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NPSR1

gene
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Also known as PGR14GPRA

Summary

NPSR1 (neuropeptide S receptor 1, HGNC:23631) is a protein-coding gene on chromosome 7p14.3, encoding Neuropeptide S receptor (Q6W5P4). G-protein coupled receptor for neuropeptide S (NPS).

This gene encodes a member of the vasopressin/oxytocin subfamily of G protein-coupled receptors. The encoded membrane protein acts as a receptor for neuropeptide S and affects a variety of cellular processes through its signaling. Increased expression of this gene in ciliated cells of the respiratory epithelium and in bronchial smooth muscle cells is associated with asthma. Polymorphisms in this gene have also been associated with asthma susceptibility, panic disorders, inflammatory bowel disease, and rheumatoid arthritis. Alternative splicing results in multiple transcript variants.

Source: NCBI Gene 387129 — RefSeq curated summary.

At a glance

  • Gene–disease (curated): asthma-related traits, susceptibility to, 2 (Limited, GenCC)
  • GWAS associations: 5
  • Clinical variants (ClinVar): 37 total — 1 pathogenic
  • Phenotypes (HPO): 2
  • Druggable target: yes — 153 molecules with ChEMBL bioactivity
  • MANE Select transcript: NM_207172

Identifiers

Gene identifiers

FieldValue
HGNC IDHGNC:23631
Approved symbolNPSR1
Nameneuropeptide S receptor 1
Location7p14.3
Locus typegene with protein product
StatusApproved
AliasesPGR14, GPRA
Ensembl geneENSG00000187258
Ensembl biotypeprotein_coding
OMIM608595
Entrez387129

Gene structure

Transcript identifiers

Ensembl transcripts: 9 — 7 protein_coding, 2 nonsense_mediated_decay

ENST00000359791, ENST00000360581, ENST00000381539, ENST00000381542, ENST00000381544, ENST00000381553, ENST00000396095, ENST00000465305, ENST00000531252

RefSeq mRNA: 5 — MANE Select: NM_207172 NM_001300933, NM_001300934, NM_001300935, NM_207172, NM_207173

CCDS: CCDS5443, CCDS5444, CCDS75579, CCDS75580, CCDS75581

Canonical transcript exons

ENST00000360581 — 9 exons

ExonStartEnd
ENSE000014084783477846234778565
ENSE000014100913468455234684684
ENSE000035143023483438434834460
ENSE000035579333484848334848663
ENSE000035913013484489634844982
ENSE000036147073482740134827602
ENSE000036590963484956534849978
ENSE000036656743481177034811863
ENSE000038922383465821834658559

Expression profiles

Bgee: expression breadth broad, 32 present calls, max score 83.55.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.3136 / max 358.1952, expressed in 20 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter IDTPM avgSamples expressed
780910.176910
780920.12218
780930.01468

Top tissues by expression

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

TissueAnatomy IDExpression scoreQuality
male germ line stem cell (sensu Vertebrata) in testisCL:0000089 ∩ UBERON:000047383.55gold quality
primordial germ cell in gonadCL:0000670 ∩ UBERON:000099182.58silver quality
ganglionic eminenceUBERON:000402352.44gold quality
hypothalamusUBERON:000189846.34gold quality
sural nerveUBERON:001548844.65gold quality
prefrontal cortexUBERON:000045142.65gold quality
mucosa of transverse colonUBERON:000499142.06silver quality
anterior cingulate cortexUBERON:000983541.37gold quality
cortical plateUBERON:000534341.01silver quality
ventricular zoneUBERON:000305340.83gold quality
granulocyteCL:000009438.78gold quality
frontal cortexUBERON:000187038.55gold quality
Brodmann (1909) area 9UBERON:001354038.31silver quality
primary visual cortexUBERON:000243637.71gold quality
cerebral cortexUBERON:000095637.64gold quality
colonic epitheliumUBERON:000039737.20gold quality
dorsolateral prefrontal cortexUBERON:000983437.13silver quality
rectumUBERON:000105236.97silver quality
olfactory segment of nasal mucosaUBERON:000538636.64gold quality
bone marrow cellCL:000209236.16gold quality
placentaUBERON:000198735.41silver quality
skeletal muscle tissueUBERON:000113435.11gold quality
C1 segment of cervical spinal cordUBERON:000646933.80silver quality
muscle tissueUBERON:000238533.64gold quality
brainUBERON:000095533.33gold quality
temporal lobeUBERON:000187133.17gold quality
amygdalaUBERON:000187632.84gold quality
corpus callosumUBERON:000233632.50gold quality
Ammon’s hornUBERON:000195432.49gold quality
substantia nigraUBERON:000203832.46gold quality

Single-cell (SCXA)

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

ExperimentMarker?Max mean expression
E-ANND-3yes3.77

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): RORA

miRNA regulators (miRDB)

5 targeting NPSR1, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNAMax scoreAvg scoremiRNA target_count
HSA-MIR-118499.9968.191458
HSA-MIR-451999.4866.10859
HSA-MIR-4687-5P99.1466.26488
HSA-MIR-429098.5165.17907
HSA-MIR-797396.4865.54502

Literature-anchored findings (GeneRIF, showing 40)

