Gene Symbol: CHRM4
Description: cholinergic receptor muscarinic 4
Alias: HM4, M4R, muscarinic acetylcholine receptor M4, acetylcholine receptor, muscarinic 4
Species: human
Products:     CHRM4

Top Publications

  1. Panossian A, Seo E, Efferth T. Novel molecular mechanisms for the adaptogenic effects of herbal extracts on isolated brain cells using systems biology. Phytomedicine. 2018;50:257-284 pubmed publisher
    ..melatonin activated adaptive signaling pathways and upregulated expression of UCN, GNRH1, TLR9, GP1BA, PLXNA4, CHRM4, GPR19, VIPR2, RORA, STAT5A, ZFPM2, ZNF396, FLT1, MAPK10, MERTK, PRKCH, and TTN, which were commonly regulated by ..
  2. Egerod K, Petersen N, Timshel P, Rekling J, Wang Y, Liu Q, et al. Profiling of G protein-coupled receptors in vagal afferents reveals novel gut-to-brain sensing mechanisms. Mol Metab. 2018;12:62-75 pubmed publisher
    ..GPCRs involved in lipid sensing and inflammation (e.g. CB1R, CYSLTR2, PTGER4), and neurotransmitters signaling (CHRM4, DRD2, CRHR2) were also highly enriched in Nav1.8-expressing neurons...
  3. Hossain F, Muthusamy V, Pandey N, Vishwakarma A, Baveja A, Zunjare R, et al. Marker-assisted introgression of opaque2 allele for rapid conversion of elite hybrids into quality protein maize. J Genet. 2018;97:287-298 pubmed
    ..These are the parental lines of three popular medium-maturing single cross hybrids (HM4, HM8 and HM9) in India...
  4. Dean B, Scarr E. Possible involvement of muscarinic receptors in psychiatric disorders: a focus on schizophrenia and mood disorders. Curr Mol Med. 2015;15:253-64 pubmed
    ..This review will focus on data suggesting changes in levels of CHRM1 and CHRM4 implicate these receptors in the pathophysiology of schizophrenia whereas data suggest a role for CHRM2 in mood ..
  5. Qvist P, Christensen J, Vardya I, Rajkumar A, Mørk A, Paternoster V, et al. The Schizophrenia-Associated BRD1 Gene Regulates Behavior, Neurotransmission, and Expression of Schizophrenia Risk Enriched Gene Sets in Mice. Biol Psychiatry. 2017;82:62-76 pubmed publisher
    ..g., calcium channel subunits [Cacna1c and Cacnb2], cholinergic muscarinic receptor 4 [Chrm4)], dopamine receptor D2 [Drd2], and transcription factor 4 [Tcf4])...
  6. Adriaenssens A, Lam B, Billing L, Skeffington K, Sewing S, Reimann F, et al. A Transcriptome-Led Exploration of Molecular Mechanisms Regulating Somatostatin-Producing D-Cells in the Gastric Epithelium. Endocrinology. 2015;156:3924-36 pubmed publisher
    ..Pyy, Gipr, Chrm4, Calcrl, Taar1, and Casr were identified as genes that are highly enriched in D-cells compared with SST-negative ..
  7. Piekarski E, Chequer R, Algalarrondo V, Eliahou L, Mahida B, Vigne J, et al. Cardiac denervation evidenced by MIBG occurs earlier than amyloid deposits detection by diphosphonate scintigraphy in TTR mutation carriers. Eur J Nucl Med Mol Imaging. 2018;45:1108-1118 pubmed publisher
    ..were classified as having normal heart-to-mediastinum (HMR) MIBG uptake ratio 4 h after injection (defined by HM4 ≥ 1.85) or abnormal HM4 < 1...
  8. Mahoney C, Agostinelli L, Brooks J, Lowell B, Scammell T. GABAergic Neurons of the Central Amygdala Promote Cataplexy. J Neurosci. 2017;37:3995-4006 pubmed publisher
    ..mice crossed with vGAT-Cre mice, resulting in selective expression of the excitatory hM3 receptor or the inhibitory hM4 receptor in GABAergic neurons of the CeA...
  9. Gogliotti R, Fisher N, Stansley B, Jones C, Lindsley C, Conn P, et al. Total RNA Sequencing of Rett Syndrome Autopsy Samples Identifies the M4 Muscarinic Receptor as a Novel Therapeutic Target. J Pharmacol Exp Ther. 2018;365:291-300 pubmed publisher
    ..A survey of our RNA-seq results also identified a significant decrease in expression of the CHRM4 gene, which encodes a receptor [muscarinic acetylcholine receptor 4 (M4)] that is the subject of ..

