HTR2A

Summary

HTR2A (5-hydroxytryptamine receptor 2A, HGNC:5293) is a protein-coding gene on chromosome 13q14.2, encoding 5-hydroxytryptamine receptor 2A (P28223). G-protein coupled receptor for 5-hydroxytryptamine (serotonin).

This gene encodes one of the receptors for serotonin, a neurotransmitter with many roles. Mutations in this gene are associated with susceptibility to schizophrenia and obsessive-compulsive disorder, and are also associated with response to the antidepressant citalopram in patients with major depressive disorder (MDD). MDD patients who also have a mutation in intron 2 of this gene show a significantly reduced response to citalopram as this antidepressant downregulates expression of this gene. Multiple transcript variants encoding different isoforms have been found for this gene.

Source: NCBI Gene 3356 — RefSeq curated summary.

At a glance

• GWAS associations: 7
• Clinical variants (ClinVar): 47 total
• Phenotypes (HPO): 13
• Druggable target: yes — 385 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_000621

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:5293
Approved symbol	HTR2A
Name	5-hydroxytryptamine receptor 2A
Location	13q14.2
Locus type	gene with protein product
Status	Approved
Aliases	5-HT2A
Ensembl gene	ENSG00000102468
Ensembl biotype	protein_coding
OMIM	182135
Entrez	3356

Gene structure

Transcript identifiers

Ensembl transcripts: 5 — 5 protein_coding

ENST00000542664, ENST00000543956, ENST00000612998, ENST00000941626, ENST00000941627

RefSeq mRNA: 3 — MANE Select: NM_000621 NM_000621, NM_001165947, NM_001378924

CCDS: CCDS53867, CCDS9405

Canonical transcript exons

ENST00000542664 — 4 exons

Exon	Start	End
ENSE00000682325	46892390	46892590
ENSE00002268575	46895495	46896234
ENSE00003482627	46896674	46897053
ENSE00003698734	46831546	46835639

Expression profiles

Bgee: expression breadth ubiquitous, 192 present calls, max score 96.65.

FANTOM5 (CAGE): breadth broad, TPM avg 2.2172 / max 148.3476, expressed in 328 samples.

FANTOM5 promoters (10 alternative TSS)

Promoter ID	TPM avg	Samples expressed
137232	0.7669	197
137227	0.3841	110
137226	0.3354	110
137224	0.2653	111
137231	0.1456	56
137230	0.1072	42
137225	0.0801	38
137233	0.0555	30
137229	0.0448	28
137228	0.0323	18

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
buccal mucosa cell	CL:0002336	96.65	gold quality
middle temporal gyrus	UBERON:0002771	95.92	gold quality
frontal pole	UBERON:0002795	95.13	gold quality
Brodmann (1909) area 23	UBERON:0013554	94.43	gold quality
Brodmann (1909) area 10	UBERON:0013541	93.92	gold quality
Brodmann (1909) area 46	UBERON:0006483	93.61	gold quality
endothelial cell	CL:0000115	92.62	gold quality
orbitofrontal cortex	UBERON:0004167	92.56	gold quality
superior frontal gyrus	UBERON:0002661	91.75	gold quality
primary visual cortex	UBERON:0002436	91.10	gold quality
postcentral gyrus	UBERON:0002581	90.76	gold quality
parietal lobe	UBERON:0001872	90.10	gold quality
occipital lobe	UBERON:0002021	88.80	gold quality
entorhinal cortex	UBERON:0002728	87.96	gold quality
ventricular zone	UBERON:0003053	87.49	gold quality
prefrontal cortex	UBERON:0000451	85.84	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	85.66	gold quality
frontal cortex	UBERON:0001870	84.97	gold quality
Brodmann (1909) area 9	UBERON:0013540	84.68	gold quality
neocortex	UBERON:0001950	83.96	gold quality
choroid plexus epithelium	UBERON:0003911	83.13	gold quality
cerebral cortex	UBERON:0000956	82.39	gold quality
ganglionic eminence	UBERON:0004023	79.97	gold quality
cingulate cortex	UBERON:0003027	79.88	gold quality
anterior cingulate cortex	UBERON:0009835	79.81	gold quality
right frontal lobe	UBERON:0002810	78.62	gold quality
popliteal artery	UBERON:0002250	77.15	gold quality
tibial artery	UBERON:0007610	77.15	gold quality
saphenous vein	UBERON:0007318	76.47	gold quality
telencephalon	UBERON:0001893	76.25	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	4.52

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): NR3C1, PITX2, TCF3

miRNA regulators (miRDB)

176 targeting HTR2A, 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-5011-5P	100.00	83.46	5820
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-LET-7A-3P	100.00	74.03	3932
HSA-LET-7B-3P	100.00	74.08	3913
HSA-LET-7F-1-3P	100.00	74.02	3928
HSA-MIR-98-3P	100.00	74.08	3907
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-200B-3P	100.00	73.31	2693
HSA-MIR-200C-3P	100.00	73.35	2685
HSA-MIR-429	100.00	73.44	2698
HSA-MIR-1252-5P	100.00	69.80	2774
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-5692B	100.00	71.32	2622
HSA-MIR-5692C	100.00	71.32	2622
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-4531	99.99	69.70	3181
HSA-MIR-12121	99.99	66.64	255
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-4789-5P	99.98	70.76	2721
HSA-MIR-4775	99.98	75.00	6394
HSA-LET-7F-2-3P	99.98	70.98	2588
HSA-MIR-1185-1-3P	99.98	71.04	2593
HSA-MIR-1185-2-3P	99.98	71.04	2593
HSA-MIR-3692-3P	99.98	70.27	2139
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-512-3P	99.97	67.35	1049
HSA-MIR-4666A-3P	99.96	71.71	3434
HSA-MIR-1468-3P	99.96	72.74	3797
HSA-MIR-1250-3P	99.96	70.04	4038

Literature-anchored findings (GeneRIF, showing 40)

• polymorphism of 5-HT2A receptor gene promoter may be causally related to the development of bipolar disorder (PMID:11702051)
• promoter region of the 5-HT2A receptor gene does not contribute to a predisposition to anorexia nervosa for Japanese (PMID:11702058)
• A multicenter European family-based transmission disequilibrium study found no evidence for a significant role of the 5-HT(2A) gene in anorexia nervosa. (PMID:11803452)
• Patients carrying 5-HT(2A)-C allele had more than five times the risk for attempting suicide than noncarriers. (PMID:11803534)
• Differential expression of the “C” and “T” alleles of the 5-HT2A receptor gene in the temporal cortex of normal individuals and schizophrenics. (PMID:11891796)
• Molecular dynamics of 5-HT1A and 5-HT2A serotonin receptors with methylated buspirone analogues. (PMID:11989622)
• possible influence of monoamine oxydase A (MAO-A), catechol-O-methyltransferase (COMT), serotonin receptor 2A (5-HT2A), dopamine receptor D2 (DRD2), and dopamine receptor D4 (DRD4) gene variants on timing of recurrence in mood disorders (PMID:11992560)
• no association seen between T102C polymorphism of 5-HT2a receptor gene and onset of schizophrenia in Kuwaiti Arabs (PMID:12109966)
• association between polymorphism of serotonin-2A receptor gene and schizophrenia among south Indians (PMID:12140776)
• possible association seen between variation in HTR2a, childhood ADHD, and later development of SAD in women (PMID:12167522)
• The A allele of the 5-HT 2A gene has bee associated with anorexia nervosa. (PMID:12231269)
• For the ADHD combined subtype, the T102T genotype is a protective factor and the T102C genotype is a risk factor. (PMID:12475403)
• THe promotr is -1438G/A polymorphic in children and adolescents with obsessive-compulsive disorders. (PMID:12476319)
• In upper epidermis in eczematous skin; more evenly distributed in epidermis of control skin. In inflammatory dermal mononuclear cells and vessel walls. In basal epidermal layer of eczematous and control skin. (PMID:12522576)
• The results did not support the association between the 5-HTR2A polymorphism and verbal fluency in normalcy, and agree with the assumed contribution of genotype A2A2 to the severity of schizophrenia (PMID:12624948)
• The interaction of a constitutively active arrestin with the arrestin-insensitive 5-HT(2A) receptor induces agonist-independent internalization. (PMID:12695524)
• An association was found between the presence of major depressive illness in Alzheimer’s disease and both the 5-HT2A and 5-HT2C polymorphisms. (PMID:12707936)
• A generally decreased neocortical binding potential of 5-HT2A receptor is found in Alzheimer’s brains with a significant regional reduction in orbitofrontal, prefrontal, lateral frontal, cingulate, sensorimotor, parietal inferior, and occipital region. (PMID:12714112)
• The study showed a positive association between panic disorder and the HTR2A gene, suggesting that HTR2A plays an important role in the pathogenesis of panic disorder. (PMID:12759158)
• An association was found between the HTR2A gene promoter polymorphism and depressed mood in elderly Swedish males. (PMID:12815744)
• -1438 G/A and T102C polymorphisms of the 5-HT2A receptor gene are not associated with increased risk of obsessive-compulsive disorder. The TT genotype of T102C and the AA genotype of the -1438 G/A polymorphism might be a factor in clinical severity (PMID:12927326)
• No association of the HTR2A polymorphism has been found in the overall sample of 142 unipolar affective disorder-control pairs regarding allele and genotype frequencies and homo-heterozygote distributions. (PMID:12957335)
• Review. Hyperactive platelet 5-HT2A receptor signal transduction occurs in depression. A possible mechanism for increased cardiac morbidity & mortality in depression may be this hyperreactivity & serotonin hyperresponsiveness of the platelet 5-HT2AR. (PMID:14508013)
• To examine whether variation at two common polymorphisms, T102C and -1438AG, of the serotonin 2A gene (5HT2A) are involved in the puerperal triggering mechanism of bipolar affective puerperal psychosis (PMID:14531760)
• This study investigated a functional variation of a memory-related serotonin receptor in 349 healthy young volunteers, and found 21% poorer memory performance in subjects with the rare variant. (PMID:14566344)
• 5-HT(2A) receptor gene polymorphism (A-1438G) appears to be associated with self-determinism and self-transcendence (PMID:14698468)
• absence of any interindividual variability in relative mRNA allele ratio suggests that the HTR2A locus is unlikely to contain common polymorphisms or epigenetic modification that alter HTR2A mRNA levels in adult brain (PMID:14699448)
• The results of this study support the hypothesis that the -1438A/G polymorphism of the promoter region of the 5-HTR2A gene is associated with MDD patients in a Korean population. (PMID:14730199)
• HTR2A gene is associated with schizophrenia (PMID:14741324)
• 5-HT(2A) receptor binding in the hippocampus was reduced by 29% in depressed subjects (PMID:14744461)
• Alterations in 5-HT(1A,) 5-HT(1B), and 5-HT(2A) mRNA levels in the brains of subjects with both mood disorders and schizophrenia add further support for hypothesis of dysregulation of the serotonergic system in these psychiatric disorders. (PMID:14744462)
• Single nucleotid polymorphism is associated with serotonin induced platelet aggregation. (PMID:14967409)
• A statistically significant difference between obsessive-compulsive patients and controls was observed on the genotypic distribution and allelic frequencies for the C516T variant of the serotonin receptor type gene. (PMID:15005715)
• Impulsive subjects exhibited decreased serotonin-induced calcium release by platelets, while fenfluramine-induced prolactin release was not affected. (PMID:15037867)
• These data did not provide evidence for a contribution of the 102T/C SNP of HTR2A gene to susceptibility to the southern Han Chinese schizophrenia. (PMID:15048642)
• No clear association was found between 5-HT2A variants and psychosis. (PMID:15048655)
• Study assessed genetic factors influencing antidepressant response to fluoxetine. Results implicate HTR2A in the specificity of response to fluoxetine. (PMID:15052272)
• No allele differences were detected regardless of whether the bulimia nervosa patients had suffered prior anorexia nervosa episodes. (PMID:15167698)
• 5-HT(2A) serotonin receptors are regulated by Caveolin-1 (PMID:15190056)
• genotype distribution suggests that T102C polymorphism is associated with maintenance, but not with initiation of the smoking habit. The CC genotype was more frequent in the current smokers (PMID:15211639)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	htr2aa	ENSDARG00000057029
danio_rerio	htr2ab	ENSDARG00000058165
mus_musculus	Htr2a	ENSMUSG00000034997
rattus_norvegicus	Htr2a	ENSRNOG00000010063
drosophila_melanogaster	5-HT2A	FBGN0087012
caenorhabditis_elegans		WBGENE00021897

