HTR1B

Summary

HTR1B (5-hydroxytryptamine receptor 1B, HGNC:5287) is a protein-coding gene on chromosome 6q14.1, encoding 5-hydroxytryptamine receptor 1B (P28222). G-protein coupled receptor for 5-hydroxytryptamine (serotonin).

The protein encoded by this intronless gene is a G-protein coupled receptor for serotonin (5-hydroxytryptamine). Ligand binding activates second messengers that inhibit the activity of adenylate cyclase and manage the release of serotonin, dopamine, and acetylcholine in the brain. The encoded protein may be involved in several neuropsychiatric disorders and therefore is often a target of antidepressant and other psychotherapeutic drugs.

Source: NCBI Gene 3351 — RefSeq curated summary.

At a glance

• GWAS associations: 5
• Clinical variants (ClinVar): 41 total
• Druggable target: yes — 41 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_000863

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:5287
Approved symbol	HTR1B
Name	5-hydroxytryptamine receptor 1B
Location	6q14.1
Locus type	gene with protein product
Status	Approved
Aliases	S12, 5-HT1B, HTR1D2, 5-HT1DB
Ensembl gene	ENSG00000135312
Ensembl biotype	protein_coding
OMIM	182131
Entrez	3351

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000369947

RefSeq mRNA: 1 — MANE Select: NM_000863 NM_000863

CCDS: CCDS4986

Canonical transcript exons

ENST00000369947 — 1 exons

Exon	Start	End
ENSE00001451305	77460924	77463491

Expression profiles

Bgee: expression breadth ubiquitous, 131 present calls, max score 80.82.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.3432 / max 22.5542, expressed in 180 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
74487	0.2192	117
74488	0.1241	57

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
popliteal artery	UBERON:0002250	80.82	gold quality
tibial artery	UBERON:0007610	80.77	gold quality
right coronary artery	UBERON:0001625	80.46	gold quality
aorta	UBERON:0000947	77.94	gold quality
descending thoracic aorta	UBERON:0002345	75.60	gold quality
left coronary artery	UBERON:0001626	74.92	gold quality
thoracic aorta	UBERON:0001515	74.62	gold quality
ascending aorta	UBERON:0001496	74.23	gold quality
stromal cell of endometrium	CL:0002255	73.70	gold quality
coronary artery	UBERON:0001621	73.49	gold quality
hair follicle	UBERON:0002073	73.38	gold quality
diaphragm	UBERON:0001103	70.11	gold quality
upper arm skin	UBERON:0004263	66.71	gold quality
prefrontal cortex	UBERON:0000451	64.88	gold quality
nucleus accumbens	UBERON:0001882	64.86	gold quality
olfactory bulb	UBERON:0002264	63.49	gold quality
type B pancreatic cell	CL:0000169	63.17	gold quality
germinal epithelium of ovary	UBERON:0001304	62.61	gold quality
lower esophagus muscularis layer	UBERON:0035833	62.27	gold quality
lower esophagus	UBERON:0013473	62.25	gold quality
superficial temporal artery	UBERON:0001614	60.70	gold quality
cervix squamous epithelium	UBERON:0006922	60.23	gold quality
caudate nucleus	UBERON:0001873	60.02	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	59.89	gold quality
pancreatic ductal cell	CL:0002079	59.81	silver quality
putamen	UBERON:0001874	58.92	gold quality
mucosa of paranasal sinus	UBERON:0005030	58.68	gold quality
gluteal muscle	UBERON:0002000	58.34	gold quality
triceps brachii	UBERON:0001509	58.15	gold quality
frontal cortex	UBERON:0001870	58.10	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.98

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

75 targeting HTR1B, 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-4747-5P	100.00	67.90	2681
HSA-MIR-5196-5P	100.00	67.98	2761
HSA-MIR-5692B	100.00	71.32	2622
HSA-MIR-5692C	100.00	71.32	2622
HSA-MIR-7110-3P	100.00	73.18	2486
HSA-MIR-196A-1-3P	99.99	72.15	2772
HSA-MIR-10401-5P	99.99	65.79	948
HSA-MIR-8068	99.98	73.85	2376
HSA-MIR-3065-5P	99.97	71.56	3281
HSA-MIR-495-3P	99.96	72.81	4197
HSA-MIR-5688	99.96	73.23	4504
HSA-MIR-570-3P	99.96	72.41	4910
HSA-MIR-1250-3P	99.96	70.04	4038
HSA-MIR-1297	99.91	73.41	3162
HSA-MIR-498-3P	99.91	71.27	1114
HSA-MIR-3529-3P	99.90	73.55	3045
HSA-MIR-627-3P	99.90	71.42	3316
HSA-MIR-374A-5P	99.90	71.34	2923
HSA-MIR-374B-5P	99.90	69.98	2734
HSA-MIR-15A-5P	99.90	72.80	2787
HSA-MIR-15B-5P	99.90	72.78	2798
HSA-MIR-16-5P	99.90	72.80	2780
HSA-MIR-195-5P	99.90	72.81	2805
HSA-MIR-6857-5P	99.87	65.32	985
HSA-MIR-369-3P	99.85	70.52	2264
HSA-MIR-629-3P	99.85	67.99	1875
HSA-MIR-548AZ-5P	99.83	69.94	3230
HSA-MIR-548T-5P	99.83	69.91	3220
HSA-MIR-3121-3P	99.82	71.96	3630
HSA-MIR-6515-3P	99.82	68.19	1933

Literature-anchored findings (GeneRIF, showing 40)

