Property Summary

NCBI Gene PubMed Count 38
Grant Count 2
Funding $294,527.75
PubMed Score 75.01
PubTator Score 43.75

Knowledge Summary

Patent (3,051)

Expression

  Differential Expression (3)

Disease log2 FC p
osteosarcoma 1.646 0.000
diabetes mellitus 1.200 0.002
psoriasis -4.000 0.000

Synonym

Accession P08173 B2RPP4 Q0VD60 Q4VBK7
Symbols HM4
M4R

Gene

PANTHER Protein Class (2)

 Grant Application (2)

PDB

5DSG  

  TechDev Info (1)

MLP Assay (19)

AID Type Active / Inconclusive / Inactive Description
2616 summary 0 / 0 / 0 Chemical optimization of in vitro pharmacology and DMPK properties of the highly selective mAChR 4 (M4) Positive Allosteric Modulator (PAM) Series with Greatly Improved Human Receptor Activity
434953 screening 0 / 0 / 0 Late-stage radioligand binding dose response assay to identify inhibitors of NADPH oxidase 1 (NOX1): PDSP screen Ki
434974 screening 0 / 0 / 0 Late-stage radioligand binding assay to identify inhibitors of NADPH oxidase 1 (NOX1): PDSP screen
449770 confirmatory 4 / 0 / 0 Discovery of a Highly Selective in vitro and in vivo M4 Positive Allosteric Modulator(PAM): Foldshift of Acetylcholine with human M4
504381 other 0 / 0 / 0 Late-stage radioligand binding assay to identify inhibitors of NADPH oxidase 1 (NOX1): PDSP screen Set 2
588743 confirmatory 34 / 0 / 3 Chemical optimization of the highly selective mAChR 4 (M4) Positive Allosteric Modulator (PAM) Series
588755 other 10 / 0 / 0 Human M4 PAM Extended Characterization Fold Shift
588758 other 1 / 0 / 0 ML253 Competition in Radioligand Binding assays (Riserca)
623923 other 1 / 0 / 0 ML293 Competition in Radioligand Binding assays (Ricerca)
623938 confirmatory 55 / 0 / 40 Chemical optimization of in vitro pharmacology and DMPK properties of the highly selective mAChR 4 (M4) Positive Allosteric Modulator (PAM) Series with Greatly Improved Human Receptor Activity (hM4 Calcium Potency)
More...

Gene RIF (15)

PMID Text
26958838 crystal structures of the M1 and M4 muscarinic receptors bound to the inverse agonist, tiotropium
26025056 This study demonstrated that CD4+ and CD8+ T cells expressed M2 and M4 muscarinic receptors which density were significantly increased in asthmatic children in comparison with controls.
24807966 [(3)H]LY2119620 to probe specifically the human M2 and M4 muscarinic receptor allosteric binding sites.
24768300 This study identify suppression of the PVHSIM1-->PAGvl/DR circuit connection as sufficient to induce overeating behavior.
24074052 Data indicate that compounds derived from VU0152100 showed M4 muscarinic receptor (M4 mAChR) direct agoinst properties.
23490763 The data of this study suggested that the rs2067482 polymorphism may help to predict susceptibility to schizophrenia and/or therapeutic responsiveness.
21295605 Use of HM4- and green fluorescent protein-expressing trangenic mice as tissue donors in cell-based therapy validates a rodent model of Huntington disease.
20406819 analysis of allosteric agonism and modulation at the M4 muscarinic acetylcholine receptor
19874574 Observational study of gene-disease association. (HuGE Navigator)
19156168 Clinical trial of gene-disease association, gene-environment interaction, and pharmacogenomic / toxicogenomic. (HuGE Navigator)
More...

AA Sequence

MANFTPVNGSSGNQSVRLVTSSSHNRYETVEMVFIATVTGSLSLVTVVGNILVMLSIKVNRQLQTVNNYF      1 - 70
LFSLACADLIIGAFSMNLYTVYIIKGYWPLGAVVCDLWLALDYVVSNASVMNLLIISFDRYFCVTKPLTY     71 - 140
PARRTTKMAGLMIAAAWVLSFVLWAPAILFWQFVVGKRTVPDNQCFIQFLSNPAVTFGTAIAAFYLPVVI    141 - 210
MTVLYIHISLASRSRVHKHRPEGPKEKKAKTLAFLKSPLMKQSVKKPPPGEAAREELRNGKLEEAPPPAL    211 - 280
PPPPRPVADKDTSNESSSGSATQNTKERPATELSTTEATTPAMPAPPLQPRALNPASRWSKIQIVTKQTG    281 - 350
NECVTAIEIVPATPAGMRPAANVARKFASIARNQVRKKRQMAARERKVTRTIFAILLAFILTWTPYNVMV    351 - 420
LVNTFCQSCIPDTVWSIGYWLCYVNSTINPACYALCNATFKKTFRHLLLCQYRNIGTAR               421 - 479
//

Text Mined References (38)

PMID Year Title
26958838 2016 Crystal structures of the M1 and M4 muscarinic acetylcholine receptors.
26025056 2015 Modified expression of peripheral blood lymphocyte muscarinic cholinergic receptors in asthmatic children.
24807966 2014 Development of a radioligand, [(3)H]LY2119620, to probe the human M(2) and M(4) muscarinic receptor allosteric binding sites.
24768300 2014 Chemogenetic synaptic silencing of neural circuits localizes a hypothalamus?midbrain pathway for feeding behavior.
24074052 2013 Probing structural requirements of positive allosteric modulators of the M4 muscarinic receptor.
23490763 2013 Cholinergic muscarinic M4 receptor gene polymorphisms: a potential risk factor and pharmacogenomic marker for schizophrenia.
21295605 2011 Validating the use of M4-BAC-GFP mice as tissue donors in cell replacement therapies in a rodent model of Huntington's disease.
20406819 2010 Structural determinants of allosteric agonism and modulation at the M4 muscarinic acetylcholine receptor: identification of ligand-specific and global activation mechanisms.
19874574 2009 Genetical genomic determinants of alcohol consumption in rats and humans.
19156168 2009 Pharmacogenetics of antipsychotic response in the CATIE trial: a candidate gene analysis.
More...