HTR1E

Summary

HTR1E (5-hydroxytryptamine receptor 1E, HGNC:5291) is a protein-coding gene on chromosome 6q14.3, encoding 5-hydroxytryptamine receptor 1E (P28566). G-protein coupled receptor for 5-hydroxytryptamine (serotonin).

Enables Gi/o-coupled serotonin receptor activity; serotonin binding activity; and serotonin receptor activity. Involved in adenylate cyclase-inhibiting serotonin receptor signaling pathway. Located in plasma membrane.

Source: NCBI Gene 3354 — RefSeq curated summary.

At a glance

• GWAS associations: 9
• Clinical variants (ClinVar): 39 total
• Druggable target: yes — 14 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_000865

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:5291
Approved symbol	HTR1E
Name	5-hydroxytryptamine receptor 1E
Location	6q14.3
Locus type	gene with protein product
Status	Approved
Aliases	5-HT1E
Ensembl gene	ENSG00000168830
Ensembl biotype	protein_coding
OMIM	182132
Entrez	3354

Gene structure

Transcript identifiers

Ensembl transcripts: 5 — 5 protein_coding

ENST00000305344, ENST00000962028, ENST00000962029, ENST00000962030, ENST00000962031

RefSeq mRNA: 1 — MANE Select: NM_000865 NM_000865

CCDS: CCDS5006

Canonical transcript exons

ENST00000305344 — 2 exons

Exon	Start	End
ENSE00001450390	86937528	86937823
ENSE00001513404	87015150	87016679

Expression profiles

Bgee: expression breadth broad, 77 present calls, max score 81.68.

FANTOM5 (CAGE): breadth broad, TPM avg 1.3028 / max 65.1478, expressed in 258 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
68826	0.9413	234
68825	0.3614	164

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	81.68	silver quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	75.36	gold quality
prefrontal cortex	UBERON:0000451	71.87	gold quality
pancreatic ductal cell	CL:0002079	68.72	silver quality
Brodmann (1909) area 9	UBERON:0013540	68.23	gold quality
frontal cortex	UBERON:0001870	67.43	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	66.56	gold quality
Brodmann (1909) area 46	UBERON:0006483	66.53	gold quality
Brodmann (1909) area 10	UBERON:0013541	66.30	gold quality
right frontal lobe	UBERON:0002810	66.26	gold quality
neocortex	UBERON:0001950	65.63	gold quality
cingulate cortex	UBERON:0003027	64.83	gold quality
anterior cingulate cortex	UBERON:0009835	64.51	gold quality
nucleus accumbens	UBERON:0001882	63.52	gold quality
cerebral cortex	UBERON:0000956	62.95	gold quality
superior frontal gyrus	UBERON:0002661	62.70	gold quality
caudate nucleus	UBERON:0001873	61.65	gold quality
endothelial cell	CL:0000115	61.50	silver quality
telencephalon	UBERON:0001893	61.36	gold quality
postcentral gyrus	UBERON:0002581	60.02	gold quality
putamen	UBERON:0001874	59.90	gold quality
forebrain	UBERON:0001890	58.19	gold quality
parietal lobe	UBERON:0001872	57.58	gold quality
cerebellar cortex	UBERON:0002129	57.40	gold quality
cerebellar hemisphere	UBERON:0002245	57.31	gold quality
brain	UBERON:0000955	57.15	gold quality
hypothalamus	UBERON:0001898	56.92	gold quality
decidua	UBERON:0002450	56.55	gold quality
central nervous system	UBERON:0001017	56.53	gold quality
right hemisphere of cerebellum	UBERON:0014890	56.40	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	1.64

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

27 targeting HTR1E, 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-3924	100.00	72.09	2394
HSA-MIR-4500	99.99	72.72	2367
HSA-LET-7A-5P	99.98	72.29	1790
HSA-LET-7B-5P	99.98	72.31	1790
HSA-LET-7C-5P	99.98	72.29	1790
HSA-LET-7E-5P	99.98	72.29	1790
HSA-LET-7F-5P	99.98	72.56	1784
HSA-LET-7G-5P	99.98	72.37	1784
HSA-LET-7I-5P	99.98	72.37	1788
HSA-MIR-98-5P	99.98	72.33	1787
HSA-MIR-495-3P	99.96	72.81	4197
HSA-MIR-5688	99.96	73.23	4504
HSA-LET-7D-5P	99.96	71.76	1632
HSA-MIR-4458	99.96	71.64	1650
HSA-MIR-589-3P	99.91	69.62	2088
HSA-MIR-33A-3P	99.70	70.27	3362
HSA-MIR-875-3P	99.63	69.47	2548
HSA-MIR-567	99.63	68.57	1219
HSA-MIR-4261	99.59	70.30	3415
HSA-MIR-409-3P	99.50	66.33	1192
HSA-MIR-147B-5P	99.45	70.62	2432
HSA-MIR-4650-3P	99.01	68.39	1062
HSA-MIR-6830-5P	99.01	68.73	1884
HSA-MIR-3149	98.77	67.13	1639
HSA-MIR-6831-5P	98.26	67.20	990
HSA-MIR-3927-3P	97.68	66.76	892
HSA-MIR-2467-5P	97.36	67.71	991

Literature-anchored findings (GeneRIF, showing 2)

• Serotonin/HTR1E signaling blocks chronic stress-promoted progression of ovarian cancer. (PMID:34093864)
• Novel interaction between neurotrophic factor-alpha1/carboxypeptidase E and serotonin receptor, 5-HTR1E, protects human neurons against oxidative/neuroexcitotoxic stress via beta-arrestin/ERK signaling. (PMID:34966948)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
drosophila_melanogaster	5-HT1A	FBGN0004168
drosophila_melanogaster	5-HT1B	FBGN0263116

