CHRNA5

Summary

CHRNA5 (cholinergic receptor nicotinic alpha 5 subunit, HGNC:1959) is a protein-coding gene on chromosome 15q25.1, encoding Neuronal acetylcholine receptor subunit alpha-5 (P30532). Component of neuronal acetylcholine receptors (nAChRs) that function as pentameric, ligand-gated cation channels with high calcium permeability among other activities. nAChRs are excitatory neurotrasnmitter receptors formed by a collection of nAChR subunits known to mediate syna….

The protein encoded by this gene is a nicotinic acetylcholine receptor subunit and a member of a superfamily of ligand-gated ion channels that mediate fast signal transmission at synapses. These receptors are thought to be heteropentamers composed of separate but similar subunits. Defects in this gene have been linked to susceptibility to lung cancer type 2 (LNCR2).

Source: NCBI Gene 1138 — RefSeq curated summary.

At a glance

• GWAS associations: 122
• Clinical variants (ClinVar): 60 total
• Druggable target: yes — 2 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_000745

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:1959
Approved symbol	CHRNA5
Name	cholinergic receptor nicotinic alpha 5 subunit
Location	15q25.1
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000169684
Ensembl biotype	protein_coding
OMIM	118505
Entrez	1138

Gene structure

Transcript identifiers

Ensembl transcripts: 5 — 5 protein_coding

ENST00000299565, ENST00000394802, ENST00000559554, ENST00000559576, ENST00000913028

RefSeq mRNA: 7 — MANE Select: NM_000745 NM_000745, NM_001307945, NM_001395171, NM_001395172, NM_001395173, NM_001395174, NM_001395175

CCDS: CCDS10304, CCDS76786

Canonical transcript exons

ENST00000299565 — 6 exons

Exon	Start	End
ENSE00001160313	78588314	78588423
ENSE00001160322	78586645	78586689
ENSE00001206520	78580811	78580962
ENSE00001383400	78565520	78565825
ENSE00001625623	78593092	78595269
ENSE00002153921	78589805	78590636

Expression profiles

Bgee: expression breadth ubiquitous, 172 present calls, max score 83.91.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 7.3239 / max 95.6768, expressed in 1147 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
147918	3.9618	851
147917	2.9160	967
147916	0.3595	216
147919	0.0866	40

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
ventricular zone	UBERON:0003053	83.91	gold quality
ganglionic eminence	UBERON:0004023	83.87	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	81.41	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	80.21	gold quality
cortical plate	UBERON:0005343	79.04	gold quality
islet of Langerhans	UBERON:0000006	77.77	gold quality
secondary oocyte	CL:0000655	77.43	gold quality
gall bladder	UBERON:0002110	75.55	gold quality
rectum	UBERON:0001052	73.58	gold quality
embryo	UBERON:0000922	73.42	gold quality
mucosa of transverse colon	UBERON:0004991	71.71	gold quality
stromal cell of endometrium	CL:0002255	70.20	gold quality
colonic epithelium	UBERON:0000397	69.04	gold quality
endometrium epithelium	UBERON:0004811	69.00	gold quality
pancreas	UBERON:0001264	68.36	gold quality
smooth muscle tissue	UBERON:0001135	68.02	gold quality
muscle layer of sigmoid colon	UBERON:0035805	66.94	gold quality
muscle of leg	UBERON:0001383	66.90	gold quality
gastrocnemius	UBERON:0001388	66.88	gold quality
body of pancreas	UBERON:0001150	65.97	gold quality
calcaneal tendon	UBERON:0003701	65.97	gold quality
transverse colon	UBERON:0001157	64.45	gold quality
esophagus mucosa	UBERON:0002469	63.54	gold quality
duodenum	UBERON:0002114	62.63	gold quality
vermiform appendix	UBERON:0001154	62.62	gold quality
muscle organ	UBERON:0001630	62.60	gold quality
colon	UBERON:0001155	62.52	gold quality
sigmoid colon	UBERON:0001159	62.46	gold quality
large intestine	UBERON:0000059	61.97	gold quality
heart left ventricle	UBERON:0002084	61.88	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	3.66
E-MTAB-6379	no	3.55

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): ASCL1

miRNA regulators (miRDB)

73 targeting CHRNA5, 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-4795-3P	100.00	74.62	4024
HSA-MIR-126-5P	100.00	72.71	3180
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-5692B	100.00	71.32	2622
HSA-MIR-5692C	100.00	71.32	2622
HSA-MIR-656-3P	100.00	72.15	2788
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-4803	99.98	71.99	3117
HSA-MIR-4482-3P	99.98	72.50	3147
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-302C-5P	99.97	72.56	3642
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-1250-3P	99.96	70.04	4038
HSA-MIR-6778-3P	99.96	67.29	2693
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-335-3P	99.93	73.36	4958
HSA-MIR-3671	99.90	73.04	3897
HSA-MIR-944	99.82	70.85	3042
HSA-MIR-4307	99.82	70.45	3374
HSA-MIR-548BC	99.82	70.61	3524
HSA-MIR-548F-3P	99.82	70.59	3540
HSA-MIR-548A-3P	99.76	70.58	3524

Literature-anchored findings (GeneRIF, showing 40)

