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MTNR1B

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Summary

MTNR1B (melatonin receptor 1B, HGNC:7464) is a protein-coding gene on chromosome 11q14.3, encoding Melatonin receptor type 1B (P49286). High affinity receptor for melatonin.

This gene encodes one of two high affinity forms of a receptor for melatonin, the primary hormone secreted by the pineal gland. This gene product is an integral membrane protein that is a G-protein coupled, 7-transmembrane receptor. It is found primarily in the retina and brain although this detection requires RT-PCR. It is thought to participate in light-dependent functions in the retina and may be involved in the neurobiological effects of melatonin.

Source: NCBI Gene 4544 — RefSeq curated summary.

At a glance

  • GWAS associations: 69
  • Clinical variants (ClinVar): 81 total
  • Phenotypes (HPO): 5
  • Druggable target: yes — 7 molecules with ChEMBL bioactivity
  • MANE Select transcript: NM_005959

Identifiers

Gene identifiers

FieldValue
HGNC IDHGNC:7464
Approved symbolMTNR1B
Namemelatonin receptor 1B
Location11q14.3
Locus typegene with protein product
StatusApproved
Ensembl geneENSG00000134640
Ensembl biotypeprotein_coding
OMIM600804
Entrez4544

Gene structure

Transcript identifiers

Ensembl transcripts: 3 — 2 protein_coding, 1 nonsense_mediated_decay

ENST00000257068, ENST00000528076, ENST00000532482

RefSeq mRNA: 1 — MANE Select: NM_005959 NM_005959

CCDS: CCDS8290

Canonical transcript exons

ENST00000257068 — 2 exons

ExonStartEnd
ENSE000009893869298144792982782
ENSE000010921349296965192969948

Expression profiles

Bgee: expression breadth broad, 46 present calls, max score 68.93.

Top tissues by expression

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

TissueAnatomy IDExpression scoreQuality
primordial germ cell in gonadCL:0000670 ∩ UBERON:000099168.93gold quality
islet of LangerhansUBERON:000000660.88gold quality
deltoidUBERON:000147658.15gold quality
oocyteCL:000002357.36gold quality
ponsUBERON:000098855.70gold quality
biceps brachiiUBERON:000150755.63gold quality
lateral nuclear group of thalamusUBERON:000273654.05gold quality
middle temporal gyrusUBERON:000277152.55gold quality
skeletal muscle tissue of biceps brachiiUBERON:000450252.11gold quality
quadriceps femorisUBERON:000137751.84gold quality
parotid glandUBERON:000183151.82gold quality
vastus lateralisUBERON:000137951.79gold quality
nasal cavity epitheliumUBERON:000538451.07gold quality
Brodmann (1909) area 23UBERON:001355450.11gold quality
substantia nigra pars compactaUBERON:000196550.02gold quality
medial globus pallidusUBERON:000247749.36gold quality
blood vessel layerUBERON:000479749.29gold quality
choroid plexus epitheliumUBERON:000391148.89gold quality
nucleus accumbensUBERON:000188248.67gold quality
lateral globus pallidusUBERON:000247648.63gold quality
globus pallidusUBERON:000187548.62gold quality
substantia nigra pars reticulataUBERON:000196647.90gold quality
Brodmann (1909) area 46UBERON:000648347.14gold quality
periodontal ligamentUBERON:000826647.14gold quality
renal glomerulusUBERON:000007446.86gold quality
metanephric glomerulusUBERON:000473646.77gold quality
nephron tubuleUBERON:000123146.71gold quality
skeletal muscle tissueUBERON:000113446.52gold quality
dorsal motor nucleus of vagus nerveUBERON:000287045.35gold quality
inferior olivary complexUBERON:000212745.14gold quality

Single-cell (SCXA)

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

ExperimentMarker?Max mean expression
E-ANND-3no1.63

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

16 targeting MTNR1B, 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-185-3P99.9567.011743
HSA-MIR-4758-3P99.1263.96869
HSA-MIR-670-3P99.0368.882404
HSA-MIR-6770-5P98.9766.761853
HSA-MIR-6829-5P98.8665.121480
HSA-MIR-6887-5P98.5668.491295
HSA-MIR-6795-5P98.5268.511277
HSA-MIR-5008-5P98.4265.871019
HSA-MIR-6784-3P98.3964.88662
HSA-MIR-6841-3P98.0866.54604
HSA-MIR-6862-3P97.9264.86531
HSA-MIR-474197.6964.14883
HSA-MIR-467597.6964.82774
HSA-MIR-191397.0766.201417
HSA-MIR-3189-3P96.8066.34896
HSA-MIR-7108-5P96.4266.17598

Literature-anchored findings (GeneRIF, showing 40)

