HTR1D

Summary

HTR1D (5-hydroxytryptamine receptor 1D, HGNC:5289) is a protein-coding gene on chromosome 1p36.12, encoding 5-hydroxytryptamine receptor 1D (P28221). G-protein coupled receptor for 5-hydroxytryptamine (serotonin).

Enables Gi/o-coupled serotonin receptor activity and serotonin receptor activity. Involved in adenylate cyclase-inhibiting serotonin receptor signaling pathway and intestine smooth muscle contraction. Located in plasma membrane.

Source: NCBI Gene 3352 — RefSeq curated summary.

At a glance

• GWAS associations: 11
• Clinical variants (ClinVar): 69 total
• Druggable target: yes — 38 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_000864

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:5289
Approved symbol	HTR1D
Name	5-hydroxytryptamine receptor 1D
Location	1p36.12
Locus type	gene with protein product
Status	Approved
Aliases	RDC4, HT1DA, 5-HT1D
Ensembl gene	ENSG00000179546
Ensembl biotype	protein_coding
OMIM	182133
Entrez	3352

Gene structure

Transcript identifiers

Ensembl transcripts: 13 — 13 protein_coding

ENST00000374619, ENST00000918575, ENST00000918576, ENST00000918577, ENST00000918578, ENST00000918579, ENST00000918580, ENST00000918581, ENST00000918582, ENST00000918583, ENST00000918584, ENST00000918585, ENST00000918586

RefSeq mRNA: 1 — MANE Select: NM_000864 NM_000864

CCDS: CCDS231

Canonical transcript exons

ENST00000374619 — 2 exons

Exon	Start	End
ENSE00001464023	23191895	23195001
ENSE00003921324	23217291	23217502

Expression profiles

Bgee: expression breadth broad, 79 present calls, max score 73.51.

FANTOM5 (CAGE): breadth broad, TPM avg 0.6026 / max 92.4446, expressed in 227 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
10949	0.5904	225
10946	0.0065	1
10947	0.0031	1
10948	0.0026	1

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	73.51	gold quality
nucleus accumbens	UBERON:0001882	73.24	gold quality
putamen	UBERON:0001874	68.65	gold quality
duodenum	UBERON:0002114	68.29	gold quality
caudate nucleus	UBERON:0001873	66.94	gold quality
gall bladder	UBERON:0002110	63.58	gold quality
small intestine	UBERON:0002108	63.19	gold quality
small intestine Peyer’s patch	UBERON:0003454	62.77	gold quality
jejunal mucosa	UBERON:0000399	61.75	silver quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	61.64	gold quality
ganglionic eminence	UBERON:0004023	60.39	gold quality
stromal cell of endometrium	CL:0002255	58.64	gold quality
prefrontal cortex	UBERON:0000451	57.06	gold quality
ventricular zone	UBERON:0003053	56.67	gold quality
amygdala	UBERON:0001876	53.68	gold quality
hypothalamus	UBERON:0001898	52.66	gold quality
Brodmann (1909) area 9	UBERON:0013540	52.42	gold quality
frontal cortex	UBERON:0001870	52.11	gold quality
jejunum	UBERON:0002115	52.02	gold quality
forebrain	UBERON:0001890	51.94	gold quality
right frontal lobe	UBERON:0002810	51.66	gold quality
islet of Langerhans	UBERON:0000006	51.57	gold quality
neocortex	UBERON:0001950	50.90	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	50.28	gold quality
brain	UBERON:0000955	49.61	gold quality
oocyte	CL:0000023	49.43	gold quality
cerebral cortex	UBERON:0000956	48.36	gold quality
temporal lobe	UBERON:0001871	47.85	gold quality
right lung	UBERON:0002167	47.40	gold quality
anterior cingulate cortex	UBERON:0009835	47.39	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	2.94
E-MTAB-6058	no	3.84

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

39 targeting HTR1D, 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-3613-3P	100.00	76.36	7965
HSA-MIR-7110-3P	100.00	73.18	2486
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-570-3P	99.96	72.41	4910
HSA-MIR-2110	99.96	66.68	1930
HSA-MIR-4725-3P	99.96	69.53	2520
HSA-MIR-6780B-5P	99.96	69.60	2562
HSA-MIR-539-5P	99.93	70.30	2855
HSA-MIR-627-3P	99.90	71.42	3316
HSA-MIR-4753-3P	99.90	71.03	3786
HSA-MIR-4271	99.88	68.32	2244
HSA-MIR-130B-5P	99.83	68.50	1888
HSA-MIR-1197	99.70	67.75	1027
HSA-MIR-3942-3P	99.57	69.03	2854
HSA-MIR-6731-5P	99.28	67.42	2375
HSA-MIR-8085	99.28	67.56	2362
HSA-MIR-892C-5P	99.16	70.56	2116
HSA-MIR-5100	99.11	67.52	1098
HSA-MIR-3675-3P	99.09	67.70	968
HSA-MIR-5000-3P	98.79	65.63	1251
HSA-MIR-11399	98.71	65.69	869
HSA-MIR-3161	98.71	67.14	816
HSA-MIR-7155-5P	98.65	66.14	1290
HSA-MIR-1267	98.24	69.05	837
HSA-MIR-340-3P	98.11	68.25	679
HSA-MIR-6827-3P	98.08	72.27	651
HSA-MIR-4436A	98.05	64.83	1140
HSA-MIR-3691-3P	97.90	65.97	791

Literature-anchored findings (GeneRIF, showing 13)