Paralogs (8): HTR1B (ENSG00000135312), HTR2B (ENSG00000135914), HTR2C (ENSG00000147246), HTR7 (ENSG00000148680), HTR5A (ENSG00000157219), HTR6 (ENSG00000158748), HTR1E (ENSG00000168830), HTR1F (ENSG00000179097)

Protein

Protein identifiers

5-hydroxytryptamine receptor 2A — P28223 (reviewed: P28223)

Alternative names: Serotonin receptor 2A

All UniProt accessions (3): P28223, A0A087WZJ9, A0A7P0PKG8

UniProt curated annotations — full annotation on UniProt →

Function. G-protein coupled receptor for 5-hydroxytryptamine (serotonin). Also functions as a receptor for various drugs and psychoactive substances, including mescaline, psilocybin, 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI) and lysergic acid diethylamide (LSD). Ligand binding causes a conformation change that triggers signaling via guanine nucleotide-binding proteins (G proteins) and modulates the activity of downstream effectors. HTR2A is coupled to G(q)/G(11) G alpha proteins and activates phospholipase C-beta, releasing diacylglycerol (DAG) and inositol 1,4,5-trisphosphate (IP3) second messengers that modulate the activity of phosphatidylinositol 3-kinase and promote the release of Ca(2+) ions from intracellular stores, respectively. Beta-arrestin family members inhibit signaling via G proteins and mediate activation of alternative signaling pathways. Affects neural activity, perception, cognition and mood. Plays a role in the regulation of behavior, including responses to anxiogenic situations and psychoactive substances. Plays a role in intestinal smooth muscle contraction, and may play a role in arterial vasoconstriction. (Microbial infection) Acts as a receptor for human JC polyomavirus/JCPyV.

Subunit / interactions. Interacts (via C-terminus) with MPDZ and PATJ. May interact (via C-terminus) with MPP3, PRDX6, DLG4, DLG1, CASK, APBA1 and MAGI2. Interacts with GRM2 and DRD2; this may affect signaling.

Subcellular location. Cell membrane. Cell projection. Dendrite. Axon. Cytoplasmic vesicle. Membrane. Caveola. Presynapse.

Tissue specificity. Detected in brain cortex (at protein level). Detected in blood platelets.

Activity regulation. G-protein coupled receptor activity is regulated by lipids: oleamide increases HTR2A-mediated activity. Inhibited by IHCH-7179 small molecule: IHCH-7179 acts both as an agonist activator for HTR1A and as an antagonist inhibitor for HTR2A.

Domain organisation. The PDZ domain-binding motif is involved in the interaction with PATJ, CASK, APBA1, DLG1 and DLG4.

Miscellaneous. Binds lysergic acid diethylamine (LSD) in the orthosteric pocket. Bound LSD dissociates extremely slowly, with a residence time of about 221 minutes at 37 degrees Celsius.

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

Isoforms (2)

UniProt ID	Names	Canonical?
P28223-1	1	yes
P28223-2	2

RefSeq proteins (3): NP_000612, NP_001159419, NP_001365853 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000276	GPCR_Rhodpsn	Family
IPR000455	5HT2A_rcpt	Family
IPR002231	5HT_rcpt	Family
IPR017452	GPCR_Rhodpsn_7TM	Domain

Pfam: PF00001

UniProt features (69 total): helix 15, mutagenesis site 12, topological domain 8, transmembrane region 7, glycosylation site 5, sequence variant 4, short sequence motif 3, binding site 2, disulfide bond 2, turn 2, strand 2, chain 1, region of interest 1, compositionally biased region 1, site 1, modified residue 1, splice variant 1, sequence conflict 1

Structure

Experimental structures (PDB)

39 structures, top 30 by resolution.

PDB	Method	Resolution (Å)
7WC8	X-RAY DIFFRACTION	2.45
7WC9	X-RAY DIFFRACTION	2.5
9AS8	ELECTRON MICROSCOPY	2.54
7WC6	X-RAY DIFFRACTION	2.6
7WC7	X-RAY DIFFRACTION	2.6
9LL8	ELECTRON MICROSCOPY	2.62
8JT8	X-RAY DIFFRACTION	2.7
9AS7	ELECTRON MICROSCOPY	2.72
9LL9	ELECTRON MICROSCOPY	2.76
8UWL	ELECTRON MICROSCOPY	2.8
9J87	ELECTRON MICROSCOPY	2.84
9LL7	ELECTRON MICROSCOPY	2.84
6A94	X-RAY DIFFRACTION	2.9
7VOE	X-RAY DIFFRACTION	2.9
9LLB	ELECTRON MICROSCOPY	2.98
6A93	X-RAY DIFFRACTION	3
8V6U	ELECTRON MICROSCOPY	3
9AS4	ELECTRON MICROSCOPY	3.06
9AS6	ELECTRON MICROSCOPY	3.07
9UJM	ELECTRON MICROSCOPY	3.07
9ASA	ELECTRON MICROSCOPY	3.12
9AS3	ELECTRON MICROSCOPY	3.18
7WC4	X-RAY DIFFRACTION	3.2
7WC5	X-RAY DIFFRACTION	3.2
9AS2	ELECTRON MICROSCOPY	3.21
9ARX	ELECTRON MICROSCOPY	3.24
9ARY	ELECTRON MICROSCOPY	3.27
9LLA	ELECTRON MICROSCOPY	3.27
7VOD	X-RAY DIFFRACTION	3.3
9AS5	ELECTRON MICROSCOPY	3.34

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P28223-F1	74.03	0.51

Antibody-complex structures (SAbDab): 7 — 6WHA, 7RAN, 8UWL, 8V6U, 9ARY, 9AS4, 9AS8

Functional residue map

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

Catalytic / active sites (1): 229 (hydrophobic barrier that decreases the speed of ligand binding and dissociation)

Ligand- & substrate-binding residues (2): 155; 343

Post-translational modifications (1): 280

Disulfide bonds (2): 148–227, 349–353

Glycosylation sites (5): 8, 38, 44, 51, 54

Mutagenesis-validated functional residues (12):

Position	Phenotype
151	decreased ability to bind serotonin and psilocybin.
155	abolished binding to serotonin and psilocybin.
229	strongly increases dissociation of bound lysergic acid diethylamine, without affecting binding affinity. reduces signali
239	decreased ability to bind serotonin and psilocybin.
242	decreased ability to bind serotonin and psilocybin.
280	increased ability of hallucinogens to desensitize the receptor.
280	reduced receptor desensitization by nonhallucinogenic agonists.
362	decreased ability to bind serotonin and psilocybin.
463	loss of interaction with patj.
465	no effect on interaction with patj. acquires the binding properties of htr2c; when associated with s-470.
470	no effect on interaction with patj. acquires the binding properties of htr2c; when associated with s-465.
471	loss of interaction with patj, cask, apba1, dlg1 and dlg4.

