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    CHRM4 cholinergic receptor muscarinic 4 [ Homo sapiens (human) ]

    Gene ID: 1132, updated on 10-Dec-2024

    Summary

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    Official Symbol
    CHRM4provided by HGNC
    Official Full Name
    cholinergic receptor muscarinic 4provided by HGNC
    Primary source
    HGNC:HGNC:1953
    See related
    Ensembl:ENSG00000180720 MIM:118495; AllianceGenome:HGNC:1953
    Gene type
    protein coding
    RefSeq status
    REVIEWED
    Organism
    Homo sapiens
    Lineage
    Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
    Also known as
    HM4; M4R
    Summary
    The muscarinic cholinergic receptors belong to a larger family of G protein-coupled receptors. The functional diversity of these receptors is defined by the binding of acetylcholine and includes cellular responses such as adenylate cyclase inhibition, phosphoinositide degeneration, and potassium channel mediation. Muscarinic receptors influence many effects of acetylcholine in the central and peripheral nervous system. The clinical implications of this receptor are unknown; however, mouse studies link its function to adenylyl cyclase inhibition. [provided by RefSeq, Jul 2008]
    Orthologs
    mouse all
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    Genomic context

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    See CHRM4 in Genome Data Viewer
    Location:
    11p11.2
    Exon count:
    2
    Annotation release Status Assembly Chr Location
    RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 11 NC_000011.10 (46383789..46391776, complement)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 11 NC_060935.1 (46539864..46547851, complement)
    RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 11 NC_000011.9 (46405339..46413326, complement)

    Chromosome 11 - NC_000011.10Genomic Context describing neighboring genes Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr11:46312695-46313398 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 3301 Neighboring gene cAMP responsive element binding protein 3 like 1 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr11:46328063-46328758 Neighboring gene ReSE screen-validated silencer GRCh37_chr11:46352624-46352765 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 4676 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 3302 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr11:46357769-46358498 Neighboring gene OCT4-NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr11:46360689-46361418 Neighboring gene Sharpr-MPRA regulatory region 11965 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 4678 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 4679 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 3303 Neighboring gene ReSE screen-validated silencer GRCh37_chr11:46369312-46369525 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr11:46369839-46370824 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr11:46373336-46374190 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr11:46374191-46375045 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr11:46375046-46375899 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr11:46377222-46378090 Neighboring gene diacylglycerol kinase zeta Neighboring gene CDK7 strongly-dependent group 2 enhancer GRCh37_chr11:46390736-46391935 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 3306 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr11:46401950-46402584 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 3307 Neighboring gene Sharpr-MPRA regulatory region 2210 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 3309 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 3310 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr11:46411613-46412218 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr11:46412219-46412822 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 3312 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 3311 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr11:46414340-46415114 Neighboring gene microRNA 4688 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr11:46428977-46429764 Neighboring gene midkine Neighboring gene autophagy and beclin 1 regulator 1 Neighboring gene OCT4-NANOG hESC enhancer GRCh37_chr11:46448914-46449505 Neighboring gene ribosomal protein S10 pseudogene 19 Neighboring gene NANOG hESC enhancer GRCh37_chr11:46467611-46468112 Neighboring gene microRNA 3160-1 Neighboring gene microRNA 3160-2

    Genomic regions, transcripts, and products

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    Go to nucleotide: Graphics FASTA GenBank

    Bibliography

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    Related articles in PubMed

    1. Genetic linkage mapping of the m4 human muscarinic receptor (CHRM4). Grewal RP, et al. Genomics, 1992 May. PMID 1577490
    2. Loss of muscarinic M4 receptors in hippocampus of Alzheimer patients. Mulugeta E, et al. Brain Res, 2003 Jan 17. PMID 12505680
    3. Muscarinic M4 receptor recycling requires a motif in the third intracellular loop. Hashimoto Y, et al. J Pharmacol Exp Ther, 2008 Jun. PMID 18337477
    4. Structural determinants of allosteric agonism and modulation at the M4 muscarinic acetylcholine receptor: identification of ligand-specific and global activation mechanisms. Nawaratne V, et al. J Biol Chem, 2010 Jun 18. PMID 20406819, Free PMC Article
    5. Validating the use of M4-BAC-GFP mice as tissue donors in cell replacement therapies in a rodent model of Huntington's disease. Döbrössy M, et al. J Neurosci Methods, 2011 Apr 15. PMID 21295605