• Gene may be linked to etiology of anorexia nervosa. (PMID:12740597)
• Polymorphisms in the serotonin 5-HT1D receptor gene are preferentially transmitted in attention-deficit hyperactivity disorder in Chinese Han subjects. (PMID:17099886)
• The density of 5HT(1D)R was significantly more in tissues known to produce migraine-like pain. 5HT(1D)R-like immunoreactivity was restricted to neuronal fibres, colocalizing with calcitonin gene-related peptide & tyrosine hydroxylase positive fibres. (PMID:18557979)
• Cell adhesion modulates 5-HT(1D) and P2Y receptor signal trafficking differentially in LTK-8 cells. (PMID:18582865)
• This study reveals sex-specific alterations in gene expression of the pre-synaptic 5-HT1D autoreceptors and 5-HT-related transcription factors, NUDR and REST, in dorsal raphe neurons of women with major depression disorder. (PMID:19878438)
• study identified the presence of genetic association at chromosome 1p36 with migraine with aura (P=0.045, Bonferroni corrected): the locus encoding the 5HT(1D) receptor gene (PMID:22107845)
• 5-HT1B- and 5-HT1D-mediated signaling play an important role in the regulation of the proliferative and invasive phenotype of pancreatic cancer cells. (PMID:25170871)
• Down-regulation of 5-HT1B and 5-HT1D receptors inhibits proliferation, clonogenicity and invasion of human pancreatic cancer cells. (PMID:25268648)
• results suggest that 5-HT signaling participates in regulation of overall islet hormone secretion in non- diabetic individuals and over-expression of HTR1D and HTR2A may either contribute to islet dysfunction in T2D (PMID:26206285)
• Data show that 5-hydroxytryptamine receptor (5-HT1DR) played an important role in cell invasion via Axin1/beta-catenin/matrix metalloproteinase 7 (MMP-7) pathway. (PMID:26214021)
• significantly promotes hepatocellular carcinoma (HCC) proliferation, epithelial-mesenchymal transition, and metastasis; elevated expression level predicts poor overall survival and high recurrence probability in HCC patients (PMID:30561038)
• Knockdown and inhibition of hydroxytryptamine receptor 1D suppress proliferation and migration of gastric cancer cells. (PMID:35785570)
• HTR1D functions as a key target of HOXA10-AS/miR-340-3p axis to promote the malignant outcome of pancreatic cancer via PI3K-AKT signaling pathway. (PMID:35813473)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
danio_rerio	htr1d	ENSDARG00000054124
caenorhabditis_elegans		WBGENE00004779

Paralogs (25): DRD4 (ENSG00000069696), HRH3 (ENSG00000101180), HRH2 (ENSG00000113749), CHRM3 (ENSG00000133019), HRH4 (ENSG00000134489), TAAR5 (ENSG00000135569), GPR84 (ENSG00000139572), GPR161 (ENSG00000143147), TAAR2 (ENSG00000146378), TAAR6 (ENSG00000146383), TAAR8 (ENSG00000146385), TAAR1 (ENSG00000146399), DRD3 (ENSG00000151577), HTR4 (ENSG00000164270), CHRM1 (ENSG00000168539), DRD5 (ENSG00000169676), HTR1A (ENSG00000178394), CHRM4 (ENSG00000180720), CHRM2 (ENSG00000181072), DRD1 (ENSG00000184845), CHRM5 (ENSG00000184984), GPR21 (ENSG00000188394), HRH1 (ENSG00000196639), GPR52 (ENSG00000203737), TAAR9 (ENSG00000237110)

Protein

Protein identifiers

5-hydroxytryptamine receptor 1D — P28221 (reviewed: P28221)

Alternative names: Serotonin 1D alpha receptor, Serotonin receptor 1D

All UniProt accessions (1): P28221

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. 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. HTR1D is coupled to G(i)/G(o) G alpha proteins and mediates inhibitory neurotransmission by inhibiting adenylate cyclase activity. Regulates the release of 5-hydroxytryptamine in the brain, and thereby affects neural activity. May also play a role in regulating the release of other neurotransmitters. May play a role in vasoconstriction.

Subunit / interactions. Homodimer. Heterodimer with HTR1B.

Subcellular location. Cell membrane.

Tissue specificity. Detected in brain neocortex and caudate nucleus (at protein level).

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

RefSeq proteins (1): NP_000855* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000276	GPCR_Rhodpsn	Family
IPR000505	5HT1D_rcpt	Family
IPR002231	5HT_rcpt	Family
IPR017452	GPCR_Rhodpsn_7TM	Domain

Pfam: PF00001

UniProt features (41 total): helix 13, topological domain 8, transmembrane region 7, binding site 3, glycosylation site 3, short sequence motif 2, chain 1, region of interest 1, disulfide bond 1, sequence variant 1, strand 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
7E32	ELECTRON MICROSCOPY	2.9

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P28221-F1	79.38	0.47

Antibody-complex structures (SAbDab): 1 — 7E32

Functional residue map

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

Ligand- & substrate-binding residues (3): 118; 122; 321

Disulfide bonds (1): 111–188

Glycosylation sites (3): 5, 17, 21

Function

Pathways and Gene Ontology

Reactome pathways

8 pathways

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

MSigDB gene sets: 103 (showing top): GOMF_G_PROTEIN_COUPLED_SEROTONIN_RECEPTOR_ACTIVITY, GOBP_BEHAVIOR, GOBP_CIRCULATORY_SYSTEM_PROCESS, GTCTACC_MIR379, GGGTGGRR_PAX4_03, GOBP_CELL_CELL_SIGNALING, GOBP_ADENYLATE_CYCLASE_MODULATING_G_PROTEIN_COUPLED_RECEPTOR_SIGNALING_PATHWAY, GOBP_REGULATION_OF_ANATOMICAL_STRUCTURE_SIZE, GOBP_REGULATION_OF_BEHAVIOR, GOBP_MUSCLE_CONTRACTION, GOBP_PHASIC_SMOOTH_MUSCLE_CONTRACTION, KEGG_NEUROACTIVE_LIGAND_RECEPTOR_INTERACTION, GOBP_SMOOTH_MUSCLE_CONTRACTION, TGANTCA_AP1_C, GOBP_SYNAPTIC_SIGNALING

GO Biological Process (12): G protein-coupled receptor signaling pathway, coupled to cyclic nucleotide second messenger (GO:0007187), adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway (GO:0007193), adenylate cyclase-inhibiting serotonin receptor signaling pathway (GO:0007198), chemical synaptic transmission (GO:0007268), intestine smooth muscle contraction (GO:0014827), regulation of locomotion (GO:0040012), vasoconstriction (GO:0042310), regulation of behavior (GO:0050795), smooth muscle contraction (GO:0006939), signal transduction (GO:0007165), G protein-coupled receptor signaling pathway (GO:0007186), adenylate cyclase-activating G protein-coupled receptor signaling pathway (GO:0007189)

