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CHRNA4 Gene

protein-coding   GIFtS: 68
GCID: GC20M061974

Cholinergic Receptor, Nicotinic, Alpha 4 (Neuronal)

(Previous names: cholinergic receptor, nicotinic, alpha polypeptide 4)
(Previous symbols: EBN, EBN1)
Microbiology & Infectious Diseases Congress
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(According to 1HGNC, 2Entrez Gene,
3UniProtKB/Swiss-Prot, 4UniProtKB/TrEMBL, 5OMIM, 6GeneLoc, 7Ensembl, 8DME, 9miRBase, 10fRNAdb, 12H-InvDB, 13NCBI, 14NONCODE, and/or 15RNAdb)
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Aliases
Cholinergic Receptor, Nicotinic, Alpha 4 (Neuronal)1 2     nicotinic1
EBN1 2     BFNC2
EBN11 2     NACHR2
Cholinergic Receptor, Nicotinic, Alpha Polypeptide 41 2     NACHRA42
NACRA42 3     Neuronal Acetylcholine Receptor Subunit Alpha-42
Acetylcholine Receptor1     Neuronal Nicotinic Acetylcholine Receptor Alpha-4 Subunit2
Alpha 4 (Neuronal)1     ENFL15

External Ids:    HGNC: 19581   Entrez Gene: 11372   Ensembl: ENSG000001012047   OMIM: 1185045   UniProtKB: P436813   

Export aliases for CHRNA4 gene to outside databases

Previous GC identifers: GC20U990005 GC20M061813 GC20M062655 GC20M062702 GC20M061446 GC20M058700


(According to Entrez Gene, GeneCards, Tocris Bioscience, Wikipedia's Gene Wiki, PharmGKB,
UniProtKB/Swiss-Prot, and/or UniProtKB/TrEMBL)
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Entrez Gene summary for CHRNA4 Gene:
This gene encodes a nicotinic acetylcholine receptor, which belongs to a superfamily of ligand-gated ion channels
that play a role in fast signal transmission at synapses. These pentameric receptors can bind acetylcholine,
which causes an extensive change in conformation that leads to the opening of an ion-conducting channel across
the plasma membrane. This protein is an integral membrane receptor subunit that can interact with either nAChR
beta-2 or nAChR beta-4 to form a functional receptor. Mutations in this gene cause nocturnal frontal lobe
epilepsy type 1. Polymorphisms in this gene that provide protection against nicotine addiction have been
described. Alternative splicing results in multiple transcript variants. (provided by RefSeq, Feb 2012)

GeneCards Summary for CHRNA4 Gene:
CHRNA4 (cholinergic receptor, nicotinic, alpha 4 (neuronal)) is a protein-coding gene. Diseases associated with CHRNA4 include chrna4-related nocturnal frontal lobe epilepsy, autosomal dominant, and nicotine addiction. GO annotations related to this gene include acetylcholine-activated cation-selective channel activity and ligand-gated ion channel activity. An important paralog of this gene is CHRNA5.

UniProtKB/Swiss-Prot: ACHA4_HUMAN, P43681
Function: After binding acetylcholine, the AChR responds by an extensive change in conformation that affects all
subunits and leads to opening of an ion-conducting channel across the plasma membrane permeable to sodium ions

summary for CHRNA4 Gene:
Nicotinic alpha4beta2 receptors have high affinity for nicotine and account for >90% of [3H]-nicotine
binding to brain tissues. A stoichiometry of (alpha4)2(beta2)3 has been proposed, generating two agonist
binding sites consistent with the model of the muscle nAChR. Manipulation of the stoichiometry of
alpha4beta2 nAChRs expressed in Xenopus oocytes indicates that (alpha4)3(beta2)2 nAChRs are also viable,
displaying lower affinity for ACh and higher Ca2+ permeability; whether native nAChRs with this subunit
stoichiometry exist is not known. Transgenic knockout of either of these subunits eliminates nicotine self
administration, whereas virally targeted re-expression of the beta2 subunit in mesolimbic areas of beta2
knockout mice recovers this behavior, implicating a role for alpha4beta2 nAChRs in nicotine addiction.
alpha4beta2 nAChRs are highly expressed in the thalamus and have been suggested to have a putative role in
the thalamo-cortical circuitry . As a consequence of their putative role in thalamo-cortical circuitry, gain
of function mutations in the M2 domain of either the alpha4 or beta2 subunit give rise to some forms of
autosomal dominant nocturnal frontal lobe epilepsy. The human genes encoding the nicotinic alpha4 and beta2
receptor subunits have been localized to chromosomes 13 (q13.2-q13.3) and 1 (1q21.3) respectively.