Paralogs (8): HTR2A (ENSG00000102468), HTR1B (ENSG00000135312), HTR2B (ENSG00000135914), HTR2C (ENSG00000147246), HTR7 (ENSG00000148680), HTR5A (ENSG00000157219), HTR6 (ENSG00000158748), HTR1F (ENSG00000179097)

Protein

Protein identifiers

5-hydroxytryptamine receptor 1E — P28566 (reviewed: P28566)

Alternative names: S31, Serotonin receptor 1E

All UniProt accessions (1): P28566

UniProt curated annotations — full annotation on UniProt →

Function. G-protein coupled receptor for 5-hydroxytryptamine (serotonin). Also functions as a receptor for various alkaloids and psychoactive substances. Ligand binding causes a conformation change that triggers signaling via guanine nucleotide-binding proteins (G proteins) and modulates the activity of downstream effectors, such as adenylate cyclase. HTR1E is coupled to G(i)/G(o) G alpha proteins and mediates inhibitory neurotransmission by inhibiting adenylate cyclase activity.

Subcellular location. Cell membrane.

Tissue specificity. Detected in brain.

Similarity. Belongs to the G-protein coupled receptor 1 family.

RefSeq proteins (1): NP_000856* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000276	GPCR_Rhodpsn	Family
IPR002231	5HT_rcpt	Family
IPR017452	GPCR_Rhodpsn_7TM	Domain

Pfam: PF00001

UniProt features (39 total): helix 12, topological domain 8, transmembrane region 7, short sequence motif 2, binding site 2, glycosylation site 2, sequence variant 2, chain 1, disulfide bond 1, mutagenesis site 1, turn 1

Structure

Experimental structures (PDB)

3 structures.

PDB	Method	Resolution (Å)
7E33	ELECTRON MICROSCOPY	2.9
8UGY	ELECTRON MICROSCOPY	3.31
8UH3	ELECTRON MICROSCOPY	3.31

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P28566-F1	78.47	0.46

Antibody-complex structures (SAbDab): 2 — 7E33, 8UH3

Functional residue map

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

Ligand- & substrate-binding residues (2): 102; 106

Disulfide bonds (1): 95–173

Glycosylation sites (2): 2, 5

Mutagenesis-validated functional residues (1):

Position	Phenotype
311	increased g(i)/(o)-coupled receptor activity.

Function

Pathways and Gene Ontology

Reactome pathways

8 pathways

ID	Pathway
R-HSA-390666	Serotonin receptors
R-HSA-418594	G alpha (i) signalling events
R-HSA-162582	Signal Transduction
R-HSA-372790	Signaling by GPCR
R-HSA-373076	Class A/1 (Rhodopsin-like receptors)
R-HSA-375280	Amine ligand-binding receptors
R-HSA-388396	GPCR downstream signalling
R-HSA-500792	GPCR ligand binding

MSigDB gene sets: 103 (showing top): GOMF_G_PROTEIN_COUPLED_SEROTONIN_RECEPTOR_ACTIVITY, MORF_MSH3, MORF_RAD51L3, GOBP_CELL_CELL_SIGNALING, GOBP_ADENYLATE_CYCLASE_MODULATING_G_PROTEIN_COUPLED_RECEPTOR_SIGNALING_PATHWAY, GCM_RING1, MORF_CTSB, MORF_IL4, MORF_PRKCA, KEGG_NEUROACTIVE_LIGAND_RECEPTOR_INTERACTION, GOBP_SYNAPTIC_SIGNALING, MORF_THPO, GOBP_ADENYLATE_CYCLASE_INHIBITING_G_PROTEIN_COUPLED_RECEPTOR_SIGNALING_PATHWAY, GOCC_NEURON_PROJECTION, MORF_ATF2

GO Biological Process (7): G protein-coupled receptor signaling pathway (GO:0007186), G protein-coupled receptor signaling pathway, coupled to cyclic nucleotide second messenger (GO:0007187), adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway (GO:0007193), adenylate cyclase-inhibiting serotonin receptor signaling pathway (GO:0007198), chemical synaptic transmission (GO:0007268), signal transduction (GO:0007165), adenylate cyclase-activating G protein-coupled receptor signaling pathway (GO:0007189)

GO Molecular Function (7): Gi/o-coupled serotonin receptor activity (GO:0001586), G protein-coupled receptor activity (GO:0004930), G protein-coupled serotonin receptor activity (GO:0004993), neurotransmitter receptor activity (GO:0030594), serotonin binding (GO:0051378), serotonin receptor activity (GO:0099589), protein binding (GO:0005515)

GO Cellular Component (4): plasma membrane (GO:0005886), dendrite (GO:0030425), synapse (GO:0045202), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-6 pathways:

Category	Pathways
Signaling by GPCR	2
Amine ligand-binding receptors	1
GPCR downstream signalling	1
Signal Transduction	1
GPCR ligand binding	1
Class A/1 (Rhodopsin-like receptors)	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
G protein-coupled receptor signaling pathway	2
adenylate cyclase-modulating G protein-coupled receptor signaling pathway	2
G protein-coupled serotonin receptor signaling pathway	2
transmembrane signaling receptor activity	2
G protein-coupled receptor activity	1
signal transduction	1
adenylate cyclase inhibitor activity	1
Gi/o-coupled serotonin receptor activity	1
adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway	1
anterograde trans-synaptic signaling	1
cell communication	1
cellular process	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
adenylate cyclase activator activity	1
G protein-coupled serotonin receptor activity	1
G protein-coupled amine receptor activity	1
serotonin binding	1
signaling receptor activity	1
cation binding	1
amine binding	1
heterocyclic compound binding	1
binding	1
membrane	1
cell periphery	1
neuron projection	1
dendritic tree	1
cell junction	1
cellular anatomical structure	1