• 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)
• A common haplotype in the CHRNA5/CHRNA3 gene cluster on chromosome 15 contains alleles, which predispose to nicotine dependence. (PMID:18227835)
• CHRNA5 and CHRNA3 are promising candidate genes in the region of 15q25.1 for lung cancer. (PMID:18385676)
• Functional studies in human brain reveal that the variants associated with alcohol dependence are also associated with altered steady-state levels of CHRNA5 mRNA. (PMID:18414406)
• Environmental tobacco smoke and nicotine up-regulated the levels of alpha5 and alpha7 expression in a time-dependent fashion (PMID:18450646)
• Increased levels of cholinergic receptor nicotinic alpha 5 is associated with squamous cell lung carcinoma (PMID:18559515)
• In the 2,827 long-term smokers examined, common susceptibility and protective haplotypes at the CHRNA5-A3-B4 locus were associated with nicotine dependence severity. (PMID:18618000)
• Correlated SNPs in the cholinergic nicotinic receptor gene cluster CHRNA5-CHRNA3-CHRNB4, in a case-control study of cocaine dependence composed of 504 European-American and 583 African-Americans. (PMID:18759969)
• A non-synonymous coding SNP in CHRNA5 was associated with case status and, in Caucasians, with experiencing a pleasurable rush or buzz during the first cigarette; these sensations were associated highly with current smoking (OR = 8.2, P = 0.0001). (PMID:18783506)
• The CHRNA5-A3 region on chromosome 15q24-25.1 is a risk factor both for nicotine dependence and for lung cancer.( (PMID:18957677)
• the association between the alpha5 subunit nicotinic acetylcholine receptor single nucleotide polymorphism and lung cancer may, in part, be confounded by chronic obstructive pulmonary disease (PMID:18978134)
• CHRNA5 seem to exert no relevant influence on smoking cessation probability in heavy smokers in the general population. (PMID:18996504)
• smokers who carry the CHRNA3 and CHRNA5 variants are expected to be at increased risk for lung cancer compared with smokers who do not carry these alleles. (PMID:19010884)
• Two distinct variant groups in the CHRNA5-CHRNA3-CHRNB4 gene cluster are strongly associated with heavy smoking. The snp rs16969968 alters the coding sequence of these genes. (PMID:19029397)
• The alpha5 and alpha3 subunits play a significant role in both nicotine dependence and alcohol abuse/dependence. (PMID:19132693)
• D398N polymorphism of the CHRNA5 gene was associated with lung adenocarcinoma. (PMID:19223495)
• The CHRNA 3/5 and the HHIP loci make a significant contribution to the risk of COPD. (PMID:19300482)
• Genetic variant in the CHRNA5-CHRNA3-CHRNB4 gene cluster is associated with smoking cessation during pregnancy. (PMID:19429911)
• The CHRNA5-A3-B4 haplotypes are associated with a broad range of nicotine dependence phenotypes, but these associations are not consistently moderated by age at initial smoking. (PMID:19436041)
• Two distinct mechanisms conferring risk for nicotine dependence and lung cancer: altered receptor function caused by a D398N amino acid variant in CHRNA5 and variability in CHRNA5 mRNA expression. (PMID:19443489)
• There was no evidence of association of CHRNA5 rs16969968 with smoking status (p=0.28) or, among daily smokers, of association with cotinine levels (p=0.49). (PMID:19482438)
• Although CHRNA5 polymorphism is rare from Japanese lung cancer, polymorphism status might be correlated with shorter survival. (PMID:19577767)
• Genetic variation at CHRNA5/CHRNA3/CHRNB4 cluster influences blood nicotine level. (PMID:19628476)
• Single Nucleotide Polymorphism in CHRNA5 is associated with non-small cell lung cancer. (PMID:19641473)
• CHRNA5 SNP rs16969968 is the most significant SNP associated with nicotine dependence (PMID:19706762)
• These results indicate that variants within CHRNA3 and among CHRNA5, CHRNA3, and CHRNB4 contribute significantly to the etiology of ND through gene-gene interactions. (PMID:19859904)
• This study suggested that the possibility that the wide individual variability in response, and sequent sensitization to nicotine are due to both a variant Single Nucleotide Polymorphism in rs16969989 and early life stress. (PMID:20381163)
• The data of this study supported the importance of variants in the CHRNA5/A3/B4 gene cluster as mediators of the genetic risk for substance dependence. (PMID:20485328)
• Smoking behavior and COPD are mediators of the association between the single nucleotide polymorphism (SNP) rs1051730 and the risk of lung cancer. (PMID:20564069)
• Genetic variation in CHRNA5-CHRNA3-CHRNB4 nicotinic acetylcholine receptor gene cluster influences cognitive flexibility differently in African Americans and European Americans. (PMID:20631687)
• Data suggest that both CHNA5 Asp398Asn and CHRNA3 rs578776 are associated with smoking. (PMID:20643934)
• The CHRNA3/5 locus was associated with increased smoking intensity and emphysema in individuals with COPD (PMID:20656943)
• This review focuses on the clustered nicotinic acetylcholine receptor genes CHRNalpha5/alpha3/beta4 and evaluates their role in nicotine addiction and lung cancer. (PMID:20685379)
• The enhancer region and the nonsynonymous polymorphism rs16969968 generate three main haplotypes that alter the risk of developing nicotine dependence. (PMID:20700147)
• Study identified four genetic variations in the CHRNA5 promoter region that define three haplotypes affecting activity of the promoter of this gene, thus modulating CHRNA5 transcript levels in normal lung tissue. (PMID:20733116)
• associations of variants in the CHRNA5/A3/B4 cluster with smoking initiation, smoking quantity and smoking cessation (PMID:20808433)
• A variation in the alpha5 subunit of nicotinic acetylcholine receptors increases the risk of nicotine dependence and lung cancer. (PMID:20881005)
• evidence that CHRNA5-CHRNA3-CHRNB4 gene cluster variants,particularly CHRNA5 variant rs16969968, could be associated with cognitive performance possibly mediating in part risk for developing nicotine dependence (PMID:20886544)
• CHRNA5-CHRNA3-CHRNB4 is involved in the transition toward heavy smoking in mid-adulthood and in smoking persistence. (PMID:21168125)
• Single nucleotide polymorphism (SNP) CHRNA5 on chromosome 15 is not associated with Parkinson’s disease risk in the overall anaylsis or after stratifying on smoking status. (PMID:21228559)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	chrna5	ENSDARG00000003420
mus_musculus	Chrna5	ENSMUSG00000035594
rattus_norvegicus	Chrna5	ENSRNOG00000013610