  • Monitoring of ligand-independent dimerization and ligand-induced conformational changes of melatonin receptors in living cells by bioluminescence resonance energy transfer (melatonin receptor 2) (PMID:11940583)
  • Melatonin inhibited ERalpha mRNA expression & enhanced induction of pancreatic spasmolytic polypeptide in MT(1)-transfected breast cancer cells, suggesting a role for the MT(1) receptor in melatonin-regulated growth-suppression & gene-modulation. (PMID:12088876)
  • Expression in cultured skin cells. (PMID:12767050)
  • residues N268 and A275 in TM6 as well as residues V291 and L295 in TM7 are essential for 2-iodomelatonin binding to the MT2 receptor (PMID:15913560)
  • melatonin receptor type 1B polymorphism is associated with the presence of rheumatoid factor in Korean rheumatoid arthritis (PMID:16098099)
  • MT(2) was localized to ganglion and bipolar cells in the inner nuclear layer, and to the inner segments of the photoreceptor cells, cellular processes in inner and outer plexiform layers . In AD patients intensity of MT(2)-staining was decreased. (PMID:17316165)
  • Polymorphisms of the promoter of MTNR1B gene were associated with AIS, but not with the curve severity in AIS patients. This suggested that MTNR1B was an AIS predisposition gene. (PMID:17632395)
  • Truncation of the C-terminal tail of both receptors (MT(1)Y7.64 and MT(2)Y7.64) inhibited internalization as well as the cAMP response, suggesting the importance of the C-terminal tail in these receptor functions. (PMID:18341518)
  • MT2 receptor is involved in mediating the insulin- and cGMP-inhibiting action of melatonin in panreatic beta cells. (PMID:18363673)
  • role of proline residues in structure & function of the MT2 receptor; results indicate residues P174, P212 & P266 are important for ligand binding and/or signaling of the MT2 receptor (PMID:18544139)
  • Melatonin synergizes with oxytocin to promote myometrial cell contractions in vitro, which in vivo would promote coordinated and forceful contractions of the late term pregnant uterus necessary for parturition. (PMID:19001515)
  • Variants in the gene encoding melatonin receptor 1B (MTNR1B) were consistently associated with fasting glucose across all ten studies. (PMID:19060907)
  • These data suggest that the circulating hormone melatonin, which is predominantly released from the pineal gland in the brain, is involved in the pathogenesis of type 2 diabetes. (PMID:19060908)
  • These data suggest a possible link between circadian rhythm regulation and glucose homeostasis through the melatonin signaling pathway. (PMID:19060909)
  • Common genetic variation within MTNR1B determines glucose-stimulated insulin secretion and plasma glucose concentrations. (PMID:19088850)
  • A common variant in the MTNR1B gene is associated with an increased risk of type 2 diabetes and increased fasting plasma glucose in Han Chinese. (PMID:19241057)
  • G-allele increases risk of type 2 diabetes and associates with estimates of beta-cell dysfunction and hepatic insulin resistance. (PMID:19324940)
  • Genetic variation of MTNR1B is associated with defective early insulin response and decreased beta cell glucose sensitivity. (PMID:19455304)
  • Variations and single-nucleotide polymorphisms are associated in variations in fasting plasma glucose and an increased risk of type 2 diabetes. (PMID:19533084)
  • Genetic variation in this protein may contribute to abnormal glucose metabolism and related metabolic disturbances among Indian Asians. (PMID:19651812)
  • Fasting glucose association at MTNR1b is replicable across ethnic groups, although ethnic diversity in the pattern and strength of linkage disequilibrium exists. (PMID:19937311)
  • MT(2) melatonin receptor may have undergone a selective pressure in response to global variation in sunshine duration. selection of rs4753426C allele would insure that carriers adapted to local daily and seasonal rhythms more quickly (PMID:20050988)
  • The results demonstrate a down-regulation of melatonin receptors in regions affected by Parkinson disease, suggesting their possible involvement in the disease process. (PMID:20110911)
  • MTNR1B variations associate with with increased body mass and decreased fasting blood glucose in Europeans. (PMID:20200315)
  • MTNR1B contributes to the phenotypic expression of polycystic ovary syndrome. (PMID:20207350)
  • A common variant in MTNR1B was associated with fasting glucose, HbA1C and HOMA-B but not with sleep status in Chinese Hans from Shanghai. (PMID:20398260)
  • The common variant in MTNR1B confers the risk of Type 2 diabetes and modulates FPG in both the Han Chinese and European populations. (PMID:20536959)
  • variants in MTNR1B confer pancreatic beta-cell dysfunction (PMID:20597807)
  • Common variants of MTNR1B, G6PC2 and GCK are associated with elevated FPG and impaired insulin secretion, both individually and jointly, suggesting that these risk alleles may precipitate or perpetuate hyperglycemia in predisposed individuals. (PMID:20628598)
  • Study identified six non-synonymous mutations for MTNR1A and ten for MTNR1B in autism spectrum disorders patients . The majority of these variations altered receptor function. (PMID:20657642)
  • Study showed that SNPs from GCK, G6PC2 and MTNR1B modulated the fasting glucose levels in the normoglycaemic population while SNPs from G6PC2 and GCKR was associated with type 2 diabetes. (PMID:20668700)
  • Melatonin has a modulating effect on dopaminergic neurotransmission in the brain. Read More: http://informahealthcare.com/doi/full/10.3109/15622975.2010.496870 (PMID:20726823)
  • No significant differences were found in the hMel-1B and RORa receptors in patients with adolescent idiopathic scoliosis compared with controls (PMID:20733416)
  • SNPs within the MTNR1B gene are associated with polycystic ovary syndrome in Han Chinese women. (PMID:20959387)
  • This is the first single study, replicating the association between the MTNR1B locus and diabetes-related traits in overweight and obese children and adolescents. (PMID:21059861)
  • Data suggest that the genetic effect of promoter polymorphisms of BMP4, IL6, leptin, MMP3, and MTNR1B can be synergistic for susceptibility to AIS. (PMID:21228692)
  • we concluded that MTNR1B SNP is not associated with either adolescent idiopathic scoliosis predisposition or curve severity in Japanese. (PMID:21308753)
  • The results of this study suggested that the Single nucleotide polymorphisms MT(2) receptor gene influence the risk of recurrent depressive disorder. (PMID:21353709)
  • The G-allele of rs10830693 in the MTNR1B gene was significantly related to glucose levels, while an impact of this genetic variant on the changes in glucose metabolism in children participating in a lifestyle intervention was not observable. (PMID:21366812)
  • There is no effect by the common gene variant rs10830963 of the melatonin receptor 1B on the association between sleep disturbances and type 2 diabetes. (PMID:21380592)

Cross-species orthologs

2 orthologs

OrganismSymbolGene ID
mus_musculusMtnr1bENSMUSG00000050901
rattus_norvegicusMtnr1bENSRNOG00000008972

Paralogs (33): TACR2 (ENSG00000075073), PROKR2 (ENSG00000101292), GPR50 (ENSG00000102195), TACR1 (ENSG00000115353), GPR75 (ENSG00000119737), PRLHR (ENSG00000119973), GPR83 (ENSG00000123901), MCHR1 (ENSG00000128285), OR11H1 (ENSG00000130538), MCHR2 (ENSG00000152034), NPY1R (ENSG00000164128), NPY5R (ENSG00000164129), MTNR1A (ENSG00000168412), PROKR1 (ENSG00000169618), TACR3 (ENSG00000169836), OR9G1 (ENSG00000174914), OR11H4 (ENSG00000176198), OR11H6 (ENSG00000176219), OR9A2 (ENSG00000179468), GPR88 (ENSG00000181656), GPR19 (ENSG00000183150), NPY2R (ENSG00000185149), OR11G2 (ENSG00000196832), NPY4R (ENSG00000204174), OR11A1 (ENSG00000204694), OR9A1P (ENSG00000237621), OR11H12 (ENSG00000257115), OR9A4 (ENSG00000258083), OR11H2 (ENSG00000258453), OR11H7 (ENSG00000258806), NPY4R2 (ENSG00000264717), OR10X1 (ENSG00000279111), OR51F1 (ENSG00000280021)

Protein

Protein identifiers

Melatonin receptor type 1B — P49286 (reviewed: P49286)

All UniProt accessions (3): P49286, E9PR36, H0YDG4

UniProt curated annotations — full annotation on UniProt →

Function. High affinity receptor for melatonin. Likely to mediate the reproductive and circadian actions of melatonin. The activity of this receptor is mediated by pertussis toxin sensitive G proteins that inhibit adenylate cyclase activity.

Subunit / interactions. Interacts with GPR61, GPR62 and GPR135.

Subcellular location. Cell membrane.

Tissue specificity. Expressed in retina and less in brain and hippocampus.

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

RefSeq proteins (1): NP_005950* (*=MANE)

Domains & families (InterPro)

IDNameType
IPR000025Melatonin_rcptFamily
IPR000276GPCR_RhodpsnFamily
IPR002278Mel_1A/1B_rcptFamily
IPR017452GPCR_Rhodpsn_7TMDomain

Pfam: PF00001

UniProt features (45 total): helix 16, topological domain 8, transmembrane region 7, sequence variant 3, turn 3, strand 3, binding site 2, chain 1, glycosylation site 1, disulfide bond 1

Structure

Experimental structures (PDB)

5 structures.