GO Molecular Function (5): Gi/o-coupled serotonin receptor activity (GO:0001586), G protein-coupled serotonin receptor activity (GO:0004993), neurotransmitter receptor activity (GO:0030594), serotonin receptor activity (GO:0099589), G protein-coupled receptor activity (GO:0004930)

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

Reactome top-level categories

Rollup of top-6 pathways:

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

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
G protein-coupled receptor signaling pathway	2
adenylate cyclase-modulating G protein-coupled receptor signaling pathway	2
G protein-coupled serotonin receptor signaling pathway	2
transmembrane signaling receptor activity	2
adenylate cyclase inhibitor activity	1
Gi/o-coupled serotonin receptor activity	1
adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway	1
anterograde trans-synaptic signaling	1
phasic smooth muscle contraction	1
gastro-intestinal system smooth muscle contraction	1
locomotion	1
regulation of biological process	1
blood vessel diameter maintenance	1
behavior	1
regulation of multicellular organismal process	1
muscle contraction	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
adenylate cyclase activator activity	1
G protein-coupled serotonin receptor activity	1
G protein-coupled amine receptor activity	1
serotonin binding	1
signaling receptor activity	1
membrane	1
cell periphery	1
neuron projection	1
dendritic tree	1
cell junction	1
cellular anatomical structure	1

Protein interactions and networks

STRING

786 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
HTR1D	SLC6A4	P31645	920
HTR1D	HTR1B	P28222	891
HTR1D	TPH1	P17752	801
HTR1D	HTR3A	P46098	790
HTR1D	MAOB	P27338	779
HTR1D	TPH2	Q8IWU9	692
HTR1D	VIPR1	P32241	681
HTR1D	MAOA	P21397	604
HTR1D	HTR3B	O95264	602
HTR1D	HTR1E	P28566	587
HTR1D	CHRNA4	P43681	579
HTR1D	HTR2B	P41595	569
HTR1D	HTR2C	P28335	550
HTR1D	HTR1A	P08908	547
HTR1D	S100A10	P08206	522

IntAct

4 interactions, top by confidence:

A	B	Type	Score
HTR1D	RAMP1	psi-mi:“MI:0915”(physical association)	0.400
RAMP2	HTR1D	psi-mi:“MI:0915”(physical association)	0.400
RAMP3	HTR1D	psi-mi:“MI:0915”(physical association)	0.400
HTR1D	RAMP3	psi-mi:“MI:0915”(physical association)	0.400

BioGRID (3): HTR1D (Affinity Capture-Western), S1PR1 (Affinity Capture-Western), HTR1B (Affinity Capture-Western)

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: A0A678XMK4, O02662, O02666, O14804, O19091, O42574, O70528, O77680, O77700, P07700, P11617, P17124, P18089, P21728, P23944, P25021, P25100, P25102, P25115, P28221, P28565, P35405, P35406, P42289, P42290, P42291, P43141, P46626, P47747, P47800, P49145, P50406, P53452, P53454, P60021, P61752, P79400, P97288, P97292, P97714

SIGNOR signaling

28 interactions.

A	Effect	B	Mechanism
“3-[4-(3-chlorophenyl)piperazin-1-yl]-1,1-diphenylpropan-2-ol hydrochloride”	down-regulates	HTR1D	“chemical inhibition”
192927-92-7	down-regulates	HTR1D	“chemical inhibition”
HTR1D	“up-regulates activity”	GNAI1	binding
HTR1D	“up-regulates activity”	GNAI3	binding
HTR1D	“up-regulates activity”	GNAO1	binding
HTR1D	“up-regulates activity”	GNAZ	binding
HTR1D	“up-regulates activity”	GNA14	binding
serotonin(1+)	“up-regulates activity”	HTR1D	“chemical activation”
naratriptan	“up-regulates activity”	HTR1D	“chemical activation”
eletriptan	“up-regulates activity”	HTR1D	“chemical activation”
sumatriptan	“up-regulates activity”	HTR1D	“chemical activation”
zolmitriptan	“up-regulates activity”	HTR1D	“chemical activation”
rizatriptan	“up-regulates activity”	HTR1D	“chemical activation”
serotonin	“up-regulates activity”	HTR1D	“chemical activation”
ziprasidone	“up-regulates activity”	HTR1D	“chemical activation”
olanzapine	“up-regulates activity”	HTR1D	“chemical activation”
clozapine	“up-regulates activity”	HTR1D	“chemical activation”
haloperidol	“down-regulates activity”	HTR1D	“chemical inhibition”
risperidone	“down-regulates activity”	HTR1D	“chemical inhibition”
quetiapine	“up-regulates activity”	HTR1D	“chemical activation”
8-[4,4-bis(4-fluorophenyl)butyl]-1-phenyl-1,3,8-triazaspiro[4.5]decan-4-one	“down-regulates activity”	HTR1D	“chemical inhibition”
sertindole	“down-regulates activity”	HTR1D	“chemical inhibition”
zotepine	“down-regulates activity”	HTR1D	“chemical inhibition”
paliperidone	“down-regulates activity”	HTR1D	“chemical inhibition”
(S,S)-asenapine	“up-regulates activity”	HTR1D	“chemical activation”
pipamperone	“down-regulates activity”	HTR1D	“chemical inhibition”
oxymetazoline	“up-regulates activity”	HTR1D	“chemical activation”
frovatriptan	“up-regulates activity”	HTR1D	“chemical activation”

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	65
Likely benign	1
Benign	3

Top pathogenic / likely-pathogenic (0)

SpliceAI

40 predictions. Top by Δscore:

Variant	Effect	Δscore
1:23194334:C:CT	acceptor_gain	0.8100
1:23194631:G:A	donor_gain	0.7500
1:23192835:C:G	acceptor_gain	0.5800
1:23192835:C:CT	acceptor_gain	0.5400
1:23194327:CG:C	acceptor_gain	0.5300
1:23192834:T:TG	acceptor_gain	0.5200
1:23193072:A:AC	donor_gain	0.5200
1:23193945:A:AC	donor_gain	0.5200
1:23194328:G:C	acceptor_gain	0.5100
1:23194284:AC:A	acceptor_gain	0.4600
1:23194491:T:A	donor_gain	0.4600
1:23194325:GCCGT:G	acceptor_gain	0.4500
1:23192836:A:T	acceptor_gain	0.4400
1:23194466:C:CT	donor_gain	0.4400
1:23194467:T:TT	donor_gain	0.4400
1:23194283:GA:G	acceptor_gain	0.4200
1:23192123:T:TC	acceptor_gain	0.4100
1:23194387:T:TC	acceptor_gain	0.3600
1:23194335:A:T	acceptor_gain	0.3500
1:23192830:C:CT	acceptor_gain	0.3400
1:23194627:T:A	donor_gain	0.3200
1:23194326:CCG:C	acceptor_gain	0.3100
1:23194387:T:C	acceptor_gain	0.2800
1:23194285:C:A	acceptor_gain	0.2700
1:23192833:C:CC	acceptor_gain	0.2600
1:23193838:G:GT	acceptor_gain	0.2600
1:23194327:C:T	acceptor_gain	0.2600
1:23194521:AGGGT:A	donor_gain	0.2600
1:23194465:A:AC	donor_gain	0.2500
1:23194282:TG:T	acceptor_gain	0.2400

AlphaMissense

2434 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:23193290:A:C	F310L	0.998
1:23193290:A:T	F310L	0.998
1:23193292:A:G	F310L	0.998
1:23193602:G:C	F206L	0.998
1:23193602:G:T	F206L	0.998
1:23193604:A:G	F206L	0.998
1:23193733:A:G	W163R	0.997
1:23193733:A:T	W163R	0.997
1:23193908:C:A	W104C	0.997
1:23193908:C:G	W104C	0.997
1:23193266:G:C	F318L	0.996
1:23193266:G:T	F318L	0.996
1:23193268:A:G	F318L	0.996
1:23193273:G:C	P316R	0.996
1:23193969:T:G	D84A	0.996
1:23193176:G:C	N348K	0.995
1:23193176:G:T	N348K	0.995
1:23193813:C:A	R136M	0.995
1:23193888:C:G	C111S	0.995
1:23193889:A:T	C111S	0.995
1:23193968:G:C	D84E	0.995
1:23193968:G:T	D84E	0.995
1:23193969:T:A	D84V	0.995
1:23193969:T:C	D84G	0.995
1:23193164:A:C	N352K	0.994
1:23193164:A:T	N352K	0.994
1:23193186:C:T	G345D	0.994
1:23193269:G:C	F317L	0.994
1:23193269:G:T	F317L	0.994
1:23193271:A:G	F317L	0.994

dbSNP variants (sampled 300 via entrez): RS1000027761 (1:23210482 T>C), RS1000080984 (1:23218926 T>C), RS1000094513 (1:23201194 A>G), RS1000354681 (1:23206328 C>G), RS1000438817 (1:23192477 T>C), RS1000616329 (1:23218717 G>A), RS1000828257 (1:23216608 A>G), RS1000958469 (1:23207914 C>T), RS1001239440 (1:23193439 G>A), RS1001296810 (1:23192814 C>T), RS1001303997 (1:23208186 T>C), RS1001332057 (1:23197091 C>A,G,T), RS1001636124 (1:23219502 G>A,C), RS1001831515 (1:23215034 G>A,C), RS1001889443 (1:23217468 C>A,G,T)

Disease associations

OMIM: gene MIM:182133 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

11 associations (top):

Study	Trait	p-value
GCST000817_145	Height	3.000000e-12
GCST007876_64	Estimated glomerular filtration rate	8.000000e-15
GCST008163_194	Height	2.000000e-07
GCST010696_9	Cortical thickness (min-P)	3.000000e-08
GCST010697_34	Cortical surface area (min-P)	5.000000e-08
GCST010698_71	Subcortical volume (min-P)	4.000000e-14
GCST010699_32	Brain morphology (min-P)	6.000000e-09
GCST010700_65	Cortical thickness (MOSTest)	3.000000e-09
GCST010701_93	Cortical surface area (MOSTest)	2.000000e-13
GCST010702_34	Subcortical volume (MOSTest)	1.000000e-10
GCST010703_189	Brain morphology (MOSTest)	7.000000e-11

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0004346	neuroimaging measurement
EFO:0004840	cortical thickness

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (5): CHEMBL1983 (SINGLE PROTEIN), CHEMBL2095230 (SELECTIVITY GROUP), CHEMBL2096904 (PROTEIN FAMILY), CHEMBL4523960 (SELECTIVITY GROUP), CHEMBL4524122 (PROTEIN FAMILY)

Molecules with ChEMBL bioactivity

38 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 263,767 (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
CHEMBL1200776	CINACALCET HYDROCHLORIDE	4	1,220
CHEMBL1200809	AZELASTINE HYDROCHLORIDE	4	3,805
CHEMBL1263	SALMETEROL	4	40,383
CHEMBL1278	NARATRIPTAN	4	12,474
CHEMBL1279	FROVATRIPTAN	4	7,695
CHEMBL128	SUMATRIPTAN	4	28,367
CHEMBL1516474	TEGASEROD MALEATE	4	1,823
CHEMBL1615374	VILAZODONE HYDROCHLORIDE	4	432
CHEMBL1621	PALIPERIDONE	4	1,701
CHEMBL1707	LOPERAMIDE HYDROCHLORIDE	4	59,532
CHEMBL2	PRAZOSIN	4	31,107
CHEMBL2024517	CARIPRAZINE HYDROCHLORIDE	4	277
CHEMBL2105760	BREXPIPRAZOLE	4	1,755
CHEMBL24778	SILODOSIN	4	2,288
CHEMBL3039520	LASMIDITAN	4	550
CHEMBL312448	XYLOMETAZOLINE	4	7,459
CHEMBL442	ERGOTAMINE	4	19,697
CHEMBL51	KETANSERIN	4
CHEMBL6437	MIANSERIN	4
CHEMBL762	OXYMETAZOLINE	4
CHEMBL85	RISPERIDONE	4
CHEMBL905	RIZATRIPTAN	4
CHEMBL11	IMIPRAMINE	4
CHEMBL15245	YOHIMBINE	3
CHEMBL39	SEROTONIN	3
CHEMBL589390	LATREPIRDINE	3
CHEMBL110317	ACETRYPTINE	2

