HTR2B

Summary

HTR2B (5-hydroxytryptamine receptor 2B, HGNC:5294) is a protein-coding gene on chromosome 2q37.1, encoding 5-hydroxytryptamine receptor 2B (P41595). G-protein coupled receptor for 5-hydroxytryptamine (serotonin).

This gene encodes one of the several different receptors for 5-hydroxytryptamine (serotonin) that belongs to the G-protein coupled receptor 1 family. Serotonin is a biogenic hormone that functions as a neurotransmitter, a hormone, and a mitogen. Serotonin receptors mediate many of the central and peripheral physiologic functions of serotonin, including regulation of cardiovascular functions and impulsive behavior. Population and family-based analyses of a minor allele (glutamine-to-stop substitution, designated Q20*) which blocks expression of this protein, and knockout studies in mice, suggest a role for this gene in impulsivity. However, other factors, such as elevated testosterone levels, may also be involved. Alternatively spliced transcript variants have been found for this gene.

Source: NCBI Gene 3357 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 68 total
• Druggable target: yes — 367 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_000867

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:5294
Approved symbol	HTR2B
Name	5-hydroxytryptamine receptor 2B
Location	2q37.1
Locus type	gene with protein product
Status	Approved
Aliases	5-HT(2B), 5-HT2B
Ensembl gene	ENSG00000135914
Ensembl biotype	protein_coding
OMIM	601122
Entrez	3357

Gene structure

Transcript identifiers

Ensembl transcripts: 6 — 6 protein_coding

ENST00000258400, ENST00000890916, ENST00000971632, ENST00000971633, ENST00000971634, ENST00000971635

RefSeq mRNA: 2 — MANE Select: NM_000867 NM_000867, NM_001320758

CCDS: CCDS2483

Canonical transcript exons

ENST00000258400 — 4 exons

Exon	Start	End
ENSE00000922519	231123413	231124130
ENSE00000922520	231113729	231113929
ENSE00000922521	231108230	231109409
ENSE00001375337	231124972	231125042

Expression profiles

Bgee: expression breadth ubiquitous, 172 present calls, max score 94.31.

FANTOM5 (CAGE): breadth broad, TPM avg 1.7335 / max 237.8552, expressed in 367 samples.

FANTOM5 promoters (9 alternative TSS)

Promoter ID	TPM avg	Samples expressed
34479	0.9100	270
34480	0.3239	147
34478	0.1978	69
34482	0.1136	54
34481	0.0942	45
34476	0.0531	21
34477	0.0251	10
34475	0.0088	4
34474	0.0070	1

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
decidua	UBERON:0002450	94.31	gold quality
cauda epididymis	UBERON:0004360	91.86	gold quality
stromal cell of endometrium	CL:0002255	89.43	gold quality
caput epididymis	UBERON:0004358	88.80	gold quality
corpus epididymis	UBERON:0004359	88.76	gold quality
left adrenal gland	UBERON:0001234	86.20	gold quality
left adrenal gland cortex	UBERON:0035825	86.20	gold quality
right adrenal gland cortex	UBERON:0035827	86.16	gold quality
adrenal cortex	UBERON:0001235	85.31	gold quality
right adrenal gland	UBERON:0001233	85.16	gold quality
adrenal gland	UBERON:0002369	83.18	gold quality
smooth muscle tissue	UBERON:0001135	81.19	gold quality
endometrium	UBERON:0001295	80.35	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	79.66	silver quality
body of uterus	UBERON:0009853	78.59	gold quality
lower esophagus muscularis layer	UBERON:0035833	77.47	gold quality
lower esophagus	UBERON:0013473	77.37	gold quality
uterus	UBERON:0000995	77.20	gold quality
myometrium	UBERON:0001296	76.90	gold quality
metanephros cortex	UBERON:0010533	75.56	gold quality
muscle layer of sigmoid colon	UBERON:0035805	75.10	gold quality
right coronary artery	UBERON:0001625	73.18	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	73.16	gold quality
right atrium auricular region	UBERON:0006631	72.11	gold quality
cardiac atrium	UBERON:0002081	71.69	gold quality
cardiac muscle of right atrium	UBERON:0003379	70.85	silver quality
endocervix	UBERON:0000458	70.79	gold quality
sigmoid colon	UBERON:0001159	68.71	gold quality
thoracic aorta	UBERON:0001515	68.71	gold quality
ascending aorta	UBERON:0001496	68.63	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-GEOD-81383	yes	421.71
E-ANND-3	no	2.62

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

23 targeting HTR2B, 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-3163	100.00	77.23	8605
HSA-MIR-5692B	100.00	71.32	2622
HSA-MIR-5692C	100.00	71.32	2622
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-552-5P	99.93	68.56	1583
HSA-MIR-4496	99.88	68.89	2236
HSA-MIR-579-3P	99.86	71.66	3628
HSA-MIR-664B-3P	99.84	71.65	3590
HSA-MIR-12124	99.68	69.17	2700
HSA-MIR-6758-3P	99.57	67.55	1078
HSA-MIR-549A-3P	99.54	68.17	825
HSA-MIR-143-3P	99.49	69.05	1457
HSA-MIR-4770	99.49	69.09	1451
HSA-MIR-4311	99.31	70.47	3041
HSA-MIR-6088	99.29	68.45	1284
HSA-MIR-4293	99.22	65.46	1263
HSA-MIR-670-3P	99.03	68.88	2404
HSA-MIR-154-5P	98.92	66.65	733
HSA-MIR-1287-5P	96.80	65.30	743
HSA-MIR-1298-5P	95.96	64.81	573
HSA-MIR-550B-3P	95.43	67.73	599
HSA-MIR-3655	86.11	61.77	117

Literature-anchored findings (GeneRIF, showing 40)