Protein interactions and networks

STRING

1086 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
HTR1E	HTR3A	P46098	773
HTR1E	HTR3B	O95264	696
HTR1E	SLC6A4	P31645	600
HTR1E	HTR1D	P28221	587
HTR1E	HTR1B	P28222	585
HTR1E	HTR2C	P28335	505
HTR1E	HTR2B	P41595	502
HTR1E	HTR3C	Q8WXA8	476
HTR1E	HTR1A	P08908	471
HTR1E	GRM6	O15303	470
HTR1E	TPH1	P17752	462
HTR1E	HTR3D	Q70Z44	453
HTR1E	OPRM1	P35372	451
HTR1E	HTR3E	A5X5Y0	450
HTR1E	COMTD1	Q86VU5	450

IntAct

17 interactions, top by confidence:

A	B	Type	Score
HTR1E	MEOX2	psi-mi:“MI:0915”(physical association)	0.560
HTR1E	ATP5F1B	psi-mi:“MI:0914”(association)	0.560
HTR1E	OPTN	psi-mi:“MI:0915”(physical association)	0.560
HTR1E	ATP5F1B	psi-mi:“MI:0915”(physical association)	0.560
RAMP1	HTR1E	psi-mi:“MI:0915”(physical association)	0.400
RAMP2	HTR1E	psi-mi:“MI:0915”(physical association)	0.400
HTR1E	RAMP3	psi-mi:“MI:0915”(physical association)	0.400
RAMP3	HTR1E	psi-mi:“MI:0915”(physical association)	0.400
HTR1E	ESYT2	psi-mi:“MI:0914”(association)	0.350
HTR1E	PSMC3	psi-mi:“MI:0915”(physical association)	0.000
HTR1E	PSMC4	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (11): MEOX2 (Two-hybrid), ATP5B (Affinity Capture-MS), CFAP74 (Affinity Capture-MS), ATP5B (Affinity Capture-MS), ACTBL2 (Affinity Capture-MS), CFAP74 (Affinity Capture-MS), HSPA8 (Affinity Capture-MS), ACTB (Affinity Capture-MS), PSMC3 (Affinity Capture-MS), PSMC4 (Affinity Capture-MS), ATP5B (Affinity Capture-MS)

ESM2 similar proteins: A0A678XMK4, A6QLE7, G3M4F8, O08890, O42384, O42574, O70528, P07550, P0C5J4, P10608, P17124, P18762, P25021, P25102, P28221, P28222, P28334, P28564, P28565, P28566, P30939, P30940, P35404, P35406, P46636, P47747, P56496, P60020, P60021, P61752, P79748, P97288, Q02284, Q0EAB5, Q13639, Q28044, Q28509, Q588Y6, Q61224, Q62758

Diamond homologs: E7EM37, G3M4F8, O02213, O08890, O18935, O19014, O19025, O42384, O42385, O73810, O77715, O77723, O77830, P08908, P08909, P08913, P11614, P14416, P18825, P18871, P19020, P20288, P21917, P22086, P22270, P22909, P24628, P28221, P28222, P28334, P28335, P28564, P28566, P30545, P30728, P30729, P30939, P32304, P32305, P34968

SIGNOR signaling

16 interactions.

A	Effect	B	Mechanism
HTR1E	“up-regulates activity”	GNAI1	binding
HTR1E	“up-regulates activity”	GNAI3	binding
HTR1E	“up-regulates activity”	GNAO1	binding
HTR1E	“up-regulates activity”	GNAZ	binding
serotonin(1+)	“up-regulates activity”	HTR1E	“chemical activation”
serotonin	“up-regulates activity”	HTR1E	“chemical activation”
ziprasidone	“up-regulates activity”	HTR1E	“chemical activation”
olanzapine	“up-regulates activity”	HTR1E	“chemical activation”
clozapine	“up-regulates activity”	HTR1E	“chemical activation”
risperidone	“down-regulates activity”	HTR1E	“chemical inhibition”
quetiapine	“up-regulates activity”	HTR1E	“chemical activation”
8-[4,4-bis(4-fluorophenyl)butyl]-1-phenyl-1,3,8-triazaspiro[4.5]decan-4-one	“down-regulates activity”	HTR1E	“chemical inhibition”
sertindole	“down-regulates activity”	HTR1E	“chemical inhibition”
zotepine	“down-regulates activity”	HTR1E	“chemical inhibition”
paliperidone	“down-regulates activity”	HTR1E	“chemical inhibition”
(S,S)-asenapine	“up-regulates activity”	HTR1E	“chemical activation”

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	31
Likely benign	4
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

481 predictions. Top by Δscore:

Variant	Effect	Δscore
6:86939990:G:GC	acceptor_gain	0.9900
6:86970447:C:A	acceptor_gain	0.9900
6:86981067:GCT:G	donor_gain	0.9900
6:86937819:ACAAG:A	donor_loss	0.9800
6:86937820:CAAG:C	donor_loss	0.9800
6:86937821:AAGGT:A	donor_loss	0.9800
6:86937822:AGG:A	donor_loss	0.9800
6:86937823:GGT:G	donor_loss	0.9800
6:86937824:GT:G	donor_loss	0.9800
6:86937825:T:G	donor_loss	0.9800
6:87013324:TTTA:T	donor_gain	0.9700
6:87015149:G:GT	acceptor_loss	0.9500
6:87015141:ATTT:A	acceptor_loss	0.9400
6:87015142:T:G	acceptor_loss	0.9400
6:87015148:A:AG	acceptor_gain	0.9200
6:87015149:G:GG	acceptor_gain	0.9200
6:87015140:T:G	acceptor_loss	0.9000
6:86939776:A:AG	acceptor_gain	0.8900
6:86939944:C:A	acceptor_gain	0.8900
6:86982518:C:A	donor_gain	0.8700
6:86971817:T:TA	donor_gain	0.8600
6:86971818:A:AA	donor_gain	0.8600
6:86937775:G:GT	donor_gain	0.8400
6:86939989:TG:T	acceptor_gain	0.8400
6:86982511:A:T	donor_gain	0.8400
6:86981083:C:T	donor_gain	0.8300
6:87015148:AG:A	acceptor_gain	0.8300
6:87015149:GG:G	acceptor_gain	0.8300
6:86939942:ATC:A	acceptor_gain	0.8100
6:86982510:G:GT	donor_gain	0.8100

AlphaMissense

2405 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
6:87015537:A:C	D68A	1.000
6:87015537:A:T	D68V	1.000
6:87015693:G:T	R120M	1.000
6:87015536:G:C	D68H	0.999
6:87015537:A:G	D68G	0.999
6:87015538:C:A	D68E	0.999
6:87015538:C:G	D68E	0.999
6:87015598:G:C	W88C	0.999
6:87015598:G:T	W88C	0.999
6:87015690:A:C	D119A	0.999
6:87015690:A:T	D119V	0.999
6:87015773:T:A	W147R	0.999
6:87015773:T:C	W147R	0.999
6:87015905:T:C	F191L	0.999
6:87015907:T:A	F191L	0.999
6:87015907:T:G	F191L	0.999
6:87016232:T:C	F300L	0.999
6:87016234:C:A	F300L	0.999
6:87016234:C:G	F300L	0.999
6:87016244:T:A	W304R	0.999
6:87016244:T:C	W304R	0.999
6:87016251:C:G	P306R	0.999
6:87016253:T:C	F307L	0.999
6:87016255:T:A	F307L	0.999
6:87016255:T:G	F307L	0.999
6:87015525:T:C	L64P	0.998
6:87015536:G:T	D68Y	0.998
6:87015596:T:A	W88R	0.998
6:87015596:T:C	W88R	0.998
6:87015672:T:C	L113P	0.998

dbSNP variants (sampled 300 via entrez): RS1000005459 (6:87004277 C>A), RS1000006379 (6:86996137 T>C), RS1000057428 (6:87003698 T>C), RS1000118371 (6:86997349 A>G), RS1000149127 (6:86977415 C>T), RS1000178031 (6:86957218 T>C), RS1000180591 (6:86977705 T>C), RS1000210482 (6:86975838 A>C), RS1000258787 (6:86938881 T>C), RS1000268459 (6:86969403 C>A), RS1000292174 (6:86983752 A>G), RS1000333640 (6:86937342 C>T), RS1000356991 (6:86938604 A>AT), RS1000380689 (6:86937581 G>C), RS1000392237 (6:86997971 T>C)

Disease associations

OMIM: gene MIM:182132 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

9 associations (top):

Study	Trait	p-value
GCST003075_124	Cognitive decline rate in late mild cognitive impairment	1.000000e-08
GCST003075_18	Cognitive decline rate in late mild cognitive impairment	2.000000e-08
GCST004639_40	Prudent dietary pattern	9.000000e-06
GCST004749_15	Lung cancer in ever smokers	2.000000e-06
GCST008181_15	Spontaneous preterm birth without premature rupture of membranes	4.000000e-06
GCST009501_3	Interstitial lung abnormalities	1.000000e-07
GCST009501_6	Interstitial lung abnormalities	3.000000e-09
GCST009502_5	Subpleural-predominant interstitial lung abnormalities	4.000000e-08
GCST011973_6	Colorectal cancer	1.000000e-06

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0007710	cognitive decline measurement
EFO:0008111	diet measurement
EFO:0006917	spontaneous preterm birth

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (3): CHEMBL2096904 (PROTEIN FAMILY), CHEMBL2182 (SINGLE PROTEIN), CHEMBL4524122 (PROTEIN FAMILY)

Molecules with ChEMBL bioactivity

14 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 339,970 (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
CHEMBL11	IMIPRAMINE	4	48,893
CHEMBL1200517	DIHYDROERGOTAMINE MESYLATE	4	2,704
CHEMBL1200809	AZELASTINE HYDROCHLORIDE	4	3,805
CHEMBL128	SUMATRIPTAN	4	28,367
CHEMBL2105760	BREXPIPRAZOLE	4	1,755
CHEMBL2138684	FROVATRIPTAN SUCCINATE	4	5
CHEMBL3039520	LASMIDITAN	4	550
CHEMBL42	CLOZAPINE	4	37,581
CHEMBL39	SEROTONIN	3	186,160
CHEMBL589390	LATREPIRDINE	3	466
CHEMBL7257	MEBUFOTENIN	2	1,595
CHEMBL263881	LYSERGIDE	2	20,287
CHEMBL267777	RITANSERIN	2	4,779
CHEMBL65547	PSILOCIN	2	3,023

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

GtoPdb / IUPHAR curated pharmacology

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

Target class: gpcr — 5-Hydroxytryptamine receptors

Most potent curated ligand interactions (47 total), top 25:

Ligand	Action	Affinity	Parameter
BRL-54443	Full agonist	8.7	pKi
[3H]5-HT	Full agonist	8.2	pKd
5-hydroxytryptamine	Full agonist	8.2	pKi
asenapine	Full agonist	8.0	pKi
naratriptan	Full agonist	7.7	pKi
zolmitriptan	Full agonist	7.7	pKi
lysergol	Full agonist	7.4	pKi
ergometrine	Full agonist	7.3	pKi
methylergonovine	Antagonist	7.2	pKi
eletriptan	Full agonist	7.2	pKi
α-methyl-5-HT	Full agonist	7.0	pKi
1-naphthylpiperazine	Antagonist	7.0	pKi
methiothepin	Antagonist	7.0	pKi
methysergide	Antagonist	6.8	pKi
rizatriptan	Full agonist	6.8	pKi
5-BODMT	Agonist	6.62	pKi
zotepine	Antagonist	6.5	pKi
tryptamine	Full agonist	6.5	pKi
clozapine	Full agonist	6.4	pKi
ziprasidone	Full agonist	6.4	pKi
sertindole	Antagonist	6.4	pKi
EMDT	Full agonist	6.3	pKi
5-MeO-DMT	Full agonist	6.3	pKi
5-fluorotryptamine	Full agonist	6.3	pKi
ergotamine	Full agonist	6.3	pKi

Binding affinities (BindingDB)

31 measured of 42 human assays (70 total across all organisms); most potent 31 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
NSC_104911	KI	0.1 nM
(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
2-Chlor-11-(2-dimethylaminoaethoxy)-dibenzo(b,f)-thiepin	KI	0.5 nM
METHIOTHEPIN	KI	1 nM
14C-5-hydroxy tryptamine creatinine disulfate	KI	1.2 nM
5-[2-(4-Benzo[d]isothiazol-3-yl-piperazin-1-yl)-ethyl]-6-chloro-1,3-dihydro-indol-2-one	KI	1.9 nM
4-[4-(4-Chloro-phenyl)-4-hydroxy-piperidin-1-yl]-1-(4-fluoro-phenyl)-butan-1-one;propionate(HCl)	KI	2.92 nM
8-[4-(4-fluorophenyl)-4-keto-butyl]-1-phenyl-1,3,8-triazaspiro[4.5]decan-4-one	KI	2.94 nM	US-9359372: Hexahydrodibenzo[a,g]quinolizine compound, preparation method thereof, pharmaceutical composition and use thereof
4-[2-methyl-4-(5-methyl-1,2,4-oxadiazol-3-yl)phenyl]phenyl-1’-methylspiro[3,5,6,7-tetrahydro-2H-furo[2,3-f]indole-3,4’-(hexahydropyridine)]-5-ylmethanone	KI	6.91 nM
Fluorocarazolol,(S)	KI	34 nM
LY 246708	KI	50.1 nM
cid_3396	KI	56 nM
SMR001230745	KI	63.1 nM
CAS_60-79-7	KI	87.1 nM
Methylergometrine	KI	89 nM
5-HT,omega-N-Me	KI	120 nM
(R)-1-(2-(1-(3-bromo-benzenesulfonyl)-pyrrolidin-2-yl)-ethyl)-4-methyl piperidine	KI	398 nM
CAS_3292447	KI	501 nM
NSC_5311097	KI	549 nM
(R)-4-Methyl-1-(2-(1-(naphthalene-1-sulfonyl)-pyrrolidin-2-yl)-ethyl)-piperidine(10)	KI	1000 nM
(R)-4-Methyl-1-(2-(1-toluene-3-sulfonyl)-pyrrolidin-2-yl)-ethyl)-piperidine (Oxalate salt)	KI	1000 nM
1-[2-[4-[5-chloro-1-(4-fluorophenyl)-indol-3-yl]-1-piperidyl]ethyl]imidazolidin-2-one	KI	1050 nM
4-(3-CHLOROPHENYL)-ALPHA-(DIPHENYLMETHYL)-1-PIPERAZINEETHANOL HYDROCHLORIDE	KI	1260 nM
(R)-1-(2-(1-(3,4-Dichloro-benzene sulfonyl)-pyrrolidin-2-yl)-ethyl)-4-methyl piperidine	KI	1580 nM
(R)-4-Methyl-1-(2-(1-(naphthalene-1-sulfonyl)-piperidin-2-yl)-ethyl)-piperidine(5)	KI	1580 nM
7-{4-[4-(2,3-dichlorophenyl)piperazin-1-yl]butoxy}-3,4-dihydroquinolin-2(1H)-one	EC50	1880 nM	US-10174011: Heterocyclic compounds, process for preparation of the same and use thereof
CAS_1893-33-0	KI	2770 nM
[125I]2,5-dimethoxy-4-iodoamphetamine	KI	2970 nM
METERGOLINE	EC50	3520 nM
SB-258719	KI	5010 nM
Quinoline-4-carboxylic acid {4-[2-(6-cyano-3,4-dihydro-1H-isoquinolin-2-yl)-ethyl]-cyclohexyl}-amide	KI	6310 nM

