing top): GOBP_MEMBRANE_DEPOLARIZATION, GOBP_RESPONSE_TO_NITROGEN_COMPOUND, MODULE_328, MODULE_64, GOBP_SYNAPTIC_TRANSMISSION_CHOLINERGIC, CHX10_01, GOBP_CELLULAR_RESPONSE_TO_OXYGEN_CONTAINING_COMPOUND, GOBP_CELL_CELL_SIGNALING, GOBP_REGULATION_OF_SYNAPTIC_PLASTICITY, chr8p21, GOBP_REGULATION_OF_POSTSYNAPTIC_MEMBRANE_POTENTIAL, WTGAAAT_UNKNOWN, KEGG_NEUROACTIVE_LIGAND_RECEPTOR_INTERACTION, MODULE_99, GOBP_RESPONSE_TO_OXYGEN_CONTAINING_COMPOUND

GO Biological Process (15): monoatomic ion transport (GO:0006811), signal transduction (GO:0007165), synaptic transmission, cholinergic (GO:0007271), neuromuscular synaptic transmission (GO:0007274), monoatomic ion transmembrane transport (GO:0034220), response to nicotine (GO:0035094), regulation of synaptic plasticity (GO:0048167), membrane depolarization (GO:0051899), cellular response to nicotine (GO:0071316), acetylcholine receptor signaling pathway (GO:0095500), modulation of inhibitory postsynaptic potential (GO:0098828), presynaptic modulation of chemical synaptic transmission (GO:0099171), regulation of postsynaptic membrane potential (GO:0060078), excitatory postsynaptic potential (GO:0060079), response to acetylcholine (GO:1905144)

GO Molecular Function (7): acetylcholine receptor activity (GO:0015464), acetylcholine-gated monoatomic cation-selective channel activity (GO:0022848), quaternary ammonium group binding (GO:0050997), heterocyclic compound binding (GO:1901363), transmembrane signaling receptor activity (GO:0004888), monoatomic ion channel activity (GO:0005216), extracellular ligand-gated monoatomic ion channel activity (GO:0005230)

GO Cellular Component (15): nucleoplasm (GO:0005654), plasma membrane (GO:0005886), acetylcholine-gated channel complex (GO:0005892), membrane (GO:0016020), cation channel complex (GO:0034703), neuron projection (GO:0043005), intercellular bridge (GO:0045171), synapse (GO:0045202), postsynaptic membrane (GO:0045211), presynapse (GO:0098793), neurotransmitter receptor complex (GO:0098878), neuron projection cytoplasm (GO:0120111), protein-containing complex (GO:0032991), cell periphery (GO:0071944), synaptic membrane (GO:0097060)

Reactome top-level categories

Rollup of top-6 pathways:

Category	Pathways
Acetylcholine binding and downstream events	2
Postsynaptic nicotinic acetylcholine receptors	1
Presynaptic nicotinic acetylcholine receptors	1
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
cellular anatomical structure	5
regulation of membrane potential	3
chemical synaptic transmission	2
modulation of chemical synaptic transmission	2
postsynaptic neurotransmitter receptor activity	2
small molecule binding	2
monoatomic ion channel complex	2
plasma membrane signaling receptor complex	2
synapse	2
transport	1
cell communication	1
cellular process	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
monoatomic ion transport	1
transmembrane transport	1
response to chemical	1
regulation of biological quality	1
response to nicotine	1
cellular response to chemical stimulus	1
acetylcholine receptor activity	1
postsynaptic signal transduction	1
cellular response to acetylcholine	1
regulation of signal transduction	1
regulation of nervous system process	1
inhibitory postsynaptic potential	1
presynapse	1
regulation of postsynaptic membrane potential	1
chemical synaptic transmission, postsynaptic	1
response to nitrogen compound	1
response to oxygen-containing compound	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
transmitter-gated monoatomic ion channel activity involved in regulation of postsynaptic membrane potential	1
signaling receptor activity	1
monoatomic ion transmembrane transporter activity	1

Protein interactions and networks

STRING

982 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CHRNA2	GABBR2	O75899	768
CHRNA2	PNOC	Q13519	757
CHRNA2	CHRM2	P08172	684
CHRNA2	KCNT1	Q5JUK3	669
CHRNA2	SLC17A6	Q9P2U8	631
CHRNA2	NAT1	P18440	609
CHRNA2	IGBP1	P78318	602
CHRNA2	DEPDC5	O75140	580
CHRNA2	CHRM1	P11229	579
CHRNA2	SLC17A7	Q9P2U7	574
CHRNA2	DRD2	P14416	574
CHRNA2	PPP3CC	P48454	574
CHRNA2	TAS2R38	P59533	560
CHRNA2	NTRK2	Q16620	559
CHRNA2	DRD1	P21728	526