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

PharmGKB variants

1 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs676643	HTR1D		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 (90 total), top 25:

Ligand	Action	Affinity	Parameter
5-HT-moduline	Negative	12.0	pIC50
dihydroergotamine	Full agonist	9.9	pKi
alniditan	Full agonist	9.4	pKi
oxymetazoline	Partial agonist	9.4	pKi
zotepine	Antagonist	9.3	pKi
donitriptan	Full agonist	9.3	pKi
lysergol	Full agonist	9.2	pKi
metergoline	Antagonist	9.2	pKi
5-CT	Full agonist	9.2	pKi
7-methoxy-1-naphthylpiperazine	Full agonist	9.2	pKi
ergotamine	Agonist	9.1	pKi
SB 714786	Antagonist	9.1	pKi
[3H]eletriptan	Full agonist	9.1	pKd
GR 127935	Partial agonist	9.1	pKi
[3H]5-CT	Agonist	9.1	pKd
PNU109291	Agonist	9.1	pKi
lysergic acid	Full agonist	9.0	pKi
L-694,247	Agonist	9.0	pKi
L-772,405	Antagonist	9.0	pIC50
[3H]8-OH-DPAT	Full agonist	9.0	pKd
lisuride	Partial agonist	9.0	pKi
naratriptan	Full agonist	9.0	pKi
5-hydroxytryptamine	Full agonist	9.0	pKi
ziprasidone	Full agonist	9.0	pKi
[3H]alniditan	Full agonist	8.92	pKd

Binding affinities (BindingDB)

77 measured of 108 human assays (139 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
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
(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
4-[3-((R)-1-Methyl-pyrrolidin-2-ylmethyl)-1H-indol-5-yl]-3,6-dihydro-2H-pyridine-1-carboxylic acid adamantan-1-ylamide	KI	4 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
Adamantane-1-carbothioic acid {4-[3-(2-pyrrolidin-1-yl-ethyl)-1H-indol-5-yl]-3,6-dihydro-2H-pyridin-1-yl}-amide	KI	29 nM
Adamantane-1-carboxylic acid {4-[3-(2-pyrrolidin-1-yl-ethyl)-1H-indol-5-yl]-3,6-dihydro-2H-pyridin-1-yl}-amide	KI	29 nM
1-(4-{3-[4-(6-Fluoro-benzo[d]isoxazol-3-yl)-piperidin-1-yl]-propoxy}-3-methoxy-phenyl)-ethanone	KI	33 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
1-(1-(4,4-bis(4-fluorophenyl)butyl)piperidin-4-yl)-1H-benzo[d]imidazol-2(3H)-one	KI	650 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

ChEMBL bioactivities

1778 potent at pChembl≥5 of 1789 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
10.70	Ki	0.01995	nM	CHEMBL1242345
10.40	Ki	0.03981	nM	CHEMBL1242081
10.30	IC50	0.05	nM	CHEMBL22744
10.30	Ki	0.05012	nM	CHEMBL513715
10.10	Ki	0.07943	nM	CHEMBL469374
10.10	Ki	0.07943	nM	CHEMBL1290487
10.05	Ki	0.09	nM	CHEMBL357478
10.00	IC50	0.1	nM	CHEMBL65824
10.00	IC50	0.1	nM	CHEMBL161723
10.00	IC50	0.1	nM	CHEMBL65367
10.00	Ki	0.1	nM	CHEMBL522257
10.00	EC50	0.1	nM	CHEMBL65367
10.00	Ki	0.1	nM	CHEMBL1242904
10.00	Ki	0.1	nM	CHEMBL1241736
10.00	Ki	0.1	nM	CHEMBL1242167
10.00	Ki	0.1	nM	CHEMBL1241913
10.00	Ki	0.1	nM	CHEMBL469345
10.00	Ki	0.1	nM	CHEMBL1290486
10.00	IC50	0.1	nM	CHEMBL112507
9.96	IC50	0.11	nM	CHEMBL22961
9.96	Ki	0.11	nM	CHEMBL144030
9.96	Ki	0.11	nM	CHEMBL356277
9.90	Ki	0.1259	nM	GR-127935
9.90	Ki	0.1259	nM	CHEMBL1241547
9.90	Ki	0.1259	nM	CHEMBL1241641
9.90	Ki	0.1259	nM	CHEMBL1241642
9.90	Ki	0.1259	nM	CHEMBL1241546
9.90	Ki	0.1259	nM	CHEMBL1241639
9.90	Ki	0.1259	nM	CHEMBL1241912
9.90	Ki	0.1259	nM	CHEMBL1290715
9.90	Ki	0.1259	nM	CHEMBL1289394
9.90	Ki	0.1259	nM	CHEMBL1631538
9.90	Ki	0.1259	nM	CHEMBL1631535
9.85	IC50	0.14	nM	CHEMBL65367
9.80	Ki	0.1585	nM	CHEMBL491839
9.80	Ki	0.1585	nM	CHEMBL521506
9.80	Ki	0.1585	nM	CHEMBL490417
9.80	Ki	0.1585	nM	CHEMBL469568
9.80	Ki	0.1585	nM	CHEMBL1241913
9.80	Ki	0.1585	nM	CHEMBL1241548
9.80	Ki	0.1585	nM	CHEMBL1241738
9.80	Ki	0.1585	nM	CHEMBL1241824
9.80	Ki	0.1585	nM	CHEMBL1241998
9.80	Ki	0.1585	nM	CHEMBL1242257
9.80	Ki	0.1585	nM	CHEMBL1242533
9.80	Ki	0.1585	nM	CHEMBL1242623
9.80	Ki	0.1585	nM	CHEMBL1242717
9.80	Ki	0.1585	nM	CHEMBL1631545
9.80	Ki	0.1585	nM	CHEMBL1631542
9.80	Ki	0.1585	nM	CHEMBL1632221