Function

Pathways and Gene Ontology

Reactome pathways

8 pathways

ID	Pathway
R-HSA-390666	Serotonin receptors
R-HSA-416476	G alpha (q) 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: 436 (showing top): GOBP_POTASSIUM_ION_TRANSPORT, GOBP_MEMORY, GOBP_REGULATION_OF_CELL_ACTIVATION, GOBP_RESPONSE_TO_NITROGEN_COMPOUND, GOBP_PROTEIN_LOCALIZATION_TO_CYTOSKELETON, GOBP_PHOSPHOLIPID_METABOLIC_PROCESS, GOBP_REGULATION_OF_FAT_CELL_DIFFERENTIATION, GOBP_NUCLEOSIDE_DIPHOSPHATE_METABOLIC_PROCESS, GOMF_G_PROTEIN_COUPLED_SEROTONIN_RECEPTOR_ACTIVITY, GOBP_COGNITION, GOBP_PHOSPHATIDYLINOSITOL_METABOLIC_PROCESS, MODULE_274, GOBP_SENSORY_PERCEPTION_OF_TEMPERATURE_STIMULUS, GOBP_BEHAVIOR, GOBP_POSITIVE_REGULATION_OF_DNA_BIOSYNTHETIC_PROCESS

GO Biological Process (41): temperature homeostasis (GO:0001659), positive regulation of cytokine production involved in immune response (GO:0002720), glycolytic process (GO:0006096), intracellular calcium ion homeostasis (GO:0006874), G protein-coupled receptor signaling pathway, coupled to cyclic nucleotide second messenger (GO:0007187), positive regulation of cytosolic calcium ion concentration (GO:0007204), phospholipase C-activating serotonin receptor signaling pathway (GO:0007208), serotonin receptor signaling pathway (GO:0007210), chemical synaptic transmission (GO:0007268), memory (GO:0007613), positive regulation of cell population proliferation (GO:0008284), response to xenobiotic stimulus (GO:0009410), positive regulation of phosphatidylinositol biosynthetic process (GO:0010513), regulation of dopamine secretion (GO:0014059), artery smooth muscle contraction (GO:0014824), urinary bladder smooth muscle contraction (GO:0014832), positive regulation of heat generation (GO:0031652), negative regulation of potassium ion transport (GO:0043267), positive regulation of neuron apoptotic process (GO:0043525), protein localization to cytoskeleton (GO:0044380), positive regulation of fat cell differentiation (GO:0045600), positive regulation of glycolytic process (GO:0045821), positive regulation of vasoconstriction (GO:0045907), sensitization (GO:0046960), behavioral response to cocaine (GO:0048148), positive regulation of inflammatory response (GO:0050729), detection of temperature stimulus involved in sensory perception of pain (GO:0050965), detection of mechanical stimulus involved in sensory perception of pain (GO:0050966), release of sequestered calcium ion into cytosol (GO:0051209), negative regulation of synaptic transmission, glutamatergic (GO:0051967), positive regulation of ERK1 and ERK2 cascade (GO:0070374), G protein-coupled serotonin receptor signaling pathway (GO:0098664), presynaptic modulation of chemical synaptic transmission (GO:0099171), positive regulation of execution phase of apoptosis (GO:1900119), positive regulation of platelet aggregation (GO:1901731), positive regulation of DNA biosynthetic process (GO:2000573), signal transduction (GO:0007165), G protein-coupled receptor signaling pathway (GO:0007186), response to cocaine (GO:0042220), symbiont entry into host cell (GO:0046718)

GO Molecular Function (12): Gq/11-coupled serotonin receptor activity (GO:0001587), virus receptor activity (GO:0001618), G protein-coupled serotonin receptor activity (GO:0004993), protein tyrosine kinase activator activity (GO:0030296), neurotransmitter receptor activity (GO:0030594), identical protein binding (GO:0042802), protein-containing complex binding (GO:0044877), serotonin binding (GO:0051378), 1-(4-iodo-2,5-dimethoxyphenyl)propan-2-amine binding (GO:0071886), serotonin receptor activity (GO:0099589), G protein-coupled receptor activity (GO:0004930), protein binding (GO:0005515)

GO Cellular Component (17): neurofilament (GO:0005883), plasma membrane (GO:0005886), caveola (GO:0005901), axon (GO:0030424), dendrite (GO:0030425), cytoplasmic vesicle (GO:0031410), presynaptic membrane (GO:0042734), neuronal cell body (GO:0043025), dendritic shaft (GO:0043198), postsynaptic membrane (GO:0045211), cell body fiber (GO:0070852), G protein-coupled serotonin receptor complex (GO:0098666), glutamatergic synapse (GO:0098978), membrane (GO:0016020), cell projection (GO:0042995), synapse (GO:0045202), presynapse (GO:0098793)

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
cellular anatomical structure	4
neuron projection	3
G protein-coupled receptor signaling pathway	2
G protein-coupled serotonin receptor signaling pathway	2
binding	2
amine binding	2
transmembrane signaling receptor activity	2
cytoplasm	2
synaptic membrane	2
synapse	2
multicellular organismal-level homeostasis	1
positive regulation of cytokine production	1
cytokine production involved in immune response	1
positive regulation of production of molecular mediator of immune response	1
regulation of cytokine production involved in immune response	1
phosphoglycerate kinase activity	1
phosphoglycerate mutase activity	1
phosphopyruvate hydratase activity	1
pyruvate kinase activity	1
pyruvate metabolic process	1
generation of precursor metabolites and energy	1
aerobic respiration	1
carbohydrate catabolic process	1
pyridine nucleotide catabolic process	1
glyceraldehyde-3-phosphate dehydrogenase [NAD(P)+] (phosphorylating) activity	1
ADP catabolic process	1
ATP metabolic process	1
nicotinamide nucleotide metabolic process	1
intracellular monoatomic cation homeostasis	1
calcium ion homeostasis	1
regulation of biological quality	1
Gq/11-coupled serotonin receptor activity	1
phospholipase C-activating G protein-coupled receptor signaling pathway	1
signal transduction	1
serotonin receptor activity	1
cellular response to dopamine	1
anterograde trans-synaptic signaling	1
learning or memory	1
cell population proliferation	1
regulation of cell population proliferation	1

Protein interactions and networks

STRING

1798 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
HTR2A	GRM2	Q14416	997
HTR2A	SLC6A4	P31645	961
HTR2A	GNAQ	P50148	905
HTR2A	TPH1	P17752	901
HTR2A	BDNF	P23560	888
HTR2A	HTR3A	P46098	882
HTR2A	DLG4	P78352	880
HTR2A	HTR1A	P08908	879
HTR2A	COMT	P21964	865
HTR2A	HTR2C	P28335	817
HTR2A	MAOA	P21397	787
HTR2A	TPH2	Q8IWU9	762
HTR2A	HTR1B	P28222	750
HTR2A	DTNBP1	Q96EV8	739
HTR2A	SLC6A3	Q01959	708

IntAct

144 interactions, top by confidence:

A	B	Type	Score
HTR2A	MPDZ	psi-mi:“MI:0407”(direct interaction)	0.620
HTR2C	HTR2A	psi-mi:“MI:2364”(proximity)	0.610
HTR2A	HTR2C	psi-mi:“MI:2364”(proximity)	0.610
HTR2A	HTR2C	psi-mi:“MI:0915”(physical association)	0.610
HTR2A	HTR2A	psi-mi:“MI:2364”(proximity)	0.580
HTR2A	HTR2A	psi-mi:“MI:0915”(physical association)	0.580
HTR1A	HTR1A	psi-mi:“MI:2364”(proximity)	0.510
HTR2A	HTR2B	psi-mi:“MI:2364”(proximity)	0.470
HTR2A	HTR2B	psi-mi:“MI:0915”(physical association)	0.470
HTR2B	HTR2A	psi-mi:“MI:2364”(proximity)	0.470
PDZD2	HTR2A	psi-mi:“MI:0407”(direct interaction)	0.440
HTR2A	SNX27	psi-mi:“MI:0407”(direct interaction)	0.440
HTR2A	HTRA1	psi-mi:“MI:0407”(direct interaction)	0.440
HTR2A	PTPN3	psi-mi:“MI:0407”(direct interaction)	0.440
HTR2A	DLG1	psi-mi:“MI:0407”(direct interaction)	0.440
DLG3	HTR2A	psi-mi:“MI:0407”(direct interaction)	0.440
HTR2A	PATJ	psi-mi:“MI:0407”(direct interaction)	0.440
HTR2A	MAGI2	psi-mi:“MI:0407”(direct interaction)	0.440
HTR2A	DLG4	psi-mi:“MI:0407”(direct interaction)	0.440
HTR2A	PDZD7	psi-mi:“MI:0407”(direct interaction)	0.440
HTR2A	IL16	psi-mi:“MI:0407”(direct interaction)	0.440
HTR2A	SNTB1	psi-mi:“MI:0407”(direct interaction)	0.440
HTR2A	RHPN1	psi-mi:“MI:0407”(direct interaction)	0.440

BioGRID (13): ARF6 (Reconstituted Complex), ARF1 (Affinity Capture-Western), ARF1 (Affinity Capture-Western), ARF6 (Affinity Capture-Western), ARF1 (Reconstituted Complex), ARF6 (Reconstituted Complex), DLG4 (Affinity Capture-Western), HTR2A (Affinity Capture-Western), DLG1 (Affinity Capture-Western), HTR2A (FRET), HTR2A (Affinity Capture-Western), CBL (Affinity Capture-Western), HTR2A (Affinity Capture-Luminescence)

ESM2 similar proteins: A0A2R9YJI3, B2ZHY2, B3DM66, B4XF06, D4A3U0, O02777, O43194, O46635, P08909, P08911, P0C0W8, P14842, P18599, P20272, P21554, P28223, P28335, P32240, P34311, P34968, P35363, P47746, P50128, P50129, P56971, P70259, Q09502, Q333S9, Q5IS53, Q5IS66, Q5IS73, Q5IS98, Q5R4Q6, Q5U431, Q60F97, Q6DWJ6, Q71SP5, Q75Z89, Q801M1, Q80UC8

Diamond homologs: A0T2N3, A6QLE7, O02213, O15973, O19091, O46635, O60755, O77621, O77721, P08908, P08909, P0C5J4, P11613, P14842, P18599, P19327, P22270, P25102, P28223, P28286, P34968, P35363, P41595, P46093, P50128, P50129, P50132, P56481, P79960, Q0EAB6, Q1JQB3, Q25321, Q25322, Q2TAD5, Q4KLH9, Q4LBB6, Q4VA82, Q5IS66, Q5R4Q6, Q60F97

SIGNOR signaling

20 interactions.