Gene Wiki entry for CHRNA4 Gene


(According to GeneLoc and/or HGNC, and/or
Entrez Gene (NCBI build 37),
and/or miRBase,
Genomic Views according to UCSC (hg19) and Ensembl (release 75), Regulatory elements and Epigenetics data according to QIAGEN, and/or SwitchGear Genomics)
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RefSeq DNA sequence:
NC_000020.11  NT_011362.11  NC_018931.2  
Regulatory elements:
   Regulatory transcription factor binding sites in the CHRNA4 gene promoter:
         CREB   p53   NRSF form 1   NRSF form 2   GATA-2   
         Other transcription factors

SwitchGear Promoter luciferase reporter plasmidCHRNA4 promoter sequence
   Search Chromatin IP Primers for CHRNA4

Epigenetics:
DNA Methylation CpG Assay Predesigned for Pyrosequencing in human, mouse, rat CHRNA4


Genomic Location:
Genomic View: UCSC Golden Path with GeneCards custom track

Entrez Gene cytogenetic band: 20q13.33   Ensembl cytogenetic band:  20q13.33   HGNC cytogenetic band: 20q13.33

CHRNA4 Gene in genomic location: bands according to Ensembl, locations according to (and/or Entrez Gene and/or Ensembl if different)
CHRNA4 gene location

GeneLoc information about chromosome 20         GeneLoc Exon Structure

GeneLoc location for GC20M061974:  view genomic region     (about GC identifiers)

Start:
61,974,665 bp from pter      End:
62,009,753 bp from pter
Size:
35,089 bases      Orientation:
minus strand

(According to 1UniProtKB, HORDE, 2neXtProt, Ensembl, and/or Reactome, Modification sites according to PhosphoSitePlus, Specific Peptides from DME, RefSeq according to NCBI, PDB rendering according to OCA and/or Proteopedia, Recombinant Proteins from EMD Millipore, R&D Systems, GenScript, Enzo Life Sciences, OriGene, Novus Biologicals, Sino Biological, ProSpec, and/or Cloud-Clone Corp.,
Biochemical Assays by EMD Millipore, R&D Systems, OriGene, GenScript, Cell Signaling Technology, Enzo Life Sciences, and/or Cloud-Clone Corp., Antibodies by EMD Millipore, R&D Systems, Cell Signaling Technology, OriGene, Novus Biologicals, Thermo Fisher Scientific, LSBio, Abcam, and/or Cloud-Clone Corp.)
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UniProtKB/Swiss-Prot: ACHA4_HUMAN, P43681 (See protein sequence)
Recommended Name: Neuronal acetylcholine receptor subunit alpha-4 precursor  
Size: 627 amino acids; 69957 Da
Subunit: Neuronal AChR is composed of two different types of subunits: alpha and beta. Alpha-4 subunit can be
combined to beta-2 or beta-4 to give rise to functional receptors, complexes with beta-2 may be heteropentamers.
Interacts with RIC3; which is required for proper folding and assembly
2 PDB 3D structures from and Proteopedia for CHRNA4:
2GVT (3D)        2LLY (3D)    
Secondary accessions: Q4JGR7 Q4VAQ6

Explore the universe of human proteins at neXtProt for CHRNA4: NX_P43681

Explore proteomics data for CHRNA4 at MOPED

Post-translational modifications: 

  • Glycosylation2 at Asn57, Asn107, Asn174
  • Modification sites at PhosphoSitePlus

  • See CHRNA4 Protein Expression from SPIRE MOPED, PaxDB, and MaxQB

    REFSEQ proteins (2 alternative transcripts): 
    NP_000735.1  NP_001243502.1  

    ENSEMBL proteins: 
     ENSP00000359285   ENSP00000429513  
    Reactome Protein details: P43681

    CHRNA4 Human Recombinant Protein Products:

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    Browse Proteins at Cloud-Clone Corp.

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    (According to HGNC, IUPHAR, InterPro, ProtoNet, UniProtKB, and/or BLOCKS, Sets of similar genes according to GeneDecks)
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    HGNC Gene Families:
    CHRN: Ligand-gated ion channels / Acetylcholine receptors, nicotinic
    CHR: Cholinergic receptors

    IUPHAR Guide to PHARMACOLOGY protein family classification: alpha4
    Nicotinic acetylcholine receptors

    Selected InterPro protein domains (see all 6):
     IPR027361 Acetylcholine_rcpt_TM
     IPR002394 Nicotinic_acetylcholine_rcpt
     IPR018000 Neurotransmitter_ion_chnl_CS
     IPR006201 Neur_channel
     IPR006202 Neur_chan_lig-bd

    Graphical View of Domain Structure for InterPro Entry P43681

    ProtoNet protein and cluster: P43681

    2 Blocks protein domains:
    IPB002394 Nicotinic acetylcholine receptor signature
    IPB006201 Neurotransmitter-gated ion-channel


    UniProtKB/Swiss-Prot: ACHA4_HUMAN, P43681
    Similarity: Belongs to the ligand-gated ion channel (TC 1.A.9) family. Acetylcholine receptor (TC 1.A.9.1)
    subfamily. Alpha-4/CHRNA4 sub-subfamily


    CHRNA4 for domains           About GeneDecksing


    (According to 1UniProtKB, Genatlas, LifeMap Discovery™, IUBMB, and/or 2DME, Human phenotypes from GenomeRNAi, Animal models from MGI Mar 06 2013, inGenious Targeting Laboratory, genOway,
    transcription factor targeting from QIAGEN and/or HOMER, miRNA Gene Targets from miRTarBase, shRNA from OriGene, siRNAs from OriGene, QIAGEN, microRNA from QIAGEN, SwitchGear Genomics, Gene Editing from DNA2.0, Clones from OriGene, GenScript, Sino Biological, DNA2.0, and Vector BioLabs, Cell Lines from GenScript, ESI BIO, In Situ Hybridization Assays from Advanced Cell Diagnostics, Ontologies according to Gene Ontology Consortium 01 Apr 2014 via Entrez Gene.)
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    Molecular Function:

         UniProtKB/Swiss-Prot Summary: ACHA4_HUMAN, P43681
    Function: After binding acetylcholine, the AChR responds by an extensive change in conformation that affects all
    subunits and leads to opening of an ion-conducting channel across the plasma membrane permeable to sodium ions

         Genatlas biochemistry entry for CHRNA4:
    cholinergic receptor,nicotinic,alpha 4 polypeptide,neuronal

         Gene Ontology (GO): Selected molecular function terms (see all 7):    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0004889acetylcholine-activated cation-selective channel activity TAS--
    GO:0005216ion channel activity ----
    GO:0005230extracellular ligand-gated ion channel activity ----
    GO:0005515protein binding ----
    GO:0015276ligand-gated ion channel activity TAS--
         
    CHRNA4 for ontologies           About GeneDecksing


    Phenotypes:
         8 MGI mutant phenotypes (inferred from 12 alleles(MGI details for Chrna4):
     behavior/neurological  hematopoietic system  homeostasis/metabolism  immune system  integument 
     mortality/aging  nervous system  no phenotypic analysis 

    CHRNA4 for phenotypes           About GeneDecksing

    Animal Models:
         MGI mouse knock-outs for CHRNA4: Chrna4tm1Jpc Chrna4tm1Dra Chrna4tm1.2Tmcg

       inGenious Targeting Laboratory: Let us create your new Knockout/Knockin mouse model for CHRNA4
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       genOway customized KO model: permanent, tissue-specific or time-controlled inactivation for CHRNA4
       genOway customized Knockin model: humanization, point mutation, expression monitoring, etc. for CHRNA4

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    1 qRT-PCR Assays for microRNA that regulate CHRNA4:
    hsa-miR-1324
    SwitchGear 3'UTR luciferase reporter plasmidCHRNA4 3' UTR sequence
    Inhib. RNA
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    Predesigned siRNA for gene silencing in human, mouse, rat CHRNA4

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    GenScript: all cDNA clones in your preferred vector: CHRNA4 (NM_000744)
    Browse Sino Biological Human cDNA Clones
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    Advanced Cell Diagnostics RNAscope RNA in situ hybridization assays for CHRNA4


    (According to UniProtKB, COMPARTMENTS Subcellular localization database, Ontologies according to Gene Ontology Consortium 01 Apr 2014 via Entrez Gene.)
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    Subcellular locations from UniProtKB/Swiss-Prot
    ACHA4_HUMAN, P43681: Cell junction, synapse, postsynaptic cell membrane; Multi-pass membrane protein. Cell
    membrane; Multi-pass membrane protein. Cell membrane; Lipid-anchor (By similarity)
    Subcellular locations from COMPARTMENTS: 

    CompartmentConfidence
    plasma membrane5
    cytoskeleton2
    endoplasmic reticulum2
    extracellular2
    nucleus2

    Gene Ontology (GO): Selected cellular component terms (see all 9):    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0005886plasma membrane TAS--
    GO:0005892acetylcholine-gated channel complex IDA8906617
    GO:0009897external side of plasma membrane ISS--
    GO:0016020membrane ISS--
    GO:0016021integral component of membrane NAS8906617

    CHRNA4 for ontologies           About GeneDecksing


    (SuperPaths according to PathCards, Pathways according to R&D Systems, Cell Signaling Technology, KEGG, PharmGKB, BioSystems, Sino Biological, Reactome, Tocris Bioscience, GeneGo (Thomson Reuters), QIAGEN, and/or UniProtKB, Sets of similar genes according to GeneDecks, Interaction Networks according to QIAGEN, and/or STRING, Interactions according to 1UniProtKB, 2MINT, 3I2D, and/or 4STRING, with links to IntAct and Ensembl, Ontologies according to Gene Ontology Consortium 01 Apr 2014 via Entrez Gene).
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    SuperPaths for CHRNA4 About   (see all 10)                                                                                              See pathways by source

    SuperPathContained pathways About
    1Nicotine Pathway (Dopaminergic Neuron), Pharmacodynamics
    Nicotine Pathway (Dopaminergic Neuron), Pharmacodynamics0.44
    Nicotine Activity on Dopaminergic Neurons0.44
    2Activation of Nicotinic Acetylcholine Receptors
    Activation of Nicotinic Acetylcholine Receptors
    Highly calcium permeable postsynaptic nicotinic acetylcholine receptors0.00
    Presynaptic nicotinic acetylcholine receptors0.00
    Postsynaptic nicotinic acetylcholine receptors0.00
    Highly calcium permeable nicotinic acetylcholine receptors0.00
    Highly sodium permeable acetylcholine nicotinic receptors0.00
    Acetylcholine Binding And Downstream Events0.00
    3Transmission across Chemical Synapses
    Transmission across Chemical Synapses0.72
    Neuronal System0.68
    Neurotransmitter Receptor Binding And Downstream Transmission In The Postsynaptic Cell0.72
    4CREB Pathway
    Intracellular Calcium Signaling0.50
    5Nanog in Mammalian ESC Pluripotency
    eNOS Signaling0.48