PDBMethodResolution (Å)
6ME6X-RAY DIFFRACTION2.8
6ME8X-RAY DIFFRACTION3.1
6ME7X-RAY DIFFRACTION3.2
6ME9X-RAY DIFFRACTION3.3
7VH0ELECTRON MICROSCOPY3.46

Predicted structure (AlphaFold)

ModelpLDDTFraction very-high
AF-P49286-F184.750.68

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 (2): 175; 194

Disulfide bonds (1): 113–190

Glycosylation sites (1): 4

Function

Pathways and Gene Ontology

Reactome pathways

6 pathways

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

MSigDB gene sets: 128 (showing top): GOBP_CIRCADIAN_RHYTHM, GOBP_NEGATIVE_REGULATION_OF_NEURON_APOPTOTIC_PROCESS, GOBP_BEHAVIOR, GOBP_CIRCULATORY_SYSTEM_PROCESS, GOBP_INSULIN_SECRETION, GOBP_REGULATION_OF_HORMONE_LEVELS, GOBP_NEGATIVE_REGULATION_OF_NERVOUS_SYSTEM_PROCESS, GOBP_NEGATIVE_REGULATION_OF_PEPTIDE_SECRETION, GOBP_HORMONE_TRANSPORT, GOBP_POSITIVE_REGULATION_OF_BEHAVIOR, GOBP_NEGATIVE_REGULATION_OF_PROTEIN_LOCALIZATION, GOBP_CELL_CELL_SIGNALING, GOBP_REGULATION_OF_CIRCADIAN_RHYTHM, GOBP_REGULATION_OF_PROTEIN_SECRETION, GOBP_REGULATION_OF_ANATOMICAL_STRUCTURE_SIZE

GO Biological Process (17): G protein-coupled receptor signaling pathway (GO:0007186), G protein-coupled receptor signaling pathway, coupled to cyclic nucleotide second messenger (GO:0007187), chemical synaptic transmission (GO:0007268), negative regulation of receptor guanylyl cyclase signaling pathway (GO:0010754), glucose homeostasis (GO:0042593), camera-type eye development (GO:0043010), negative regulation of neuron apoptotic process (GO:0043524), negative regulation of vasoconstriction (GO:0045906), positive regulation of circadian sleep/wake cycle, non-REM sleep (GO:0046010), negative regulation of insulin secretion (GO:0046676), regulation of insulin secretion (GO:0050796), negative regulation of cytosolic calcium ion concentration (GO:0051481), negative regulation of transmission of nerve impulse (GO:0051970), positive regulation of transmission of nerve impulse (GO:0051971), regulation of neuronal action potential (GO:0098908), signal transduction (GO:0007165), positive regulation of circadian rhythm (GO:0042753)

GO Molecular Function (3): G protein-coupled receptor activity (GO:0004930), melatonin receptor activity (GO:0008502), protein binding (GO:0005515)

GO Cellular Component (3): plasma membrane (GO:0005886), synapse (GO:0045202), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-4 pathways:

CategoryPathways
Signaling by GPCR2
GPCR ligand binding1
GPCR downstream signalling1
Signal Transduction1

GO top-level categories

Rollup of top GO terms by namespace:

CategoryTerms
regulation of transmission of nerve impulse3
G protein-coupled receptor activity2
G protein-coupled receptor signaling pathway2
insulin secretion2
transmission of nerve impulse2
signal transduction1
anterograde trans-synaptic signaling1
receptor guanylyl cyclase signaling pathway1
negative regulation of signal transduction1
carbohydrate homeostasis1
eye development1
negative regulation of apoptotic process1
regulation of neuron apoptotic process1
neuron apoptotic process1
regulation of vasoconstriction1
vasoconstriction1
negative regulation of multicellular organismal process1
circadian sleep/wake cycle, non-REM sleep1
regulation of circadian sleep/wake cycle, non-REM sleep1
positive regulation of circadian sleep/wake cycle, sleep1
negative regulation of protein secretion1
regulation of insulin secretion1
negative regulation of peptide hormone secretion1
regulation of protein secretion1
regulation of peptide hormone secretion1
regulation of biological quality1
negative regulation of cell communication1
negative regulation of nervous system process1
positive regulation of cell communication1
positive regulation of nervous system process1
neuronal action potential1
regulation of action potential1
cell communication1
cellular process1
signaling1
regulation of cellular process1
cellular response to stimulus1
circadian rhythm1
regulation of circadian rhythm1
positive regulation of biological process1

Protein interactions and networks

STRING

960 interactions, top by confidence (×1000):

Protein AProtein BPartner UniProtScore
MTNR1BADCY5O95622912
MTNR1BDGKBQ9Y6T7884
MTNR1BGCKP35557864
MTNR1BFAT3Q8TDW7828
MTNR1BCDKAL1Q5VV42801
MTNR1BG6PC2Q9NQR9800
MTNR1BSLC30A8Q8IWU4763
MTNR1BKCNJ11Q14654745
MTNR1BGCKRQ14397737
MTNR1BINSP01308724
MTNR1BFAT1Q14517720
MTNR1BTCF7L2Q9NQB0720
MTNR1BHHEXQ03014696
MTNR1BIGF2BP2Q9Y6M1670
MTNR1BCDC123O75794668

IntAct

173 interactions, top by confidence:

ABTypeScore
MTNR1BIRS4psi-mi:“MI:0914”(association)0.530
ARAFBAG2psi-mi:“MI:0914”(association)0.530
MTNR1BHTR2Cpsi-mi:“MI:0915”(physical association)0.520
HTR2CMTNR1Bpsi-mi:“MI:2364”(proximity)0.520
MTNR1BHTR2Cpsi-mi:“MI:0403”(colocalization)0.520
RGS20MTNR1Bpsi-mi:“MI:0915”(physical association)0.500
MTNR1BRGS20psi-mi:“MI:0914”(association)0.500
MTNR1BMTNR1Apsi-mi:“MI:0915”(physical association)0.500
MTNR1BStxbp3psi-mi:“MI:0915”(physical association)0.400
MTNR1BRAMP1psi-mi:“MI:0915”(physical association)0.400
MTNR1BRAMP2psi-mi:“MI:0915”(physical association)0.400
RAMP2MTNR1Bpsi-mi:“MI:0915”(physical association)0.400
RAMP3MTNR1Bpsi-mi:“MI:0915”(physical association)0.400
MTNR1BRNF41psi-mi:“MI:0915”(physical association)0.370
SLC2A3MTNR1Bpsi-mi:“MI:0915”(physical association)0.370
MECP2MTNR1Bpsi-mi:“MI:0915”(physical association)0.370
MTNR1BSDHDpsi-mi:“MI:0915”(physical association)0.370
MTNR1BTMEM230psi-mi:“MI:0915”(physical association)0.370
MTNR1BYWHABpsi-mi:“MI:0915”(physical association)0.370
GGT7MTNR1Bpsi-mi:“MI:0915”(physical association)0.370
SLC3A2MTNR1Bpsi-mi:“MI:0915”(physical association)0.370
MTNR1BPCDHB10psi-mi:“MI:0915”(physical association)0.370
MTNR1BPSME3IP1psi-mi:“MI:0915”(physical association)0.370
MFFMTNR1Bpsi-mi:“MI:0915”(physical association)0.370
CLDND1MTNR1Bpsi-mi:“MI:0915”(physical association)0.370

BioGRID (218): Stxbp1 (Reconstituted Complex), Cacna1b (Reconstituted Complex), Atp1a3 (Reconstituted Complex), Ctnnd1 (Reconstituted Complex), Dusp3 (Reconstituted Complex), Prkcz (Reconstituted Complex), Ptpn13 (Reconstituted Complex), Gmfb (Reconstituted Complex), Map2 (Reconstituted Complex), Tuba1c (Reconstituted Complex), Tubb3 (Reconstituted Complex), Hspa9 (Reconstituted Complex), Hsph1 (Reconstituted Complex), Pygb (Reconstituted Complex), Crym (Reconstituted Complex)

ESM2 similar proteins: A6QLE7, O02769, O02781, O12000, O15974, O17899, O70528, P23820, P30966, P32251, P35364, P47898, P48039, P48040, P49217, P49218, P49219, P49285, P49286, P49287, P49288, P51046, P51047, P51048, P51049, P51050, P51051, P51052, P97288, Q03566, Q03613, Q13639, Q16950, Q16951, Q2KI97, Q59E83, Q61184, Q62758, Q62953, Q86ME6

Diamond homologs: A0A287A2K5, C8YUV0, O00155, O02836, O08786, O15973, O18935, O19012, O19014, O19025, O19032, O19054, O19091, O62729, O77408, O77700, O77721, O77830, O97665, O97772, P04761, P08482, P0C5I1, P11229, P12657, P17200, P18089, P19328, P22270, P25021, P30545, P30551, P30552, P30553, P30796, P32211, P32238, P32239, P32302, P46627

SIGNOR signaling

5 interactions.