A	Effect	B	Mechanism
HTR2A	“up-regulates activity”	GNAI1	binding
HTR2A	“up-regulates activity”	GNAI3	binding
HTR2A	“up-regulates activity”	GNAZ	binding
HTR2A	“up-regulates activity”	GNAQ	binding
HTR2A	“up-regulates activity”	GNA14	binding
serotonin(1+)	“up-regulates activity”	HTR2A	“chemical activation”
serotonin	“up-regulates activity”	HTR2A	“chemical activation”
ziprasidone	“down-regulates activity”	HTR2A	“chemical inhibition”
olanzapine	“down-regulates activity”	HTR2A	“chemical inhibition”
clozapine	“down-regulates activity”	HTR2A	“chemical inhibition”
haloperidol	“down-regulates activity”	HTR2A	“chemical inhibition”
risperidone	“down-regulates activity”	HTR2A	“chemical inhibition”
quetiapine	“up-regulates activity”	HTR2A	“chemical activation”
8-[4,4-bis(4-fluorophenyl)butyl]-1-phenyl-1,3,8-triazaspiro[4.5]decan-4-one	“down-regulates activity”	HTR2A	“chemical inhibition”
sertindole	“down-regulates activity”	HTR2A	“chemical inhibition”
zotepine	“down-regulates activity”	HTR2A	“chemical inhibition”
paliperidone	“down-regulates activity”	HTR2A	“chemical inhibition”
pipamperone	“down-regulates activity”	HTR2A	“chemical inhibition”
lurasidone	“down-regulates activity”	HTR2A	“chemical inhibition”

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 83 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Ras activation upon Ca2+ influx through NMDA receptor	5	52.9×	2e-06
Unblocking of NMDA receptors, glutamate binding and activation	5	50.4×	2e-06
Negative regulation of NMDA receptor-mediated neuronal transmission	5	50.4×	2e-06
Long-term potentiation	5	44.1×	3e-06
Assembly and cell surface presentation of NMDA receptors	7	32.9×	1e-07
Neurexins and neuroligins	8	29.2×	5e-08
RHOA GTPase cycle	5	6.9×	7e-03
Signaling by Rho GTPases	7	4.4×	8e-03

GO biological processes:

GO term	Partners	Fold	FDR
establishment or maintenance of epithelial cell apical/basal polarity	11	79.9×	3e-16
protein localization to synapse	6	57.5×	1e-07
receptor clustering	7	54.6×	1e-08
regulation of postsynaptic membrane neurotransmitter receptor levels	7	43.4×	4e-08
cellular response to hormone stimulus	5	23.9×	1e-04
bicellular tight junction assembly	5	20.6×	2e-04
cell-cell adhesion	9	11.4×	6e-06
protein-containing complex assembly	8	11.4×	3e-05

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	28
Likely benign	10
Benign	4

Top pathogenic / likely-pathogenic (0)

SpliceAI

408 predictions. Top by Δscore:

Variant	Effect	Δscore
13:46892385:CTTA:C	donor_loss	1.0000
13:46892386:TTAC:T	donor_loss	1.0000
13:46892387:TACC:T	donor_loss	1.0000
13:46892388:A:T	donor_loss	1.0000
13:46892389:C:CA	donor_loss	1.0000
13:46892389:CCTA:C	donor_gain	1.0000
13:46892392:A:AC	donor_gain	1.0000
13:46892393:C:CC	donor_gain	1.0000
13:46892586:GTACC:G	acceptor_gain	1.0000
13:46892587:TACC:T	acceptor_gain	1.0000
13:46892589:CC:C	acceptor_gain	1.0000
13:46892589:CCCTA:C	acceptor_loss	1.0000
13:46892590:CC:C	acceptor_gain	1.0000
13:46892591:C:CC	acceptor_gain	1.0000
13:46892592:T:G	acceptor_loss	1.0000
13:46835637:TAC:T	acceptor_gain	0.9900
13:46835638:ACC:A	acceptor_loss	0.9900
13:46835646:T:C	acceptor_gain	0.9900
13:46835646:T:TC	acceptor_gain	0.9900
13:46892383:CACTT:C	donor_loss	0.9900
13:46892384:ACTTA:A	donor_loss	0.9900
13:46892388:A:AC	donor_gain	0.9900
13:46892389:C:CC	donor_gain	0.9900
13:46892588:ACC:A	acceptor_gain	0.9900
13:46892589:CCC:C	acceptor_gain	0.9900
13:46892591:C:T	acceptor_gain	0.9900
13:46892593:A:AC	acceptor_gain	0.9900
13:46892593:A:C	acceptor_gain	0.9900
13:46895490:CT:C	donor_loss	0.9900
13:46895491:T:TA	donor_loss	0.9900

AlphaMissense

3098 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
13:46892485:C:G	R173P	1.000
13:46835123:G:T	P377Q	0.999
13:46835147:C:T	G369D	0.999
13:46835154:A:G	W367R	0.999
13:46835154:A:T	W367R	0.999
13:46835236:G:C	F339L	0.999
13:46835236:G:T	F339L	0.999
13:46835238:A:G	F339L	0.999
13:46835247:A:G	W336R	0.999
13:46835247:A:T	W336R	0.999
13:46835257:A:C	F332L	0.999
13:46835257:A:T	F332L	0.999
13:46835259:A:G	F332L	0.999
13:46835573:C:G	C227S	0.999
13:46835574:A:T	C227S	0.999
13:46892405:A:G	W200R	0.999
13:46892405:A:T	W200R	0.999
13:46892486:G:T	R173S	0.999
13:46892559:A:C	C148W	0.999
13:46892560:C:G	C148S	0.999
13:46892560:C:T	C148Y	0.999
13:46892561:A:G	C148R	0.999
13:46892561:A:T	C148S	0.999
13:46892580:C:A	W141C	0.999
13:46892580:C:G	W141C	0.999
13:46892582:A:G	W141R	0.999
13:46892582:A:T	W141R	0.999
13:46895548:T:A	D120V	0.999
13:46895548:T:C	D120G	0.999
13:46895548:T:G	D120A	0.999

dbSNP variants (sampled 300 via entrez): RS1000055091 (13:46898219 A>G), RS1000158183 (13:46861954 T>C), RS1000162432 (13:46856164 T>C), RS1000212998 (13:46855937 C>T), RS1000280037 (13:46848742 A>C), RS1000298491 (13:46892735 C>G), RS1000392619 (13:46884849 T>C), RS1000398334 (13:46850837 T>C), RS1000407629 (13:46843460 G>A,C), RS1000443038 (13:46861665 A>G), RS1000551799 (13:46857028 G>A), RS1000570309 (13:46893584 C>T), RS1000616760 (13:46852043 C>T), RS1000618093 (13:46898691 G>A,T), RS1000637933 (13:46891262 T>G)

Disease associations

OMIM: gene MIM:182135 | disease phenotypes:

GenCC curated gene-disease

Mondo (1): schizophrenia, susceptibility to (MONDO:0100182)

Orphanet (0):

HPO phenotypes

13 total (13 of 13 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000716	Depression
HP:0000722	Compulsive behaviors
HP:0000738	Hallucinations
HP:0000739	Anxiety
HP:0000746	Delusion
HP:0002353	EEG abnormality
HP:0007086	Social and occupational deterioration
HP:0010982	Polygenic inheritance
HP:0012166	Skin-picking
HP:0030212	Collectionism
HP:0100753	Schizophrenia
HP:0410291	Negativism

GWAS associations

7 associations (top):

Study	Trait	p-value
GCST000960_6	Cardiac hypertrophy	6.000000e-06
GCST001521_9	Subcutaneous adipose tissue	6.000000e-06
GCST002778_8	Parkinson disease and lewy body pathology	2.000000e-06
GCST004061_7	Sjögren’s syndrome	1.000000e-06
GCST005782_7	Serum 25-Hydroxyvitamin D levels	4.000000e-09
GCST012490_249	Femur bone mineral density x serum urate levels interaction	8.000000e-09
GCST012796_8	Sjögren’s syndrome	3.000000e-06

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0002503	cardiac hypertrophy
EFO:0004531	urate measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (6): CHEMBL2095200 (PROTEIN FAMILY), CHEMBL2096662 (SELECTIVITY GROUP), CHEMBL2096904 (PROTEIN FAMILY), CHEMBL2111468 (SELECTIVITY GROUP), CHEMBL224 (SINGLE PROTEIN), CHEMBL4630758 (PROTEIN COMPLEX)

Molecules with ChEMBL bioactivity

385 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 839,149 (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
CHEMBL1423	PIMOZIDE	4	17,310
CHEMBL1729	CISAPRIDE	4	14,365
CHEMBL42	CLOZAPINE	4	37,581
CHEMBL54	HALOPERIDOL	4	60,883
CHEMBL715	OLANZAPINE	4	40,057
CHEMBL716	QUETIAPINE	4	26,465
CHEMBL360328	LORCASERIN	4	2,132
CHEMBL11	IMIPRAMINE	4	48,893
CHEMBL1000	CETIRIZINE	4	26,030
CHEMBL1008	BEPRIDIL	4	11,776
CHEMBL1009	LEVODOPA	4	103,854
CHEMBL1014	CANDESARTAN CILEXETIL	4	11,194
CHEMBL1017	TELMISARTAN	4	27,457
CHEMBL103	PROGESTERONE	4	162,141
CHEMBL104	CLOTRIMAZOLE	4	56,325
CHEMBL1064	SIMVASTATIN	4	123,163
CHEMBL1065	METHYSERGIDE	4	8,455
CHEMBL1071	OXAPROZIN	4	51,044
CHEMBL1078261	PROPIVERINE	4	4,890
CHEMBL1085	ACETOPHENAZINE	4	5,134
CHEMBL109	VALPROIC ACID	4
CHEMBL1095777	INDACATEROL	4
CHEMBL1108	DROPERIDOL	4
CHEMBL111	RIMONABANT	4
CHEMBL1110	ALOSETRON	4
CHEMBL1112	ARIPIPRAZOLE	4
CHEMBL1113	AMOXAPINE	4
CHEMBL1123	DICYCLOMINE	4
CHEMBL1171837	PONATINIB	4
CHEMBL1172	DESLORATADINE	4

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

PharmGKB clinical annotations

50 annotations.