• Genetic variability of the 5HT1B receptor is involved in the development of some type of alcohol dependence. (PMID:11956970)
• a potential susceptibility locus at the 5-HT(1B) receptor gene in attention deficit hyperactivity disorder (PMID:12192616)
• substance abuse disorder and major depression appear to be associated with the 5-HT1B receptor G861C locus in the patient population, but other psychopathologies such as bipolar disorder, schizophrenia, alcoholism, and suicide attempts were not (PMID:12496953)
• may be a good candidate for genetic studies of ADHD. (PMID:12556913)
• G861C, G261T, and C129T are not playing any direct role in the development of susceptibility to alcoholism (PMID:12898580)
• Population-based association study tested the hypothesis that the serotonin 1B receptor (HTR1B) A-161T polymorphisms was associated with TPQ personality trait scores in a sample population of 209 young healthy Chinese. (PMID:14504413)
• HTR1B is the target of substantial transcriptional genetic regulation by common haplotypes, which are in linkage disequalibrium with the HTR1B single-nucleotide polymorphism (SNP) most commonly used in association studies. (PMID:14593427)
• Based on the examination of 164 alcoholic subjects, an association is found between a lower frequency of the 5-HT1B 861cytosine allele, antisocial personality traits and conduct disorder in alcohol-dependent subjects. (PMID:14714219)
• 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 support the hypothesis of dysregulation of the serotonergic system in these psychiatric disorders. (PMID:14744462)
• data provide no support for the hypothesis that polymorphisms at 5-HT1Dalpha (TaqI) and 5-HT1Dbeta (T261G and G861C) genes contributes to susceptibility to schizophrenia in the Portuguese population (PMID:15211620)
• Not significantly associated with aggression. (5HT1Dbeta receptor) (PMID:15318027)
• Evidence is provided for mismatch of 5-HT1B receptor mRNA expression and receptor distribution in human brain, giving support to species differences in the cortical mRNA expression and localization of this receptor subtype. (PMID:15700286)
• this is the first association study to suggest how a particular gene might influence OCD pathology in an eating disorder population. (PMID:15944142)
• Postsynaptic 5-HT(1B) receptors directly influence the executive, consummatory phases of agonistic behavior, whereas presynaptic serotonergic feedback systems are particularly useful in the introductory phases of the agonistic behavioral complex. (PMID:16310769)
• results of the present study indicate that the dynamic modulation of 5-HT1B receptor function by p11 may be involved in molecular adaptations occurring in neuronal networks that are dysfunctional in depression-like states (PMID:16400147)
• The contribution of 5-HT1B receptors to the mediation of the effects of 5-HT is increased in 124Cys/Phe individuals. (PMID:16847428)
• lack of association of obsessive behaviors/perfectionism and the HTR1B gene in a sample of 203 families with an ADHD proband (PMID:16958036)
• antagonism of the 5-HT(1B) receptor inhibits the proliferation of both human and murine primary helper T cells and of human helper T cell lines (PMID:17011639)
• investigate seven genetic variants in three genes (serotonin transporter (5-HTT), serotonin receptor 1B (5-HTR1B) and serotonin receptor 2A (5-HTR2A)), which have previously been shown to be associated with ADHD (PMID:17093889)
• The 5-HT1B receptor promoter polymorphism G861C plays a role in headache intensity. (PMID:17417740)
• Genetic variation of the serotonin 1B receptor gene is associated with impulsive aggressive behavior and suicide (PMID:17510950)
• there was no significant association between the HTR1B G861C polymorphism and suicidal behavior (Meta-Analysis) (PMID:17525973)
• a G-G haplotype (rs1213368-rs6296) and the respective G-alleles were found to be related to a strong loudness dependence of auditory evoked potentials response of the left tangential dipole, indicating low serotonergic activity (PMID:17948897)
• Individuals homozygous for the ancestral A-element reported more conduct-disorder behaviors than individuals with the G-element (PMID:18283276)
• Examination of genetic variants at the HTR1B locus indicated no association between the selected polymorphisms and childhood-onset mood disorder. (PMID:18349694)
• In the human internal thoracic artery, 5-hydroxytryptamine (5-HT)-induced vasoconstriction is mediated by activation of both 5-HT2A and 5-HT1B receptors. (PMID:18430065)
• findings showed evidence of undertransmission of the HTR1B haplotypes containing alleles -161G and -261A at HTR1B gene to autism spectrum disorders (ASD) (P=0.003), but no involvement of HTR2C to the predisposition to ASD (PMID:19038234)
• findings extend our understanding of the genetic basis of anger and hostility by showing that newly characterized HTR1B haplotypes, particularly those with rs13212041, which modulates microRNA-mediated regulation of HTR1B expression (PMID:19350534)
• the 5HT1B gene A-161T polymorphism alone is not a risk factor for increasing susceptibility to either alcohol dependence or its subtypes (PMID:19519719)
• There were no significant differences between groups in genotype or haplotype distribution of HTR1B markers in Borderline personality disorder. (PMID:19626271)
• Our results provide additional evidence that HRT1B gene may be an important risk factor for the development of ADHD, but this effect seems not to be attributable to inattentive cases. (PMID:19756364)
• This study indicated that the HTR1B gene might be involved in the development of suicidal ideation in MD among a Chinese Han population. (PMID:19897250)
• There was no assocition of HTR1B with adolescent idiopathic scoliosis. (PMID:20388441)
• our findings suggest abnormally reduced function of ventral striatum/ventral pallidum 5-HT1B receptors in humans with major depressive disorder (PMID:20480149)
• results support previous studies suggesting that HTR1A and HTR1B polymorphisms are associated with stress-related neuropsychiatric conditions, such as depression and anxiety in the presence of environmental stress factors (PMID:20638825)
• This study found haplotype of HTR1B gene that was significantly more frequent in worman then in mam. (PMID:20674037)
• Data show that selected polymorphisms of the 5-HT receptor genes and transporter gene are not involved in genetic susceptibility to completed suicide under acute influence of alcohol or among alcohol-dependent individuals. (PMID:21169892)
• The HTR1B A-161T polymorphism may be particularly valuable as a functional genetic marker for alcoholis (PMID:21172311)
• Sumatriptan and tegaserod were more potent at the 124Cys-variant h5-HT1B receptor (PMID:21478802)
• findings suggest that allelic variability in SLC1A2/3, 5-HTR1B and NTRK2 may be relevant to the underlying diathesis for suicidal acts. (PMID:21711518)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
mus_musculus	Htr1b	ENSMUSG00000049511
rattus_norvegicus	Htr1b	ENSRNOG00000013042
drosophila_melanogaster	5-HT1A	FBGN0004168
drosophila_melanogaster	5-HT1B	FBGN0263116

Paralogs (8): HTR2A (ENSG00000102468), HTR2B (ENSG00000135914), HTR2C (ENSG00000147246), HTR7 (ENSG00000148680), HTR5A (ENSG00000157219), HTR6 (ENSG00000158748), HTR1E (ENSG00000168830), HTR1F (ENSG00000179097)

Protein

Protein identifiers

5-hydroxytryptamine receptor 1B — P28222 (reviewed: P28222)

Alternative names: S12, Serotonin 1D beta receptor, Serotonin receptor 1B

All UniProt accessions (2): P28222, X5D7I5

UniProt curated annotations — full annotation on UniProt →

Function. G-protein coupled receptor for 5-hydroxytryptamine (serotonin). Also functions as a receptor for ergot alkaloid derivatives, various anxiolytic and antidepressant drugs and other psychoactive substances, such as 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, such as adenylate cyclase. HTR1B is coupled to G(i)/G(o) G alpha proteins and mediates inhibitory neurotransmission by inhibiting adenylate cyclase activity. Arrestin family members inhibit signaling via G proteins and mediate activation of alternative signaling pathways. Regulates the release of 5-hydroxytryptamine, dopamine and acetylcholine in the brain, and thereby affects neural activity, nociceptive processing, pain perception, mood and behavior. Besides, plays a role in vasoconstriction of cerebral arteries.

Subunit / interactions. Homodimer. Heterodimer with HTR1D.

Subcellular location. Cell membrane.

Tissue specificity. Detected in cerebral artery smooth muscle cells (at protein level). Detected in brain cortex, striatum, amygdala, medulla, hippocampus, caudate nucleus and putamen.

Post-translational modifications. Phosphorylated. Desensitization of the receptor may be mediated by its phosphorylation. Palmitoylated.

Domain organisation. Ligands are bound in a hydrophobic pocket formed by the transmembrane helices. A residue in the 7th transmembrane region (Thr-355 in human, ‘Asn-351’ in mouse and rat) is important for species-specific sensitivity to various agonists.

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

RefSeq proteins (1): NP_000854* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000276	GPCR_Rhodpsn	Family
IPR002147	5HT1B_rcpt	Family
IPR002231	5HT_rcpt	Family
IPR017452	GPCR_Rhodpsn_7TM	Domain

Pfam: PF00001

UniProt features (67 total): mutagenesis site 21, helix 13, topological domain 8, transmembrane region 7, sequence variant 4, binding site 3, short sequence motif 2, glycosylation site 2, chain 1, region of interest 1, compositionally biased region 1, site 1, lipid moiety-binding region 1, disulfide bond 1, turn 1

Structure

Experimental structures (PDB)

5 structures.

