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CHRM4 Gene(Protein Coding)

Cholinergic Receptor Muscarinic 4

GCID:
GC11M054893
GIFtS:
50
Genes Participants
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Aliases for CHRM4 Gene

Aliases for CHRM4 Gene

  • Cholinergic Receptor Muscarinic 4 2 3 5
  • Acetylcholine Receptor, Muscarinic 4 2 3
  • Muscarinic Acetylcholine Receptor M4 3
  • HM4 3
  • M4R 3

External Ids for CHRM4 Gene

Previous GeneCards Identifiers for CHRM4 Gene

  • GC11M048191
  • GC11M047097
  • GC11M046438
  • GC11M046370
  • GC11M046363
  • GC11M046113
  • GC11M046406
  • GC11M047073
  • GC11M047919
  • GC11M050776
  • GC11M051571
  • GC11M052233
  • GC11M052893
  • GC11M053561
  • GC11M054227

Summaries for CHRM4 Gene

Entrez Gene Summary for CHRM4 Gene

  • 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]

GeneCards Summary for CHRM4 Gene

CHRM4 (Cholinergic Receptor Muscarinic 4) is a Protein Coding gene. Among its related pathways are Monoamine GPCRs and Peptide ligand-binding receptors. Gene Ontology (GO) annotations related to this gene include G-protein coupled receptor activity and G-protein coupled acetylcholine receptor activity. An important paralog of this gene is CHRM2.

UniProtKB/Swiss-Prot for CHRM4 Gene

  • The muscarinic acetylcholine receptor mediates various cellular responses, including inhibition of adenylate cyclase, breakdown of phosphoinositides and modulation of potassium channels through the action of G proteins. Primary transducing effect is inhibition of adenylate cyclase.

Tocris Summary for CHRM4 Gene

  • Muscarinic receptors are widely distributed throughout the body and control distinct functions according to location and subtype (M1 - M5).They are predominantly expressed in the parasympathetic nervous system where they exert both inhibitory and excitatory effects.

Gene Wiki entry for CHRM4 Gene

Additional gene information for CHRM4 Gene

No data available for CIViC summary , PharmGKB "VIP" Summary , fRNAdb sequence ontologies and piRNA Summary for CHRM4 Gene

Genomics for CHRM4 Gene

Products:

  1. Regulatory Element

GeneHancer (GH) Regulatory Elements for CHRM4 Gene

Promoters and enhancers for CHRM4 Gene
GeneHancer (GH) Identifier GH Type GH
Score		 GH Sources Gene Association Score Total Score TSS distance (kb) Number of Genes Away Size (kb) Transcription Factor
Binding Sites		 Gene Targets
GH11J046344 Promoter/Enhancer 2.4 EPDnew Ensembl ENCODE dbSUPER 12 +36.7 36702 10.4 HDGF SMAD1 FOXA2 ARNT SIN3A ZNF2 YY1 E2F8 ZNF143 SP3 GC11P046351 DGKZ C11orf49 LOC105376662 ENSG00000255314 SNORD67 ENSG00000255447 ENSG00000254514 MDK CHRM4
GH11J046552 Enhancer 1.3 Ensembl ENCODE 10.8 -169.0 -169018 5.5 HDGF PKNOX1 FOXA2 MLX ARNT ARID4B SIN3A DMAP1 SLC30A9 FOS ATG13 AMBRA1 HARBI1 CHRM4 MDK DGKZ C11orf49 ZNF408 MIR3160-1
GH11J046314 Enhancer 1.3 Ensembl ENCODE dbSUPER 10.5 +69.2 69212 5.4 HDGF PKNOX1 ARNT SIN3A YY1 TCF12 GLIS2 ZNF143 NFYC NCOA1 CREB3L1 LINC02489 MDK CHRM4 PACSIN3 ATG13 C11orf49 LRP4 GC11P046331
GH11J046538 Enhancer 0.9 ENCODE 12.1 -151.4 -151408 0.2 HDGF PKNOX1 ARID4B SIN3A ZNF2 ZNF48 ARID2 ZNF143 DEK REST CHRM4 AMBRA1 MDK DGKZ HARBI1 ATG13 MIR3160-1
GH11J046647 Enhancer 1 Ensembl ENCODE dbSUPER 10.7 -262.6 -262628 2.8 NFIA RXRA JUN RAD21 ATF2 NR2F2 SP1 JUND POLR2A ZBTB48 GC11M055307 ATG13 ARHGAP1 ZNF408 HARBI1 F2 AMBRA1 CHRM4 SNORD67 CKAP5
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around CHRM4 on UCSC Golden Path with GeneCards custom track