Variant	Type	Level	Drugs	Phenotypes
rs2770296	Efficacy	3	bupropion	Major Depressive Disorder
rs6305	Toxicity	3	Analgesics;Antiinflammatory agents;non-steroids;Ergot alkaloids;opioids;sumatriptan
rs6311	Efficacy	3	risperidone	Autism
rs6311	Efficacy	4	venlafaxine	Major Depressive Disorder
rs6311	Efficacy	4	paroxetine	Major Depressive Disorder;Obsessive-Compulsive Disorder
rs6311	Efficacy	4	escitalopram	Major Depressive Disorder
rs6311	Efficacy	4	citalopram	Major Depressive Disorder
rs6311	Toxicity	4	fluvoxamine	Major Depressive Disorder
rs6311	Efficacy	4	fluvoxamine	Major Depressive Disorder
rs6311	Toxicity	4	fluoxetine	Major Depressive Disorder
rs6311	Toxicity	4	sertraline	Major Depressive Disorder;Physiological sexual disorder
rs6311	Efficacy	4	sertraline	Major Depressive Disorder
rs6311	Efficacy	3	antipsychotics	Tardive Dyskinesia
rs6311	Toxicity	3	antidepressants	adverse events;Bipolar Disorder;Depression;Major Depressive Disorder
rs6311	Toxicity	3	citalopram	Major Depressive Disorder;Nausea;Vomiting
rs6311	Toxicity	3	escitalopram	Anxiety Disorders;Major Depressive Disorder
rs6311	Toxicity	3	paroxetine	Depression;Major Depressive Disorder
rs6311	Toxicity	3	Selective serotonin reuptake inhibitors	Diarrhea;Diminished ability to concentrate;Dizziness;Major Depressive Disorder;Tremor
rs6311	Efficacy	4	fluoxetine
rs6311	Efficacy	4	antidepressants	Bipolar Disorder;Depression;Major Depressive Disorder
rs6313	Efficacy	3	olanzapine;risperidone	Alzheimer Disease
rs6313	Efficacy	4	fluoxetine
rs6313	Efficacy	4	antidepressants	Bipolar Disorder;Depression;Major Depressive Disorder
rs6313	Efficacy	4	sertraline	Anxiety Disorders;Depression
rs6313	Efficacy	4	venlafaxine	Major Depressive Disorder
rs6313	Efficacy	4	fluvoxamine	Major Depressive Disorder
rs6313	Efficacy	4	paroxetine	Major Depressive Disorder
rs6313	Efficacy	4	escitalopram	Major Depressive Disorder
rs6313	Efficacy	4	citalopram	Major Depressive Disorder
rs6313	Toxicity	4	sertraline	Major Depressive Disorder;Physiological sexual disorder
rs6313	Toxicity	3	olanzapine	Schizophrenia;Weight gain
rs6313	Toxicity	3	efavirenz	HIV infectious disease
rs6313	Toxicity	3	risperidone	Drug Toxicity
rs6313	Efficacy	3	risperidone	Schizophrenia
rs6313	Efficacy	3	olanzapine	Schizophrenia
rs6313	Toxicity	3	antidepressants	adverse events;Bipolar Disorder;Depression;Major Depressive Disorder
rs6313	Toxicity	3	citalopram	Major Depressive Disorder;Physiological sexual disorder
rs6313	Toxicity	3	paroxetine	Depression
rs6314	Efficacy	3	olanzapine	Schizophrenia
rs6314	Efficacy	3	antidepressants	Major Depressive Disorder

PharmGKB variants

16 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs6305	HTR2A	3	1.50	1	Analgesics;Antiinflammatory agents;non-steroids;Ergot alkaloids;opioids;sumatriptan
rs6311	HTR2A	3	2.25	18	citalopram;sertraline;Selective serotonin reuptake inhibitors;paroxetine;risperidone;antidepressants;escitalopram;fluvoxamine;fluoxetine;venlafaxine
rs6312	HTR2A		0.00	0
rs6313	HTR2A	3	2.75	18	paroxetine;escitalopram;citalopram;efavirenz;risperidone;sertraline;olanzapine;olanzapine;risperidone;antidepressants;fluoxetine
rs6314	HTR2A	3	6.00	2	olanzapine;antidepressants
rs659734	HTR2A		0.00	0
rs1928040	HTR2A		0.00	0
rs7997012	HTR2A	3	6.75	8	paroxetine;venlafaxine;olanzapine;citalopram;antidepressants;escitalopram;fluoxetine;sertraline
rs9316233	HTR2A	3	2.75	1	escitalopram
rs17288723	HTR2A		0.00	0
rs2274639	HTR2A		0.00	0
rs9567746	HTR2A		0.00	0
rs2770296	HTR2A	3	2.25	1	bupropion
rs17289304	HTR2A		0.00	0
rs3803189	HTR2A		0.00	0
rs3742278	HTR2A		0.00	0

PharmGKB dosing guidelines

2 guidelines.

Source	Drug	Guideline	Dosing?	Recommendation?
CPIC	citalopram;escitalopram	Annotation of CPIC Guideline for citalopram, escitalopram and HTR2A
CPIC	desvenlafaxine;duloxetine;fluoxetine;fluvoxamine;levomilnacipran;milnacipran;paroxetine;sertraline;venlafaxine;vilazodone;vortioxetine	Annotation of CPIC Guideline for desvenlafaxine, duloxetine, fluoxetine, fluvoxamine, levomilnacipran, milnacipran, paroxetine, sertraline, venlafaxine, vilazodone, vortioxetine and HTR2A

GtoPdb / IUPHAR curated pharmacology

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

Target class: gpcr — 5-Hydroxytryptamine receptors

Most potent curated ligand interactions (144 total), top 25:

Ligand	Action	Affinity	Parameter
compound 3b [PMID:28943244]	Antagonist	10.65	pKi
asenapine	Antagonist	10.22	pKi
MT-1207	Antagonist	10.1	pKi
risperidone	Inverse agonist	10.0	pKi
[3H]fananserin	Antagonist	9.9	pKd
AC-90179	Inverse agonist	9.7	pKi
[3H]ketanserin	Antagonist	9.7	pKd
ketanserin	Antagonist	9.7	pKi
mianserin	Antagonist	9.6	pKi
ziprasidone	Antagonist	9.51	pKi
methylergonovine	Full agonist	9.4	pKi
Lysergide	Full agonist	9.4	pKi
spiperone	Antagonist	9.4	pKi
sertindole	Antagonist	9.4	pKi
pimavanserin	Inverse agonist	9.3	pKi
lumateperone	Antagonist	9.3	pKi
volinanserin	Antagonist	9.3	pIC50
(R)-DOI	Full agonist	9.2	pKi
brolamfetamine	Full agonist	9.2	pKi
LY86057	Antagonist	9.2	pKi
DOI	Full agonist	9.2	pKi
2C-B	Agonist	9.18	pKi
[11C]GSK215083	Antagonist	9.1	pKi
(+)-LSD	Full agonist	9.1	pKi
3HDOB	Full agonist	9.1	pKd

Binding affinities (BindingDB)