PDB	Method	Resolution (Å)
4IAR	X-RAY DIFFRACTION	2.7
4IAQ	X-RAY DIFFRACTION	2.8
7C61	X-RAY DIFFRACTION	3
6G79	ELECTRON MICROSCOPY	3.78
5V54	X-RAY DIFFRACTION	3.9

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P28222-F1	79.84	0.50

Antibody-complex structures (SAbDab): 1 — 7C61

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): 355 (important for species-specific agonist sensitivity)

Ligand- & substrate-binding residues (3): 129; 134; 201

Post-translational modifications (1): 388

Disulfide bonds (1): 122–199

Glycosylation sites (2): 24, 32

Mutagenesis-validated functional residues (21):

Position	Phenotype
126	no effect on agonist binding.
129	abolishes agonist binding.
130	abolishes agonist binding.
133	abolishes agonist binding.
134	slightly decreases agonist binding.
200	no effect on agonist binding.
201	no effect on agonist binding.
203	no effect on agonist binding.
209	no effect on agonist binding.
212	no effect on agonist binding.
216	no effect on agonist binding.
327	abolishes agonist binding.
330	abolishes agonist binding.
331	no effect on agonist binding.
334	no effect on agonist binding.
334	reduced g(i)/(o)-coupled receptor activity.
337	no effect on agonist binding.
351	no effect on agonist binding.
352	no effect on agonist binding.
355	no effect on agonist binding.
359	no effect on agonist binding.

Function

Pathways and Gene Ontology

Reactome pathways

8 pathways

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

MSigDB gene sets: 171 (showing top): GOBP_RESPONSE_TO_NITROGEN_COMPOUND, GOMF_G_PROTEIN_COUPLED_SEROTONIN_RECEPTOR_ACTIVITY, GOBP_BEHAVIOR, GOBP_CIRCULATORY_SYSTEM_PROCESS, TGACCTY_ERR1_Q2, GOBP_MUSCLE_CELL_PROLIFERATION, MORF_RAD51L3, GOBP_CELL_CELL_SIGNALING, GOBP_ORGANIC_HYDROXY_COMPOUND_TRANSPORT, GOBP_ADENYLATE_CYCLASE_MODULATING_G_PROTEIN_COUPLED_RECEPTOR_SIGNALING_PATHWAY, GOBP_REGULATION_OF_ANATOMICAL_STRUCTURE_SIZE, CATRRAGC_UNKNOWN, GOBP_REGULATION_OF_BEHAVIOR, GOBP_NEGATIVE_REGULATION_OF_TRANSPORT, GOBP_RESPONSE_TO_ALKALOID

GO Biological Process (14): G protein-coupled receptor signaling pathway, coupled to cyclic nucleotide second messenger (GO:0007187), adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway (GO:0007193), adenylate cyclase-inhibiting serotonin receptor signaling pathway (GO:0007198), phospholipase C-activating serotonin receptor signaling pathway (GO:0007208), chemical synaptic transmission (GO:0007268), negative regulation of serotonin secretion (GO:0014063), vasoconstriction (GO:0042310), bone remodeling (GO:0046849), regulation of behavior (GO:0050795), cellular response to alkaloid (GO:0071312), cellular response to xenobiotic stimulus (GO:0071466), positive regulation of vascular associated smooth muscle cell proliferation (GO:1904707), signal transduction (GO:0007165), G protein-coupled receptor signaling pathway (GO:0007186)

GO Molecular Function (7): Gi/o-coupled serotonin receptor activity (GO:0001586), G protein-coupled serotonin receptor activity (GO:0004993), 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): endoplasmic reticulum (GO:0005783), plasma membrane (GO:0005886), dendrite (GO:0030425), presynaptic membrane (GO:0042734), G protein-coupled serotonin receptor complex (GO:0098666), serotonergic synapse (GO:0099154), cytoplasm (GO:0005737), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-6 pathways:

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

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
G protein-coupled serotonin receptor signaling pathway	3
G protein-coupled receptor signaling pathway	2
transmembrane signaling receptor activity	2
cellular anatomical structure	2
adenylate cyclase-modulating G protein-coupled receptor signaling pathway	1
adenylate cyclase inhibitor activity	1
Gi/o-coupled serotonin receptor activity	1
adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway	1
Gq/11-coupled serotonin receptor activity	1
phospholipase C-activating G protein-coupled receptor signaling pathway	1
anterograde trans-synaptic signaling	1
serotonin secretion	1
regulation of serotonin secretion	1
negative regulation of monoatomic ion transport	1
negative regulation of secretion by cell	1
blood vessel diameter maintenance	1
tissue remodeling	1
behavior	1
regulation of multicellular organismal process	1
response to alkaloid	1
cellular response to nitrogen compound	1
response to xenobiotic stimulus	1
cellular response to chemical stimulus	1
positive regulation of smooth muscle cell proliferation	1
regulation of vascular associated smooth muscle cell proliferation	1
vascular associated smooth muscle cell proliferation	1
cell communication	1
cellular process	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
G protein-coupled receptor activity	1
signal transduction	1
G protein-coupled serotonin receptor activity	1
G protein-coupled amine receptor activity	1
serotonin binding	1
signaling receptor activity	1
cation binding	1
amine binding	1
heterocyclic compound binding	1

Protein interactions and networks

STRING

1254 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
HTR1B	SLC6A4	P31645	932
HTR1B	TPH1	P17752	895
HTR1B	HTR1D	P28221	891
HTR1B	HTR1A	P08908	873
HTR1B	S100A10	P08206	842
HTR1B	TPH2	Q8IWU9	805
HTR1B	MAOB	P27338	803
HTR1B	HTR2A	P28223	750
HTR1B	SLC6A3	Q01959	745
HTR1B	MAOA	P21397	735
HTR1B	HTR3A	P46098	734
HTR1B	SNAP25	P13795	687
HTR1B	HTR3B	O95264	676
HTR1B	CHRNA4	P43681	646
HTR1B	POMC	P01189	626

IntAct

25 interactions, top by confidence:

A	B	Type	Score
MDFI	HTR1B	psi-mi:“MI:0915”(physical association)	0.780
HTR1B	MDFI	psi-mi:“MI:0915”(physical association)	0.780
HTR1B	ACTN2	psi-mi:“MI:0915”(physical association)	0.560
HTR1A	HTR1A	psi-mi:“MI:2364”(proximity)	0.510
	HTR1B	psi-mi:“MI:0915”(physical association)	0.400
RAMP2	HTR1B	psi-mi:“MI:0915”(physical association)	0.400
HTR1B	RAMP3	psi-mi:“MI:0915”(physical association)	0.400
CD209	HMGCR	psi-mi:“MI:0914”(association)	0.350
CD209	NCK2	psi-mi:“MI:0914”(association)	0.350
HTR1B	SCAMP2	psi-mi:“MI:0914”(association)	0.350
HTR1B	GNAO1	psi-mi:“MI:0915”(physical association)	0.320
NME2	HTR1B	psi-mi:“MI:0915”(physical association)	0.000
HTR1B	GSTK1	psi-mi:“MI:0915”(physical association)	0.000
HTR1B	ACTN2	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (66): MDFI (Two-hybrid), HTR1B (Affinity Capture-MS), MDFI (Two-hybrid), HTR1B (Affinity Capture-MS), HTR1B (Affinity Capture-MS), HTR1B (Affinity Capture-MS), HTR1B (Two-hybrid), HTR1B (Affinity Capture-Western), HTR1B (Affinity Capture-MS), HTR1B (Affinity Capture-MS), FUT8 (Affinity Capture-MS), FAM134C (Affinity Capture-MS), TTYH3 (Affinity Capture-MS), SYNE2 (Affinity Capture-MS), XXYLT1 (Affinity Capture-MS)

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

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

SIGNOR signaling

18 interactions.