• The serotonin binding site of human and murine 5-HT2B receptors: molecular modeling and site-directed mutagenesis. (PMID:11859080)
• the excitatory effects of 5-HT in human colon are mediated by 5-HT(2B) receptors. 5-HT(2B) receptors contribute to the putative 5-HT-induced colonic smooth muscle hypersensitivity associated with irritable bowel syndrome. (PMID:11877320)
• Expression in cultured skin cells. (PMID:12767050)
• 5-HT2B single nucleotide polymorphisms have significant association with substance-related disorders. (PMID:15608559)
• Interactions between AT(1) and 5-HT(2B) receptors coexpressed by noncardiomyocytes are limiting key events in adrenergic agonist-induced, angiotensin-dependent cardiac hypertrophy. (PMID:19023134)
• The 5-HT(2B) receptor plays a key regulatory role in both neuroendocrine tumor cell proliferation and the modulation of the fibroblast component of the neoplastic microenvironment (PMID:20564397)
• Study confirms expression of transgenic 5-HT2b receptors in astrocytes freshly dissociated from mouse brain, isolated by fluorescence-activated cell sorting (FACS) and investigated in cultured cells. (PMID:20846463)
• indicates a role for HTR2B in impulsivity (PMID:21179162)
• Genetic variants in HTR2B and TPH1 were not associated with the risk of GDM. (PMID:21836641)
• staining pattern of serotonin receptors in ovary indicates functional role in ovarian physiology. In ovarian tumours, expression is in harmony with a tumour suppressor role in ovarian carcinogenesis, which is supported by observations in the literature (PMID:22493371)
• The HTR2B gene may play little or no role in the development of Tourette syndrome. (PMID:22917605)
• Serotonin skews human macrophage polarization through HTR2B and HTR7. (PMID:23355731)
• study determined the crystal structure of the 5-HT2B receptor bound to ergotamine (ERG) and compared it with the 5-HT1B/ERG structure (PMID:23519215)
• results of the present study suggest that the HTR2B polymorphism is not likely to be associated with personality traits, including novelty seeking and impulsivity. (PMID:23774082)
• 5-HT2AR, 5-HT2BR, and 5-HT2CR expression in HEK293A cells significantly increases susceptibility to JCPyV infection (PMID:24089568)
• a new and unanticipated role of the 5-HT2B receptor N terminus as a negative modulator, affecting both constitutive and agonist-stimulated activity. (PMID:24174497)
• Structure-activity relationships of constrained phenylethylamine ligands for the serotonin 5-HT2 receptors. (PMID:24244317)
• Data indicate that hydrogen bonding interactions with Ser3.36 and Thr3.37 were important for isoflurane binding with the 5HT2B receptor. (PMID:24365264)
• Studies have found that the HTR2B Q20* connected with impulsive behavior and cognitive impulsivity. (PMID:26575222)
• Activation of 5-HT2B receptors stimulates GSIS in beta cells by triggering downstream changes in cellular Ca(2+) flux that enhance mitochondrial metabolism. (PMID:26733006)
• the 5-HT2B receptor limits degeneration of spinal cord mononuclear phagocytes, most likely microglia, and slows disease progression in amyotrophic lateral sclerosis (PMID:26744351)
• Authors hypothesize that HTR2B expression in the infarcted territory may render degenerating neurons susceptible to attack by activated microglia and thus aggravate the consequences of stroke. (PMID:27013593)
• MFSD2B, CCL20 and STAT1, or STARD7 and ZNF512 genes may be risk or protect factors in prognosis of ADC; HTR2B, DPP4, and TGFBRAP1 genes may be risk factors in prognosis of SQC. (PMID:27301951)
• The HTR2B Q20* allele and testosterone predicted lower BMI independently, but an interaction between HTR2B Q20* and testosterone lead to increased insulin sensitivity among HTR2B Q20* carriers with low testosterone levels. (PMID:27420381)
• The 5-HT2B receptor may contribute to the regulation of human glucagon and glucose homeostasis and the interplay between glucagon and insulin secretion. (PMID:27437919)
• Study describes the crystal structure of Lysergic acid diethylamide (LSD) in complex with the human serotonin receptor 5-HT2B. The complex reveals conformational rearrangements to accommodate LSD, providing a structural explanation for the conformational selectivity of LSD’s key diethylamide moiety. (PMID:28129538)
• heterodimerization with 5-HT2C receptors does not alter 5-HT2C Galphaq-dependent inositol phosphate signaling, 5-HT2A or 5-HT2B receptor-mediated signaling was totally blunted. This feature can be explained by a dominance of 5-HT2C on 5-HT2A and 5-HT2B receptor binding; in 5-HT2C-containing heterodimers, ligands bind and activate the 5-HT2C protomer exclusively. (PMID:28258217)
• The 3.0-A resolution structure of a complex between the human 5-hydroxytryptamine 2B (5-HT2B) receptor and an antibody Fab fragment bound to the extracellular side of the receptor reveals the mechanism of selectivity in extracellular recognition of the receptor by monoclonal antibodies. (PMID:28716900)
• These findings suggest that 5-HT promotes CCN2 production through the 5-HT2AR in growth plates, and that it represses CCN2 production through the 5-HT2BR in articular cartilage for harmonized development of long bones (PMID:29145495)
• In humans, mitral valve prolapse is associated with an upregulation in 5HTR2B expression and increased 5HT receptor signaling in the leaflets. (PMID:29291394)
• The biological role of 5-HT2B which may act not only as a neurotransmitter receptor. (PMID:29379077)
• findings support a role for the serotonin receptor 2B in the proliferation and migration of uveal melanoma cells, through activation of many signaling pathways such as WNT, Focal adhesion kinase and Janus kinase/STAT (PMID:29696577)
• We identified genome-wide significant risk loci contributing to CRA in AAs at the serotonin receptor 2B receptor gene (HTR2B), and the lead SNP, HTR2B*rs17440378, showed nominal association to aggression in the GTP cohort of cannabis-exposed subjects. (PMID:29875475)
• HTR2B transcription is regulated by NFI and RUNX1 in uveal melanoma cells. (PMID:30347896)
• A positive association between a polymorphism in the HTR2B gene and cocaine-crack in a French Afro-Caribbean population. (PMID:30608182)
• This study uses over 25mus of unbiased atomistic molecular dynamics simulations to identify cholesterol interaction sites in the 5-HT1B and 5-HT2B receptors and evaluate their impact on receptor structure. (PMID:30857969)
• Free energy calculations of the functional selectivity of 5-HT2B G protein-coupled receptor. (PMID:33296400)
• The role of 5-HT2B-receptors in fluoxetine-mediated modulation of Th17- and Th1-cells in multiple sclerosis. (PMID:34000471)
• Contribution of the STAT Family of Transcription Factors to the Expression of the Serotonin 2B (HTR2B) Receptor in Human Uveal Melanoma. (PMID:35163491)
• miRNA-203b-3p Induces Acute and Chronic Pruritus through 5-HTR2B and TRPV4. (PMID:36049541)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	htr2b	ENSDARG00000115925
mus_musculus	Htr2b	ENSMUSG00000026228
rattus_norvegicus	Htr2b	ENSRNOG00000017625
drosophila_melanogaster	5-HT2A	FBGN0087012
caenorhabditis_elegans		WBGENE00021897

Paralogs (8): HTR2A (ENSG00000102468), HTR1B (ENSG00000135312), HTR2C (ENSG00000147246), HTR7 (ENSG00000148680), HTR5A (ENSG00000157219), HTR6 (ENSG00000158748), HTR1E (ENSG00000168830), HTR1F (ENSG00000179097)

Protein

Protein identifiers

5-hydroxytryptamine receptor 2B — P41595 (reviewed: P41595)

Alternative names: Serotonin receptor 2B

All UniProt accessions (1): P41595

UniProt curated annotations — full annotation on UniProt →

Function. G-protein coupled receptor for 5-hydroxytryptamine (serotonin). Also functions as a receptor for various ergot alkaloid derivatives 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. HTR2B 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. Plays a role in the regulation of dopamine and 5-hydroxytryptamine release, 5-hydroxytryptamine uptake and in the regulation of extracellular dopamine and 5-hydroxytryptamine levels, and thereby affects neural activity. May play a role in the perception of pain. Plays a role in the regulation of behavior, including impulsive behavior. Required for normal proliferation of embryonic cardiac myocytes and normal heart development. Protects cardiomyocytes against apoptosis. Plays a role in the adaptation of pulmonary arteries to chronic hypoxia. Plays a role in vasoconstriction. Required for normal osteoblast function and proliferation, and for maintaining normal bone density. Required for normal proliferation of the interstitial cells of Cajal in the intestine.

Subunit / interactions. Interacts (via C-terminus) with MPDZ.

Subcellular location. Cell membrane. Synapse. Synaptosome.

Tissue specificity. Ubiquitous. Detected in liver, kidney, heart, pulmonary artery, and intestine. Detected at lower levels in blood, placenta and brain, especially in cerebellum, occipital cortex and frontal cortex.

Domain organisation. Ligands are bound in a hydrophobic pocket formed by the transmembrane helices.

Polymorphism. A variation at a single nucleotide base, which results in an erroneous stop codon and affects Gln-20, triggers non-sense mediated RNA decay, such that no HTR2B-receptor protein is expressed. It is associated with impulsive behavior and co-segregates with disorders characterized by impulsivity. However, the presence of this variant is not in itself sufficient to cause impulsive behavior: male sex, testosterone level, alcohol and stress exposure are other factors playing important roles.

Miscellaneous. Binds lysergic acid diethylamine (LSD) in the orthosteric pocket, but is not the principal LSD receptor in the brain. Bound LSD dissociates extremely slowly, with a residence time of about 46 minutes at 37 degrees Celsius.

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

RefSeq proteins (2): NP_000858, NP_001307687 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000276	GPCR_Rhodpsn	Family
IPR000482	5HT2B_rcpt	Family
IPR002231	5HT_rcpt	Family
IPR017452	GPCR_Rhodpsn_7TM	Domain

Pfam: PF00001

UniProt features (76 total): mutagenesis site 20, helix 18, topological domain 8, transmembrane region 7, short sequence motif 4, sequence variant 4, binding site 3, disulfide bond 2, sequence conflict 2, turn 2, strand 2, chain 1, site 1, lipid moiety-binding region 1, glycosylation site 1

Structure

Experimental structures (PDB)

12 structures.