    Pathways by source                                                                                                                                                                 See SuperPaths
    Show all pathways

    2 Downloadable PowerPoint Slides of GeneGlobe Pathway Central Maps for CHRNA4
        eNOS Signaling
    Intracellular Calcium Signaling

    2 BioSystems Pathways for CHRNA4
        SIDS Susceptibility Pathways
    Nicotine Activity on Dopaminergic Neurons

    3 Reactome Pathways for CHRNA4
        Highly calcium permeable postsynaptic nicotinic acetylcholine receptors
    Highly calcium permeable nicotinic acetylcholine receptors
    Highly sodium permeable acetylcholine nicotinic receptors

    1 PharmGKB Pathway for CHRNA4
        Nicotine Pathway (Dopaminergic Neuron), Pharmacodynamics

    3 Kegg Pathways  (Kegg details for CHRNA4):
        Neuroactive ligand-receptor interaction
    Cholinergic synapse
    Nicotine addiction


    CHRNA4 for pathways           About GeneDecksing

        Pathway & Disease-focused RT2 Profiler PCR Array including CHRNA4: 
              Neurotransmitter Receptors in human mouse rat

    Interactions:

        GeneGlobe Interaction Network for CHRNA4

    STRING Interaction Network Preview (showing 5 interactants - click image to see 22)

    Selected Interacting proteins for CHRNA4 (P436812, 3 ENSP000003592854) via UniProtKB, MINT, STRING, and/or I2D (see all 29)
    InteractantInteraction Details
    GeneCardExternal ID(s)
    CSNK2BP678702, 3MINT-8253143 I2D: score=2 
    ENSG00000206406P678702, 3MINT-8253143 I2D: score=2 
    ENSG00000224398P678702, 3MINT-8253143 I2D: score=2 
    ENSG00000224774P678702, 3MINT-8253143 I2D: score=2 
    ENSG00000228875P678702, 3MINT-8253143 I2D: score=2 
    About this table

    Gene Ontology (GO): Selected biological process terms (see all 24):    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0001508action potential ISS--
    GO:0001666response to hypoxia IDA12189247
    GO:0006281DNA repair IMP16332175
    GO:0006810transport ----
    GO:0006811ion transport NAS8906617

    CHRNA4 for ontologies           About GeneDecksing



    (Chemical Compounds according to UniProtKB, Enzo Life Sciences, EMD Millipore, Tocris Bioscience, ApexBio, HMDB, BitterDB, and/or Novoseek, Ligands according to IUPHAR, and Drugs according to DrugBank, Enzo Life Sciences, and/or PharmGKB)
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      Browse compounds at ApexBio 

    Compounds for CHRNA4 available from Tocris Bioscience    About this table
    CompoundAction CAS #
    RJR 2403 oxalatealpha4beta2 selective nicotinic agonist[220662-95-3]
    Desformylflustrabromine hydrochloridePositive allosteric modulator of alpha4beta2[474657-72-2]
    (-)-Nicotine ditartratePrototypical nAChR agonist[65-31-6]
    Varenicline tartrate Orally active, subtype-selective alpha4beta2 partial agonist [375815-87-5]
    Sazetidine A dihydrochloridealpha4beta2 receptor ligand; may act as an agonist or a desensitizer[1197329-42-2]

    Selected DrugBank Compounds for CHRNA4 (see all 20)    About this table
    CompoundSynonyms CAS #TypeActionsPubMed Ids
    NicotineL-Nicotine (see all 2)54-11-5targetagonist19560048 20081230 17226798 16636791 20400469 11006350 17590520 17613539 17146052
    Galantamine(-)-Galanthamine (see all 3)357-70-0targetallosteric modulator12137632 11129124 12481195 20480924 12177686 10971048
    VareniclineCP-526,555 (see all 2)249296-44-4targetpartial agonist17573127 17626178 18288085 11752352 17692720
    Amobarbital-- 57-43-2targetantagonist11264449 16248797 10487207
    Aprobarbital-- 77-02-1targetantagonist11264449 16248797 10487207
    Barbital-- 57-44-3targetantagonist11264449 16248797 10487207
    Barbituric acid derivative-- --targetantagonist11264449 16248797 10487207
    ButabarbitalButabarbital Sodium (see all 8)125-40-6targetantagonist11264449 16248797 10487207
    ButalbitalAllylbarbital (see all 2)77-26-9targetantagonist11264449 16248797 10487207
    Butethal5-Butyl-5-ethyl-2,4,6(1H,3H,5H)-pyrimidinetrione (see all 10)77-28-1targetantagonist11264449 16248797 10487207

    Selected IUPHAR Ligands for CHRNA4 (alpha4) (see all 11)    About this table
    LigandTypeActionAffinityPubmed IDs
    [3H]cytisine
    NoneNone10--
    [125I]epibatidine
    NoneNone9.73--
    [3H]epibatidine
    NoneNone9.73--
    mecamylamine
    Channel blockerNone6.48 - 5.31--
    hexamethonium
    Channel blockerNone4.04--
    LY2087101
    Allosteric regulatorPositive4.0416738207
    TC-2559
    AgonistFull agonist4.0412871651
    NS9283
    Allosteric regulatorPositive4.0421763685
    A-867744
    Channel blockerNone4.0419389923
    TC-2403
    AgonistFull agonist4.0410854263