  • Vasopressin receptor-related receptor 1, also called G protein-coupled receptor 154, has dual signaling properties in coupling to both G(q) and G(S) pathways. (PMID:14757815)
  • properties of GPRA make it a strong candidate for involvement in the pathogenesis of asthma and other IgE-mediated diseases; GPRA encodes isoforms produced in distinct patterns by bronchial epithelial & smooth muscle cells in asthma & healthy individuals (PMID:15073379)
  • Our results indicate that polymorphisms and haplotypes in the haplotype block of GPR154 are associated with asthma, rhinoconjunctivitis, and sensitization in European children. (PMID:15710598)
  • GPRA gene polymorphism is associated with asthma in a large german population. (PMID:15764725)
  • GPRA gene is associated with asthma and bronchial hyperreactivity. (PMID:15941840)
  • GPRA might have functional relevance in modulating asthma by increased expression levels in the relevant tissues under diseased state and by potential inhibitory effect of GPRA-A activation on cell growth (PMID:15947423)
  • the GPRA gene does not contribute to the shared genetic predisposition of atopic dermatitis and allergic airways disease (PMID:15990798)
  • No difference in allele frequency or haplotype for asthma (PMID:16098057)
  • There is a role of the GPR154 gene in the genetic susceptibility of asthma. (PMID:16522461)
  • the key residues of NPS involved in NPSR activation and suggest a molecular basis for the functional effects of the N107I mutation and for its putative pathophysiological link with asthma (PMID:16790440)
  • GPRA may contribute to the asthmatic phenotype by altering the activity of other pathways, such as neurally mediated mechanisms, that contribute to disease (PMID:16829631)
  • Because remodeling of airway epithelium is a feature of chronic asthma, the up-regulation of MMP10 and TIMP3 by NPS-NPSR1 signaling may be of relevance in the pathogenesis of asthma. (PMID:16926187)
  • In infants with respiratory distress syndrome (RDS) born at 32-35 weeks of gestation, GPRA haplotype H1 was significantly underrepresented in RDS, whereas haplotype H4/H5 was associated with an increased risk. (PMID:16938805)
  • a common susceptibility factor for atopic manifestations in asthma is likely conferred by the locus containing the GPR154 gene (PMID:17210045)
  • The polymorphisms of SNP563704 and SNP522363 are not associated with allergic asthma in Han nationality in Hubei Chinese population. However, the haplotypes are associated with allergic asthma. (PMID:17285544)
  • evidence for a gender-specific effect of Neuropeptide S receptor in the pathogenesis of panic disorder (PMID:17669576)
  • Results provide some further support for the role of genetic variation in GPR154 (NPSR1) in asthma susceptibility. (PMID:17702965)
  • NPSR1 polymorphism is associated with IBD susceptibility. Specific NPSR1 alleles might act as genetic risk factors for chronic inflammatory diseases of the epithelial barrier organs. (PMID:17854592)
  • A strong interaction was seen between current regular contact to farm animals and several NPSR1 polymorphisms. Suggests the effect of farm animal contact on the development of allergic symptoms in children is modified by NPSR1 genetic background. (PMID:18285428)
  • In asthma and atopic sensitization significant gene-gene interactions were found between TNC and NPSR1 SNPs. (PMID:18305139)
  • Relatively high level of expression of mRNA for SLC9A3RI was detected wheres lower level of S100A7 and GPRA were found. (PMID:18588753)
  • strongly suggest that NPSR1 is not involved in the pathogenesis of eczema. (PMID:19325992)
  • Data suggest that the NPS/NPSR1 pathway may participate in the regulation of the peptide hormone production in enteroendocrine cells of the small intestine. (PMID:19614867)
  • Association of G-protein-coupled receptor 154 with asthma and total IgE in a population of the Caribbean coast of Colombia. (PMID:19624525)
  • Expression of several neuropeptides is induced upon NPS-NPSR1 signaling; NPSR1 variants are associated with colonic transit in functional gastrointestinal diseases (PMID:19732772)
  • The available information regarding NPS and its receptor and the biological actions modulated by the NPS-NPSR system, is summarized. (PMID:19824051)
  • Results suggest that N-linked glycosylation is not important for neuropeptide S receptor biogenesis or function, and that residue D105 might be critical for receptor binding. (PMID:19874863)
  • Data show that NPSR1 polymorphism may be relevant to RA susceptibility and its clinical manifestation. (PMID:20179762)
  • results provide converging evidence for a female-dominant role of NPSR gene variation in panic disorder through heightened autonomic arousal and distorted processing of anxiety-relevant emotional stimuli. (PMID:20603625)
  • data suggest a genetic and neuroanatomical substrate for catastrophizing overinterpretations of fear reactions. (PMID:20628342)
  • NPS-NPSR1 signaling is likely involved in anxiety (PMID:20705147)
  • Ther neuropeptide S receptor genotype is associated with increased amygdala responsiveness to fear-relevant stimuli. (PMID:21525857)
  • There is an NPSR1 isoform-specific link to pathogenetic processes in asthma and allergy. (PMID:21707994)
  • we consider NPSR as a promising target for antipsychotic drug development (PMID:22078257)
  • findings represent a first step to decipher NPSR1 locus complexity and its impact on several human conditions NPS antagonists have been recently described, and our results are of potential pharmacogenetic relevance (PMID:22216302)
  • Differential gene-environment effects of the NPSR rs324981 T allele indicate recent life events with respect to anxiety sensitivity. (PMID:22404660)
  • analysis of molecular evolution of the neuropeptide S receptor and cross-species comparison (PMID:22479518)
  • NPSR1 gene is associated with reduced risk of rheumatoid arthritis. (PMID:22548958)
  • results suggest a potential protective function of the NPSR1 rs324981 A/A genotype against pathologically enhanced anxiety that might be explained by stronger reflective prefrontal regulation over the subcortical fear response. (PMID:23103692)
  • NPS is able to stimulate human monocyte chemotaxis and that this effect is entirely due to selective NPSR activation. (PMID:23142110)

Cross-species orthologs

3 orthologs

OrganismSymbolGene ID
danio_reriosi:dkey-78k11.9ENSDARG00000037155
mus_musculusNpsr1ENSMUSG00000043659
rattus_norvegicusNpsr1ENSRNOG00000015863

Protein

Protein identifiers

Neuropeptide S receptor — Q6W5P4 (reviewed: Q6W5P4)

Alternative names: G-protein coupled receptor 154, G-protein coupled receptor PGR14, G-protein coupled receptor for asthma susceptibility

All UniProt accessions (2): Q6W5P4, A0A090N8Z1

UniProt curated annotations — full annotation on UniProt →

Function. G-protein coupled receptor for neuropeptide S (NPS). Receptor activation by NPS initiates a G(q)/GNAQ-dependent phospholipase C-activating signaling pathway, resulting in Ca(2+) mobilization from intracellular stores and increased intracellular Ca(2+) levels. In addition to this pathway, NPS binding to its receptor activates cAMP/PKA signal transduction. Finally, both pathways converge to activate ERK1/ERK2 phosphorylation and signaling cascade. Inhibits cell growth in response to NPS binding.

Subcellular location. Cell membrane Cell membrane Cell membrane Cytoplasm Cytoplasm Cytoplasm Cytoplasm Cytoplasm.

Tissue specificity. Isoform 4 is ubiquitous; it is detected in glandular epithelia of bronchus, stomach, small intestine, colon, uterus, esophagus, spleen, kidney, pancreas, prostate and breast. Isoform 1 is detected in uterus, colon and prostate, and in the smooth muscle cell layer in bronchial and arterial walls (at protein level). Isoform 1 is predominantly expressed in smooth muscle. Isoform 4 is predominantly expressed in epithelial cells. In bronchial biopsies, it is expressed in smooth muscle cells of asthma patients, but not in control patients; whereas in epithelial cells, its expression is consistently stronger in asthma patients.

Polymorphism. Genetic variations in NPSR1 are associated with the familial natural short sleep 3 (FNSS3) phenotype, an autosomal dominant trait [MIM:621336]. Individuals with this trait require less sleep in any 24-hour period than is typical for their age group. Usually, they have a lifelong tendency to sleep only 4 to 6 hours per night, while still feeling well rested.

Miscellaneous. Only isoforms with 7 transmembrane topology (isoform 1, isoform 3 and isoform 4) are transported into the plasma membrane in transfected cells, while the truncated ones retain intracellular compartments.

Similarity. Belongs to the G-protein coupled receptor 1 family. Vasopressin/oxytocin receptor subfamily.