More Information


  1. Gibbons A, Dean B. The Cholinergic System: An Emerging Drug Target for Schizophrenia. Curr Pharm Des. 2016;22:2124-33 pubmed
    ..Amongst the most promising drug targets for treating schizophrenia are the ?7 nicotinic receptor and the CHRM1 and CHRM4 muscarinic receptors...
  2. Bonner T, Young A, Brann M, Buckley N. Cloning and expression of the human and rat m5 muscarinic acetylcholine receptor genes. Neuron. 1988;1:403-10 pubmed
    ..Expression of mRNA has yet to be observed in brain or selected peripheral tissues, suggesting that either it is substantially less abundant than m1-m4 or its distribution is quite different. ..
  3. Cherubini E, Tabbì L, Scozzi D, Mariotta S, Galli E, Carello R, et al. Modified expression of peripheral blood lymphocyte muscarinic cholinergic receptors in asthmatic children. J Neuroimmunol. 2015;284:37-43 pubmed publisher
    ..Increased lymphocyte muscarinic cholinergic receptor expression may concur with lung cholinergic dysfunction and with inflammatory molecular framework in asthma. ..
  4. Muthuri S, Saunders F, Hardy R, Pavlova A, Martin K, Gregory J, et al. Associations between body mass index across adult life and hip shapes at age 60 to 64: Evidence from the 1946 British birth cohort. Bone. 2017;105:115-121 pubmed publisher
    ..In men, higher BMI at all ages was also associated with lower HM4 scores (with negative HM4 values representing a flatter femoral head, a wider neck and smaller neck shaft angle) ..
  5. Stachniak T, Ghosh A, Sternson S. Chemogenetic synaptic silencing of neural circuits localizes a hypothalamus?midbrain pathway for feeding behavior. Neuron. 2014;82:797-808 pubmed publisher
    ..This synaptic silencing approach is broadly applicable for cell-type-specific and axon projection-selective functional analysis of diverse neural circuits. ..
  6. Huynh T, Valant C, Crosby I, Sexton P, Christopoulos A, Capuano B. Probing structural requirements of positive allosteric modulators of the M4 muscarinic receptor. J Med Chem. 2013;56:8196-200 pubmed publisher
    ..These compounds investigate the pharmacological effects of previously identified methoxy and fluoro substituents, providing useful estimates of affinity (KB), cooperativity (??), and direct agonist properties (?B). ..
  7. Scarr E, Um J, Cowie T, Dean B. Cholinergic muscarinic M4 receptor gene polymorphisms: a potential risk factor and pharmacogenomic marker for schizophrenia. Schizophr Res. 2013;146:279-84 pubmed publisher
    ..schizophrenia is a widespread disorder of unknown aetiology, we have previously shown that muscarinic M4 receptor (CHRM4) expression is decreased in the hippocampus and caudate-putamen from subjects with the disorder, implicating the ..
  8. Döbrössy M, Klein A, Janghra N, Nikkhah G, Dunnett S. Validating the use of M4-BAC-GFP mice as tissue donors in cell replacement therapies in a rodent model of Huntington's disease. J Neurosci Methods. 2011;197:6-13 pubmed publisher
    ..The data confirm that embryonic striatal tissue from the M4-BAC-GFP mice survives, stably expresses GFP, and thus represents a powerful novel way to study graft-host interaction in this animal model neurodegeneration. ..
  9. Grewal R, Martinez M, Hoehe M, Bonner T, Gershon E, Detera Wadleigh S. Genetic linkage mapping of the m4 human muscarinic receptor (CHRM4). Genomics. 1992;13:239-40 pubmed
  10. Thal D, Sun B, Feng D, Nawaratne V, Leach K, Felder C, et al. Crystal structures of the M1 and M4 muscarinic acetylcholine receptors. Nature. 2016;531:335-40 pubmed publisher
  11. Sato K, Fujii T, Watanabe Y, Yamada S, Ando T, Kazuko F, et al. Diversity of mRNA expression for muscarinic acetylcholine receptor subtypes and neuronal nicotinic acetylcholine receptor subunits in human mononuclear leukocytes and leukemic cell lines. Neurosci Lett. 1999;266:17-20 pubmed
    ..These results indicate that both neuronal-type Nc and Ms ACh receptors are present on the surface of lymphocytes. ..