Paralogs (45): GABRA3 (ENSG00000011677), GABRA1 (ENSG00000022355), CHRNA3 (ENSG00000080644), GABRP (ENSG00000094755), CHRNA4 (ENSG00000101204), GLRA2 (ENSG00000101958), GABRE (ENSG00000102287), CHRNE (ENSG00000108556), GABRA4 (ENSG00000109158), GLRB (ENSG00000109738), GABRR2 (ENSG00000111886), GABRG2 (ENSG00000113327), CHRNB4 (ENSG00000117971), CHRNA2 (ENSG00000120903), CHRNA10 (ENSG00000129749), CHRND (ENSG00000135902), CHRNA1 (ENSG00000138435), GLRA3 (ENSG00000145451), GABRA6 (ENSG00000145863), GABRB2 (ENSG00000145864), GLRA1 (ENSG00000145888), GABRR1 (ENSG00000146276), CHRNB3 (ENSG00000147432), CHRNA6 (ENSG00000147434), HTR3B (ENSG00000149305), GABRA2 (ENSG00000151834), CHRNB2 (ENSG00000160716), GABRG1 (ENSG00000163285), GABRB1 (ENSG00000163288), GABRB3 (ENSG00000166206), CHRFAM7A (ENSG00000166664), HTR3A (ENSG00000166736), CHRNB1 (ENSG00000170175), CHRNA9 (ENSG00000174343), CHRNA7 (ENSG00000175344), HTR3C (ENSG00000178084), GABRG3 (ENSG00000182256), GABRR3 (ENSG00000183185), HTR3E (ENSG00000186038), HTR3D (ENSG00000186090)

Protein

Protein identifiers

Neuronal acetylcholine receptor subunit alpha-5 — P30532 (reviewed: P30532)

All UniProt accessions (4): P30532, H0YK34, H0YM98, H7BYM0

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. Has an accessory rather than functional role and is only able to form functional nAChRs when co-assembled with another beta subunit. Participates in pentameric assemblies along with CHRNA3, CHRNA4, CHRNB2 and CHRNB4. Increases receptor sensitivity to acetylcholine and nicotine when associated with CHRNA4 and CHRNB2. Plays a role in nicotine addiction.

Subunit / interactions. Neuronal AChR that forms heteropentamers composed of two different type of subunits: alpha and non-alpha (beta). CHRNA5/alpha-5 subunit is only able to form functional nAChRs when co-assembled with another alpha subunit, can be combined to CHRNA4/alpha-4 or CHRNA3/alpha-3 and CHRNB4/beta-4 or CHRNB2/beta-2 to give rise to functional receptors. Interacts with LYPD6.

Subcellular location. Synaptic cell membrane. Cell membrane.

Activity regulation. Activated by a myriad of ligands such as acetylcholine, cytisine, nicotine, choline and epibatidine.

Polymorphism. Genetic variations in CHRNA5 have been associated with susceptibility to smoking-related behavioral traits and lung cancer, contributing to the smoking quantitative trait locus 3 (SQTL3) [MIM:612052].

Similarity. Belongs to the ligand-gated ion channel (TC 1.A.9) family. Acetylcholine receptor (TC 1.A.9.1) subfamily. Alpha-5/CHRNA5 sub-subfamily.

RefSeq proteins (7): NP_000736, NP_001294874, NP_001382100, NP_001382101, NP_001382102, NP_001382103, NP_001382104 (=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 (20 total): sequence conflict 4, transmembrane region 4, glycosylation site 3, topological domain 3, disulfide bond 2, sequence variant 2, signal peptide 1, chain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P30532-F1	82.04	0.45

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): 170–184, 234–235

Glycosylation sites (3): 183, 229, 155

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: 175 (showing top): GOBP_MEMBRANE_DEPOLARIZATION, GOBP_RESPONSE_TO_NITROGEN_COMPOUND, GOBP_BEHAVIOR, RODRIGUES_THYROID_CARCINOMA_POORLY_DIFFERENTIATED_UP, GOBP_ADULT_BEHAVIOR, GOBP_SYNAPTIC_TRANSMISSION_CHOLINERGIC, GOBP_CELLULAR_RESPONSE_TO_OXYGEN_CONTAINING_COMPOUND, GOBP_CELL_CELL_SIGNALING, PUJANA_CHEK2_PCC_NETWORK, WEI_MYCN_TARGETS_WITH_E_BOX, BROWNE_HCMV_INFECTION_24HR_UP, GOBP_REGULATION_OF_POSTSYNAPTIC_MEMBRANE_POTENTIAL, KEGG_NEUROACTIVE_LIGAND_RECEPTOR_INTERACTION, MODULE_99, GOBP_RESPONSE_TO_OXYGEN_CONTAINING_COMPOUND

GO Biological Process (13): signal transduction (GO:0007165), chemical synaptic transmission (GO:0007268), synaptic transmission, cholinergic (GO:0007271), neuromuscular synaptic transmission (GO:0007274), monoatomic ion transmembrane transport (GO:0034220), response to nicotine (GO:0035094), behavioral response to nicotine (GO:0035095), membrane depolarization (GO:0051899), acetylcholine receptor signaling pathway (GO:0095500), presynaptic modulation of chemical synaptic transmission (GO:0099171), monoatomic ion transport (GO:0006811), regulation of postsynaptic membrane potential (GO:0060078), excitatory postsynaptic potential (GO:0060079)