Isoforms (9)

UniProt IDNamesCanonical?
Q6W5P4-11, Isoform Ayes
Q6W5P4-22, Isoform F
Q6W5P4-33, Isoform G
Q6W5P4-44, Isoform B long form
Q6W5P4-55, Isoform B short form
Q6W5P4-66, Isoform D
Q6W5P4-77, Isoform E
Q6W5P4-88
Q6W5P4-99, Isoform C

RefSeq proteins (5): NP_001287862, NP_001287863, NP_001287864, NP_997055, NP_997056 (=MANE)

Domains & families (InterPro)

IDNameType
IPR000276GPCR_RhodpsnFamily
IPR001817Vasoprsn_rcptFamily
IPR017452GPCR_Rhodpsn_7TMDomain
IPR027294NPS_rcptFamily

Pfam: PF00001

UniProt features (41 total): splice variant 12, sequence variant 9, topological domain 8, transmembrane region 7, chain 1, region of interest 1, compositionally biased region 1, glycosylation site 1, disulfide bond 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

ModelpLDDTFraction very-high
AF-Q6W5P4-F181.880.55

Functional residue map

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

Disulfide bonds (1): 121–197

Glycosylation sites (1): 4

Function

Pathways and Gene Ontology

Reactome pathways

3 pathways

IDPathway
R-HSA-375276Peptide ligand-binding receptors
R-HSA-416476G alpha (q) signalling events
R-HSA-418555G alpha (s) signalling events

MSigDB gene sets: 87 (showing top): GOBP_POSITIVE_REGULATION_OF_CALCIUM_ION_TRANSPORT, RNGTGGGC_UNKNOWN, GOBP_EXCRETION, GOBP_DIGESTION, GOBP_BEHAVIOR, GOBP_POSITIVE_REGULATION_OF_MAPK_CASCADE, GOBP_REFLEX, GOBP_POSITIVE_REGULATION_OF_TRANSMEMBRANE_TRANSPORT, GOBP_MONOATOMIC_CATION_TRANSPORT, GOBP_POSITIVE_REGULATION_OF_RELEASE_OF_SEQUESTERED_CALCIUM_ION_INTO_CYTOSOL, REACTOME_PEPTIDE_LIGAND_BINDING_RECEPTORS, GOBP_REGULATION_OF_BEHAVIOR, GOBP_REGULATION_OF_FEEDING_BEHAVIOR, GOBP_NEGATIVE_REGULATION_OF_MULTICELLULAR_ORGANISMAL_PROCESS, GOBP_NEGATIVE_REGULATION_OF_TRANSPORT

GO Biological Process (9): neuropeptide signaling pathway (GO:0007218), eating behavior (GO:0042755), positive regulation of release of sequestered calcium ion into cytosol (GO:0051281), righting reflex (GO:0060013), positive regulation of ERK1 and ERK2 cascade (GO:0070374), negative regulation of eating behavior (GO:1903999), negative regulation of defecation (GO:2000293), signal transduction (GO:0007165), G protein-coupled receptor signaling pathway (GO:0007186)

GO Molecular Function (3): vasopressin receptor activity (GO:0005000), neuropeptide receptor activity (GO:0008188), G protein-coupled receptor activity (GO:0004930)

GO Cellular Component (3): cytoplasm (GO:0005737), plasma membrane (GO:0005886), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-2 pathways:

CategoryPathways
GPCR downstream signalling2
Class A/1 (Rhodopsin-like receptors)1

GO top-level categories

Rollup of top GO terms by namespace:

CategoryTerms
G protein-coupled receptor signaling pathway2
G protein-coupled peptide receptor activity2
cellular anatomical structure2
feeding behavior1
release of sequestered calcium ion into cytosol1
regulation of release of sequestered calcium ion into cytosol1
positive regulation of calcium ion transmembrane transport1
reflex1
positive regulation of MAPK cascade1
ERK1 and ERK2 cascade1
regulation of ERK1 and ERK2 cascade1
eating behavior1
regulation of eating behavior1
negative regulation of feeding behavior1
defecation1
negative regulation of secretion1
negative regulation of digestive system process1
regulation of defecation1
cell communication1
cellular process1
signaling1
regulation of cellular process1
cellular response to stimulus1
G protein-coupled receptor activity1
signal transduction1
neuropeptide signaling pathway1
neuropeptide binding1
transmembrane signaling receptor activity1
intracellular anatomical structure1
membrane1
cell periphery1

Protein interactions and networks

STRING

3591 interactions, top by confidence (×1000):

Protein AProtein BPartner UniProtScore
NPSR1NPSP0C0P6999
NPSR1PHF11Q9UIL8717
NPSR1ORMDL3Q8N138717
NPSR1ADAM33Q9BZ11698
NPSR1DPP10Q8N608664
NPSR1HCRTO43612598
NPSR1OXTP01178567
NPSR1PTGDRQ13258556
NPSR1IRAK3Q9Y616540
NPSR1TAC1P20366522
NPSR1CHI3L1P30923513
NPSR1TNCP24821513
NPSR1HNMTP50135507
NPSR1DPY19L1Q2PZI1503
NPSR1ACANP16112491

IntAct

138 interactions, top by confidence:

ABTypeScore
NPSR1GORASP2psi-mi:“MI:0407”(direct interaction)0.440
NPSR1HTRA3psi-mi:“MI:0407”(direct interaction)0.440
NPSR1RADILpsi-mi:“MI:0407”(direct interaction)0.440
NPSR1HTRA4psi-mi:“MI:0407”(direct interaction)0.440
NPSR1APBA1psi-mi:“MI:0407”(direct interaction)0.440
NPSR1DLG3psi-mi:“MI:0407”(direct interaction)0.440
NPSR1GORASP1psi-mi:“MI:0407”(direct interaction)0.440
NPSR1HTRA1psi-mi:“MI:0407”(direct interaction)0.440
PARD3BNPSR1psi-mi:“MI:0407”(direct interaction)0.440
NPSR1PICK1psi-mi:“MI:0407”(direct interaction)0.440
NPSR1TIAM2psi-mi:“MI:0407”(direct interaction)0.440
NPSR1PARD3psi-mi:“MI:0407”(direct interaction)0.440
NPSR1PTPN3psi-mi:“MI:0407”(direct interaction)0.440
NPSR1APBA3psi-mi:“MI:0407”(direct interaction)0.440
NPSR1PDZD7psi-mi:“MI:0407”(direct interaction)0.440
NPSR1MPP2psi-mi:“MI:0407”(direct interaction)0.440
NPSR1DLG4psi-mi:“MI:0407”(direct interaction)0.440
NPSR1SNX27psi-mi:“MI:0407”(direct interaction)0.440
NPSR1TAX1BP3psi-mi:“MI:0407”(direct interaction)0.440
NPSR1PDZRN4psi-mi:“MI:0407”(direct interaction)0.440
NPSR1LIN7Cpsi-mi:“MI:0407”(direct interaction)0.440
NPSR1SCRIBpsi-mi:“MI:0407”(direct interaction)0.440
NPSR1NHERF4psi-mi:“MI:0407”(direct interaction)0.440
NPSR1SNTG1psi-mi:“MI:0407”(direct interaction)0.440
NPSR1MAGI3psi-mi:“MI:0407”(direct interaction)0.440
NPSR1PDLIM1psi-mi:“MI:0407”(direct interaction)0.440
NPSR1LDB3psi-mi:“MI:0407”(direct interaction)0.440
NPSR1GRIP1psi-mi:“MI:0407”(direct interaction)0.440
NPSR1MAST2psi-mi:“MI:0407”(direct interaction)0.440
NPSR1DLG1psi-mi:“MI:0407”(direct interaction)0.440