  12. von Der Kammer H, Mayhaus M, Albrecht C, Enderich J, Wegner M, Nitsch R. Muscarinic acetylcholine receptors activate expression of the EGR gene family of transcription factors. J Biol Chem. 1998;273:14538-44 pubmed
    ..The data suggest that transcription of EGR-dependent target genes, including the AChE gene, can be under the control of extracellular and intracellular signals coupled to muscarinic receptors. ..
  13. Chernyavsky A, Arredondo J, Wess J, Karlsson E, Grando S. Novel signaling pathways mediating reciprocal control of keratinocyte migration and wound epithelialization through M3 and M4 muscarinic receptors. J Cell Biol. 2004;166:261-72 pubmed
    ..These findings offer novel insights into the mechanisms of ACh-mediated modulation of KC migration and wound reepithelialization, and may aid the development of novel methods to promote wound healing. ..
  14. Shi J, Hattori E, Zou H, Badner J, Christian S, Gershon E, et al. No evidence for association between 19 cholinergic genes and bipolar disorder. Am J Med Genet B Neuropsychiatr Genet. 2007;144B:715-23 pubmed
    ..Thus, it is unlikely that these 19 cholinergic genes play a major role in the pre-disposition to BD in these pedigrees. ..
  15. Brann M, Ellis J, Jørgensen H, Hill Eubanks D, Jones S. Muscarinic acetylcholine receptor subtypes: localization and structure/function. Prog Brain Res. 1993;98:121-7 pubmed
    ..The residues that contribute to ligand binding and G-protein coupling are described, as well as the implied structures of these functional domains. ..
  16. Nobles M, Benians A, Tinker A. Heterotrimeric G proteins precouple with G protein-coupled receptors in living cells. Proc Natl Acad Sci U S A. 2005;102:18706-11 pubmed
    ..Our work suggests that GPCR dimers and the G protein heterotrimer are present at the cell membrane in the resting state in a pentameric complex. ..
  17. van Koppen C, Lenz W, Nathanson N. Isolation, sequence and functional expression of the mouse m4 muscarinic acetylcholine receptor gene. Biochim Biophys Acta. 1993;1173:342-4 pubmed
  18. Nawaratne V, Leach K, Felder C, Sexton P, Christopoulos A. Structural determinants of allosteric agonism and modulation at the M4 muscarinic acetylcholine receptor: identification of ligand-specific and global activation mechanisms. J Biol Chem. 2010;285:19012-21 pubmed publisher
  19. Haga K, Kameyama K, Haga T, Kikkawa U, Shiozaki K, Uchiyama H. Phosphorylation of human m1 muscarinic acetylcholine receptors by G protein-coupled receptor kinase 2 and protein kinase C. J Biol Chem. 1996;271:2776-82 pubmed
  20. Levran O, Randesi M, Peles E, Correa Da Rosa J, Ott J, Rotrosen J, et al. African-specific variability in the acetylcholine muscarinic receptor M4: association with cocaine and heroin addiction. Pharmacogenomics. 2016;17:995-1003 pubmed publisher
    ..Of the 20 SNPs that showed nominally significant associations, the association of the African-specific CHRM4 SNP rs2229163 (Asn417=) with cocaine dependence survived correction for multiple testing (Pcorrected = 0.047)...
  21. Bonner T, Buckley N, Young A, Brann M. Identification of a family of muscarinic acetylcholine receptor genes. Science. 1987;237:527-32 pubmed
    ..This gene family provides a new basis for evaluating the diversity of muscarinic mechanisms in the nervous system. ..
  22. Hashimoto Y, Morisawa K, Saito H, Jojima E, Yoshida N, Haga T. Muscarinic M4 receptor recycling requires a motif in the third intracellular loop. J Pharmacol Exp Ther. 2008;325:947-53 pubmed publisher
    The present study was performed to identify sequence(s) in the third intracellular loop (i3) of the muscarinic acetylcholine receptor M4 subtype (M4 receptor) involved in its internalization and recycling...
  23. Heydorn A, Søndergaard B, Ersbøll B, Holst B, Nielsen F, Haft C, et al. A library of 7TM receptor C-terminal tails. Interactions with the proposed post-endocytic sorting proteins ERM-binding phosphoprotein 50 (EBP50), N-ethylmaleimide-sensitive factor (NSF), sorting nexin 1 (SNX1), and G protein-coupled receptor-associat. J Biol Chem. 2004;279:54291-303 pubmed
    ..It is concluded that the tail library provides useful information on the general importance of certain adaptor proteins, for example, in this case, ruling out EBP50 as being a broad spectrum-recycling adaptor. ..
