HTR3A

Summary

HTR3A (5-hydroxytryptamine receptor 3A, HGNC:5297) is a protein-coding gene on chromosome 11q23.2, encoding 5-hydroxytryptamine receptor 3A (P46098). Forms serotonin (5-hydroxytryptamine/5-HT3)-activated cation-selective channel complexes, which when activated cause fast, depolarizing responses in neurons.

The product of this gene belongs to the ligand-gated ion channel receptor superfamily. This gene encodes subunit A of the type 3 receptor for 5-hydroxytryptamine (serotonin), a biogenic hormone that functions as a neurotransmitter, a hormone, and a mitogen. This receptor causes fast, depolarizing responses in neurons after activation. It appears that the heteromeric combination of A and B subunits is necessary to provide the full functional features of this receptor, since either subunit alone results in receptors with very low conductance and response amplitude. Alternatively spliced transcript variants encoding different isoforms have been identified.

Source: NCBI Gene 3359 — RefSeq curated summary.

At a glance

• GWAS associations: 3
• Clinical variants (ClinVar): 104 total — 1 pathogenic
• Druggable target: yes — 98 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_000869

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:5297
Approved symbol	HTR3A
Name	5-hydroxytryptamine receptor 3A
Location	11q23.2
Locus type	gene with protein product
Status	Approved
Aliases	5-HT3R, 5-HT3A
Ensembl gene	ENSG00000166736
Ensembl biotype	protein_coding
OMIM	182139
Entrez	3359

Gene structure

Transcript identifiers

Ensembl transcripts: 9 — 7 protein_coding, 1 retained_intron, 1 nonsense_mediated_decay

ENST00000299961, ENST00000355556, ENST00000375498, ENST00000502622, ENST00000504030, ENST00000506841, ENST00000510849, ENST00000936750, ENST00000936751

RefSeq mRNA: 3 — MANE Select: NM_000869 NM_000869, NM_001161772, NM_213621

CCDS: CCDS53710, CCDS8365, CCDS8366

Canonical transcript exons

ENST00000504030 — 9 exons

Exon	Start	End
ENSE00002023877	113989465	113990313
ENSE00002074317	113975108	113975392
ENSE00003493854	113977771	113977922
ENSE00003521883	113986825	113987046
ENSE00003629456	113979233	113979277
ENSE00003650983	113983120	113983289
ENSE00003679762	113981203	113981312
ENSE00003681031	113986015	113986175
ENSE00003687368	113986518	113986728

Expression profiles

Bgee: expression breadth ubiquitous, 120 present calls, max score 83.77.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.0536 / max 11.0269, expressed in 20 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
116765	0.0442	19
116766	0.0094	7

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
dorsal root ganglion	UBERON:0000044	83.77	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	81.02	silver quality
pancreatic ductal cell	CL:0002079	75.77	silver quality
trigeminal ganglion	UBERON:0001675	75.55	gold quality
ileal mucosa	UBERON:0000331	72.56	silver quality
diaphragm	UBERON:0001103	66.94	gold quality
lymph node	UBERON:0000029	66.86	gold quality
islet of Langerhans	UBERON:0000006	66.78	gold quality
vermiform appendix	UBERON:0001154	66.72	gold quality
gingival epithelium	UBERON:0001949	65.92	gold quality
olfactory bulb	UBERON:0002264	65.04	gold quality
type B pancreatic cell	CL:0000169	64.99	gold quality
muscle layer of sigmoid colon	UBERON:0035805	63.73	gold quality
hair follicle	UBERON:0002073	63.41	gold quality
Brodmann (1909) area 46	UBERON:0006483	62.80	gold quality
CA1 field of hippocampus	UBERON:0003881	62.51	gold quality
caecum	UBERON:0001153	62.29	gold quality
caudate nucleus	UBERON:0001873	61.99	gold quality
gingiva	UBERON:0001828	61.90	gold quality
tongue squamous epithelium	UBERON:0006919	61.49	gold quality
minor salivary gland	UBERON:0001830	60.94	gold quality
mucosa of urinary bladder	UBERON:0001259	60.21	gold quality
mouth mucosa	UBERON:0003729	60.00	gold quality
pancreas	UBERON:0001264	59.88	gold quality
penis	UBERON:0000989	59.86	gold quality
secondary oocyte	CL:0000655	59.48	gold quality
sigmoid colon	UBERON:0001159	59.41	gold quality
orbitofrontal cortex	UBERON:0004167	59.22	gold quality
putamen	UBERON:0001874	59.09	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	59.03	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	2.59

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

30 targeting HTR3A, 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-4650-5P	99.98	64.69	999
HSA-MIR-9-3P	99.96	70.88	2068
HSA-MIR-9718	99.94	68.91	918
HSA-MIR-4525	99.94	64.38	675
HSA-MIR-5010-5P	99.94	64.11	705
HSA-MIR-22-3P	99.93	68.13	917
HSA-MIR-10527-5P	99.91	72.28	3754
HSA-MIR-548E-5P	99.89	72.73	4486
HSA-MIR-3659	99.70	67.97	694
HSA-MIR-3202	99.66	67.70	2737
HSA-MIR-4261	99.59	70.30	3415
HSA-MIR-143-3P	99.49	69.05	1457
HSA-MIR-4770	99.49	69.09	1451
HSA-MIR-147B-5P	99.45	70.62	2432
HSA-MIR-4797-5P	99.39	68.01	1354
HSA-MIR-6088	99.29	68.45	1284
HSA-MIR-7160-5P	99.11	67.17	2207
HSA-MIR-7854-3P	99.08	66.26	1117
HSA-MIR-452-3P	99.01	66.25	1241
HSA-MIR-1294	98.91	69.26	1030
HSA-MIR-9986	98.91	69.28	1024
HSA-MIR-423-5P	98.69	67.48	1522
HSA-MIR-6811-3P	98.62	66.54	944
HSA-MIR-3184-5P	98.56	67.13	1491
HSA-MIR-628-5P	98.36	67.74	844
HSA-MIR-506-5P	98.02	67.41	1065
HSA-MIR-558	97.50	67.16	977
HSA-MIR-4714-3P	96.53	67.44	452
HSA-MIR-500B-3P	96.49	65.40	1087
HSA-MIR-1256	95.44	66.33	784

Literature-anchored findings (GeneRIF, showing 40)