GO Molecular Function (7): ligand-gated monoatomic ion channel activity (GO:0015276), acetylcholine receptor activity (GO:0015464), acetylcholine-gated monoatomic cation-selective channel activity (GO:0022848), 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 (12): plasma membrane (GO:0005886), acetylcholine-gated channel complex (GO:0005892), cation channel complex (GO:0034703), neuron projection (GO:0043005), synapse (GO:0045202), postsynaptic membrane (GO:0045211), dopaminergic synapse (GO:0098691), presynapse (GO:0098793), neurotransmitter receptor complex (GO:0098878), cholinergic synapse (GO:0098981), membrane (GO:0016020), 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
synapse	4
chemical synaptic transmission	2
regulation of membrane potential	2
postsynaptic neurotransmitter receptor activity	2
monoatomic ion channel complex	2
plasma membrane signaling receptor complex	2
cellular anatomical structure	2
cell communication	1
cellular process	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
anterograde trans-synaptic signaling	1
monoatomic ion transport	1
transmembrane transport	1
response to chemical	1
adult behavior	1
response to nicotine	1
acetylcholine receptor activity	1
postsynaptic signal transduction	1
cellular response to acetylcholine	1
modulation of chemical synaptic transmission	1
presynapse	1
transport	1
regulation of postsynaptic membrane potential	1
chemical synaptic transmission, postsynaptic	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
transmitter-gated monoatomic ion channel activity involved in regulation of postsynaptic membrane potential	1
signaling receptor activity	1
monoatomic ion transmembrane transporter activity	1
channel activity	1
ligand-gated monoatomic ion channel activity	1
binding	1
membrane	1

Protein interactions and networks

STRING

1082 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CHRNA5	PSMA4	P25789	945
CHRNA5	CHRNA3	P32297	855
CHRNA5	CYP2A6	P00190	822
CHRNA5	HYKK	A2RU49	728
CHRNA5	CHRNA4	P43681	695
CHRNA5	IREB2	P48200	664
CHRNA5	GABBR2	O75899	660
CHRNA5	FAM13A	O94988	641
CHRNA5	CHRM2	P08172	628
CHRNA5	SLC6A4	P31645	623
CHRNA5	ANKK1	Q8NFD2	586
CHRNA5	CLPTM1L	Q96KA5	581
CHRNA5	ADH1B	P00325	578
CHRNA5	HHIP	Q96QV1	573
CHRNA5	DRD2	P14416	572

IntAct

66 interactions, top by confidence:

A	B	Type	Score
ENTREP1	WWP2	psi-mi:“MI:0914”(association)	0.850
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
ADGRG5	KLRG2	psi-mi:“MI:0914”(association)	0.530
DEFA1	MANBA	psi-mi:“MI:0914”(association)	0.530
CLGN	NPC1	psi-mi:“MI:0914”(association)	0.530
CHRND	TPST2	psi-mi:“MI:0914”(association)	0.530
CTSG	MANBA	psi-mi:“MI:0914”(association)	0.530
CMA1	MANBA	psi-mi:“MI:0914”(association)	0.530
ADAMTS4	MANBA	psi-mi:“MI:0914”(association)	0.530
CHRNA5	SRPK2	psi-mi:“MI:0217”(phosphorylation reaction)	0.440
PIEZO1	CHRNA5	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
TMEM30A	UPK3BL1	psi-mi:“MI:0914”(association)	0.350
SLAMF1	RTCA	psi-mi:“MI:0914”(association)	0.350
CANX	HLA-A	psi-mi:“MI:0914”(association)	0.350
CHRNB2	TMEM131L	psi-mi:“MI:0914”(association)	0.350
CHRNB4	GPR89A	psi-mi:“MI:0914”(association)	0.350
TMEM30A	TLCD2	psi-mi:“MI:0914”(association)	0.350
TAFAZZIN	MANBA	psi-mi:“MI:0914”(association)	0.350
DEFB135	MANBA	psi-mi:“MI:0914”(association)	0.350
P2RX5	TNPO2	psi-mi:“MI:0914”(association)	0.350
VEGFD	RPSA2	psi-mi:“MI:0914”(association)	0.350
BRICD5	TMEM131L	psi-mi:“MI:0914”(association)	0.350

BioGRID (66): CHRNA5 (Affinity Capture-MS), CHRNA5 (Affinity Capture-MS), CHRNA5 (Affinity Capture-MS), CHRNA5 (Affinity Capture-MS), CHRNA5 (Affinity Capture-MS), CHRNA5 (Affinity Capture-MS), CHRNA5 (Proximity Label-MS), CHRNA5 (Affinity Capture-MS), CHRNA5 (Affinity Capture-MS), CHRNA5 (Affinity Capture-MS), CHRNA5 (Affinity Capture-MS), CHRNA5 (Affinity Capture-MS), CHRNA5 (Affinity Capture-MS), CHRNA5 (Affinity Capture-MS), CHRNA5 (Affinity Capture-MS)

ESM2 similar proteins: A8WQK3, O00591, O16926, P02708, P02709, P02710, P02711, P02712, P04755, P04756, P04757, P05377, P09478, P09479, P09481, P12391, P13908, P17644, P18257, P18845, P20420, P22456, P25108, P25162, P26152, P30532, P32297, P43143, P43679, P45963, P48181, P49581, P54247, Q05901, Q07263, Q15825, Q23022, Q27218, Q2MKA5, Q5IS51

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

3 interactions.