AEffectBMechanism
MTNR1B“up-regulates activity”GNAI1binding
MTNR1B“up-regulates activity”GNAI3binding
MTNR1B“up-regulates activity”GNAO1binding
MTNR1B“up-regulates activity”GNAZbinding
melatonin“up-regulates activity”MTNR1B“chemical activation”

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 159 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.

GO biological processes:

GO termPartnersFoldFDR
regulation of focal adhesion assembly525.5×1e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

ClassificationCount (floor)
Pathogenic0
Likely pathogenic0
Uncertain significance66
Likely benign6
Benign4

Top pathogenic / likely-pathogenic (0)

SpliceAI

146 predictions. Top by Δscore:

VariantEffectΔscore
11:92969945:GCAG:Gdonor_gain1.0000
11:92969949:G:GGdonor_gain1.0000
11:92969949:GTGA:Gdonor_loss1.0000
11:92969944:CGCAG:Cdonor_gain0.9900
11:92969945:GCAGG:Gdonor_gain0.9900
11:92969947:AG:Adonor_gain0.9900
11:92969948:GG:Gdonor_gain0.9900
11:92981439:T:Aacceptor_gain0.9900
11:92981441:CTTCA:Cacceptor_loss0.9900
11:92981444:CAG:Cacceptor_loss0.9900
11:92981445:A:AGacceptor_gain0.9900
11:92981445:A:Cacceptor_loss0.9900
11:92981446:G:GAacceptor_loss0.9900
11:92981446:G:GGacceptor_gain0.9900
11:92981446:GGT:Gacceptor_gain0.9900
11:92981446:GGTA:Gacceptor_gain0.9900
11:92981446:GGTAA:Gacceptor_gain0.9900
11:92969946:CAG:Cdonor_gain0.9800
11:92969950:T:Gdonor_loss0.9800
11:92981445:AG:Aacceptor_gain0.9200
11:92981446:GG:Gacceptor_gain0.9200
11:92969926:G:GTdonor_gain0.8700
11:92981436:T:TAacceptor_gain0.8700
11:92981436:T:Aacceptor_loss0.8200
11:92969949:G:Tdonor_gain0.8100
11:92976278:G:Tdonor_gain0.8000
11:92978143:C:Tdonor_gain0.7700
11:92980807:G:GTdonor_gain0.7400
11:92979016:G:GTdonor_gain0.7300
11:92976278:G:GTdonor_gain0.7200

AlphaMissense

2354 scored. Top likely-pathogenic:

VariantProtein changeam_pathogenicity
11:92981464:A:CS81R0.997
11:92981466:T:AS81R0.997
11:92981466:T:GS81R0.997
11:92981480:A:CD86A0.995
11:92982001:T:CF260L0.995
11:92982003:T:AF260L0.995
11:92982003:T:GF260L0.995
11:92981480:A:TD86V0.994
11:92981590:A:CS123R0.994
11:92981592:C:AS123R0.994
11:92981592:C:GS123R0.994
11:92981480:A:GD86G0.993
11:92981481:C:AD86E0.992
11:92981481:C:GD86E0.992
11:92981541:G:CW106C0.992
11:92981541:G:TW106C0.992
11:92981791:T:AC190S0.992
11:92981792:G:AC190Y0.992
11:92981792:G:CC190S0.992
11:92981479:G:CD86H0.991
11:92981793:C:GC190W0.990
11:92982100:A:CS293R0.990
11:92982102:C:AS293R0.990
11:92982102:C:GS293R0.990
11:92982124:A:CS301R0.990
11:92982126:C:AS301R0.990
11:92982126:C:GS301R0.990
11:92969899:C:AN58K0.989
11:92969899:C:GN58K0.989
11:92981716:T:AW165R0.989

dbSNP variants (sampled 300 via entrez): RS1000054341 (11:92983988 A>C,G), RS1000290345 (11:92973846 T>C), RS1000343628 (11:92967977 A>G), RS1000506402 (11:92972276 A>C,G), RS1000577111 (11:92973608 C>T), RS1000610744 (11:92972801 A>T), RS1001025023 (11:92972610 A>T), RS1001123101 (11:92979041 C>T), RS1001146759 (11:92978715 C>G,T), RS1001383410 (11:92978873 A>G), RS1001383631 (11:92984665 GTGC>G), RS1001587776 (11:92969022 A>G), RS1002239754 (11:92979511 A>G), RS1002455450 (11:92973108 G>A,T), RS1002675518 (11:92979084 A>G)

Disease associations

OMIM: gene MIM:600804 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

5 total (5 of 5 shown, HPO-id order):

HPOTerm
HP:0000006Autosomal dominant inheritance
HP:0000855Insulin resistance
HP:0003584Late onset
HP:0005978Type II diabetes mellitus
HP:0031819Increased waist to hip ratio

GWAS associations

69 associations (top):

StudyTraitp-value
GCST000276_1Fasting plasma glucose3.000000e-50
GCST000291_1Fasting plasma glucose2.000000e-36
GCST000292_11Metabolic traits6.000000e-08
GCST000457_1Fasting plasma glucose2.000000e-09
GCST000568_15Fasting blood glucose6.000000e-175
GCST000712_18Type 2 diabetes8.000000e-15
GCST000803_4Glycated hemoglobin levels4.000000e-11
GCST001233_1Metabolite levels1.000000e-16
GCST001375_1Diabetes (gestational)2.000000e-13
GCST001391_12Metabolite levels3.000000e-11
GCST001436_16Metabolic syndrome5.000000e-16
GCST001486_1Fasting plasma glucose1.000000e-12
GCST001527_15Fasting blood glucose (BMI interaction)4.000000e-105
GCST001586_7Insomnia (caffeine-induced)5.000000e-06
GCST001762_506Obesity-related traits4.000000e-08
GCST001965_10Glycemic traits3.000000e-12
GCST001965_6Glycemic traits5.000000e-13
GCST002034_2Adverse response to radiation therapy5.000000e-08
GCST002110_10Glycemic traits (pregnancy)2.000000e-12
GCST002110_9Glycemic traits (pregnancy)3.000000e-16
GCST002352_16Type 2 diabetes2.000000e-07
GCST002586_13Fasting plasma glucose2.000000e-11
GCST002726_41Glucose homeostasis traits5.000000e-12
GCST002726_50Glucose homeostasis traits1.000000e-11
GCST002792_3Vincristine-induced peripheral neuropathy in acute lymphoblastic leukemia3.000000e-08
GCST004487_1Peak insulin response1.000000e-24
GCST004488_2Insulin secretion rate9.000000e-08
GCST004489_1Insulin disposition index3.000000e-17
GCST004575_2Acute insulin response4.000000e-21
GCST004758_4Type 2 diabetes2.000000e-07