IntAct

0 interactions, top by confidence:

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

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	2
Likely pathogenic	2
Uncertain significance	446
Likely benign	240
Benign	61

Top pathogenic / likely-pathogenic (4)

Variant ID	HGVS	Classification
17504	NM_000742.4(CHRNA2):c.836T>A (p.Ile279Asn)	Pathogenic
522582	NM_000742.4(CHRNA2):c.889A>T (p.Ile297Phe)	Pathogenic
1299110	NM_000742.4(CHRNA2):c.1293dup (p.Ser432fs)	Likely pathogenic
4277698	NM_000742.4(CHRNA2):c.487G>A (p.Ala163Thr)	Likely pathogenic

SpliceAI

1068 predictions. Top by Δscore:

Variant	Effect	Δscore
8:27467223:T:TA	donor_gain	1.0000
8:27467227:A:AC	donor_gain	1.0000
8:27467228:C:CC	donor_gain	1.0000
8:27469386:C:CT	acceptor_gain	1.0000
8:27469386:C:T	acceptor_gain	1.0000
8:27469387:A:T	acceptor_gain	1.0000
8:27469729:T:TA	donor_gain	1.0000
8:27461753:ACC:A	acceptor_loss	0.9900
8:27461755:C:G	acceptor_loss	0.9900
8:27461756:T:A	acceptor_loss	0.9900
8:27463939:C:CT	acceptor_gain	0.9900
8:27463939:C:T	acceptor_gain	0.9900
8:27463994:C:CC	acceptor_gain	0.9900
8:27467223:TCCTA:T	donor_loss	0.9900
8:27467224:CCTA:C	donor_loss	0.9900
8:27467225:CTAC:C	donor_loss	0.9900
8:27467226:TAC:T	donor_loss	0.9900
8:27467227:ACTTG:A	donor_loss	0.9900
8:27467334:CACTC:C	acceptor_gain	0.9900
8:27467336:CTC:C	acceptor_gain	0.9900
8:27467337:TCC:T	acceptor_loss	0.9900
8:27467339:CTGT:C	acceptor_loss	0.9900
8:27467340:T:G	acceptor_loss	0.9900
8:27469329:CCTCA:C	donor_loss	0.9900
8:27469330:CTCAC:C	donor_loss	0.9900
8:27469331:TCA:T	donor_loss	0.9900
8:27469332:CACC:C	donor_loss	0.9900
8:27469333:A:AG	donor_loss	0.9900
8:27469334:C:CT	donor_loss	0.9900
8:27469380:C:CC	acceptor_gain	0.9900

AlphaMissense

3457 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
8:27463628:A:G	L272P	1.000
8:27463750:C:A	W231C	1.000
8:27463750:C:G	W231C	1.000
8:27463751:C:G	W231S	1.000
8:27463752:A:G	W231R	1.000
8:27463752:A:T	W231R	1.000
8:27463852:G:C	C197W	1.000
8:27463853:C:G	C197S	1.000
8:27463853:C:T	C197Y	1.000
8:27463854:A:G	C197R	1.000
8:27463854:A:T	C197S	1.000
8:27463871:G:T	P191H	1.000
8:27463874:A:C	F190C	1.000
8:27463894:G:C	C183W	1.000
8:27463895:C:A	C183F	1.000
8:27463895:C:G	C183S	1.000
8:27463895:C:T	C183Y	1.000
8:27463896:A:G	C183R	1.000
8:27463896:A:T	C183S	1.000
8:27463900:G:C	S181R	1.000
8:27463900:G:T	S181R	1.000
8:27463902:T:G	S181R	1.000
8:27467257:A:G	W141R	1.000
8:27467257:A:T	W141R	1.000
8:27467333:C:A	W115C	1.000
8:27467333:C:G	W115C	1.000
8:27467335:A:G	W115R	1.000
8:27467335:A:T	W115R	1.000
8:27463448:A:G	L332P	0.999
8:27463487:G:C	P319R	0.999

dbSNP variants (sampled 300 via entrez): RS1000347952 (8:27460487 G>A), RS1000413072 (8:27460027 C>T), RS1000477519 (8:27465511 A>C), RS1000561126 (8:27475345 C>G), RS1000645912 (8:27465249 T>G), RS1000667967 (8:27470219 G>A), RS1000779957 (8:27464898 G>C), RS1000782647 (8:27460255 G>A), RS1000796855 (8:27476516 G>A), RS1001028323 (8:27470630 G>A), RS1001152179 (8:27479133 G>A,C), RS1001233758 (8:27476169 C>A,T), RS1001279 (8:27466026 A>G), RS1001466650 (8:27468019 C>A,G), RS1001470243 (8:27473503 C>T)