PubChem BioAssay actives

1641 with measured affinity, of 2881 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
N-(cyclopropylmethyl)-6-[2-[4-(2-methylquinolin-5-yl)piperazin-1-yl]ethyl]-4H-imidazo[5,1-c][1,4]benzoxazine-3-carboxamide	510119: Antagonist activity against human recombinant 5HT1D receptor expressed in CHO cells assessed as inhibition of 5HT-induced [35S]GTPgammaS binding by scintillation proximity assay	ki	<0.0001	uM
N-cyclopropyl-6-[2-[4-(2-methylquinolin-5-yl)piperazin-1-yl]ethyl]-4H-imidazo[5,1-c][1,4]benzoxazine-3-carboxamide	510119: Antagonist activity against human recombinant 5HT1D receptor expressed in CHO cells assessed as inhibition of 5HT-induced [35S]GTPgammaS binding by scintillation proximity assay	ki	<0.0001	uM
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	4622: Ability to inhibit the forskolin-stimulated c-AMP formation mediated by human 5-hydroxytryptamine 1D receptor in CHO-K1 cells	ki	0.0001	uM
3-[3-[4-fluoro-4-[(2-fluorophenyl)methyl]piperidin-1-yl]propyl]-5-(1,2,4-triazol-4-yl)-1H-indole	4604: Displacement of specific [3H]5-HT binding to cloned human 5-hydroxytryptamine 1D receptor expressed in CHO cells	ic50	0.0001	uM
3-[3-(4-benzylpiperazin-1-yl)propyl]-5-(1,2,4-triazol-4-yl)-1H-indole	1254744: Displacement of [3H]-5-HT from human 5HT-1D receptor expressed in CHO cells	ic50	0.0001	uM
3-[3-[4-[(4-fluorophenyl)methyl]piperazin-1-yl]propyl]-5-(1,2,4-triazol-4-yl)-1H-indole	4603: Displacement of [3H]5-HT binding to the cloned human 5-hydroxytryptamine 1D receptor stably expressed in CHO cells	ic50	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	4944: Binding affinity against 5-hydroxytryptamine 1D receptor beta	ki	0.0001	uM
6-[2-[4-(2-methylquinolin-5-yl)piperazin-1-yl]ethyl]-4H-imidazo[5,1-c][1,4]benzoxazine-3-carboxamide	510146: Displacement of [3H]-5-HT from human recombinant 5HT1D receptor expressed in CHO cells after 45 mins by scintillation counting	ki	0.0001	uM
4-benzyl-1-[3-[5-(1,2,4-triazol-4-yl)-1H-indol-3-yl]propyl]piperidin-4-ol	4593: Ability to displace [3H]-5-HT from recombinant human 5-hydroxytryptamine 1D receptor stably expressed in CHO cells determined in vitro	ic50	0.0001	uM
N-methyl-6-[2-[4-(2-methylquinolin-5-yl)piperazin-1-yl]ethyl]-4H-imidazo[5,1-c][1,4]benzoxazine-3-carboxamide	510119: Antagonist activity against human recombinant 5HT1D receptor expressed in CHO cells assessed as inhibition of 5HT-induced [35S]GTPgammaS binding by scintillation proximity assay	ki	0.0001	uM
2-[5-[[4-[[3-(2-aminoethyl)-1H-indol-5-yl]oxymethyl]phenyl]methoxy]-1H-indol-3-yl]ethanamine	404703: Displacement of [3H]5-hydroxytryptamine from human cloned 5HT1D receptor expressed in CHOK1 cells by liquid scintillation counting	ki	0.0001	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	4622: Ability to inhibit the forskolin-stimulated c-AMP formation mediated by human 5-hydroxytryptamine 1D receptor in CHO-K1 cells	ki	0.0001	uM
8-[2-[4-(2-methylquinolin-5-yl)piperazin-1-yl]ethyl]-4H-1,4-benzoxazin-3-one	353214: Antagonist activity at human 5HT1D assessed as GTPgammaS binding by scintillation proximity assay in presence of 5-HT	ki	0.0001	uM
4-methyl-8-[2-[4-(2-methylquinolin-5-yl)piperazin-1-yl]ethyl]-1,4-benzoxazin-3-one	538501: Antagonist activity at human 5-HT1D receptor expressed in CHO cells assessed as inhibition of GTPgammaS binding by scintillation proximity assay	ki	0.0001	uM
8-[2-[4-(7-fluoro-2-methylquinolin-5-yl)piperazin-1-yl]ethyl]-4-methyl-1,4-benzoxazin-3-one	353214: Antagonist activity at human 5HT1D assessed as GTPgammaS binding by scintillation proximity assay in presence of 5-HT	ki	0.0001	uM
6-[2-[4-(2-methylquinolin-5-yl)piperazin-1-yl]ethyl]-4H-imidazo[2,1-c][1,4]benzoxazine	510119: Antagonist activity against human recombinant 5HT1D receptor expressed in CHO cells assessed as inhibition of 5HT-induced [35S]GTPgammaS binding by scintillation proximity assay	ki	0.0001	uM
2-methyl-6-[2-[4-(2-methylquinolin-5-yl)piperazin-1-yl]ethyl]-4H-imidazo[2,1-c][1,4]benzoxazine	510119: Antagonist activity against human recombinant 5HT1D receptor expressed in CHO cells assessed as inhibition of 5HT-induced [35S]GTPgammaS binding by scintillation proximity assay	ki	0.0001	uM
6-[2-[4-(2-methylquinolin-5-yl)piperazin-1-yl]ethyl]-2-(trifluoromethyl)-4H-imidazo[2,1-c][1,4]benzoxazine	510119: Antagonist activity against human recombinant 5HT1D receptor expressed in CHO cells assessed as inhibition of 5HT-induced [35S]GTPgammaS binding by scintillation proximity assay	ki	0.0001	uM
6-[2-[4-(2-methylquinolin-5-yl)piperazin-1-yl]ethyl]-4H-imidazo[5,1-c][1,4]benzoxazine	510119: Antagonist activity against human recombinant 5HT1D receptor expressed in CHO cells assessed as inhibition of 5HT-induced [35S]GTPgammaS binding by scintillation proximity assay	ki	0.0001	uM
