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Aliases for CHRNA4 Gene

Aliases for CHRNA4 Gene

  • Cholinergic Receptor, Nicotinic, Alpha 4 (Neuronal) 2 3
  • Cholinergic Receptor, Nicotinic, Alpha Polypeptide 4 2 3
  • NACRA4 3 4
  • Neuronal Nicotinic Acetylcholine Receptor Alpha-4 Subunit 3
  • Neuronal Acetylcholine Receptor Subunit Alpha-4 3
  • Acetylcholine Receptor 2
  • Alpha 4 (Neuronal) 2
  • Nicotinic 2
  • NACHRA4 3
  • NACHR 3
  • ENFL1 6
  • BFNC 3
  • EBN1 3
  • EBN 3

External Ids for CHRNA4 Gene

Previous Symbols for CHRNA4 Gene

  • EBN
  • EBN1

Summaries for CHRNA4 Gene

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 epilepsy, nocturnal frontal lobe, 1 and chrna4-related nocturnal frontal lobe epilepsy, autosomal dominant. Among its related pathways are CREB Pathway and Nanog in Mammalian ESC Pluripotency. 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 CHRNA3.

UniProtKB/Swiss-Prot for CHRNA4 Gene

  • 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.

Tocris 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

No data available for PharmGKB "VIP" Summary , fRNAdb sequence ontologies and piRNA Summary for CHRNA4 Gene

Genomics for CHRNA4 Gene

Genomic Location for CHRNA4 Gene

Start:
63,343,310 bp from pter
End:
63,378,401 bp from pter
Size:
35,092 bases
Orientation:
Minus strand

Genomic View for CHRNA4 Gene

UCSC Golden Path with GeneCards custom track
Cytogenetic band:
Genomic Location for CHRNA4 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for CHRNA4 Gene

Regulatory Elements for CHRNA4 Gene

Proteins for CHRNA4 Gene

  • Protein details for CHRNA4 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    P43681-ACHA4_HUMAN
    Recommended name:
    Neuronal acetylcholine receptor subunit alpha-4
    Protein Accession:
    P43681
    Secondary Accessions:
    • Q4JGR7
    • Q4VAQ5
    • Q4VAQ6

    Protein attributes for CHRNA4 Gene

    Size:
    627 amino acids
    Molecular mass:
    69957 Da
    Quaternary structure:
    • 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.

    Three dimensional structures from OCA and Proteopedia for CHRNA4 Gene

    Alternative splice isoforms for CHRNA4 Gene

    UniProtKB/Swiss-Prot:

neXtProt entry for CHRNA4 Gene

Proteomics data for CHRNA4 Gene at MOPED

Post-translational modifications for CHRNA4 Gene

  • Modification sites at PhosphoSitePlus
  • Glycosylation at Asn57, Asn107, and Asn174

Other Protein References for CHRNA4 Gene

ENSEMBL proteins:
Reactome Protein details:
REFSEQ proteins:

No data available for DME Specific Peptides for CHRNA4 Gene

Domains for CHRNA4 Gene

Gene Families for CHRNA4 Gene

HGNC:
  • CHRN :Ligand-gated ion channels / Acetylcholine receptors, nicotinic
  • CHR :Cholinergic receptors
IUPHAR :

Graphical View of Domain Structure for InterPro Entry

P43681

UniProtKB/Swiss-Prot:

ACHA4_HUMAN
Family:
  • 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.:
    • P43681
genes like me logo Genes that share domains with CHRNA4: view

Function for CHRNA4 Gene

Molecular function for CHRNA4 Gene

GENATLAS Biochemistry: cholinergic receptor,nicotinic,alpha 4 polypeptide,neuronal
UniProtKB/Swiss-Prot 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.

Gene Ontology (GO) - Molecular Function for CHRNA4 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0004889 acetylcholine-activated cation-selective channel activity TAS 20438829
GO:0005216 ion channel activity --
GO:0005230 extracellular ligand-gated ion channel activity --
GO:0005515 protein binding --
GO:0015276 ligand-gated ion channel activity TAS 20438829
genes like me logo Genes that share ontologies with CHRNA4: view
genes like me logo Genes that share phenotypes with CHRNA4: view

Animal Models for CHRNA4 Gene

MGI Knock Outs for CHRNA4:

No data available for Enzyme Numbers (IUBMB) , miRNA , Transcription Factor Targeting and HOMER Transcription for CHRNA4 Gene

Localization for CHRNA4 Gene

Subcellular locations from UniProtKB/Swiss-Prot for CHRNA4 Gene

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

Subcellular locations from

COMPARTMENTS
Jensen Localization Image for CHRNA4 Gene COMPARTMENTS Subcellular localization image for CHRNA4 gene
Compartment Confidence
plasma membrane 5
cytoskeleton 2
endoplasmic reticulum 2
extracellular 2
nucleus 2

