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HTR3C

gene
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Summary

HTR3C (5-hydroxytryptamine receptor 3C, HGNC:24003) is a protein-coding gene on chromosome 3q27.1, encoding 5-hydroxytryptamine receptor 3C (Q8WXA8). 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 C 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. Genes encoding subunits C, D and E form a cluster on chromosome 3.

Source: NCBI Gene 170572 — RefSeq curated summary.

At a glance

  • GWAS associations: 4
  • Clinical variants (ClinVar): 78 total — 1 pathogenic
  • Druggable target: yes — 19 molecules with ChEMBL bioactivity
  • MANE Select transcript: NM_130770

Identifiers

Gene identifiers

FieldValue
HGNC IDHGNC:24003
Approved symbolHTR3C
Name5-hydroxytryptamine receptor 3C
Location3q27.1
Locus typegene with protein product
StatusApproved
Ensembl geneENSG00000178084
Ensembl biotypeprotein_coding
OMIM610121
Entrez170572

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000318351

RefSeq mRNA: 1 — MANE Select: NM_130770 NM_130770

CCDS: CCDS3250

Canonical transcript exons

ENST00000318351 — 9 exons

ExonStartEnd
ENSE00001238660184059436184059640
ENSE00001238666184058427184058587
ENSE00001238678184056177184056286
ENSE00001238682184055312184055356
ENSE00001238695184060150184060673
ENSE00001238703184053047184053147
ENSE00002469017184056875184057044
ENSE00002479844184059828184060043
ENSE00002527817184054721184054887

Expression profiles

Bgee: expression breadth broad, 20 present calls, max score 84.78.

Top tissues by expression

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

TissueAnatomy IDExpression scoreQuality
male germ line stem cell (sensu Vertebrata) in testisCL:0000089 ∩ UBERON:000047384.78gold quality
right lungUBERON:000216774.62gold quality
mucosa of transverse colonUBERON:000499159.98gold quality
upper lobe of left lungUBERON:000895256.20gold quality
lungUBERON:000204854.57gold quality
duodenumUBERON:000211452.99gold quality
colonic epitheliumUBERON:000039741.91gold quality
transverse colonUBERON:000115741.42gold quality
small intestineUBERON:000210839.16gold quality
small intestine Peyer’s patchUBERON:000345438.48gold quality
right lobe of thyroid glandUBERON:000111937.53silver quality
rectumUBERON:000105237.35silver quality
ventricular zoneUBERON:000305336.48gold quality
cortical plateUBERON:000534336.47gold quality
bone marrow cellCL:000209236.16gold quality
intestineUBERON:000016036.07gold quality
thyroid glandUBERON:000204635.85silver quality
apex of heartUBERON:000209835.68gold quality
left lobe of thyroid glandUBERON:000112035.55silver quality
ganglionic eminenceUBERON:000402335.49gold quality
colonUBERON:000115535.35gold quality
gall bladderUBERON:000211034.57silver quality
fundus of stomachUBERON:000116034.38gold quality
bone marrowUBERON:000237134.08gold quality
urinary bladderUBERON:000125533.45gold quality
skeletal muscle tissueUBERON:000113433.38gold quality
mucosa of stomachUBERON:000119932.43gold quality
fallopian tubeUBERON:000388932.33gold quality
vermiform appendixUBERON:000115432.32gold quality
hindlimb stylopod muscleUBERON:000425232.15gold quality

Single-cell (SCXA)

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

ExperimentMarker?Max mean expression
E-ANND-3yes4.14

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

20 targeting HTR3C, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNAMax scoreAvg scoremiRNA target_count
HSA-MIR-444199.4966.563216
HSA-MIR-425499.1165.151315
HSA-MIR-427099.0266.261987
HSA-MIR-6754-5P98.6065.541627
HSA-MIR-6804-5P98.3965.771084
HSA-MIR-317998.2265.901445
HSA-MIR-211-3P98.1466.771052
HSA-MIR-446898.0166.851187
HSA-MIR-6819-5P97.9666.591071
HSA-MIR-429497.8665.721110
HSA-MIR-319897.8465.64579
HSA-MIR-430997.8465.45588
HSA-MIR-366197.8367.30705
HSA-MIR-6737-5P97.7566.541044
HSA-MIR-6812-5P97.5665.391059
HSA-MIR-468996.9765.791209
HSA-MIR-61796.7965.96738
HSA-MIR-382-5P96.7165.90762
HSA-MIR-369096.4465.18737
HSA-MIR-4772-5P95.6068.04617

Literature-anchored findings (GeneRIF, showing 8)