EFO canonical traits (19, from GWAS)

EFO IDTrait name
EFO:0004468glucose measurement
EFO:0004541HbA1c measurement
EFO:0004725metabolite measurement
EFO:0000195metabolic syndrome
EFO:0004340body mass index
EFO:0007876insomnia measurement
EFO:0004307glucose tolerance test
EFO:0006831acute insulin response measurement
EFO:0006832disposition index measurement
EFO:0008000peak insulin response measurement
EFO:0004344birth weight
EFO:0004469HOMA-B
EFO:0008473insulin response measurement
EFO:0004471insulin sensitivity measurement
EFO:0004467insulin measurement
EFO:0005939parental genotype effect measurement
EFO:0005763pulse pressure measurement
EFO:0008328chronotype measurement
EFO:0007828daytime rest measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (2): CHEMBL1946 (SINGLE PROTEIN), CHEMBL2094268 (PROTEIN FAMILY)

Molecules with ChEMBL bioactivity

7 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 344,948 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

MoleculeNamePhasePatents
CHEMBL10878AGOMELATINE44,528
CHEMBL1218RAMELTEON45,217
CHEMBL2103822TASIMELTEON4516
CHEMBL311498CIANIDANOL459,647
CHEMBL45MELATONIN456,417
CHEMBL59DOPAMINE4217,028
CHEMBL7257MEBUFOTENIN21,595

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

PharmGKB variants

1 variants.

VariantGenesLevelScore#Clin annotsDrugs
rs8192552MTNR1B0.000

GtoPdb / IUPHAR curated pharmacology

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

Target class: gpcr — Melatonin receptors

Most potent curated ligand interactions (46 total), top 25:

LigandActionAffinityParameter
UCM1014Full agonist12.0pKi
isoamyl-agomelatinePartial agonist11.0pKi
CIFEAFull agonist10.9pKi
agomelatineFull agonist10.5pKi
LY 156735Full agonist10.4pKi
2-iodo-melatoninFull agonist10.3pKi
IIK7Full agonist10.3pKi
tasimelteonFull agonist10.2pKi
UCM 765Full agonist10.2pKi
[125I]SD6Full agonist10.18pKd
2-[125I]melatoninFull agonist10.0pKd
ramelteonFull agonist10.0pKi
6-Cl-MLTFull agonist9.8pKi
melatoninFull agonist9.8pKi
GR 196429Full agonist9.8pKi
[125I]DIV880Partial agonist9.7pKd
5-methoxy-luzindolePartial agonist9.6pKi
[125I]S70254Partial agonist9.6pKd
S24014Partial agonist9.6pKi
S24773Partial agonist9.6pKi
[3H]melatoninFull agonist9.6pKd
BOMPPAFull agonist9.5pKi
4P-PDOTAntagonist9.41pKi
EFPPEAFull agonist9.4pKi
(hydroxymethylphenyl)agomelatineAntagonist9.4pKi

Binding affinities (BindingDB)

63 measured of 65 human assays (66 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

LigandMeasureValuePatent
Melatonin,2-IodoKI0.01 nM
Melatonin,2-PhenylKI0.02 nM
Melatonin,2-BromoKI0.02 nM
N-[2-[2-(4-phenylbutyl)-7,8-dihydro-6H-cyclopenta[g][1,3]benzoxazol-8-yl]ethyl]acetamideIC500.022 nMUS-8552037: Tricyclic compound and pharmaceutical use thereof
N-[2-[(8S)-2-methyl-7,8-dihydro-6H-cyclopenta[g][1,3]benzoxazol-8-yl]ethyl]propanamideIC500.03 nMUS-8552037: Tricyclic compound and pharmaceutical use thereof
N-[2-[(8S)-2-methyl-7,8-dihydro-6H-cyclopenta[g][1,3]benzothiazol-8-yl]ethyl]acetamideIC500.038 nMUS-8552037: Tricyclic compound and pharmaceutical use thereof
N-[2-[(8S)-2-methyl-7,8-dihydro-6H-cyclopenta[g][1,3]benzoxazol-8-yl]ethyl]acetamideIC500.057 nMUS-8552037: Tricyclic compound and pharmaceutical use thereof
N-[2-(2-methyl-6H-cyclopenta[g][1,3]benzoxazol-8-yl)ethyl]acetamideIC500.068 nMUS-8552037: Tricyclic compound and pharmaceutical use thereof
N-[(2E)-2-[2-(4-phenylbutyl)-6,7-dihydrocyclopenta[g][1,3]benzoxazol-8-ylidene]ethyl]acetamideIC500.079 nMUS-8552037: Tricyclic compound and pharmaceutical use thereof
2,2,2-trifluoro-N-[2-(2-methyl-7,8-dihydro-6H-cyclopenta[g][1,3]benzoxazol-8-yl)ethyl]acetamideIC500.095 nMUS-8552037: Tricyclic compound and pharmaceutical use thereof
N-[2-(2-methyl-7,8-dihydro-6H-cyclopenta[g][1,3]benzoxazol-8-yl)ethyl]propanamideIC500.13 nMUS-8552037: Tricyclic compound and pharmaceutical use thereof
NSC_5311134KI0.14 nM
N-[2-(2-methyl-7,8-dihydro-6H-cyclopenta[g][1,3]benzoxazol-8-yl)ethyl]acetamideIC500.15 nMUS-8552037: Tricyclic compound and pharmaceutical use thereof
N-[2-(2-methyl-7,8-dihydro-6H-cyclopenta[g][1,3]benzothiazol-8-yl)ethyl]acetamideIC500.15 nMUS-8552037: Tricyclic compound and pharmaceutical use thereof
N-[(2E)-2-(2-methyl-6,7-dihydrocyclopenta[g][1,3]benzothiazol-8-ylidene)ethyl]acetamideIC500.19 nMUS-8552037: Tricyclic compound and pharmaceutical use thereof
Melatonin,2-ChloroKI0.2 nM
N-[(2E)-2-(2-methyl-6,7-dihydrocyclopenta[g][1,3]benzoxazol-8-ylidene)ethyl]propanamideIC500.25 nMUS-8552037: Tricyclic compound and pharmaceutical use thereof
N-[2-(2-methyl-7,8-dihydro-6H-cyclopenta[g][1,3]benzoxazol-8-yl)ethyl]cyclopropanecarboxamideIC500.25 nMUS-8552037: Tricyclic compound and pharmaceutical use thereof
5-MeOT-N-propionylKI0.26 nM
N-[(2E)-2-(2-methyl-6,7-dihydrocyclopenta[g][1,3]benzoxazol-8-ylidene)ethyl]acetamideIC500.33 nMUS-8552037: Tricyclic compound and pharmaceutical use thereof
N-[2-(2-ethyl-7,8-dihydro-6H-cyclopenta[g][1,3]benzoxazol-8-yl)ethyl]acetamideIC500.36 nMUS-8552037: Tricyclic compound and pharmaceutical use thereof
5-MeOT-N-butanylKI0.45 nM
N-[2-(2-methoxy-7,8-dihydro-6H-cyclopenta[g][1,3]benzoxazol-8-yl)ethyl]acetamideIC500.54 nMUS-8552037: Tricyclic compound and pharmaceutical use thereof
melatonin, 6-HydroxyKI0.54 nM
N-[2-(2-cyclopropyl-7,8-dihydro-6H-cyclopenta[g][1,3]benzoxazol-8-yl)ethyl]acetamideIC500.66 nMUS-8552037: Tricyclic compound and pharmaceutical use thereof
N-[2-(6-Chloro-5-methoxy-1H-indol-3-yl)-ethyl]-acetamideKI0.67 nM
N-[2-(7,8-dihydro-6H-cyclopenta[g][1,3]benzoxazol-8-yl)ethyl]acetamideIC500.88 nMUS-8552037: Tricyclic compound and pharmaceutical use thereof
14C-5-hydroxy tryptamine creatinine disulfateKI1.2 nM
CAS_73-31-4KI1.34 nM
CAS_73-31-4KI4.8 nM
8-M-CADOTKI5.4 nM
5-MeOT-N-pentanylKI5.88 nM
N-[2-[(8R)-2-methyl-7,8-dihydro-6H-cyclopenta[g][1,3]benzoxazol-8-yl]ethyl]propanamideIC5011 nMUS-8552037: Tricyclic compound and pharmaceutical use thereof
Melatonin,6-ClKI11.4 nM
N-[2-[(8R)-2-methyl-7,8-dihydro-6H-cyclopenta[g][1,3]benzoxazol-8-yl]ethyl]acetamideIC5015 nMUS-8552037: Tricyclic compound and pharmaceutical use thereof
N-[2-[(8R)-2-methyl-7,8-dihydro-6H-cyclopenta[g][1,3]benzothiazol-8-yl]ethyl]acetamideIC5019 nMUS-8552037: Tricyclic compound and pharmaceutical use thereof
Luzindole,5-MethoxyKI32.7 nM
8-M-ADOTKI46.9 nM
8-M-PDOTKI60.2 nM
1-[3-(5-Methoxy-1H-indol-3-yl)piperidino]ethanoneKI90.4 nM
N-Acetyltryptamine,5-BenzyloxyKI118 nM
Luzindole,N-propanoylKI154 nM
N-Acetyltryptamine,5-MethylKI156 nM
CAS_117946-91-5KI158 nM
N-AcetyltryptamineKI196 nM
N-CBCPTKI200 nM
Melatonin,6-MethoxyKI207 nM
N-Acetyltryptamine,5-HydroxyKI223 nM
1-[2-(5-Methoxy-1H-indol-3-yl)ethyl]pyrrolidin-2-oneKI289 nM
4-P-CADOTKI326 nM