ChEMBL bioactivities

104 potent at pChembl≥5 of 113 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
9.80	Kd	0.1585	nM	CHEMBL323208
8.96	IC50	1.1	nM	IMIPRAMINE
8.96	Ki	1.1	nM	IMIPRAMINE
8.40	Ki	4	nM	SEROTONIN
8.20	Ki	6.31	nM	CHEMBL432713
7.97	Ki	10.72	nM	SEROTONIN
7.96	Ki	11	nM	SEROTONIN
7.36	Ki	44	nM	PSILOCIN
7.10	Kd	79.43	nM	MEBUFOTENIN
7.03	Ki	93	nM	LYSERGIDE
7.00	IC50	99	nM	CHEMBL22744
6.90	Ki	126.9	nM	LASMIDITAN
6.85	Ki	140	nM	CHEMBL138989
6.75	Ki	180	nM	CHEMBL5091373
6.70	Ki	200	nM	CHEMBL137781
6.55	Ki	280	nM	CHEMBL343755
6.51	Ki	310.7	nM	FROVATRIPTAN SUCCINATE
6.45	Ki	354.8	nM	CHEMBL3752900
6.42	Ki	380.2	nM	CHEMBL3752576
6.41	IC50	392	nM	CHEMBL22961
6.39	Ki	403	nM	CHEMBL4163428
6.38	Ki	413	nM	CHEMBL2391541
6.38	Ki	416.9	nM	CHEMBL2391541
6.32	Ki	478.6	nM	CHEMBL3754496
6.32	Ki	478	nM	BREXPIPRAZOLE
6.31	Ki	489.8	nM	CHEMBL3753318
6.30	Ki	501.2	nM	CHEMBL2391541
6.29	Ki	512.9	nM	CHEMBL3754166
6.28	Ki	520	nM	CHEMBL267615
6.25	Ki	556.4	nM	RITANSERIN
6.18	Ki	660	nM	CHEMBL103479
6.18	Ki	666	nM	CHEMBL5207529
6.17	Ki	682.2	nM	DIHYDROERGOTAMINE MESYLATE
6.12	Ki	762	nM	CHEMBL5934096
6.11	Ki	770	nM	CHEMBL105261
6.11	Ki	770	nM	CHEMBL5077293
6.10	Ki	793	nM	CHEMBL4209274
6.05	Ki	890	nM	CHEMBL4210782
6.02	Ki	949.1	nM	CHEMBL1256863
6.01	Ki	980.6	nM	CHEMBL5089005
6.00	Ki	1000	nM	CLOZAPINE
6.00	Ki	1000	nM	CHEMBL282971
6.00	IC50	1000	nM	CHEMBL31783
5.91	Ki	1242	nM	CHEMBL4173095
5.90	Ki	1270	nM	CHEMBL2424668
5.90	IC50	1253	nM	CHEMBL1380914
5.87	Ki	1366	nM	CHEMBL4207884
5.85	Ki	1400	nM	CHEMBL4216860
5.85	Ki	1409	nM	CHEMBL5204071
5.84	Ki	1446	nM	CHEMBL4743049