  • Polymorphisms in the HTR3C gene could serve as a predictive factor for chemotherapy-induced nausea and vomiting in patients undergoing moderately emetogenic chemotherapy. (PMID:18389280)
  • HTR3C represents a novel candidate locus for autism spectrum disorders and should be tested in other populations. (PMID:19035560)
  • Six functional and coding variants of the subunit genes HTR3A, HTR3B as well as the novel HTR3C, HTR3D, and HTR3E subunits in the response to haloperidol or risperidone, were assessed. (PMID:19794330)
  • Polymorphisms in the subunit gene HTR3C of the serotonin receptor may be involved in the pathogenesis of pregnancy-associated nausea. (PMID:20021265)
  • Data show that 5-HT3C, 5-HT3D, and 5-HT3E subunits are coexpressed with 5-HT3A in cell bodies of myenteric neurons, and that 5-HT3A and 5-HT3D were expressed in submucosal plexus of the human large intestine. (PMID:21192076)
  • The association findings of the HTR3C and the HTR3E remained significant after correction for the number of variants investigated. (PMID:23928294)
  • Our study indicates, for the first time, an association between variants of HTR3C and severity of chemotherapy-induced symptoms (PMID:24477975)
  • These findings enrich the allelic spectrum of ABCC5 in PACG. We identified no tagging SNP responsible for the association of the whole region. (PMID:28813580)

Cross-species orthologs

0 orthologs

Paralogs (45): GABRA3 (ENSG00000011677), GABRA1 (ENSG00000022355), CHRNA3 (ENSG00000080644), GABRP (ENSG00000094755), CHRNA4 (ENSG00000101204), GLRA2 (ENSG00000101958), GABRE (ENSG00000102287), CHRNE (ENSG00000108556), GABRA4 (ENSG00000109158), GLRB (ENSG00000109738), GABRR2 (ENSG00000111886), GABRG2 (ENSG00000113327), CHRNB4 (ENSG00000117971), CHRNA2 (ENSG00000120903), CHRNA10 (ENSG00000129749), CHRND (ENSG00000135902), CHRNA1 (ENSG00000138435), GLRA3 (ENSG00000145451), GABRA6 (ENSG00000145863), GABRB2 (ENSG00000145864), GLRA1 (ENSG00000145888), GABRR1 (ENSG00000146276), CHRNB3 (ENSG00000147432), CHRNA6 (ENSG00000147434), HTR3B (ENSG00000149305), GABRA2 (ENSG00000151834), CHRNB2 (ENSG00000160716), GABRG1 (ENSG00000163285), GABRB1 (ENSG00000163288), GABRB3 (ENSG00000166206), CHRFAM7A (ENSG00000166664), HTR3A (ENSG00000166736), CHRNA5 (ENSG00000169684), CHRNB1 (ENSG00000170175), CHRNA9 (ENSG00000174343), CHRNA7 (ENSG00000175344), GABRG3 (ENSG00000182256), GABRR3 (ENSG00000183185), HTR3E (ENSG00000186038), HTR3D (ENSG00000186090)

Protein

Protein identifiers

5-hydroxytryptamine receptor 3C — Q8WXA8 (reviewed: Q8WXA8)

Alternative names: Serotonin receptor 3C

All UniProt accessions (1): Q8WXA8

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 HTR3A. The homomeric complex is not functional. Heteropentameric complexes display properties which resemble that of neuronal serotonin-activated channels in vivo.

Subcellular location. Postsynaptic cell membrane. Cell membrane.

Tissue specificity. Expressed in many tissues including adult brain, colon, intestine, lung, muscle and stomach as well as fetal colon and kidney.

Domain organisation. The HA-stretch region of HTR3C seems to confer increased conductance to HTR3A/HTR3C heteropentamers compared to that of HTR3A homopentamers.

Similarity. Belongs to the ligand-gated ion channel (TC 1.A.9) family. 5-hydroxytryptamine receptor (TC 1.A.9.2) subfamily. HTR3C sub-subfamily.

RefSeq proteins (1): NP_570126* (*=MANE)

Domains & families (InterPro)

IDNameType
IPR006029Neurotrans-gated_channel_TMDomain
IPR006201Neur_channelFamily
IPR006202Neur_chan_lig-bdDomain
IPR018000Neurotransmitter_ion_chnl_CSConserved_site
IPR036719Neuro-gated_channel_TM_sfHomologous_superfamily
IPR036734Neur_chan_lig-bd_sfHomologous_superfamily
IPR038050Neuro_actylchol_recHomologous_superfamily
IPR049944LGIC_TM_5-HT3Domain

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 (18 total): topological domain 5, transmembrane region 4, sequence variant 3, region of interest 2, signal peptide 1, chain 1, compositionally biased region 1, disulfide bond 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

ModelpLDDTFraction very-high
AF-Q8WXA8-F181.380.56

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): 162–176

Function

Pathways and Gene Ontology

Reactome pathways

3 pathways

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

MSigDB gene sets: 67 (showing top): GOBP_RESPONSE_TO_NITROGEN_COMPOUND, GOBP_CELLULAR_RESPONSE_TO_OXYGEN_CONTAINING_COMPOUND, GOBP_CELL_CELL_SIGNALING, GOBP_REGULATION_OF_POSTSYNAPTIC_MEMBRANE_POTENTIAL, GOBP_RESPONSE_TO_OXYGEN_CONTAINING_COMPOUND, GOBP_CELLULAR_RESPONSE_TO_NITROGEN_COMPOUND, GOBP_SYNAPTIC_SIGNALING, GOCC_NEURON_PROJECTION, REACTOME_TRANSMISSION_ACROSS_CHEMICAL_SYNAPSES, ACEVEDO_METHYLATED_IN_LIVER_CANCER_DN, GOBP_TRANSMEMBRANE_TRANSPORT, GOCC_PLASMA_MEMBRANE_SIGNALING_RECEPTOR_COMPLEX, GOCC_POSTSYNAPSE, GOBP_REGULATION_OF_MEMBRANE_POTENTIAL, GOCC_SYNAPSE