Disease associations

OMIM: gene MIM:118502 | disease phenotypes: MIM:600513, MIM:610353, MIM:601764

GenCC curated gene-disease

Disease	Classification	Inheritance
autosomal dominant nocturnal frontal lobe epilepsy 4	Strong	Autosomal dominant
autosomal dominant nocturnal frontal lobe epilepsy	Supportive	Autosomal dominant

ClinGen Gene-Disease Validity (2)

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

Disease	Classification	Inheritance
familial sleep-related hypermotor epilepsy	Limited	AD
benign familial infantile epilepsy	Disputed	AD

Mondo (7): familial sleep-related hypermotor epilepsy (MONDO:0000030), autosomal dominant nocturnal frontal lobe epilepsy 4 (MONDO:0012474), myoclonic epilepsy (MONDO:0100577), benign familial infantile epilepsy (MONDO:0017615), intellectual disability (MONDO:0001071), epilepsy (MONDO:0005027), (MONDO:0020300)

Orphanet (3): Sleep-related hypermotor epilepsy (Orphanet:98784), Self-limited infantile epilepsy (Orphanet:306), NON RARE IN EUROPE: Unexplained intellectual disability (Orphanet:319658)

HPO phenotypes

30 total (30 of 30 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:0001256	Mild intellectual disability
HP:0001289	Confusion
HP:0001332	Dystonia
HP:0001345	Psychotic mentation
HP:0002069	Bilateral tonic-clonic seizure
HP:0002268	Paroxysmal dystonia
HP:0002883	Hyperventilation
HP:0003621	Juvenile onset
HP:0003829	Typified by incomplete penetrance
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:0011463	Childhood onset
HP:0012759	Neurodevelopmental abnormality
HP:0025144	Shivering
HP:0025235	NREM parasomnia
HP:0025236	Sleep walking
HP:0025710	Late young adult onset
HP:0031535	Increased theta frequency activity in EEG
HP:0031589	Suicidal ideation
HP:0031951	Nocturnal seizures
HP:0100543	Cognitive impairment

GWAS associations

10 associations (top):

Study	Trait	p-value
GCST002951_12	Response to zileuton treatment in asthma (FEV1 change interaction)	8.000000e-06
GCST004521_193	Autism spectrum disorder or schizophrenia	3.000000e-09
GCST004748_131	Lung cancer	2.000000e-08
GCST006803_90	Schizophrenia	8.000000e-12
GCST007320_85	Alzheimer’s disease or family history of Alzheimer’s disease	3.000000e-09
GCST008414_1	Cannabis use disorder	9.000000e-12
GCST011179_3	Cannabis use disorder	3.000000e-09
GCST011179_4	Cannabis use disorder	6.000000e-09
GCST011701_1	Smoking status (current vs mixed)	1.000000e-10
GCST011704_8	Smoking status (current vs never)	1.000000e-10

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0005921	FEV change measurement
EFO:0009268	family history of Alzheimer’s disease
EFO:0006527	smoking status measurement

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
C579932	Autosomal Dominant Nocturnal Frontal Lobe Epilepsy (supp.)
C563679	Epilepsy, Nocturnal Frontal Lobe, Type 4 (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (4): CHEMBL2109230 (PROTEIN COMPLEX), CHEMBL2109236 (PROTEIN COMPLEX), CHEMBL4524133 (PROTEIN COMPLEX GROUP), CHEMBL4804182 (PROTEIN COMPLEX GROUP)

Molecules with ChEMBL bioactivity

4 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 196,528 (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
CHEMBL3	NICOTINE	4	184,969
CHEMBL111659	ALTINICLINE	2	129

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

PharmGKB variants

1 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs2472553	CHRNA2		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 (3 total), top 3:

Ligand	Action	Affinity	Parameter
[125I]epibatidine	Full agonist	10.38	pKd
[3H]epibatidine	Full agonist	10.38	pKd
CP-601927	Partial agonist	8.92	pKi

Binding affinities (BindingDB)

11 measured of 25 human assays (30 total across all organisms); most potent 11 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
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
(2S,4aR,6aR,7R,9S,10aS,10bR)-9-(acetyloxy)-2-(furan-3-yl)dodecahydro-6a,10b-dimethyl-4,10-dioxo-2H-naphtho-[2,1-c]pyran-7-carboxylic acid methyl ester	EC50	0.3 nM
VARENICLINE	KI	0.48 nM	US-9993465: 2,5-disubstituted-pyridyl nicotinic ligands, and methods of use thereof
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
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
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
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
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
Dihydro-Beta-erythroidine	KI	5090 nM
NSC_123990	KI	8750 nM