  24. Dean B, McLeod M, Keriakous D, McKenzie J, Scarr E. Decreased muscarinic1 receptors in the dorsolateral prefrontal cortex of subjects with schizophrenia. Mol Psychiatry. 2002;7:1083-91 pubmed
    ..receptors are involved in the pathology of schizophrenia, we measured muscarinic(1) (M1R) and muscarinic(4)(M4R) protein and mRNA as well as [(3)H]pirenzepine binding in Brodmann's areas (BA) 9 and 40 obtained postmortem from ..
  25. McClatchy D, Knudsen C, Clark B, Kahn R, Hall R, Levey A. Novel interaction between the M4 muscarinic acetylcholine receptor and elongation factor 1A2. J Biol Chem. 2002;277:29268-74 pubmed
    ..eEF1A2 is an essential GTP-binding protein for protein synthesis. Thus, our data suggest a novel role for M4 in the regulation of protein synthesis through its interaction with eEF1A2. ..
  26. Buchli R, Ndoye A, Arredondo J, Webber R, Grando S. Identification and characterization of muscarinic acetylcholine receptor subtypes expressed in human skin melanocytes. Mol Cell Biochem. 2001;228:57-72 pubmed
  27. Wang H, Han H, Zhang L, Shi H, Schram G, Nattel S, et al. Expression of multiple subtypes of muscarinic receptors and cellular distribution in the human heart. Mol Pharmacol. 2001;59:1029-36 pubmed
  28. Oldenhof J, Vickery R, Anafi M, Oak J, Ray A, Schoots O, et al. SH3 binding domains in the dopamine D4 receptor. Biochemistry. 1998;37:15726-36 pubmed
    ..The data indicates that the D4 receptor contains SH3 binding sites and that these sites fall within a region involved in the control of receptor internalization. ..
  29. Warren N, Piggott M, Lees A, Perry E, Burn D. Intact coupling of M1 receptors and preserved M2 and M4 receptors in the cortex in progressive supranuclear palsy: contrast with other dementias. J Chem Neuroanat. 2008;35:268-74 pubmed publisher
    ..We conclude from this first systematic study of cortical muscarinic receptors in PSP that functioning cortical muscarinic receptors are preserved. A further, larger trial of cholinergic therapy, such as an M1 agonist, may be warranted. ..
  30. Thomson S, Seo S, Barnes S, Louros S, Muscas M, Dando O, et al. Cell-Type-Specific Translation Profiling Reveals a Novel Strategy for Treating Fragile X Syndrome. Neuron. 2017;95:550-563.e5 pubmed publisher
    ..In these neurons, we find that the Chrm4 transcript encoding muscarinic acetylcholine receptor 4 (M4) is excessively translated, and synthesis ..
  31. Schober D, Croy C, Xiao H, Christopoulos A, Felder C. Development of a radioligand, [(3)H]LY2119620, to probe the human M(2) and M(4) muscarinic receptor allosteric binding sites. Mol Pharmacol. 2014;86:116-23 pubmed publisher
    ..Our results therefore demonstrate the development of a radioligand, [(3)H]LY2119620 to probe specifically the human M2 and M4 muscarinic receptor allosteric binding sites. ..
  32. Mulugeta E, Karlsson E, Islam A, Kalaria R, Mangat H, Winblad B, et al. Loss of muscarinic M4 receptors in hippocampus of Alzheimer patients. Brain Res. 2003;960:259-62 pubmed
    ..Our findings suggest that, relative to other muscarinic receptor subtypes, the M(4) receptor could be the subtype which is selectively compromised in Alzeheimer's disease (AD). ..
  33. Peralta E, Ashkenazi A, Winslow J, Smith D, Ramachandran J, Capon D. Distinct primary structures, ligand-binding properties and tissue-specific expression of four human muscarinic acetylcholine receptors. EMBO J. 1987;6:3923-9 pubmed
    ..M1 and M2 muscarinic receptors (mAChR) as well as two previously undiscovered mAChR subtypes, designated HM3 and HM4. The amino acid sequence of each subtype reflects a structure consisting of seven, highly conserved transmembrane ..
  34. Ashkenazi A, Ramachandran J, Capon D. Acetylcholine analogue stimulates DNA synthesis in brain-derived cells via specific muscarinic receptor subtypes. Nature. 1989;340:146-50 pubmed
  35. Goyal R. Muscarinic receptor subtypes. Physiology and clinical implications. N Engl J Med. 1989;321:1022-9 pubmed
  36. Detera Wadleigh S, Wiesch D, Bonner T. An SstI polymorphism for the human muscarinic acetylcholine receptor gene, m4 (CHRM 4). Nucleic Acids Res. 1989;17:6431 pubmed