PDB	Method	Resolution (Å)
4IB4	X-RAY DIFFRACTION	2.7
7SRQ	ELECTRON MICROSCOPY	2.7
4NC3	X-RAY DIFFRACTION	2.8
5TVN	X-RAY DIFFRACTION	2.9
7SRR	ELECTRON MICROSCOPY	2.9
6DRY	X-RAY DIFFRACTION	2.92
5TUD	X-RAY DIFFRACTION	3
6DRX	X-RAY DIFFRACTION	3.1
6DRZ	X-RAY DIFFRACTION	3.1
6DS0	X-RAY DIFFRACTION	3.19
7SRS	ELECTRON MICROSCOPY	3.3
9JGK	ELECTRON MICROSCOPY	3.6

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P41595-F1	71.48	0.37

Antibody-complex structures (SAbDab): 3 — 5TUD, 7SRR, 7SRS

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): 209 (hydrophobic barrier that decreases the speed of ligand binding and dissociation)

Ligand- & substrate-binding residues (3): 135; 140; 209

Post-translational modifications (1): 397

Disulfide bonds (2): 128–207, 350–353

Glycosylation sites (1): 30

Mutagenesis-validated functional residues (20):

Position	Phenotype
132	no effect on agonist binding.
135	abolishes agonist binding.
136	slightly decreases agonist binding.
139	slightly decreases agonist binding.
140	decreased agonist binding.
208	no effect on agonist binding.
209	no effect on agonist binding. strongly increases dissociation of bound lysergic acid diethylamine, without affecting bin
211	impairs protein folding and stability. strongly reduced cell surface expression.
217	slightly decreases agonist binding.
218	no effect on agonist binding.
225	does not affect agonist binding.
337	slightly decreases agonist binding.
340	slightly decreases agonist binding.
344	slightly decreases agonist binding.
347	no effect on agonist binding.
348	no effect on agonist binding.
362	no effect on agonist binding.
363	no effect on agonist binding.
366	no effect on agonist binding.
370	slightly decreases agonist binding.

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: 253 (showing top): LEE_SP4_THYMOCYTE, GOBP_RESPONSE_TO_NITROGEN_COMPOUND, GOBP_PHOSPHOLIPID_METABOLIC_PROCESS, GOMF_G_PROTEIN_COUPLED_SEROTONIN_RECEPTOR_ACTIVITY, GOBP_PHOSPHATIDYLINOSITOL_METABOLIC_PROCESS, GOBP_BEHAVIOR, GOBP_CIRCULATORY_SYSTEM_PROCESS, MODULE_64, GOBP_CANONICAL_NF_KAPPAB_SIGNAL_TRANSDUCTION, GOBP_POSITIVE_REGULATION_OF_MAPK_CASCADE, GOBP_ORGANOPHOSPHATE_METABOLIC_PROCESS, GOBP_POSITIVE_REGULATION_OF_CYTOKINE_PRODUCTION, GOBP_CELLULAR_RESPONSE_TO_OXYGEN_CONTAINING_COMPOUND, GOBP_ORGANOPHOSPHATE_BIOSYNTHETIC_PROCESS, GOBP_REGULATION_OF_PHOSPHOLIPID_METABOLIC_PROCESS

GO Biological Process (31): neural crest cell migration (GO:0001755), positive regulation of cytokine production (GO:0001819), positive regulation of endothelial cell proliferation (GO:0001938), heart morphogenesis (GO:0003007), cardiac muscle hypertrophy (GO:0003300), intracellular calcium ion homeostasis (GO:0006874), G protein-coupled receptor signaling pathway (GO:0007186), G protein-coupled receptor signaling pathway, coupled to cyclic nucleotide second messenger (GO:0007187), phospholipase C-activating serotonin receptor signaling pathway (GO:0007208), serotonin receptor signaling pathway (GO:0007210), chemical synaptic transmission (GO:0007268), positive regulation of cell population proliferation (GO:0008284), response to xenobiotic stimulus (GO:0009410), positive regulation of phosphatidylinositol biosynthetic process (GO:0010513), neural crest cell differentiation (GO:0014033), intestine smooth muscle contraction (GO:0014827), calcium-mediated signaling (GO:0019722), obsolete cGMP-mediated signaling (GO:0019934), vasoconstriction (GO:0042310), negative regulation of apoptotic process (GO:0043066), positive regulation of canonical NF-kappaB signal transduction (GO:0043123), embryonic morphogenesis (GO:0048598), regulation of behavior (GO:0050795), release of sequestered calcium ion into cytosol (GO:0051209), positive regulation of cell division (GO:0051781), ERK1 and ERK2 cascade (GO:0070371), positive regulation of ERK1 and ERK2 cascade (GO:0070374), G protein-coupled serotonin receptor signaling pathway (GO:0098664), smooth muscle contraction (GO:0006939), signal transduction (GO:0007165), heart development (GO:0007507)

GO Molecular Function (9): Gq/11-coupled serotonin receptor activity (GO:0001587), G-protein alpha-subunit binding (GO:0001965), G protein-coupled serotonin receptor activity (GO:0004993), GTPase activator activity (GO:0005096), neurotransmitter receptor activity (GO:0030594), serotonin binding (GO:0051378), serotonin receptor activity (GO:0099589), G protein-coupled receptor activity (GO:0004930), protein binding (GO:0005515)

GO Cellular Component (8): nucleoplasm (GO:0005654), cytoplasm (GO:0005737), plasma membrane (GO:0005886), dendrite (GO:0030425), synapse (GO:0045202), G protein-coupled serotonin receptor complex (GO:0098666), membrane (GO:0016020), neuron projection (GO:0043005)

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	3
signal transduction	2
G protein-coupled receptor signaling pathway	2
G protein-coupled serotonin receptor signaling pathway	2
transmembrane signaling receptor activity	2
neural crest cell development	1
mesenchymal cell migration	1
cytokine production	1
regulation of cytokine production	1
positive regulation of gene expression	1
positive regulation of multicellular organismal process	1
endothelial cell proliferation	1
regulation of endothelial cell proliferation	1
positive regulation of epithelial cell proliferation	1
heart development	1
animal organ morphogenesis	1
striated muscle hypertrophy	1
intracellular monoatomic cation homeostasis	1
calcium ion homeostasis	1
G protein-coupled receptor activity	1
Gq/11-coupled serotonin receptor activity	1
phospholipase C-activating G protein-coupled receptor signaling pathway	1
serotonin receptor activity	1
cellular response to dopamine	1
anterograde trans-synaptic signaling	1
cell population proliferation	1
regulation of cell population proliferation	1
positive regulation of cellular process	1
response to chemical	1
phosphatidylinositol biosynthetic process	1
positive regulation of biosynthetic process	1
regulation of phosphatidylinositol biosynthetic process	1
positive regulation of phosphorus metabolic process	1
mesenchymal cell differentiation	1
stem cell differentiation	1
phasic smooth muscle contraction	1
gastro-intestinal system smooth muscle contraction	1
intracellular signaling cassette	1
blood vessel diameter maintenance	1
apoptotic process	1

Protein interactions and networks

STRING

1082 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
HTR2B	GNAQ	P50148	955
HTR2B	TPH1	P17752	892
HTR2B	SLC6A4	P31645	872
HTR2B	GRM2	Q14416	780
HTR2B	HTR3A	P46098	777
HTR2B	HTR2C	P28335	700
HTR2B	ARRB1	P49407	649
HTR2B	RHO	P08100	625
HTR2B	HTR3B	O95264	621
HTR2B	MAOA	P21397	605
HTR2B	HTR1B	P28222	582
HTR2B	TPM3	P06753	575
HTR2B	SAG	P10523	570
HTR2B	HTR1D	P28221	569
HTR2B	SLC6A2	P23975	556

IntAct

43 interactions, top by confidence:

A	B	Type	Score
HTR2A	HTR2B	psi-mi:“MI:2364”(proximity)	0.470
HTR2B	HTR2C	psi-mi:“MI:2364”(proximity)	0.470
HTR2A	HTR2B	psi-mi:“MI:0915”(physical association)	0.470
HTR2C	HTR2B	psi-mi:“MI:0915”(physical association)	0.470
HTR2C	HTR2B	psi-mi:“MI:2364”(proximity)	0.470
HTR2B	HTR2A	psi-mi:“MI:2364”(proximity)	0.470
HTR2B	MPDZ	psi-mi:“MI:0407”(direct interaction)	0.440
HTR2B	OAT	psi-mi:“MI:0915”(physical association)	0.400
HTR2B	WRNIP1	psi-mi:“MI:0915”(physical association)	0.400
HTR2B	RAMP1	psi-mi:“MI:0915”(physical association)	0.400
RAMP1	HTR2B	psi-mi:“MI:0915”(physical association)	0.400
RAMP2	HTR2B	psi-mi:“MI:0915”(physical association)	0.400
HTR2B	RAMP3	psi-mi:“MI:0915”(physical association)	0.400
ABCA3	HTR2B	psi-mi:“MI:0915”(physical association)	0.370
ATP1B1	HTR2B	psi-mi:“MI:0915”(physical association)	0.370
BNIP3	HTR2B	psi-mi:“MI:0915”(physical association)	0.370
BNIP3L	HTR2B	psi-mi:“MI:0915”(physical association)	0.370
CBR1	HTR2B	psi-mi:“MI:0915”(physical association)	0.370
CHPT1	HTR2B	psi-mi:“MI:0915”(physical association)	0.370
G6PC3	HTR2B	psi-mi:“MI:0915”(physical association)	0.370
HDGFL2	HTR2B	psi-mi:“MI:0915”(physical association)	0.370
HAT1	HTR2B	psi-mi:“MI:0915”(physical association)	0.370
INSIG1	HTR2B	psi-mi:“MI:0915”(physical association)	0.370
KIF19	HTR2B	psi-mi:“MI:0915”(physical association)	0.370
MATR3	HTR2B	psi-mi:“MI:0915”(physical association)	0.370

BioGRID (29): HTR2B (Proximity Label-MS), ABCA3 (Two-hybrid), ATP1B1 (Two-hybrid), BNIP3 (Two-hybrid), BNIP3L (Two-hybrid), CBR1 (Two-hybrid), CHPT1 (Two-hybrid), G6PC3 (Two-hybrid), HDGFRP2 (Two-hybrid), HAT1 (Two-hybrid), INSIG1 (Two-hybrid), KIF19 (Two-hybrid), MATR3 (Two-hybrid), METRN (Two-hybrid), NAT14 (Two-hybrid)

ESM2 similar proteins: A0A2L0VBG2, A1ZAX0, O62169, O77408, P08483, P08911, P08912, P11483, P16395, P17970, P20309, P30974, P30994, P32240, P41595, P41984, P43114, P49578, P56490, Q09388, Q09502, Q18007, Q24352, Q24563, Q28691, Q29J90, Q2KNE5, Q4LBB9, Q4V622, Q5IS53, Q5IS98, Q7JQF1, Q7KVW5, Q868T3, Q8ITC7, Q8ITC9, Q8MJ08, Q920H4, Q9ERZ3, Q9N2A2

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

22 interactions.

A	Effect	B	Mechanism
4-(4-fluoronaphthalen-1-yl)-6-isopropylpyrimidin-2-amine	down-regulates	HTR2B	“chemical inhibition”
HTR2B	“up-regulates activity”	GNAI1	binding
HTR2B	“up-regulates activity”	GNAI3	binding
HTR2B	“up-regulates activity”	GNAZ	binding
HTR2B	“up-regulates activity”	GNAQ	binding
HTR2B	“up-regulates activity”	GNA14	binding
serotonin(1+)	“up-regulates activity”	HTR2B	“chemical activation”
serotonin	“up-regulates activity”	HTR2B	“chemical activation”
haloperidol	“down-regulates activity”	HTR2B	“chemical inhibition”
clozapine	“down-regulates activity”	HTR2B	“chemical inhibition”
yohimbine	“down-regulates activity”	HTR2B	“chemical inhibition”
1-(1-naphthalenyl)piperazine	“down-regulates activity”	HTR2B	“chemical inhibition”
1-(3-chlorophenyl)piperazine	“up-regulates activity”	HTR2B	“chemical activation”
ketanserin	“down-regulates activity”	HTR2B	“chemical inhibition”
mesulergine	“down-regulates activity”	HTR2B	“chemical inhibition”
methiothepin	“down-regulates activity”	HTR2B	“chemical inhibition”
(6aR,9R)-N-[(2S)-1-hydroxybutan-2-yl]-4,7-dimethyl-6,6a,8,9-tetrahydroindolo[4,3-fg]quinoline-9-carboxamide	“up-regulates activity”	HTR2B	“chemical activation”
mianserin	“down-regulates activity”	HTR2B	“chemical inhibition”
rauwolscine	“down-regulates activity”	HTR2B	“chemical inhibition”
ritanserin	“down-regulates activity”	HTR2B	“chemical inhibition”
spiperone	“down-regulates activity”	HTR2B	“chemical inhibition”
8-(2,3-dihydro-1,4-benzodioxin-3-ylmethyl)-1-phenyl-1,3,8-triazaspiro[4.5]decan-4-one	“down-regulates activity”	HTR2B	“chemical inhibition”

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	58
Likely benign	2
Benign	6

Top pathogenic / likely-pathogenic (0)

SpliceAI

640 predictions. Top by Δscore:

Variant	Effect	Δscore
2:231124971:CCT:C	donor_gain	1.0000
2:231113928:CT:C	acceptor_gain	0.9900
2:231123673:CAGT:C	acceptor_gain	0.9900
2:231124966:GCTTA:G	donor_loss	0.9900
2:231124967:CTTA:C	donor_loss	0.9900
2:231124968:TTAC:T	donor_loss	0.9900
2:231124970:A:AC	donor_gain	0.9900
2:231124970:A:C	donor_loss	0.9900
2:231124971:C:CC	donor_gain	0.9900
2:231109407:TGC:T	acceptor_gain	0.9800
2:231113926:GCCT:G	acceptor_gain	0.9800
2:231113927:CCTC:C	acceptor_gain	0.9800
2:231123474:C:CT	acceptor_gain	0.9800
2:231123674:A:T	acceptor_gain	0.9800
2:231109409:CCT:C	acceptor_loss	0.9700
2:231109410:C:CA	acceptor_loss	0.9700
2:231109410:C:CC	acceptor_gain	0.9700
2:231109411:T:G	acceptor_loss	0.9700
2:231113721:CTACA:C	donor_loss	0.9700
2:231113722:TACAT:T	donor_loss	0.9700
2:231113723:ACATA:A	donor_loss	0.9700
2:231113724:CA:C	donor_loss	0.9700
2:231113725:ATAC:A	donor_loss	0.9700
2:231113726:TAC:T	donor_loss	0.9700
2:231113728:C:CT	donor_loss	0.9700
2:231113930:C:CC	acceptor_gain	0.9700
2:231123412:CCAAA:C	donor_gain	0.9700
2:231113720:TCTAC:T	donor_loss	0.9600
2:231113927:CCT:C	acceptor_gain	0.9600
2:231113928:CTC:C	acceptor_gain	0.9600

AlphaMissense

3127 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
2:231113744:A:G	W180R	0.998
2:231113744:A:T	W180R	0.998
2:231108964:A:C	F333L	0.997
2:231108964:A:T	F333L	0.997
2:231108966:A:G	F333L	0.997
2:231113824:C:G	R153P	0.997
2:231123466:T:A	D100V	0.997
2:231123466:T:G	D100A	0.997
2:231108864:A:G	W367R	0.996
2:231108864:A:T	W367R	0.996
2:231108943:G:C	F340L	0.996
2:231108943:G:T	F340L	0.996
2:231108945:A:G	F340L	0.996
2:231108954:A:G	W337R	0.996
2:231108954:A:T	W337R	0.996
2:231123466:T:C	D100G	0.996
2:231123467:C:G	D100H	0.996
2:231123549:A:C	N72K	0.996
2:231123549:A:T	N72K	0.996
2:231108940:A:C	F341L	0.995
2:231108940:A:T	F341L	0.995
2:231108942:A:G	F341L	0.995
2:231113861:C:G	A141P	0.995
2:231123465:A:C	D100E	0.995
2:231123465:A:T	D100E	0.995
2:231123541:A:T	V75D	0.995
2:231109285:G:C	F226L	0.994
2:231109285:G:T	F226L	0.994
2:231109287:A:G	F226L	0.994
2:231113919:C:A	W121C	0.994

dbSNP variants (sampled 300 via entrez): RS1000012769 (2:231126126 G>A), RS1000023009 (2:231123042 G>T), RS1000347784 (2:231113592 G>A), RS1000383137 (2:231120814 T>G), RS1000436922 (2:231121079 A>G,T), RS1000678879 (2:231110708 A>G), RS1001232909 (2:231109888 T>C), RS1001307534 (2:231116292 A>G), RS1001359662 (2:231116525 T>A), RS1001577652 (2:231109512 C>T), RS1001832223 (2:231114690 A>C,G), RS1001951254 (2:231121231 A>G), RS1002181240 (2:231114443 A>T), RS1002362182 (2:231124177 G>A), RS1002660735 (2:231123953 G>A)