A	Effect	B	Mechanism
HTR1B	“up-regulates activity”	GNAI1	binding
HTR1B	“up-regulates activity”	GNAI3	binding
HTR1B	“up-regulates activity”	GNAO1	binding
HTR1B	“up-regulates activity”	GNAZ	binding
HTR1B	“up-regulates activity”	GNA14	binding
serotonin(1+)	“up-regulates activity”	HTR1B	“chemical activation”
serotonin	“up-regulates activity”	HTR1B	“chemical activation”
ziprasidone	“up-regulates activity”	HTR1B	“chemical activation”
olanzapine	“up-regulates activity”	HTR1B	“chemical activation”
clozapine	“up-regulates activity”	HTR1B	“chemical activation”
risperidone	“down-regulates activity”	HTR1B	“chemical inhibition”
sertindole	“down-regulates activity”	HTR1B	“chemical inhibition”
zotepine	“down-regulates activity”	HTR1B	“chemical inhibition”
paliperidone	“down-regulates activity”	HTR1B	“chemical inhibition”
(S,S)-asenapine	“up-regulates activity”	HTR1B	“chemical activation”
pipamperone	“down-regulates activity”	HTR1B	“chemical inhibition”
oxymetazoline	“up-regulates activity”	HTR1B	“chemical activation”
frovatriptan	“up-regulates activity”	HTR1B	“chemical activation”

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	36
Likely benign	5
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

272 predictions. Top by Δscore:

Variant	Effect	Δscore
6:77462760:CCCA:C	donor_loss	0.6900
6:77462761:CCAC:C	donor_loss	0.6900
6:77462762:CA:C	donor_loss	0.6900
6:77462763:ACC:A	donor_loss	0.6900
6:77462764:CCGT:C	donor_loss	0.6900
6:77462759:ACCC:A	donor_loss	0.6800
6:77462638:G:C	donor_gain	0.6700
6:77462757:GCAC:G	donor_loss	0.6700
6:77462758:CACC:C	donor_loss	0.6700
6:77462529:A:AC	donor_gain	0.6600
6:77462530:C:CC	donor_gain	0.6600
6:77462756:AGCAC:A	donor_loss	0.6500
6:77462549:CA:C	donor_gain	0.6300
6:77462660:G:A	donor_gain	0.6300
6:77462708:G:C	acceptor_gain	0.6300
6:77462532:TTG:T	donor_gain	0.6200
6:77462614:TGG:T	donor_gain	0.6100
6:77462484:G:C	donor_gain	0.5700
6:77462531:T:C	donor_gain	0.5700
6:77462719:C:CT	acceptor_gain	0.5700
6:77462820:T:TA	donor_gain	0.5700
6:77462505:T:A	donor_gain	0.5600
6:77462527:G:A	donor_gain	0.5600
6:77462548:A:AC	donor_gain	0.5600
6:77462549:C:CC	donor_gain	0.5600
6:77462928:G:C	donor_gain	0.5600
6:77462478:T:A	donor_gain	0.5500
6:77462635:T:C	donor_gain	0.5500
6:77462457:A:AC	donor_gain	0.5400
6:77462665:T:TA	donor_gain	0.5400

AlphaMissense

2510 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
6:77462425:A:G	W327R	1.000
6:77462425:A:T	W327R	1.000
6:77463059:C:A	W115C	1.000
6:77463059:C:G	W115C	1.000
6:77463120:T:G	D95A	1.000
6:77462307:G:T	P366H	0.999
6:77462309:G:C	N365K	0.999
6:77462309:G:T	N365K	0.999
6:77462321:G:C	N361K	0.999
6:77462321:G:T	N361K	0.999
6:77462331:C:T	G358D	0.999
6:77462411:G:C	F331L	0.999
6:77462411:G:T	F331L	0.999
6:77462413:A:G	F331L	0.999
6:77462414:G:C	F330L	0.999
6:77462414:G:T	F330L	0.999
6:77462416:A:G	F330L	0.999
6:77462418:G:C	P329R	0.999
6:77462418:G:T	P329H	0.999
6:77462421:A:G	L328P	0.999
6:77462423:C:A	W327C	0.999
6:77462423:C:G	W327C	0.999
6:77462428:A:G	C326R	0.999
6:77462435:A:C	F323L	0.999
6:77462435:A:T	F323L	0.999
6:77462437:A:G	F323L	0.999
6:77462753:G:C	F217L	0.999
6:77462753:G:T	F217L	0.999
6:77462755:A:G	F217L	0.999
6:77462884:A:G	W174R	0.999

dbSNP variants (sampled 300 via entrez): RS1002111567 (6:77461557 A>C), RS1002400822 (6:77461229 T>C), RS1003089769 (6:77464823 G>A,T), RS1003549925 (6:77464474 T>A,C,G), RS1003838728 (6:77463691 C>A,T), RS1003900176 (6:77463657 G>A), RS1004788258 (6:77461607 T>A,C), RS1005538448 (6:77463918 C>A,G,T), RS1006237486 (6:77464770 G>A), RS1006439789 (6:77465112 G>A), RS1006852256 (6:77460896 T>A), RS1007372969 (6:77461234 T>C), RS1008433837 (6:77462546 A>G,T), RS1008836173 (6:77461144 C>G), RS1008888414 (6:77460630 T>C)

Disease associations

OMIM: gene MIM:182131 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

5 associations (top):

Study	Trait	p-value
GCST003487_13	Response to fenofibrate (total cholesterol levels)	7.000000e-06
GCST004795_3	Brain volume in infants (white matter)	9.000000e-07
GCST007297_6	Psychological distress	5.000000e-06
GCST011743_44	HDL cholesterol levels in HIV infection	2.000000e-06
GCST011793_7	Early chronic obstructive pulmonary disease in never smokers	1.000000e-06

EFO canonical traits (4, from GWAS)

EFO ID	Trait name
EFO:0007806	total cholesterol change measurement
EFO:0008370	infant white matter volume measurement
EFO:0007006	depressive symptom measurement
EFO:0004612	high density lipoprotein cholesterol measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (5): CHEMBL1898 (SINGLE PROTEIN), CHEMBL2095230 (SELECTIVITY GROUP), CHEMBL2096904 (PROTEIN FAMILY), CHEMBL4523959 (SELECTIVITY GROUP), CHEMBL4524122 (PROTEIN FAMILY)

Molecules with ChEMBL bioactivity

41 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 198,904 (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
CHEMBL1112	ARIPIPRAZOLE	4	24,205
CHEMBL1185	ZOLMITRIPTAN	4	13,569
CHEMBL1200492	NEFAZODONE HYDROCHLORIDE	4	5,428
CHEMBL1200517	DIHYDROERGOTAMINE MESYLATE	4	2,704
CHEMBL1200809	AZELASTINE HYDROCHLORIDE	4	3,805
CHEMBL1263	SALMETEROL	4	40,383
CHEMBL12713	SERTINDOLE	4	8,984
CHEMBL1278	NARATRIPTAN	4	12,474
CHEMBL1279	FROVATRIPTAN	4	7,695
CHEMBL128	SUMATRIPTAN	4	28,367
CHEMBL1510	ELETRIPTAN	4	9,393
CHEMBL1615374	VILAZODONE HYDROCHLORIDE	4	432
CHEMBL1621	PALIPERIDONE	4	1,701
CHEMBL1633	KETOTIFEN FUMARATE	4	3,954
CHEMBL2024517	CARIPRAZINE HYDROCHLORIDE	4	277
CHEMBL2105760	BREXPIPRAZOLE	4	1,755
CHEMBL2138684	FROVATRIPTAN SUCCINATE	4	5
CHEMBL24778	SILODOSIN	4	2,288
CHEMBL301265	PRAMIPEXOLE	4	24,026
CHEMBL312448	XYLOMETAZOLINE	4	7,459
CHEMBL42	CLOZAPINE	4
CHEMBL442	ERGOTAMINE	4
CHEMBL500	PINDOLOL	4
CHEMBL51	KETANSERIN	4
CHEMBL715	OLANZAPINE	4
CHEMBL762	OXYMETAZOLINE	4
CHEMBL85	RISPERIDONE	4
CHEMBL905	RIZATRIPTAN	4
CHEMBL11	IMIPRAMINE	4
CHEMBL15245	YOHIMBINE	3

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

PharmGKB clinical annotations

9 annotations.