    7 Novoseek inferred chemical compound relationships for CHRNA4 gene    About this table
    Compound   -log (P-Val)   Hits   PubMed IDs for Articles with Shared Sentences (# sentences)
    nicotine 64.4 16 15154117 (4), 17768273 (2), 15790597 (2), 18534558 (2) (see all 7)
    acetylcholine 25.1 3 17008177 (1), 19628475 (1), 11752213 (1)
    potassium 23.9 4 7620586 (1), 11888238 (1), 11579435 (1)
    dopamine 15.3 5 17948872 (2)
    sodium 5.29 1 11579435 (1)
    phenylalanine 1.75 1 7550350 (1)
    serine 0 2 9216991 (1), 7550350 (1)

    1 PharmGKB related drug/compound annotation for CHRNA4 gene    About this table
    Drug/compound PharmGKB Annotation
    nicotineCA  



    CHRNA4 for compounds           About GeneDecksing



    (Secondary structures according to fRNAdb,
    GenBank/EMBL/DDBJ Accessions according to
    Unigene (Build 236 Homo sapiens; Apr 25 2013) or GenBank,
    RefSeq according to Entrez Gene,
    DOTS (version 10), and/or AceView, transcript ids from Ensembl with links to UCSC,
    Conferences by KenesGroup, exon structure from GeneLoc, alternative splicing isoforms according to ASD and/or ECgene,
    siRNAs from OriGene, QIAGEN, shRNA from OriGene, microRNA from QIAGEN, SwitchGear Genomics,
    Tagged/untagged cDNA clones from OriGene, GenScript, DNA2.0, Vector BioLabs, Primers from OriGene, and/or QIAGEN )
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    REFSEQ mRNAs for CHRNA4 gene (2 alternative transcripts): 
    NM_000744.6  NM_001256573.1  

    Unigene Cluster for CHRNA4:

    Cholinergic receptor, nicotinic, alpha 4 (neuronal)
    Hs.10734  [show with all ESTs]
    Unigene Representative Sequence: NR_046317
    6 Ensembl transcripts including schematic representations, and UCSC links where relevant:
    ENST00000370263(uc010gke.1 uc002yev.1 uc002yes.2 uc010gkf.1)
    ENST00000463705(uc002yet.1) ENST00000498043 ENST00000467563 ENST00000475033
    ENST00000480012
    Congresses - knowledge worth sharing:
    European Congress of Clinical Microbiology and Infectious Diseases (ECCMID) 10 - 13 May 2014

    miRNA
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    1 qRT-PCR Assays for microRNA that regulate CHRNA4:
    hsa-miR-1324
    SwitchGear 3'UTR luciferase reporter plasmidCHRNA4 3' UTR sequence
    Inhib. RNA
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    Additional mRNA sequence: 

    AK296430.1 AK314907.1 BC096290.1 BC096291.1 BC096292.1 BC096293.3 L35901.1 NR_046317.1 
    X87629.1 Y08421.1 

    6 DOTS entries:

    DT.120804469  DT.455403  DT.92416817  DT.120804474  DT.120804492  DT.120804482 

    Selected AceView cDNA sequences (see all 30):

    NM_000744 BM929812 BM710937 R56604 Z40094 BM929424 AI937242 Z44054 
    U62433 H30878 X87629 X89745 CB156220 L35901 H28110 BM666038 
    BF594703 BI917752 H27913 Y08421 X89741 R56603 R88602 BF511254 

    GeneLoc Exon Structure

    4 Alternative Splicing Database (ASD) splice patterns (SP) for CHRNA4    About this scheme

    ExUns: 1a · 1b · 1c ^ 2 ^ 3 ^ 4a · 4b ^ 5 ^ 6a · 6b ^ 7a · 7b
    SP1:              -                             -                           
    SP2:                                      -     -                           
    SP3:                                      -                                 
    SP4:                                            -                           


    ECgene alternative splicing isoforms for CHRNA4

    (RNA expression data according to H-InvDB, NONCODE, miRBase, and RNAdb, Expression images according to data from BioGPS, Illumina Human BodyMap, and CGAP SAGE, Sets of similar genes according to GeneDecks, in vivo and in vitro expression data from LifeMap Discovery™, Protein expression images according to data from SPIRE 1MOPED, 2PaxDb, and 3MaxQB, plus additional links to SOURCE, and/or BioGPS, and/or UniProtKB,
    PCR Arrays from QIAGEN, Primers from OriGene, and/or QIAGEN, In Situ Hybridization Assays from Advanced Cell Diagnostics)
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    CHRNA4 expression in normal human tissues (normalized intensities)      CHRNA4 embryonic expression: see
    See probesets specificity/sensitivity at GeneAnnot
    About this imageBioGPS <intensity>2/3
    CGAP TAG: GACCAAGCCC
    CHRNA4 Expression
    About this image


    CHRNA4 expression in embryonic tissues and stem cells    About this table
    Data from LifeMap, the Embryonic Development and Stem Cells Database
     selected tissues (see all 4) fully expand
     