Gene Ontology (GO) - Cellular Components for CHRNA4 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005886 plasma membrane TAS --
GO:0005892 acetylcholine-gated channel complex IDA 8906617
GO:0009897 external side of plasma membrane ISS --
GO:0016020 membrane ISS --
GO:0016021 integral component of membrane NAS 8906617
genes like me logo Genes that share ontologies with CHRNA4: view

Pathways for CHRNA4 Gene

genes like me logo Genes that share pathways with CHRNA4: view

Gene Ontology (GO) - Biological Process for CHRNA4 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0001508 action potential ISS --
GO:0001666 response to hypoxia IDA 12189247
GO:0006281 DNA repair IMP 16332175
GO:0006810 transport --
GO:0006811 ion transport NAS 8906617
genes like me logo Genes that share ontologies with CHRNA4: view

Compounds for CHRNA4 Gene

(5) Tocris Compounds for CHRNA4 Gene

Compound Action Cas Number
(-)-Nicotine ditartrate Prototypical nAChR agonist [65-31-6]
Desformylflustrabromine hydrochloride Positive allosteric modulator of alpha4beta2 [474657-72-2]
RJR 2403 oxalate alpha4beta2 selective nicotinic agonist [220662-95-3]
Sazetidine A dihydrochloride alpha4beta2 receptor ligand; may act as an agonist or a desensitizer [1197329-42-2]
Varenicline tartrate Orally active, subtype-selective alpha4beta2 partial agonist [375815-87-5]

(20) Drugbank Compounds for CHRNA4 Gene

Compound Synonyms Cas Number Type Actions PubMed IDs
Amobarbital
57-43-2 target antagonist
Aprobarbital
77-02-1 target antagonist
Barbital
57-44-3 target antagonist
Barbituric acid derivative
target antagonist
Butabarbital
  • Butabarbital Sodium
125-40-6 target antagonist

(11) IUPHAR Ligand for CHRNA4 Gene

Ligand Type Action Affinity Pubmed IDs
[125I]epibatidine None None 9.64
[3H]epibatidine None None 9.64
mecamylamine Channel blocker None 6.41
[3H]cytisine None None
hexamethonium Channel blocker None
LY2087101 Allosteric regulator Positive
TC-2559 Agonist Full agonist
NS9283 Allosteric regulator Positive
A-867744 Channel blocker None
TC-2403 Agonist Full agonist
NS1738 Channel blocker None

(7) Novoseek inferred chemical compound relationships for CHRNA4 Gene

Compound -log(P) Hits PubMed IDs
nicotine 64.4 14
acetylcholine 25.1 3
potassium 23.9 3
dopamine 15.3 2
sodium 5.29 1

(1) PharmGKB related drug/compound annotations for CHRNA4 Gene

Drug/compound Annotation
nicotine CA
genes like me logo Genes that share compounds with CHRNA4: view

Transcripts for CHRNA4 Gene

Unigene Clusters for CHRNA4 Gene

Cholinergic receptor, nicotinic, alpha 4 (neuronal):
Representative Sequences:

Alternative Splicing Database (ASD) splice patterns (SP) for CHRNA4 Gene

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

Relevant External Links for CHRNA4 Gene

GeneLoc Exon Structure for
CHRNA4
ECgene alternative splicing isoforms for
CHRNA4

Expression for CHRNA4 Gene

mRNA expression in normal human tissues for CHRNA4 Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

mRNA differential expression in normal tissues according to GTEx for CHRNA4 Gene

This gene is overexpressed in Liver (18.5) and Brain - Substantia nigra (4.3).

Integrated Proteomics: protein expression from ProteomicsDB, PaxDb, and MOPED for CHRNA4 Gene

SOURCE GeneReport for Unigene cluster for CHRNA4 Gene Hs.10734

genes like me logo Genes that share expressions with CHRNA4: view

No data available for mRNA Expression by UniProt/SwissProt for CHRNA4 Gene

Orthologs for CHRNA4 Gene

This gene was present in the common ancestor of animals.