1256 measured of 1310 human assays (1353 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
(R)-2-(4-Bromo-2,5-dimethoxy-phenyl)-1-methyl-ethylamine	EC50	0.018 nM
N-[4-(2-aminoethoxy)-3-(2-methylpyrazol-3-yl)phenyl]-2-(4-fluorophenyl)-2-oxoacetamide	IC50	0.025 nM	US-8664258: Primary amines and derivatives thereof as modulators of the 5-HT2A serotonin receptor useful for the treatment of disorders related thereto
2-(8-Bromo-2,3,6,7-tetrahydro-benzo[1,2-b;4,5-b’]difuran-4-yl)-ethylamine	EC50	0.029 nM
BW-501C	KI	0.07 nM
N-[3-(4-chloro-1-methylpyrazol-5-yl)-4-[2-(2-methoxyethylamino)ethoxy]phenyl]-3-(trifluoromethyl)benzamide	IC50	0.082 nM	US-8680119: Ethers, secondary amines and derivatives thereof as modulators of the 5-HT2A serotonin receptor useful for the treatment of disorders related thereto
DOHx	KI	0.1 nM
NSC_104911	KI	0.1 nM
roxindole	KI	0.11 nM
N-(Trans-4-(2-(4-(benzo[b]thiophen-4-yl)piperazin-1-yl)ethyl)cyclohexyl)furan-2-carboxamide	IC50	0.12 nM	US-12459931: Benzothiophene derivative regulator, preparation method therefor and use thereof
(2,3-Dimethoxy-phenyl)-{1-[2-(4-fluoro-phenyl)-ethyl]-piperidin-4-yl}-methanol(MDL 100907)	KI	0.14 nM
3,3-diethyl-1-[(4R,7R)-6-methyl-6,11-diazatetracyclo[7.6.1.0^{2,7}.0^{12,16}]hexadeca-1(15),2,9,12(16),13-pentaen-4-yl]urea	KI	0.15 nM
CHEMBL1434583	EC50	0.181 nM
ethyl N-[4-[2-[4-(1,2-benzothiazol-3-yl)piperazin-1-yl]ethyl]cyclohexyl]carbamate	KI	0.2 nM	US-9550741: Benzoisothiazole compounds and methods of treating schizophrenia
N-(Trans-4-(2-(4-(benzo[b]thiophen-4-yl)piperazin-1-yl)ethyl)cyclohexyl)-1-hydroxycyclopropane-1-carboxamide	IC50	0.2 nM	US-12459931: Benzothiophene derivative regulator, preparation method therefor and use thereof
6-(2-(4-(benzo[b]thiophen-4-yl)piperidin-1-yl)ethyl)-2H-benzo[b][1,4]oxazin-3(4H)-one	EC50	0.223 nM	US-10174011: Heterocyclic compounds, process for preparation of the same and use thereof
5-(2-(4-(6-fluorobenzo[b]thiophen-4-yl)piperazin-1-yl)ethyl)indolin-2-one	EC50	0.235 nM	US-10174011: Heterocyclic compounds, process for preparation of the same and use thereof
N-[4-(2-aminoethoxy)-3-(4-chloro-1-methylpyrazol-5-yl)phenyl]-4-(trifluoromethyl)cyclohexane-1-carboxamide	IC50	0.26 nM	US-8664258: Primary amines and derivatives thereof as modulators of the 5-HT2A serotonin receptor useful for the treatment of disorders related thereto
(S,S)-reboxetine	KI	0.3 nM
NSC_8226	KI	0.35 nM
2C-T-2	EC50	0.354 nM
N-(Trans-4-(2-(4-(benzo[b]thiophen-4-yl)piperazin-1-yl)ethyl)cyclohexyl)-3-hydroxy-3-methylbutanamide	IC50	0.36 nM	US-12459931: Benzothiophene derivative regulator, preparation method therefor and use thereof
1-[2-(4-methylphenyl)-5-tert-butyl-pyrazol-3-yl]-3-[4-(2-morpholin-4-ylethoxy)naphthalen-1-yl]urea	KD	0.37 nM
5-(2-(4-(benzo[b]thiophen-4-yl)piperazin-1-yl)ethyl)benzo[d]thiazol-2-amine	EC50	0.379 nM	US-10174011: Heterocyclic compounds, process for preparation of the same and use thereof
7-(2-(4-(benzo[b]thiophen-4-yl)piperazin-1-yl)ethyl)benzo[d]thiazol-2-amine	EC50	0.397 nM	US-10174011: Heterocyclic compounds, process for preparation of the same and use thereof
DOBz	KI	0.4 nM
2-[4-(3,3-difluoropropylsulfanyl)-2,5-dimethoxyphenyl]ethanamine	KI	0.4 nM	US-20250236589: THERAPEUTIC PHENETHYLAMINE COMPOSITIONS AND METHODS OF USE
CAS_82830-44-2	EC50	0.418 nM
N-(Trans-4-(2-(4-(benzo[b]thiophen-4-yl)piperazin-1-yl)ethyl)cyclohexyl)oxazole-2-carboxamide	IC50	0.43 nM	US-12459931: Benzothiophene derivative regulator, preparation method therefor and use thereof
N-(Trans-4-(2-(4-(benzo[b]thiophen-4-yl)piperazin-1-yl)ethyl)cyclohexyl)-2-methoxyacetamide	IC50	0.47 nM	US-12459931: Benzothiophene derivative regulator, preparation method therefor and use thereof
LSD,2-Bromo	KI	0.48 nM
2-(4-Ethylsulfanyl-2,5-dimethoxy-phenyl)-1-methyl-ethylamine	EC50	0.489 nM
2-Chlor-11-(2-dimethylaminoaethoxy)-dibenzo(b,f)-thiepin	KI	0.5 nM
CHEMBL5198213	EC50	0.5 nM
(2S)-N-ethyl-N-[2-[4-(6-fluoro-1H-indol-3-yl)piperidin-1-yl]ethyl]-2-hydroxypropanamide	KI	0.5 nM	US-11339151: Aliphatic acid amide derivative
N-[3-(4-chloro-1-methylpyrazol-5-yl)-4-(2-hydroxyethoxy)phenyl]-3-methoxybenzamide	IC50	0.51 nM	US-8680119: Ethers, secondary amines and derivatives thereof as modulators of the 5-HT2A serotonin receptor useful for the treatment of disorders related thereto
N-[4-[2-[4-(1,2-benzothiazol-3-yl)piperazin-1-yl]ethyl]cyclohexyl]-1H-pyrrole-2-carboxamide	KI	0.52 nM	US-9550741: Benzoisothiazole compounds and methods of treating schizophrenia
2-[2,5-bis(trideuteriomethoxy)-4-(trifluoromethylsulfanyl)phenyl]ethanamine	KI	0.54 nM	US-20250236589: THERAPEUTIC PHENETHYLAMINE COMPOSITIONS AND METHODS OF USE
1-(Cis-4-(2-(4-(benzo[b]thiophen-4-yl)piperazin-1-yl)ethyl)-4-fluorocyclohexyl)-3-ethylurea	IC50	0.57 nM	US-12459931: Benzothiophene derivative regulator, preparation method therefor and use thereof
phenyl N-[4-[2-[4-(1,2-benzothiazol-3-yl)piperazin-1-yl]ethyl]cyclohexyl]carbamate	KI	0.58 nM	US-9550741: Benzoisothiazole compounds and methods of treating schizophrenia
6-(2-(4-(6-fluorobenzo[b]thiophen-4-yl)piperazin-1-yl)ethyl)-2H-benzo[b][1,4]oxazin-3(4H)-one	EC50	0.599 nM	US-10174011: Heterocyclic compounds, process for preparation of the same and use thereof
N-(Trans-4-(2-(4-(benzo[b]thiophen-4-yl)piperazin-1-yl)ethyl)cyclohexyl)-5-methylfuran-2-carboxamide	IC50	0.6 nM	US-12459931: Benzothiophene derivative regulator, preparation method therefor and use thereof
N-(5-(2-(4-(benzo[b]thiophen-4-yl)piperazin-1-yl)ethyl)benzo[d]thiazol-2-yl)acetamide	EC50	0.602 nM	US-10174011: Heterocyclic compounds, process for preparation of the same and use thereof
6-(2-(4-(benzo[b]thiophen-4-yl)piperazin-1-yl)ethyl)-2H-benzo[b][1,4]oxazin-3(4H)-one	EC50	0.626 nM	US-10174011: Heterocyclic compounds, process for preparation of the same and use thereof
(S)-1-(4-bromo-2,5-dimethoxyphenyl)propan-2-amine	EC50	0.66 nM
6-(2-(4-(benzo[b]thiophen-4-yl)piperazin-1-yl)ethyl)-2H-benzo[b][1,4]thiazin-3(4H)-one	EC50	0.68 nM	US-10174011: Heterocyclic compounds, process for preparation of the same and use thereof
(3aR,4R,6aS)-4-(5-(4-(benzo[b]thiophen-4-yl)piperazin-1-yl)pentyl)tetrahydro-1H-thieno[3,4-d]imidazol-2(3H)-one	EC50	0.75 nM	US-10174011: Heterocyclic compounds, process for preparation of the same and use thereof
N-(Trans-4-(2-(4-(benzo[b]thiophen-4-yl)piperazin-1-yl)ethyl)cyclohexyl)-3,3-difluoro azetidine-1-carboxamide	IC50	0.76 nM	US-12459931: Benzothiophene derivative regulator, preparation method therefor and use thereof
N-(4-(2-(4-(Benzo[b]thiophen-4-yl)piperazin-1-yl)ethyl)-2-fluorocyclohexyl)furan-2-carboxamide	IC50	0.76 nM	US-12459931: Benzothiophene derivative regulator, preparation method therefor and use thereof
NSC_3981	KI	0.76 nM
4-(2-(4-(benzo[b]thiophen-4-yl)piperazin-1-yl)ethyl)benzo[d]thiazol-2-amine	EC50	0.761 nM	US-10174011: Heterocyclic compounds, process for preparation of the same and use thereof

ChEMBL bioactivities

6100 potent at pChembl≥5 of 6100 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
11.00	Ki	0.01	nM	CHEMBL253022
11.00	Ki	0.01	nM	CHEMBL252818
10.80	Ki	0.016	nM	CHEMBL6023465
10.65	EC50	0.02239	nM	LISURIDE
10.60	IC50	0.025	nM	CHEMBL3652592
10.50	Ki	0.03162	nM	CHEMBL5414080
10.49	Ki	0.032	nM	CHEMBL5838844
10.48	Ki	0.033	nM	CHEMBL1172812
10.40	Ki	0.04	nM	CHEMBL253878
10.40	Ki	0.04	nM	CHEMBL149024
10.40	Ki	0.04	nM	FANANSERIN
10.39	Ki	0.041	nM	APLYSINOPSIN
10.30	Ki	0.05	nM	CHEMBL194455
10.30	Ki	0.05012	nM	CHEMBL5414859
10.30	IC50	0.05012	nM	CHEMBL5414859
10.22	Ki	0.06	nM	CHEMBL5414859
10.22	Ki	0.06	nM	CHEMBL504699
10.20	Ki	0.0631	nM	PIMAVANSERIN
10.20	IC50	0.0631	nM	CHEMBL5414859
10.20	Ki	0.063	nM	CHEMBL5774073
10.15	Ki	0.07	nM	CHEMBL1084721
10.10	Ki	0.08	nM	ZIPRASIDONE
10.10	Ki	0.08	nM	CHEMBL251834
10.10	Ki	0.079	nM	CHEMBL5618291
10.10	Ki	0.079	nM	CHEMBL5868199
10.10	Ki	0.079	nM	CHEMBL1173408
10.10	Ki	0.08	nM	CHEMBL328595
10.09	IC50	0.082	nM	CHEMBL3665544
10.05	Ki	0.09	nM	CHEMBL404000
10.05	Ki	0.09	nM	CHEMBL540982
10.05	Ki	0.09	nM	CHEMBL296512
10.05	Ki	0.09	nM	CHEMBL497064
10.05	Ki	0.09	nM	CHEMBL1774077
10.04	Ki	0.091	nM	CHEMBL4758966
10.03	Ki	0.094	nM	CHEMBL4745124
10.01	Kd	0.097	nM	CHEMBL482496
10.00	Ki	0.1	nM	CHEMBL253439
10.00	Ki	0.1	nM	CHEMBL5815231
10.00	Ki	0.1	nM	CHEMBL5992937
10.00	Ki	0.1	nM	CHEMBL5980062
10.00	Ki	0.1	nM	CHEMBL5931409
10.00	Ki	0.1	nM	CHEMBL5768941
10.00	Ki	0.1	nM	CHEMBL5753586
10.00	Ki	0.1	nM	CHEMBL6062697
10.00	Ki	0.1	nM	CHEMBL5983937
10.00	Ki	0.1	nM	CHEMBL5879745
10.00	Ki	0.1	nM	CHEMBL5773488
10.00	Ki	0.1	nM	CHEMBL6063997
10.00	Ki	0.1	nM	CHEMBL5844608
10.00	Ki	0.1	nM	CHEMBL5783899