BioGRID (35): ATP5A1 (Two-hybrid), CCT2 (Two-hybrid), ENTPD6 (Two-hybrid), GABARAPL2 (Two-hybrid), IPO13 (Two-hybrid), PMPCB (Two-hybrid), PGM2L1 (Two-hybrid), RABGGTB (Two-hybrid), SLC3A2 (Two-hybrid), SLC41A3 (Two-hybrid), TERF2IP (Two-hybrid), MFSD10 (Two-hybrid), TMED10 (Two-hybrid), TMEM101 (Two-hybrid), PRR36 (Two-hybrid)

ESM2 similar proteins: O02667, O13076, O77621, P0C0L6, P0DMS8, P25099, P28190, P28647, P29275, P29276, P35342, P35382, P47745, P47936, P49892, P79945, Q0VC81, Q1LZD0, Q28309, Q32ZE2, Q56H79, Q5QD05, Q5QD06, Q5QD07, Q5QD08, Q5QD10, Q5QD11, Q5QD12, Q5QD13, Q5QD21, Q5RF57, Q5W8W0, Q60612, Q60614, Q61618, Q6W3F4, Q6W5P4, Q7TQP3, Q8BZP8, Q923X5

Diamond homologs: O08858, O42329, O77808, O88721, P08588, P0C0L6, P30518, P30559, P30560, P30938, P31391, P32306, P32307, P35346, P37288, P47901, P48043, P48044, P48974, P56449, P56494, P70536, P79393, P97926, Q00788, Q16581, Q28756, Q56H79, Q5REI5, Q5WA50, Q62463, Q6TAC8, Q6W5P4, Q75W84, Q7YW31, Q868T3, Q8BZP8, Q90252, Q90334, Q90352

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 97 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

PathwayPartnersFoldFDR
Ras activation upon Ca2+ influx through NMDA receptor544.6×5e-06
Unblocking of NMDA receptors, glutamate binding and activation542.5×5e-06
Negative regulation of NMDA receptor-mediated neuronal transmission542.5×5e-06
Long-term potentiation537.2×7e-06
Assembly and cell surface presentation of NMDA receptors935.7×3e-10
Neurexins and neuroligins1030.8×2e-10
Protein-protein interactions at synapses624.9×6e-06
RHOB GTPase cycle512.1×1e-03

GO biological processes:

GO termPartnersFoldFDR
establishment or maintenance of epithelial cell apical/basal polarity1170.2×1e-15
protein localization to synapse650.5×2e-07
receptor clustering748.0×2e-08
regulation of postsynaptic membrane neurotransmitter receptor levels738.1×9e-08
bicellular tight junction assembly518.2×3e-04
protein-containing complex assembly911.3×6e-06
cell-cell adhesion1011.2×2e-06
protein localization to plasma membrane89.6×9e-05

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

ClassificationCount (floor)
Pathogenic1
Likely pathogenic0
Uncertain significance23
Likely benign1
Benign5

Top pathogenic / likely-pathogenic (1)

Variant IDHGVSClassification
4082152NPSR1, TYR206HISPathogenic

SpliceAI

2012 predictions. Top by Δscore:

VariantEffectΔscore
7:34658556:TAAGG:Tdonor_loss1.0000
7:34658557:AAGG:Adonor_loss1.0000
7:34658558:AGG:Adonor_loss1.0000
7:34658560:G:GGdonor_gain1.0000
7:34658560:GTA:Gdonor_loss1.0000
7:34684550:A:AGacceptor_gain1.0000
7:34684551:G:GAacceptor_gain1.0000
7:34684551:GACT:Gacceptor_gain1.0000
7:34684682:CAG:Cdonor_gain1.0000
7:34778461:GA:Gacceptor_gain1.0000
7:34778461:GAT:Gacceptor_gain1.0000
7:34778461:GATT:Gacceptor_gain1.0000
7:34778561:TGCAG:Tdonor_loss1.0000
7:34778562:GCAGG:Gdonor_loss1.0000
7:34778563:CAG:Cdonor_loss1.0000
7:34778565:GGTA:Gdonor_loss1.0000
7:34778567:T:Gdonor_loss1.0000
7:34779629:GTTTG:Gdonor_gain1.0000
7:34811764:CTTTA:Cacceptor_loss1.0000
7:34811765:TTTAG:Tacceptor_loss1.0000
7:34811766:TTAGG:Tacceptor_loss1.0000
7:34811767:TAGG:Tacceptor_loss1.0000
7:34811769:G:Aacceptor_loss1.0000
7:34811769:GGTT:Gacceptor_gain1.0000
7:34811861:G:GTdonor_gain1.0000
7:34827600:CAGGT:Cdonor_loss1.0000
7:34827601:AGGTA:Adonor_loss1.0000
7:34827602:GGTAA:Gdonor_loss1.0000
7:34827603:G:Cdonor_loss1.0000
7:34827604:T:Adonor_loss1.0000

AlphaMissense

2440 scored. Top likely-pathogenic:

VariantProtein changeam_pathogenicity
7:34811812:A:CS143R0.999
7:34811814:C:AS143R0.999
7:34811814:C:GS143R0.999
7:34848500:A:CS288R0.999
7:34848502:T:AS288R0.999
7:34848502:T:GS288R0.999
7:34827475:T:CF185L0.997
7:34827477:T:AF185L0.997
7:34827477:T:GF185L0.997
7:34844964:A:CS276R0.997
7:34844966:C:AS276R0.997
7:34844966:C:GS276R0.997
7:34848485:T:CF283L0.997
7:34848487:C:AF283L0.997
7:34848487:C:GF283L0.997
7:34827433:T:AW171R0.996
7:34827433:T:CW171R0.996
7:34827601:A:CS227R0.996
7:34834384:C:AS227R0.996
7:34834384:C:GS227R0.996
7:34684605:C:AN67K0.994
7:34684605:C:GN67K0.994
7:34827455:C:AS178Y0.994
7:34827455:C:TS178F0.994
7:34827511:T:AC197S0.994
7:34827512:G:CC197S0.994
7:34811785:G:CA134P0.993
7:34811830:G:CA149P0.993
7:34827525:G:CW201C0.993
7:34827525:G:TW201C0.993

dbSNP variants (sampled 300 via entrez): RS1000034503 (7:34733076 T>C), RS1000041024 (7:34686010 A>G), RS1000044990 (7:34692020 A>C), RS1000049450 (7:34726014 G>A,C), RS1000053845 (7:34785636 C>T), RS1000114673 (7:34720297 C>T), RS1000145920 (7:34749358 G>T), RS1000187650 (7:34708293 A>T), RS1000190142 (7:34720602 G>A), RS1000194907 (7:34835591 T>C), RS1000212092 (7:34842304 C>G,T), RS1000223413 (7:34761589 C>T), RS1000226573 (7:34662444 C>T), RS1000234384 (7:34871602 T>C), RS1000240875 (7:34749684 C>A)

Disease associations

OMIM: gene MIM:608595 | disease phenotypes: MIM:608584

GenCC curated gene-disease

DiseaseClassificationInheritance
asthma-related traits, susceptibility to, 2LimitedAutosomal dominant

Mondo (1): asthma-related traits, susceptibility to, 2 (MONDO:0012067)

Orphanet (0):

HPO phenotypes

2 total (2 of 2 shown, HPO-id order):