Variant	Type	Level	Drugs	Phenotypes
rs11568817	Toxicity	3	escitalopram	Anxiety Disorders
rs130058	Other	3	paroxetine	Depression
rs130058	Toxicity	3	clomipramine;liothyronine;lithium;nefazodone;venlafaxine	Depression
rs130060	PD	3	dihydroergotamine
rs130060	PD	3	methysergide
rs130060	PD	3	ketanserin
rs130060	PD	3	sumatriptan
rs6296	Toxicity	3	citalopram	Anxiety Disorders;Major Depressive Disorder
rs9361233	Efficacy	3	fluoxetine	Major Depressive Disorder

PharmGKB variants

6 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs6296	HTR1B	3	1.75	1	citalopram
rs130058	HTR1B	3	2.25	2	paroxetine;clomipramine;liothyronine;lithium;nefazodone;venlafaxine
rs11568817	HTR1B	3	2.50	1	escitalopram
rs13212041	HTR1B		0.00	0
rs130060	HTR1B	3	0.00	4	dihydroergotamine;methysergide;sumatriptan;ketanserin
rs1778258	HTR1B		0.00	0

GtoPdb / IUPHAR curated pharmacology

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

Target class: gpcr — 5-Hydroxytryptamine receptors

Most potent curated ligand interactions (87 total), top 25:

Ligand	Action	Affinity	Parameter
5-HT-moduline	Negative	11.0	pIC50
GR 127935	Partial agonist	9.8	pKi
oxymetazoline	Full agonist	9.5	pKi
donitriptan	Full agonist	9.4	pKi
[3H]N-methyl-AZ10419369	Partial agonist	9.4	pKd
dihydroergotamine	Full agonist	9.2	pKi
[3H]GR 125,743	Antagonist	9.2	pKd
L-694,247	Full agonist	9.2	pKi
[3H]alniditan	Full agonist	9.0	pKd
alniditan	Full agonist	9.0	pKi
SB 216641	Partial agonist	9.0	pKi
lysergol	Full agonist	8.9	pKi
[3H]8-OH-DPAT	Full agonist	8.9	pKd
[125I]GTI	Agonist	8.9	pKd
5-CT	Full agonist	8.8	pKi
CGS-12066	Full agonist	8.7	pKi
CP94253	Full agonist	8.7	pKi
7-methoxy-1-naphthylpiperazine	Full agonist	8.7	pKi
SB 224289	Inverse agonist	8.6	pKi
[3H]eletriptan	Partial agonist	8.5	pKd
methiothepin	Inverse agonist	8.5	pKi
5-OH-DPAT	Antagonist	8.4	pKi
5-hydroxytryptamine	Full agonist	8.4	pKd
mianserin	Antagonist	8.3	pKi
ziprasidone	Full agonist	8.3	pKi

Binding affinities (BindingDB)

68 measured of 96 human assays (127 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
NSC_104911	KI	0.1 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
(S,S)-reboxetine	KI	0.3 nM
(2S,4aR,6aR,7R,9S,10aS,10bR)-9-(acetyloxy)-2-(furan-3-yl)dodecahydro-6a,10b-dimethyl-4,10-dioxo-2H-naphtho-[2,1-c]pyran-7-carboxylic acid methyl ester	EC50	0.3 nM
2-Chlor-11-(2-dimethylaminoaethoxy)-dibenzo(b,f)-thiepin	KI	0.5 nM
METHIOTHEPIN	KI	1 nM
14C-5-hydroxy tryptamine creatinine disulfate	KI	1.2 nM
7-Methyl-4,6,6a,7,8,9,10,10a-octahydro-indolo[4,3-fg]quinoline-9-carboxylic acid ((2R,5S,10bS)-5-benzyl-10b-hydroxy-2-methyl-3,6-dioxo-octahydro-oxazolo[3,2-a]pyrrolo[2,1-c]pyrazin-2-yl)-amide	KI	1.5 nM
5-[2-(4-Benzo[d]isothiazol-3-yl-piperazin-1-yl)-ethyl]-6-chloro-1,3-dihydro-indol-2-one	KI	1.9 nM
Permax	KI	1.91 nM
4-[4-(4-Chloro-phenyl)-4-hydroxy-piperidin-1-yl]-1-(4-fluoro-phenyl)-butan-1-one;propionate(HCl)	KI	2.92 nM
8-[4-(4-fluorophenyl)-4-keto-butyl]-1-phenyl-1,3,8-triazaspiro[4.5]decan-4-one	KI	2.94 nM	US-9359372: Hexahydrodibenzo[a,g]quinolizine compound, preparation method thereof, pharmaceutical composition and use thereof
Terguride	KI	3.47 nM
5-Methoxy-3-(1,2,3,6-tetrahydro-pyridin-4-yl)-1H-indole(RU-24969)	KI	4.78 nM
N-methyl-2-[3-(1-methylpiperidin-4-yl)-1H-indol-5-yl]ethanesulfonamide	KI	5.1 nM
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
Bromocriptine+ (GTP+)	KI	12.9 nM
NSC_54746	KI	19.9 nM
NSC_155346	KI	21.4 nM
CP-122288	KI	24 nM
Fluorocarazolol,(S)	KI	34 nM
LY 246708	KI	50.1 nM
cid_3396	KI	56 nM
SMR001230745	KI	63.1 nM
2-[4-[3-[2-(trifluoromethyl)phenothiazin-10-yl]propyl]piperazin-1-yl]ethanol;hydrochloride	KI	146 nM
CAS_105182-45-4	KI	158 nM
MESULERGINE	KI	195 nM
S32504	KI	257 nM
Propanolol,(+/-)	KI	272 nM
4-[2-(dipropylamino)ethyl]-1,3-dihydro-2H-indol-2-one	KI	288 nM
(R)-1-(2-(1-(3-bromo-benzenesulfonyl)-pyrrolidin-2-yl)-ethyl)-4-methyl piperidine	KI	398 nM
4-[3-(2-chlorophenothiazin-10-yl)propyl]-1-piperazineethanol	KI	421 nM
NSC_4850	KI	447 nM
CAS_85760-74-3	IC50	462 nM	US-9359372: Hexahydrodibenzo[a,g]quinolizine compound, preparation method thereof, pharmaceutical composition and use thereof
10-(2-(1-methylpiperidin-2-yl)ethyl)-2-(methylsulfinyl)-10H-phenothiazine	KI	500 nM
CAS_3292447	KI	501 nM
NSC_5311097	KI	549 nM
Pramipexole	KI	692 nM
cid_2913535	KI	950 nM
L741,626	KI	1000 nM
(R)-4-Methyl-1-(2-(1-(naphthalene-1-sulfonyl)-pyrrolidin-2-yl)-ethyl)-piperidine(10)	KI	1000 nM
(R)-4-Methyl-1-(2-(1-toluene-3-sulfonyl)-pyrrolidin-2-yl)-ethyl)-piperidine (Oxalate salt)	KI	1000 nM
SR 147778	KI	1000 nM
S33084	KI	1000 nM
SL65.0155	KI	1020 nM
1-[2-[4-[5-chloro-1-(4-fluorophenyl)-indol-3-yl]-1-piperidyl]ethyl]imidazolidin-2-one	KI	1050 nM
4-(3-CHLOROPHENYL)-ALPHA-(DIPHENYLMETHYL)-1-PIPERAZINEETHANOL HYDROCHLORIDE	KI	1260 nM
MLS000028463	KI	1410 nM
(R)-1-(2-(1-(3,4-Dichloro-benzene sulfonyl)-pyrrolidin-2-yl)-ethyl)-4-methyl piperidine	KI	1580 nM
(R)-4-Methyl-1-(2-(1-(naphthalene-1-sulfonyl)-piperidin-2-yl)-ethyl)-piperidine(5)	KI	1580 nM