A	Effect	B	Mechanism
CHRNA5	“form complex”	“Neuronal nicotinic acetylcholine receptor complex, alpha3-alpha5-beta2”	binding
CHRNA5	“form complex”	“Neuronal nicotinic acetylcholine receptor complex, alpha3-alpha5-beta4”	binding
CHRNA5	“form complex”	“Neuronal nicotinic acetylcholine receptor complex, alpha4-alpha5-beta2”	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 85 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Neutrophil degranulation	10	4.1×	7e-03

GO biological processes:

GO term	Partners	Fold	FDR
acetylcholine receptor signaling pathway	5	40.5×	9e-05

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	41
Likely benign	7
Benign	8

Top pathogenic / likely-pathogenic (0)

SpliceAI

1531 predictions. Top by Δscore:

Variant	Effect	Δscore
15:78565823:GAGGT:G	donor_loss	1.0000
15:78565827:T:A	donor_loss	1.0000
15:78588311:AAGG:A	acceptor_loss	1.0000
15:78588313:G:GA	acceptor_loss	1.0000
15:78588419:GATAA:G	donor_gain	1.0000
15:78588420:A:G	donor_gain	1.0000
15:78588420:ATAA:A	donor_gain	1.0000
15:78588421:TAA:T	donor_gain	1.0000
15:78588422:AA:A	donor_gain	1.0000
15:78588423:AG:A	donor_loss	1.0000
15:78588424:G:C	donor_loss	1.0000
15:78588424:G:GG	donor_gain	1.0000
15:78588425:T:A	donor_loss	1.0000
15:78589803:A:AG	acceptor_gain	1.0000
15:78589804:G:GG	acceptor_gain	1.0000
15:78593086:TAACA:T	acceptor_loss	1.0000
15:78593088:ACAGG:A	acceptor_loss	1.0000
15:78593089:CAGG:C	acceptor_loss	1.0000
15:78593091:G:A	acceptor_loss	1.0000
15:78565821:GAGAG:G	donor_gain	0.9900
15:78565823:GAG:G	donor_gain	0.9900
15:78586641:AAAG:A	acceptor_gain	0.9900
15:78586643:A:AG	acceptor_gain	0.9900
15:78586644:G:GG	acceptor_gain	0.9900
15:78588310:A:AG	acceptor_gain	0.9900
15:78588310:AAAG:A	acceptor_gain	0.9900
15:78588311:A:G	acceptor_gain	0.9900
15:78588312:A:G	acceptor_gain	0.9900
15:78588313:G:GC	acceptor_gain	0.9900
15:78588313:GGA:G	acceptor_gain	0.9900

AlphaMissense

3068 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
15:78588317:T:A	W103R	1.000
15:78588317:T:C	W103R	1.000
15:78588338:T:A	W110R	1.000
15:78588338:T:C	W110R	1.000
15:78588395:T:A	W129R	1.000
15:78588395:T:C	W129R	1.000
15:78589899:T:A	C170S	1.000
15:78589899:T:C	C170R	1.000
15:78589900:G:A	C170Y	1.000
15:78589900:G:C	C170S	1.000
15:78589901:T:G	C170W	1.000
15:78589921:T:G	F177C	1.000
15:78589941:T:C	C184R	1.000
15:78589942:G:A	C184Y	1.000
15:78589943:T:G	C184W	1.000
15:78590043:T:A	W218R	1.000
15:78590043:T:C	W218R	1.000
15:78590045:G:C	W218C	1.000
15:78590045:G:T	W218C	1.000
15:78580895:C:A	P64H	0.999
15:78580952:T:C	L83S	0.999
15:78586676:T:A	V97D	0.999
15:78588319:G:C	W103C	0.999
15:78588319:G:T	W103C	0.999
15:78588340:G:C	W110C	0.999
15:78588340:G:T	W110C	0.999
15:78588397:G:C	W129C	0.999
15:78588397:G:T	W129C	0.999
15:78589858:G:T	G156V	0.999
15:78589893:A:C	S168R	0.999

dbSNP variants (sampled 300 via entrez): RS1000227050 (15:78589606 C>G), RS1000249068 (15:78571467 T>C), RS1000379646 (15:78592514 T>C), RS1000509773 (15:78577195 C>A,G), RS1000599464 (15:78584538 G>A,T), RS1000637637 (15:78565515 C>T), RS1000651720 (15:78584221 G>A), RS1000797122 (15:78586212 T>A,C), RS1000829301 (15:78591086 T>C), RS1000860563 (15:78577576 T>C,G), RS1001005920 (15:78574565 T>C), RS1001102704 (15:78587555 G>A), RS1001197368 (15:78582354 C>T), RS1001293627 (15:78582012 C>G), RS1001543099 (15:78574242 T>C)

Disease associations

OMIM: gene MIM:118505 | disease phenotypes:

GenCC curated gene-disease

Mondo (1): lung adenocarcinoma (MONDO:0005061)

Orphanet (1): NON RARE IN EUROPE: Adenocarcinoma of the lung (Orphanet:415268)

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

122 associations (top):