GO Biological Process (9): 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)

GO Molecular Function (7): excitatory extracellular ligand-gated monoatomic ion channel activity (GO:0005231), serotonin-gated monoatomic cation channel activity (GO:0022850), 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)

GO Cellular Component (7): plasma membrane (GO:0005886), 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:

CategoryPathways
Transmission across Chemical Synapses1
Neuronal System1

GO top-level categories

Rollup of top GO terms by namespace:

CategoryTerms
serotonin receptor activity2
serotonin receptor signaling pathway2
regulation of postsynaptic membrane potential2
transmitter-gated monoatomic ion channel activity2
signal transduction1
cellular response to dopamine1
anterograde trans-synaptic signaling1
monoatomic ion transport1
transmembrane transport1
monoatomic ion transmembrane transport1
regulation of biological quality1
serotonin-gated monoatomic cation channel activity1
ligand-gated ion channel signaling pathway1
transport1
regulation of membrane potential1
chemical synaptic transmission, postsynaptic1
extracellular ligand-gated monoatomic ion channel activity1
excitatory postsynaptic potential1
ligand-gated monoatomic cation channel activity1
signaling receptor activity1
monoatomic ion transmembrane transporter activity1
channel activity1
ligand-gated monoatomic ion channel activity1
binding1
membrane1
cell periphery1
plasma membrane bounded cell projection1
cell junction1
synaptic membrane1
postsynapse1
membrane protein complex1
transporter complex1
cation channel complex1
serotonin receptor complex1
neurotransmitter receptor complex1
cellular anatomical structure1

Protein interactions and networks

STRING

432 interactions, top by confidence (×1000):

Protein AProtein BPartner UniProtScore
HTR3CHTR3DQ70Z44955
HTR3CHTR3EA5X5Y0919
HTR3CHTR3AP46098912
HTR3CHTR3BO95264831
HTR3CADRA2AP08913546
HTR3CHTR5AP47898532
HTR3CHTR2BP41595505
HTR3CHTR2AP28223505
HTR3CHTR7P34969497
HTR3CHTR1FP30939491
HTR3CHTR1DP28221478
HTR3CHTR1EP28566476
HTR3CHTR1BP28222449
HTR3CHTR2CP28335438
HTR3CHTR1AP08908434

IntAct

10 interactions, top by confidence:

ABTypeScore
HTR3AHTR3Cpsi-mi:“MI:0915”(physical association)0.610
HTR3AHTR3Cpsi-mi:“MI:0403”(colocalization)0.610
HTR3Apsi-mi:“MI:0915”(physical association)0.400
HTR3CTMEM223psi-mi:“MI:0914”(association)0.350
ARHGAP8PRR5-ARHGAP8psi-mi:“MI:0914”(association)0.350
HTR3CGET1psi-mi:“MI:0914”(association)0.350
PRR5-ARHGAP8ARHGAP8psi-mi:“MI:0914”(association)0.350

BioGRID (167): MBOAT7 (Affinity Capture-MS), LSR (Affinity Capture-MS), METTL25 (Affinity Capture-MS), TMEM87A (Affinity Capture-MS), PIGO (Affinity Capture-MS), MGAT1 (Affinity Capture-MS), ALG9 (Affinity Capture-MS), GPAA1 (Affinity Capture-MS), ENTPD6 (Affinity Capture-MS), TMTC3 (Affinity Capture-MS), KIAA2013 (Affinity Capture-MS), NSDHL (Affinity Capture-MS), TPST2 (Affinity Capture-MS), MANEAL (Affinity Capture-MS), SLC38A10 (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.

AEffectBMechanism
serotonin“up-regulates activity”HTR3C“chemical activation”
HTR3Cup-regulatesExcitatory_synaptic_transmission

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

ClassificationCount (floor)
Pathogenic1
Likely pathogenic0
Uncertain significance57
Likely benign11
Benign5

Top pathogenic / likely-pathogenic (1)

Variant IDHGVSClassification
986756GRCh37/hg19 3q26.33-27.2(chr3:181171210-184706091)x1Pathogenic

SpliceAI

1176 predictions. Top by Δscore:

VariantEffectΔscore
3:184056869:A:AGacceptor_gain1.0000
3:184056870:A:Gacceptor_gain1.0000
3:184056872:C:Gacceptor_gain1.0000
3:184056872:CAGCA:Cacceptor_loss1.0000
3:184056873:A:AGacceptor_gain1.0000
3:184056873:AGCAT:Aacceptor_gain1.0000
3:184056874:G:Aacceptor_loss1.0000
3:184056874:G:GTacceptor_gain1.0000
3:184056874:GC:Gacceptor_gain1.0000
3:184056874:GCA:Gacceptor_gain1.0000
3:184056874:GCAT:Gacceptor_gain1.0000
3:184056874:GCATG:Gacceptor_gain1.0000
3:184057040:CACAG:Cdonor_gain1.0000
3:184057041:ACAG:Adonor_gain1.0000
3:184057042:CAG:Cdonor_gain1.0000
3:184057045:G:GAdonor_loss1.0000
3:184057045:G:GGdonor_gain1.0000
3:184058425:A:AGacceptor_gain1.0000
3:184058425:AGT:Aacceptor_gain1.0000
3:184058426:G:GGacceptor_gain1.0000
3:184058426:GTG:Gacceptor_gain1.0000
3:184058588:G:GGdonor_gain1.0000
3:184059562:A:Gdonor_gain1.0000
3:184059641:G:GGdonor_gain1.0000
3:184059663:G:GTdonor_gain1.0000
3:184059727:G:GTdonor_gain1.0000
3:184059975:G:GTdonor_gain1.0000
3:184060004:GGAAA:Gdonor_gain1.0000
3:184060005:G:Tdonor_gain1.0000
3:184053144:CAAGG:Cdonor_loss0.9900

AlphaMissense

2950 scored. Top likely-pathogenic:

VariantProtein changeam_pathogenicity
3:184059517:A:CS268R0.981
3:184059519:C:AS268R0.981
3:184059519:C:GS268R0.981
3:184059487:A:CS258R0.972
3:184059489:T:AS258R0.972
3:184059489:T:GS258R0.972
3:184056990:T:CF169L0.971
3:184056992:C:AF169L0.971
3:184056992:C:GF169L0.971
3:184059866:A:CS322R0.969
3:184059868:C:AS322R0.969
3:184059868:C:GS322R0.969
3:184056996:T:CF171L0.961
3:184056998:T:AF171L0.961
3:184056998:T:GF171L0.961
3:184059561:G:CK282N0.959
3:184059561:G:TK282N0.959
3:184058512:G:CW215C0.957
3:184058512:G:TW215C0.957
3:184059520:T:CF269L0.954
3:184059522:C:AF269L0.954
3:184059522:C:GF269L0.954
3:184059589:T:CF292L0.950
3:184059591:C:AF292L0.950
3:184059591:C:GF292L0.950
3:184056991:T:GF169C0.948
3:184059490:A:CS259R0.941
3:184059492:C:AS259R0.941
3:184059492:C:GS259R0.941
3:184056963:A:CS160R0.935

dbSNP variants (sampled 300 via entrez): RS1000307042 (3:184056401 A>G), RS1000624634 (3:184056140 C>T), RS1000639516 (3:184056029 A>G,T), RS1000699950 (3:184055559 C>A,G), RS1000899841 (3:184054486 T>A), RS1001024372 (3:184060082 C>A,G), RS1001389289 (3:184051284 C>T), RS1001571143 (3:184057184 G>A,T), RS1001939614 (3:184057211 C>G), RS1002242811 (3:184053785 C>A,T), RS1002320900 (3:184060883 G>A), RS1003540863 (3:184058277 C>G,T), RS1003650933 (3:184052613 C>G,T), RS1003768510 (3:184052562 G>A), RS1003898222 (3:184058041 T>C,G)

Disease associations

OMIM: gene MIM:610121 | disease phenotypes: MIM:206900

GenCC curated gene-disease

Mondo (1): anophthalmia/microphthalmia-esophageal atresia syndrome (MONDO:0008799)

Orphanet (1): Anophthalmia/microphthalmia-esophageal atresia syndrome (Orphanet:77298)

HPO phenotypes

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

GWAS associations

4 associations (top):

StudyTraitp-value
GCST001469_1Major depressive disorder5.000000e-06
GCST002383_1Anterior chamber depth8.000000e-09
GCST003739_3Esophageal adenocarcinoma2.000000e-08
GCST009391_331Metabolite levels9.000000e-06

EFO canonical traits (1, from GWAS)

EFO IDTrait name
EFO:0010432triacylglycerol 56:5 measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (3): CHEMBL2094132 (PROTEIN COMPLEX GROUP), CHEMBL2096904 (PROTEIN FAMILY), CHEMBL4296091 (PROTEIN COMPLEX)

Molecules with ChEMBL bioactivity

19 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 680,184 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

MoleculeNamePhasePatents
CHEMBL1112ARIPIPRAZOLE424,205
CHEMBL1729CISAPRIDE414,365
CHEMBL289469GRANISETRON4431
CHEMBL3NICOTINE4184,969
CHEMBL42CLOZAPINE437,581
CHEMBL46ONDANSETRON441,386
CHEMBL56564TROPISETRON419,312
CHEMBL6437MIANSERIN414,778
CHEMBL708ZIPRASIDONE421,536
CHEMBL715OLANZAPINE440,057
CHEMBL86METOCLOPRAMIDE437,825
CHEMBL11IMIPRAMINE448,893
CHEMBL39SEROTONIN3186,160
CHEMBL18041ZACOPRIDE21,760
CHEMBL18772QUIPAZINE21,108
CHEMBL2107804BEMESETRON21,019
CHEMBL478CHLOROPHENYLPIPERAZINE23,138
CHEMBL7257MEBUFOTENIN21,595
CHEMBL214268PHA-543613166

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

PharmGKB variants

4 variants.