ChEMBL bioactivities

1396 potent at pChembl≥5 of 1402 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
10.05	EC50	0.09	nM	CHEMBL144397
10.00	Ki	0.1	nM	CHEMBL438619
10.00	Ki	0.1	nM	CHEMBL374973
10.00	Ki	0.1	nM	CHEMBL144030
10.00	EC50	0.1	nM	CHEMBL342323
9.96	Ki	0.11	nM	CHEMBL147851
9.85	Ki	0.14	nM	CHEMBL339308
9.85	Ki	0.14	nM	GR-127935
9.85	Ki	0.14	nM	CHEMBL357478
9.80	Ki	0.16	nM	CHEMBL147901
9.80	Kd	0.1585	nM	CHEMBL323208
9.72	EC50	0.19	nM	CHEMBL144128
9.70	Ki	0.2	nM	CHEMBL2112662
9.70	IC50	0.2	nM	CHEMBL194837
9.70	Ki	0.1995	nM	CHEMBL247428
9.70	Ki	0.1995	nM	CHEMBL490417
9.70	Ki	0.2	nM	CHEMBL344127
9.70	Ki	0.2	nM	CHEMBL147677
9.66	Ki	0.22	nM	CHEMBL357830
9.66	EC50	0.22	nM	CHEMBL147851
9.60	Ki	0.2512	nM	CHEMBL199088
9.59	EC50	0.26	nM	CHEMBL357830
9.59	Ki	0.26	nM	CHEMBL144128
9.57	Ki	0.27	nM	CHEMBL356277
9.55	EC50	0.28	nM	CHEMBL146720
9.52	Ki	0.3	nM	CHEMBL340786
9.52	Ki	0.3	nM	CHEMBL199443
9.52	Ki	0.3	nM	OXYMETAZOLINE
9.52	Ki	0.3	nM	CHEMBL144397
9.52	EC50	0.3	nM	CHEMBL356277
9.50	Ki	0.3162	nM	CHEMBL473186
9.50	Ki	0.3162	nM	CHEMBL370852
9.50	Ki	0.3162	nM	CHEMBL484059
9.49	Ki	0.32	nM	CHEMBL148022
9.44	Ki	0.36	nM	CHEMBL146720
9.42	Ki	0.38	nM	CHEMBL2112660
9.42	Ki	0.38	nM	CHEMBL342323
9.40	Ki	0.4	nM	CHEMBL197344
9.40	Ki	0.3981	nM	CHEMBL444398
9.40	Ki	0.3981	nM	CHEMBL496520
9.40	Ki	0.4	nM	ZOLMITRIPTAN
9.40	EC50	0.4	nM	CHEMBL357478
9.37	Ki	0.43	nM	CHEMBL129813
9.37	Ki	0.43	nM	CHEMBL2112661
9.37	Ki	0.43	nM	CHEMBL605785
9.37	Ki	0.4266	nM	CHEMBL605785
9.36	Ki	0.44	nM	CHEMBL338015
9.36	EC50	0.44	nM	CHEMBL147901
9.30	Ki	0.5012	nM	CHEMBL282229
9.30	Ki	0.5012	nM	CHEMBL194647

