HTR7

Summary

HTR7 (5-hydroxytryptamine receptor 7, HGNC:5302) is a protein-coding gene on chromosome 10q23.31, encoding 5-hydroxytryptamine receptor 7 (P34969). G-protein coupled receptor for 5-hydroxytryptamine (serotonin), a biogenic hormone that functions as a neurotransmitter, a hormone and a mitogen.

The neurotransmitter, serotonin, is thought to play a role in various cognitive and behavioral functions. The serotonin receptor encoded by this gene belongs to the superfamily of G protein-coupled receptors and the gene is a candidate locus for involvement in autistic disorder and other neuropsychiatric disorders. Three splice variants have been identified which encode proteins that differ in the length of their carboxy terminal ends.

Source: NCBI Gene 3363 — RefSeq curated summary.

At a glance

• GWAS associations: 4
• Clinical variants (ClinVar): 72 total
• Druggable target: yes — 93 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_019859

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:5302
Approved symbol	HTR7
Name	5-hydroxytryptamine receptor 7
Location	10q23.31
Locus type	gene with protein product
Status	Approved
Aliases	5-HT7
Ensembl gene	ENSG00000148680
Ensembl biotype	protein_coding
OMIM	182137
Entrez	3363

Gene structure

Transcript identifiers

Ensembl transcripts: 3 — 3 protein_coding

ENST00000277874, ENST00000336152, ENST00000371719

RefSeq mRNA: 3 — MANE Select: NM_019859 NM_000872, NM_019859, NM_019860

CCDS: CCDS7408, CCDS7409, CCDS7410

Canonical transcript exons

ENST00000336152 — 4 exons

Exon	Start	End
ENSE00001092190	90743593	90743690
ENSE00001385665	90748839	90749594
ENSE00003643177	90740823	90742528
ENSE00003850987	90857133	90858039

Expression profiles

Bgee: expression breadth ubiquitous, 162 present calls, max score 85.39.

FANTOM5 (CAGE): breadth broad, TPM avg 0.8809 / max 104.6855, expressed in 430 samples.

FANTOM5 promoters (7 alternative TSS)

Promoter ID	TPM avg	Samples expressed
110612	0.7328	379
110610	0.0640	13
110608	0.0433	12
110609	0.0116	2
110613	0.0111	1
110611	0.0102	1
110607	0.0077	3

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	85.39	gold quality
sperm	CL:0000019	82.48	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	81.40	gold quality
male germ cell	CL:0000015	79.76	silver quality
secondary oocyte	CL:0000655	79.27	gold quality
oocyte	CL:0000023	77.02	silver quality
tendon of biceps brachii	UBERON:0008188	77.00	silver quality
cervix squamous epithelium	UBERON:0006922	75.76	gold quality
buccal mucosa cell	CL:0002336	72.41	gold quality
triceps brachii	UBERON:0001509	71.98	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	71.55	gold quality
gluteal muscle	UBERON:0002000	71.34	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	69.10	gold quality
testis	UBERON:0000473	68.54	gold quality
endothelial cell	CL:0000115	68.44	gold quality
upper arm skin	UBERON:0004263	68.34	gold quality
dorsal motor nucleus of vagus nerve	UBERON:0002870	68.22	gold quality
left testis	UBERON:0004533	68.21	gold quality
lateral nuclear group of thalamus	UBERON:0002736	67.46	gold quality
right testis	UBERON:0004534	67.25	gold quality
inferior olivary complex	UBERON:0002127	67.19	gold quality
heart right ventricle	UBERON:0002080	67.04	gold quality
parotid gland	UBERON:0001831	66.71	gold quality
mucosa of stomach	UBERON:0001199	66.69	gold quality
vastus lateralis	UBERON:0001379	66.57	gold quality
vena cava	UBERON:0004087	66.01	gold quality
quadriceps femoris	UBERON:0001377	65.69	gold quality
descending thoracic aorta	UBERON:0002345	65.67	gold quality
stromal cell of endometrium	CL:0002255	65.56	gold quality
adult organism	UBERON:0007023	65.10	silver quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	3.23

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): SP1, SP3

miRNA regulators (miRDB)

83 targeting HTR7, 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-5692B	100.00	71.32	2622
HSA-MIR-5692C	100.00	71.32	2622
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-3120-5P	100.00	65.56	965
HSA-MIR-188-3P	100.00	68.76	1240
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-6888-3P	99.97	65.95	1170
HSA-MIR-302C-5P	99.97	72.56	3642
HSA-MIR-8075	99.97	67.20	962
HSA-MIR-3065-5P	99.97	71.56	3281
HSA-MIR-1250-3P	99.96	70.04	4038
HSA-MIR-545-3P	99.95	70.74	2783
HSA-LET-7C-3P	99.95	73.42	2862
HSA-MIR-141-3P	99.94	72.79	2421
HSA-MIR-200A-3P	99.94	72.68	2420
HSA-MIR-218-5P	99.93	72.22	2103
HSA-MIR-205-3P	99.92	69.92	3165
HSA-MIR-1305	99.91	71.43	3443
HSA-MIR-4753-3P	99.90	71.03	3786
HSA-MIR-3529-3P	99.90	73.55	3045
HSA-MIR-3671	99.90	73.04	3897
HSA-MIR-380-3P	99.89	70.18	1978
HSA-MIR-579-3P	99.86	71.66	3628
HSA-MIR-664B-3P	99.84	71.65	3590
HSA-MIR-576-5P	99.84	70.46	2582
HSA-MIR-4713-5P	99.78	67.80	1794
HSA-MIR-1299	99.77	71.24	2389
HSA-MIR-187-5P	99.74	70.26	1404
HSA-MIR-4428	99.73	66.41	1733

Literature-anchored findings (GeneRIF, showing 38)