• These data provide direct evidence for an extracellular N-terminal domain and an intracellular loop between the third and fourth transmembrane domains, thus supporting the conventional ligand-gated ion channel subunit topological model. (PMID:12059035)
• species-dependent gating mechanisms of 5-HT(3) receptors (PMID:12457738)
• Cell surface expression of 5-hydroxytryptamine type 3 receptors is controlled by an endoplasmic reticulum retention signal (PMID:12750374)
• 5HT3A receptor function and trafficking is regulated by protein kinase c through an F-actin-dependent mechanism (PMID:12791692)
• By constructing chimaeric 5-HT3A and 5-HT3B subunits we identified a region (the ‘HA-stretch’) within the large cytoplasmic loop of the receptor that markedly influences channel conductance (PMID:12867984)
• Results describe homology modeling of the N-terminal extracellular regions of human, mouse, and guinea pig 5-hydroxytryptamine type 3A receptors. (PMID:14626451)
• 5-HT3A receptor gene may not serve as a pharmacogenetic predictor of the antiemetic treatment with 5-HT3 receptor antagonists in cancer patients (PMID:15115912)
• the cytoplasmic selectivity filter of 5-HT(3A) receptors maintains a narrow pore during channel gating (PMID:15131114)
• 5-HT3 receptor trafficking has roles in biosynthesis and endocytosis (PMID:15452106)
• RIC-3 may play a role in 5-HT(3A) receptor folding, assembly, or transport to the cell surface (PMID:15809299)
• 5-HT excited human enteric neurons via 5-HT3 receptors, which may comprise both 5-HT3A and 5-HT3B receptor subunits (PMID:15887114)
• The C178T variation in the HTR3A has a critical influence on the amygdaloid activity and on human face processing, probably through regulation of the receptor expression. (PMID:16000636)
• Five sequence variants found in Gilles de la Tourette syndrome. (PMID:16314763)
• analysis of single channel conductance within the large cytoplasmic loop of 5-hydroxytryptamine type 3 and alpha4beta2 nicotinic acetylcholine receptors (PMID:16407231)
• there is a flexible 5-HT(3) receptor F-loop with two regions that have specific but distinct roles in ligand binding (PMID:16595668)
• Thus, position 57 located at the complementary face of the binding site plays a key role in the selective activation of AChRs by pyrantel. (PMID:16825485)
• 5-HT3A receptors respond to morphine in a species-specific manner (PMID:16931691)
• Quantification of HTR3A versus HTR3B transcript expression demonstrates significant variation in the ratio of both transcripts in different tissues. (PMID:17010535)
• 5-HT3 receptors are known to be involved in mediation of nausea/emesis caused by chemo/radio-therapy and anaesthesia, and more recently have also been found to be involved in irritable bowel syndrome (PMID:17052218)
• Description of a fully human chimeric receptor (h-alpha7/5HT3A), which is characterized by desensitization, and recovery kinetics that deviate from the human WT alpha7. (PMID:17192651)
• dynamic modification of the charge of a cytoplasmic residue regulates gamma, consistent with the existence of cytoplasmic portals that impose a rate-limiting barrier to ion conduction in Cys loop receptors. (PMID:17200121)
• functional 5-HT3A receptor variant C178T does not associated with early-onset obsessive compulsive-disorder. (PMID:17259209)
• tested the hypothesis that loop F plays a significant role in conferring interspecies curare potency differences; two loop F residues make a significant contribution in determining curare potency at the 5-HT3A receptor (PMID:17260949)
• P391R but not the R344H site directed mutagenesis may be involved in the pathology of schizophrenia. (PMID:17401153)
• Three polymorphisms of the 5-HT3A gene gave rise to functionally impaired receptors whose function could not be rescued by either wild-type 5-HT3A or 5-HT3B. (PMID:17496724)
• Results describe regional differences in expression of TPH-1, SERT, 5-HT(3) and 5-HT(4) receptors in the stomach and duodenum. (PMID:17509016)
• The light chain (LC1) of microtubule-associated protein 1B (MAP1B)-5-HT(3A) receptor interaction contributes to a mechanism that regulates receptor desensitization kinetics. (PMID:18063656)
• an HTR3B variant associated with major depression dramatically augments the signaling of the human 5-HT3AB receptor (PMID:18184810)
• HTR3A may have a role in the personality trait of anxiety, but may not play a major role in the etiology of panic disorder. (PMID:18197086)
• Examine effects of propofol, 2-isopropylphenol and phenol on HTR3A receptor. (PMID:18292429)
• The daily neuroleptic dosage that patients had been receiving during their maintenance therapy was significantly higher in patients with the T/T genotype of HTR3A polymorphism. (PMID:18359159)
• Serotonin receptors, novel targets of sulforaphane identified by proteomic analysis in Caco-2 cells. (PMID:18593952)
• MicroRNA-510 target site of the 3’UTR of HTR3A and HTR3E are associated with the irritable bowel syndrome with diarrhea. (PMID:18614545)
• The binding site for miR-510 is solely located in the 3’ UTR of the HTR3E gene. No predicted binding site for miR-510 exists in the 3’ UTR of HTR3A. (PMID:18614545)
• The results of this study are the first to suggest that the polymorphism of HTR3A may be a useful predictor of therapeutic response to risperidone treatment in Chinese schizophrenic patients. (PMID:18622264)
• Genetic variants of HTR3C 5-hydroxytryptamine (serotonin) receptor 3 (family member C) do not predict a response to 5HT3 antagonists, necessitating further investigation. (PMID:18681779)
• 5-HT3B(I143T)-containing 5-HT3AB receptors display significantly reduced cell surface expression and different signalling properties compared with WT 5-HT3AB receptors. (PMID:19008750)
• Substitution of the human 5-HT3A subunit proline303 by either a histidine or tryptophan did not appear to significantly compromise cell surface expression of functional receptors, as measured indirectly by the magnitude of the serotonin evoked currents. (PMID:19457066)
• Genetic variations in the HTR3A and HTR3B gene seem to be associated with the individual risk of developing postoperative vomiting. (PMID:19713259)
• an involvement of serotonin receptor type 3A variants in the aetiopathology of eating disorders in humans (PMID:19741568)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	htr3a	ENSDARG00000089212
mus_musculus	Htr3a	ENSMUSG00000032269
rattus_norvegicus	Htr3a	ENSRNOG00000006595

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), CHRNA5 (ENSG00000169684), CHRNB1 (ENSG00000170175), CHRNA9 (ENSG00000174343), CHRNA7 (ENSG00000175344), HTR3C (ENSG00000178084), GABRG3 (ENSG00000182256), GABRR3 (ENSG00000183185), HTR3E (ENSG00000186038), HTR3D (ENSG00000186090)

Protein

Protein identifiers

5-hydroxytryptamine receptor 3A — P46098 (reviewed: P46098)

Alternative names: 5-hydroxytryptamine receptor 3, Serotonin receptor 3A, Serotonin-gated ion channel receptor

All UniProt accessions (2): A0A0B4J205, P46098

UniProt curated annotations — full annotation on UniProt →

Function. Forms serotonin (5-hydroxytryptamine/5-HT3)-activated cation-selective channel complexes, which when activated cause fast, depolarizing responses in neurons.

Subunit / interactions. Forms homopentameric as well as heteropentameric serotonin-activated cation-selective channel complexes with HTR3B or HTR3C or HTR3D or HTR3E. The homomeric complex is functional but exhibits low conductance with modified voltage dependence, and decreased agonist and antagonist affinity. Heteropentameric complexes display properties which resemble that of neuronal serotonin-activated channels in vivo. Interacts with RIC3.

Subcellular location. Postsynaptic cell membrane. Cell membrane.

Tissue specificity. Expressed in cerebral cortex, amygdala, hippocampus, and testis. Detected in monocytes of the spleen and tonsil, in small and large intestine, uterus, prostate, ovary and placenta.

Domain organisation. The HA-stretch region of HTR3A seems to be responsible for the low conductance of HTR3A homomers compared to that of HTR3A/HTR3B heteromers.

Similarity. Belongs to the ligand-gated ion channel (TC 1.A.9) family. 5-hydroxytryptamine receptor (TC 1.A.9.2) subfamily. HTR3A sub-subfamily.

Isoforms (5)

UniProt ID	Names	Canonical?
P46098-1	1, 5-HT3R-AS	yes
P46098-2	2, 5-HT3R-AL
P46098-3	3
P46098-4	4
P46098-5	5

RefSeq proteins (3): NP_000860, NP_001155244, NP_998786 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR006029	Neurotrans-gated_channel_TM	Domain
IPR006201	Neur_channel	Family
IPR006202	Neur_chan_lig-bd	Domain
IPR008132	5HT3_rcpt	Family
IPR008133	5HT3_rcpt_A	Family
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
IPR049944	LGIC_TM_5-HT3	Domain

Pfam: PF02931, PF02932

Catalyzed reactions (Rhea), 4 shown:

• K(+)(in) = K(+)(out) (RHEA:29463)
• Ca(2+)(in) = Ca(2+)(out) (RHEA:29671)
• Mg(2+)(in) = Mg(2+)(out) (RHEA:29827)
• Na(+)(in) = Na(+)(out) (RHEA:34963)

UniProt features (65 total): strand 14, helix 12, topological domain 5, sequence variant 5, sequence conflict 5, glycosylation site 4, mutagenesis site 4, transmembrane region 4, splice variant 3, turn 3, region of interest 2, signal peptide 1, chain 1, compositionally biased region 1, disulfide bond 1

Structure

Experimental structures (PDB)

4 structures.