     Neural Tube (Nervous System)    fully expand to see all 3 entries
             Metencephalon
     
     Brain (Nervous System)    fully expand to see all 2 entries
             Midbrain tegmentum
     
     Gut Tube (Gastrointestinal Tract)
             Foregut
     
     NULL (Uncategorized)
             Neural rosettes
    CHRNA4 Protein expression data from MOPED1, PaxDb2 and MaxQB3    About this image

    CHRNA4 Protein Expression

    SOURCE GeneReport for Unigene cluster: Hs.10734
        Pathway & Disease-focused RT2 Profiler PCR Array including CHRNA4: 
              Neurotransmitter Receptors in human mouse rat

    Primer
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    Advanced Cell Diagnostics RNAscope RNA in situ hybridization assays for CHRNA4

    (Orthologs according to 1,2HomoloGene (2older version, for species not in 1newer version), 3euGenes, 4SGD , 5MGI Mar 06 2013, with possible further links to Flybase and/or WormBase, and/or 6Ensembl pan taxonomic compara , Gene Trees according to Ensembl and TreeFam)
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    This gene was present in the common ancestor of animals.

    Orthologs for CHRNA4 gene from Selected species (see all 14)    About this table
    Organism Taxonomic
    classification
    Gene Description Human
    Similarity
    Orthology
    Type
    Details
    mouse
    (Mus musculus)
    Mammalia Chrna41 , 5 cholinergic receptor, nicotinic, alpha polypeptide more1, 5 83.64(n)1
    85.48(a)1
      2 (103.54 cM)5
    114381  NM_015730.51  NP_056545.31 
     1810183805 
    chicken
    (Gallus gallus)
    Aves CHRNA41 cholinergic receptor, nicotinic, alpha 4 75.82(n)
    78.64(a)
      395606  NM_204814.1  NP_990145.1 
    lizard
    (Anolis carolinensis)
    Reptilia CHRNA46
    cholinergic receptor, nicotinic, alpha 4 (neuronal...
    74(a)
    1 ↔ 1
    4(153720844-153833532)
    tropical clawed frog
    (Xenopus tropicalis)
    Amphibia chrna41 cholinergic receptor, nicotinic, alpha 4 (neuronal) 70.94(n)
    74.54(a)
      100135106  NM_001113843.1  NP_001107315.1 
    zebrafish
    (Danio rerio)
    Actinopterygii LOC5636961 neuronal acetylcholine receptor subunit alpha-4-like 68.74(n)
    69.68(a)
      563696  XM_687056.5  XP_692148.2 
    fruit fly
    (Drosophila melanogaster)
    Insecta nAcRalpha-96Aa3
    nAcRbeta-64B1
    nicotinic acetylcholine-activated
    cation-selective more3
    nicotinic Acetylcholine Receptor beta 64B1
    58(a)
    (best of 7)3
    60.93(n)1
    53.16(a)1
      385451  NM_079203.31  NP_523927.21 


    ENSEMBL Gene Tree for CHRNA4 (if available)
    TreeFam Gene Tree for CHRNA4 (if available)

    (Paralogs according to 1HomoloGene,
    2Ensembl, and 3SIMAP, Pseudogenes according to 4Pseudogene.org Build 68)
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    Paralogs for CHRNA4 gene
    CHRNA52  CHRNA22  CHRNA12  CHRNB22  CHRNA62  CHRNG2  CHRNA32  CHRNE2  
    CHRND2  CHRNB32  CHRNB12  CHRNB42  
    17 SIMAP similar genes for CHRNA4 using alignment to 7 protein entries:     ACHA4_HUMAN (see all proteins):
    CHRNA5    CHRNB3    CHRNA1    CHRNA7-2    CHRNA9    CHRNE
    CHRND    CHRNA2    HTR3A    CHRNA3    CHRNA7    CHRNG
    CHRNA10    CHRNA6    CHRNB1    CHRFAM7A    CHRNB4

    CHRNA4 for paralogs           About GeneDecksing



    (SNPs/Variants according to the 1NCBI SNP Database, 2Ensembl, 3PupaSUITE, 4UniProtKB, and DNA2.0, Linkage Disequilibrium by HapMap, Structural Variations(CNVs/InDels/Inversions) from the Database of Genomic Variants, Mutations from the Human Gene Mutation Database (HGMD), the Human Cytochrome P450 Allele Nomenclature Database, and the Locus Specific Mutation Databases (LSDB), Blood group antigen gene mutations by BGMUT, Resequencing Primers, Cancer Mutation PCR Arrays and Assays, and Copy Number PCR Arrays from QIAGEN)
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    Selected SNPs for CHRNA4 (see all 1253)    About this table    
    Genomic DataTranscription Related DataAllele Frequencies
    SNP IDValidClinical
    significance
    Chr 20 posSequence#AA
    Chg
    TypeMore#Allele
    freq
    PopTotal
    sample
    More
    ----------
    VAR_0175314
    Epilepsy, nocturnal frontal lobe, 1 (ENFL1)4--see VAR_0175312 S L mis40--------
    VAR_0002954
    Epilepsy, nocturnal frontal lobe, 1 (ENFL1)4--see VAR_0002952 S F mis40--------
    rs289315911,2
    Cpathogenic161981912(-) GCTGTC/TGCTCA 5 S L mis10--------
    rs1219095801,2
    Cpathogenic161981924(-) CATCTC/TCGTGC 5 S F mis10--------
    rs1219122851,2
    C,Funtested161981052(-) AGGGCG/ATCCAG 5 /I /V mis12Minor allele frequency- A:0.00NA EU 5769
    rs1219122841,2
    C,Funtested161981101(-) GCGCCG/ACCCCC 5 /P syn11Minor allele frequency- A:0.00NA 4308
    rs1219122831,2
    Cuntested161981128(-) GCCACA/GGTCAA 5 T syn10--------
    rs1219122821,2
    Cuntested161981129(-) CGCCAC/TGGTCA 5 T M mis10--------
    rs1219122811,2
    Cuntested161981138(-) GTCCCC/TGAGCG 5 P L mis11Minor allele frequency- T:0.00NA 4306
    rs1219122801,2
    Cuntested161981303(-) GTCTCA/GGAGCA 5 Q R mis10--------