• HEK293 cells stably or transiently expressing either of the 5-HT7 receptor splice variants show elevated basal adenylyl cyclase (AC) activity as well as concentration-dependent inhibition of basal AC activity by 5-HT7 antagonists (inverse agonism). (PMID:11906971)
• report the activation of the extracellular signal-regulated kinases (ERKs) 1 and 2 (p44 and p42 MAP kinase) through the human serotonin receptors 5-HT(4(b)) and 5-HT(7(a)) (PMID:12446729)
• Expression in cultured skin cells. (PMID:12767050)
• The decrease in affinity of 5-HT and other 5-HT receptor agonists at the (Thr92Lys) h5-HT7 receptor may be associated with changes of sleep physiology and of actions of new 5-HT7 receptor agonists designed to treat circadian dysregulation. (PMID:15896881)
• HTR7 is a susceptibility gene for schizophrenia in this Japanese group. (PMID:16192982)
• This may indicate that the h5-HT7 receptor is part of a subfamily of G-protein-coupled receptors (GPCRs) possessing this property or that many GPCRs have the potential to be irreversibly blocked, but only select drugs can induce this effect. (PMID:16870886)
• These observations suggest that PLAC-24 may play a role in the transport and the stabilisation of newly synthesised 5-HT(7) receptor towards the plasma membrane. (PMID:16935469)
• Results support the essential role of Sp factors in regulating 5-HT(7) promoter activity. (PMID:17321075)
• data demonstrate a role for sphingomyelin and gangliosides in regulating binding of [(3)H]5-HT to 5-HT(7) receptors; these observations further strengthen that actions of 5-HT via 5-HT(7) receptors are dependent upon lipid raft integrity (PMID:17428232)
• Caveolin-1, specifically localized in cholesterol-enriched lipid rafts, appears to regulate constitutive and agonist-stimulated cell surface levels of 5-HT7 receptors via a clathrin-independent mechanism. (PMID:17936759)
• Data show that 5-HT(7) receptors are involved in the modulation of learning and memory processes. (PMID:18243350)
• The results of this study demonstrate that variations in the HTR7 gene may not be good genetic markers for predicting the therapeutic efficacy of risperidone. (PMID:19233240)
• The results demonstrate mRNA and protein expression of 5-HTR(1A) and 5-HTR(7) in Caco-2 cells; both receptors are shown to modulate SERT activity; 5-HTR(1A) activation increased 5-HT uptake and 5-HTR(7) activation inhibited it (PMID:19439818)
• Ability of non-inactivating drugs to bind h5-HT(7) orthosteric sites and reverse wash-resistant effects of risperidone/9-OH-risperidone, also bound to h5-HT(7) orthosteric sites, is evidence for protomer-protomer interactions between h5-HT(7) homodimers. (PMID:20827463)
• The association with rs7916403 in serotonin receptor gene HTR7 on chromosome 10q23 (combined P = 1.53 x 10), implicates the serotonergic system in the neurophysiological underpinnings of theta event-related brain oscillations. (PMID:21184583)
• The role of the 5-HT7 receptor in the central nervous system, is discussed. (PMID:21424680)
• The interaction between RhoBTB3 and the 5-HT7a receptor strongly inhibits proteasomal degradation of the 5-HT7a receptor. (PMID:22245496)
• the expression of 5-HT7 receptors in brain tissues was higher in the epilepsy group compared with the nonepileptic group; the results suggested that 5-HT7 receptors participate in the pathogenesis of temporal lobe epilepsy (PMID:22543085)
• Serotonin skews human macrophage polarization through HTR2B and HTR7. (PMID:23355731)
• There is a cross-reactivity between 5-HT7 and 5-HT1A receptors and in this review they are shown to have a role in depressive disorders. (PMID:24935787)
• Genetic variations in HTR7 serotonin receptor contribute to the predisposition for alcohol dependence. (PMID:25070732)
• This is a review of literature about how 5-HT7 receptor has been implicated in cognitive disturbances, sleep and circadian rhythmicity disorders, anxiety and depression (PMID:25228519)
• Study demonstrated that binding of clozapine or olanzapine to the 5-HT7 receptor leads to antagonist-mediated lysosomal degradation by exposing key residues in the C-terminal tail that interact with GASP-1 (PMID:25706089)
• Study shows that HTR7 variants are not related to the overall improvement in schizophrenia symptoms following perospirone or aripiprazole treatment (PMID:26609891)
• Placental expression of HTR7 was significantly increased in women with pre-eclampsia compared to controls. (PMID:26797415)
• PTP1B directly regulates STAT5 phosphorylation and its activation via the cAMP/PKA pathway downstream of the 5-HT7 receptor is involved in the suppression of beta-casein expression in MCF-12A cells (PMID:27016479)
• The dizygotic twins presented here carry a compound heterozygous variant in the HTR7 gene. No other coding sequence abnormalities (CNVs and SVs) were observed in their fully sequenced genomes consistent with either dominant or recessive inheritance. This provides a first suggestive genetic link between the 5-HT7 receptor and autism spectrum disorder in patients. (PMID:27380831)
• zinc can act as a negative allosteric inhibitor of 5-HT7 receptors. (PMID:28455702)
• the impact of template choice, alignment, and model building methods on the homology model of 5-HT7R is addressed. (PMID:28745550)
• Related GPCRs couple differently to Gs: preassociation between G protein and 5-HT7 serotonin receptor reveals movement of Galphas upon receptor activation. (PMID:29079700)
• MiRNA-29a is upregulated in and HTR7 is downregulated in irritable bowel syndrome (IBS). HTR7 is a direct target of miRNA-29a. MiRNA-29a plays a role in visceral hyperalgesia pathogenesis of IBS. (PMID:30827505)
• Stimulating DDX3 expression by serotonin 5-HT receptor 7 through phosphorylation of p53 via the AC-PKA-ERK signaling pathway. (PMID:31172579)
• 5-HT7 receptors are widely expressed in a vast repertoire of immune and non-immune cells. The receptor has diverse -and even discrepant- roles in the immune response. [review] (PMID:31892309)
• Role of the Serotonin Receptor 7 in Brain Plasticity: From Development to Disease. (PMID:31941109)
• Effects of 5-HT7 receptors on circadian rhythm of mice anesthetized with isoflurane. (PMID:33081564)
• 5-HT7 receptors as a new target for prostate cancer physiopathology and treatment: an experimental study on PC-3 cells and FFPE tissues. (PMID:33528589)
• 5-HT7 receptors in Alzheimer’s disease. (PMID:34555475)
• Serotonin 5-HT7 receptor is a biomarker poor prognostic factor and induces proliferation of triple-negative breast cancer cells through FOXM1. (PMID:36006564)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	htr7a	ENSDARG00000056949
danio_rerio	htr7d	ENSDARG00000099854
mus_musculus	Htr7	ENSMUSG00000024798
rattus_norvegicus	Htr7	ENSRNOG00000018827
drosophila_melanogaster	5-HT7	FBGN0004573

Paralogs (8): HTR2A (ENSG00000102468), HTR1B (ENSG00000135312), HTR2B (ENSG00000135914), HTR2C (ENSG00000147246), HTR5A (ENSG00000157219), HTR6 (ENSG00000158748), HTR1E (ENSG00000168830), HTR1F (ENSG00000179097)

Protein

Protein identifiers

5-hydroxytryptamine receptor 7 — P34969 (reviewed: P34969)

Alternative names: 5-HT-X, Serotonin receptor 7

All UniProt accessions (1): P34969

UniProt curated annotations — full annotation on UniProt →

Function. G-protein coupled receptor for 5-hydroxytryptamine (serotonin), a biogenic hormone that functions as a neurotransmitter, a hormone and a mitogen. Ligand binding causes a conformation change that triggers signaling via guanine nucleotide-binding proteins (G proteins) and modulates the activity of downstream effectors. HTR7 is coupled to G(s) G alpha proteins and mediates activation of adenylate cyclase activity.

Subcellular location. Cell membrane.

Tissue specificity. Predominant isoform in spleen, caudate and hippocampus. Expressed at lower levels. Minor isoform in terms of expression.

Domain organisation. Specificity for G(s) G alpha proteins is determined by the length of transmembrane regions 5 and 6 (TM5 and TM6).

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

Isoforms (3)

UniProt ID	Names	Canonical?
P34969-1	D	yes
P34969-2	A
P34969-3	B

RefSeq proteins (3): NP_000863, NP_062873, NP_062874 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000276	GPCR_Rhodpsn	Family
IPR001069	5HT_7_rcpt	Family
IPR017452	GPCR_Rhodpsn_7TM	Domain

Pfam: PF00001

UniProt features (54 total): helix 15, mutagenesis site 10, topological domain 8, transmembrane region 7, sequence variant 3, turn 3, glycosylation site 2, splice variant 2, chain 1, binding site 1, lipid moiety-binding region 1, disulfide bond 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
7XTC	ELECTRON MICROSCOPY	3.2

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P34969-F1	73.49	0.40

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

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 (1): 162

Post-translational modifications (1): 401

Disulfide bonds (1): 155–231

Glycosylation sites (2): 5, 66

Mutagenesis-validated functional residues (10):

Position	Phenotype
162	abolished g-protein coupled receptor activity in response to serotonin.
166	decreased g-protein coupled receptor activity in response to serotonin.
167	decreased g-protein coupled receptor activity in response to serotonin.
233	decreased g-protein coupled receptor activity in response to serotonin.
240	decreased g-protein coupled receptor activity in response to serotonin.
243	decreased g-protein coupled receptor activity in response to serotonin.
340	decreased g-protein coupled receptor activity in response to serotonin.
343	decreased g-protein coupled receptor activity in response to serotonin.
344	decreased g-protein coupled receptor activity in response to serotonin.
374	decreased g-protein coupled receptor activity in response to serotonin.