PubChem BioAssay actives

1345 with measured affinity, of 2810 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-[[3-(2-aminoethyl)-1H-indol-5-yl]oxy]-N-[4-[4-[2-[[3-(2-aminoethyl)-1H-indol-5-yl]oxy]acetyl]piperazin-1-yl]phenyl]acetamide	4252: Ability to inhibit the forskolin-stimulated c-AMP formation mediated by human 5-hydroxytryptamine 1B receptor in CHO-K1 cells	ki	0.0001	uM
2-[[3-(2-aminoethyl)-1H-indol-5-yl]oxy]-N-[3-[[2-[[3-(2-aminoethyl)-1H-indol-5-yl]oxy]acetyl]amino]propyl]acetamide	4495: Inhibition of forskolin-stimulated c-AMP formation by human 5-hydroxytryptamine 1B receptor expressed in CHO-K1 cells	ec50	0.0001	uM
2-[[3-(2-aminoethyl)-1H-indol-5-yl]oxy]-1-[4-[2-[[3-(2-aminoethyl)-1H-indol-5-yl]oxy]ethyl]piperazin-1-yl]ethanone	4252: Ability to inhibit the forskolin-stimulated c-AMP formation mediated by human 5-hydroxytryptamine 1B receptor in CHO-K1 cells	ki	0.0001	uM
N-[4-methoxy-3-(4-methylpiperazin-1-yl)phenyl]-4-[2-methyl-4-(5-methyl-1,2,4-oxadiazol-3-yl)phenyl]benzamide	254346: Affinity towards cloned human 5-hydroxytryptamine 1B receptor	ki	0.0001	uM
2-[5-[[4-[[3-(2-aminoethyl)-1H-indol-5-yl]oxymethyl]phenyl]methoxy]-1H-indol-3-yl]ethanamine	404702: Displacement of [3H]5-hydroxytryptamine from human cloned 5HT1B receptor expressed in CHOK1 cells by liquid scintillation counting	ki	0.0001	uM
N,N’-bis[3-(1-methylpiperidin-4-yl)-1H-indol-5-yl]tridecanediamide	404702: Displacement of [3H]5-hydroxytryptamine from human cloned 5HT1B receptor expressed in CHOK1 cells by liquid scintillation counting	ki	0.0001	uM
N-[4-methoxy-3-(4-methylpiperazin-1-yl)phenyl]-4-[2-methyl-4-(5-methyl-2,5-dihydro-1,2,4-oxadiazol-3-yl)phenyl]benzamide	4257: Receptor binding affinity for cloned human 5-hydroxytryptamine 1B receptor in Cos-7 cells	ki	0.0001	uM
4-[2-(4-isoquinolin-8-ylpiperazin-1-yl)ethyl]-11-methyl-8-thia-4,6,11-triazatricyclo[7.4.0.02,7]trideca-1(9),2(7),5-trien-3-one	257243: Inhibitory activity against human recombinant 5HT1B receptor co-expressed with G-protein chimera Gqo5 in HEK293 cells by FLIPR	ki	0.0001	uM
N-[6-[[3-(2-aminoethyl)-1H-indol-5-yl]oxy]hexyl]-4-[4-[6-[[3-(2-aminoethyl)-1H-indol-5-yl]oxy]hexylsulfamoyl]phenyl]benzenesulfonamide	4495: Inhibition of forskolin-stimulated c-AMP formation by human 5-hydroxytryptamine 1B receptor expressed in CHO-K1 cells	ec50	0.0001	uM
2-[[3-(2-aminoethyl)-1H-indol-5-yl]oxy]-1-[4-[1-[2-[[3-(2-aminoethyl)-1H-indol-5-yl]oxy]acetyl]piperidin-4-yl]piperidin-1-yl]ethanone	4252: Ability to inhibit the forskolin-stimulated c-AMP formation mediated by human 5-hydroxytryptamine 1B receptor in CHO-K1 cells	ki	0.0002	uM
2-[5-[2-[4-[2-[[3-(2-aminoethyl)-1H-indol-5-yl]oxy]ethyl]piperazin-1-yl]ethoxy]-1H-indol-3-yl]ethanamine	4495: Inhibition of forskolin-stimulated c-AMP formation by human 5-hydroxytryptamine 1B receptor expressed in CHO-K1 cells	ec50	0.0002	uM
1,3-bis[2-[[3-(2-aminoethyl)-1H-indol-5-yl]oxy]ethyl]urea	4252: Ability to inhibit the forskolin-stimulated c-AMP formation mediated by human 5-hydroxytryptamine 1B receptor in CHO-K1 cells	ki	0.0002	uM
2-(2,4-dichlorophenoxy)-N-[2-[2-(dimethylamino)ethoxy]-4-methylquinolin-6-yl]acetamide	254868: Inhibitory concentration against 5-hydroxytryptamine 1B receptor	ic50	0.0002	uM
2-[[3-(2-aminoethyl)-1H-indol-5-yl]oxy]-N-[2-[[3-(2-aminoethyl)-1H-indol-5-yl]oxy]ethyl]acetamide	4252: Ability to inhibit the forskolin-stimulated c-AMP formation mediated by human 5-hydroxytryptamine 1B receptor in CHO-K1 cells	ki	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
8-fluoro-4-methyl-6-[[4-[2-(2-methylquinolin-5-yl)oxyethyl]piperazin-1-yl]methyl]-1,4-benzoxazin-3-one	308953: Displacement of [3H]5-HT from human recombinant 5HT1B receptor expressed in CHO cells	ki	0.0002	uM
(E)-3-[3-[2-(dimethylamino)ethyl]-1H-indol-5-yl]-N-[(4-methoxyphenyl)methyl]prop-2-enamide	4931: Compound was tested for binding affinity against cloned human 5-hydroxytryptamine 1D receptor beta expressed in CHO-K1 cells.	ki	0.0002	uM
1-[4-[(2-methylphenyl)methyl]piperazin-1-yl]-2-[8-(4-methylpiperazin-1-yl)naphthalen-2-yl]oxyethanone	4257: Receptor binding affinity for cloned human 5-hydroxytryptamine 1B receptor in Cos-7 cells	ki	0.0002	uM
6-[2-[4-(2-methylquinolin-5-yl)piperazin-1-yl]ethyl]-4H-1,4-benzoxazin-3-one	344710: Displacement of [3H]5HT from human 5HT1B receptor expressed in CHO cells	ki	0.0002	uM
6-[2-[4-(2-phenylquinolin-5-yl)piperazin-1-yl]ethyl]-4H-1,4-benzoxazin-3-one	344710: Displacement of [3H]5HT from human 5HT1B receptor expressed in CHO cells	ki	0.0003	uM
2-[5-[[3-[[3-(2-aminoethyl)-1H-indol-5-yl]oxymethyl]phenyl]methoxy]-1H-indol-3-yl]ethanamine	4252: Ability to inhibit the forskolin-stimulated c-AMP formation mediated by human 5-hydroxytryptamine 1B receptor in CHO-K1 cells	ki	0.0003	uM
2-[[3-(2-aminoethyl)-1H-indol-5-yl]oxy]-N-[4-[[2-[[3-(2-aminoethyl)-1H-indol-5-yl]oxy]acetyl]amino]phenyl]acetamide	4252: Ability to inhibit the forskolin-stimulated c-AMP formation mediated by human 5-hydroxytryptamine 1B receptor in CHO-K1 cells	ki	0.0003	uM
4-(4-fluoronaphthalen-1-yl)-6-propan-2-ylpyrimidin-2-amine	1242894: Binding affinity to 5HT1B receptor (unknown origin)	ki	0.0003	uM
(4-chlorophenyl)-[8-(4-methylpiperazin-1-yl)-2,3-dihydropyrrolo[3,2-g]isoquinolin-1-yl]methanone	254612: Mean binding affinity towards 5-hydroxytryptamine 1B receptor using [3H]5-HT or [3H]-8-OH-DPAT as the radioligand	ki	0.0003	uM
[8-(4-methylpiperazin-1-yl)-2,3-dihydropyrrolo[3,2-g]isoquinolin-1-yl]-[6-(trifluoromethyl)-3-pyridinyl]methanone	254612: Mean binding affinity towards 5-hydroxytryptamine 1B receptor using [3H]5-HT or [3H]-8-OH-DPAT as the radioligand	ki	0.0003	uM
Oxymetazoline	4249: Binding affinity towards human 5-hydroxytryptamine 1B receptor using [3H]5-HT trifluoroacetate as radioligand	ki	0.0003	uM
11-methyl-4-[2-(4-quinolin-8-ylpiperazin-1-yl)ethyl]-8-thia-4,6,11-triazatricyclo[7.4.0.02,7]trideca-1(9),2(7),5-trien-3-one	257243: Inhibitory activity against human recombinant 5HT1B receptor co-expressed with G-protein chimera Gqo5 in HEK293 cells by FLIPR	ki	0.0003	uM
1-[4-(2-methylphenyl)piperazin-1-yl]-2-[8-(4-methylpiperazin-1-yl)naphthalen-2-yl]oxyethanone	4257: Receptor binding affinity for cloned human 5-hydroxytryptamine 1B receptor in Cos-7 cells	ki	0.0003	uM
2-[[3-(2-aminoethyl)-1H-indol-5-yl]oxy]-1-[4-[2-[[3-(2-aminoethyl)-1H-indol-5-yl]oxy]acetyl]piperazin-1-yl]ethanone	4495: Inhibition of forskolin-stimulated c-AMP formation by human 5-hydroxytryptamine 1B receptor expressed in CHO-K1 cells	ec50	0.0003	uM
5-fluoro-6-[2-[4-(2-methylquinolin-5-yl)piperazin-1-yl]ethyl]-4H-1,4-benzoxazin-3-one	344710: Displacement of [3H]5HT from human 5HT1B receptor expressed in CHO cells	ki	0.0004	uM
1-[4-(2,3-dimethoxyphenyl)piperazin-1-yl]-2-[8-(4-methylpiperazin-1-yl)naphthalen-2-yl]oxyethanone	4257: Receptor binding affinity for cloned human 5-hydroxytryptamine 1B receptor in Cos-7 cells	ki	0.0004	uM
1-[4-(2,3-dihydro-1,4-benzodioxin-5-yl)piperazin-1-yl]-2-[8-(4-methylpiperazin-1-yl)naphthalen-2-yl]oxyethanone	4257: Receptor binding affinity for cloned human 5-hydroxytryptamine 1B receptor in Cos-7 cells	ki	0.0004	uM
2-[8-(4-methylpiperazin-1-yl)naphthalen-2-yl]oxy-1-(4-naphthalen-1-ylpiperazin-1-yl)ethanone	4257: Receptor binding affinity for cloned human 5-hydroxytryptamine 1B receptor in Cos-7 cells	ki	0.0004	uM
2-[4-[2-[8-(4-methylpiperazin-1-yl)naphthalen-2-yl]oxyacetyl]piperazin-1-yl]benzonitrile	4257: Receptor binding affinity for cloned human 5-hydroxytryptamine 1B receptor in Cos-7 cells	ki	0.0004	uM
4-[2-[4-(1-benzothiophen-7-yl)piperazin-1-yl]ethyl]-11-methyl-8-thia-4,6,11-triazatricyclo[7.4.0.02,7]trideca-1(9),2(7),5-trien-3-one	257243: Inhibitory activity against human recombinant 5HT1B receptor co-expressed with G-protein chimera Gqo5 in HEK293 cells by FLIPR	ki	0.0004	uM
6-fluoro-N-[6-(4-methoxyoxan-4-yl)-3-pyridinyl]-4-oxo-8-(1,3,5-trimethylpyrazol-4-yl)chromene-2-carboxamide	459896: Binding affinity to 5HT1B receptor expressed in CHO cells	ki	0.0004	uM
Zolmitriptan	1993606: Binding affinity to 5-HT1B receptor (unknown origin) assessed as inhibition constant	ki	0.0004	uM
6-[2-[4-(2-methyl-1H-indol-4-yl)piperazin-1-yl]ethyl]-4H-1,4-benzoxazin-3-one	344710: Displacement of [3H]5HT from human 5HT1B receptor expressed in CHO cells	ki	0.0004	uM
6-[2-[4-(7-chloro-2-methylquinolin-5-yl)piperazin-1-yl]ethyl]-4H-1,4-benzoxazin-3-one	344710: Displacement of [3H]5HT from human 5HT1B receptor expressed in CHO cells	ki	0.0005	uM
6-[2-[4-(8-chloro-2-methylquinolin-5-yl)piperazin-1-yl]ethyl]-4H-1,4-benzoxazin-3-one	344710: Displacement of [3H]5HT from human 5HT1B receptor expressed in CHO cells	ki	0.0005	uM
[6-[2-(dimethylamino)ethoxy]-5-methoxy-2,3-dihydroindol-1-yl]-[4-[2-methyl-4-(5-methyl-1,2,4-oxadiazol-3-yl)phenyl]phenyl]methanone	4282: Binding affinity for human 5-hydroxytryptamine 1B receptor	ki	0.0005	uM
2-[5-[6-[[3-(2-aminoethyl)-1H-indol-5-yl]oxy]hexoxy]-1H-indol-3-yl]ethanamine	4252: Ability to inhibit the forskolin-stimulated c-AMP formation mediated by human 5-hydroxytryptamine 1B receptor in CHO-K1 cells	ki	0.0005	uM
11-methyl-4-[2-(4-naphthalen-1-ylpiperazin-1-yl)ethyl]-8-thia-4,6,11-triazatricyclo[7.4.0.02,7]trideca-1(9),2(7),5-trien-3-one	257243: Inhibitory activity against human recombinant 5HT1B receptor co-expressed with G-protein chimera Gqo5 in HEK293 cells by FLIPR	ki	0.0005	uM
N,N’-bis[3-(1-methylpiperidin-4-yl)-1H-indol-5-yl]tetradecanediamide	404702: Displacement of [3H]5-hydroxytryptamine from human cloned 5HT1B receptor expressed in CHOK1 cells by liquid scintillation counting	ki	0.0005	uM
4-[8-(4-methylpiperazin-1-yl)-2,3-dihydropyrrolo[3,2-g]isoquinoline-1-carbonyl]benzonitrile	254612: Mean binding affinity towards 5-hydroxytryptamine 1B receptor using [3H]5-HT or [3H]-8-OH-DPAT as the radioligand	ki	0.0005	uM
4-[2-[4-(2,3-dihydro-1-benzofuran-7-yl)piperazin-1-yl]ethyl]-11-methyl-8-thia-4,6,11-triazatricyclo[7.4.0.02,7]trideca-1(9),2(7),5-trien-3-one	257243: Inhibitory activity against human recombinant 5HT1B receptor co-expressed with G-protein chimera Gqo5 in HEK293 cells by FLIPR	ki	0.0005	uM
4-[2-[4-(3-chloro-2-methoxyphenyl)piperazin-1-yl]ethyl]-11-methyl-8-thia-4,6,11-triazatricyclo[7.4.0.02,7]trideca-1(9),2(7),5-trien-3-one	257243: Inhibitory activity against human recombinant 5HT1B receptor co-expressed with G-protein chimera Gqo5 in HEK293 cells by FLIPR	ki	0.0005	uM
N-cyclopropyl-6-[2-[4-(2-methylquinolin-5-yl)piperazin-1-yl]ethyl]-4H-imidazo[5,1-c][1,4]benzoxazine-3-carboxamide	510118: Antagonist activity against human recombinant 5HT1B receptor expressed in CHO cells assessed as inhibition of 5HT-induced [35S]GTPgammaS binding by scintillation proximity assay	ki	0.0005	uM
methyl N-[3-[2-[4-(2-methylquinolin-5-yl)piperazin-1-yl]ethyl]phenyl]carbamate	541182: Displacement of [3H]5-HT from human recombinant 5-HT1B receptor expressed in CHO cells	ki	0.0005	uM
N-[3-[2-[4-(2-methylquinolin-5-yl)piperazin-1-yl]ethyl]phenyl]acetamide	541182: Displacement of [3H]5-HT from human recombinant 5-HT1B receptor expressed in CHO cells	ki	0.0005	uM