ChEMBL bioactivities

41 potent at pChembl≥5 of 52 total, top 38 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
10.06	Ki	0.087	nM	CHEMBL2024096
10.06	Ki	0.087	nM	CHEMBL6007325
10.04	Ki	0.091	nM	EPIBATIDINE
9.32	Ki	0.48	nM	VARENICLINE
9.12	IC50	0.75	nM	CHEMBL429557
8.82	IC50	1.5	nM	CHEMBL411146
8.28	Ki	5.3	nM	CHEMBL2323570
8.28	Ki	5.3	nM	CHEMBL5896203
8.26	Ki	5.5	nM	NICOTINE
8.07	Ki	8.6	nM	CHEMBL2323572
8.07	Ki	8.6	nM	CHEMBL5873522
8.06	Ki	8.7	nM	CHEMBL2323571
8.06	Ki	8.7	nM	CHEMBL5912650
8.02	IC50	9.6	nM	CHEMBL409988
7.92	Ki	12	nM	NICOTINE
7.92	Ki	12	nM	(+/-)NICOTINE
7.89	Ki	13	nM	CHEMBL2323569
7.89	Ki	13	nM	CHEMBL5773270
7.80	Ki	16	nM	CHEMBL2323566
7.80	Ki	16	nM	CHEMBL5751653
7.51	Ki	31	nM	CHEMBL421553
7.16	Ki	70	nM	NICOTINE
7.03	Ki	94	nM	VARENICLINE
6.99	Ki	103	nM	NICOTINE
6.96	Ki	110	nM	NICOTINE
6.89	Ki	130	nM	CHEMBL2323568
6.89	Ki	130	nM	CHEMBL5813361
6.68	Ki	210	nM	CHEMBL2024096
6.01	Ki	970	nM	CHEMBL2323565
6.01	Ki	970	nM	CHEMBL5751653
5.89	Ki	1300	nM	CHEMBL5575320
5.74	Ki	1820	nM	CHEMBL2203550
5.64	IC50	2300	nM	CHEMBL405936
5.51	IC50	3100	nM	MECAMYLAMINE
5.50	EC50	3200	nM	ALTINICLINE
5.40	IC50	4000	nM	CHEMBL405936
5.29	IC50	5100	nM	CHEMBL335712
5.02	Ki	9600	nM	CHEMBL2323569