PDB	Method	Resolution (Å)
8AXD	ELECTRON MICROSCOPY	2.98
8BL8	ELECTRON MICROSCOPY	3.21
8BLA	ELECTRON MICROSCOPY	3.3
8BLB	ELECTRON MICROSCOPY	3.3

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P46098-F1	83.28	0.56

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 (1): 157–171

Glycosylation sites (4): 28, 104, 170, 186

Mutagenesis-validated functional residues (4):

Position	Phenotype
178	abolished 5-hydroxytryptamine (serotonin) binding to the heteromeric receptor.
432	little effect on conductance. massive increase of conductance; when associated with d-436 and a-440.
436	increased conductance. massive increase of conductance; when associated with q-432 and a-440.
440	increased conductance. massive increase of conductance; when associated with q-432 and d-436.

Function

Pathways and Gene Ontology

Reactome pathways

3 pathways

ID	Pathway
R-HSA-112314	Neurotransmitter receptors and postsynaptic signal transmission
R-HSA-112315	Transmission across Chemical Synapses
R-HSA-112316	Neuronal System

MSigDB gene sets: 162 (showing top): GOBP_RESPONSE_TO_NITROGEN_COMPOUND, MODULE_274, MODULE_169, MODULE_45, MODULE_64, MODULE_16, BROWNE_HCMV_INFECTION_12HR_UP, GOBP_CELLULAR_RESPONSE_TO_OXYGEN_CONTAINING_COMPOUND, CAGCTG_AP4_Q5, MORF_RAD51L3, GOBP_CELL_CELL_SIGNALING, WEI_MYCN_TARGETS_WITH_E_BOX, MODULE_120, GOBP_REGULATION_OF_POSTSYNAPTIC_MEMBRANE_POTENTIAL, GOBP_RESPONSE_TO_OXYGEN_CONTAINING_COMPOUND

GO Biological Process (10): serotonin receptor signaling pathway (GO:0007210), chemical synaptic transmission (GO:0007268), monoatomic ion transmembrane transport (GO:0034220), regulation of membrane potential (GO:0042391), obsolete inorganic cation transmembrane transport (GO:0098662), serotonin-gated cation-selective signaling pathway (GO:0140227), monoatomic ion transport (GO:0006811), regulation of postsynaptic membrane potential (GO:0060078), excitatory postsynaptic potential (GO:0060079), regulation of presynaptic membrane potential (GO:0099505)

GO Molecular Function (12): excitatory extracellular ligand-gated monoatomic ion channel activity (GO:0005231), serotonin-gated monoatomic cation channel activity (GO:0022850), identical protein binding (GO:0042802), serotonin binding (GO:0051378), ligand-gated monoatomic ion channel activity involved in regulation of presynaptic membrane potential (GO:0099507), transmitter-gated monoatomic ion channel activity involved in regulation of postsynaptic membrane potential (GO:1904315), 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), ligand-gated monoatomic ion channel activity (GO:0015276), acetylcholine-gated monoatomic cation-selective channel activity (GO:0022848)

GO Cellular Component (8): plasma membrane (GO:0005886), cleavage furrow (GO:0032154), neuron projection (GO:0043005), synapse (GO:0045202), postsynaptic membrane (GO:0045211), transmembrane transporter complex (GO:1902495), serotonin-activated cation-selective channel complex (GO:1904602), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Transmission across Chemical Synapses	1
Neuronal System	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
serotonin receptor activity	2
serotonin receptor signaling pathway	2
regulation of membrane potential	2
regulation of postsynaptic membrane potential	2
transmitter-gated monoatomic ion channel activity	2
ligand-gated monoatomic cation channel activity	2
ligand-gated monoatomic ion channel activity	2
signal transduction	1
cellular response to dopamine	1
anterograde trans-synaptic signaling	1
monoatomic ion transport	1
transmembrane transport	1
monoatomic ion transmembrane transport	1
regulation of biological quality	1
serotonin-gated monoatomic cation channel activity	1
ligand-gated ion channel signaling pathway	1
transport	1
chemical synaptic transmission, postsynaptic	1
extracellular ligand-gated monoatomic ion channel activity	1
excitatory postsynaptic potential	1
protein binding	1
cation binding	1
amine binding	1
heterocyclic compound binding	1
presynaptic membrane	1
regulation of presynaptic membrane potential	1
signaling receptor activity	1
monoatomic ion transmembrane transporter activity	1
channel activity	1
binding	1
monoatomic ion channel activity	1
ligand-gated channel activity	1
excitatory extracellular ligand-gated monoatomic ion channel activity	1
postsynaptic neurotransmitter receptor activity	1
transmitter-gated monoatomic ion channel activity involved in regulation of postsynaptic membrane potential	1
membrane	1
cell periphery	1
cell division site	1
plasma membrane region	1
plasma membrane bounded cell projection	1

Protein interactions and networks

STRING

1210 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
HTR3A	HTR3B	O95264	978
HTR3A	RIC3	Q7Z5B4	938
HTR3A	HTR3D	Q70Z44	932
HTR3A	HTR3C	Q8WXA8	912
HTR3A	HTR2A	P28223	882
HTR3A	HTR2C	P28335	796
HTR3A	HTR1D	P28221	790
HTR3A	HTR2B	P41595	777
HTR3A	HTR1E	P28566	773
HTR3A	DEGS2	Q6QHC5	767
HTR3A	HTR1A	P08908	735
HTR3A	HTR1B	P28222	734
HTR3A	SLC6A4	P31645	726
HTR3A	HTR5A	P47898	723
HTR3A	HTR7	P34969	722

IntAct

25 interactions, top by confidence:

A	B	Type	Score
HTR3A	HTR3C	psi-mi:“MI:0915”(physical association)	0.610
HTR3A	HTR3D	psi-mi:“MI:0915”(physical association)	0.610
HTR3A	HTR3E	psi-mi:“MI:0915”(physical association)	0.610
HTR3A	HTR3C	psi-mi:“MI:0403”(colocalization)	0.610
HTR3A	HTR3D	psi-mi:“MI:0403”(colocalization)	0.610
HTR3A	HTR3E	psi-mi:“MI:0403”(colocalization)	0.610
HTR3A	HTR3E	psi-mi:“MI:0915”(physical association)	0.560
HTR3A	HTR3E	psi-mi:“MI:0403”(colocalization)	0.560
HTR3A	HTR3B	psi-mi:“MI:0407”(direct interaction)	0.500
HTR3A	HTR3B	psi-mi:“MI:0403”(colocalization)	0.500
	HTR3A	psi-mi:“MI:0915”(physical association)	0.400
HTR3A		psi-mi:“MI:0915”(physical association)	0.400
HTR3A	HTR3A	psi-mi:“MI:0407”(direct interaction)	0.360
HTR3A	EXTL3	psi-mi:“MI:0914”(association)	0.350
HTR3A	ZZEF1	psi-mi:“MI:0914”(association)	0.350

BioGRID (190): OCA2 (Affinity Capture-MS), HLA-DOA (Affinity Capture-MS), ABCA7 (Affinity Capture-MS), UGT3A2 (Affinity Capture-MS), LRRC8D (Affinity Capture-MS), SLC41A3 (Affinity Capture-MS), PANX1 (Affinity Capture-MS), LPPR3 (Affinity Capture-MS), MARCH6 (Affinity Capture-MS), TUSC3 (Affinity Capture-MS), COA1 (Affinity Capture-MS), LRRC8C (Affinity Capture-MS), DPY19L4 (Affinity Capture-MS), LRP12 (Affinity Capture-MS), SIDT2 (Affinity Capture-MS)