Study	Trait	p-value
GCST000170_1	Lung cancer	5.000000e-20
GCST000171_1	Nicotine dependence	6.000000e-20
GCST000172_1	Lung cancer	3.000000e-18
GCST000233_1	Lung cancer	1.000000e-08
GCST000359_1	Chronic obstructive pulmonary disease	1.000000e-10
GCST000506_2	Lung adenocarcinoma	2.000000e-51
GCST000603_3	Chronic obstructive pulmonary disease	2.000000e-08
GCST000668_1	Smoking behavior	2.000000e-66
GCST001251_3	Pulmonary function	7.000000e-07
GCST001321_4	Chronic obstructive pulmonary disease	1.000000e-06
GCST001539_1	Smoking behavior	2.000000e-08
GCST001539_4	Smoking behavior	2.000000e-07
GCST001621_20	Airflow obstruction	2.000000e-07
GCST001699_13	Serum albumin levels	6.000000e-07
GCST002525_1	Local histogram emphysema pattern	8.000000e-13
GCST002525_15	Local histogram emphysema pattern	5.000000e-10
GCST002539_77	Schizophrenia	2.000000e-13
GCST002584_1	Exhaled carbon monoxide levels	2.000000e-09
GCST002798_1	Pulmonary artery enlargement and chronic obstructive pulmonary disease	7.000000e-10
GCST002945_16	Emphysema imaging phenotypes	3.000000e-07
GCST003185_2	Nicotine dependence	4.000000e-17
GCST003262_1	Post bronchodilator FEV1	1.000000e-09
GCST003262_1086	Post bronchodilator FEV1	2.000000e-06
GCST003262_2	Post bronchodilator FEV1	1.000000e-09
GCST003262_212	Post bronchodilator FEV1	2.000000e-09
GCST003262_227	Post bronchodilator FEV1	7.000000e-14
GCST003262_234	Post bronchodilator FEV1	2.000000e-15
GCST003262_235	Post bronchodilator FEV1	1.000000e-15
GCST003262_236	Post bronchodilator FEV1	3.000000e-18
GCST003262_3	Post bronchodilator FEV1	2.000000e-09

EFO canonical traits (17, from GWAS)

EFO ID	Trait name
EFO:0004318	smoking behavior
EFO:0003892	pulmonary function measurement
EFO:0004314	forced expiratory volume
EFO:0005850	emphysema pattern measurement
EFO:0006520	carbon monoxide exhalation measurement
EFO:0006347	pulmonary artery enlargement
EFO:0007626	emphysema imaging measurement
EFO:0004713	FEV/FVC ratio
EFO:0007796	parental longevity
EFO:0007813	cotinine measurement
EFO:0009369	diffusing capacity of the lung for carbon monoxide
EFO:0010126	time to first cigarette measurement
EFO:0009262	nicotine dependence symptom count
EFO:0006525	cigarettes per day measurement
EFO:0004531	urate measurement
EFO:0009762	healthspan
EFO:0004319	smoking cessation

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (6): CHEMBL2221346 (PROTEIN COMPLEX GROUP), CHEMBL3038461 (PROTEIN COMPLEX), CHEMBL3137272 (PROTEIN COMPLEX), CHEMBL3137273 (PROTEIN COMPLEX), CHEMBL4524133 (PROTEIN COMPLEX GROUP), CHEMBL4804182 (PROTEIN COMPLEX GROUP)

Molecules with ChEMBL bioactivity

2 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 190,776 (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
CHEMBL3	NICOTINE	4	184,969

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

PharmGKB clinical annotations

20 annotations.

Variant	Type	Level	Drugs	Phenotypes
rs16969968	Dosage,Efficacy	3	nicotine
rs16969968	Toxicity	3	cocaine	Cocaine dependence
rs16969968	Toxicity	2B	nicotine	Tobacco Use Disorder
rs16969968	Metabolism/PK	3	cotinine	Tobacco Use Disorder
rs16969968	Toxicity	3	Opium alkaloids and derivatives	Pain
rs16969968	Other	3	ethanol	Alcohol abuse
rs16969968	Efficacy	3	bupropion;Drugs used in nicotine dependence;nicotine;varenicline	Tobacco Use Disorder
rs2036527	Efficacy	3	varenicline	Tobacco Use Disorder
rs2036527	Efficacy	3	bupropion	Tobacco Use Disorder
rs2036527	Efficacy	3	nicotine	Tobacco Use Disorder
rs503464	Efficacy,Toxicity	3	bupropion;nicotine;varenicline	Tobacco Use Disorder
rs55781567	Toxicity	3	nicotine	Tobacco Use Disorder
rs578776	Toxicity	3	nicotine
rs588765	Efficacy	3	Drugs used in nicotine dependence;nicotine;varenicline	Tobacco Use Disorder
rs588765	Toxicity	3	cocaine	Cocaine dependence
rs615470	Other	3	ethanol	Alcohol abuse
rs637137	Toxicity	3	nicotine	Tobacco Use Disorder
rs660652	Toxicity	3	nicotine;Opium alkaloids and derivatives	Pain;Tobacco Use Disorder
rs684513	Toxicity	3	nicotine	Tobacco Use Disorder
rs684513	Other	3	cocaine	Cocaine dependence

PharmGKB variants

21 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs569207	CHRNA5		0.00	0
rs578776	CHRNA3, CHRNA5	3	3.25	3	ethanol;nicotine
rs588765	CHRNA5	3	2.50	2	Drugs used in nicotine dependence;nicotine;varenicline;cocaine
rs615470	CHRNA3, CHRNA5	3	0.50	1	ethanol
rs637137	CHRNA5	3	2.00	1	nicotine
rs660652	CHRNA3, CHRNA5	3	2.25	1	nicotine;Opium alkaloids and derivatives
rs680244	CHRNA5		0.00	0
rs684513	CHRNA5	3	1.50	2	nicotine;cocaine
rs16969968	CHRNA3, CHRNA5	2B	11.50	7	cotinine;bupropion;Drugs used in nicotine dependence;nicotine;varenicline;nicotine;ethanol;Opium alkaloids and derivatives;cocaine
rs17408276	CHRNA5		0.00	0
rs503464	CHRNA5	3	5.00	1	bupropion;nicotine;varenicline
rs55853698	CHRNA5		0.00	0
rs55781567	CHRNA5	3	2.75	1	nicotine
rs667282	CHRNA5		0.00	0
rs555018	CHRNA5		0.00	0
rs621849	CHRNA5		0.00	0
rs692780	CHRNA5		0.00	0
rs6495306	CHRNA5		0.00	0
rs514743	CHRNA5		0.00	0
rs647041	CHRNA5		0.00	0
rs67624739	CHRNA5		0.00	0