PubChem BioAssay actives

3417 with measured affinity, of 6100 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
2-(4-bromo-2,3,6,7-tetrahydrofuro[2,3-f][1]benzofuran-8-yl)ethanamine	2060762: Ray2010 Assay 75 from Article : “Psychedelics and the human receptorome.”	ec50	<0.0001	uM
N-[6-[2-[4-(1,2-benzothiazol-3-yl)piperazin-1-yl]ethyl]-2,3-dihydro-1H-inden-1-yl]acetamide	313955: Displacement of [3H]ketanserin from human 5HT2A receptor expressed in Swiss 3T3 cells	ki	<0.0001	uM
(2R)-1-(4-bromo-2,5-dimethoxyphenyl)propan-2-amine	2060762: Ray2010 Assay 75 from Article : “Psychedelics and the human receptorome.”	ec50	<0.0001	uM
4-[(E,3E)-3-[2-(dimethylamino)ethoxyimino]-3-(2-fluorophenyl)prop-1-enyl]phenol	1800763: Radioligand Binding Assay from Article 10.1124/jpet.105.097006: “Pharmacological and behavioral profile of N-(4-fluorophenylmethyl)-N-(1-methylpiperidin-4-yl)-N’-(4-(2-methylpropyloxy)phenylmethyl) carbamide (2R,3R)-dihydroxybutanedioate (2:1) (ACP-103), a novel 5-hydroxytryptamine(2A) receptor inverse agonist.”	ki	<0.0001	uM
3-[(2,2-dimethyl-3H-1-benzofuran-5-yl)methyl]-1-[(4-fluorophenyl)methyl]-1-(1-methylpiperidin-4-yl)urea	1982013: Displacement of [3H]ketanserin human recombinant 5-HT2A receptor by Cheng-Prusoff equation analysis	ki	<0.0001	uM
1-[(4-fluorophenyl)methyl]-3-[(2-methyl-2,3-dihydro-1-benzofuran-5-yl)methyl]-1-(1-methylpiperidin-4-yl)urea	1982016: Displacement of [3H]ketanserin from human 5-HT2A receptor incubated for 120 mins by microbeta liquid scintillation counter analysis	ki	<0.0001	uM
Pimavanserin	1982016: Displacement of [3H]ketanserin from human 5-HT2A receptor incubated for 120 mins by microbeta liquid scintillation counter analysis	ki	0.0001	uM
6-fluoro-3-[(3R,4R)-4-fluoropiperidin-3-yl]-2-thiophen-3-yl-1H-indole	5176: Ability to displace [3H]ketanserin binding to human 5-hydroxytryptamine 2A receptor stably expressed in CHO cells	ki	0.0001	uM
6-fluoro-2-(4-fluorophenyl)-3-[(3R,4R)-4-fluoropiperidin-3-yl]-1H-indole	5176: Ability to displace [3H]ketanserin binding to human 5-hydroxytryptamine 2A receptor stably expressed in CHO cells	ki	0.0001	uM
6-fluoro-3-[(3R,4R)-4-fluoropiperidin-3-yl]-N-phenyl-1H-indole-2-carboxamide	5176: Ability to displace [3H]ketanserin binding to human 5-hydroxytryptamine 2A receptor stably expressed in CHO cells	ki	0.0001	uM
7-[4-[4-(2,3-dichlorophenyl)piperazin-1-yl]butoxy]-3,4-dihydro-1H-1,8-naphthyridin-2-one	595497: Binding affinity to human 5HT2A receptor	ki	0.0001	uM
7-[4-[4-(5,6,7,8-tetrahydronaphthalen-1-yl)piperazin-1-yl]butoxy]-3,4-dihydro-1H-1,8-naphthyridin-2-one	595497: Binding affinity to human 5HT2A receptor	ki	0.0001	uM
2-[3-[(4-fluorophenyl)methyl]-1-benzothiophen-2-yl]-N,N-dimethylethanamine	431640: Displacement of [3H]ketanserin from human 5HT2A receptor expressed in HEK293 Flp-In cells by liquid scintillation counting	ki	0.0001	uM
7-[4-(4-naphthalen-1-ylpiperazin-1-yl)butoxy]-3,4-dihydro-1H-1,8-naphthyridin-2-one	595497: Binding affinity to human 5HT2A receptor	ki	0.0001	uM
6-fluoro-3-[(3R,4R)-4-fluoropiperidin-3-yl]-2-phenyl-1H-indole	5176: Ability to displace [3H]ketanserin binding to human 5-hydroxytryptamine 2A receptor stably expressed in CHO cells	ki	0.0001	uM
3-chloro-6-[(6S)-1,6-dimethyl-3,6-dihydro-2H-pyridin-4-yl]-8-ethoxy-11H-benzo[b][1,4]benzodiazepine	1677158: Binding affinity to human 5HT2A receptor	ki	0.0001	uM
3-chloro-6-[(6S)-1,6-dimethyl-3,6-dihydro-2H-pyridin-4-yl]-8-ethyl-11H-benzo[b][1,4]benzodiazepine	1677158: Binding affinity to human 5HT2A receptor	ki	0.0001	uM
3-chloro-6-[(6S)-1,6-dimethyl-3,6-dihydro-2H-pyridin-4-yl]-8-methyl-11H-benzo[b][1,4]benzodiazepine	1677158: Binding affinity to human 5HT2A receptor	ki	0.0001	uM
3-chloro-6-[(6S)-1,6-dimethyl-3,6-dihydro-2H-pyridin-4-yl]-8-(trifluoromethoxy)-11H-benzo[b][1,4]benzodiazepine	1677158: Binding affinity to human 5HT2A receptor	ki	0.0001	uM
3-[4-[4-(benzotriazol-1-yl)butyl]piperazin-1-yl]-1,2-benzothiazole;hydrochloride	2128216: Displacement of [3H]Ketanserin from recombinant human 5-HT2A receptor extracted from CHO cell membrane incubated for 60 mins by radioligand binding assay	ki	0.0001	uM
8-[2-[4-(1,2-benzothiazol-3-yl)piperazin-1-yl]ethyl]-4-phenyl-3,4-dihydro-1H-quinolin-2-one	254429: Binding affinity for 5-hydroxytryptamine 2A receptor expressed in 3T3 cells	ki	0.0002	uM
6-fluoro-3-[(3R,4R)-4-fluoropiperidin-3-yl]-2-naphthalen-2-yl-1H-indole	5176: Ability to displace [3H]ketanserin binding to human 5-hydroxytryptamine 2A receptor stably expressed in CHO cells	ki	0.0002	uM
1-[3-(4-chloro-1-methylpyrazol-5-yl)-4-methoxyphenyl]-3-(4-chlorophenyl)urea	461510: Displacement of [3H]DOI from human recombinant 5HT2A receptor expressed in HEK293 cells by scintillation counting	ki	0.0002	uM
1-[3-(4-bromo-1-methylpyrazol-5-yl)-4-methoxyphenyl]-3-(2,4-dichlorophenyl)urea	461510: Displacement of [3H]DOI from human recombinant 5HT2A receptor expressed in HEK293 cells by scintillation counting	ki	0.0002	uM
1-[3-(4-bromo-1-methylpyrazol-5-yl)-4-(2-pyrrolidin-1-ylethoxy)phenyl]-3-(2,4-difluorophenyl)urea	449168: Displacement of [125I]DOI from 5HT2A receptor expressed in HEK cells	ki	0.0002	uM
(1S)-1-[2-[4-[(E)-2-(4-fluorophenyl)ethenyl]phenyl]sulfonylphenyl]ethanol	483025: Displacement of [3H]- ketanserin from human 5HT2A receptor expressed CHO cells	ki	0.0002	uM
7-[4-[4-(2,3-dihydro-1H-inden-4-yl)piperazin-1-yl]butoxy]-3,4-dihydro-1H-1,8-naphthyridin-2-one	595497: Binding affinity to human 5HT2A receptor	ki	0.0002	uM
3-(3-fluorophenyl)sulfonyl-8-(4-(111C)methylpiperazin-1-yl)quinoline	1855140: Binding affinity to human recombinant 5-HT2A assessed as inhibition constant	ki	0.0002	uM
2-(4-bromo-2,5-dimethoxyphenyl)-N-(2,3-dihydro-1-benzofuran-7-ylmethyl)ethanamine	1232234: Binding affinity to 5-HT2A receptor (unknown origin) by PDSP assay	ki	0.0002	uM
2-[[2-(4-bromo-2,5-dimethoxyphenyl)ethylamino]methyl]-6-methoxyphenol	1232234: Binding affinity to 5-HT2A receptor (unknown origin) by PDSP assay	ki	0.0002	uM
N-[4-[2-[4-(1,2-benzothiazol-3-yl)piperazin-1-yl]ethyl]cyclohexyl]-2-methoxyacetamide	1332827: Displacement of [3H]ketanserin from recombinant human 5-HT2A receptor expressed in HEK293 cell membranes after 60 mins by scintillation counting method	ki	0.0002	uM
5-fluoro-2-[(E)-2-[5-(2-fluorophenyl)sulfonyl-2-pyridinyl]ethenyl]phenol	306617: Displacement of [3H]ketanserin from human 5HT2A receptor expressed in CHO cells	ki	0.0002	uM
N-[(3R)-1-[3-(1,2-benzoxazol-3-yl)propyl]pyrrolidin-3-yl]naphthalene-2-sulfonamide	1690390: Displacement of [3H]-ketanserin from recombinant human 5HT2A receptor expressed in CHOK1 cell membranes measured after 1 hr by microbeta counting method	ki	0.0002	uM
N-[(3S)-1-[3-(1,2-benzoxazol-3-yl)propyl]pyrrolidin-3-yl]-1-benzofuran-2-sulfonamide	1690390: Displacement of [3H]-ketanserin from recombinant human 5HT2A receptor expressed in CHOK1 cell membranes measured after 1 hr by microbeta counting method	ki	0.0002	uM
N-[(3R)-1-[3-(1,2-benzoxazol-3-yl)propyl]pyrrolidin-3-yl]-1-methylindole-5-sulfonamide	1690390: Displacement of [3H]-ketanserin from recombinant human 5HT2A receptor expressed in CHOK1 cell membranes measured after 1 hr by microbeta counting method	ki	0.0002	uM
6-fluoro-3-[3-[3-(naphthalen-2-ylsulfonylmethyl)pyrrolidin-1-yl]propyl]-1,2-benzoxazole	1823823: Displacement of [3H]-ketanserin from human human 5-HT2A receptor transfected in CHO-K1 cells measured after 60 mins by scintillation counting method	ki	0.0002	uM
1-[(5-fluoro-2-pyridinyl)methyl]-1-(1-methylpiperidin-4-yl)-3-[[4-(2,2,2-trifluoroethoxy)phenyl]methyl]urea	1879762: Displacement of [3H]-Ketanserin from human 5-HT2A receptor at 50 nM incubated for 1 hr by microbeta scintillation counter analysis	ki	0.0002	uM
(6aR,9R)-N-(2,2-difluoroethyl)-N-ethyl-7-methyl-6,6a,8,9-tetrahydro-4H-indolo[4,3-fg]quinoline-9-carboxamide	2130939: Displacement of [125I]DOI from 5-HT2A receptor (unknown origin) assessed as inhibition constant	ki	0.0002	uM
(2S)-2-amino-3-[4-[3-[4-(6-fluoro-1,2-benzoxazol-3-yl)piperidin-1-yl]propoxy]phenyl]propanoic acid;dihydrochloride	1999479: Inhibition of 5HT2A receptor (unknown origin) expressed in HEK293 cells by FLIPR Calcium 6 dye based assay	ic50	0.0002	uM
1-[(4-fluorophenyl)methyl]-3-[(3-methyl-2,3-dihydro-1-benzofuran-5-yl)methyl]-1-(1-methylpiperidin-4-yl)urea	1982016: Displacement of [3H]ketanserin from human 5-HT2A receptor incubated for 120 mins by microbeta liquid scintillation counter analysis	ki	0.0002	uM
(6aR,9R)-N-(cyanomethyl)-N-ethyl-7-methyl-6,6a,8,9-tetrahydro-4H-indolo[4,3-fg]quinoline-9-carboxamide	2130939: Displacement of [125I]DOI from 5-HT2A receptor (unknown origin) assessed as inhibition constant	ki	0.0002	uM
N-benzyl-2-(4-bromo-2,5-dimethoxyphenyl)ethanamine	5396: Affinity against 5-hydroxytryptamine 2A receptor (D) labeled with [125I]DOI.	ki	0.0003	uM
8-[2-[4-(1,2-benzothiazol-3-yl)piperazin-1-yl]ethyl]-3,4-dihydro-1H-quinolin-2-one	254429: Binding affinity for 5-hydroxytryptamine 2A receptor expressed in 3T3 cells	ki	0.0003	uM
6-fluoro-3-[(3R,4R)-4-fluoropiperidin-3-yl]-2-naphthalen-1-yl-1H-indole	5176: Ability to displace [3H]ketanserin binding to human 5-hydroxytryptamine 2A receptor stably expressed in CHO cells	ki	0.0003	uM
6-fluoro-3-[(3R,4R)-4-fluoropiperidin-3-yl]-2-pyridin-3-yl-1H-indole	5176: Ability to displace [3H]ketanserin binding to human 5-hydroxytryptamine 2A receptor stably expressed in CHO cells	ki	0.0003	uM
2-cyclohexyl-6-fluoro-3-[(3R,4R)-4-fluoropiperidin-3-yl]-1H-indole	5176: Ability to displace [3H]ketanserin binding to human 5-hydroxytryptamine 2A receptor stably expressed in CHO cells	ki	0.0003	uM
1-[3-(4-bromo-1-methylpyrazol-5-yl)-4-methoxyphenyl]-3-(3,5-difluorophenyl)urea	461510: Displacement of [3H]DOI from human recombinant 5HT2A receptor expressed in HEK293 cells by scintillation counting	ki	0.0003	uM
1-[3-(4-bromo-1-methylpyrazol-5-yl)-4-ethoxyphenyl]-3-(4-chlorophenyl)urea	461510: Displacement of [3H]DOI from human recombinant 5HT2A receptor expressed in HEK293 cells by scintillation counting	ki	0.0003	uM
1-[3-(4-bromo-1-methylpyrazol-5-yl)-4-methoxyphenyl]-3-(4-bromophenyl)urea	461510: Displacement of [3H]DOI from human recombinant 5HT2A receptor expressed in HEK293 cells by scintillation counting	ki	0.0003	uM
1-[3-(4-bromo-1-methylpyrazol-5-yl)-4-propan-2-yloxyphenyl]-3-(4-chlorophenyl)urea	461510: Displacement of [3H]DOI from human recombinant 5HT2A receptor expressed in HEK293 cells by scintillation counting	ki	0.0003	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Clozapine	affects binding, decreases activity, decreases reaction, increases response to substance, affects response to substance	5
Ketanserin	affects binding, decreases reaction, decreases activity	5
sarpogrelate	affects binding, decreases activity	3
volinanserin	affects activity, affects binding, decreases activity	3
Risperidone	decreases activity, affects reaction, increases expression, increases response to substance, affects response to substance (+1 more)	3
4-iodo-2,5-dimethoxyphenylisopropylamine	decreases reaction, increases activity, decreases response to substance, affects response to substance, affects binding	2
Aripiprazole	affects binding, decreases activity, increases activity, decreases reaction, decreases response to substance (+1 more)	2
Paliperidone Palmitate	affects binding, decreases activity	2
Olanzapine	affects binding, decreases activity	2
Serotonin	affects binding, increases activity, increases expression, increases secretion, decreases response to substance (+1 more)	2
aristolochic acid I	increases expression	1
ammonium 2,3,3,3-tetrafluoro-2-(heptafluoropropoxy)-propanoate	affects cotreatment, affects expression	1
2,5,2’,5’-tetrachlorobiphenyl	increases expression	1
tributyltin	decreases expression	1
1-(3-chlorophenyl)piperazine	increases activity, increases response to substance, affects response to substance, affects binding	1
perfluorooctanoic acid	affects cotreatment, affects expression	1
tryptamine	decreases response to substance, affects response to substance, affects binding, increases activity	1
norclozapine	decreases expression	1
perfluorooctane sulfonic acid	affects cotreatment, affects expression	1
tebuconazole	decreases expression	1
ziprasidone	affects binding, decreases reaction	1
CGP 52608	affects binding, increases reaction	1
7-methyl-6,7,8,9,14,15-hexahydro-5H-benz(d)indolo(2,3-g)azecine	affects binding, decreases activity	1
7-fluoro-2-oxo-4-(2-(4-(thieno(3,2-c)pyridin-4-yl)piperazin-1-yl)ethyl)-1,2-dihydroquinoline-1-acetamide	affects activity	1
bardoxolone methyl	decreases activity	1
perfluorobutanesulfonic acid	affects cotreatment, affects expression	1
perphenazine GABA ester	affects binding, decreases activity	1
1-(8-bromobenzo(1,2-b;4,5-b’)difuran-4-yl)-2-aminopropane	affects binding, decreases reaction	1
(+)-JQ1 compound	decreases expression	1
Quetiapine Fumarate	affects binding, decreases reaction	1