ESM2 similar proteins: A2A259, A5X5Y0, H2Q5A1, O46547, O70212, O95264, O97741, P01906, P01909, P02713, P02715, P02716, P04758, P04759, P04760, P07510, P09660, P09690, P11230, P13536, P18916, P20782, P23979, P25109, P25110, P35563, P37088, P37089, P46098, P55270, P78334, Q04844, Q07001, Q14246, Q5Y4N8, Q60HE8, Q61180, Q61549, Q70Z44, Q7Z418

Diamond homologs: A5X5Y0, O70212, O95264, P04757, P05376, P18845, P19370, P22770, P23979, P26153, P32297, P35563, P36544, P43143, P43679, P46098, P48182, P49581, P49582, P54131, Q05941, Q07263, Q15825, Q494W8, Q5IS76, Q68RJ7, Q70Z44, Q866A2, Q8R4G9, Q8WXA8, Q9I8C7, Q9JHJ5, Q9JJ16, A8WQK3, A8XNX8, O16926, O70174, O76554, P02716, P02717

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
serotonin	“up-regulates activity”	HTR3A	“chemical activation”
HTR3A	up-regulates	Excitatory_synaptic_transmission

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	84
Likely benign	6
Benign	6

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
973579	NC_000011.9:g.104288964_134937416dup	Pathogenic

SpliceAI

1352 predictions. Top by Δscore:

Variant	Effect	Δscore
11:113977871:G:GT	donor_gain	1.0000
11:113981201:A:AG	acceptor_gain	1.0000
11:113981202:G:GG	acceptor_gain	1.0000
11:113981308:GAGTT:G	donor_gain	1.0000
11:113981310:GTT:G	donor_gain	1.0000
11:113981311:TT:T	donor_gain	1.0000
11:113981313:G:A	donor_loss	1.0000
11:113981313:G:GG	donor_gain	1.0000
11:113981314:TGAG:T	donor_loss	1.0000
11:113981315:GAGTA:G	donor_loss	1.0000
11:113981316:AGTAC:A	donor_loss	1.0000
11:113983118:A:AG	acceptor_gain	1.0000
11:113983118:AGCGT:A	acceptor_gain	1.0000
11:113983119:G:GA	acceptor_gain	1.0000
11:113983119:GC:G	acceptor_gain	1.0000
11:113983119:GCGT:G	acceptor_gain	1.0000
11:113983119:GCGTG:G	acceptor_gain	1.0000
11:113983285:CACCA:C	donor_gain	1.0000
11:113983286:ACCA:A	donor_gain	1.0000
11:113983287:CCA:C	donor_gain	1.0000
11:113983288:CA:C	donor_gain	1.0000
11:113983289:AG:A	donor_loss	1.0000
11:113983290:G:T	donor_loss	1.0000
11:113983290:GTGA:G	donor_gain	1.0000
11:113983291:T:A	donor_loss	1.0000
11:113983292:GA:G	donor_gain	1.0000
11:113983294:GTAT:G	donor_gain	1.0000
11:113986144:GCA:G	donor_gain	1.0000
11:113986147:G:GG	donor_gain	1.0000
11:113986176:G:GG	donor_gain	1.0000

AlphaMissense

3111 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
11:113981227:T:A	W97R	0.999
11:113981227:T:C	W97R	0.999
11:113981284:T:A	W116R	0.999
11:113981284:T:C	W116R	0.999
11:113986097:G:C	W209C	0.999
11:113986097:G:T	W209C	0.999
11:113981286:G:C	W116C	0.998
11:113981286:G:T	W116C	0.998
11:113983235:T:C	F164L	0.998
11:113983236:T:G	F164C	0.998
11:113983237:C:A	F164L	0.998
11:113983237:C:G	F164L	0.998
11:113983274:A:C	S177R	0.998
11:113983276:T:A	S177R	0.998
11:113983276:T:G	S177R	0.998
11:113986095:T:A	W209R	0.998
11:113986095:T:C	W209R	0.998
11:113986569:A:C	S253R	0.998
11:113986571:C:A	S253R	0.998
11:113986571:C:G	S253R	0.998
11:113981208:G:C	W90C	0.997
11:113981208:G:T	W90C	0.997
11:113981229:G:C	W97C	0.997
11:113981229:G:T	W97C	0.997
11:113983214:T:C	C157R	0.997
11:113983216:T:G	C157W	0.997
11:113983256:T:A	C171S	0.997
11:113983257:G:C	C171S	0.997
11:113983258:C:G	C171W	0.997
11:113983263:T:C	L173P	0.997

dbSNP variants (sampled 300 via entrez): RS1000353375 (11:113974711 A>G), RS1000530277 (11:113979312 C>G,T), RS1000771764 (11:113989860 C>G,T), RS1000963538 (11:113986967 G>C,T), RS1001089654 (11:113981729 G>A), RS1001184276 (11:113980937 G>A,C), RS1001417832 (11:113986446 A>C), RS1001870376 (11:113986235 A>G), RS1001931384 (11:113979896 C>T), RS1002098733 (11:113984810 C>T), RS1002160206 (11:113975103 C>A,T), RS1002831400 (11:113987555 A>T), RS1003220195 (11:113976266 C>G), RS1003312670 (11:113983534 A>G), RS1003523545 (11:113986008 C>A,G,T)

Disease associations

OMIM: gene MIM:182139 | disease phenotypes:

GenCC curated gene-disease

Mondo (1): distal trisomy 11q (MONDO:0019885)

Orphanet (1): Distal duplication 11q syndrome (Orphanet:96103)

HPO phenotypes

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

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST002875_44	Diisocyanate-induced asthma	2.000000e-07
GCST003140_1	Chronic kidney disease	5.000000e-06
GCST009597_46	Multiple sclerosis	7.000000e-08

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0006995	response to diisocyanate

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
C538294	Chromosome 11, partial trisomy 11q (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (6): CHEMBL1899 (SINGLE PROTEIN), CHEMBL2094132 (PROTEIN COMPLEX GROUP), CHEMBL2096904 (PROTEIN FAMILY), CHEMBL2111332 (PROTEIN COMPLEX), CHEMBL4296087 (PROTEIN COMPLEX), CHEMBL4296091 (PROTEIN COMPLEX)

Molecules with ChEMBL bioactivity

98 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 377,619 (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
CHEMBL1110	ALOSETRON	4	10,794
CHEMBL1112	ARIPIPRAZOLE	4	24,205
CHEMBL1113	AMOXAPINE	4	20,128
CHEMBL1117	IDARUBICIN	4	136,065
CHEMBL117287	PRUCALOPRIDE	4	2,516
CHEMBL1175	DULOXETINE	4	28,527
CHEMBL1179047	CHLOROPROCAINE	4	52,577
CHEMBL1186610	ANISOTROPINE	4	473
CHEMBL1189679	PALONOSETRON	4	9,399
CHEMBL1201	THIOTHIXENE	4	13,101
CHEMBL1201303	PYRVINIUM	4	1,797
CHEMBL1201304	INDOCYANINE GREEN ACID FORM	4	7,044
CHEMBL1201340	DIPHEMANIL	4	9
CHEMBL1201346	BALSALAZIDE	4	8,319
CHEMBL1219	RABEPRAZOLE	4	12,441
CHEMBL1242	PHENAZOPYRIDINE	4	4,686
CHEMBL128	SUMATRIPTAN	4	28,367
CHEMBL1401	NITAZOXANIDE	4	9,504
CHEMBL1454910	NITROXOLINE	4	1,860
CHEMBL1491	AMLODIPINE	4
CHEMBL1516474	TEGASEROD MALEATE	4
CHEMBL1633	KETOTIFEN FUMARATE	4
CHEMBL1643895	RAMOSETRON	4
CHEMBL1689772	OMADACYCLINE	4
CHEMBL1729	CISAPRIDE	4
CHEMBL178	DAUNORUBICIN	4
CHEMBL2103737	HYDROXOCOBALAMIN	4
CHEMBL2104993	VORTIOXETINE	4
CHEMBL2105695	TELOTRISTAT ETHYL	4

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

PharmGKB clinical annotations

3 annotations.