Function

Pathways and Gene Ontology

Reactome pathways

9 pathways

ID	Pathway
R-HSA-390666	Serotonin receptors
R-HSA-418555	G alpha (s) signalling events
R-HSA-9706019	RHOBTB3 ATPase cycle
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: 235 (showing top): GOBP_CIRCADIAN_RHYTHM, MORF_RAGE, TGGTGCT_MIR29A_MIR29B_MIR29C, GOBP_RESPONSE_TO_NITROGEN_COMPOUND, MORF_FLT1, GOMF_G_PROTEIN_COUPLED_SEROTONIN_RECEPTOR_ACTIVITY, BENPORATH_ES_WITH_H3K27ME3, MODULE_274, YAGI_AML_WITH_INV_16_TRANSLOCATION, MORF_MSH3, GOBP_CIRCULATORY_SYSTEM_PROCESS, TTTGTAG_MIR520D, MODULE_45, MODULE_64, MORF_BRCA1

GO Biological Process (10): smooth muscle contraction (GO:0006939), G protein-coupled receptor signaling pathway, coupled to cyclic nucleotide second messenger (GO:0007187), adenylate cyclase-activating serotonin receptor signaling pathway (GO:0007192), chemical synaptic transmission (GO:0007268), circadian rhythm (GO:0007623), blood circulation (GO:0008015), vasoconstriction (GO:0042310), signal transduction (GO:0007165), G protein-coupled receptor signaling pathway (GO:0007186), G protein-coupled serotonin receptor signaling pathway (GO:0098664)

GO Molecular Function (5): G protein-coupled serotonin receptor activity (GO:0004993), neurotransmitter receptor activity (GO:0030594), G protein-coupled receptor activity (GO:0004930), protein binding (GO:0005515), serotonin receptor activity (GO:0099589)

GO Cellular Component (7): nucleoplasm (GO:0005654), plasma membrane (GO:0005886), cilium (GO:0005929), dendrite (GO:0030425), trans-Golgi network membrane (GO:0032588), synapse (GO:0045202), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-7 pathways:

Category	Pathways
Signaling by GPCR	2
Amine ligand-binding receptors	1
GPCR downstream signalling	1
Signaling by Rho GTPases, Miro GTPases and RHOBTB3	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	3
transmembrane signaling receptor activity	2
cellular anatomical structure	2
muscle contraction	1
adenylate cyclase-activating G protein-coupled receptor signaling pathway	1
serotonin receptor signaling pathway	1
anterograde trans-synaptic signaling	1
rhythmic process	1
circulatory system process	1
blood vessel diameter maintenance	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
G protein-coupled serotonin receptor signaling pathway	1
signaling receptor activity	1
binding	1
nuclear lumen	1
membrane	1
cell periphery	1
intraciliary transport particle	1
membrane-bounded organelle	1
plasma membrane bounded cell projection	1
neuron projection	1
dendritic tree	1
trans-Golgi network	1
organelle membrane	1
cell junction	1

Protein interactions and networks

STRING

786 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
HTR7	KIF20B	Q96Q89	786
HTR7	CYP2C18	P33260	757
HTR7	HTR3A	P46098	722
HTR7	HTR1A	P08908	702
HTR7	CYP2C19	P33259	691
HTR7	HTR3B	O95264	690
HTR7	CYP2C9	P11712	681
HTR7	SLC6A4	P31645	640
HTR7	TPH1	P17752	604
HTR7	GRIP1	Q9Y3R0	578
HTR7	IDE	P14735	547
HTR7	HTR3C	Q8WXA8	497
HTR7	CALHM1	Q8IU99	497
HTR7	DRD2	P14416	486
HTR7	PDPN	Q86YL7	482

IntAct

8 interactions, top by confidence:

A	B	Type	Score
HTR7	MATR3	psi-mi:“MI:0915”(physical association)	0.560
GPRASP1	HTR7	psi-mi:“MI:0407”(direct interaction)	0.440
HTR7	GPRASP2	psi-mi:“MI:0407”(direct interaction)	0.440
	HTR7	psi-mi:“MI:0915”(physical association)	0.400
HTR7	RAMP1	psi-mi:“MI:0915”(physical association)	0.400
HTR7	WBP4	psi-mi:“MI:0914”(association)	0.350

BioGRID (7): MATR3 (Proximity Label-MS), HTR7 (Cross-Linking-MS (XL-MS)), HTR7 (Affinity Capture-Western), RHOBTB3 (Affinity Capture-Western), CUL3 (Affinity Capture-Western), GPRASP1 (Reconstituted Complex), GPRASP2 (Reconstituted Complex)

ESM2 similar proteins: A1ZAX0, O02835, O02836, O43613, O43614, O62809, O93603, O97661, P25929, P25931, P30731, P32247, P34969, P34981, P47751, P49146, P56718, P56719, P58307, P58308, P70031, P79113, P79945, P97295, Q0GBZ5, Q1RMU8, Q28596, Q5IS62, Q8K458, Q8NFJ6, Q8R415, Q8R416, Q8SPN1, Q8SPN2, Q8TCW9, Q8VHD7, Q8WPA2, Q91559, Q924H0, Q9BZJ6

Diamond homologs: A1ZAX0, B2ZI34, E7F7V7, F1MV99, F1R332, O08726, O08786, O43603, O54798, O54799, O62709, O88626, O88854, O97666, O97772, O97967, P05363, P08911, P08912, P21451, P21729, P22270, P24053, P24530, P25101, P26684, P28088, P28336, P28646, P30550, P30551, P30552, P30553, P30796, P30872, P30873, P30937, P30974, P31391, P32238

SIGNOR signaling

11 interactions.

A	Effect	B	Mechanism
HTR7	“up-regulates activity”	GNAS	binding
HTR7	“up-regulates activity”	GNAL	binding
HTR7	“up-regulates activity”	GNAI1	binding
HTR7	“up-regulates activity”	GNAI3	binding
HTR7	“up-regulates activity”	GNAO1	binding
HTR7	“up-regulates activity”	GNAZ	binding
HTR7	“up-regulates activity”	GNAQ	binding
HTR7	“up-regulates activity”	GNA14	binding
serotonin(1+)	“up-regulates activity”	HTR7	“chemical activation”
serotonin	“up-regulates activity”	HTR7	“chemical activation”
lurasidone	“down-regulates activity”	HTR7	“chemical inhibition”

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	57
Likely benign	3
Benign	3

Top pathogenic / likely-pathogenic (0)

SpliceAI

1064 predictions. Top by Δscore:

Variant	Effect	Δscore
10:90748837:A:AC	donor_gain	1.0000
10:90748838:C:CC	donor_gain	1.0000
10:90748838:CAG:C	donor_gain	1.0000
10:90748838:CAGCA:C	donor_gain	1.0000
10:90857128:CTTAC:C	donor_loss	1.0000
10:90857129:TTAC:T	donor_loss	1.0000
10:90857130:TA:T	donor_loss	1.0000
10:90857132:C:CG	donor_loss	1.0000
10:90748846:A:AC	donor_gain	0.9900
10:90748847:C:CC	donor_gain	0.9900
10:90839688:A:AC	donor_gain	0.9900
10:90857131:A:AC	donor_gain	0.9900
10:90857132:C:CC	donor_gain	0.9900
10:90742529:C:CC	acceptor_gain	0.9800
10:90748837:ACAG:A	donor_gain	0.9800
10:90748838:CAGC:C	donor_gain	0.9800
10:90748850:A:AC	donor_gain	0.9800
10:90748851:G:C	donor_gain	0.9800
10:90749594:CC:C	acceptor_loss	0.9800
10:90749595:C:CA	acceptor_loss	0.9800
10:90749596:T:A	acceptor_loss	0.9800
10:90750862:A:AC	donor_gain	0.9800
10:90750863:C:CC	donor_gain	0.9800
10:90839657:TTAAC:T	donor_gain	0.9800
10:90839689:G:C	donor_gain	0.9800
10:90857132:CCTGT:C	donor_gain	0.9800
10:90748892:G:A	donor_gain	0.9700
10:90748909:T:TA	donor_gain	0.9700
10:90750863:CTT:C	donor_gain	0.9700
10:90750863:CTTCT:C	donor_gain	0.9700

AlphaMissense

3148 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
10:90749006:G:C	N376K	1.000
10:90749006:G:T	N376K	1.000
10:90749016:C:T	G373D	1.000
10:90749017:C:G	G373R	1.000
10:90749023:A:G	W371R	1.000
10:90749023:A:T	W371R	1.000
10:90749102:G:C	F344L	1.000
10:90749102:G:T	F344L	1.000
10:90749104:A:G	F344L	1.000
10:90749116:A:G	W340R	1.000
10:90749116:A:T	W340R	1.000
10:90749126:A:C	F336L	1.000
10:90749126:A:T	F336L	1.000
10:90749128:A:G	F336L	1.000
10:90749133:C:T	G334E	1.000
10:90749145:C:T	G330E	1.000
10:90749157:G:T	A326D	1.000
10:90749158:C:G	A326P	1.000
10:90749382:G:C	P251R	1.000
10:90749382:G:T	P251H	1.000
10:90749390:A:C	F248L	1.000
10:90749390:A:T	F248L	1.000
10:90749392:A:G	F248L	1.000
10:90749441:G:C	C231W	1.000
10:90749442:C:G	C231S	1.000
10:90749442:C:T	C231Y	1.000
10:90749443:A:G	C231R	1.000
10:90749443:A:T	C231S	1.000
10:90749471:C:A	W221C	1.000
10:90749471:C:G	W221C	1.000

dbSNP variants (sampled 300 via entrez): RS1000008358 (10:90803651 C>A), RS1000057222 (10:90838352 C>T), RS1000058477 (10:90745320 A>G), RS1000110615 (10:90756316 G>A), RS1000118211 (10:90832052 C>T), RS1000143471 (10:90796246 C>T), RS1000188160 (10:90748048 G>C), RS1000205248 (10:90840516 G>A), RS1000259465 (10:90781121 C>T), RS1000307384 (10:90769905 G>C), RS1000344260 (10:90741163 A>G,T), RS1000388784 (10:90784503 C>G), RS1000479141 (10:90822060 G>T), RS1000502135 (10:90799196 T>C,G), RS1000512403 (10:90758032 C>T)

Disease associations

OMIM: gene MIM:182137 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

4 associations (top):

Study	Trait	p-value
GCST002409_2	White matter microstructure (global fractional anisotropy)	3.000000e-10
GCST003427_195	Alzheimer disease and age of onset	3.000000e-07
GCST010171_2	Midgestational total 25-hydroxyvitamin D levels (maternal genetic effect)	5.000000e-07
GCST010677_6	Liver fibrogenesis (alpha smooth muscle actin levels)	2.000000e-06

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0005674	white matter microstructure measurement
EFO:0004847	age at onset
EFO:0010576	liver fibrosis measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (2): CHEMBL2096904 (PROTEIN FAMILY), CHEMBL3155 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

93 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 414,758 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL11	IMIPRAMINE	4	48,893
CHEMBL1065	METHYSERGIDE	4	8,455
CHEMBL1112	ARIPIPRAZOLE	4	24,205
CHEMBL1113	AMOXAPINE	4	20,128
CHEMBL1200492	NEFAZODONE HYDROCHLORIDE	4	5,428
CHEMBL1200517	DIHYDROERGOTAMINE MESYLATE	4	2,704
CHEMBL1200776	CINACALCET HYDROCHLORIDE	4	1,220
CHEMBL1200809	AZELASTINE HYDROCHLORIDE	4	3,805
CHEMBL1201	THIOTHIXENE	4	13,101
CHEMBL1215	PHENYLEPHRINE	4	37,782
CHEMBL1237021	LURASIDONE	4	2,517
CHEMBL1263	SALMETEROL	4	40,383
CHEMBL128	SUMATRIPTAN	4	28,367
CHEMBL1336	SORAFENIB	4	86,060
CHEMBL1442422	DIBENZEPIN	4	3,679
CHEMBL1615374	VILAZODONE HYDROCHLORIDE	4	432
CHEMBL1621	PALIPERIDONE	4	1,701
CHEMBL1628227	DOXEPIN	4	28,171
CHEMBL163	RITONAVIR	4	53,773
CHEMBL1633	KETOTIFEN FUMARATE	4	3,954
CHEMBL1705	CLONIDINE HYDROCHLORIDE	4
CHEMBL1729	CISAPRIDE	4
CHEMBL2024517	CARIPRAZINE HYDROCHLORIDE	4
CHEMBL2028019	CARIPRAZINE	4
CHEMBL2104993	VORTIOXETINE	4
CHEMBL2105760	BREXPIPRAZOLE	4
CHEMBL2106195	DEXMEDETOMIDINE HYDROCHLORIDE	4
CHEMBL2138684	FROVATRIPTAN SUCCINATE	4
CHEMBL243712	AMISULPRIDE	4
CHEMBL24778	SILODOSIN	4

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

PharmGKB clinical annotations

5 annotations.

Variant	Type	Level	Drugs	Phenotypes
rs1935349	Toxicity	3	atorvastatin;HMG-CoA reductase inhibitors;pravastatin;simvastatin	Myalgia
rs7905446	Efficacy	3	Selective serotonin reuptake inhibitors	Depression
rs7905446	Efficacy	3	antidepressants	Depression
rs7905446	Efficacy	3	paroxetine	Bipolar Disorder
rs7905446	Efficacy	3	escitalopram	Depression

PharmGKB variants

3 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs1891311	HTR7		0.00	0
rs1935349	HTR7	3	2.00	1	atorvastatin;HMG-CoA reductase inhibitors;pravastatin;simvastatin
rs7905446	HTR7, RPP30	3	4.75	4	antidepressants;paroxetine;escitalopram;Selective serotonin reuptake inhibitors

GtoPdb / IUPHAR curated pharmacology

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

Target class: gpcr — 5-Hydroxytryptamine receptors

Most potent curated ligand interactions (82 total), top 25:

Ligand	Action	Affinity	Parameter
5-CT	Full agonist	10.0	pKi
LP-12	Agonist	9.89	pKi
LP-44	Agonist	9.66	pKi
5-hydroxytryptamine	Full agonist	9.6	pKi
5-MeOT	Full agonist	9.5	pKi
[3H]5-CT	Agonist	9.4	pKd
methiothepin	Antagonist	9.4	pKi
lurasidone	Antagonist	9.31	pKi
pimozide	Antagonist	9.3	pKi
lisuride	Full agonist	9.3	pKi
LP-211	Agonist	9.24	pKi
AS-19	Agonist	9.22	pKi
tiospirone	Antagonist	9.2	pKi
[3H]5-HT	Full agonist	9.0	pKd
pergolide	Full agonist	9.0	pKi
[3H]SB269970	Antagonist	8.92	pKd
metergoline	Antagonist	8.9	pKi
[125I]LSD	Full agonist	8.9	pKd
SB269970	Antagonist	8.9	pKi
SB656104	Antagonist	8.7	pKi
risperidone	Inverse agonist	8.7	pKi
DR-4004	Antagonist	8.7	pKi
[3H]LSD	Full agonist	8.6	pKd
oleamide	Negative	8.6	pKd
E55888	Full agonist	8.6	pKi