PubChem BioAssay actives

122 with measured affinity, of 742 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
(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
Imipramine	2198785: Inhibition of 5HT receptor (unknown origin)	ic50	0.0011	uM
Serotonin	4950: Binding affinity was determined against 5-hydroxytryptamine 1E receptor in human cortical homogenate	ki	0.0040	uM
(E)-3-(3,4-dichlorophenyl)-N-[5-[4-(5-hydroxy-1H-indol-3-yl)piperidin-1-yl]pentyl]prop-2-enamide	4969: Binding affinity for 5-hydroxytryptamine 1E receptor was determined	ki	0.0063	uM
3-[(6aR,9S)-7-methyl-6,6a,8,9-tetrahydro-4H-indolo[4,3-fg]quinolin-9-yl]-1,1-diethylurea	2060761: Ray2010 Assay 74 from Article : “Psychedelics and the human receptorome.”	ki	0.0443	uM
3-[2-(dimethylamino)ethyl]-1H-indol-4-ol	2060761: Ray2010 Assay 74 from Article : “Psychedelics and the human receptorome.”	ki	0.0443	uM
2-(5-methoxy-1H-indol-3-yl)-N,N-dimethylethanamine	1146451: Antagonist activity at 5-HT serotonin receptor (unknown origin)	kd	0.0794	uM
(6aR,9R)-N,N-diethyl-7-methyl-6,6a,8,9-tetrahydro-4H-indolo[4,3-fg]quinoline-9-carboxamide	2060761: Ray2010 Assay 74 from Article : “Psychedelics and the human receptorome.”	ki	0.0929	uM
3-[4-[7-[[4-(5-carbamoyl-1H-indol-3-yl)cyclohex-3-en-1-yl]amino]heptylamino]cyclohexen-1-yl]-1H-indole-5-carboxamide	404710: Binding affinity to 5HT1E receptor	ic50	0.0990	uM
7-[2-[2-(3-chlorophenyl)ethylamino]ethyl]quinolin-2-amine	1458754: Displacement of [3H]5-HT from human 5-HT1E receptor expressed in HEK cells after 90 mins by scintillation counting method	ki	0.1000	uM
2-(4-bromo-2,3,6,7-tetrahydrofuro[2,3-f][1]benzofuran-8-yl)ethanamine	2060761: Ray2010 Assay 74 from Article : “Psychedelics and the human receptorome.”	ki	0.1099	uM
2-(4-bromo-2,5-dimethoxyphenyl)ethanamine	2060761: Ray2010 Assay 74 from Article : “Psychedelics and the human receptorome.”	ki	0.1195	uM
[(6aR)-7-methyl-6,6a,8,9-tetrahydro-4H-indolo[4,3-fg]quinolin-9-yl]-[(2R,4R)-2,4-dimethylazetidin-1-yl]methanone	2060761: Ray2010 Assay 74 from Article : “Psychedelics and the human receptorome.”	ki	0.1378	uM
[(2R,4R)-2,4-dimethylazetidin-1-yl]-[(9R)-7-methyl-6,6a,8,9-tetrahydro-4H-indolo[4,3-fg]quinolin-9-yl]methanone	4971: Binding affinity towards 5-hydroxytryptamine 1E receptor	ki	0.1400	uM
2-[4-chloro-3-(2-methoxyphenyl)phenyl]-N-methylethanamine;hydrochloride	1817165: Binding affinity to 5-HT1ER (unknown origin)	ki	0.1800	uM
[(6aR)-7-methyl-6,6a,8,9-tetrahydro-4H-indolo[4,3-fg]quinolin-9-yl]-[(2S,4R)-2,4-dimethylazetidin-1-yl]methanone	2060761: Ray2010 Assay 74 from Article : “Psychedelics and the human receptorome.”	ki	0.1946	uM
[(2S,4R)-2,4-dimethylazetidin-1-yl]-[(9R)-7-methyl-6,6a,8,9-tetrahydro-4H-indolo[4,3-fg]quinolin-9-yl]methanone	4971: Binding affinity towards 5-hydroxytryptamine 1E receptor	ki	0.2000	uM
[(2S,4S)-2,4-dimethylazetidin-1-yl]-[(9R)-7-methyl-6,6a,8,9-tetrahydro-4H-indolo[4,3-fg]quinolin-9-yl]methanone	4971: Binding affinity towards 5-hydroxytryptamine 1E receptor	ki	0.2800	uM
N-[2-(5-chloro-1H-indol-3-yl)ethyl]-N-prop-2-enylprop-2-en-1-amine	1272369: Binding affinity to 5-HT 1E (unknown origin) by competition binding assay	ki	0.3548	uM
N-[2-(1H-indol-3-yl)ethyl]-N-prop-2-enylprop-2-en-1-amine	1272369: Binding affinity to 5-HT 1E (unknown origin) by competition binding assay	ki	0.3802	uM
benzyl 5-(4-methylpiperazin-1-yl)-1,3-dihydroisoindole-2-carboxylate	1358250: Displacement of [3H]-5-HT from human 5-HT1E receptor expressed in stable HEK cells after 90 mins by microbeta scintillation counting method	ki	0.4030	uM
N-[2-(5-methoxy-1H-indol-3-yl)ethyl]-N-prop-2-enylprop-2-en-1-amine	752487: Displacement of [3H]5-HT from human recombinant 5-HT1E receptor expressed in HEK293 cells after 1 to 1.5 hrs by scintillation counting analysis	ki	0.4130	uM
2-(4-ethylsulfanyl-2,5-dimethoxyphenyl)ethanamine	2060761: Ray2010 Assay 74 from Article : “Psychedelics and the human receptorome.”	ki	0.4151	uM
2-(1H-indol-3-yl)-N,N-dimethylethanamine	2060761: Ray2010 Assay 74 from Article : “Psychedelics and the human receptorome.”	ki	0.4557	uM
2-(6-fluoro-1H-indol-3-yl)-N,N-dimethylethanamine	2060761: Ray2010 Assay 74 from Article : “Psychedelics and the human receptorome.”	ki	0.4608	uM
N-[2-(5-fluoro-1H-indol-3-yl)ethyl]-N-prop-2-enylprop-2-en-1-amine	1272369: Binding affinity to 5-HT 1E (unknown origin) by competition binding assay	ki	0.4786	uM
N-[2-(5-methyl-1H-indol-3-yl)ethyl]-N-prop-2-enylprop-2-en-1-amine	1272369: Binding affinity to 5-HT 1E (unknown origin) by competition binding assay	ki	0.4898	uM
N-[2-(5-bromo-1H-indol-3-yl)ethyl]-N-prop-2-enylprop-2-en-1-amine	1272369: Binding affinity to 5-HT 1E (unknown origin) by competition binding assay	ki	0.5129	uM
2-(2-ethyl-5-methoxy-1H-indol-3-yl)-N,N-dimethylethanamine	2060761: Ray2010 Assay 74 from Article : “Psychedelics and the human receptorome.”	ki	0.5200	uM
2-(4-ethyl-2,5-dimethoxyphenyl)ethanamine	2060761: Ray2010 Assay 74 from Article : “Psychedelics and the human receptorome.”	ki	0.6263	uM
4-fluoro-N-[3-(1-methylpiperidin-4-yl)-1H-pyrrolo[3,2-b]pyridin-5-yl]benzamide	4953: In vitro binding affinity by radioligand binding assay using cell line expressing human 5-hydroxytryptamine 1E receptor	ki	0.6600	uM
6-chloro-1-(2,4,5-trimethoxyphenyl)-2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indole;hydrochloride	1880170: Binding affinity to 5HT1E receptor (unknown origin) assessed as inhibition constant	ki	0.6660	uM
3-[4-chloro-3-(2-methoxyphenyl)phenyl]pyrrolidine	1817165: Binding affinity to 5-HT1ER (unknown origin)	ki	0.7700	uM
N-[3-(1-methylpiperidin-4-yl)-1H-pyrrolo[3,2-b]pyridin-5-yl]propanamide	4953: In vitro binding affinity by radioligand binding assay using cell line expressing human 5-hydroxytryptamine 1E receptor	ki	0.7700	uM
3-(4-fluorophenyl)-1,4,5,6,7,8-hexahydropyrazolo[4,5-d]azepine	1384662: Displacement of [3H]LSD from human 5-HT1E receptor expressed in HEK cell membranes after 1.5 hrs by microbeta scintillation counting method	ki	0.7930	uM
3-(4-methylphenyl)-1,4,5,6,7,8-hexahydropyrazolo[4,5-d]azepine	1384662: Displacement of [3H]LSD from human 5-HT1E receptor expressed in HEK cell membranes after 1.5 hrs by microbeta scintillation counting method	ki	0.8900	uM
N,N-dimethyl-2-(5-methylsulfanyl-1H-indol-3-yl)ethanamine	6391: Ability to displace [3H]5-HT binding from 5-hydroxytryptamine receptor site using 1 uM LSD as masking ligand	ic50	1.0000	uM
N-[3-(1,3,4,6,7,8,9,9a-octahydropyrido[1,2-a]pyrazin-2-yl)-4-methoxyphenyl]-5-chloro-3-methyl-1-benzothiophene-2-sulfonamide	4967: The compound was tested for the binding affinity towards human cloned 5-hydroxytryptamine 1E receptor in CHO cells, using [3H]5-HT as radioligand	ki	1.0000	uM
N-[3-[(8aR)-3,4,6,7,8,8a-hexahydro-1H-pyrrolo[1,2-a]pyrazin-2-yl]-4-methoxyphenyl]-5-chloro-3-methyl-1-benzothiophene-2-sulfonamide	4967: The compound was tested for the binding affinity towards human cloned 5-hydroxytryptamine 1E receptor in CHO cells, using [3H]5-HT as radioligand	ki	1.0000	uM
(2R)-1-(4-iodo-2,5-dimethoxyphenyl)propan-2-amine	2060761: Ray2010 Assay 74 from Article : “Psychedelics and the human receptorome.”	ki	1.0130	uM
benzyl 7-[4-(2-methylprop-2-enyl)piperazin-1-yl]-3,4-dihydro-1H-isoquinoline-2-carboxylate	1358250: Displacement of [3H]-5-HT from human 5-HT1E receptor expressed in stable HEK cells after 90 mins by microbeta scintillation counting method	ki	1.2420	uM
1-[1-[2-[2-(2-fluoroethoxy)-4-piperidin-4-yloxyphenyl]acetyl]piperidin-4-yl]-3,4-dihydroquinolin-2-one;hydrochloride	771127: Binding affinity to human 5HTB receptor by competitive binding assay	ki	1.2700	uM
3-(4-chlorophenyl)-1,4,5,6,7,8-hexahydropyrazolo[4,5-d]azepine	1384662: Displacement of [3H]LSD from human 5-HT1E receptor expressed in HEK cell membranes after 1.5 hrs by microbeta scintillation counting method	ki	1.3660	uM
methyl (2S)-2-[[(4R,5R)-2-(2-hydroxyphenyl)-5-methyl-4,5-dihydro-1,3-thiazole-4-carbonyl]amino]-3-(1H-imidazol-5-yl)propanoate	1378560: Displacement of [3H]5-HT from human 5-HT1E receptor expressed in HEK cells after 90 mins by microbeta scintillation counting analysis	ki	1.4000	uM
2-(6-fluoro-2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indol-1-yl)-5-methoxyphenol	1880170: Binding affinity to 5HT1E receptor (unknown origin) assessed as inhibition constant	ki	1.4090	uM
1-(4-bromo-2,5-dimethoxyphenyl)propan-2-amine	2060761: Ray2010 Assay 74 from Article : “Psychedelics and the human receptorome.”	ki	1.4270	uM
4-bromo-N-[4-methoxy-3-(4-methylpiperazin-1-yl)phenyl]benzenesulfonamide	4962: Compound was tested for its binding affinity against cloned human 5-hydroxytryptamine 1E receptor in CHO cells using [3H]-5-HT	ki	1.5849	uM
N-[3-[(8aS)-3,4,6,7,8,8a-hexahydro-1H-pyrrolo[1,2-a]pyrazin-2-yl]-4-methoxyphenyl]-5-chloro-3-methyl-1-benzothiophene-2-sulfonamide	4967: The compound was tested for the binding affinity towards human cloned 5-hydroxytryptamine 1E receptor in CHO cells, using [3H]5-HT as radioligand	ki	1.5849	uM
benzyl 7-[4-(3-ethoxy-3-oxopropyl)piperazin-1-yl]-3,4-dihydro-1H-isoquinoline-2-carboxylate	1358250: Displacement of [3H]-5-HT from human 5-HT1E receptor expressed in stable HEK cells after 90 mins by microbeta scintillation counting method	ki	1.6660	uM
2-(6-chloro-2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indol-1-yl)-5-methoxyphenol	1880170: Binding affinity to 5HT1E receptor (unknown origin) assessed as inhibition constant	ki	1.7500	uM