GtoPdb / IUPHAR curated pharmacology

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

Target class: lgic — Nicotinic acetylcholine receptors (nACh)

ChEMBL bioactivities

17 potent at pChembl≥5 of 20 total, top 17 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
7.96	IC50	11	nM	CHEMBL293950
6.16	Ki	692	nM	CHEMBL2165444
6.16	EC50	700	nM	CHEMBL3103985
6.16	EC50	690	nM	CHEMBL3104001
6.10	EC50	790	nM	CHEMBL3103988
6.00	EC50	1000	nM	CHEMBL3104068
5.92	EC50	1200	nM	CHEMBL2165444
5.90	Ki	1270	nM	CHEMBL2165443
5.89	EC50	1300	nM	CHEMBL3103999
5.77	EC50	1700	nM	CHEMBL3104126
5.70	EC50	2000	nM	CHEMBL3104079
5.66	EC50	2200	nM	VARENICLINE
5.66	EC50	2200	nM	CHEMBL3103983
5.47	EC50	3400	nM	CHEMBL2165443
5.22	IC50	6000	nM	CHEMBL2381563
5.06	Ki	8780	nM	CHEMBL2165445
5.04	Ki	9062	nM	CHEMBL3110043

PubChem BioAssay actives

17 with measured affinity, of 168 total; 15 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
(1S,16S)-16-methoxy-5-oxa-10-azatetracyclo[8.7.0.01,13.02,7]heptadeca-2(7),13-dien-4-one	746420: Antagonist activity at (alpha4beta2)2alpha5 nAChR (unknown origin) expressed in Xenopus oocytes assessed as inhibition of acetylcholine-induced current after 2 mins by two-electrode voltage clamp assay	ic50	0.0110	uM
5-(3-nitrophenyl)-3-pyridin-3-yl-1,2,4-oxadiazole	1063765: Positive allosteric modulation of human alpha4beta2alpha5 nACHR expressed in HEK-tsA201 cells assessed as potentiation of nicotine-induced current preincubated for 15 mins followed by nicotine-treatment by fluorometric analysis	ec50	0.6900	uM
5-[[(2S)-azetidin-2-yl]methoxy]-3-methyl-1,2-oxazole	700127: Inhibition of alpha3beta4alpha5beta2 nACHR in human SH-SY5Y cells by 86Rb+ efflux assay	ki	0.6920	uM
3-(2-pyridin-3-yltetrazol-5-yl)pyridine	1063765: Positive allosteric modulation of human alpha4beta2alpha5 nACHR expressed in HEK-tsA201 cells assessed as potentiation of nicotine-induced current preincubated for 15 mins followed by nicotine-treatment by fluorometric analysis	ec50	0.7000	uM
3-(3-pyridin-3-yl-1,2,4-oxadiazol-5-yl)benzonitrile	1063765: Positive allosteric modulation of human alpha4beta2alpha5 nACHR expressed in HEK-tsA201 cells assessed as potentiation of nicotine-induced current preincubated for 15 mins followed by nicotine-treatment by fluorometric analysis	ec50	0.7900	uM
3,5-dipyridin-3-yl-1,2,4-oxadiazole	1063765: Positive allosteric modulation of human alpha4beta2alpha5 nACHR expressed in HEK-tsA201 cells assessed as potentiation of nicotine-induced current preincubated for 15 mins followed by nicotine-treatment by fluorometric analysis	ec50	1.0000	uM
5-[[(2S)-azetidin-2-yl]methoxy]-3-(fluoromethyl)-1,2-oxazole	700127: Inhibition of alpha3beta4alpha5beta2 nACHR in human SH-SY5Y cells by 86Rb+ efflux assay	ki	1.2700	uM
5-(3,4-difluorophenyl)-3-pyridin-3-yl-1,2,4-oxadiazole	1063765: Positive allosteric modulation of human alpha4beta2alpha5 nACHR expressed in HEK-tsA201 cells assessed as potentiation of nicotine-induced current preincubated for 15 mins followed by nicotine-treatment by fluorometric analysis	ec50	1.3000	uM
5-(4-nitrophenyl)-3-pyridin-3-yl-1,2,4-oxadiazole	1063765: Positive allosteric modulation of human alpha4beta2alpha5 nACHR expressed in HEK-tsA201 cells assessed as potentiation of nicotine-induced current preincubated for 15 mins followed by nicotine-treatment by fluorometric analysis	ec50	1.7000	uM
3-(5-pyridin-3-yltetrazol-2-yl)benzonitrile	1063765: Positive allosteric modulation of human alpha4beta2alpha5 nACHR expressed in HEK-tsA201 cells assessed as potentiation of nicotine-induced current preincubated for 15 mins followed by nicotine-treatment by fluorometric analysis	ec50	2.0000	uM
Varenicline	700122: Agonist activity at alpha3beta4alpha5beta2 nACHR in human SH-SY5Y cells by 86Rb+ efflux assay	ec50	2.2000	uM
4-(5-pyridin-3-yltetrazol-2-yl)benzonitrile	1063765: Positive allosteric modulation of human alpha4beta2alpha5 nACHR expressed in HEK-tsA201 cells assessed as potentiation of nicotine-induced current preincubated for 15 mins followed by nicotine-treatment by fluorometric analysis	ec50	2.2000	uM
[(2S)-1-methylpyrrolidin-2-yl]methyl 4-chlorobenzoate	746420: Antagonist activity at (alpha4beta2)2alpha5 nAChR (unknown origin) expressed in Xenopus oocytes assessed as inhibition of acetylcholine-induced current after 2 mins by two-electrode voltage clamp assay	ic50	6.0000	uM
3-methyl-5-[[(2S)-pyrrolidin-2-yl]methoxy]-1,2-oxazole	700127: Inhibition of alpha3beta4alpha5beta2 nACHR in human SH-SY5Y cells by 86Rb+ efflux assay	ki	8.7800	uM
(5S)-5-[4-[(4R)-4-benzyl-3-[(4-tert-butylcyclohexyl)methyl]-2-iminoimidazolidin-1-yl]butyl]-1-(2-pyridin-3-ylethyl)-4,5-dihydroimidazol-2-amine	1065657: Binding affinity to alpha3beta4alpha5 nAChR (unknown origin)	ki	9.0620	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Nicotine	decreases reaction, affects reaction, increases phosphorylation, increases secretion, increases expression (+3 more)	6
Valproic Acid	affects expression, increases expression	4
Benzo(a)pyrene	decreases methylation, increases expression	3
Tobacco Smoke Pollution	decreases reaction, increases expression, affects reaction	3
trichostatin A	affects cotreatment, decreases expression	2
Phenylmercuric Acetate	affects cotreatment, decreases expression	2
Particulate Matter	affects cotreatment, increases abundance, increases expression	2
afuresertib	decreases expression	1
N-(1,2,3,5,6,7-hexahydro-S-indacen-4-ylcarbamoyl)-4-(2-hydroxy-2-propanyl)-2-furansulfonamide	affects reaction, decreases expression	1
N’-nitrosonornicotine	affects binding	1
beta-lapachone	decreases expression	1
gaboxadol	affects binding, affects cotreatment, increases activity	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
sodium arsenite	decreases expression	1
zinc chromate	decreases expression, increases abundance	1
manumycin	decreases reaction, increases expression	1
KN 62	increases expression, decreases reaction	1
1,2-bis(2-aminophenoxy)ethane N,N,N’,N’-tetraacetic acid acetoxymethyl ester	decreases reaction, increases expression	1
chromium hexavalent ion	decreases expression, increases abundance	1
Go 6976	decreases reaction, increases expression	1
4-(4-fluorophenyl)-2-(4-hydroxyphenyl)-5-(4-pyridyl)imidazole	increases expression, decreases reaction	1
alpha-conotoxin MII	increases expression, decreases reaction	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
erucylphospho-N,N,N-trimethylpropylammonium	increases expression	1
5-iodo-3-((3,5-dibromo-4-hydroxyphenyl)methylene)-2-indolinone	decreases reaction, increases expression	1
abrine	decreases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
jinfukang	decreases expression	1
NSC 689534	affects binding, decreases expression	1
4-(4-((5-(4,5-dimethyl-2-nitrophenyl)-2-furanyl)methylene)-4,5-dihydro-3-methyl-5-oxo-1H-pyrazol-1-yl)benzoic acid	increases expression	1