Top Transcription factor binding sites by QIAGEN in the CHRM4 gene promoter:
  • STAT3
  • NF-1/L
  • NF-1

Regulatory Element Products

Genomic Locations for CHRM4 Gene

Genomic Locations for CHRM4 Gene
chr11:46,384,792-46,386,608
(GRCh38/hg38)
Size:
1,817 bases
Orientation:
Minus strand
chr11:46,406,640-46,408,107
(GRCh37/hg19)
Size:
1,468 bases
Orientation:
Minus strand

Genomic View for CHRM4 Gene

Genes around CHRM4 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
CHRM4 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for CHRM4 Gene
GeneLoc Logo Genomic Neighborhood • Exon Structure • Gene Density

RefSeq DNA sequence for CHRM4 Gene

Proteins for CHRM4 Gene

Products:

  1. Antibody
  2. Protein
  3. Assay

  • Protein details for CHRM4 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    P08173-ACM4_HUMAN
    Recommended name:
    Muscarinic acetylcholine receptor M4
    Protein Accession:
    P08173
    Secondary Accessions:
    • B2RPP4
    • Q0VD60
    • Q4VBK7

    Protein attributes for CHRM4 Gene

    Size:
    479 amino acids
    Molecular mass:
    53049 Da
    Quaternary structure:
    No Data Available

    Three dimensional structures from OCA and Proteopedia for CHRM4 Gene

neXtProt entry for CHRM4 Gene

Protein Expression for CHRM4 Gene

See protein expression from ProteomicsDB, MOPED, PaxDb, and MaxQB

Post-translational modifications for CHRM4 Gene

  • Glycosylation at posLast=1313 and Asn8
  • Modification sites at PhosphoSitePlus

Other Protein References for CHRM4 Gene

ENSEMBL proteins:
REFSEQ proteins:

No data available for DME Specific Peptides for CHRM4 Gene

Domains & Families for CHRM4 Gene

Gene Families for CHRM4 Gene

HGNC:
IUPHAR :
Human Protein Atlas (HPA):
  • FDA approved drug targets
  • G-protein coupled receptors
  • Predicted membrane proteins

Protein Domains for CHRM4 Gene

InterPro:
Blocks:
ProtoNet:

Suggested Antigen Peptide Sequences for CHRM4 Gene

GenScript: Design optimal peptide antigens:

Graphical View of Domain Structure for InterPro Entry

P08173

UniProtKB/Swiss-Prot:

ACM4_HUMAN :
  • Belongs to the G-protein coupled receptor 1 family. Muscarinic acetylcholine receptor subfamily. CHRM4 sub-subfamily.
Family:
  • Belongs to the G-protein coupled receptor 1 family. Muscarinic acetylcholine receptor subfamily. CHRM4 sub-subfamily.
genes like me logo Genes that share domains with CHRM4: view

Function for CHRM4 Gene

Products:

  1. Animal Model
  2. CRISPR
  3. miRNA
  4. Inhibitory RNA
  5. Clone
  6. Cell Line

Molecular function for CHRM4 Gene

UniProtKB/Swiss-Prot Function:
The muscarinic acetylcholine receptor mediates various cellular responses, including inhibition of adenylate cyclase, breakdown of phosphoinositides and modulation of potassium channels through the action of G proteins. Primary transducing effect is inhibition of adenylate cyclase.
GENATLAS Biochemistry:
cholinergic receptor,muscarinic 4,G protein coupled receptor superfamily

Phenotypes From GWAS Catalog for CHRM4 Gene

Gene Ontology (GO) - Molecular Function for CHRM4 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0004930 G-protein coupled receptor activity IEA --
GO:0016907 G-protein coupled acetylcholine receptor activity IBA --
genes like me logo Genes that share ontologies with CHRM4: view
genes like me logo Genes that share phenotypes with CHRM4: view

Animal Models for CHRM4 Gene

MGI Knock Outs for CHRM4:

Animal Model Products

CRISPR Products

Inhibitory RNA Products

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for CHRM4

No data available for Enzyme Numbers (IUBMB) , Human Phenotype Ontology , miRNA , Transcription Factor Targets and HOMER Transcription for CHRM4 Gene

Localization for CHRM4 Gene

Subcellular locations from UniProtKB/Swiss-Prot for CHRM4 Gene

Cell membrane; Multi-pass membrane protein. Cell junction, synapse, postsynaptic cell membrane; Multi-pass membrane protein.