Disease associations

OMIM: gene MIM:601122 | disease phenotypes: MIM:209900

GenCC curated gene-disease

Mondo (1): Bardet-Biedl syndrome (MONDO:0015229)

Orphanet (1): Bardet-Biedl syndrome (Orphanet:110)

HPO phenotypes

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

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST001859_46	Thiazide-induced adverse metabolic effects in hypertensive patients	4.000000e-06
GCST010917_4	Proportion of activated microglia (midfrontal cortex)	6.000000e-06

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D020788	Bardet-Biedl Syndrome	C10.228.140.617.200; C11.270.684.624; C16.131.077.245.125; C16.320.184.125

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (4): CHEMBL1833 (SINGLE PROTEIN), CHEMBL2095200 (PROTEIN FAMILY), CHEMBL2096904 (PROTEIN FAMILY), CHEMBL2111466 (SELECTIVITY GROUP)

Molecules with ChEMBL bioactivity

367 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 706,424 (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
CHEMBL1000	CETIRIZINE	4	26,030
CHEMBL1008	BEPRIDIL	4	11,776
CHEMBL1014	CANDESARTAN CILEXETIL	4	11,194
CHEMBL1017	TELMISARTAN	4	27,457
CHEMBL103	PROGESTERONE	4	162,141
CHEMBL104	CLOTRIMAZOLE	4	56,325
CHEMBL1059	PREGABALIN	4	26,074
CHEMBL1064	SIMVASTATIN	4	123,163
CHEMBL1065	METHYSERGIDE	4	8,455
CHEMBL107	COLCHICINE	4	93,932
CHEMBL1078261	PROPIVERINE	4	4,890
CHEMBL1085	ACETOPHENAZINE	4	5,134
CHEMBL10878	AGOMELATINE	4	4,528
CHEMBL11	IMIPRAMINE	4	48,893
CHEMBL1108	DROPERIDOL	4	16,888
CHEMBL111	RIMONABANT	4	15,726
CHEMBL1110	ALOSETRON	4	10,794
CHEMBL1112	ARIPIPRAZOLE	4	24,205
CHEMBL1113	AMOXAPINE	4	20,128
CHEMBL1123	DICYCLOMINE	4	8,691
CHEMBL114	SAQUINAVIR	4
CHEMBL1171837	PONATINIB	4
CHEMBL1172	DESLORATADINE	4
CHEMBL1175	DULOXETINE	4
CHEMBL117785	TETRABENAZINE	4
CHEMBL1198	PRAMOXINE	4
CHEMBL1200374	EXEMESTANE	4
CHEMBL1200406	DIMENHYDRINATE	4
CHEMBL1200661	UNOPROSTONE ISOPROPYL	4
CHEMBL1200776	CINACALCET HYDROCHLORIDE	4

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 (100 total), top 25:

Ligand	Action	Affinity	Parameter
balovaptan	Antagonist	11.57	pKd
BF-1	Antagonist	10.05	pKi
RS-127445	Antagonist	9.49	pKi
methysergide	Partial agonist	9.4	pKi
methylergonovine	Partial agonist	9.3	pKi
methiothepin	Antagonist	9.2	pKi
ritanserin	Antagonist	9.2	pKi
LY53857	Antagonist	9.1	pKi
(+)-LSD	Full agonist	9.0	pKi
EGIS-7625	Antagonist	9.0	pKi
1-naphthylpiperazine	Antagonist	9.0	pKi
ergotamine	Partial agonist	8.9	pKi
cabergoline	Full agonist	8.9	pKi
lisuride	Antagonist	8.9	pKi
mianserin	Antagonist	8.8	pKi
metergoline	Antagonist	8.8	pKi
mesulergine	Antagonist	8.8	pKi
clozapine	Antagonist	8.8	pKi
[3H]LSD	Full agonist	8.7	pKd
BW723C86	Full agonist	8.6	pKi
SB 221284	Antagonist	8.6	pKi
m-chlorophenylpiperazine	Partial agonist	8.5	pKi
SB 206553	Antagonist	8.5	pKi
Lysergide	Biased agonist	8.43	pKi
rauwolscine	Antagonist	8.4	pKi

Binding affinities (BindingDB)

196 measured of 216 human assays (254 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
DOHx	KI	0.1 nM
NSC_104911	KI	0.1 nM
roxindole	KI	0.11 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
1-(2-Chloro-3,4-dimethoxybenzyl)-6-methyl-2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indole	KI	0.2 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
NSC_8226	KI	0.35 nM
DOBz	KI	0.4 nM
LSD,2-Bromo	KI	0.48 nM
NSC_3981	KI	0.76 nM
2-(2,5-Dimethoxy-4-propyl-phenyl)-1-methyl-ethylamine(DOPR)	KI	0.9 nM
LY-193525	KI	0.9 nM
5,6-difluoroindol-methylethylamine	KI	0.98 nM
CAS_113-15-5	KI	0.98 nM
8-(2,3-Dihydro-benzo[1,4]dioxin-2-ylmethyl)-1-phenyl-1,3,8-triaza-spiro[4.5]decan-4-one	KI	1 nM
METHIOTHEPIN	KI	1 nM
LY-23728	KI	1 nM
3-{2-[4-(4-Fluoro-benzoyl)-piperidin-1-yl]-ethyl}-2-methyl-pyrido[1,2-a]pyrimidin-4-one	KI	1.08 nM
(4R,7R)-N,N-diethyl-6-methyl-6,11-diazatetracyclo[7.6.1.0^{2,7}.0^{12,16}]hexadeca-1(16),2,9,12,14-pentaene-4-carboxamide	KI	1.09 nM
14C-5-hydroxy tryptamine creatinine disulfate	KI	1.2 nM
(1S,2R,10S,11S,14S,15S)-14-(2-hydroxyacetyl)-2,15-dimethyltetracyclo[8.7.0.0^{2,7}.0^{11,15}]heptadec-6-en-5-one	KI	1.4 nM
SB 215505	KI	1.48 nM
Permax	KI	1.91 nM
CAS_17692-51-2	KI	2.29 nM
2-[2,5-dimethoxy-4-(trifluoromethylsulfanyl)phenyl]ethanamine	KI	2.5 nM	US-20250236589: THERAPEUTIC PHENETHYLAMINE COMPOSITIONS AND METHODS OF USE
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
(S)-mianserin	KI	3 nM
(3R)-3-[4-chloro-2-[(3-chlorophenyl)methoxy]phenoxy]-1-methylpyrrolidine	KI	3 nM	US-9981909: Serotonin receptor modulators
Terguride	KI	3.47 nM
DOTB	KI	3.7 nM
(6aR,10aR)-7-propyl-6a,8,9,10,10a,11-hexahydro-6H-[1,3]benzodioxolo[7,6-g]quinoline	EC50	3.8 nM	US-12384765: Catecholamine prodrugs for use in the treatment of Parkinson’s Disease
3-[5-chloro-2-[2-(4-methoxyphenyl)ethoxy]phenoxy]azetidine	KI	4 nM	US-9981909: Serotonin receptor modulators
S33526	KI	4.07 nM
5-Methoxy-3-(1,2,3,6-tetrahydro-pyridin-4-yl)-1H-indole(RU-24969)	KI	4.78 nM
(3R)-3-(4-chloro-2-phenylmethoxyphenoxy)-1-methylpyrrolidine	KI	5 nM	US-9981909: Serotonin receptor modulators
3-[5-chloro-2-[[6-(trifluoromethyl)-2,3-dihydro-1H-inden-1-yl]oxy]phenoxy]azetidine	KI	5 nM	US-9981909: Serotonin receptor modulators
3-[5-chloro-2-(2,2-difluoro-2-phenylethoxy)phenoxy]azetidine	KI	5 nM	US-9981909: Serotonin receptor modulators
DON	KI	5.5 nM
3-[5-chloro-2-[(6-chloro-2,3-dihydro-1H-inden-1-yl)oxy]phenoxy]azetidine	KI	6 nM	US-9981909: Serotonin receptor modulators
3-[5-bromo-2-(2-phenylethoxy)phenoxy]-3-methylazetidine	KI	6 nM	US-9981909: Serotonin receptor modulators
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
L017811	KI	7.94 nM
3-[5-chloro-2-[(6-methyl-2,3-dihydro-1H-inden-1-yl)oxy]phenoxy]azetidine	KI	8 nM	US-9981909: Serotonin receptor modulators
3-[5-chloro-2-(2-methoxy-2-phenylethoxy)phenoxy]azetidine	KI	8 nM	US-9981909: Serotonin receptor modulators
3-[5-chloro-2-[2-(3-chlorophenyl)ethoxy]phenoxy]azetidine	KI	8 nM	US-9981909: Serotonin receptor modulators
3-[5-chloro-2-[[1-(4-chlorophenyl)cyclobutyl]methoxy]phenoxy]azetidine	KI	8 nM	US-9981909: Serotonin receptor modulators
3-[5-chloro-2-[2-(3-fluorophenyl)ethoxy]phenoxy]azetidine	KI	8 nM	US-9981909: Serotonin receptor modulators
3-[5-chloro-2-[2-(4-chlorophenyl)ethoxy]phenoxy]azetidine	KI	9 nM	US-9981909: Serotonin receptor modulators
3-[5-bromo-2-(2-phenylethoxy)phenoxy]azetidine	KI	10 nM	US-9981909: Serotonin receptor modulators