Binding affinities (BindingDB)

125 measured of 174 human assays (235 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
(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
LSD,2-Bromo	KI	0.48 nM
METHIOTHEPIN	KI	1 nM
3-{2-[4-(4-Fluoro-benzoyl)-piperidin-1-yl]-ethyl}-2-methyl-pyrido[1,2-a]pyrimidin-4-one	KI	1.08 nM
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
CAS_62865	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
4-[4-(4-Chloro-phenyl)-4-hydroxy-piperidin-1-yl]-1-(4-fluoro-phenyl)-butan-1-one;propionate(HCl)	KI	2.92 nM
8-[4-(4-fluorophenyl)-4-keto-butyl]-1-phenyl-1,3,8-triazaspiro[4.5]decan-4-one	KI	2.94 nM	US-9359372: Hexahydrodibenzo[a,g]quinolizine compound, preparation method thereof, pharmaceutical composition and use thereof
(S)-mianserin	KI	3 nM
3-Cyclohexyl-5-{4-[4-(2-methoxyphenyl)piperazin-1-yl]butyl}-4,5-dihydro-1,2,4-triazin-6(1H)-one (18)	KI	5 nM
1-[(2,3,5-trimethylphenoxy)propyl]-4-(2-methoxyphenyl)piperazine hydrochloride (3)	KI	6 nM
3,3-diethyl-5-[2-[4-(2-propan-2-ylphenyl)piperazin-1-yl]ethyl]oxolan-2-one	IC50	6 nM	US-9802924: 5-hydroxytryptamine receptor 7 activity modulators and their method of use
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
5-{4-[4-(2-Methoxyphenyl)piperazin-1-yl]butyl}-3-phenyl-4,5-dihydro-1,2,4-triazin-6(1H)-one (12)	KI	9 nM
3,3-diethyl-5-[2-[4-(4-methylphenyl)piperazin-1-yl]ethyl]oxolan-2-one	IC50	10 nM	US-9802924: 5-hydroxytryptamine receptor 7 activity modulators and their method of use
5-[2-(3,4-dihydro-1H-isoquinolin-2-yl)ethyl]-3,3-diethyloxolan-2-one	IC50	13 nM	US-9802924: 5-hydroxytryptamine receptor 7 activity modulators and their method of use
3-Cyclohexyl-5-{4-[4-(2-(methylthio)phenyl)piperazin-1-yl]butyl}-4,5-dihydro-1,2,4-triazin-6(1H)-one (19)	KI	14 nM
3-[2-[4-(2-morpholin-4-ylphenyl)piperazin-1-yl]ethyl]-2-oxaspiro[4.4]nonan-1-one	IC50	17 nM	US-9802924: 5-hydroxytryptamine receptor 7 activity modulators and their method of use
3,3-diethyl-5-[2-(4-phenylpiperazin-1-yl)ethyl]oxolan-2-one	IC50	21 nM	US-9802924: 5-hydroxytryptamine receptor 7 activity modulators and their method of use
3-[2-[4-(2-propan-2-ylphenyl)piperazin-1-yl]ethyl]-2-oxaspiro[4.4]nonan-1-one	IC50	24 nM	US-9802924: 5-hydroxytryptamine receptor 7 activity modulators and their method of use
5-{4-[4-(2-(Methylthio)phenyl)piperazin-1-yl]butyl}-3-phenyl-4,5-dihydro-1,2,4-triazin-6(1H)-one (13)	KI	28 nM
3-Cyclohexyl-5-{4-[4-(2,3-dichlorophenyl)piperazin-1-yl]butyl}-4,5-dihydro-1,2,4-triazin-6(1H)-one (20)	KI	32 nM
3-[2-(4-phenylpiperazin-1-yl)ethyl]-2-oxaspiro[4.5]decan-1-one	IC50	33 nM	US-9802924: 5-hydroxytryptamine receptor 7 activity modulators and their method of use
3-[2-[4-(5-chloro-2-pyridinyl)piperazin-1-yl]ethyl]-2-oxaspiro[4.5]decan-1-one	IC50	33 nM	US-9802924: 5-hydroxytryptamine receptor 7 activity modulators and their method of use
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
3-(2-Chlorophenyl)-5-{4-[4-(2-fluorophenyl)piperazin-1-yl]butyl}-4,5-dihydro-1,2,4-triazin-6(1H)-one (17)	KI	37 nM
3-[2-[4-(4-chlorophenyl)piperazin-1-yl]ethyl]-2-oxaspiro[4.5]decan-1-one	IC50	40 nM	US-9802924: 5-hydroxytryptamine receptor 7 activity modulators and their method of use
1-[(2,6-dimethylphenoxy)ethoxyethyl]-4-(2-methoxyphenyl)piperazine hydrochloride (5)	KI	41 nM
3-[2-(4-pyridin-2-ylpiperazin-1-yl)ethyl]-2-oxaspiro[4.5]decan-1-one	IC50	44 nM	US-9802924: 5-hydroxytryptamine receptor 7 activity modulators and their method of use
3,3-diethyl-5-[2-(4-pyridin-2-ylpiperazin-1-yl)ethyl]oxolan-2-one	IC50	46 nM	US-9802924: 5-hydroxytryptamine receptor 7 activity modulators and their method of use
3-[2-[4-(2-methyl-1H-benzimidazol-4-yl)piperazin-1-yl]ethyl]-8-methylsulfonyl-2-oxa-8-azaspiro[4.5]decan-1-one	IC50	46 nM	US-10858368: Modulators of the 5-hydroxytryptamine receptor 7 and their method of use
3-[2-[4-(2-hydroxyphenyl)piperazin-1-yl]ethyl]-2-oxaspiro[4.5]decan-1-one	IC50	49 nM	US-9802924: 5-hydroxytryptamine receptor 7 activity modulators and their method of use
LY 246708	KI	50.1 nM
3,3-diethyl-5-[2-[4-(4-nitrophenyl)piperazin-1-yl]ethyl]oxolan-2-one	IC50	54 nM	US-9802924: 5-hydroxytryptamine receptor 7 activity modulators and their method of use
3-[2-[4-(3-methoxyphenyl)piperazin-1-yl]ethyl]-2-oxaspiro[4.5]decan-1-one	IC50	56 nM	US-9802924: 5-hydroxytryptamine receptor 7 activity modulators and their method of use
3-[2-[4-(1H-indol-5-yl)piperazin-1-yl]ethyl]-2-oxaspiro[4.4]nonan-1-one	IC50	56 nM	US-10544117: 5-hydroxytryptamine receptor 7 activity modulators and their method of use
5-(1-methylpiperidylidene-4)-5H-dibenzo(a,d)cyclopheptene	KI	59 nM
SMR001230745	KI	63.1 nM
3-[2-[4-(1H-indol-5-yl)piperazin-1-yl]ethyl]-2-oxaspiro[4.5]decan-1-one	IC50	65.3 nM	US-10544117: 5-hydroxytryptamine receptor 7 activity modulators and their method of use
5-{4-[4-(2,3-Dichlorophenyl)piperazin-1-yl]butyl}-3-phenyl-4,5-dihydro-1,2,4-triazin-6(1H)-one (16)	KI	70 nM
3-[2-[4-(2-methoxyphenyl)piperazin-1-yl]ethyl]-2-oxaspiro[4.5]decan-1-one	IC50	72 nM	US-9802924: 5-hydroxytryptamine receptor 7 activity modulators and their method of use
2-[4-[2-(4,4-dimethyl-5-oxooxolan-2-yl)ethyl]piperazin-1-yl]benzonitrile	IC50	74 nM	US-9802924: 5-hydroxytryptamine receptor 7 activity modulators and their method of use
5-[2-(4-benzhydrylidenepiperidin-1-yl)ethyl]-3,3-diethyloxolan-2-one	IC50	78 nM	US-9802924: 5-hydroxytryptamine receptor 7 activity modulators and their method of use
3-Phenyl-5-[4-(4-phenylpiperazin-1-yl)butyl]-4,5-dihydro-1,2,4-triazin-6(1H)-one (11)	KI	79 nM
3-[2-[4-(2-chlorophenyl)piperazin-1-yl]ethyl]-2-oxaspiro[4.5]decan-1-one	IC50	81 nM	US-9802924: 5-hydroxytryptamine receptor 7 activity modulators and their method of use
5-[2-(4-benzhydrylpiperazin-1-yl)ethyl]-3,3-diethyloxolan-2-one	IC50	83 nM	US-9802924: 5-hydroxytryptamine receptor 7 activity modulators and their method of use