ChEMBL bioactivities

1621 potent at pChembl≥5 of 1638 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChemblTypeValueUnitMolecule
11.00IC500.01nMCHEMBL421013
11.00Ki0.01nMCHEMBL5555481
11.00Ki0.01nMCHEMBL314512
11.00Ki0.01nMCHEMBL1774516
10.96Ki0.011nMCHEMBL1774529
10.96Ki0.011nMCHEMBL1774514
10.92Ki0.012nMCHEMBL1774519
10.91Ki0.0123nMCHEMBL134874
10.86Ki0.0138nMRAMELTEON
10.85Ki0.014nMCHEMBL64664
10.85Ki0.014nMCHEMBL433237
10.85Ki0.014nMCHEMBL1774521
10.82IC500.0153nMCHEMBL320267
10.80Ki0.01585nMCHEMBL285718
10.77IC500.017nMMELATONIN
10.77Ki0.017nMCHEMBL15060
10.76Ki0.0174nMCHEMBL134330
10.74Ki0.018nMCHEMBL1774513
10.70Ki0.02nMCHEMBL287560
10.70Ki0.02nMCHEMBL3612471
10.70Ki0.02nMCHEMBL330137
10.70Ki0.02nMCHEMBL1774525
10.68Ki0.021nMIODOMELATONIN
10.67Ki0.0214nMCHEMBL135072
10.66Ki0.022nMCHEMBL1774512
10.65Ki0.0225nMCHEMBL134295
10.64Ki0.0231nMCHEMBL334645
10.62EC500.024nMCHEMBL2326201
10.62Ki0.0241nMCHEMBL336960
10.56Ki0.02754nMCHEMBL394273
10.52Ki0.03nMCHEMBL2314255
10.52Ki0.03nMCHEMBL3763503
10.52Ki0.03nMCHEMBL4089965
10.49Ki0.0321nMCHEMBL334404
10.49Ki0.0326nMCHEMBL1091998
10.47Ki0.034nMCHEMBL130214
10.47Ki0.034nMCHEMBL1774524
10.46Ki0.035nMCHEMBL1774515
10.44Ki0.036nMCHEMBL394273
10.44Ki0.036nMCHEMBL33415
10.43Ki0.037nMCHEMBL1774527
10.42Ki0.03802nMCHEMBL15060
10.40Ki0.03981nMCHEMBL4079759
10.40Ki0.04nMCHEMBL14417
10.40IC500.04nMCHEMBL34730
10.40EC500.04nMCHEMBL5561006
10.40Ki0.04nMCHEMBL94838
10.40Ki0.04nMCHEMBL19211
10.39Ki0.041nMCHEMBL337910
10.39Ki0.0408nMCHEMBL134447