HPOTerm
HP:0000006Autosomal dominant inheritance
HP:0033063Shortened sleep phase

GWAS associations

5 associations (top):

StudyTraitp-value
GCST005212_25Asthma3.000000e-06
GCST006225_2Anti-chlamydia trachomatis IgG seropositivity3.000000e-07
GCST006616_8Uterine fibroid number (single vs multiple)8.000000e-07
GCST006857_1Leisure-time exercise behaviour2.000000e-09
GCST008369_15Plasma anti-thyroglobulin levels3.000000e-07

EFO canonical traits (3, from GWAS)

EFO IDTrait name
EFO:0009330Chlamydia trachomatis seropositivity
EFO:0009410uterine fibroid measurement
EFO:0000483exercise

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL5162 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

153 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 610,428 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

MoleculeNamePhasePatents
CHEMBL101PHENYLBUTAZONE459,455
CHEMBL1010CEFOTAXIME SODIUM44,928
CHEMBL1017TELMISARTAN427,457
CHEMBL103PROGESTERONE4162,141
CHEMBL104CLOTRIMAZOLE456,325
CHEMBL107COLCHICINE493,932
CHEMBL1072BUMETANIDE422,087
CHEMBL1083993AMIODARONE HYDROCHLORIDE43,265
CHEMBL1086440TRICLABENDAZOLE44,136
CHEMBL1094FELBAMATE410,652
CHEMBL110691CHLORMADINONE ACETATE49,747
CHEMBL1109SULFAPHENAZOLE44,065
CHEMBL1112ARIPIPRAZOLE424,205
CHEMBL1113AMOXAPINE420,128
CHEMBL1116RALOXIFENE HYDROCHLORIDE428,574
CHEMBL1133OXYBUTYNIN CHLORIDE48,751
CHEMBL1138EZETIMIBE429,509
CHEMBL1159PINACIDIL ANHYDROUS46,303
CHEMBL1159650CLOBETASOL PROPIONATE430,865
CHEMBL1200326NICARDIPINE HYDROCHLORIDE43,903
CHEMBL1200348SULCONAZOLE NITRATE4
CHEMBL1200469PROMAZINE HYDROCHLORIDE4
CHEMBL1200479DICYCLOMINE HYDROCHLORIDE4
CHEMBL1200492NEFAZODONE HYDROCHLORIDE4
CHEMBL1200503BROMOCRIPTINE MESYLATE4
CHEMBL1200517DIHYDROERGOTAMINE MESYLATE4
CHEMBL1200560GUANABENZ ACETATE4
CHEMBL1200585OXYMETHOLONE4
CHEMBL1200710CLOMIPRAMINE HYDROCHLORIDE4
CHEMBL1200732AMCINONIDE4

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

GtoPdb / IUPHAR curated pharmacology

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

Target class: gpcr — Neuropeptide S receptor

Most potent curated ligand interactions (15 total), top 15:

LigandActionAffinityParameter
[125I]Tyr10NPS (human)Full agonist9.5pKd
PWT1-NPSFull agonist8.99pEC50
NCGC 84Antagonist8.98pA2
neuropeptide SFull agonist8.5pEC50
SHA 68Antagonist8.1pA2
QA1Antagonist8.0pIC50
neuropeptide SFull agonist7.34pEC50
PI1Antagonist7.3pIC50
[tBu-D-Gly5]NPSAntagonist7.1pA2
SHA 68RAntagonist7.06pIC50
[D-Val5]NPSAntagonist6.5pKB
[D-Cys(tBu)5]NPSAntagonist6.4pA2
SFKN-NH2Full agonist6.0pEC50
[Cy5-Lys19]NPSFull agonist5.82pEC50

ChEMBL bioactivities

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

pChemblTypeValueUnitMolecule
9.17EC500.6761nMNEUROPEPTIDE S
9.07EC500.8511nMNEUROPEPTIDE S
9.02IC500.96nMCHEMBL1474387
9.00Potency1nMCHEMBL1978331
8.92IC501.2nMCHEMBL1210313
8.89IC501.3nMCHEMBL1474387
8.89IC501.3nMCHEMBL1210313
8.70IC501.995nMCHEMBL469696
8.70Potency2nMCHEMBL1541027
8.66IC502.2nMCHEMBL3086823
8.49IC503.2nMCHEMBL3086836
8.49Potency3.2nMCHEMBL1493765
8.49Potency3.2nMCHEMBL1339217
8.49Potency3.2nMCHEMBL1517046
8.49Potency3.2nMCHEMBL1322287
8.49Potency3.2nMCHEMBL1368940
8.49Potency3.2nMCHEMBL1471358
8.47IC503.4nMCHEMBL3086821
8.47IC503.4nMCHEMBL3086837
8.46IC503.5nMCHEMBL1474387
8.40Potency4nMCHEMBL3192616
8.40Potency4nMCHEMBL1302894
8.40Potency4nMCHEMBL1527869
8.40Potency4nMCHEMBL1400395
8.40Potency4nMCHEMBL1460146
8.40Potency4nMCHEMBL1325875
8.40Potency4nMCHEMBL118009
8.40Potency4nMCHEMBL1444688
8.40Potency4nMCHEMBL1415524
8.40Potency4nMCHEMBL1565191
8.40Potency4nMCHEMBL1511656
8.40Potency4nMCHEMBL3199798
8.40Potency4nMCHEMBL1425537
8.40Potency4nMCHEMBL1418483
8.40Potency4nMCHEMBL1346371
8.40Potency4nMCHEMBL1484736
8.40Potency4nMCHEMBL1329723
8.40Potency4nMCHEMBL1359353
8.40Potency4nMCHEMBL1340021
8.40Potency4nMCHEMBL1322060
8.40Potency4nMCHEMBL1343825
8.40Potency4nMCHEMBL1458907
8.40Potency4nMCHEMBL1599780
8.40Potency4nMCHEMBL1347258
8.40Potency4nMCHEMBL1544119
8.40Potency4nMCHEMBL1351072
8.40Potency4nMCHEMBL1380530
8.40Potency4nMCHEMBL1344183
8.40Potency4nMCHEMBL1449173
8.40Potency4nMCHEMBL1557073

PubChem BioAssay actives

136 with measured affinity, of 203 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.

