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HTR3D

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Summary

HTR3D (5-hydroxytryptamine receptor 3D, HGNC:24004) is a protein-coding gene on chromosome 3q27.1, encoding 5-hydroxytryptamine receptor 3D (Q70Z44). Forms serotonin (5-hydroxytryptamine/5-HT3)-activated cation-selective channel complexes, which when activated cause fast, depolarizing responses in neurons.

The protein encoded this gene belongs to the ligand-gated ion channel receptor superfamily. This gene encodes subunit D of the type 3 receptor for 5-hydroxytryptamine (serotonin), a biogenic hormone that functions as a neurotransmitter, a mitogen and a hormone. This hormone has been linked to neuropsychiatric disorders, including anxiety, depression, and migraine. Serotonin receptors causes fast and depolarizing responses in neurons following activation. The genes encoding subunits C, D and E of this type 3 receptor form a cluster on chromosome 3. Alternatively spliced transcript variants encoding different isoforms have been found for this gene.

Source: NCBI Gene 200909 — RefSeq curated summary.

At a glance

  • GWAS associations: 6
  • Clinical variants (ClinVar): 92 total
  • Druggable target: yes — 19 molecules with ChEMBL bioactivity
  • MANE Select transcript: NM_001145143

Identifiers

Gene identifiers

FieldValue
HGNC IDHGNC:24004
Approved symbolHTR3D
Name5-hydroxytryptamine receptor 3D
Location3q27.1
Locus typegene with protein product
StatusApproved
Ensembl geneENSG00000186090
Ensembl biotypeprotein_coding
OMIM610122
Entrez200909

Gene structure

Transcript identifiers

Ensembl transcripts: 4 — 4 protein_coding

ENST00000334128, ENST00000382489, ENST00000428798, ENST00000453435

RefSeq mRNA: 4 — MANE Select: NM_001145143 NM_001145143, NM_001163646, NM_001410851, NM_182537

CCDS: CCDS3249, CCDS46966, CCDS54685, CCDS93429

Canonical transcript exons

ENST00000428798 — 8 exons

ExonStartEnd
ENSE00001339722184038021184038273
ENSE00001492301184036748184036896
ENSE00001621745184036015184036100
ENSE00001686329184036375184036544
ENSE00001746102184031742184031807
ENSE00001786430184035178184035222
ENSE00002481290184038409184038624
ENSE00003933945184038746184039369

Expression profiles

Bgee: expression breadth tissue_specific, 4 present calls, max score 93.10.

Top tissues by expression

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

TissueAnatomy IDExpression scoreQuality
primordial germ cell in gonadCL:0000670 ∩ UBERON:000099193.10gold quality
olfactory segment of nasal mucosaUBERON:000538642.48gold quality
colonic epitheliumUBERON:000039737.20gold quality
ventricular zoneUBERON:000305336.48gold quality
cortical plateUBERON:000534336.47gold quality
bone marrow cellCL:000209236.16gold quality
sural nerveUBERON:001548835.86gold quality
mucosa of transverse colonUBERON:000499135.84gold quality
ganglionic eminenceUBERON:000402335.49gold quality
skeletal muscle tissueUBERON:000113433.38gold quality
right lungUBERON:000216733.06gold quality
monocyteCL:000057632.56gold quality
hindlimb stylopod muscleUBERON:000425232.15gold quality
leukocyteCL:000073832.12gold quality
metanephros cortexUBERON:001053331.88silver quality
bone marrowUBERON:000237131.74gold quality
muscle tissueUBERON:000238531.06gold quality
stromal cell of endometriumCL:000225529.87gold quality
prefrontal cortexUBERON:000045129.54gold quality
right uterine tubeUBERON:000130229.37gold quality
liverUBERON:000210728.84gold quality
duodenumUBERON:000211428.14gold quality
cortex of kidneyUBERON:000122528.08silver quality
placentaUBERON:000198727.59gold quality
lymph nodeUBERON:000002927.57gold quality
primary visual cortexUBERON:000243627.51gold quality
right coronary arteryUBERON:000162527.44gold quality
tonsilUBERON:000237227.05gold quality
bloodUBERON:000017827.03gold quality
vermiform appendixUBERON:000115426.42gold quality