CTD chemical–gene interactions

22 total (human), top 22 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
trimellitic anhydride	decreases expression	1
S-(1,2-dichlorovinyl)cysteine	affects cotreatment, decreases expression, affects response to substance, increases expression	1
naratriptan	affects binding	1
N-(3-(2-dimethylamino)ethoxy-4-methoxyphenyl)-2’-methyl-4’-(5-methyl-1,2,4-oxadiazol-3-yl)-(1,1’-biphenyl)-4-carboxamide	increases activity, affects binding	1
BRL 15572	affects binding, increases activity	1
almotriptan	decreases reaction, increases abundance, affects reaction	1
abrine	decreases expression	1
Resveratrol	affects cotreatment, decreases expression	1
Decitabine	increases expression	1
Sunitinib	increases expression	1
Vortioxetine	affects binding, affects activity	1
Acetaminophen	decreases expression	1
Cyclic AMP	affects reaction, decreases reaction, increases abundance	1
Benzo(a)pyrene	affects methylation, decreases expression, increases methylation	1
Bleomycin	decreases expression	1
Colforsin	affects reaction, decreases reaction, increases abundance	1
Lipopolysaccharides	decreases expression, affects response to substance, increases expression, affects cotreatment	1
Plant Extracts	decreases expression, affects cotreatment	1
Serotonin	affects binding, decreases reaction, increases activity	1
Smoke	increases expression	1
Triclosan	decreases expression	1
Endocannabinoids	affects binding, decreases reaction, increases activity	1

ChEMBL screening assays

640 unique, capped per target: 516 binding, 120 functional, 3 admet, 1 toxicity

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1000200	Binding	Binding affinity to 5HT1B receptor	Synthesis and evaluation of dibenzothiazepines: a novel class of selective cannabinoid-1 receptor inverse agonists. — J Med Chem
CHEMBL1020888	Functional	Activity at 5HT1B receptor assessed as calcium mobilization by FLIPR	Structure-activity relationships of the cycloalkanol ethylamine scaffold: discovery of selective norepinephrine reuptake inhibitors. — J Med Chem
CHEMBL4406601	ADMET	Displacement of [3H]5-CT from recombinant human 5HT1B receptor stably expressed in HEK cell membranes measured after 90 mins by microbeta scintillation counting method	Discovery, Optimization, and Characterization of ML417: A Novel and Highly Selective D3 Dopamine Receptor Agonist. — J Med Chem

Cellosaurus cell lines

4 cell lines: 3 spontaneously immortalized cell line, 1 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_K239	Ltk-8-30-84	Spontaneously immortalized cell line	Male
CVCL_KV39	cAMP Hunter CHO-K1 HTR1B Gi	Spontaneously immortalized cell line	Female
CVCL_LA52	PathHunter U2OS HTR1B beta-arrestin	Cancer cell line	Female
CVCL_XD05	CHO-5-HT1B	Spontaneously immortalized cell line	Female

Clinical trials (associated diseases)

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