CompoundAssayTypeValueUnit
[2-methyl-1-(4-phenylbutyl)imidazo[1,2-a]pyridin-4-ium-3-yl]-diphenyl-sulfanylidene-lambda5-phosphane bromide1055407: Antagonist activity at neuropeptide S receptor (unknown origin) expressed in CHO cells assessed as inhibition of NPS-induced calcium mobilization after 10 mins by fluorescence assayic500.0005uM
[2-methyl-1-(3-phenylpropyl)imidazo[1,2-a]pyridin-4-ium-3-yl]-diphenyl-sulfanylidene-lambda5-phosphane;2,2,2-trifluoroacetate1055406: Antagonist activity at neuropeptide S receptor (unknown origin) expressed in CHO cells assessed as inhibition of NPS-induced ERK activation after 20 mins by HTRF assayic500.0005uM
(2S)-2-[[(2S)-6-amino-2-[[(2S)-2-[[(2S)-2-[[(2S)-5-amino-2-[[(2S)-2-[[(2S)-2-[[(2S,3R)-2-[[(2S)-6-amino-2-[[(2S)-6-amino-2-[[(2S)-2-[[2-[[(2S,3R)-2-[[2-[[(2S)-2-[[2-[[(2S)-4-amino-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-amino-3-hydroxypropanoyl]amino]-3-phenylpropanoyl]amino]-5-carbamimidamidopentanoyl]amino]-4-oxobutanoyl]amino]acetyl]amino]-3-methylbutanoyl]amino]acetyl]amino]-3-hydroxybutanoyl]amino]acetyl]amino]-4-methylsulfanylbutanoyl]amino]hexanoyl]amino]hexanoyl]amino]-3-hydroxybutanoyl]amino]-3-hydroxypropanoyl]amino]-3-phenylpropanoyl]amino]-5-oxopentanoyl]amino]-5-carbamimidamidopentanoyl]amino]propanoyl]amino]hexanoyl]amino]-3-hydroxypropanoic acid593084: Agonist activity at human NPSR Ile107 expressed in HEK293 cells assessed as induction of calcium mobilization after 30 minsec500.0007uM
[2-methyl-1-[(E)-3-phenylprop-2-enyl]imidazo[1,2-a]pyridin-4-ium-3-yl]-diphenyl-sulfanylidene-lambda5-phosphane bromide1055407: Antagonist activity at neuropeptide S receptor (unknown origin) expressed in CHO cells assessed as inhibition of NPS-induced calcium mobilization after 10 mins by fluorescence assayic500.0010uM
N-(3-methyl-1-morpholin-4-ylpentan-3-yl)-N-[(1-methyl-2-oxoquinolin-3-yl)methyl]cyclohexanecarboxamide1055408: Antagonist activity at neuropeptide S receptor (unknown origin) expressed in CHO cells assessed as cAMP level after 30 mins by phosphate-buffered saline assayic500.0012uM
N-benzyl-3-oxo-1,1-diphenyl-5,6,8,8a-tetrahydro-[1,3]oxazolo[3,4-a]pyrazine-7-carboxamide539478: Antagonist activity at human recombinant GPR154 receptor expressed in HEK293 cells assessed as inhibition of neuropeptide S-induced increase of intracellular calcium level by FLIPR assayic500.0020uM
[1-[(E)-3-(4-chlorophenyl)prop-2-enyl]-2-methylimidazo[1,2-a]pyridin-4-ium-3-yl]-diphenyl-sulfanylidene-lambda5-phosphane;2,2,2-trifluoroacetate1055407: Antagonist activity at neuropeptide S receptor (unknown origin) expressed in CHO cells assessed as inhibition of NPS-induced calcium mobilization after 10 mins by fluorescence assayic500.0022uM
[1-[(E)-3-(3-methoxyphenyl)prop-2-enyl]-2-methylimidazo[1,2-a]pyridin-4-ium-3-yl]-diphenyl-sulfanylidene-lambda5-phosphane;2,2,2-trifluoroacetate1055407: Antagonist activity at neuropeptide S receptor (unknown origin) expressed in CHO cells assessed as inhibition of NPS-induced calcium mobilization after 10 mins by fluorescence assayic500.0032uM
[1-[(E)-3-(2-chlorophenyl)prop-2-enyl]-2-methylimidazo[1,2-a]pyridin-4-ium-3-yl]-diphenyl-sulfanylidene-lambda5-phosphane;2,2,2-trifluoroacetate1055407: Antagonist activity at neuropeptide S receptor (unknown origin) expressed in CHO cells assessed as inhibition of NPS-induced calcium mobilization after 10 mins by fluorescence assayic500.0034uM
[1-[(E)-3-(4-fluorophenyl)prop-2-enyl]-2-methylimidazo[1,2-a]pyridin-4-ium-3-yl]-diphenyl-sulfanylidene-lambda5-phosphane;2,2,2-trifluoroacetate1055407: Antagonist activity at neuropeptide S receptor (unknown origin) expressed in CHO cells assessed as inhibition of NPS-induced calcium mobilization after 10 mins by fluorescence assayic500.0034uM
[2-methyl-1-[(E)-3-[4-(trifluoromethyl)phenyl]prop-2-enyl]imidazo[1,2-a]pyridin-4-ium-3-yl]-diphenyl-sulfanylidene-lambda5-phosphane;2,2,2-trifluoroacetate1055407: Antagonist activity at neuropeptide S receptor (unknown origin) expressed in CHO cells assessed as inhibition of NPS-induced calcium mobilization after 10 mins by fluorescence assayic500.0045uM
N-[(4-fluorophenyl)methyl]-3-oxo-1,1-diphenyl-5,6,8,8a-tetrahydro-[1,3]oxazolo[3,4-a]pyrazine-7-carboxamide1055408: Antagonist activity at neuropeptide S receptor (unknown origin) expressed in CHO cells assessed as cAMP level after 30 mins by phosphate-buffered saline assayic500.0053uM
[1-[(E)-3-(4-bromophenyl)prop-2-enyl]-2-methylimidazo[1,2-a]pyridin-4-ium-3-yl]-diphenyl-sulfanylidene-lambda5-phosphane;2,2,2-trifluoroacetate1055407: Antagonist activity at neuropeptide S receptor (unknown origin) expressed in CHO cells assessed as inhibition of NPS-induced calcium mobilization after 10 mins by fluorescence assayic500.0057uM
[2-methyl-1-(5-phenylpentyl)imidazo[1,2-a]pyridin-4-ium-3-yl]-diphenyl-sulfanylidene-lambda5-phosphane;2,2,2-trifluoroacetate1055406: Antagonist activity at neuropeptide S receptor (unknown origin) expressed in CHO cells assessed as inhibition of NPS-induced ERK activation after 20 mins by HTRF assayic500.0062uM
N-[(1-methyl-2-oxoquinolin-3-yl)methyl]-N-(3-methyl-1-piperidin-1-ylpentan-3-yl)cyclohexanecarboxamide494450: Antagonist activity at human recombinant NPS receptor expressed in CHOK1 cells assessed as inhibition of NPS-induced calcium mobilization by FLIPR assayic500.0070uM
[2-methyl-1-[(E)-3-(4-methylphenyl)prop-2-enyl]imidazo[1,2-a]pyridin-4-ium-3-yl]-diphenyl-sulfanylidene-lambda5-phosphane bromide1055407: Antagonist activity at neuropeptide S receptor (unknown origin) expressed in CHO cells assessed as inhibition of NPS-induced calcium mobilization after 10 mins by fluorescence assayic500.0090uM
(2-methylimidazo[1,2-a]pyridin-3-yl)-diphenyl-sulfanylidene-lambda5-phosphane1055406: Antagonist activity at neuropeptide S receptor (unknown origin) expressed in CHO cells assessed as inhibition of NPS-induced ERK activation after 20 mins by HTRF assayic500.0091uM
[1-[(E)-3-(3-chlorophenyl)prop-2-enyl]-2-methylimidazo[1,2-a]pyridin-4-ium-3-yl]-diphenyl-sulfanylidene-lambda5-phosphane;2,2,2-trifluoroacetate1055407: Antagonist activity at neuropeptide S receptor (unknown origin) expressed in CHO cells assessed as inhibition of NPS-induced calcium mobilization after 10 mins by fluorescence assayic500.0092uM
5-phenyl-2-[2-(piperidine-1-carbonyl)phenyl]-3H-pyrrolo[1,2-c]imidazol-1-one1055416: Antagonist activity at neuropeptide S receptor (unknown origin) assessed as intracellular calcium level by cell based assayic500.0100uM
1-(3-diphenylphosphinothioyl-2-methylimidazo[1,2-a]pyridin-4-ium-1-yl)-2-phenylethanone bromide1055406: Antagonist activity at neuropeptide S receptor (unknown origin) expressed in CHO cells assessed as inhibition of NPS-induced ERK activation after 20 mins by HTRF assayic500.0130uM
N-[1-(4-fluoropiperidin-1-yl)-3-methylpentan-3-yl]-N-[(1-methyl-2-oxoquinolin-3-yl)methyl]cyclohexanecarboxamide494450: Antagonist activity at human recombinant NPS receptor expressed in CHOK1 cells assessed as inhibition of NPS-induced calcium mobilization by FLIPR assayic500.0140uM
[2-methyl-1-(2-phenylethyl)imidazo[1,2-a]pyridin-4-ium-3-yl]-diphenyl-sulfanylidene-lambda5-phosphane bromide1055406: Antagonist activity at neuropeptide S receptor (unknown origin) expressed in CHO cells assessed as inhibition of NPS-induced ERK activation after 20 mins by HTRF assayic500.0160uM