PubChem BioAssay actives

17 with measured affinity, of 85 total; 12 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-azabicyclo[2.2.1]heptane	145990: Binding affinity against nicotinic acetylcholine receptor alpha2-beta4 using [3H]epibatidine as radioligand expressed in HEK293 cells or tsA cells	ki	0.0001	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	242180: Inhibitory concentration against Nicotinic acetylcholine receptor alpha2-beta2; Range is 0.3-1.5 nM	ic50	0.0008	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	242180: Inhibitory concentration against Nicotinic acetylcholine receptor alpha2-beta2; Range is 0.3-1.5 nM	ic50	0.0015	uM
Nicotine	712668: Displacement of [3H]epibatidine from alpha2beta2 nAChR after 4 hrs by liquid scintillation counting analysis	ki	0.0055	uM
(3S)-3-[[(2S)-1-[(2S)-4-amino-2-[[(2S)-4-amino-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]-4-methylpentanoyl]pyrrolidine-2-carbonyl]pyrrolidine-2-carbonyl]amino]-3-sulfanylpropanoyl]amino]propanoyl]amino]propanoyl]amino]-4-oxobutanoyl]amino]-4-oxobutanoyl]pyrrolidine-2-carbonyl]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	241630: Inhibitory concentration against Nicotinic acetylcholine receptor alpha2-beta2	ic50	0.0096	uM
6-(6-chloro-3-pyridinyl)-8-azabicyclo[3.2.1]octan-3-ol	145990: Binding affinity against nicotinic acetylcholine receptor alpha2-beta4 using [3H]epibatidine as radioligand expressed in HEK293 cells or tsA cells	ki	0.0310	uM
5-[(1R,2R,5R)-4,4,8-trimethyl-3-azabicyclo[3.3.1]non-7-en-2-yl]quinoline	2093421: Displacement of [3H]-epibatidine from human alpha2beta4 nAChR	ki	1.3000	uM
3-[[(2S)-azetidin-2-yl]methoxy]-5-[(5-chloro-3-pyridinyl)oxymethyl]-1,2-oxazole	712667: Displacement of [3H]epibatidine from alpha2beta4 nAChR after 4 hrs by liquid scintillation counting analysis	ki	1.8200	uM
(16R)-10,25-dimethoxy-15,15,30-trimethyl-7,23-dioxa-30-aza-15-azoniaheptacyclo[22.6.2.23,6.18,12.118,22.027,31.016,34]hexatriaconta-3(36),4,6(35),8(34),9,11,18(33),19,21,24,26,31-dodecaene-9,33-diol	241631: Inhibitory concentration against Nicotinic acetylcholine receptor alpha2-beta4	ic50	2.3000	uM
Mecamylamine	241631: Inhibitory concentration against Nicotinic acetylcholine receptor alpha2-beta4	ic50	3.1000	uM
3-ethynyl-5-[(2S)-1-methylpyrrolidin-2-yl]pyridine	240101: Effective concentration against Nicotinic acetylcholine receptor alpha2-beta4	ec50	3.2000	uM
(1R,16R)-16-methoxy-5-oxa-10-azatetracyclo[8.7.0.01,13.02,7]heptadeca-2(7),13-dien-4-one	241631: Inhibitory concentration against Nicotinic acetylcholine receptor alpha2-beta4	ic50	5.1000	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Acetylcholine	affects response to substance, decreases reaction, affects binding, affects reaction, increases reaction (+2 more)	3
sodium arsenite	affects methylation, increases expression	2
Benzo(a)pyrene	affects methylation, decreases methylation, increases methylation	2
Nicotine	affects response to substance, affects binding, increases activity	2
cytisine	affects binding, increases activity	1
triphenyl phosphate	affects expression	1
crotonyl alcohol	affects binding, decreases reaction, increases reaction, increases transport	1
n-pentanol	affects binding, decreases reaction, increases reaction, increases transport	1
benzo(e)pyrene	decreases methylation	1
isobutyl alcohol	affects binding, affects reaction, increases reaction, increases transport	1
2-butanol	increases transport, affects binding, affects reaction, increases reaction	1
epibatidine	affects binding	1
bisphenol S	increases methylation	1
Resveratrol	affects cotreatment, decreases expression	1
Persistent Organic Pollutants	increases abundance, increases expression	1
1-Propanol	affects binding, increases reaction, increases transport	1
Atrazine	increases expression	1
Barium	affects binding, affects reaction, increases reaction, increases transport, decreases reaction	1
Calcitriol	affects cotreatment, increases expression	1
Carbamazepine	affects response to substance	1
Copper	decreases expression, affects cotreatment	1
Dimethylphenylpiperazinium Iodide	affects binding, increases activity	1
Endosulfan	increases expression	1
Methapyrilene	decreases methylation	1
Pesticides	increases expression, increases abundance	1
Testosterone	increases expression, affects cotreatment	1
Tetrachlorodibenzodioxin	increases expression	1
Valproic Acid	increases methylation	1
Aflatoxin B1	increases methylation	1
2-Propanol	affects binding, increases reaction, increases transport	1

ChEMBL screening assays

40 unique, capped per target: 37 binding, 2 functional, 1 admet

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL2209675	Binding	Displacement of [3H]epibatidine from alpha2beta4 nAChR at 10 uM after 4 hrs by liquid scintillation counting analysis	From α4β2 Nicotinic Ligands to the Discovery of σ1 Receptor Ligands: Pharmacophore Analysis and Rational Design. — ACS Med Chem Lett
CHEMBL750089	Functional	Compound was evaluated for agonist activity against activated human recombinant Nicotinic acetylcholine receptor alpha2-beta4 in Xenopus Oocytes	Conformationally restricted analogues of nicotine and anabasine. — Bioorg Med Chem Lett
CHEMBL4810209	ADMET	Inhibition of neuronal nicotinic receptor (unknown origin) at 0.1 to 1 uM	Discovery of Pemigatinib: A Potent and Selective Fibroblast Growth Factor Receptor (FGFR) Inhibitor. — J Med Chem

Cellosaurus cell lines

1 cell lines: 1 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_YA35	IDG-HEK293T-CHRNA2-V5-OE	Transformed cell line	Female

Clinical trials (associated diseases)

300 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
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
NCT01127165	PHASE4	COMPLETED	Low and High Dose Zonisamide in Children as Monotherapy
NCT01127256	PHASE4	COMPLETED	Comparative Study of Zonisamide and Carbamazepine as an Initial Monotherapy: Efficacy and Safety Evaluation