Variant	Type	Level	Drugs	Phenotypes
rs1062613	Efficacy	3	clozapine	Schizophrenia
rs1150226	Efficacy	3	clozapine	Schizophrenia
rs2276302	Efficacy	3	clozapine	Schizophrenia

PharmGKB variants

7 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs1062613	HTR3A	3	2.50	1	clozapine
rs1150226	HTR3A	3	0.00	1	clozapine
rs1176713	HTR3A		0.00	0
rs1176722	HTR3A		0.00	0
rs2276302	HTR3A	3	2.50	1	clozapine
rs1176719	HTR3A		0.00	0
rs1985242	HTR3A		0.00	0

GtoPdb / IUPHAR curated pharmacology

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

Target class: lgic — 5-HT₃ receptors

Binding affinities (BindingDB)

477 measured of 605 human assays (613 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
Ramosetron	KI	0.06 nM	US-9045501: 5-HT3 receptor modulators, methods of making, and use thereof
(9-methyl-9-azabicyclo[3.3.1]nonan-3-yl) 1-(2-fluoroethyl)indole-3-carboxylate	IC50	0.18 nM	US-9303045: 5-HT3 receptor antagonists
(9-methyl-9-azabicyclo[3.3.1]nonan-3-yl) 2-chloro-1-(2-fluoroethyl)indole-3-carboxylate	IC50	0.2 nM	US-9303045: 5-HT3 receptor antagonists
10-[(3S)-1-azabicyclo[2.2.2]octan-3-yl]-6-chloro-3-methyl-1,10-diazatricyclo[6.4.1.04,13]trideca-2,4(13),5,7-tetraen-9-one	KI	0.2 nM	US-9045501: 5-HT3 receptor modulators, methods of making, and use thereof
1-(2-fluoroethyl)-N-(9-methyl-3-oxa-9-azabicyclo[3.3.1]nonan-7-yl)indole-3-carboxamide	IC50	0.22 nM	US-9303045: 5-HT3 receptor antagonists
(9-methyl-9-azabicyclo[3.3.1]nonan-3-yl) 1-(2-fluoroethyl)-2-methylindole-3-carboxylate	IC50	0.22 nM	US-9303045: 5-HT3 receptor antagonists
1-(2,2-difluoroethyl)-N-(9-methyl-3-oxa-9-azabicyclo[3.3.1]nonan-7-yl)indole-3-carboxamide	IC50	0.23 nM	US-9303045: 5-HT3 receptor antagonists
(9-methyl-3-oxa-9-azabicyclo[3.3.1]nonan-7-yl) 1-(2,2-difluoroethyl)-5-fluoroindole-3-carboxylate	IC50	0.24 nM	US-9303045: 5-HT3 receptor antagonists
N-(9-methyl-3-oxa-9-azabicyclo[3.3.1]nonan-7-yl)-1-pyridazin-3-ylindole-3-carboxamide	IC50	0.28 nM	US-9303045: 5-HT3 receptor antagonists
(9-methyl-3-oxa-9-azabicyclo[3.3.1]nonan-7-yl) 5-fluoro-1-methylsulfonylindole-3-carboxylate	IC50	0.29 nM	US-9303045: 5-HT3 receptor antagonists
1-(cyanomethyl)-N-(9-methyl-3-oxa-9-azabicyclo[3.3.1]nonan-7-yl)indole-3-carboxamide	IC50	0.298 nM	US-9303045: 5-HT3 receptor antagonists
(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
1-(3-methylimidazol-4-yl)-N-(9-methyl-3-oxa-9-azabicyclo[3.3.1]nonan-7-yl)indole-3-carboxamide	IC50	0.328 nM	US-9303045: 5-HT3 receptor antagonists
(9-methyl-3-oxa-9-azabicyclo[3.3.1]nonan-7-yl) 1-methylsulfonylindole-3-carboxylate	IC50	0.33 nM	US-9303045: 5-HT3 receptor antagonists
N-(9-methyl-3-oxa-9-azabicyclo[3.3.1]nonan-7-yl)-1-pyrimidin-5-ylindole-3-carboxamide	IC50	0.39 nM	US-9303045: 5-HT3 receptor antagonists
1-(2,2-difluoroethyl)-N-(9-methyl-3-oxa-9-azabicyclo[3.3.1]nonan-7-yl)indazole-3-carboxamide	IC50	0.4 nM	US-9303045: 5-HT3 receptor antagonists
N-(9-methyl-3-oxa-9-azabicyclo[3.3.1]nonan-7-yl)-1-(1,3-thiazol-5-yl)indole-3-carboxamide	IC50	0.4 nM	US-9303045: 5-HT3 receptor antagonists
N-(9-methyl-3-oxa-9-azabicyclo[3.3.1]nonan-7-yl)-1-(1,3-thiazol-4-yl)pyrrolo[2,3-b]pyridine-3-carboxamide	IC50	0.4 nM	US-9303045: 5-HT3 receptor antagonists
N-(9-methyl-3-oxa-9-azabicyclo[3.3.1]nonan-7-yl)-1-(1,3-thiazol-5-yl)pyrrolo[2,3-b]pyridine-3-carboxamide	IC50	0.4 nM	US-9303045: 5-HT3 receptor antagonists
1-(2,2-difluoroethyl)-N-(3-oxa-9-azabicyclo[3.3.1]nonan-7-yl)indole-3-carboxamide	IC50	0.4 nM	US-9303045: 5-HT3 receptor antagonists
3-oxa-9-azabicyclo[3.3.1]nonan-7-yl 1-(1,2-thiazol-4-yl)indole-3-carboxylate	IC50	0.415 nM	US-9303045: 5-HT3 receptor antagonists
N-(8-methyl-8-azabicyclo[3.2.1]octan-3-yl)-1-methylsulfonylindole-3-carboxamide	IC50	0.42 nM	US-9303045: 5-HT3 receptor antagonists
(9-methyl-9-azabicyclo[3.3.1]nonan-3-yl) 1-(2,2-difluoroethyl)-5-fluoroindole-3-carboxylate	IC50	0.44 nM	US-9303045: 5-HT3 receptor antagonists
1-(2-fluoroethyl)-N-(9-methyl-9-azabicyclo[3.3.1]nonan-3-yl)indazole-3-carboxamide	IC50	0.45 nM	US-9303045: 5-HT3 receptor antagonists
(9-methyl-3-oxa-9-azabicyclo[3.3.1]nonan-7-yl) 1-pyrimidin-5-ylindole-3-carboxylate	IC50	0.46 nM	US-9303045: 5-HT3 receptor antagonists
(1r,5s,7s)-9-methyl-3-oxa-9-azabicyclo [3.3.1]nonan-7-yl 1-(1h-pyrazol-4-yl)- 1h-indole-3-carboxylate	IC50	0.462 nM	US-9670229: 5-HT3 receptor antagonists
[(1S,5R)-9-methyl-3-oxa-9-azabicyclo[3.3.1]nonan-7-yl] 1-pyrazolidin-4-ylindole-3-carboxylate	IC50	0.462 nM	US-9346829: 5-HT3 receptor antagonists
1-(2,2-difluoroethyl)-N-(9-methyl-9-azabicyclo[3.3.1]nonan-3-yl)indazole-3-carboxamide	IC50	0.49 nM	US-9303045: 5-HT3 receptor antagonists
1-(2,2-difluoroethyl)-5-fluoro-N-(9-methyl-3-oxa-9-azabicyclo[3.3.1]nonan-7-yl)indole-3-carboxamide	IC50	0.49 nM	US-9303045: 5-HT3 receptor antagonists
5-fluoro-N-(9-methyl-3-oxa-9-azabicyclo[3.3.1]nonan-7-yl)-1-methylsulfonylindole-3-carboxamide	IC50	0.5 nM	US-9303045: 5-HT3 receptor antagonists
10-[(3S)-1-azabicyclo[2.2.2]octan-3-yl]-6-chloro-1,2,10-triazatricyclo[6.4.1.04,13]trideca-2,4(13),5,7-tetraen-9-one	KI	0.5 nM	US-9045501: 5-HT3 receptor modulators, methods of making, and use thereof
CHEBI:253342	KI	0.5 nM	US-9045501: 5-HT3 receptor modulators, methods of making, and use thereof
(1r,5s,7s)-3-oxa-9-azabicyclo[3.3.1]nonan- 7-yl 1-(pyridin-4-yl)-1h-indole-3-carboxylate, 2,2,2-trifluoroacetate	IC50	0.51 nM	US-9670229: 5-HT3 receptor antagonists
N-[(1S,5R)-9-methyl-3-oxa-9-azabicyclo[3.3.1]nonan-7-yl]-1-pyridin-3-ylindole-3-carboxamide	IC50	0.51 nM	US-9346829: 5-HT3 receptor antagonists
N-(9-methyl-3-oxa-9-azabicyclo[3.3.1]nonan-7-yl)-1-(2,2,2-trifluoroethyl)indole-3-carboxamide	IC50	0.53 nM	US-9303045: 5-HT3 receptor antagonists
(8-methyl-8-azabicyclo[3.2.1]octan-3-yl) 1-(2-fluoroethyl)-2-methylindole-3-carboxylate	IC50	0.53 nM	US-9303045: 5-HT3 receptor antagonists
(8-methyl-8-azabicyclo[3.2.1]octan-3-yl) 1-(2-fluoroethyl)indole-3-carboxylate	IC50	0.53 nM	US-9303045: 5-HT3 receptor antagonists
(8-methyl-8-azabicyclo[3.2.1]octan-3-yl) 1-methylsulfonylindole-3-carboxylate	IC50	0.54 nM	US-9303045: 5-HT3 receptor antagonists
5-fluoro-N-(9-methyl-3-oxa-9-azabicyclo[3.3.1]nonan-7-yl)-1-(2,2,2-trifluoroethyl)indole-3-carboxamide	IC50	0.54 nM	US-9303045: 5-HT3 receptor antagonists
N-(9-methyl-3-oxa-9-azabicyclo[3.3.1]nonan-7-yl)-1-pyrazin-2-ylindole-3-carboxamide	IC50	0.55 nM	US-9303045: 5-HT3 receptor antagonists
N-(9-methyl-3-oxa-9-azabicyclo[3.3.1]nonan-7-yl)-1-propan-2-ylsulfonylindole-3-carboxamide	IC50	0.57 nM	US-9303045: 5-HT3 receptor antagonists
N-(9-methyl-9-azabicyclo[3.3.1]nonan-3-yl)-1-methylsulfonylindazole-3-carboxamide	IC50	0.59 nM	US-9303045: 5-HT3 receptor antagonists
(9-methyl-3-oxa-9-azabicyclo[3.3.1]nonan-7-yl) 1-(6-oxo-1H-pyridazin-3-yl)indole-3-carboxylate	IC50	0.598 nM	US-9303045: 5-HT3 receptor antagonists
N-(9-methyl-3-oxa-9-azabicyclo[3.3.1]nonan-7-yl)-1-pyridin-3-ylpyrrolo[2,3-b]pyridine-3-carboxamide	IC50	0.6 nM	US-9670229: 5-HT3 receptor antagonists
(9-methyl-3-oxa-9-azabicyclo[3.3.1]nonan-7-yl) 1-(2-fluoroethyl)pyrrolo[2,3-b]pyridine-3-carboxylate	IC50	0.6 nM	US-9303045: 5-HT3 receptor antagonists
N-[(1S,5R)-9-methyl-3-oxa-9-azabicyclo[3.3.1]nonan-7-yl]-1-pyridin-3-ylpyrrolo[2,3-b]pyridine-3-carboxamide	IC50	0.6 nM	US-9346829: 5-HT3 receptor antagonists
(9-methyl-3-oxa-9-azabicyclo[3.3.1]nonan-7-yl) 1-(2-fluoroethyl)indole-3-carboxylate	IC50	0.6 nM	US-9695195: 5-HT3 receptor antagonists
N-(9-methyl-3-oxa-9-azabicyclo[3.3.1]nonan-7-yl)-1-(1,2-thiazol-4-yl)indole-3-carboxamide	IC50	0.61 nM	US-9303045: 5-HT3 receptor antagonists
3-oxa-9-azabicyclo[3.3.1]nonan-7-yl 1-pyridin-3-ylindole-3-carboxylate	IC50	0.62 nM	US-9670229: 5-HT3 receptor antagonists
[(1S,5R)-3-oxa-9-azabicyclo[3.3.1]nonan-7-yl] 1-pyridin-3-ylindole-3-carboxylate	IC50	0.62 nM	US-9346829: 5-HT3 receptor antagonists