3-methyl-6-[2-[4-(2-methylquinolin-5-yl)piperazin-1-yl]ethyl]-4H-triazolo[5,1-c][1,4]benzoxazine	510119: Antagonist activity against human recombinant 5HT1D receptor expressed in CHO cells assessed as inhibition of 5HT-induced [35S]GTPgammaS binding by scintillation proximity assay	ki	0.0001	uM
6-[2-[4-(2-methylquinolin-5-yl)piperazin-1-yl]ethyl]-4H-tetrazolo[5,1-c][1,4]benzoxazine	510119: Antagonist activity against human recombinant 5HT1D receptor expressed in CHO cells assessed as inhibition of 5HT-induced [35S]GTPgammaS binding by scintillation proximity assay	ki	0.0001	uM
1-[6-[2-[4-(2-methylquinolin-5-yl)piperazin-1-yl]ethyl]-4H-imidazo[5,1-c][1,4]benzoxazin-3-yl]ethanone	510119: Antagonist activity against human recombinant 5HT1D receptor expressed in CHO cells assessed as inhibition of 5HT-induced [35S]GTPgammaS binding by scintillation proximity assay	ki	0.0001	uM
N-cyclobutyl-6-[2-[4-(2-methylquinolin-5-yl)piperazin-1-yl]ethyl]-4H-imidazo[5,1-c][1,4]benzoxazine-3-carboxamide	510119: Antagonist activity against human recombinant 5HT1D receptor expressed in CHO cells assessed as inhibition of 5HT-induced [35S]GTPgammaS binding by scintillation proximity assay	ki	0.0001	uM
ethyl N-[3-[2-[4-(2-methylquinolin-5-yl)piperazin-1-yl]ethyl]phenyl]carbamate	541183: Displacement of [3H]5-HT from human recombinant 5-HT1D receptor expressed in CHO cells	ki	0.0001	uM
N-[3-[2-[4-(2-methylquinolin-5-yl)piperazin-1-yl]ethyl]phenyl]methanesulfonamide	541183: Displacement of [3H]5-HT from human recombinant 5-HT1D receptor expressed in CHO cells	ki	0.0001	uM
5-[2-[4-(2-methylquinolin-5-yl)piperazin-1-yl]ethyl]-3,4-dihydro-1H-quinolin-2-one	538501: Antagonist activity at human 5-HT1D receptor expressed in CHO cells assessed as inhibition of GTPgammaS binding by scintillation proximity assay	ki	0.0001	uM
5-[2-[4-(2-methylquinolin-5-yl)piperazin-1-yl]ethyl]-1H-quinolin-2-one	538501: Antagonist activity at human 5-HT1D receptor expressed in CHO cells assessed as inhibition of GTPgammaS binding by scintillation proximity assay	ki	0.0001	uM
1-methyl-5-[2-[4-(2-methylquinolin-5-yl)piperazin-1-yl]ethyl]-3,4-dihydroquinolin-2-one	538501: Antagonist activity at human 5-HT1D receptor expressed in CHO cells assessed as inhibition of GTPgammaS binding by scintillation proximity assay	ki	0.0001	uM
5-[2-[(2R)-4-(7-fluoro-2-methylquinolin-5-yl)-2-methylpiperazin-1-yl]ethyl]-1-methylquinolin-2-one	538501: Antagonist activity at human 5-HT1D receptor expressed in CHO cells assessed as inhibition of GTPgammaS binding by scintillation proximity assay	ki	0.0001	uM
3-[4-[7-[[4-(5-carbamoyl-1H-indol-3-yl)cyclohex-3-en-1-yl]amino]heptylamino]cyclohexen-1-yl]-1H-indole-5-carboxamide	404703: Displacement of [3H]5-hydroxytryptamine from human cloned 5HT1D receptor expressed in CHOK1 cells by liquid scintillation counting	ic50	0.0001	uM
4-methyl-6-[2-[4-(2-methylquinolin-5-yl)piperazin-1-yl]ethyl]-1,4-benzoxazin-3-one	353214: Antagonist activity at human 5HT1D assessed as GTPgammaS binding by scintillation proximity assay in presence of 5-HT	ki	0.0001	uM
6-[2-[4-(7-chloro-2-methylquinolin-5-yl)piperazin-1-yl]ethyl]-4H-1,4-benzoxazin-3-one	344711: Displacement of [3H]5HT from human 5HT1D receptor expressed in CHO cells	ki	0.0002	uM
6-[2-[4-(2,2-dimethyl-3H-1-benzofuran-7-yl)piperazin-1-yl]ethyl]-4H-1,4-benzoxazin-3-one	344711: Displacement of [3H]5HT from human 5HT1D receptor expressed in CHO cells	ki	0.0002	uM
2-(5-tert-butyl-1H-indol-3-yl)-N-methylethanamine	4571: Ability to inhibit forskolin-stimulated adenylate cyclase in a cell line expressing human 5-hydroxytryptamine 1D receptor	ec50	0.0002	uM
8-fluoro-6-[2-[4-(2-methylquinolin-5-yl)piperazin-1-yl]ethyl]-4H-1,4-benzoxazin-3-one	344711: Displacement of [3H]5HT from human 5HT1D receptor expressed in CHO cells	ki	0.0002	uM
6-[2-[4-(7-fluoro-2-methylquinolin-5-yl)piperazin-1-yl]ethyl]-4H-1,4-benzoxazin-3-one	344711: Displacement of [3H]5HT from human 5HT1D receptor expressed in CHO cells	ki	0.0002	uM
6-[2-[4-(8-chloro-2-methylquinolin-5-yl)piperazin-1-yl]ethyl]-4H-1,4-benzoxazin-3-one	344711: Displacement of [3H]5HT from human 5HT1D receptor expressed in CHO cells	ki	0.0002	uM
3-[3-[4-fluoro-4-[[2-(trifluoromethyl)phenyl]methyl]piperidin-1-yl]propyl]-5-(1,2,4-triazol-4-yl)-1H-indole	4582: Agonist-induced [35S]GTP-gamma-S, binding in CHO cells stably transfected with human 5-hydroxytryptamine 1D receptor	ec50	0.0002	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	4622: Ability to inhibit the forskolin-stimulated c-AMP formation mediated by human 5-hydroxytryptamine 1D receptor in CHO-K1 cells	ki	0.0002	uM
1-[3-[2-[4-(2-methylquinolin-5-yl)piperazin-1-yl]ethyl]phenyl]imidazolidin-2-one	541183: Displacement of [3H]5-HT from human recombinant 5-HT1D receptor expressed in CHO cells	ki	0.0002	uM
3-[3-[2-[4-(2-methylquinolin-5-yl)piperazin-1-yl]ethyl]phenyl]-1,3-oxazolidin-2-one	541183: Displacement of [3H]5-HT from human recombinant 5-HT1D receptor expressed in CHO cells	ki	0.0002	uM