ChEMBL bioactivities

3421 potent at pChembl≥5 of 3568 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
10.15	EC50	0.07079	nM	SEROTONIN
10.00	IC50	0.1	nM	CHEMBL6163540
9.96	Ki	0.11	nM	CHEMBL3310115
9.82	Ki	0.151	nM	CARIPRAZINE
9.80	Kd	0.1585	nM	CHEMBL323208
9.72	Ki	0.19	nM	BRILAROXAZINE
9.72	Ki	0.19	nM	CHEMBL149024
9.70	Ki	0.2	nM	CHEMBL95121
9.70	IC50	0.2	nM	CHEMBL473185
9.68	Ki	0.21	nM	ASENAPINE
9.61	IC50	0.245	nM	CHEMBL5081637
9.55	Ki	0.281	nM	METERGOLINE
9.52	Ki	0.3	nM	CHEMBL473186
9.52	Ki	0.3	nM	CHEMBL5193649
9.52	IC50	0.3	nM	CHEMBL475407
9.45	Ki	0.358	nM	METHYSERGIDE
9.44	Ki	0.36	nM	ARIPIPRAZOLE
9.44	EC50	0.3631	nM	SEROTONIN HYDROCHLORIDE
9.44	EC50	0.36	nM	SEROTONIN HYDROCHLORIDE
9.43	IC50	0.37	nM	CHEMBL5419724
9.41	Ki	0.39	nM	CHEMBL5201983
9.40	Ki	0.4	nM	CHEMBL3092758
9.40	Ki	0.3981	nM	BREXPIPRAZOLE
9.40	Ki	0.4	nM	CHEMBL5191141
9.40	IC50	0.4	nM	CHEMBL475245
9.36	IC50	0.442	nM	METERGOLINE
9.30	EC50	0.5	nM	SEROTONIN
9.30	Ki	0.5	nM	CHEMBL5204619
9.29	Ki	0.51	nM	CHEMBL3343668
9.27	Ki	0.54	nM	CHEMBL2323581
9.25	IC50	0.563	nM	METHYSERGIDE
9.24	Ki	0.57	nM	CHEMBL45491
9.24	EC50	0.58	nM	CHEMBL5207529
9.24	EC50	0.5754	nM	CHEMBL5207529
9.22	Ki	0.6	nM	CHEMBL2165137
9.22	Ki	0.6	nM	CHEMBL2165126
9.22	IC50	0.6	nM	CHEMBL472990
9.17	Ki	0.67	nM	CHEMBL3310116
9.15	Ki	0.71	nM	CHEMBL3310714
9.15	IC50	0.7	nM	CHEMBL473186
9.12	Ki	0.75	nM	CHEMBL6616
9.10	Ki	0.8	nM	METHYLERGONOVINE
9.09	Ki	0.81	nM	CHEMBL3310111
9.07	EC50	0.86	nM	SEROTONIN
9.07	EC50	0.8511	nM	SEROTONIN
9.05	Ki	0.9	nM	CHEMBL3310121
9.04	Ki	0.91	nM	CHEMBL3310112
9.04	EC50	0.92	nM	SEROTONIN
9.02	Ki	0.958	nM	METHYLERGONOVINE
9.01	Ki	0.97	nM	CHEMBL2323580