ChEMBL bioactivities

1640 potent at pChembl≥5 of 1791 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
11.00	Kd	0.01	nM	CHEMBL143197
10.70	Kd	0.01995	nM	GRANISETRON
10.60	Kd	0.02512	nM	TROPISETRON
10.60	Kd	0.02512	nM	CHEMBL143197
10.50	Ki	0.03162	nM	PALONOSETRON
10.40	Ki	0.04	nM	CHEMBL261010
10.29	Ki	0.05129	nM	CHEMBL475331
10.22	Ki	0.06	nM	RAMOSETRON
10.20	Kd	0.0631	nM	TROPISETRON
10.15	Ki	0.071	nM	CHEMBL325422
10.10	Kd	0.07943	nM	ONDANSETRON
10.10	Kd	0.07943	nM	GRANISETRON
10.10	Kd	0.07943	nM	ZACOPRIDE
10.09	IC50	0.08128	nM	CHEMBL416662
10.05	IC50	0.09	nM	ONDANSETRON
9.90	Kd	0.1259	nM	GRANISETRON
9.86	Ki	0.138	nM	CHEMBL145033
9.84	Ki	0.1445	nM	CHEMBL145725
9.80	Kd	0.1585	nM	CHEMBL323208
9.80	Kd	0.1585	nM	CHEMBL40935
9.77	Ki	0.17	nM	CHEMBL596951
9.74	Kd	0.18	nM	PALONOSETRON
9.74	IC50	0.18	nM	CHEMBL3916920
9.74	Ki	0.182	nM	CHEMBL28992
9.72	Kd	0.19	nM	GRANISETRON
9.70	Kd	0.2	nM	GRANISETRON
9.70	Ki	0.2	nM	CHEMBL3261480
9.70	IC50	0.2	nM	CHEMBL3933362
9.66	Kd	0.22	nM	PALONOSETRON
9.66	IC50	0.22	nM	CHEMBL3891400
9.66	IC50	0.22	nM	CHEMBL3948240
9.64	Ki	0.23	nM	CHEMBL43355
9.64	Ki	0.23	nM	CHEMBL327197
9.64	IC50	0.23	nM	CHEMBL3979389
9.64	Ki	0.23	nM	CHEMBL605772
9.62	IC50	0.24	nM	CHEMBL3900767
9.60	Kd	0.25	nM	PALONOSETRON
9.59	Kd	0.26	nM	PALONOSETRON
9.55	IC50	0.28	nM	CHEMBL3923591
9.54	IC50	0.2884	nM	CHEMBL299634
9.54	IC50	0.29	nM	CHEMBL3968090
9.53	IC50	0.2985	nM	CHEMBL3895177
9.52	Kd	0.3	nM	PALONOSETRON
9.52	IC50	0.3	nM	CHEMBL3895177
9.49	Kd	0.32	nM	PALONOSETRON
9.49	Ki	0.32	nM	CHEMBL111448
9.48	IC50	0.33	nM	CHEMBL3956338
9.48	IC50	0.328	nM	CHEMBL3979838
9.48	Ki	0.33	nM	CHEMBL15056
9.48	IC50	0.33	nM	CHEMBL3979838