CTD chemical–gene interactions

15 total (human), top 15 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	decreases methylation, affects expression	2
sodium arsenite	affects methylation	1
NSC 689534	affects binding, decreases expression	1
Resveratrol	affects cotreatment, decreases expression	1
Benzo(a)pyrene	affects methylation, increases methylation	1
Copper	affects binding, decreases expression	1
Diethylhexyl Phthalate	increases expression	1
Hydrogen Peroxide	increases expression	1
Niclosamide	decreases expression	1
Plant Extracts	decreases expression, affects cotreatment	1
Sarin	decreases expression	1
Serotonin	affects binding, decreases reaction, increases activity	1
Tretinoin	decreases expression	1
Triclosan	increases expression	1
Endocannabinoids	affects binding, decreases reaction, increases activity	1

ChEMBL screening assays

184 unique, capped per target: 161 binding, 20 functional, 3 admet

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL2060606	Binding	Inhibition of 5HT	Discovery and optimization of novel purines as potent and selective CB2 agonists. — Bioorg Med Chem Lett
CHEMBL4413391	ADMET	Antagonist 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 method	Identification of a novel DGKα inhibitor for XLP-1 therapy by virtual screening. — Eur J Med Chem
CHEMBL619167	Functional	5-HT level in K+ induced 5-hydroxytryptamine release in guinea pig cortex.	New selective and potent 5-HT(1B/1D) antagonists: chemistry and pharmacological evaluation of N-piperazinylphenyl biphenylcarboxamides and biphenylsulfonamides. — J Med Chem

Cellosaurus cell lines

1 cell lines: 1 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_LA53	PathHunter U2OS HTR1E beta-arrestin	Cancer cell line	Female

Clinical trials (associated diseases)

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