    HapMap Linkage Disequilibrium report for CHRNA4 (61974665 - 62009753 bp)

    Structural Variations
         Database of Genomic Variants (DGV) Selected variations for CHRNA4 (see all 26):    About this table    
    Variant IDTypeSubtypePubMed ID
    esv2722910CNV Deletion23290073
    esv1955955CNV Deletion18987734
    esv3964CNV Deletion18987735
    esv2722912CNV Deletion23290073
    esv2722913CNV Deletion23290073
    dgv722e201CNV Deletion23290073
    esv1443132CNV Insertion17803354
    nsv180574CNV Insertion16902084
    esv1436907CNV Insertion17803354
    esv1299744CNV Insertion17803354

    Human Gene Mutation Database (HGMD): CHRNA4
    Site Specific Mutation Identification with PCR Assays
    SeqTarget long-range PCR primers for resequencing CHRNA4
    DNA2.0 Custom Variant and Variant Library Synthesis for CHRNA4

    (in which this Gene is Involved, According to MalaCards, OMIM, UniProtKB, the University of Copenhagen DISEASES database, Conferences by KenesGroup, Novoseek, Genatlas, GeneTests, GAD, HuGE Navigator, and/or TGDB.)
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    OMIM gene information: 118504   
    OMIM disorders: 600513  188890  
    UniProtKB/Swiss-Prot: ACHA4_HUMAN, P43681
  • Epilepsy, nocturnal frontal lobe, 1 (ENFL1) [MIM:600513]: An autosomal dominant focal epilepsy
    characterized by nocturnal seizures with hyperkinetic automatisms and poorly organized stereotyped movements.
    Note=The disease is caused by mutations affecting the gene represented in this entry

  • Selected diseases for CHRNA4 (see all 41):    About MalaCards
    chrna4-related nocturnal frontal lobe epilepsy, autosomal dominant    nicotine addiction    epilepsy, nocturnal frontal lobe, 1    frontal lobe epilepsy
    exfoliation syndrome    autosomal dominant nocturnal frontal lobe epilepsy    childhood absence epilepsy    nicotine dependence
    lewy body dementia    idiopathic generalized epilepsy    pain agnosia    attention deficit hyperactivity disorder
    epilepsy syndrome    agnosia    juvenile myoclonic epilepsy    focal epilepsy
    toxic encephalopathy    patent ductus arteriosus    neuronitis    panic disorder

    10 diseases from the University of Copenhagen DISEASES database for CHRNA4:
    Nicotine dependence     Schizophrenia     Alzheimer's disease     Myasthenia gravis
    Parkinson's disease     Toxic encephalopathy     Pain agnosia     Focal epilepsy
    Idiopathic generalized epilepsy     Attention deficit hyperactivity disorder

    CHRNA4 for disorders           About GeneDecksing


    Congresses - knowledge worth sharing:
    Alzheimer's & Parkinson's Diseases Congress (ADPD) 18 - 22 March 2015

    Selected Novoseek inferred disease relationships for CHRNA4 gene (see all 19)    About this table

    Disease   -log (P-Val)   Hits   PubMed IDs for Articles with Shared Sentences (# sentences)
    epilepsy frontal lobe 96 47 10939581 (2), 12887446 (2), 19058950 (2), 10448807 (2) (see all 32)
    familial benign neonatal convulsions 92.3 10 12204289 (1), 11888238 (1), 7647781 (1), 8833159 (1) (see all 9)
    myoclonic epilepsy juvenile 81.4 5 19577488 (3), 17008177 (1), 9259383 (1)
    childhood absence epilepsy 74.5 2 17008177 (1), 9259383 (1)
    seizures febrile 74.3 7 12887442 (2), 19853223 (1), 10896263 (1), 17008177 (1) (see all 6)
    epilepsy generalized 71.2 4 16049035 (1), 16278970 (1), 17008177 (1), 11579435 (1)
    epilepsies partial 69.2 7 10446744 (1), 9758605 (1), 11121188 (1), 9259383 (1) (see all 6)
    epilepsy 68.2 19 9921897 (2), 9216991 (2), 9259280 (1), 16049035 (1) (see all 16)
    epilepsy, idiopathic generalized 65.3 3 9259383 (2), 19577488 (1)
    epilepsies myoclonic 59.1 1 17008177 (1)