ChEMBL bioactivities

4131 potent at pChembl≥5 of 4262 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
10.00	Ki	0.1	nM	CHEMBL3289972
10.00	Ki	0.1	nM	CHEMBL5789483
9.96	Ki	0.11	nM	SEROTONIN
9.89	Ki	0.13	nM	SEROTONIN
9.85	Ki	0.14	nM	SEROTONIN
9.81	Ki	0.153	nM	MARITUPIRDINE
9.80	Kd	0.1585	nM	CHEMBL323208
9.77	Ki	0.17	nM	SEROTONIN
9.77	Ki	0.17	nM	CHEMBL5179460
9.70	Ki	0.2	nM	CHEMBL363452
9.70	Ki	0.2	nM	CHEMBL3290016
9.70	Ki	0.2	nM	SEROTONIN
9.70	EC50	0.2	nM	CHEMBL18840
9.70	Ki	0.1995	nM	CHEMBL363452
9.68	Ki	0.2089	nM	CHEMBL605405
9.66	Ki	0.22	nM	CHEMBL225284
9.66	Ki	0.22	nM	SEROTONIN
9.66	Ki	0.22	nM	CHEMBL5196234
9.60	IC50	0.25	nM	SEROTONIN
9.60	Ki	0.2512	nM	MARITUPIRDINE
9.59	Ki	0.26	nM	CHEMBL4291322
9.54	IC50	0.29	nM	SEROTONIN
9.52	Ki	0.3	nM	CHEMBL2159465
9.52	Ki	0.3	nM	CHEMBL1256863
9.52	Ki	0.3	nM	CHEMBL183277
9.52	Ki	0.3	nM	CHEMBL182923
9.52	IC50	0.3	nM	METHIOTHEPIN MESYLATE
9.52	Ki	0.3	nM	CHEMBL596959
9.50	Ki	0.3162	nM	CHEMBL414628
9.49	Ki	0.32	nM	CHEMBL5184712
9.47	Ki	0.34	nM	CHEMBL282199
9.47	Ki	0.3388	nM	CHEMBL282199
9.46	Ki	0.35	nM	CHEMBL18840
9.42	Ki	0.38	nM	CHEMBL260994
9.42	Ki	0.38	nM	CHEMBL261719
9.42	Ki	0.3802	nM	CHEMBL261719
9.41	IC50	0.39	nM	CHEMBL4128926
9.41	Ki	0.389	nM	CHEMBL605081
9.40	Ki	0.4	nM	CHEMBL18840
9.40	Ki	0.4	nM	CHEMBL184607
9.40	Ki	0.4	nM	CHEMBL183423
9.40	Ki	0.4	nM	CHEMBL181605
9.40	Ki	0.4	nM	CHEMBL181356
9.40	Ki	0.4	nM	CHEMBL3290004
9.40	Ki	0.4	nM	RISPERIDONE
9.40	Ki	0.4	nM	CHEMBL4245263
9.40	IC50	0.4	nM	SEROTONIN
9.40	Ki	0.4	nM	CHEMBL6011569
9.40	Ki	0.4	nM	CHEMBL408976
9.40	Ki	0.3981	nM	CHEMBL18840