VariantGenesLevelScore#Clin annotsDrugs
rs6766410HTR3C0.000
rs6807362HTR3C0.000
rs6808122HTR3C0.000
rs6807670HTR3C0.000

GtoPdb / IUPHAR curated pharmacology

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

Target class: lgic — 5-HT3 receptors

Binding affinities (BindingDB)

4 measured of 4 human assays (4 total across all organisms); most potent 4 below. Values come from heterogeneous assays and are not directly comparable.

LigandMeasureValue
5’-phenyl-(2’R)-spiro[4-azabicyclo[2.2.2]octane-2,2’-furo[2,3-b]pyridine]KI73 nM
[2,2’]Bithiophenyl-5-carboxylic acid (1-aza-bicyclo[2.2.2]oct-3-yl)-amideKI1040 nM
N-[(3R)-1-azabicyclo[2.2.2]oct-3-yl]-5-phenylthiophene-2-carboxamideKI2020 nM
5-Phenyl-thiophene-2-carboxylic acid (1-aza-bicyclo[2.2.2]oct-3-yl)-amideKI2020 nM

ChEMBL bioactivities

318 potent at pChembl≥5 of 324 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChemblTypeValueUnitMolecule
11.00Kd0.01nMCHEMBL143197
10.70Kd0.01995nMGRANISETRON
10.60Kd0.02512nMTROPISETRON
10.60Kd0.02512nMCHEMBL143197
10.20Kd0.0631nMTROPISETRON
10.15Ki0.071nMCHEMBL325422
10.10Kd0.07943nMONDANSETRON
10.10Kd0.07943nMGRANISETRON
10.10Kd0.07943nMZACOPRIDE
10.09IC500.08128nMCHEMBL416662
9.90Kd0.1259nMGRANISETRON
9.80Kd0.1585nMCHEMBL323208
9.80Kd0.1585nMCHEMBL40935
9.64Ki0.23nMCHEMBL43355
9.64Ki0.23nMCHEMBL327197
9.54IC500.2884nMCHEMBL299634
9.49Ki0.32nMCHEMBL111448
9.45IC500.3548nMCHEMBL53416
9.41Ki0.39nMCHEMBL111059
9.40Kd0.3981nMONDANSETRON
9.36Ki0.44nMCHEMBL113742
9.35IC500.4467nMQUIPAZINE
9.35Ki0.45nMCHEMBL325349
9.33Ki0.47nMCHEMBL113519
9.32Ki0.48nMCHEMBL320480
9.30Kd0.5012nMBEMESETRON
9.29Ki0.51nMCHEMBL315861
9.29Ki0.51nMCHEMBL333371
9.24Ki0.58nMCHEMBL112941
9.20Kd0.631nMCHEMBL40324
9.20Kd0.631nMONDANSETRON
9.17Ki0.68nMCHEMBL112237
9.16Ki0.69nMCHEMBL109322
9.15Ki0.7nMCHEMBL13535
9.10IC500.7943nMCHEMBL49932
9.10IC500.7943nMCHEMBL334923
9.08Ki0.83nMCHEMBL287987
9.07Ki0.86nMCHEMBL321477
9.06Ki0.88nMCHEMBL325235
9.04IC500.912nMCHEMBL51118
9.02Ki0.96nMCHEMBL113204
9.01IC500.9772nMCHEMBL54914
9.00Ki1nMCHEMBL54720
9.00EC501nMQUIPAZINE
9.00Kd1nMCHEMBL40883
9.00Kd1nMCHEMBL434999
8.96IC501.1nMIMIPRAMINE
8.96Ki1.1nMIMIPRAMINE
8.96Ki1.1nMCHEMBL108799
8.96Ki1.1nMCHEMBL112224

PubChem BioAssay actives

281 with measured affinity, of 612 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.