    See all (53) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. Muscarinic Receptors Expression in the Peripheral Blood Cells Differentiate Dementia with Lewy Bodies from Alzheimer's Disease.
      Title: Muscarinic Receptors Expression in the Peripheral Blood Cells Differentiate Dementia with Lewy Bodies from Alzheimer's Disease.
    2. Group II muscarinic acetylcholine receptors attenuate hepatic injury via Nrf2/ARE pathway.
      Title: Group II muscarinic acetylcholine receptors attenuate hepatic injury via Nrf2/ARE pathway.
    3. Authors discuss how M4 activity regulates DA release and signaling, the potential sources of ACh that can regulate M4 activity, and the implications of targeting M4 activity for the treatment of the motor symptoms in movement disorders. [Review]
      Title: Roles of the M(4) acetylcholine receptor in the basal ganglia and the treatment of movement disorders.
    4. the association of the African-specific CHRM4 SNP with cocaine dependence survived correction for multiple testing
      Title: African-specific variability in the acetylcholine muscarinic receptor M4: association with cocaine and heroin addiction.
    5. crystal structures of the M1 and M4 muscarinic receptors bound to the inverse agonist, tiotropium
      Title: Crystal structures of the M1 and M4 muscarinic acetylcholine receptors.
    6. 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.
      Title: Modified expression of peripheral blood lymphocyte muscarinic cholinergic receptors in asthmatic children.
    7. This study identify suppression of the PVHSIM1-->PAGvl/DR circuit connection as sufficient to induce overeating behavior.
      Title: Chemogenetic synaptic silencing of neural circuits localizes a hypothalamus→midbrain pathway for feeding behavior.
    8. [(3)H]LY2119620 to probe specifically the human M2 and M4 muscarinic receptor allosteric binding sites.
      Title: Development of a radioligand, [(3)H]LY2119620, to probe the human M(2) and M(4) muscarinic receptor allosteric binding sites.
    9. Data indicate that compounds derived from VU0152100 showed M4 muscarinic receptor (M4 mAChR) direct agoinst properties.
      Title: Probing structural requirements of positive allosteric modulators of the M4 muscarinic receptor.
    10. The data of this study suggested that the rs2067482 polymorphism may help to predict susceptibility to schizophrenia and/or therapeutic responsiveness.
      Title: Cholinergic muscarinic M4 receptor gene polymorphisms: a potential risk factor and pharmacogenomic marker for schizophrenia.
    Submit: New GeneRIF Correction See all GeneRIFs (18)

    Phenotypes

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    Find tests for this gene in the NIH Genetic Testing Registry (GTR)

    Review eQTL and phenotype association data in this region using PheGenI

    Variation

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    See variants in ClinVar

    See studies and variants in dbVar

    See Variation Viewer (GRCh37.p13)

    See Variation Viewer (GRCh38)

    Pathways from PubChem

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    Interactions

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    Products Interactant Other Gene Complex Source Pubs Description

    General gene information

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    Markers

    Homology

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    enables G protein-coupled acetylcholine receptor activity IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    Process Evidence Code Pubs
    involved_in G protein-coupled acetylcholine receptor signaling pathway TAS
    Traceable Author Statement
    more info
    		 PubMed 
    involved_in G protein-coupled receptor signaling pathway, coupled to cyclic nucleotide second messenger IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in adenylate cyclase-inhibiting G protein-coupled acetylcholine receptor signaling pathway IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in cell surface receptor signaling pathway TAS
    Traceable Author Statement
    more info
    		 PubMed 
    involved_in chemical synaptic transmission IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in regulation of locomotion IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in signal transduction TAS
    Traceable Author Statement
    more info
    		 PubMed 
    Component Evidence Code Pubs
    is_active_in dendrite IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    is_active_in plasma membrane IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    located_in plasma membrane TAS
    Traceable Author Statement
    more info
    		  
    located_in postsynaptic membrane IEA
    Inferred from Electronic Annotation
    more info
    		  
    is_active_in synapse IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  

    General protein information

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    Preferred Names
    muscarinic acetylcholine receptor M4
    Names
    acetylcholine receptor, muscarinic 4

    NCBI Reference Sequences (RefSeq)

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    RefSeqs maintained independently of Annotated Genomes

    These reference sequences exist independently of genome builds. Explain

    These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

    mRNA and Protein(s)

    1. NM_000741.5 → NP_000732.2  muscarinic acetylcholine receptor M4

      See identical proteins and their annotated locations for NP_000732.2

      Status: REVIEWED

      Source sequence(s)
      AC116021
      Consensus CDS
      CCDS44581.1
      UniProtKB/Swiss-Prot
      B2RPP4, P08173, Q0VD60, Q4VBK7
      UniProtKB/TrEMBL
      Q96RG8
      Related
      ENSP00000507561.1, ENST00000682254.1
      Conserved Domains (1) summary
      cd15298
      Location:33 → 464
      7tmA_mAChR_M4; muscarinic acetylcholine receptor subtype M4, member of the class A family of seven-transmembrane G protein-coupled receptors

    2. NM_001366692.2 → NP_001353621.1  muscarinic acetylcholine receptor M4

      Status: REVIEWED

      Source sequence(s)
      AC116021
      Consensus CDS
      CCDS44581.1
      UniProtKB/Swiss-Prot
      B2RPP4, P08173, Q0VD60, Q4VBK7
      UniProtKB/TrEMBL
      Q96RG8
      Related
      ENSP00000409378.2, ENST00000433765.3
      Conserved Domains (1) summary
      cd15298
      Location:33 → 464
      7tmA_mAChR_M4; muscarinic acetylcholine receptor subtype M4, member of the class A family of seven-transmembrane G protein-coupled receptors

    RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2024_08

    The following sections contain reference sequences that belong to a specific genome build. Explain

    Reference GRCh38.p14 Primary Assembly

    Genomic

    1. NC_000011.10 Reference GRCh38.p14 Primary Assembly

      Range
      46383789..46391776 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060935.1 Alternate T2T-CHM13v2.0

      Range
      46539864..46547851 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)
    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    P08173.2 GenPept UniProtKB/Swiss-Prot:P08173

    Gene LinkOut

    The following LinkOut resources are supplied by external providers. These providers are responsible for maintaining the links.

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