PubChem BioAssay actives

3601 with measured affinity, of 5762 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
Serotonin	2198815: Binding affinity to 5HT7 receptor (unknown origin) assessed as inhibition constant	ki	0.0001	uM
N-[4-[4-(1,2-benzoxazol-3-yl)piperazin-1-yl]butyl]-3-chloro-4-fluorobenzenesulfonamide	1152667: Displacement of [3H]LSD from human recombinant 5-HT7 receptor expressed in CHO-K1 cell membrane after 120 mins by liquid scintillation counting analysis	ki	0.0001	uM
2-N-[2-(4-fluorophenoxy)ethyl]-4-N-[(1S)-1-phenylethyl]pyridine-2,4-diamine	238460: Binding affinity against 5-Hydroxy tryptamine 7 receptor	ki	0.0002	uM
6-[4-(2-methylsulfanylphenyl)piperazin-1-yl]-N-(1,2,3,4-tetrahydronaphthalen-1-yl)hexanamide	1126169: Displacement of [3H]-5-CT from human 5-HT7 receptor expressed in HEK293 cells after 1 hr by beta-counting	ki	0.0002	uM
1-[3-[(2S)-1-(2-fluorophenyl)sulfonylpyrrolidin-2-yl]propyl]-4-pyridin-2-ylpiperazine	1855144: Binding affinity to human recombinant 5-HT7 receptor expressed in CHO cells assessed as inhibition constant	ki	0.0002	uM
1-(4-chlorophenyl)-4-[3-[(2S)-1-(2-fluorophenyl)sulfonylpyrrolidin-2-yl]propyl]piperazine	1855144: Binding affinity to human recombinant 5-HT7 receptor expressed in CHO cells assessed as inhibition constant	ki	0.0002	uM
3-(2-aminoethyl)-1H-indole-5-carboxamide	2119131: Agonist activity at human 5-HT7 expressed in HEK293 cells assessed as receptor activation incubated for 60 mins by FLIPR fluorimetry based calcium flux assay	ec50	0.0002	uM
2,8-dimethyl-5-(2-phenylethyl)-3,4-dihydro-1H-pyrido[4,3-b]indole	1384593: Displacement of [3H]lysergic acid from 5-HT7 receptor (unknown origin)	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
2,8-dimethyl-5-[(Z)-2-phenylethenyl]-3,4-dihydro-1H-pyrido[4,3-b]indole	452268: Displacement of [3H]LSD from human recombinant 5HT7 receptor expressed in CHO cells	ki	0.0002	uM
5-fluoro-N-[4-[4-(6-fluoro-1,2-benzoxazol-3-yl)piperidin-1-yl]butyl]-3-methyl-1-benzothiophene-2-sulfonamide	1152667: Displacement of [3H]LSD from human recombinant 5-HT7 receptor expressed in CHO-K1 cell membrane after 120 mins by liquid scintillation counting analysis	ki	0.0002	uM
6-iodo-1-(4-methoxy-3-piperazin-1-ylphenyl)sulfonyl-2,3-dihydroindole	6619: Compound was evaluated for binding affinity against human cloned 5-hydroxytryptamine 7 receptor in HEK 293 cells using [3H]5-CT as the radioligand (n=3)	ki	0.0003	uM
3-(2-aminoethyl)-1H-indole-5-carboxamide;(Z)-but-2-enedioic acid	699068: Displacement of [3H]-5-CT from human cloned 5HT7 receptor	ki	0.0003	uM
5-fluoro-3-[2-[4-(2-phenylphenyl)piperazin-1-yl]ethyl]-1H-indole	1403538: Displacement of [3H]LSD from recombinant human 5-HT7 receptor expressed in CHO cell membranes after 120 mins by TopCount scintillation counting method	ki	0.0003	uM
1-(4-chlorophenyl)-4-[3-[(2S)-1-(4-fluorophenyl)sulfonylpyrrolidin-2-yl]propyl]piperazine	1855144: Binding affinity to human recombinant 5-HT7 receptor expressed in CHO cells assessed as inhibition constant	ki	0.0003	uM
methanesulfonic acid;1-methyl-4-(3-methylsulfanyl-5,6-dihydrobenzo[b][1]benzothiepin-5-yl)piperazine	2119133: Antagonist activity at human 5-HT7 expressed in HEK293 cells assessed as inhibition of 3-(2-aminoethyl)-1H-indole-5-carboxamide induced response preincubated for 30 mins followed by 3-(2-aminoethyl)-1H-indole-5-carboxamide addition and measured after 60 mins by FLIPR fluorimetry based calcium flux assay	ic50	0.0003	uM
4-N-[(1S)-1-phenylethyl]-2-N-(2-phenylethyl)pyridine-2,4-diamine	238460: Binding affinity against 5-Hydroxy tryptamine 7 receptor	ki	0.0003	uM
2-N-[2-(4-fluorophenoxy)ethyl]-4-N-[(1S)-1-phenylethyl]pyrimidine-2,4-diamine	238460: Binding affinity against 5-Hydroxy tryptamine 7 receptor	ki	0.0003	uM
(2S)-5-naphthalen-1-yl-N,N-dipropyl-1,2,3,4-tetrahydronaphthalen-2-amine	460909: Displacement of [3H]5CT from human cloned 5HT7B receptor expressed in HEK293 cells	ki	0.0003	uM
3-[(2R)-2-[2-(4-methylpiperidin-1-yl)ethyl]pyrrolidin-1-yl]sulfonylphenol	1187932: Displacement of [3H]LSD from 5-HT7R (unknown origin) expressed in CHO-K1 cells by liquid scintillation counting method	ki	0.0003	uM
4-fluoro-N-[1-[2-(2-propan-2-ylphenoxy)ethyl]piperidin-4-yl]benzenesulfonamide	694794: Displacement of [3H]-5-CT from human 5-HT7b receptor expressed in HEK293 cells after 1 hr	ki	0.0003	uM
3-[4-[4-(4-chlorophenyl)piperazin-1-yl]butyl]-3-ethyl-1H-indol-2-one	327983: Displacement of [3H]LSD from human recombinant 5HT7 receptor expressed in CHO cells	ki	0.0004	uM
3-[4-[4-(4-chlorophenyl)piperazin-1-yl]butyl]-1,3-dihydroindol-2-one	327983: Displacement of [3H]LSD from human recombinant 5HT7 receptor expressed in CHO cells	ki	0.0004	uM
6-fluoro-3-[1-[2-[(2S)-1-isoquinolin-4-ylsulfonylpyrrolidin-2-yl]ethyl]piperidin-4-yl]-1,2-benzoxazole	1393367: Displacement of [3H]-5-CT from human 5-HT7R expressed in HEK293 cell membranes after 1 hr at 37 degC by microbeta counting method	ki	0.0004	uM
3-ethyl-3-[4-[4-(4-fluorophenyl)piperazin-1-yl]butyl]-1H-indol-2-one	327983: Displacement of [3H]LSD from human recombinant 5HT7 receptor expressed in CHO cells	ki	0.0004	uM
3-[4-[4-(3-chlorophenyl)piperazin-1-yl]butyl]-3-ethyl-1H-indol-2-one	327983: Displacement of [3H]LSD from human recombinant 5HT7 receptor expressed in CHO cells	ki	0.0004	uM
1-methyl-4-(3-methylsulfanyl-5,6-dihydrobenzo[b][1]benzothiepin-5-yl)piperazine	1802635: Radioligand Binding Assay ([3H]-LSD)) from Article 10.1111/cbdd.12842: “Design, synthesis, and anticonvulsant activity of some derivatives of xanthone with aminoalkanol moieties.”	ki	0.0004	uM
2,8-dimethyl-5-[2-(4-methylphenyl)ethyl]-3,4-dihydro-1H-pyrido[4,3-b]indole	452268: Displacement of [3H]LSD from human recombinant 5HT7 receptor expressed in CHO cells	ki	0.0004	uM
2-[2-[4-(1H-indol-3-yl)piperidin-1-yl]ethyl]-4,5-dihydro-3H-2-benzazepin-1-one	6608: Binding affinity at human cloned 5-hydroxytryptamine 7 receptor.	ki	0.0004	uM
2-N-(2-phenoxyethyl)-4-N-[(1S)-1-phenylethyl]pyridine-2,4-diamine	238460: Binding affinity against 5-Hydroxy tryptamine 7 receptor	ki	0.0004	uM
2-N-[2-(4-fluorophenyl)ethyl]-4-N-[(1S)-1-phenylethyl]pyridine-2,4-diamine	238460: Binding affinity against 5-Hydroxy tryptamine 7 receptor	ki	0.0004	uM
4-N-(2-phenoxyethyl)-2-N-[(1S)-1-phenylethyl]pyridine-2,4-diamine	238460: Binding affinity against 5-Hydroxy tryptamine 7 receptor	ki	0.0004	uM
4-N-[2-(4-fluorophenoxy)ethyl]-2-N-[(1S)-1-phenylethyl]pyridine-2,4-diamine	238460: Binding affinity against 5-Hydroxy tryptamine 7 receptor	ki	0.0004	uM
Risperidone	1393367: Displacement of [3H]-5-CT from human 5-HT7R expressed in HEK293 cell membranes after 1 hr at 37 degC by microbeta counting method	ki	0.0004	uM
N-[2-[4-(6-fluoro-1,2-benzoxazol-3-yl)piperidin-1-yl]ethyl]naphthalene-2-sulfonamide	1152667: Displacement of [3H]LSD from human recombinant 5-HT7 receptor expressed in CHO-K1 cell membrane after 120 mins by liquid scintillation counting analysis	ki	0.0004	uM
3-[[5-[4-(tert-butylsulfamoyl)naphthalen-1-yl]-4-(cyclohexylmethyl)-1,3-thiazole-2-carbonyl]amino]cyclobutane-1-carboxylic acid	1494770: Displacement of [3H]LSD from human recombinant 5-HT7 receptor after 120 mins by scintillation counting analysis	ic50	0.0004	uM
3-[4-[4-(3-chlorophenyl)piperazin-1-yl]butyl]-1,3-dihydroindol-2-one	327983: Displacement of [3H]LSD from human recombinant 5HT7 receptor expressed in CHO cells	ki	0.0005	uM
5-chloro-2-[2-(3,4-dihydro-1H-isoquinolin-2-yl)ethyl]-2,3-dihydroinden-1-one;hydrochloride	1324265: Displacement of [3H]-LSD from human 5-HT7 receptor by liquid scintillation counting method	ki	0.0005	uM
Lurasidone	1517962: Displacement of [3H]-5-CT from human 5HT7 receptor expressed in HEK293 cells incubated for 1 hr by liquid scintillation counting method	ki	0.0005	uM
2-[2-(dimethylamino)ethyl]-4-(1,3,5-trimethylpyrazol-4-yl)phenol	1384577: Binding affinity to 5-HT7 receptor (unknown origin)	ki	0.0005	uM
6-[(2R)-2-[2-[4-(4-fluorophenoxy)piperidin-1-yl]ethyl]pyrrolidin-1-yl]sulfonyl-1H-indole	6626: Binding affinity for human cloned 5-hydroxytryptamine 7 receptor in HEK 293 using [3H]5-CT as a radioligand	ki	0.0005	uM
N-[3-[4-(6-fluoro-1,2-benzoxazol-3-yl)piperidin-1-yl]propyl]naphthalene-1-sulfonamide	1152667: Displacement of [3H]LSD from human recombinant 5-HT7 receptor expressed in CHO-K1 cell membrane after 120 mins by liquid scintillation counting analysis	ki	0.0005	uM
N-(diaminomethylidene)-9-ethyl-9-methoxyfluorene-2-carboxamide;hydrochloride	1167374: Displacement of [3H]5-HT from human 5-HT7 receptor expressed in CHO cells	ki	0.0006	uM
5-fluoro-3-[3-[4-[3-fluoro-2-(3-fluorophenyl)phenyl]piperazin-1-yl]propyl]-1H-indole	1403538: Displacement of [3H]LSD from recombinant human 5-HT7 receptor expressed in CHO cell membranes after 120 mins by TopCount scintillation counting method	ki	0.0006	uM
(2S)-N,N-dimethyl-5-(1,3,5-trimethylpyrazol-4-yl)-1,2,3,4-tetrahydronaphthalen-2-amine	1384577: Binding affinity to 5-HT7 receptor (unknown origin)	ki	0.0006	uM
3-[4-[4-(3-chloro-4-fluorophenyl)piperazin-1-yl]butyl]-3-ethyl-1H-indol-2-one	327983: Displacement of [3H]LSD from human recombinant 5HT7 receptor expressed in CHO cells	ki	0.0006	uM
3-[4-[4-(3,4-dichlorophenyl)piperazin-1-yl]butyl]-3-ethyl-1H-indol-2-one	327983: Displacement of [3H]LSD from human recombinant 5HT7 receptor expressed in CHO cells	ki	0.0006	uM
N-[(4-cyanophenyl)methyl]-6-[4-(2-phenylphenyl)piperazin-1-yl]hexanamide	1126169: Displacement of [3H]-5-CT from human 5-HT7 receptor expressed in HEK293 cells after 1 hr by beta-counting	ki	0.0006	uM
2-[2-[4-(5-fluoroindol-1-yl)piperidin-1-yl]ethyl]-4,5-dihydro-3H-2-benzazepin-1-one	6608: Binding affinity at human cloned 5-hydroxytryptamine 7 receptor.	ki	0.0006	uM
2-[4-[4-(2-methoxyphenyl)piperazin-1-yl]butyl]isoindole-1,3-dione	1188130: Displacement of [3H]5-HT from human 5HT7 receptor transfected in CFO-K1 cells after 30 mins by liquid scintillation spectrometry	ki	0.0006	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	increases expression, affects expression	3
Paliperidone Palmitate	affects binding, decreases activity, decreases reaction, increases abundance	3
Cyclic AMP	increases activity, decreases abundance, affects binding, decreases activity, decreases reaction (+1 more)	3
Metergoline	affects binding, decreases activity, decreases reaction, increases abundance	3
Methiothepin	affects binding, decreases activity, decreases reaction, increases abundance, decreases abundance	3
Risperidone	affects binding, decreases activity, decreases reaction, increases abundance	3
mesulergine	decreases activity, decreases reaction, increases abundance, affects binding	2
SB 269970	decreases expression, decreases reaction, affects binding, decreases activity	2
Bromocriptine	affects binding, decreases activity, decreases reaction, increases abundance	2
Clozapine	affects binding, decreases activity, decreases reaction, increases abundance	2
Lisuride	affects binding, decreases activity, decreases reaction, increases abundance	2
Mianserin	decreases activity, decreases reaction, increases abundance, affects binding	2
bisphenol A	decreases methylation	1
testosterone undecanoate	affects cotreatment, increases expression	1
mono-(2-ethylhexyl)phthalate	increases expression	1
nickel sulfate	decreases expression	1
5-carboxamidotryptamine	affects binding, decreases activity, decreases reaction, increases abundance, increases activity	1
2-((2-(dimethylamino)ethyl)thio)-3-phenylquinoline	affects binding, decreases activity, decreases reaction	1
volinanserin	decreases activity, decreases reaction, increases abundance, affects binding	1
3,N-dimethyl-N-(1-methyl-3-(4-methylpiperidin-1-yl)propyl)benzenesulfonamide	affects binding, decreases activity, decreases reaction, increases abundance	1
7-fluoro-2-oxo-4-(2-(4-(thieno(3,2-c)pyridin-4-yl)piperazin-1-yl)ethyl)-1,2-dihydroquinoline-1-acetamide	affects activity	1
4-(2-methylthiophenyl)-N-(1,2,3,4-tetrahydronaphthalen-1-yl)-1-piperazinehexanamide	decreases expression, decreases reaction	1
abrine	increases expression	1
mirdametinib	decreases expression, affects cotreatment	1
(+)-JQ1 compound	affects cotreatment, decreases expression	1
Lurasidone Hydrochloride	affects binding, decreases activity	1
Vortioxetine	affects binding, decreases activity	1
Benzo(a)pyrene	increases methylation	1
Cyproheptadine	affects binding, decreases activity, decreases reaction	1
Estradiol	affects cotreatment, increases expression	1