PubChem BioAssay actives

936 with measured affinity, of 3517 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
7-(4-prop-2-enylpiperazin-1-yl)-2,8,13-triazatricyclo[7.4.0.02,6]trideca-1(9),3,5,7,10,12-hexaene	6355: Binding affinity against 5-hydroxytryptamine 3 receptor was measured using [3H]granisetron as radioligand	ic50	<0.0001	uM
2-chloro-3-(4-methylpiperazin-1-yl)quinoxaline	1387997: Displacement of [3H]granisetron from human 5-HT3A receptor expressed in HEK293 cells by scintillation counting method	ki	<0.0001	uM
1-methyl-N-(9-methyl-9-azabicyclo[3.3.1]nonan-3-yl)indazole-3-carboxamide	6027: Potency at neuronal 5-hydroxytryptamine 3 receptor in the rabbit heart	kd	<0.0001	uM
Palonosetron	537659: Binding affinity to 5HT3A receptor	ki	<0.0001	uM
7-(4-benzylpiperazin-1-yl)-2,8,13-triazatricyclo[7.4.0.02,6]trideca-1(9),3,5,7,10,12-hexaene	6355: Binding affinity against 5-hydroxytryptamine 3 receptor was measured using [3H]granisetron as radioligand	ic50	<0.0001	uM
(1-methylindol-3-yl)-[(5R)-4,5,6,7-tetrahydro-3H-benzimidazol-5-yl]methanone	552106: Binding affinity to human 5HT3A receptor	ki	0.0001	uM
2-(4-methylpiperazin-1-yl)quinazolin-4-amine	703982: Displacement of [3H]granisetron from 5HT3A receptor expressed in HEK293 cells after 24 hrs by scintillation counting in presence of quipazine	ki	0.0001	uM
4-[4-(1,3-benzodioxol-5-ylmethyl)piperazin-1-yl]-7-chloropyrrolo[1,2-a]quinoxaline	6355: Binding affinity against 5-hydroxytryptamine 3 receptor was measured using [3H]granisetron as radioligand	ic50	0.0001	uM
(1-methylindol-3-yl)-(4,5,6,7-tetrahydro-3H-benzimidazol-5-yl)methanone	5980: Binding affinity towards [3H]quipazine labeled 5-hydroxytryptamine 3 receptor sites in HG108-15	ki	0.0001	uM
Ondansetron	6027: Potency at neuronal 5-hydroxytryptamine 3 receptor in the rabbit heart	kd	0.0001	uM
[(1R,5S)-8-methyl-8-azabicyclo[3.2.1]octan-3-yl] 1H-indole-3-carboxylate	6026: Binding affinity to 5-hydroxytryptamine 3 receptor of neuronal in the afferent rabbit vagus	kd	0.0001	uM
4-(4-methylpiperazin-1-yl)pyrrolo[1,2-a]quinoxaline	6335: Binding affinity towards 5-hydroxytryptamine 3 receptor	ki	0.0002	uM
4-hydroxy-1-methyl-N-[(1S,5S)-9-methyl-9-azabicyclo[3.3.1]nonan-3-yl]indazole-3-carboxamide	461556: Displacement of [3H]granisetron from human 5HT3A receptor expressed in HEK293 cells by scintillation counting	ki	0.0002	uM
6-(4-methylpiperazin-1-yl)-7,8,9,10-tetrahydrophenanthridine	6335: Binding affinity towards 5-hydroxytryptamine 3 receptor	ki	0.0002	uM
(2-methyl-4-oxo-2-azabicyclo[3.3.1]nonan-8-yl) 1H-indole-3-carboxylate	6028: Potency at neuronal 5-hydroxytryptamine 3 receptors in the rabbit heart	kd	0.0002	uM
(4-oxo-2-azatricyclo[3.3.1.02,7]nonan-8-yl) 1H-indole-3-carboxylate	200911: Potency was evaluated on rabbit heart serotonergic receptors	kd	0.0002	uM
1-methyl-N-[(1S,5S)-9-methyl-9-azabicyclo[3.3.1]nonan-3-yl]-7-phenylmethoxyindazole-3-carboxamide	461556: Displacement of [3H]granisetron from human 5HT3A receptor expressed in HEK293 cells by scintillation counting	ki	0.0002	uM
10-[(3S)-1-azabicyclo[2.2.2]octan-3-yl]-6-chloro-3-methyl-1,10-diazatricyclo[6.4.1.04,13]trideca-2,4(13),5,7-tetraen-9-one	1141224: Displacement of [9-methyl-3H]BRL-43694 from human 5-HT3A receptor after overnight incubation by scintillation proximity assay	ki	0.0002	uM
4-(4-benzylpiperazin-1-yl)-7-chloropyrrolo[1,2-a]quinoxaline	6355: Binding affinity against 5-hydroxytryptamine 3 receptor was measured using [3H]granisetron as radioligand	ic50	0.0003	uM
N-[2-[4-(3-piperidin-1-ylpropoxy)phenyl]ethyl]-1,2,3,4-tetrahydroacridin-9-amine	314097: Binding affinity to 5HT3 receptor	ki	0.0003	uM
(8-methyl-8-azabicyclo[3.2.1]octan-3-yl) 2-oxo-1-propan-2-ylquinoline-4-carboxylate	5980: Binding affinity towards [3H]quipazine labeled 5-hydroxytryptamine 3 receptor sites in HG108-15	ki	0.0003	uM
1-[(4-methoxyphenyl)methyl]-2-piperazin-1-ylbenzimidazole	6379: Binding affinity against human 5-hydroxytryptamine 3A receptor	ki	0.0004	uM
4-(4-benzylpiperazin-1-yl)pyrrolo[1,2-a]quinoxaline	6355: Binding affinity against 5-hydroxytryptamine 3 receptor was measured using [3H]granisetron as radioligand	ic50	0.0004	uM
4-amino-N-(1-azabicyclo[2.2.2]octan-3-yl)-5-chloro-2-methoxybenzamide	1063801: Displacement of [3H]GR65630 from 5-HT3 receptor (unknown origin)	ki	0.0004	uM
4-(2-methoxyphenyl)-2-[(5-methyl-1H-imidazol-4-yl)methyl]-1,3-thiazole	6364: Binding affinity towards 5-hydroxytryptamine 3 receptor by displacement of [3H]2 in Neuroblastoma-Glioma NG-108-15 cells	ki	0.0004	uM
(8-methyl-8-azabicyclo[3.2.1]octan-3-yl) 2-butoxyquinoline-4-carboxylate	5980: Binding affinity towards [3H]quipazine labeled 5-hydroxytryptamine 3 receptor sites in HG108-15	ki	0.0004	uM
(8-methyl-8-azabicyclo[3.2.1]octan-3-yl) 2-(2-methylpropoxy)quinoline-4-carboxylate	5980: Binding affinity towards [3H]quipazine labeled 5-hydroxytryptamine 3 receptor sites in HG108-15	ki	0.0004	uM
(8-methyl-8-azabicyclo[3.2.1]octan-3-yl) 2-oxo-1-propylquinoline-4-carboxylate	5980: Binding affinity towards [3H]quipazine labeled 5-hydroxytryptamine 3 receptor sites in HG108-15	ki	0.0004	uM
2-piperazin-1-ylquinoline	6355: Binding affinity against 5-hydroxytryptamine 3 receptor was measured using [3H]granisetron as radioligand	ic50	0.0004	uM
1-benzyl-2-piperazin-1-ylbenzimidazole	6379: Binding affinity against human 5-hydroxytryptamine 3A receptor	ki	0.0004	uM
(8-methyl-8-azabicyclo[3.2.1]octan-3-yl) 1-(2-methylpropyl)-2-oxoquinoline-4-carboxylate	5980: Binding affinity towards [3H]quipazine labeled 5-hydroxytryptamine 3 receptor sites in HG108-15	ki	0.0005	uM
Alosetron	1141224: Displacement of [9-methyl-3H]BRL-43694 from human 5-HT3A receptor after overnight incubation by scintillation proximity assay	ki	0.0005	uM
7-fluoro-4-(4-methylpiperazin-1-yl)pyrrolo[1,2-a]quinoline	6335: Binding affinity towards 5-hydroxytryptamine 3 receptor	ki	0.0005	uM