[6-[2-[4-(2-methylquinolin-5-yl)piperazin-1-yl]ethyl]-4H-imidazo[5,1-c][1,4]benzoxazin-3-yl]-morpholin-4-ylmethanone	510119: Antagonist activity against human recombinant 5HT1D receptor expressed in CHO cells assessed as inhibition of 5HT-induced [35S]GTPgammaS binding by scintillation proximity assay	ki	0.0002	uM
2-[[3-(2-aminoethyl)-1H-indol-5-yl]oxy]-N-[2-[[3-(2-aminoethyl)-1H-indol-5-yl]oxy]ethyl]acetamide	4622: Ability to inhibit the forskolin-stimulated c-AMP formation mediated by human 5-hydroxytryptamine 1D receptor in CHO-K1 cells	ki	0.0002	uM
N-[3-[[4-[3-[5-(1,2,4-triazol-4-yl)-1H-indol-3-yl]propyl]piperazin-1-yl]methyl]phenyl]acetamide	4579: Stimulation of [35S]GTP-gamma-S, binding in CHO cells expressing the human 5-hydroxytryptamine 1D receptor.	ec50	0.0002	uM
2-phenyl-2-[4-[3-[5-(1,2,4-triazol-4-yl)-1H-indol-3-yl]propyl]piperazin-1-yl]acetamide	4579: Stimulation of [35S]GTP-gamma-S, binding in CHO cells expressing the human 5-hydroxytryptamine 1D receptor.	ec50	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-ethyl-8-[2-[4-(2-methylquinolin-5-yl)piperazin-1-yl]ethyl]-1,4-benzoxazin-3-one	353214: Antagonist activity at human 5HT1D assessed as GTPgammaS binding by scintillation proximity assay in presence of 5-HT	ki	0.0002	uM
4-cyclopropyl-8-[2-[4-(2-methylquinolin-5-yl)piperazin-1-yl]ethyl]-1,4-benzoxazin-3-one	353214: Antagonist activity at human 5HT1D assessed as GTPgammaS binding by scintillation proximity assay in presence of 5-HT	ki	0.0002	uM
azetidin-1-yl-[6-[2-[4-(2-methylquinolin-5-yl)piperazin-1-yl]ethyl]-4H-imidazo[5,1-c][1,4]benzoxazin-3-yl]methanone	510119: Antagonist activity against human recombinant 5HT1D receptor expressed in CHO cells assessed as inhibition of 5HT-induced [35S]GTPgammaS binding by scintillation proximity assay	ki	0.0002	uM
[6-[2-[4-(2-methylquinolin-5-yl)piperazin-1-yl]ethyl]-4H-imidazo[5,1-c][1,4]benzoxazin-3-yl]-pyrrolidin-1-ylmethanone	510119: Antagonist activity against human recombinant 5HT1D receptor expressed in CHO cells assessed as inhibition of 5HT-induced [35S]GTPgammaS binding by scintillation proximity assay	ki	0.0002	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
bisphenol A	affects cotreatment, decreases methylation, decreases expression, increases expression	3
(+)-JQ1 compound	decreases expression	3
sodium arsenite	decreases expression, increases abundance, increases expression, affects cotreatment	2
Benzo(a)pyrene	affects methylation, increases mutagenesis	2
ethyl-p-hydroxybenzoate	decreases expression	1
butyraldehyde	decreases expression	1
tetrabromobisphenol A	decreases expression	1
manganese chloride	affects cotreatment, decreases expression, increases abundance	1
potassium chromate(VI)	affects cotreatment, decreases expression	1
nickel sulfate	increases expression	1
epigallocatechin gallate	affects cotreatment, decreases expression	1
perfluorooctane sulfonic acid	decreases 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	affects binding, increases activity	1
BRL 15572	affects binding, increases activity	1
2-palmitoylglycerol	increases expression	1
abrine	decreases expression	1
jinfukang	increases expression	1
theaflavin-3,3’-digallate	affects expression	1
Resveratrol	decreases expression, affects cotreatment	1
Temozolomide	affects response to substance, decreases response to substance, affects cotreatment, decreases expression	1
Arsenic Trioxide	decreases response to substance	1
Fulvestrant	affects cotreatment, decreases methylation	1
Vortioxetine	affects cotreatment, decreases expression, affects binding, affects response to substance	1
Air Pollutants	increases expression, increases abundance	1
Ethanol	affects cotreatment, increases expression	1
Arsenic	affects cotreatment, decreases expression, increases abundance	1
Cannabidiol	decreases expression	1
Carbon Tetrachloride	increases expression	1
Folic Acid	increases expression, affects cotreatment	1

ChEMBL screening assays

509 unique, capped per target: 409 binding, 96 functional, 4 admet

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1009489	Binding	Binding affinity to 5HT1D receptor	Urotensin-II receptor antagonists: synthesis and SAR of N-cyclic azaalkyl benzamides. — Bioorg Med Chem Lett
CHEMBL1020890	Functional	Activity at 5HT1D receptor assessed as calcium mobilization by FLIPR	Structure-activity relationships of the cycloalkanol ethylamine scaffold: discovery of selective norepinephrine reuptake inhibitors. — J Med Chem
CHEMBL4406602	ADMET	Displacement of [3H]5-CT from recombinant human 5HT1D receptor transiently expressed in HEKT 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

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

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

Cellosaurus	Name	Category	Sex
CVCL_3738	Ltk-11	Spontaneously immortalized cell line	Male
CVCL_ZK94	Tango HTR1D-bla U2OS	Cancer cell line	Female

Clinical trials (associated diseases)

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