CompoundAssayTypeValueUnit
7-(4-prop-2-enylpiperazin-1-yl)-2,8,13-triazatricyclo[7.4.0.02,6]trideca-1(9),3,5,7,10,12-hexaene6355: Binding affinity against 5-hydroxytryptamine 3 receptor was measured using [3H]granisetron as radioligandic50<0.0001uM
1-methyl-N-(9-methyl-9-azabicyclo[3.3.1]nonan-3-yl)indazole-3-carboxamide6027: Potency at neuronal 5-hydroxytryptamine 3 receptor in the rabbit heartkd<0.0001uM
7-(4-benzylpiperazin-1-yl)-2,8,13-triazatricyclo[7.4.0.02,6]trideca-1(9),3,5,7,10,12-hexaene6355: Binding affinity against 5-hydroxytryptamine 3 receptor was measured using [3H]granisetron as radioligandic50<0.0001uM
4-[4-(1,3-benzodioxol-5-ylmethyl)piperazin-1-yl]-7-chloropyrrolo[1,2-a]quinoxaline6355: Binding affinity against 5-hydroxytryptamine 3 receptor was measured using [3H]granisetron as radioligandic500.0001uM
(1-methylindol-3-yl)-(4,5,6,7-tetrahydro-3H-benzimidazol-5-yl)methanone5980: Binding affinity towards [3H]quipazine labeled 5-hydroxytryptamine 3 receptor sites in HG108-15ki0.0001uM
Ondansetron6027: Potency at neuronal 5-hydroxytryptamine 3 receptor in the rabbit heartkd0.0001uM
[(1R,5S)-8-methyl-8-azabicyclo[3.2.1]octan-3-yl] 1H-indole-3-carboxylate6026: Binding affinity to 5-hydroxytryptamine 3 receptor of neuronal in the afferent rabbit vaguskd0.0001uM
4-(4-methylpiperazin-1-yl)pyrrolo[1,2-a]quinoxaline6335: Binding affinity towards 5-hydroxytryptamine 3 receptorki0.0002uM
6-(4-methylpiperazin-1-yl)-7,8,9,10-tetrahydrophenanthridine6335: Binding affinity towards 5-hydroxytryptamine 3 receptorki0.0002uM
(2-methyl-4-oxo-2-azabicyclo[3.3.1]nonan-8-yl) 1H-indole-3-carboxylate6028: Potency at neuronal 5-hydroxytryptamine 3 receptors in the rabbit heartkd0.0002uM
(4-oxo-2-azatricyclo[3.3.1.02,7]nonan-8-yl) 1H-indole-3-carboxylate200911: Potency was evaluated on rabbit heart serotonergic receptorskd0.0002uM
4-(4-benzylpiperazin-1-yl)-7-chloropyrrolo[1,2-a]quinoxaline6355: Binding affinity against 5-hydroxytryptamine 3 receptor was measured using [3H]granisetron as radioligandic500.0003uM
(8-methyl-8-azabicyclo[3.2.1]octan-3-yl) 2-oxo-1-propan-2-ylquinoline-4-carboxylate5980: Binding affinity towards [3H]quipazine labeled 5-hydroxytryptamine 3 receptor sites in HG108-15ki0.0003uM
4-(4-benzylpiperazin-1-yl)pyrrolo[1,2-a]quinoxaline6355: Binding affinity against 5-hydroxytryptamine 3 receptor was measured using [3H]granisetron as radioligandic500.0004uM
(8-methyl-8-azabicyclo[3.2.1]octan-3-yl) 2-butoxyquinoline-4-carboxylate5980: Binding affinity towards [3H]quipazine labeled 5-hydroxytryptamine 3 receptor sites in HG108-15ki0.0004uM
(8-methyl-8-azabicyclo[3.2.1]octan-3-yl) 2-(2-methylpropoxy)quinoline-4-carboxylate5980: Binding affinity towards [3H]quipazine labeled 5-hydroxytryptamine 3 receptor sites in HG108-15ki0.0004uM
(8-methyl-8-azabicyclo[3.2.1]octan-3-yl) 2-oxo-1-propylquinoline-4-carboxylate5980: Binding affinity towards [3H]quipazine labeled 5-hydroxytryptamine 3 receptor sites in HG108-15ki0.0004uM
2-piperazin-1-ylquinoline6355: Binding affinity against 5-hydroxytryptamine 3 receptor was measured using [3H]granisetron as radioligandic500.0004uM
(8-methyl-8-azabicyclo[3.2.1]octan-3-yl) 1-(2-methylpropyl)-2-oxoquinoline-4-carboxylate5980: Binding affinity towards [3H]quipazine labeled 5-hydroxytryptamine 3 receptor sites in HG108-15ki0.0005uM
7-fluoro-4-(4-methylpiperazin-1-yl)pyrrolo[1,2-a]quinoline6335: Binding affinity towards 5-hydroxytryptamine 3 receptorki0.0005uM
(8-methyl-8-azabicyclo[3.2.1]octan-3-yl) 2-oxo-1-phenylquinoline-4-carboxylate5980: Binding affinity towards [3H]quipazine labeled 5-hydroxytryptamine 3 receptor sites in HG108-15ki0.0005uM
1-butyl-4-hydroxy-N-(8-methyl-8-azabicyclo[3.2.1]octan-3-yl)-2-oxoquinoline-3-carboxamide5980: Binding affinity towards [3H]quipazine labeled 5-hydroxytryptamine 3 receptor sites in HG108-15ki0.0005uM
[(1R,5S)-8-methyl-8-azabicyclo[3.2.1]octan-3-yl] 3,5-dichlorobenzoate6027: Potency at neuronal 5-hydroxytryptamine 3 receptor in the rabbit heartkd0.0005uM
(1,1-dimethylpiperidin-1-ium-4-yl)-(1H-indol-3-yl)methanone iodide6028: Potency at neuronal 5-hydroxytryptamine 3 receptors in the rabbit heartkd0.0006uM
(8-methyl-8-azabicyclo[3.2.1]octan-3-yl) 2-methoxyquinoline-4-carboxylate5980: Binding affinity towards [3H]quipazine labeled 5-hydroxytryptamine 3 receptor sites in HG108-15ki0.0006uM
2-(3,4,5-trichlorophenyl)guanidine6339: Binding affinity to 5-HT3 serotonin receptor in NG 108-15 neuroblastoma glioma cells using [3H]GR-65630 radioligand.ki0.0007uM