Subcellular locations from

COMPARTMENTS
Extracellular space Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi Apparatus Nucleus Mitochondrion 0 1 2 3 4 5 Confidence
COMPARTMENTS Subcellular localization image for CHRM4 gene
Compartment Confidence
plasma membrane 5
endosome 1

Subcellular locations from the

Human Protein Atlas (HPA)
  • Golgi apparatus (1)
  • Nucleus (1)
See all subcellular structures

Gene Ontology (GO) - Cellular Components for CHRM4 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005886 plasma membrane TAS --
GO:0005887 integral component of plasma membrane IEA,TAS --
GO:0016020 membrane IEA --
GO:0016021 integral component of membrane IEA --
GO:0030054 cell junction IEA --
genes like me logo Genes that share ontologies with CHRM4: view

Pathways & Interactions for CHRM4 Gene

genes like me logo Genes that share pathways with CHRM4: view

Gene Ontology (GO) - Biological Process for CHRM4 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0007165 signal transduction TAS 9603968
GO:0007166 cell surface receptor signaling pathway TAS 2739737
GO:0007186 G-protein coupled receptor signaling pathway TAS --
GO:0007197 adenylate cyclase-inhibiting G-protein coupled acetylcholine receptor signaling pathway IBA,IEA --
GO:0007207 phospholipase C-activating G-protein coupled acetylcholine receptor signaling pathway IBA --
genes like me logo Genes that share ontologies with CHRM4: view

No data available for SIGNOR curated interactions for CHRM4 Gene

Drugs & Compounds for CHRM4 Gene

Products:

  1. Drug

(160) Drugs for CHRM4 Gene - From: DrugBank, DGIdb, FDA Approved Drugs, IUPHAR, HMDB, Tocris, and Novoseek

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
Tropicamide Approved, Investigational Pharma antagonist, Target Antimuscarinic drug, Selective M4 muscarinic antagonist 25
Atropine Approved, Vet_approved Pharma Antagonist, antagonist, Target MAChRs antagonist 153
Darifenacin Approved, Investigational Pharma Antagonist, Inverse agonist, antagonist, Target M3 receptor antagonist and antimuscarinic agents 22
Acetylcholine Approved Pharma Full agonist, Agonist, Target 863
Fesoterodine Approved Pharma Target, antagonist 64

(8) Additional Compounds for CHRM4 Gene - From: HMDB, IUPHAR, Novoseek, and Tocris

Name Synonyms Role CAS Number PubChem IDs PubMed IDs
(-)aceclidine
Partial agonist, Agonist
(+)aceclidine
Full agonist, Agonist
Gouml 7874
Neutral, Allosteric regulator, Negative
HHSiD
Antagonist
N-Dealkylated tolterodine

(4) Tocris Compounds for CHRM4 Gene

Compound Action Cas Number
PD 102807 Selective M4 antagonist 23062-91-1
Tropicamide Selective M4 muscarinic antagonist 1508-75-4
VU 10010 Selective allosteric potentiator of M4 receptors 633283-39-3
VU 152100 Positive allosteric modulator of M4 receptors 409351-28-6
genes like me logo Genes that share compounds with CHRM4: view

Transcripts for CHRM4 Gene

Products:

  1. CRISPR
  2. miRNA
  3. Inhibitory RNA
  4. Clone

mRNA/cDNA for CHRM4 Gene

(1) REFSEQ mRNAs :
(6) Additional mRNA sequences :
(10) Selected AceView cDNA sequences:
(1) Ensembl transcripts including schematic representations, and UCSC links where relevant :

Unigene Clusters for CHRM4 Gene

Cholinergic receptor, muscarinic 4:
Representative Sequences:

CRISPR Products

Inhibitory RNA Products

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for CHRM4

Alternative Splicing Database (ASD) splice patterns (SP) for CHRM4 Gene

No ASD Table

Relevant External Links for CHRM4 Gene

GeneLoc Exon Structure for
CHRM4
ECgene alternative splicing isoforms for
CHRM4

Expression for CHRM4 Gene

Products:

  1. Primer
  2. Gene Expression Assay

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and CGAP SAGE for CHRM4 Gene

mRNA expression in normal human tissues for CHRM4 Gene
mRNA expression by GTEx for CHRM4 GenemRNA expression by BioGPS for CHRM4 Gene

mRNA differential expression in normal tissues according to GTEx for CHRM4 Gene

This gene is overexpressed in Brain - Putamen (basal ganglia) (x8.6), Brain - Nucleus accumbens (basal ganglia) (x8.0), Brain - Caudate (basal ganglia) (x7.5), and Spleen (x4.2).

Protein differential expression in normal tissues from HIPED for CHRM4 Gene

This gene is overexpressed in Platelet (69.0).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB and MOPED for CHRM4 Gene



Protein tissue co-expression partners for CHRM4 Gene

- Elite partner

NURSA nuclear receptor signaling pathways regulating expression of CHRM4 Gene:

CHRM4

SOURCE GeneReport for Unigene cluster for CHRM4 Gene:

Hs.248100

Evidence on tissue expression from TISSUES for CHRM4 Gene

  • Nervous system(4.4)
genes like me logo Genes that share expression patterns with CHRM4: view

No data available for mRNA Expression by UniProt/SwissProt and Phenotype-based relationships between genes and organs from Gene ORGANizer for CHRM4 Gene

Orthologs for CHRM4 Gene

This gene was present in the common ancestor of animals.

Orthologs for CHRM4 Gene

Organism Taxonomy Gene Similarity Type Details
cow
(Bos Taurus)
 Mammalia CHRM4 34
  • 95 (a)
 OneToOne
chimpanzee
(Pan troglodytes)
 Mammalia CHRM4 34
  • 93 (a)
 OneToOne
dog
(Canis familiaris)
 Mammalia CHRM4 34 33
  • 92.47 (n)
 OneToOne
mouse
(Mus musculus)
 Mammalia Chrm4 16 34 33
  • 89.61 (n)
rat
(Rattus norvegicus)
 Mammalia Chrm4 33
  • 89.4 (n)
platypus
(Ornithorhynchus anatinus)
 Mammalia -- 34
  • 87 (a)
 OneToMany
-- 34
  • 72 (a)
 OneToMany
chicken
(Gallus gallus)
 Aves CHRM4 34 33
  • 75.43 (n)
 OneToOne
lizard
(Anolis carolinensis)
 Reptilia CHRM4 34
  • 74 (a)
 OneToOne
tropical clawed frog
(Silurana tropicalis)
 Amphibia chrm4 33
  • 71.61 (n)
zebrafish
(Danio rerio)
 Actinopterygii chrm4a 34 33
  • 71.21 (n)
 OneToOne
fruit fly
(Drosophila melanogaster)
 Insecta CG7918 35
  • 38 (a)
mAcR-60C 34 35
  • 24 (a)
 OneToMany
worm
(Caenorhabditis elegans)
 Secernentea gar-3 34
  • 27 (a)
 OneToMany
sea squirt
(Ciona savignyi)
 Ascidiacea -- 34
  • 34 (a)
 OneToMany
Species where no ortholog for CHRM4 was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Ashbya gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African clawed frog (Xenopus laevis)
  • African malaria mosquito (Anopheles gambiae)
  • Alicante grape (Vitis vinifera)
  • alpha proteobacteria (Wolbachia pipientis)
  • amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • baker's yeast (Saccharomyces cerevisiae)
  • barley (Hordeum vulgare)
  • beta proteobacteria (Neisseria meningitidis)
  • bread mold (Neurospora crassa)
  • Chromalveolata (Phytophthora infestans)
  • common water flea (Daphnia pulex)
  • corn (Zea mays)
  • E. coli (Escherichia coli)
  • filamentous fungi (Aspergillus nidulans)
  • Firmicute bacteria (Streptococcus pneumoniae)
  • fission yeast (Schizosaccharomyces pombe)
  • green algae (Chlamydomonas reinhardtii)
  • honey bee (Apis mellifera)
  • K. lactis yeast (Kluyveromyces lactis)
  • loblloly pine (Pinus taeda)
  • malaria parasite (Plasmodium falciparum)
  • medicago trunc (Medicago Truncatula)
  • moss (Physcomitrella patens)
  • oppossum (Monodelphis domestica)
  • orangutan (Pongo pygmaeus)
  • pig (Sus scrofa)
  • rainbow trout (Oncorhynchus mykiss)
  • rice (Oryza sativa)
  • rice blast fungus (Magnaporthe grisea)
  • schistosome parasite (Schistosoma mansoni)
  • sea anemone (Nematostella vectensis)
  • sea urchin (Strongylocentrotus purpuratus)
  • sorghum (Sorghum bicolor)
  • soybean (Glycine max)
  • stem rust fungus (Puccinia graminis)
  • sugarcane (Saccharum officinarum)
  • thale cress (Arabidopsis thaliana)
  • tomato (Lycopersicon esculentum)
  • toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • wheat (Triticum aestivum)