ChEMBL screening assays

836 unique, capped per target: 674 binding, 153 functional, 9 admet

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL2060606	Binding	Inhibition of 5HT	Discovery and optimization of novel purines as potent and selective CB2 agonists. — Bioorg Med Chem Lett
CHEMBL4413391	ADMET	Antagonist activity at serotonin receptor in human PBMC assessed as inhibition of PMA-stimulated superoxide anion generation at 10 uM preincubated for 1 hr followed by PMA-stimulation and measured after 30 mins by spectrophotometric method	Identification of a novel DGKα inhibitor for XLP-1 therapy by virtual screening. — Eur J Med Chem
CHEMBL619167	Functional	5-HT level in K+ induced 5-hydroxytryptamine release in guinea pig cortex.	New selective and potent 5-HT(1B/1D) antagonists: chemistry and pharmacological evaluation of N-piperazinylphenyl biphenylcarboxamides and biphenylsulfonamides. — J Med Chem

Cellosaurus cell lines

8 cell lines: 4 cancer cell line, 2 transformed cell line, 2 spontaneously immortalized cell line

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

Cellosaurus	Name	Category	Sex
CVCL_C0T1	ACTOne HTR7B	Transformed cell line	Female
CVCL_D1T5	Abcam U-87MG HTR7 KO	Cancer cell line	Male
CVCL_D8MN	Ubigene HCT 116 HTR7 KO	Cancer cell line	Male
CVCL_H361	293/5-HT7/CRE-Luc	Transformed cell line	Female
CVCL_KS00	GeneBLAzer HTR7-CRE-bla CHO-K1	Spontaneously immortalized cell line	Female
CVCL_KV42	cAMP Hunter CHO-K1 HTR7A Gs	Spontaneously immortalized cell line	Female
CVCL_KV92	cAMP Hunter DLD1 HTR7D Gs	Cancer cell line	Male
CVCL_KV94	cAMP Hunter U2OS HTR7B Gs	Cancer cell line	Female

Clinical trials (associated diseases)

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