(8-methyl-8-azabicyclo[3.2.1]octan-3-yl) 1-butyl-2-oxoquinoline-4-carboxylate5980: Binding affinity towards [3H]quipazine labeled 5-hydroxytryptamine 3 receptor sites in HG108-15ki0.0007uM
(8-methyl-8-azabicyclo[3.2.1]octan-3-yl) 2-(2-methylpropyl)quinoline-4-carboxylate5980: Binding affinity towards [3H]quipazine labeled 5-hydroxytryptamine 3 receptor sites in HG108-15ki0.0007uM
10-(4-methylpiperazin-1-yl)-9-azatetracyclo[11.2.1.02,11.03,8]hexadeca-2(11),3,5,7,9-pentaene6335: Binding affinity towards 5-hydroxytryptamine 3 receptorki0.0008uM
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-hexaene6355: Binding affinity against 5-hydroxytryptamine 3 receptor was measured using [3H]granisetron as radioligandic500.0008uM
N,N-dimethyl-2-[(Z)-(3-methylthieno[2,3-b]pyrrolizin-8-ylidene)amino]oxyethanamine6316: Compound was tested for binding affinity towards 5-hydroxytryptamine 3 receptoric500.0008uM
8-(4-prop-2-enylpiperazin-1-yl)-5-thia-1,7-diazatricyclo[7.3.0.02,6]dodeca-2(6),3,7,9,11-pentaene6355: Binding affinity against 5-hydroxytryptamine 3 receptor was measured using [3H]granisetron as radioligandic500.0009uM
(8-methyl-8-azabicyclo[3.2.1]octan-3-yl) 2-pentoxyquinoline-4-carboxylate5980: Binding affinity towards [3H]quipazine labeled 5-hydroxytryptamine 3 receptor sites in HG108-15ki0.0009uM
(8-methyl-8-azabicyclo[3.2.1]octan-3-yl) 2-ethoxyquinoline-4-carboxylate5980: Binding affinity towards [3H]quipazine labeled 5-hydroxytryptamine 3 receptor sites in HG108-15ki0.0009uM
7-(4-methylpiperazin-1-yl)-2,8,13-triazatricyclo[7.4.0.02,6]trideca-1(9),3,5,7,10,12-hexaene6355: Binding affinity against 5-hydroxytryptamine 3 receptor was measured using [3H]granisetron as radioligandic500.0010uM
(8-methyl-8-azabicyclo[3.2.1]octan-3-yl) 3,5-dimethylbenzoate6027: Potency at neuronal 5-hydroxytryptamine 3 receptor in the rabbit heartkd0.0010uM
(8-methyl-8-azabicyclo[3.2.1]octan-3-yl) 2-oxo-1-pentylquinoline-4-carboxylate5980: Binding affinity towards [3H]quipazine labeled 5-hydroxytryptamine 3 receptor sites in HG108-15ki0.0010uM
8-(4-benzylpiperazin-1-yl)-3-thia-1,7-diazatricyclo[7.3.0.02,6]dodeca-2(6),4,7,9,11-pentaene1855131: Binding affinity to 5-HT3 receptor (unknown origin) assessed as inhibition constantki0.0010uM
1-azabicyclo[2.2.2]octan-3-yl 1H-indole-3-carboxylate6344: In vitro Binding affinity towards 5-hydroxytryptamine 3 receptor was determinedki0.0011uM
Imipramine2198785: Inhibition of 5HT receptor (unknown origin)ic500.0011uM
(8-methyl-8-azabicyclo[3.2.1]octan-3-yl) 1-ethyl-2-oxoquinoline-4-carboxylate5980: Binding affinity towards [3H]quipazine labeled 5-hydroxytryptamine 3 receptor sites in HG108-15ki0.0011uM
(8-methyl-8-azabicyclo[3.2.1]octan-3-yl) 1-hexyl-2-oxoquinoline-4-carboxylate5980: Binding affinity towards [3H]quipazine labeled 5-hydroxytryptamine 3 receptor sites in HG108-15ki0.0011uM
8-[4-[(4-fluorophenyl)methyl]piperazin-1-yl]-5-thia-1,7-diazatricyclo[7.3.0.02,6]dodeca-2(6),3,7,9,11-pentaene6355: Binding affinity against 5-hydroxytryptamine 3 receptor was measured using [3H]granisetron as radioligandic500.0012uM
(8-methyl-8-azabicyclo[3.2.1]octan-3-yl) 1-benzyl-2-oxoquinoline-4-carboxylate5980: Binding affinity towards [3H]quipazine labeled 5-hydroxytryptamine 3 receptor sites in HG108-15ki0.0013uM
4-amino-N-[(4S,5R)-1-azabicyclo[3.3.1]nonan-4-yl]-5-chloro-2-methoxybenzamide6028: Potency at neuronal 5-hydroxytryptamine 3 receptors in the rabbit heartkd0.0013uM
4-hydroxy-N-(8-methyl-8-azabicyclo[3.2.1]octan-3-yl)-2-oxo-1-phenylquinoline-3-carboxamide5980: Binding affinity towards [3H]quipazine labeled 5-hydroxytryptamine 3 receptor sites in HG108-15ki0.0014uM
7-piperazin-1-yl-2,8,13-triazatricyclo[7.4.0.02,6]trideca-1(9),3,5,7,10,12-hexaene6355: Binding affinity against 5-hydroxytryptamine 3 receptor was measured using [3H]granisetron as radioligandic500.0015uM
N-(8-methyl-8-azabicyclo[3.2.1]octan-3-yl)-4-oxo-1H-quinoline-3-carboxamide5980: Binding affinity towards [3H]quipazine labeled 5-hydroxytryptamine 3 receptor sites in HG108-15ki0.0015uM
(8-methyl-8-azabicyclo[3.2.1]octan-3-yl) 1-(3-methylbutyl)-2-oxoquinoline-4-carboxylate5980: Binding affinity towards [3H]quipazine labeled 5-hydroxytryptamine 3 receptor sites in HG108-15ki0.0015uM
4-(4-methylpiperazin-1-yl)pyrrolo[1,2-a]quinoxalin-7-ol143671: Effective concentration against 5-Hydroxytryptamine 3 receptor by measuring [14C]guanidinium uptake on NG108-15 cells.ec500.0016uM