Evolution for CHRM4 Gene

ENSEMBL:
Gene Tree for CHRM4 (if available)
TreeFam:
Gene Tree for CHRM4 (if available)
Aminode:
Evolutionary constrained regions (ECRs) for CHRM4: view image

Paralogs for CHRM4 Gene

Paralogs for CHRM4 Gene

(9) SIMAP similar genes for CHRM4 Gene using alignment to 2 proteins:

  • ACM4_HUMAN
  • Q96RG8_HUMAN
genes like me logo Genes that share paralogs with CHRM4: view

Variants for CHRM4 Gene

Products:

  1. SNP Genotyping and Copy Number Assay

Sequence variations from dbSNP and Humsavar for CHRM4 Gene

SNP ID Clin Chr 11 pos Variation AA Info Type
rs1000159355 -- 46,386,758(-) C/G upstream_transcript_variant
rs1000209568 -- 46,386,312(-) G/A coding_sequence_variant, synonymous_variant
rs1000320104 -- 46,387,010(-) G/A upstream_transcript_variant
rs1001164681 -- 46,388,087(-) C/T upstream_transcript_variant
rs1001216819 -- 46,387,927(-) G/T upstream_transcript_variant

Structural Variations from Database of Genomic Variants (DGV) for CHRM4 Gene

Variant ID Type Subtype PubMed ID
esv3626183 CNV gain 21293372
esv3626185 CNV loss 21293372
nsv309 CNV deletion 18451855
nsv554201 CNV loss 21841781
nsv554202 CNV loss 21841781
nsv825867 CNV gain 20364138
nsv951610 CNV deletion 24416366

Variation tolerance for CHRM4 Gene

Residual Variation Intolerance Score: 19.3% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 0.49; 10.59% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for CHRM4 Gene

SNPedia medical, phenotypic, and genealogical associations of SNPs for
CHRM4

SNP Genotyping and Copy Number Assay Products

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for CHRM4 Gene

Disorders for CHRM4 Gene

Additional Disease Information for CHRM4

Genetic Association Database
(GAD)
Human Genome Epidemiology Navigator
(HuGE)
ATLAS of Genetics and Cytogenetics in Oncology and Haematology

No disorders were found for CHRM4 Gene.

No data available for MalaCards , UniProtKB/Swiss-Prot and Genatlas for CHRM4 Gene

Publications for CHRM4 Gene

  1. Pharmacogenetics of antipsychotic response in the CATIE trial: a candidate gene analysis. (PMID: 19156168) Need AC … Goldstein DB (European journal of human genetics : EJHG 2009) 3 44 58
  2. Genetical genomic determinants of alcohol consumption in rats and humans. (PMID: 19874574) Tabakoff B … WHO/ISBRA Study on State and Trait Markers of Alcoholism (BMC biology 2009) 3 44 58
  3. Muscarinic M4 receptor recycling requires a motif in the third intracellular loop. (PMID: 18337477) Hashimoto Y … Haga T (The Journal of pharmacology and experimental therapeutics 2008) 3 22 58
  4. No evidence for association between 19 cholinergic genes and bipolar disorder. (PMID: 17373692) Shi J … Liu C (American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics 2007) 3 44 58
  5. The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). (PMID: 15489334) Gerhard DS … MGC Project Team (Genome research 2004) 3 4 58

Products for CHRM4 Gene

  • Addgene plasmids for CHRM4

Sources for CHRM4 Gene

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