(8-methyl-8-azabicyclo[3.2.1]octan-3-yl) 2-oxo-1-phenylquinoline-4-carboxylate	5980: Binding affinity towards [3H]quipazine labeled 5-hydroxytryptamine 3 receptor sites in HG108-15	ki	0.0005	uM
2-(4-methylpiperazin-1-yl)quinoline	703982: Displacement of [3H]granisetron from 5HT3A receptor expressed in HEK293 cells after 24 hrs by scintillation counting in presence of quipazine	ki	0.0005	uM
1-butyl-4-hydroxy-N-(8-methyl-8-azabicyclo[3.2.1]octan-3-yl)-2-oxoquinoline-3-carboxamide	5980: Binding affinity towards [3H]quipazine labeled 5-hydroxytryptamine 3 receptor sites in HG108-15	ki	0.0005	uM
[(1R,5S)-8-methyl-8-azabicyclo[3.2.1]octan-3-yl] 3,5-dichlorobenzoate	6027: Potency at neuronal 5-hydroxytryptamine 3 receptor in the rabbit heart	kd	0.0005	uM
10-[(3S)-1-azabicyclo[2.2.2]octan-3-yl]-6-chloro-1,2,10-triazatricyclo[6.4.1.04,13]trideca-2,4(13),5,7-tetraen-9-one	1141224: Displacement of [9-methyl-3H]BRL-43694 from human 5-HT3A receptor after overnight incubation by scintillation proximity assay	ki	0.0005	uM
(1,1-dimethylpiperidin-1-ium-4-yl)-(1H-indol-3-yl)methanone iodide	6028: Potency at neuronal 5-hydroxytryptamine 3 receptors in the rabbit heart	kd	0.0006	uM
2-[(3S,5S)-3,5-dimethylmorpholin-4-yl]-N-[(1S,5R)-9-methyl-9-azabicyclo[3.3.1]nonan-3-yl]-1,3-benzoxazole-4-carboxamide	526452: Binding affinity to human HT3A receptor	ki	0.0006	uM
(8-methyl-8-azabicyclo[3.2.1]octan-3-yl) 2-methoxyquinoline-4-carboxylate	5980: Binding affinity towards [3H]quipazine labeled 5-hydroxytryptamine 3 receptor sites in HG108-15	ki	0.0006	uM
2-(3,4,5-trichlorophenyl)guanidine	6339: Binding affinity to 5-HT3 serotonin receptor in NG 108-15 neuroblastoma glioma cells using [3H]GR-65630 radioligand.	ki	0.0007	uM
(8-methyl-8-azabicyclo[3.2.1]octan-3-yl) 1-butyl-2-oxoquinoline-4-carboxylate	5980: Binding affinity towards [3H]quipazine labeled 5-hydroxytryptamine 3 receptor sites in HG108-15	ki	0.0007	uM
(8-methyl-8-azabicyclo[3.2.1]octan-3-yl) 2-(2-methylpropyl)quinoline-4-carboxylate	5980: Binding affinity towards [3H]quipazine labeled 5-hydroxytryptamine 3 receptor sites in HG108-15	ki	0.0007	uM
7-hydroxy-1-methyl-N-[(1S,5S)-9-methyl-9-azabicyclo[3.3.1]nonan-3-yl]indazole-3-carboxamide	461556: Displacement of [3H]granisetron from human 5HT3A receptor expressed in HEK293 cells by scintillation counting	ki	0.0007	uM
6-[(3S)-1-azabicyclo[2.2.2]octan-3-yl]-2-methyl-2,6-diazatricyclo[6.3.1.04,12]dodeca-1(11),3,8(12),9-tetraen-7-one	552106: Binding affinity to human 5HT3A receptor	ki	0.0007	uM
6-[(3S)-1-azabicyclo[2.2.2]octan-3-yl]-2-methyl-2,3,6-triazatricyclo[6.3.1.04,12]dodeca-1(11),3,8(12),9-tetraen-7-one	552106: Binding affinity to human 5HT3A receptor	ki	0.0007	uM
10-(4-methylpiperazin-1-yl)-9-azatetracyclo[11.2.1.02,11.03,8]hexadeca-2(11),3,5,7,9-pentaene	6335: Binding affinity towards 5-hydroxytryptamine 3 receptor	ki	0.0008	uM
7-[4-(1,3-benzodioxol-5-ylmethyl)piperazin-1-yl]-2,8,13-triazatricyclo[7.4.0.02,6]trideca-1(9),3,5,7,10,12-hexaene	6355: Binding affinity against 5-hydroxytryptamine 3 receptor was measured using [3H]granisetron as radioligand	ic50	0.0008	uM
N,N-dimethyl-2-[(Z)-(3-methylthieno[2,3-b]pyrrolizin-8-ylidene)amino]oxyethanamine	6316: Compound was tested for binding affinity towards 5-hydroxytryptamine 3 receptor	ic50	0.0008	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, increases expression	3
bisphenol A	affects cotreatment, decreases methylation, increases expression	2
ramosetron	affects cotreatment, decreases activity, affects binding	2
entinostat	affects cotreatment, increases expression	2
Benzo(a)pyrene	affects methylation, increases expression, increases methylation	2
Clozapine	decreases activity, affects response to substance, affects binding	2
Metoclopramide	decreases activity, affects binding, decreases reaction, affects cotreatment	2
Tamoxifen	affects expression, affects cotreatment, decreases expression	2
Ondansetron	affects binding, affects reaction, decreases activity, affects activity	2
methyleugenol	increases expression	1
citronellol	decreases activity	1
geraniol	decreases activity	1
gingerol	decreases activity	1
sodium arsenite	increases expression	1
polygodial	decreases activity	1
2-methyl-5-HT	affects binding, increases activity	1
GR 65630	affects binding, decreases reaction	1
carvacrol	increases activity	1
fipronil	affects cotreatment, increases expression	1
CGP 52608	affects binding, increases reaction	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	increases expression, affects cotreatment	1
dorsomorphin	increases expression, affects cotreatment	1
Rosiglitazone	increases expression	1
Remifentanil	affects activity	1
Decitabine	affects expression	1
Fulvestrant	affects cotreatment, decreases methylation	1
Vortioxetine	affects binding, affects reaction, affects activity	1
Ethanol	affects binding, increases activity, increases reaction	1
1-Propanol	affects binding, increases activity, increases reaction	1
Pentanols	affects binding, increases activity, increases reaction	1

ChEMBL screening assays

707 unique, capped per target: 599 binding, 98 functional, 9 admet, 1 toxicity

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1000203	Binding	Binding affinity to 5HT3 receptor	Synthesis and evaluation of dibenzothiazepines: a novel class of selective cannabinoid-1 receptor inverse agonists. — J Med Chem
CHEMBL1023913	Functional	Antagonist activity at human 5HT3A receptor expressed in HEK293 cells assessed as inhibition of serotonin-induced inward Na+ current at >= 10 uM	Molecular properties of psychopharmacological drugs determining non-competitive inhibition of 5-HT3A receptors. — Eur J Med Chem
CHEMBL3878923	ADMET	Antagonist activity at 5-HT3A (unknown origin) at 10 uM	Design and Synthesis of a New Series of 4-Heteroarylamino-1’-azaspiro[oxazole-5,3’-bicyclo[2.2.2]octanes as α7 Nicotinic Receptor Agonists. 1. Development of Pharmacophore and Early Structure-Activity Relationship. — J Med Chem

Clinical trials (associated diseases)

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