PubChem BioAssay actives

1532 with measured affinity, of 3195 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
N-[2-(2-bromo-6-methoxyindol-1-yl)ethyl]propanamide107564: Binding affinity against melatonin receptor in the quail optica tecta using 2-[125] iodomelatonin (100 pM) as labelled ligandki<0.0001uM
2,2,2-trifluoro-N-[2-(7-methoxynaphthalen-1-yl)ethyl]acetamide107706: Monophasic inhibitory concentration against melatonin receptor was measured on ovine pars tuberalis membrane.ic50<0.0001uM
N-[2-(6-methoxy-2-phenylindol-1-yl)ethyl]propanamide107564: Binding affinity against melatonin receptor in the quail optica tecta using 2-[125] iodomelatonin (100 pM) as labelled ligandki<0.0001uM
N-[2-(2-phenylindol-1-yl)ethyl]propanamide1527843: Displacement of 2-[125I]iodomelatonin from melatonin receptor (unknown origin)ki<0.0001uM
1-[2-(5-methoxy-2-phenyl-1-benzofuran-3-yl)ethyl]-3-methylurea108045: Binding affinity on human melatonin receptor type 1B stably transfected in human embryonic kidney (HEK 293) cells using 2-[125I]iodomelatonin as radioligand.ki<0.0001uM
N-[2-(5-methoxy-2-phenyl-1-benzofuran-3-yl)ethyl]but-3-enamide108045: Binding affinity on human melatonin receptor type 1B stably transfected in human embryonic kidney (HEK 293) cells using 2-[125I]iodomelatonin as radioligand.ki<0.0001uM
N-[2-(7,8-dihydro-6H-cyclopenta[g][1,3]benzodioxol-8-yl)ethyl]propanamide107729: Binding affinity against human Melatonin receptor type 1A (MT1) in CHO cellski<0.0001uM
2,2,2-trifluoro-N-[2-(6-methoxy-3H-inden-1-yl)ethyl]acetamide107728: Ability to inhibit 2-[125I]iodomelatonin specific binding to human melatonin receptor type 1A (MT1) expressed in CHO cells.ki<0.0001uM
2,2,2-trifluoro-N-[2-(7-methoxy-1,2,3,4-tetrahydronaphthalen-1-yl)ethyl]acetamide107728: Ability to inhibit 2-[125I]iodomelatonin specific binding to human melatonin receptor type 1A (MT1) expressed in CHO cells.ki<0.0001uM
N-[2-(2-iodo-5-methoxy-1-methylindol-3-yl)ethyl]acetamide108186: Inhibition of 2-[125I]iodomelatonin binding to human Melatonin receptor type 1B expressed in HEK293 cellski<0.0001uM
N-[2-(6-methoxy-3H-inden-1-yl)ethyl]propanamide107728: Ability to inhibit 2-[125I]iodomelatonin specific binding to human melatonin receptor type 1A (MT1) expressed in CHO cells.ki<0.0001uM
N-[2-(2-iodo-5-methoxy-1H-indol-3-yl)ethyl]acetamide107567: Inhibition of 2-[125I]iodomelatonin binding to melatonin receptor in quail brain as 1/Kaki<0.0001uM
N-[2-(5-methoxy-2-phenyl-1-benzofuran-3-yl)ethyl]prop-2-enamide108045: Binding affinity on human melatonin receptor type 1B stably transfected in human embryonic kidney (HEK 293) cells using 2-[125I]iodomelatonin as radioligand.ki<0.0001uM
N-[2-(2,6,7,8-tetrahydro-1H-cyclopenta[e][1]benzofuran-8-yl)ethyl]butanamide107729: Binding affinity against human Melatonin receptor type 1A (MT1) in CHO cellski<0.0001uM
N-[2-[(1S)-6-methoxy-2,3-dihydro-1H-inden-1-yl]ethyl]butanamide107728: Ability to inhibit 2-[125I]iodomelatonin specific binding to human melatonin receptor type 1A (MT1) expressed in CHO cells.ki<0.0001uM
N-[(1-benzyl-3,4-dihydro-2H-quinolin-2-yl)methyl]cyclopropanecarboxamide2073509: Binding affinity to human MT2 receptor assessed as inhibition constantki<0.0001uM
N-[2-(2-bromo-5-methoxy-1H-indol-3-yl)ethyl]acetamide107564: Binding affinity against melatonin receptor in the quail optica tecta using 2-[125] iodomelatonin (100 pM) as labelled ligandki<0.0001uM
N-[2-[2-(4-fluorophenyl)-5-methoxyfuro[3,2-b]pyridin-3-yl]ethyl]acetamide1277516: Displacement of [125I]2-Iodomelatonin from human MT2 receptor expressed in HEK293 cells after 120 mins by radioligand competition assayki<0.0001uM
N-[2-(6,7-dichloro-5-methoxy-2-methyl-1H-indol-3-yl)ethyl]acetamide165366: Inhibition of 2-[125I]iodomelatonin stimulated calcium dependent dopamine release from the rabbit retina.ic50<0.0001uM
3-(2-methoxyquinolin-8-yl)-N-methylsulfonylpropanamide1427148: Displacement of 2-[125I]iodomelatonin from human MT2 receptor expressed in HEK or CHO cell membranes after 120 minski<0.0001uM
N-[2-(2-bromoindol-1-yl)ethyl]propanamide1527843: Displacement of 2-[125I]iodomelatonin from melatonin receptor (unknown origin)ki<0.0001uM
1-[2-(10-methoxy-5,6-dihydroindolo[2,1-a]isoquinolin-12-yl)propyl]-3-methylurea2073509: Binding affinity to human MT2 receptor assessed as inhibition constantki<0.0001uM
N-[(8-methoxy-1,2-dihydroacenaphthylen-1-yl)methyl]butanamide108026: Binding affinity for melatonin receptor type 1B, expressed in HEK293 cells (2-[125I]iodomelatonin is used as radioligand)ki<0.0001uM
N-[2-(6-chloro-5-methoxy-1H-indol-3-yl)ethyl]acetamide165366: Inhibition of 2-[125I]iodomelatonin stimulated calcium dependent dopamine release from the rabbit retina.ic50<0.0001uM
Ramelteon107729: Binding affinity against human Melatonin receptor type 1A (MT1) in CHO cellski<0.0001uM
2,2,2-trifluoro-N-[2-(6-methoxy-2,3-dihydro-1H-inden-1-yl)ethyl]acetamide107728: Ability to inhibit 2-[125I]iodomelatonin specific binding to human melatonin receptor type 1A (MT1) expressed in CHO cells.ki<0.0001uM
N-[2-(2,6-dihydro-1H-cyclopenta[e][1]benzofuran-8-yl)ethyl]acetamide595899: Displacement of [125I]-2-iodomelatonin from human MT2 receptor expressed on CHO cells microscintillation countingki<0.0001uM
N-[2-(7-phenyl-2,6-dihydro-1H-cyclopenta[e][1]benzofuran-8-yl)ethyl]acetamide595899: Displacement of [125I]-2-iodomelatonin from human MT2 receptor expressed on CHO cells microscintillation countingki<0.0001uM
N-[2-(3-methoxy-N-(3-methoxyphenyl)anilino)ethyl]acetamide2073505: Binding affinity to MT2 receptor (unknown origin) expressed in HEK293 cells assessed as inhibition constantki<0.0001uM
N-[2-[2-(2,3-dihydroindol-1-ylmethyl)-5-methoxy-1H-indol-3-yl]ethyl]cyclobutanecarboxamide369282: Displacement of 2-[125I]iodomelatonin from human MT2 receptor expressed in CHO cellski<0.0001uM
N-[2-(5-methoxy-1H-indol-3-yl)ethyl]cyclopropanecarboxamide107706: Monophasic inhibitory concentration against melatonin receptor was measured on ovine pars tuberalis membrane.ic50<0.0001uM
4-chloro-N-[2-(7-methoxynaphthalen-1-yl)ethyl]butanamide107706: Monophasic inhibitory concentration against melatonin receptor was measured on ovine pars tuberalis membrane.ic50<0.0001uM
2-bromo-N-[2-(7-methoxynaphthalen-1-yl)ethyl]acetamide107706: Monophasic inhibitory concentration against melatonin receptor was measured on ovine pars tuberalis membrane.ic50<0.0001uM
N-[2-(7-methoxynaphthalen-1-yl)ethyl]butanamide107706: Monophasic inhibitory concentration against melatonin receptor was measured on ovine pars tuberalis membrane.ic50<0.0001uM
N-(4-phenyl-1,2,3,4-tetrahydronaphthalen-2-yl)propanamide239966: Inhibition of 2-[125I]iodomelatonin binding to human melatonin receptor MT2 expressed in NIH3T3 rat fibroblast cellski<0.0001uM
N-[2-(5-methoxy-2-phenyl-1H-indol-3-yl)ethyl]acetamide107564: Binding affinity against melatonin receptor in the quail optica tecta using 2-[125] iodomelatonin (100 pM) as labelled ligandki<0.0001uM
N-[[(1R,2R)-2-(2-propyl-2,3-dihydro-1,3-benzoxazol-7-yl)cyclopropyl]methyl]butanamide108046: Binding of 2-[125I]iodomelatonin to membrane preparations of NIH3T3 cells stably expressing human Melatonin receptor type 1Bki<0.0001uM
N-[3-[2-[(3,5-dimethoxyphenyl)methoxy]-5-methoxyphenyl]propyl]acetamide474097: Displacement of [3H]melatonin from human melatonin MT2 receptor expressed in CHO cells after 60 mins by scintillation countingki<0.0001uM
N-[3-[5-methoxy-2-[(3-methoxyphenyl)methoxy]phenyl]propyl]acetamide474097: Displacement of [3H]melatonin from human melatonin MT2 receptor expressed in CHO cells after 60 mins by scintillation countingki<0.0001uM
N-[3-(5-methoxy-2-phenylmethoxyphenyl)propyl]acetamide474097: Displacement of [3H]melatonin from human melatonin MT2 receptor expressed in CHO cells after 60 mins by scintillation countingki<0.0001uM
N-[3-(5-methoxy-2-phenylmethoxyphenyl)propyl]propanamide474097: Displacement of [3H]melatonin from human melatonin MT2 receptor expressed in CHO cells after 60 mins by scintillation countingki<0.0001uM
N-[3-(5-methoxy-2-phenylmethoxyphenyl)propyl]butanamide474097: Displacement of [3H]melatonin from human melatonin MT2 receptor expressed in CHO cells after 60 mins by scintillation countingki<0.0001uM
N-[2-(7-propan-2-yl-2,6-dihydro-1H-cyclopenta[e][1]benzofuran-8-yl)ethyl]acetamide595899: Displacement of [125I]-2-iodomelatonin from human MT2 receptor expressed on CHO cells microscintillation countingki<0.0001uM
N-[2-(7-propan-2-yl-2,6-dihydro-1H-cyclopenta[e][1]benzofuran-8-yl)ethyl]propanamide595899: Displacement of [125I]-2-iodomelatonin from human MT2 receptor expressed on CHO cells microscintillation countingki<0.0001uM
N-[2-(7-propan-2-yl-2,6-dihydro-1H-cyclopenta[e][1]benzofuran-8-yl)ethyl]cyclopropanecarboxamide595899: Displacement of [125I]-2-iodomelatonin from human MT2 receptor expressed on CHO cells microscintillation countingki<0.0001uM
2,2,2-trifluoro-N-[2-(7-propan-2-yl-2,6-dihydro-1H-cyclopenta[e][1]benzofuran-8-yl)ethyl]acetamide595899: Displacement of [125I]-2-iodomelatonin from human MT2 receptor expressed on CHO cells microscintillation countingki<0.0001uM
N-[2-(7-benzyl-2,6-dihydro-1H-cyclopenta[e][1]benzofuran-8-yl)ethyl]acetamide595899: Displacement of [125I]-2-iodomelatonin from human MT2 receptor expressed on CHO cells microscintillation countingki<0.0001uM
N-[2-[7-(cyclohexylmethyl)-2,6-dihydro-1H-cyclopenta[e][1]benzofuran-8-yl]ethyl]acetamide595899: Displacement of [125I]-2-iodomelatonin from human MT2 receptor expressed on CHO cells microscintillation countingki<0.0001uM
N-[2-[7-(thiophen-3-ylmethyl)-2,6-dihydro-1H-cyclopenta[e][1]benzofuran-8-yl]ethyl]acetamide595899: Displacement of [125I]-2-iodomelatonin from human MT2 receptor expressed on CHO cells microscintillation countingki<0.0001uM
N-[2-(7-bromo-2,6-dihydro-1H-cyclopenta[e][1]benzofuran-8-yl)ethyl]acetamide595899: Displacement of [125I]-2-iodomelatonin from human MT2 receptor expressed on CHO cells microscintillation countingki<0.0001uM