(1-benzyl-2-methylimidazo[1,2-a]pyridin-4-ium-3-yl)-diphenyl-sulfanylidene-lambda5-phosphane;2,2,2-trifluoroacetate1055406: Antagonist activity at neuropeptide S receptor (unknown origin) expressed in CHO cells assessed as inhibition of NPS-induced ERK activation after 20 mins by HTRF assayic500.0160uM
N-[(1-methyl-2-oxoquinolin-3-yl)methyl]-N-[[1-(4-methylpiperazin-1-yl)cyclohexyl]methyl]cyclohexanecarboxamide494450: Antagonist activity at human recombinant NPS receptor expressed in CHOK1 cells assessed as inhibition of NPS-induced calcium mobilization by FLIPR assayic500.0180uM
6-phenyl-N-[2-(piperidine-1-carbonyl)phenyl]pyridine-2-carboxamide539478: Antagonist activity at human recombinant GPR154 receptor expressed in HEK293 cells assessed as inhibition of neuropeptide S-induced increase of intracellular calcium level by FLIPR assayic500.0199uM
N-[1-(4,4-difluoropiperidin-1-yl)-3-methylpentan-3-yl]-N-[(1-methyl-2-oxoquinolin-3-yl)methyl]cyclohexanecarboxamide494450: Antagonist activity at human recombinant NPS receptor expressed in CHOK1 cells assessed as inhibition of NPS-induced calcium mobilization by FLIPR assayic500.0220uM
[1-[(E)-3-(3-bromophenyl)prop-2-enyl]-2-methylimidazo[1,2-a]pyridin-4-ium-3-yl]-diphenyl-sulfanylidene-lambda5-phosphane;2,2,2-trifluoroacetate1055407: Antagonist activity at neuropeptide S receptor (unknown origin) expressed in CHO cells assessed as inhibition of NPS-induced calcium mobilization after 10 mins by fluorescence assayic500.0230uM
2-(4-benzylpiperazin-1-yl)-2-phenylindene-1,3-dione1055416: Antagonist activity at neuropeptide S receptor (unknown origin) assessed as intracellular calcium level by cell based assayic500.0270uM
(1,2-dimethylimidazo[1,2-a]pyridin-4-ium-3-yl)-diphenyl-sulfanylidene-lambda5-phosphane iodide1055406: Antagonist activity at neuropeptide S receptor (unknown origin) expressed in CHO cells assessed as inhibition of NPS-induced ERK activation after 20 mins by HTRF assayic500.0300uM
N-[(1-methyl-2-oxoquinolin-3-yl)methyl]-N-(2-methyl-4-piperidin-1-ylbutan-2-yl)cyclohexanecarboxamide494450: Antagonist activity at human recombinant NPS receptor expressed in CHOK1 cells assessed as inhibition of NPS-induced calcium mobilization by FLIPR assayic500.0310uM
5-phenyl-N-[2-(piperidine-1-carbonyl)phenyl]furan-2-carboxamide539478: Antagonist activity at human recombinant GPR154 receptor expressed in HEK293 cells assessed as inhibition of neuropeptide S-induced increase of intracellular calcium level by FLIPR assayic500.0316uM
3-[5-(4-chlorophenyl)-6-methoxyimidazo[1,2-b]isoindol-5-yl]-N,N-diethylpropanamide1055416: Antagonist activity at neuropeptide S receptor (unknown origin) assessed as intracellular calcium level by cell based assayic500.0430uM
[1-[(E)-3-(3-bromo-4-fluorophenyl)prop-2-enyl]-2-methylimidazo[1,2-a]pyridin-4-ium-3-yl]-diphenyl-sulfanylidene-lambda5-phosphane;2,2,2-trifluoroacetate1055407: Antagonist activity at neuropeptide S receptor (unknown origin) expressed in CHO cells assessed as inhibition of NPS-induced calcium mobilization after 10 mins by fluorescence assayic500.0450uM
5-(4-chlorophenyl)-6-methoxy-5-(oxan-4-ylmethyl)imidazo[2,1-a]isoindole605364: Antagonist activity at human recombinant NPS receptor expressed in CHOK1 cells assessed as inhibition of NPS-induced calcium mobilization by FLIPR assayic500.0460uM
3-[5-(4-chlorophenyl)-7-methoxyimidazo[1,2-b]isoindol-5-yl]-1-[(2S,5R)-2,5-dimethylpyrrolidin-1-yl]propan-1-one605364: Antagonist activity at human recombinant NPS receptor expressed in CHOK1 cells assessed as inhibition of NPS-induced calcium mobilization by FLIPR assayic500.0500uM
[2-methyl-1-[(E)-3-naphthalen-2-ylprop-2-enyl]imidazo[1,2-a]pyridin-4-ium-3-yl]-diphenyl-sulfanylidene-lambda5-phosphane bromide1055407: Antagonist activity at neuropeptide S receptor (unknown origin) expressed in CHO cells assessed as inhibition of NPS-induced calcium mobilization after 10 mins by fluorescence assayic500.0640uM
5-(4-chlorophenyl)-7-methoxy-5-(oxan-4-ylmethyl)imidazo[2,1-a]isoindole605364: Antagonist activity at human recombinant NPS receptor expressed in CHOK1 cells assessed as inhibition of NPS-induced calcium mobilization by FLIPR assayic500.0820uM
3-[5-(4-chlorophenyl)imidazo[1,2-b]isoindol-5-yl]-N,N-diethylpropanamide605364: Antagonist activity at human recombinant NPS receptor expressed in CHOK1 cells assessed as inhibition of NPS-induced calcium mobilization by FLIPR assayic500.0900uM
3-[5-(4-chlorophenyl)imidazo[1,2-b]isoindol-5-yl]-1-[(2S,5R)-2,5-dimethylpyrrolidin-1-yl]propan-1-one605364: Antagonist activity at human recombinant NPS receptor expressed in CHOK1 cells assessed as inhibition of NPS-induced calcium mobilization by FLIPR assayic500.0920uM
5-(4-bromophenyl)-5-(oxan-4-ylmethyl)imidazo[2,1-a]isoindole605364: Antagonist activity at human recombinant NPS receptor expressed in CHOK1 cells assessed as inhibition of NPS-induced calcium mobilization by FLIPR assayic500.0920uM
1-(8-azabicyclo[3.2.1]octan-8-yl)-3-[5-(4-chlorophenyl)imidazo[1,2-b]isoindol-5-yl]propan-1-one605364: Antagonist activity at human recombinant NPS receptor expressed in CHOK1 cells assessed as inhibition of NPS-induced calcium mobilization by FLIPR assayic500.0950uM
3-[5-(4-chlorophenyl)imidazo[1,2-b]isoindol-5-yl]-N,N-di(propan-2-yl)propanamide605364: Antagonist activity at human recombinant NPS receptor expressed in CHOK1 cells assessed as inhibition of NPS-induced calcium mobilization by FLIPR assayic500.0960uM
N-(3-ethyl-1-morpholin-4-ylpentan-3-yl)-N-[(1-methyl-2-oxoquinolin-3-yl)methyl]cyclohexanecarboxamide494450: Antagonist activity at human recombinant NPS receptor expressed in CHOK1 cells assessed as inhibition of NPS-induced calcium mobilization by FLIPR assayic500.1030uM
4-[5-(cyclohexylmethyl)imidazo[1,2-b]isoindol-5-yl]benzonitrile605364: Antagonist activity at human recombinant NPS receptor expressed in CHOK1 cells assessed as inhibition of NPS-induced calcium mobilization by FLIPR assayic500.1140uM
3-[5-(4-chlorophenyl)imidazo[1,2-b]isoindol-5-yl]-1-[4-(1-pyrrolidin-1-ylethyl)piperidin-1-yl]propan-1-one605364: Antagonist activity at human recombinant NPS receptor expressed in CHOK1 cells assessed as inhibition of NPS-induced calcium mobilization by FLIPR assayic500.1260uM
3-[5-(4-chlorophenyl)imidazo[1,2-b]isoindol-5-yl]-1-(2-ethylpiperidin-1-yl)propan-1-one605364: Antagonist activity at human recombinant NPS receptor expressed in CHOK1 cells assessed as inhibition of NPS-induced calcium mobilization by FLIPR assayic500.1310uM
5-(4-chlorophenyl)-5-(oxan-4-ylmethyl)imidazo[2,1-a]isoindole605364: Antagonist activity at human recombinant NPS receptor expressed in CHOK1 cells assessed as inhibition of NPS-induced calcium mobilization by FLIPR assayic500.1340uM
3-[5-(4-chlorophenyl)imidazo[1,2-b]isoindol-5-yl]-N-ethyl-N-propan-2-ylpropanamide605364: Antagonist activity at human recombinant NPS receptor expressed in CHOK1 cells assessed as inhibition of NPS-induced calcium mobilization by FLIPR assayic500.1380uM
N-(2-methyl-4-morpholin-4-ylbutan-2-yl)-N-[(1-methyl-2-oxoquinolin-3-yl)methyl]cyclohexanecarboxamide494450: Antagonist activity at human recombinant NPS receptor expressed in CHOK1 cells assessed as inhibition of NPS-induced calcium mobilization by FLIPR assayic500.1440uM
4-[5-(cyclopentylmethyl)imidazo[1,2-b]isoindol-5-yl]benzonitrile605364: Antagonist activity at human recombinant NPS receptor expressed in CHOK1 cells assessed as inhibition of NPS-induced calcium mobilization by FLIPR assayic500.1450uM