Single-cell (SCXA)

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

ExperimentMarker?Max mean expression
E-ANND-3yes4.44

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

29 targeting HTR3D, 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-4481100.0066.421669
HSA-MIR-4745-5P99.9865.951028
HSA-MIR-185-3P99.9567.011743
HSA-MIR-4728-5P99.8569.394718
HSA-MIR-544A99.8468.661965
HSA-MIR-6785-5P99.8268.684428
HSA-MIR-2681-5P99.7567.641655
HSA-MIR-516B-5P99.5666.331495
HSA-MIR-312899.5067.851258
HSA-MIR-444199.4966.563216
HSA-MIR-6743-5P99.4863.60721
HSA-MIR-468899.4864.68828
HSA-MIR-3191-5P99.2466.521722
HSA-MIR-6799-5P99.1465.722093
HSA-MIR-447899.0765.162320
HSA-MIR-6868-5P99.0665.691284
HSA-MIR-2276-3P98.7667.751384
HSA-MIR-1139998.7165.69869
HSA-MIR-394598.6864.21553
HSA-MIR-506-5P98.0267.411065
HSA-MIR-6819-5P97.9666.591071
HSA-MIR-6847-5P97.9366.741808
HSA-MIR-4799-3P97.7865.97893
HSA-MIR-6737-5P97.7566.541044
HSA-MIR-6812-5P97.5665.391059
HSA-MIR-4720-5P97.4665.67893
HSA-MIR-5588-5P97.4665.70913
HSA-MIR-6515-5P97.0865.481219
HSA-MIR-1212896.6766.981471

Literature-anchored findings (GeneRIF, showing 4)

  • 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)
  • Polymorphism in HTR3D shows differential risks for acute chemotherapy-induced vomiting after anthracycline chemotherapy. (PMID:20602613)
  • 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)
  • 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), HTR3C (ENSG00000178084), GABRG3 (ENSG00000182256), GABRR3 (ENSG00000183185), HTR3E (ENSG00000186038)

Protein

Protein identifiers

5-hydroxytryptamine receptor 3D — Q70Z44 (reviewed: Q70Z44)

Alternative names: Serotonin receptor 3D

All UniProt accessions (2): Q70Z44, F6WC43

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 liver, as well as fetal and adult colon and kidney.

Domain organisation. The HA-stretch region of HTR3D seems to confer increased conductance to HTR3A/HTR3D 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. HTR3D sub-subfamily.

Isoforms (4)

UniProt IDNamesCanonical?
Q70Z44-11yes
Q70Z44-22
Q70Z44-33
Q70Z44-44

RefSeq proteins (4): NP_001138615, NP_001157118, NP_001397780, NP_872343 (=MANE)

Domains & families (InterPro)

IDNameType
IPR006029Neurotrans-gated_channel_TMDomain
IPR006201Neur_channelFamily
IPR006202Neur_chan_lig-bdDomain
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 (27 total): splice variant 8, topological domain 5, transmembrane region 4, sequence variant 3, region of interest 2, sequence conflict 2, signal peptide 1, chain 1, glycosylation site 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

ModelpLDDTFraction very-high
AF-Q70Z44-F164.010.05

Functional residue map

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

Glycosylation sites (1): 66

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: 65 (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, GOBP_TRANSMEMBRANE_TRANSPORT, GOCC_PLASMA_MEMBRANE_SIGNALING_RECEPTOR_COMPLEX, GOCC_POSTSYNAPSE, GOBP_REGULATION_OF_MEMBRANE_POTENTIAL, GOCC_SYNAPSE, GOCC_POSTSYNAPTIC_MEMBRANE