CTD chemical–gene interactions

27 total (human), top 27 by PubMed support.

ChemicalActions (top 5)PubMed papers
Melatoninaffects binding, decreases reaction, increases expression, increases reaction5
agomelatineaffects binding, increases activity2
chrysoeriolaffects binding1
2-iodomelatoninaffects binding, increases activity, increases reaction1
CGP 52608affects binding, increases reaction1
4-phenyl-2-propionamidotetralineaffects binding1
ramelteondecreases reaction, affects binding1
bisphenol Saffects cotreatment, decreases methylation1
N-(2-(2-methoxy-6H-dipyrido(2,3-a-3,2-e)pyrrolizin-11-yl)ethyl)-2-furamideaffects binding1
N-(2-(7-(cyclohexylmethyl)-1,6-dihydro-2H-indeno(5,4-b)furan-8-yl)ethyl)acetamideaffects binding, increases activity1
N-(2-(2-ethyl-8,9-dihydrofuro(3,2-c)pyrazolo(1,5-a)pyridin-1-yl)ethyl)acetamideaffects binding1
Acenaphthenesaffects binding1
Resveratrolaffects binding1
Fulvestrantaffects cotreatment, decreases methylation1
Benzo(a)pyreneincreases methylation1
Carbofuranaffects binding, decreases reaction1
Guanosine Triphosphateaffects binding, decreases reaction1
Methamphetaminedecreases reaction, increases expression, increases reaction1
Methotrexateincreases expression1
Pesticidesdecreases methylation1
Carbarylaffects binding, decreases reaction1
Testosteroneaffects abundance1
Valproic Aciddecreases methylation1
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxidedecreases reaction, affects localization, decreases expression, affects binding1
Cyclosporinedecreases methylation1
Phenalenesaffects binding1
Endocannabinoidsincreases reaction, affects binding, increases activity1

ChEMBL screening assays

311 unique, capped per target: 196 binding, 115 functional

Representative assays (with source publication via chembl_document):

Assay IDTypeDescriptionSource paper
CHEMBL1031360FunctionalActivity at human MT2 receptor expressed in CHO cells assessed as inhibition of forskolin-stimulated cAMP formation at >10 nM2-[(2,3-dihydro-1H-indol-1-yl)methyl]melatonin analogues: a novel class of MT2-selective melatonin receptor antagonists. — J Med Chem
CHEMBL1031364BindingDisplacement of 2-[125I]iodomelatonin from human MT2 receptor expressed in CHO cells2-[(2,3-dihydro-1H-indol-1-yl)methyl]melatonin analogues: a novel class of MT2-selective melatonin receptor antagonists. — J Med Chem

Cellosaurus cell lines

5 cell lines: 3 spontaneously immortalized cell line, 2 cancer cell line

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

CellosaurusNameCategorySex
CVCL_H467CHO-K1/MT2/Galpha15Spontaneously immortalized cell lineFemale
CVCL_KV54cAMP Hunter CHO-K1 MTNR1B GiSpontaneously immortalized cell lineFemale
CVCL_KY56PathHunter CHO-K1 MTNR1B beta-arrestinSpontaneously immortalized cell lineFemale
CVCL_LA87PathHunter U2OS MTNR1B Total GPCR InternalizationCancer cell lineFemale
CVCL_ZL00Tango MTNR1B-bla U2OSCancer 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
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Sources 81

This page pulls from 81 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_studyhgnchpointactinterprointogenjasparmeshmimmirdbmondomsigdborphanetorthologparalogpatentpatent_compoundpdbpfampharmgkb_clinicalpharmgkb_genepharmgkb_guidelinepharmgkb_variantpubchempubchem_activitypubchem_assaypubmedreactomereactomeparentrefseqrhearnacentralscxa_expressionscxa_gene_experimentsignorspliceaistring_interactiontranscriptufeatureuniprot