ChEMBL screening assays

21 unique, capped per target: 16 binding, 4 functional, 1 admet

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL2025970	Functional	Agonist activity at alpha3beta4alpha5beta2 in human SH-SY5Y cells at 10 uM by 86Rb+ flux assay	Chemistry and behavioral studies identify chiral cyclopropanes as selective α4β2-nicotinic acetylcholine receptor partial agonists exhibiting an antidepressant profile. — J Med Chem
CHEMBL2169199	Binding	Inhibition of alpha3beta4alpha5beta2 nACHR in human SH-SY5Y cells by 86Rb+ efflux assay	Identification of novel α4β2-nicotinic acetylcholine receptor (nAChR) agonists based on an isoxazole ether scaffold that demonstrate antidepressant-like activity. — J Med Chem
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 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_D1RY	Abcam U-87MG CHRNA5 KO	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT02399566	PHASE4	UNKNOWN	Clinical Trial of Erlotinib and Pemetrexed for Maintenance Treatment in Lung Adenocarcinoma
NCT02804646	PHASE4	UNKNOWN	Endostar Durative Transfusion Combined With Chemotherapy in the Treatment of Advanced Lung Adenocarcinoma
NCT00002852	PHASE3	COMPLETED	Surgery With or Without Chemotherapy in Treating Patients With Stage I Non-small Cell Lung Cancer
NCT00005838	PHASE3	COMPLETED	Combination Chemotherapy Plus Radiation Therapy With or Without AE-941 in Treating Patients With Stage III Non-small Cell Lung Cancer That Cannot Be Removed By Surgery
NCT00020709	PHASE3	COMPLETED	Combination Chemotherapy and Radiation Therapy With or Without Gefitinib in Treating Patients With Stage III Non-Small Cell Lung Cancer That Cannot Be Removed By Surgery
NCT00049543	PHASE3	COMPLETED	Gefitinib in Treating Patients With Stage IB, II, or IIIA Non-small Cell Lung Cancer That Was Completely Removed by Surgery
NCT00946712	PHASE3	TERMINATED	S0819: Carboplatin and Paclitaxel With or Without Bevacizumab and/or Cetuximab in Treating Patients With Stage IV or Recurrent Non-Small Cell Lung Cancer
NCT01798485	PHASE3	TERMINATED	A Phase 3 Study of Ganetespib in Combination With Docetaxel Versus Docetaxel Alone in Patients With Advanced NSCLC
NCT02011997	PHASE3	UNKNOWN	Comparison of cVATS Segmentectomy Versus Lobectomy for Lung Adenocarcinoma in Situ and With Microinvasion
NCT03391869	PHASE3	ACTIVE_NOT_RECRUITING	Nivolumab and Ipilimumab With or Without Local Consolidation Therapy in Treating Patients With Stage IV Non-Small Cell Lung Cancer
NCT03676192	PHASE3	COMPLETED	To Compare Efficacy and Safety of CT-P16 and European Union-Approved Avastin as First-Line Treatment for Metastatic or Recurrent Non-Squamous Non-Small Cell Lung Cancer
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