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

372 interactions, top by confidence (×1000):

Protein AProtein BPartner UniProtScore
HTR3DHTR3CQ8WXA8955
HTR3DHTR3AP46098932
HTR3DHTR3BO95264874
HTR3DHTR3EA5X5Y0760
HTR3DHTR5AP47898564
HTR3DHTR1FP30939486
HTR3DRIC3Q7Z5B4481
HTR3DHTR1EP28566453
HTR3DHTR1DP28221450
HTR3DHTR2AP28223448
HTR3DHTR2BP41595419
HTR3DHTR1BP28222414
HTR3DHTR2CP28335411
HTR3DPARLQ9H300409
HTR3DA0A1W2PP11A0A1W2PP11392

IntAct

7 interactions, top by confidence:

ABTypeScore
HTR3AHTR3Dpsi-mi:“MI:0915”(physical association)0.610
HTR3AHTR3Dpsi-mi:“MI:0403”(colocalization)0.610
HTR3Apsi-mi:“MI:0915”(physical association)0.400
HTR3DLRFN4psi-mi:“MI:0915”(physical association)0.400

BioGRID (6): HTR3D (Affinity Capture-MS), LRFN4 (Affinity Capture-MS), RSPRY1 (Affinity Capture-MS), HSDL1 (Affinity Capture-MS), HTR3D (Synthetic Lethality), LRFN4 (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, P02718

SIGNOR signaling

2 interactions.

AEffectBMechanism
serotonin“up-regulates activity”HTR3D“chemical activation”
HTR3Dup-regulatesExcitatory_synaptic_transmission

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

ClassificationCount (floor)
Pathogenic0
Likely pathogenic0
Uncertain significance74
Likely benign16
Benign0

Top pathogenic / likely-pathogenic (0)

SpliceAI

860 predictions. Top by Δscore:

VariantEffectΔscore
3:184038018:CAG:Cacceptor_loss1.0000
3:184038019:AGGT:Aacceptor_gain1.0000
3:184038020:GGT:Gacceptor_gain1.0000
3:184038020:GGTG:Gacceptor_gain1.0000
3:184038240:G:GGdonor_gain1.0000
3:184038585:GGAAA:Gdonor_gain1.0000
3:184038586:G:Tdonor_gain1.0000
3:184038016:A:AGacceptor_gain0.9900
3:184038016:ACCAG:Aacceptor_gain0.9900
3:184038019:A:AGacceptor_gain0.9900
3:184038019:AG:Aacceptor_gain0.9900
3:184038019:AGGTG:Aacceptor_gain0.9900
3:184038020:G:GCacceptor_gain0.9900
3:184038020:GG:Gacceptor_gain0.9900
3:184038020:GGTGG:Gacceptor_gain0.9900
3:184038127:A:Tdonor_gain0.9900
3:184038269:GCGAG:Gdonor_gain0.9900
3:184038271:GAGGT:Gdonor_loss0.9900
3:184038272:AGGTG:Adonor_loss0.9900
3:184038273:GGTG:Gdonor_loss0.9900
3:184038274:G:Tdonor_loss0.9900
3:184038275:T:Adonor_loss0.9900
3:184038408:GGT:Gacceptor_gain0.9900
3:184038520:G:GAdonor_gain0.9900
3:184038556:G:GTdonor_gain0.9900
3:184038557:G:Tdonor_gain0.9900
3:184038586:GAAA:Gdonor_gain0.9900
3:184038631:G:GTdonor_gain0.9900
3:184038631:G:Tdonor_gain0.9900
3:184035055:A:AGacceptor_gain0.9800

AlphaMissense

2609 scored. Top likely-pathogenic:

VariantProtein changeam_pathogenicity
3:184038111:T:CF251L0.939
3:184038113:C:AF251L0.939
3:184038113:C:GF251L0.939
3:184038180:T:CF274L0.898
3:184038182:C:AF274L0.898
3:184038182:C:GF274L0.898
3:184038910:T:CF434L0.896
3:184038912:C:AF434L0.896
3:184038912:C:GF434L0.896
3:184038152:G:CK264N0.883
3:184038152:G:TK264N0.883
3:184038108:A:CS250R0.881
3:184038110:T:AS250R0.881
3:184038110:T:GS250R0.881
3:184036891:T:CF219L0.865
3:184036893:C:AF219L0.865
3:184036893:C:GF219L0.865
3:184036087:T:CF123L0.842
3:184036089:C:AF123L0.842
3:184036089:C:GF123L0.842
3:184038447:A:CS320R0.820
3:184038449:C:AS320R0.820
3:184038449:C:GS320R0.820
3:184038417:T:CF310L0.817
3:184038419:C:AF310L0.817
3:184038419:C:GF310L0.817
3:184038147:T:CF263L0.802
3:184038149:C:AF263L0.802
3:184038149:C:GF263L0.802
3:184038174:A:CS272R0.787

dbSNP variants (sampled 300 via entrez): RS1000011749 (3:184032274 G>A,T), RS1000524753 (3:184032811 G>A), RS1000588217 (3:184037534 A>G), RS1000952 (3:184038034 G>A,C,T), RS1001013167 (3:184037779 T>G), RS1001346936 (3:184032580 G>A), RS1002215965 (3:184039335 A>C), RS1002465732 (3:184030330 C>A), RS1002730689 (3:184030539 C>T), RS1003482854 (3:184035204 G>A), RS1003568112 (3:184039416 G>A,C), RS1004918032 (3:184034786 C>G), RS1004930916 (3:184034947 G>A,T), RS1004953415 (3:184030567 A>G), RS1005154267 (3:184037226 G>A)

Disease associations

OMIM: gene MIM:610122 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

6 associations (top):

StudyTraitp-value
GCST001469_1Major depressive disorder5.000000e-06
GCST002383_1Anterior chamber depth8.000000e-09
GCST002783_173Body mass index9.000000e-06
GCST002783_227Body mass index1.000000e-06
GCST90002392_722Mean corpuscular volume2.000000e-10
GCST90002395_555Mean platelet volume1.000000e-23

EFO canonical traits (1, from GWAS)

EFO IDTrait name
EFO:0004340body mass index

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (2): CHEMBL2094132 (PROTEIN COMPLEX GROUP), CHEMBL2096904 (PROTEIN FAMILY)

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

3 variants.

VariantGenesLevelScore#Clin annotsDrugs
rs6443930HTR3D0.000
rs939334HTR3D0.000
rs6792482HTR3D0.000

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

317 potent at pChembl≥5 of 323 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

280 with measured affinity, of 611 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

7 total (human), top 7 by PubMed support.

ChemicalActions (top 5)PubMed papers
bisphenol Aaffects cotreatment, decreases methylation1
sodium arsenitedecreases methylation, increases expression1
Fulvestrantaffects cotreatment, decreases methylation1
Air Pollutantsincreases expression1
Benzo(a)pyrenedecreases methylation1
Silicon Dioxidedecreases expression1
Aflatoxin B1increases methylation1

ChEMBL screening assays

183 unique, capped per target: 118 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

3 cell lines: 2 cancer cell line, 1 transformed cell line

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

CellosaurusNameCategorySex
CVCL_B1FMAbcam A-549 HTR3D KO 1Cancer cell lineMale
CVCL_B2N6Abcam A-549 HTR3D KO 2Cancer cell lineMale
CVCL_YA55IDG-HEK293T-HTR3D-V5-OETransformed cell lineFemale

Clinical trials (associated diseases)

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

No linked Atlas pages yet — the cross-entity mesh grows as the corpus expands.

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
v1.1.4
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