PubChem BioAssay actives

2148 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
8-chloro-N-(diaminomethylidene)-9-hydroxy-9H-fluorene-2-carboxamide;hydrochloride	1179665: Displacement of [3H]Mesulergine from human 5-HT2B receptor expressed in HEK293-EBNA cells by liquid scintillation counting	ki	0.0001	uM
3-[4-[2-[4-(2,3-dichlorophenyl)piperazin-1-yl]ethyl]cyclohexyl]-1,1-dimethylurea	2026904: Displacement of [3H]-5-HT from 5HT2B receptor in HEK293 cell membranes by scintillation counting method	ki	0.0002	uM
3-[2-[cyclopropylmethyl(methyl)amino]ethyl]-1-methylindol-4-ol	1834409: Modulation of human 5HT2B expressed in HEK293T cells co-transfected with Galphaq-RLuc8, Ggamma1-GFP2 and Gbeta1 assessed as dissociation of Galphaq from Ggamma1 preincubated for 1 hr followed by addition of coelenterazine 400a substrate and measured after 15 mins by BRET assay	ic50	0.0002	uM
[4-(4-fluorophenyl)phenyl]-[4-(1H-imidazol-2-ylmethyl)piperidin-1-yl]methanone	351748: Antagonist activity at 5-HT2B receptor expressed in CHOK1 cells assessed as inhibition of serotonin-induced intracellular Ca2+ flux by aequorin luminescence assay	ic50	0.0002	uM
(4-oxo-2-azatricyclo[3.3.1.02,7]nonan-8-yl) 1H-indole-3-carboxylate	200911: Potency was evaluated on rabbit heart serotonergic receptors	kd	0.0002	uM
4-(4-fluoronaphthalen-1-yl)-6-propan-2-ylpyrimidin-2-amine	1855160: Binding affinity to 5-HT2B (unknown origin) assessed as inhibition constant	ki	0.0003	uM
4-(1H-imidazol-2-yl)-1-(4-phenylphenyl)sulfonylpiperidine	351748: Antagonist activity at 5-HT2B receptor expressed in CHOK1 cells assessed as inhibition of serotonin-induced intracellular Ca2+ flux by aequorin luminescence assay	ic50	0.0003	uM
Brexpiprazole	1517956: Binding affinity to 5-HT2BR (unknown origin)	ki	0.0004	uM
Serotonin Hydrochloride	1880147: Agonist activity at human 5HT2B receptor stably expressed in Flp-In-T-REx-293 cells assessed as increase in Gq-mediated calcium flux by Fluo-4 direct dye based FLIPR Tetra assay	ec50	0.0004	uM
N-(diaminomethylidene)-9-oxofluorene-2-carboxamide	1058096: Displacement of [3H]Mesulergine from human 5-HT2B receptor expressed in HEK293 cells by liquid scintillation counting analysis	ki	0.0004	uM
[4-(1H-imidazol-2-ylmethyl)piperidin-1-yl]-(4-phenylphenyl)methanone	351748: Antagonist activity at 5-HT2B receptor expressed in CHOK1 cells assessed as inhibition of serotonin-induced intracellular Ca2+ flux by aequorin luminescence assay	ic50	0.0004	uM
N-(diaminomethylidene)spiro[cyclopropane-1,9’-fluorene]-2’-carboxamide;hydrochloride	1167373: Displacement of [3H]mesulergine from human 5-HT2B receptor expressed in HEK293 cells	ki	0.0005	uM
(9R)-5-bromo-N,N-diethyl-7-methyl-4-(111C)methyl-6,6a,8,9-tetrahydroindolo[4,3-fg]quinoline-9-carboxamide	1855061: Binding affinity to cerebrum 5-HT2 receptor (unknown origin)	ki	0.0005	uM
6-chloro-1-(2,4,5-trimethoxyphenyl)-2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indole;hydrochloride	1880147: Agonist activity at human 5HT2B receptor stably expressed in Flp-In-T-REx-293 cells assessed as increase in Gq-mediated calcium flux by Fluo-4 direct dye based FLIPR Tetra assay	ec50	0.0006	uM
5’-chloro-N,N-dimethylspiro[cyclohex-2-ene-4,2’-tricyclo[9.4.0.03,8]pentadeca-1(15),3(8),4,6,11,13-hexaene]-1-amine	5125: The compound was tested for binding affinity against 5-hydroxytryptamine 2 receptor using ketanserin as radioligand	ki	0.0006	uM
1-[4-(4-fluorophenyl)phenyl]sulfonyl-4-(1H-imidazol-2-yl)piperidine	351748: Antagonist activity at 5-HT2B receptor expressed in CHOK1 cells assessed as inhibition of serotonin-induced intracellular Ca2+ flux by aequorin luminescence assay	ic50	0.0006	uM
N-(diaminomethylidene)-9-hydroxy-8-methyl-9H-fluorene-2-carboxamide;hydrochloride	1179665: Displacement of [3H]Mesulergine from human 5-HT2B receptor expressed in HEK293-EBNA cells by liquid scintillation counting	ki	0.0007	uM
N-(diaminomethylidene)-5-ethyl-9-hydroxy-9-methylfluorene-2-carboxamide;hydrochloride	1179665: Displacement of [3H]Mesulergine from human 5-HT2B receptor expressed in HEK293-EBNA cells by liquid scintillation counting	ki	0.0007	uM
N-(diaminomethylidene)-9-hydroxy-5-methyl-9H-fluorene-2-carboxamide;hydrochloride	1179665: Displacement of [3H]Mesulergine from human 5-HT2B receptor expressed in HEK293-EBNA cells by liquid scintillation counting	ki	0.0008	uM
1-(4-iodo-2,5-dimethoxyphenyl)propan-2-amine	2198813: Binding affinity to 5HT2B receptor (unknown origin) assessed as inhibition constant	ki	0.0008	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	0.0009	uM
N-(diaminomethylidene)-5-fluoro-9-hydroxy-9H-fluorene-2-carboxamide;hydrochloride	1179665: Displacement of [3H]Mesulergine from human 5-HT2B receptor expressed in HEK293-EBNA cells by liquid scintillation counting	ki	0.0009	uM
N-(diaminomethylidene)-9-fluoro-9H-fluorene-2-carboxamide;hydrochloride	1179665: Displacement of [3H]Mesulergine from human 5-HT2B receptor expressed in HEK293-EBNA cells by liquid scintillation counting	ki	0.0009	uM
3-(4-methoxyphenyl)-2-propan-2-yl-5,6,7,8-tetrahydro-4H-pyrazolo[3,4-d]azepine	1682693: Displacement of [3H]-ketanserin from human 5-HT2B receptor by competitive radioligand binding assay	ki	0.0010	uM
3-(4-chlorophenyl)-2-propan-2-yl-5,6,7,8-tetrahydro-4H-pyrazolo[3,4-d]azepine	1682693: Displacement of [3H]-ketanserin from human 5-HT2B receptor by competitive radioligand binding assay	ki	0.0010	uM
2-cyclopentyl-4-(4-methylphenyl)-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepine	315813: Displacement of [3H]mesulergine from human recombinant 5HT2B receptor expressed in CHO cells	ki	0.0010	uM
5’-chloro-N,N-dimethylspiro[cyclohex-2-ene-4,2’-tricyclo[9.4.0.03,8]pentadeca-1(15),3(8),4,6,9,11,13-heptaene]-1-amine	5125: The compound was tested for binding affinity against 5-hydroxytryptamine 2 receptor using ketanserin as radioligand	ki	0.0010	uM
Oxitriptan	1280454: Agonist activity at recombinant human 5HT2B receptor expressed in Flp-In-293 cells assessed as calcium flux by FLIPR assay	ec50	0.0010	uM
1-(4-bromo-2,3,6,7-tetrahydrofuro[2,3-f][1]benzofuran-8-yl)propan-2-amine	5391: Antagonistic activity at cloned human 5-hydroxytryptamine 2B receptor using [3H]rauwolscine as radioligand	ki	0.0011	uM
(2S)-1-pyrrolo[2,3-f]quinolin-1-ylpropan-2-amine	259794: Binding to human 5HT2B receptor expressed in CHO cells	ec50	0.0011	uM
(2R)-1-(4-bromo-2,3,6,7-tetrahydrofuro[2,3-f][1]benzofuran-8-yl)propan-2-amine	5394: Binding ability of compound at cloned human 5-hydroxytryptamine 2B receptor using [3H]rauwolscine as radioligand	ki	0.0011	uM
N-(diaminomethylidene)-9-hydroxy-5,9-dimethylfluorene-2-carboxamide;hydrochloride	1179665: Displacement of [3H]Mesulergine from human 5-HT2B receptor expressed in HEK293-EBNA cells by liquid scintillation counting	ki	0.0011	uM
3-[(6aR,9S)-7-methyl-6,6a,8,9-tetrahydro-4H-indolo[4,3-fg]quinolin-9-yl]-1,1-diethylurea	2011804: Displacement of [3H]-5HT from human 5-HT2B receptor expressed in CHO-K1 cells assessed as inhibition constant	ki	0.0011	uM
Imipramine	2198785: Inhibition of 5HT receptor (unknown origin)	ic50	0.0011	uM
[4-(4-fluorophenyl)phenyl]-[4-(1H-imidazol-2-yl)piperidin-1-yl]methanone	351748: Antagonist activity at 5-HT2B receptor expressed in CHOK1 cells assessed as inhibition of serotonin-induced intracellular Ca2+ flux by aequorin luminescence assay	ic50	0.0011	uM
4-[(E,3Z)-3-[2-(dimethylamino)ethoxyimino]-3-(2-fluorophenyl)prop-1-enyl]phenol	1855068: Binding affinity to 5-HT2 receptor (unknown origin) assessed as dissociation constant	kd	0.0012	uM
(5R)-7-chloro-5-methyl-2,3,4,5-tetrahydro-1H-3-benzazepine	731445: Agonist activity at 5-HT2B receptor (unknown origin)	ki	0.0013	uM
cyclopropyl-(4-imidazol-1-ylphenyl)methanone	1623964: Positive allosteric modulation of 5HT2B receptor (unknown origin) expressed in HEK293 cells co-expressing NFAT-RE assessed as increase in serotonin-induced reponse after 6 to 12 hrs by Bright-Glo luciferase reporter gene assay	ec50	0.0013	uM
cyclopropyl-[4-(4-nitroimidazol-1-yl)phenyl]methanone	1623964: Positive allosteric modulation of 5HT2B receptor (unknown origin) expressed in HEK293 cells co-expressing NFAT-RE assessed as increase in serotonin-induced reponse after 6 to 12 hrs by Bright-Glo luciferase reporter gene assay	ec50	0.0013	uM
2-(6-fluoro-2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indol-1-yl)-5-methoxyphenol	1880147: Agonist activity at human 5HT2B receptor stably expressed in Flp-In-T-REx-293 cells assessed as increase in Gq-mediated calcium flux by Fluo-4 direct dye based FLIPR Tetra assay	ec50	0.0013	uM
N-[4-[2-[4-(2-chloro-3-ethylphenyl)piperazin-1-yl]ethyl]cyclohexyl]quinoline-4-carboxamide	2026904: Displacement of [3H]-5-HT from 5HT2B receptor in HEK293 cell membranes by scintillation counting method	ki	0.0013	uM
5-chloro-N-(diaminomethylidene)-9-hydroxy-9H-fluorene-2-carboxamide;hydrochloride	1179665: Displacement of [3H]Mesulergine from human 5-HT2B receptor expressed in HEK293-EBNA cells by liquid scintillation counting	ki	0.0015	uM
N-[4-[2-[4-(2,3-dichlorophenyl)piperazin-1-yl]ethyl]cyclohexyl]-3-methoxypropanamide	2026904: Displacement of [3H]-5-HT from 5HT2B receptor in HEK293 cell membranes by scintillation counting method	ki	0.0015	uM
Cyproheptadine	2011804: Displacement of [3H]-5HT from human 5-HT2B receptor expressed in CHO-K1 cells assessed as inhibition constant	ki	0.0015	uM
1-(4-ethylsulfanyl-2,5-dimethoxyphenyl)propan-2-amine	2060761: Ray2010 Assay 74 from Article : “Psychedelics and the human receptorome.”	ki	0.0016	uM
N-(diaminomethylidene)-5-ethyl-9-hydroxy-9H-fluorene-2-carboxamide	1179665: Displacement of [3H]Mesulergine from human 5-HT2B receptor expressed in HEK293-EBNA cells by liquid scintillation counting	ki	0.0016	uM
(2S)-1-(6-chloro-5-fluoroindol-1-yl)propan-2-amine	312494: Agonist activity at human 5HT2B receptor expressed in HEK293 cells assessed as intracellular IP3 accumulation	ec50	0.0016	uM
4-N-(3-iodophenyl)-1,3,5-triazaspiro[5.5]undeca-1,4-diene-2,4-diamine	1422920: Displacement of [3H]LSD from 5HT2B (unknown origin) after 1.5 hrs by microbeta scintillation counting method	ki	0.0017	uM
7-chloro-N-(diaminomethylidene)-9-hydroxy-9H-fluorene-2-carboxamide;hydrochloride	1179665: Displacement of [3H]Mesulergine from human 5-HT2B receptor expressed in HEK293-EBNA cells by liquid scintillation counting	ki	0.0017	uM
N-(diaminomethylidene)spiro[cyclopentane-1,9’-fluorene]-2’-carboxamide;hydrochloride	1167373: Displacement of [3H]mesulergine from human 5-HT2B receptor expressed in HEK293 cells	ki	0.0017	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
bisphenol A	decreases methylation, increases expression	3
Fenfluramine	increases expression, increases response to substance, affects binding	3
Lysergic Acid Diethylamide	increases activity, affects binding, decreases reaction	2
Norfenfluramine	affects binding, increases activity	2
Serotonin	increases activity, affects binding, decreases reaction	2
afuresertib	increases expression	1
ammonium 2,3,3,3-tetrafluoro-2-(heptafluoropropoxy)-propanoate	affects expression, affects cotreatment	1
propionaldehyde	decreases expression	1
2-aminoindan	affects binding, decreases reaction	1
butyraldehyde	decreases expression	1
perfluorooctanoic acid	affects cotreatment, affects expression	1
pentanal	decreases expression	1
perfluorooctane sulfonic acid	affects cotreatment, affects expression	1
lipopolysaccharide, E. coli O26-B6	increases expression	1
2,2’,4,4’,5-brominated diphenyl ether	increases expression	1
perfluorobutanesulfonic acid	affects cotreatment, affects expression	1
1-(8-bromobenzo(1,2-b;4,5-b’)difuran-4-yl)-2-aminopropane	affects binding, decreases reaction	1
incobotulinumtoxinA	increases expression	1
1-pentyl-3-(1-naphthoyl)indole	affects binding, decreases reaction, increases activity	1
JWH-073	decreases reaction, increases activity, affects binding	1
1-(5-fluoropentyl)-3-(1-naphthoyl)indole	decreases reaction, increases activity, affects binding	1
4-ethylnaphthalen-1-yl-(1-pentylindol-3-yl)methanone	affects binding, decreases reaction, increases activity	1
Bortezomib	decreases expression	1
Dasatinib	increases expression	1
Aldehydes	decreases expression	1
Benzo(a)pyrene	increases methylation	1
Copper	affects binding, increases expression	1
Dexamethasone	affects cotreatment, decreases expression	1
Disulfiram	increases expression, affects binding	1
Endosulfan	decreases expression	1