ChEMBL screening assays

1639 unique, capped per target: 1250 binding, 345 functional, 41 admet, 2 toxicity, 1 unclassified

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5109939	Binding	Binding affinity to cerebrum 5-HT2 receptor (unknown origin)	Positron Emission Tomography (PET) Imaging Tracers for Serotonin Receptors. — J Med Chem
CHEMBL859802	Functional	Lowering of intraocular pressure in lasered cynomolgus monkey after 1 hr at 250 ug	1-((S)-2-aminopropyl)-1H-indazol-6-ol: a potent peripherally acting 5-HT2 receptor agonist with ocular hypotensive activity. — J Med Chem
CHEMBL4013769	Unclassified	Selectivity ratio of EC50 for human 5HT2A receptor to EC50 for human 5HT2C-INI receptor	Discovery of N-Substituted (2-Phenylcyclopropyl)methylamines as Functionally Selective Serotonin 2C Receptor Agonists for Potential Use as Antipsychotic Medications. — J Med Chem

Cellosaurus cell lines

11 cell lines: 4 spontaneously immortalized cell line, 4 cancer cell line, 3 induced pluripotent stem cell

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

Cellosaurus	Name	Category	Sex
CVCL_6498	L-NGC-5HT2 L-cells	Spontaneously immortalized cell line	Male
CVCL_B7ND	CGRM03SB3CC	Induced pluripotent stem cell	Female
CVCL_B7NF	KOL01SB1CC	Induced pluripotent stem cell	Female
CVCL_B7NH	KOL02SB2CC	Induced pluripotent stem cell	Female
CVCL_F2AJ	CHO-K1 (+Galpha16) AequoScreen Serotonin 5-HT2A	Spontaneously immortalized cell line	Female
CVCL_F2AP	NIH/3T3 HTR2A	Spontaneously immortalized cell line	Male
CVCL_H379	CHO-K1/5-HT2A	Spontaneously immortalized cell line	Female
CVCL_LA55	PathHunter U2OS HTR2A beta-arrestin	Cancer cell line	Female
CVCL_LA56	PathHunter U2OS HTR2A Total GPCR Internalization	Cancer cell line	Female
CVCL_YK50	U2OS HTR2A HiTSeeker	Cancer cell line	Female

Clinical trials (associated diseases)

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