CTD chemical–gene interactions

9 total (human), top 9 by PubMed support.

ChemicalActions (top 5)PubMed papers
bisphenol Adecreases methylation1
3-oxo-1,1-diphenyltetrahydrooxazolo(3,4-a)pyrazine-7-carboxylic acid 4-fluorobenzylamideaffects binding, decreases activity1
Amiodaroneincreases expression1
Atrazineincreases expression1
Benzo(a)pyrenedecreases methylation1
Cadmiumdecreases expression1
Valproic Aciddecreases methylation1
Aflatoxin B1increases methylation1
Permethrinincreases expression1

ChEMBL screening assays

34 unique, capped per target: 25 functional, 9 binding

Representative assays (with source publication via chembl_document):

Assay IDTypeDescriptionSource paper
CHEMBL1001576FunctionalAntagonist activity at human NPSR expressed in HEK293 cells assessed as inhibition of NPS-induced increase in intracellular calcium mobilizationFurther studies at neuropeptide s position 5: discovery of novel neuropeptide S receptor antagonists. — J Med Chem
CHEMBL3088792BindingAntagonist activity at neuropeptide S receptor (unknown origin) expressed in CHO cells assessed as inhibition of NPS-induced ERK activation at 50 uM after 20 mins by HTRF assay relative to controlStructure-activity relationship of imidazopyridinium analogues as antagonists of neuropeptide s receptor. — J Med Chem

Cellosaurus cell lines

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

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

CellosaurusNameCategorySex
CVCL_H477CHO-K1/NPS1a/Galpha15Spontaneously immortalized cell lineFemale
CVCL_H478CHO-K1/NPS1b/Galpha15Spontaneously immortalized cell lineFemale
CVCL_LA91PathHunter U2OS NPSR1 beta-arrestinCancer cell lineFemale
CVCL_LB58GeneBLAzer NPSR1-B-NFAT-bla CHO-K1Spontaneously immortalized cell lineFemale
CVCL_ZK61GeneBLAzer NPSR1-A-NFAT-bla CHO-K1Spontaneously immortalized cell lineFemale

Clinical trials (associated diseases)

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

About this page

Generated deterministically by Sugi Atlas from primary biomedical databases via BioBTree. Every record on this page traces to a primary source.

Generated
Atlas version
v1.1.2
BioBTree
v2.0.2

Sources 80

This page pulls from 80 datasets indexed by BioBTree:

alphafoldalphamissenseantibodybgeebgee_evidencebindingdbbiogrid_interactionbrendabrenda_kineticsccdscellosauruschembl_activitychembl_assaychembl_documentchembl_moleculechembl_targetciviccivic_evidenceclingen_dosageclingen_gene_validityclinical_trialsclinvarcollectrictd_gene_interactiondbsnpdepmapdiamond_similarityefoensemblentrezesm2_similarityexonfantom5_genefantom5_promotergenccgenerifgogoparentgtopdbgtopdb_interactiongwasgwas_studyhgnchpointactinterprointogenjasparmeshmimmirdbmondomsigdborphanetorthologparalogpatent_compoundpdbpfampharmgkb_clinicalpharmgkb_genepharmgkb_guidelinepharmgkb_variantpubchempubchem_activitypubchem_assaypubmedreactomereactomeparentrefseqrhearnacentralscxa_expressionscxa_gene_experimentsignorspliceaistring_interactiontranscriptufeatureuniprot