ChEMBL screening assays

1090 unique, capped per target: 786 binding, 249 functional, 49 admet, 4 toxicity, 2 unclassified

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1000202	Binding	Binding affinity to 5HT2B receptor	Synthesis and evaluation of dibenzothiazepines: a novel class of selective cannabinoid-1 receptor inverse agonists. — J Med Chem
CHEMBL1020894	Functional	Activity at 5HT2B receptor assessed as calcium mobilization by FLIPR	Structure-activity relationships of the cycloalkanol ethylamine scaffold: discovery of selective norepinephrine reuptake inhibitors. — J Med Chem
CHEMBL1737953	Unclassified	PUBCHEM_BIOASSAY: Late-stage radioligand binding dose response assay to identify inhibitors of NADPH oxidase 1 (NOX1): PDSP screen Ki Set 2. (Class of assay: confirmatory) [Related pubchem assays (depositor defined):AID1792, AID1796, AID182	PubChem BioAssay data set

Cellosaurus cell lines

5 cell lines: 2 transformed cell line, 2 spontaneously immortalized cell line, 1 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_D7RK	Ubigene A-549 HTR2B KO	Cancer cell line	Male
CVCL_E5JQ	HEK293/5-HT2B	Transformed cell line	Female
CVCL_H380	CHO-K1/5-HT2B	Spontaneously immortalized cell line	Female
CVCL_KU63	HEK 293 HTR2B Gq	Transformed cell line	Female
CVCL_ZK71	GeneBLAzer HTR2B-NFAT-bla CHO-K1	Spontaneously immortalized cell line	Female

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT03746522	PHASE3	COMPLETED	Setmelanotide (RM-493), Melanocortin-4 Receptor (MC4R) Agonist, in Bardet-Biedl Syndrome (BBS) and Alström Syndrome (AS) Participants With Moderate to Severe Obesity
NCT04966741	PHASE3	COMPLETED	Setmelanotide in Pediatric Participants With Rare Genetic Diseases of Obesity
NCT05194124	PHASE3	COMPLETED	Phase 3 Crossover Trial of Two Formulations of Setmelanotide in Participants With Specific Gene Defects in the MC4R Pathway
NCT03490019	PHASE2	WITHDRAWN	Treatment of Bardet-Biedl-Syndrome With Metformin for Evaluation of a Possible Visual Improvement
NCT00078091	Not specified	TERMINATED	Genetics and Clinical Characteristics of Bardet-Biedl Syndrome
NCT00213811	Not specified	COMPLETED	Bardet-Biedl Syndrome Study: Clinical and Genetic Epidemiology Study in Adults
NCT01401998	Not specified	RECRUITING	ARPKD Database Study
NCT02329210	Not specified	RECRUITING	Clinical Registry Investigating Bardet-Biedl Syndrome
NCT02435940	Not specified	RECRUITING	Inherited Retinal Degenerative Disease Registry
NCT04461444	Not specified	RECRUITING	COhort for Bardet-Bield Syndrome and Alström Syndrome for Translational Research Monocentric Interventional Study
NCT04463316	Not specified	RECRUITING	GROWing Up With Rare GENEtic Syndromes
NCT04874909	Not specified	COMPLETED	Classification, Functional Stratification and Biomarkers in Ciliopathy (CILLICORIRCM)
NCT05183802	Not specified	APPROVED_FOR_MARKETING	An Expanded Access Protocol for Setmelanotide for Treatment of Bardet-Biedl Syndrome (BBS)
NCT05400278	Not specified	COMPLETED	Characterizing the Genotype and Phenotype in Adults With Bardet-Biedl Syndrome
NCT06239064	Not specified	ACTIVE_NOT_RECRUITING	Early Genetic Identification of Obesity
NCT06615011	Not specified	NOT_YET_RECRUITING	Bardet Beidle Syndrome in a Syrian Adolescent : a Rare Case Report
NCT07602803	Not specified	COMPLETED	The Effect of GLP1 Agonists on Weight Loss in BBS Cohort in the UK