CTD chemical–gene interactions

4 total (human), top 4 by PubMed support.

ChemicalActions (top 5)PubMed papers
bisphenol Aincreases expression1
CGP 52608affects binding, increases reaction1
Benzo(a)pyreneaffects methylation, decreases methylation1
Okadaic Acidincreases expression1

ChEMBL screening assays

184 unique, capped per target: 119 binding, 64 functional, 1 admet

Representative assays (with source publication via chembl_document):

Assay IDTypeDescriptionSource paper
CHEMBL4368604BindingDisplacement of [3H]BRL 43694 from recombinant human 5-HT3 receptor at 10 uM after 120 mins by radiometric scintillation analysis relative to controlDesign, synthesis and evaluation of activity and pharmacokinetic profile of new derivatives of xanthone and piperazine in the central nervous system. — Bioorg Med Chem Lett
CHEMBL615717FunctionalCompound was tested for agonistic activity against 5-HT uptakeFirst tricyclic oximino derivatives as 5-HT3 ligands. — Bioorg Med Chem Lett
CHEMBL4413391ADMETAntagonist activity at serotonin receptor in human PBMC assessed as inhibition of PMA-stimulated superoxide anion generation at 10 uM preincubated for 1 hr followed by PMA-stimulation and measured after 30 mins by spectrophotometric methodIdentification of a novel DGKα inhibitor for XLP-1 therapy by virtual screening. — Eur J Med Chem

Cellosaurus cell lines

1 cell lines: 1 transformed cell line

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

CellosaurusNameCategorySex
CVCL_YA54IDG-HEK293T-HTR3C-V5-OETransformed cell lineFemale

Clinical trials (associated diseases)

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

About this page

Generated deterministically by Sugi Atlas from primary biomedical databases via BioBTree. Every record on this page traces to a primary source.

Generated
Atlas version
v1.1.2
BioBTree
v2.0.2

Sources 80

This page pulls from 80 datasets indexed by BioBTree:

alphafoldalphamissenseantibodybgeebgee_evidencebindingdbbiogrid_interactionbrendabrenda_kineticsccdscellosauruschembl_activitychembl_assaychembl_documentchembl_moleculechembl_targetciviccivic_evidenceclingen_dosageclingen_gene_validityclinical_trialsclinvarcollectrictd_gene_interactiondbsnpdepmapdiamond_similarityefoensemblentrezesm2_similarityexonfantom5_genefantom5_promotergenccgenerifgogoparentgtopdbgtopdb_interactiongwasgwas_studyhgnchpointactinterprointogenjasparmeshmimmirdbmondomsigdborphanetorthologparalogpatent_compoundpdbpfampharmgkb_clinicalpharmgkb_genepharmgkb_guidelinepharmgkb_variantpubchempubchem_activitypubchem_assaypubmedreactomereactomeparentrefseqrhearnacentralscxa_expressionscxa_gene_experimentsignorspliceaistring_interactiontranscriptufeatureuniprot