    GeneTests: CHRNA4
    GeneReviews: CHRNA4
    Genetic Association Database (GAD): CHRNA4
    Human Genome Epidemiology (HuGE) Navigator: CHRNA4 (62 documents)

    Export disorders for CHRNA4 gene to outside databases

    (in PubMed. Associations of this gene to articles via 1Entrez Gene, 2UniProtKB/Swiss-Prot, 3HGNC, 4GAD, 5PharmGKB, 6HMDB, 7DrugBank, 8UniProtKB/TrEMBL, 9 Novoseek, and/or 10fRNAdb)
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    PubMed articles for CHRNA4 gene, integrated from 10 sources (see all 247):
    (articles sorted by number of sources associating them with CHRNA4)
        Utopia: connect your pdf to the dynamic
    world of online information

    1. Genetic interaction between alpha4 and beta2 subunits of high affinity nicotinic receptor: analysis in schizophrenia. (PubMed id 16636791)1, 4, 7, 9 De Luca V....Kennedy J.L. (Exp Brain Res 2006)
    2. Association of attentional network function with exon 5 variations of the CHRNA4 gene. (PubMed id 17613539)1, 4, 7 Winterer G....Gallinat J. (Hum. Mol. Genet. 2007)
    3. Association of the neuronal nicotinic receptor beta2 subunit gene (CHRNB2) with subjective responses to alcohol and nicotine. (PubMed id 17226798)1, 4, 7 Ehringer M.A....Zeiger J.S. (Am. J. Med. Genet. B Neuropsychiatr. Genet. 2007)
    4. Association of the neuronal nicotinic acetylcholine receptor subunit alpha4 polymorphisms with febrile convulsions. (PubMed id 12887442)1, 4, 9 Chou I.C....Tsai F.J. (Epilepsia 2003)
    5. Association study of the nicotinic acetylcholine receptor alpha4 subunit gene, CHRNA4, in attention-deficit hyperactivity disorder. (PubMed id 17504247)1, 4, 9 Lee J....Barr C.L. (Genes Brain Behav. 2008)
    6. Exon-intron structure of the human neuronal nicotinic acetylcholine receptor alpha 4 subunit (CHRNA4). (PubMed id 8833159)1, 2, 9 Steinlein O.K.... Propping P. (Genomics 1996)
    7. Gene-gene interactions among CHRNA4, CHRNB2, BDNF, and NTRK2 in nicotine dependence. (PubMed id 18534558)1, 4, 9 Li M.D....Elston R.C. (Biol. Psychiatry 2008)
    8. Effects of APOE and CHRNA4 genotypes on retinal nerve fibre layer thickness at the optic disc and on risk for developing exfoliation syndrome. (PubMed id 17488453)1, 4, 9 Ritland J.S....ElsAYs T. (Acta Ophthalmol Scand 2007)
    9. Association of polymorphisms in nicotinic acetylcholine receptor alpha 4 subunit gene (CHRNA4), mu-opioid receptor gene (OPRM1), and ethanol-metabolizing enzyme genes with alcoholism in Korean patients. (PubMed id 15902904)1, 4, 9 Kim S.A....Chung J.H. (Alcohol 2004)
    10. A novel mutation of CHRNA4 responsible for autosomal dominant nocturnal frontal lobe epilepsy. (PubMed id 10563623)1, 2, 9 Hirose S.... Mitsudome A. (Neurology 1999)

    (in PubMed, OMIM, and NCBI Bookshelf)
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     ANDOR
    Aliases
    Disorders
    Free Text  

      Query String
    PubMed
    OMIM
    NCBI Bookshelf
      (Note: In FireFox, select the above section and copy using Ctrl-C)

    (According to Entrez Gene, HGNC, AceView, euGenes, Ensembl, miRBase, ECgene, Kegg, and/or H-InvDB)
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    Entrez Gene: 1137 HGNC: 1958 AceView: CHRNA4 Ensembl:ENSG00000101204 euGenes: HUgn1137
    ECgene: CHRNA4 Kegg: 1137 H-InvDB: CHRNA4

    (According to HUGE)
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      --

    (According to PharmGKB, ATLAS, HORDE, IMGT, LEIDEN, UniProtKB/Swiss-Prot, UniProtKB/TrEMBL, and/or others, e.g. Wikipedia and GeneReviews, via UniProtKB/Swiss-Prot)
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    NameDescription
    PharmGKB entry for CHRNA4 Pharmacogenomics, SNPs, Pathways
    GeneReviewshttp://www.ncbi.nlm.nih.gov/books/NBK1116/?term=CHRNA4[genesymbol]
    NIEHS-SNPshttp://egp.gs.washington.edu/data/chrna4/

    (Patent information from GeneIP,
    Licensable technologies from WIS Yeda, Salk, Tufts,
    IP news from LifeMap Sciences, Inc.)
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    Patent Information for CHRNA4 gene:
    Search GeneIP for patents involving CHRNA4

    GeneCards and IP:
    Japan Patent Office Licenses GeneCards     European Patent Office Licenses GeneCards     Improving the IP Search



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