Orthologs for CHRNA4 Gene

Organism Taxonomy Gene Similarity Type Details
chimpanzee
(Pan troglodytes)
Mammalia CHRNA4 35
  • 98.51 (n)
  • 98.41 (a)
CHRNA4 36
  • 95 (a)
OneToOne
cow
(Bos Taurus)
Mammalia CHRNA4 35
  • 85.75 (n)
  • 85.97 (a)
CHRNA4 36
  • 86 (a)
OneToOne
dog
(Canis familiaris)
Mammalia CHRNA4 35
  • 88.87 (n)
  • 88.98 (a)
CHRNA4 36
  • 88 (a)
OneToOne
mouse
(Mus musculus)
Mammalia Chrna4 35
  • 83.64 (n)
  • 85.48 (a)
Chrna4 16
Chrna4 36
  • 84 (a)
OneToOne
oppossum
(Monodelphis domestica)
Mammalia CHRNA4 36
  • 76 (a)
OneToOne
platypus
(Ornithorhynchus anatinus)
Mammalia CHRNA4 36
  • 76 (a)
OneToOne
rat
(Rattus norvegicus)
Mammalia Chrna4 35
  • 83.92 (n)
  • 85.14 (a)
chicken
(Gallus gallus)
Aves CHRNA4 35
  • 75.82 (n)
  • 78.64 (a)
CHRNA4 36
  • 75 (a)
OneToOne
lizard
(Anolis carolinensis)
Reptilia CHRNA4 36
  • 74 (a)
OneToOne
tropical clawed frog
(Silurana tropicalis)
Amphibia chrna4 35
  • 70.94 (n)
  • 74.54 (a)
zebrafish
(Danio rerio)
Actinopterygii CHRNA4 (3 of 3) 36
  • 59 (a)
OneToMany
chrna4b 36
  • 61 (a)
OneToMany
chrna4b 36
  • 61 (a)
OneToMany
LOC563696 35
  • 68.74 (n)
  • 69.68 (a)
African malaria mosquito
(Anopheles gambiae)
Insecta AgaP_AGAP000966 35
  • 59.41 (n)
  • 49.05 (a)
fruit fly
(Drosophila melanogaster)
Insecta nAcRbeta-64B 35
  • 60.93 (n)
  • 53.16 (a)
nAcRalpha-96Aa 37
  • 58 (a)
nAcRalpha-96Ab 37
  • 55 (a)
nAcRalpha-30D 37
  • 35 (a)
nAcRbgr-96A 37
  • 51 (a)
nAcRbgr-21C 37
  • 30 (a)
nAcRalpha-7E 37
  • 52 (a)
nAcRbgr-64B 37
  • 51 (a)
worm
(Caenorhabditis elegans)
Secernentea deg-3 37
  • 31 (a)
Y57G11C.2 37
  • 24 (a)
acr-23 37
  • 30 (a)
Y44A6E.1 37
  • 29 (a)
acr-10 37
  • 37 (a)
acr-2 37
  • 45 (a)
acr-13 37
  • 37 (a)
lev-1 37
  • 46 (a)
acr-5 37
  • 29 (a)
C04C3.2 37
  • 25 (a)
acr-7 37
  • 38 (a)
acr-15 37
  • 38 (a)
unc-63 37
  • 52 (a)
acr-3 37
  • 46 (a)
acr-12 37
  • 45 (a)
Y73F8A.30 37
  • 31 (a)
acr-14 37
  • 33 (a)
acr-18 37
  • 29 (a)
unc-29 37
  • 43 (a)
unc-38 37
  • 49 (a)
acr-22 37
  • 29 (a)
ZK973.5 37
  • 37 (a)
acr-17 37
  • 31 (a)
acr-8 37
  • 38 (a)
Species with no ortholog for CHRNA4:
  • A. gosspyii yeast (Ashbya gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African clawed frog (Xenopus laevis)
  • 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)
  • 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 squirt (Ciona intestinalis)
  • sea squirt (Ciona savignyi)
  • 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 CHRNA4 Gene

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

Paralogs for CHRNA4 Gene

genes like me logo Genes that share paralogs with CHRNA4: view

Variants for CHRNA4 Gene

Sequence variations from dbSNP and Humsavar for CHRNA4 Gene

SNP ID Clin Chr 20 pos Sequence Context AA Info Type MAF
rs1044393 Likely benign 63,350,772(-) GTGGA(C/T)GCCGT synonymous-codon, reference, nc-transcript-variant
rs1044394 Likely benign 63,350,733(-) TGCTG(C/T)GCCGA synonymous-codon, reference, nc-transcript-variant
rs1044396 other 63,349,782(-) CCGAG(C/T)GCCAC reference, synonymous-codon, nc-transcript-variant
rs1044397 other 63,349,752(-) AAAGC(A/G)CCGCC synonymous-codon, reference, nc-transcript-variant
rs1044398 -- 63,345,914(-) GGGGG(C/G)CTAGT utr-variant-3-prime, nc-transcript-variant

Structural Variations from Database of Genomic Variants (DGV) for CHRNA4 Gene

Variant ID Type Subtype PubMed ID
nsv913073 CNV Loss 21882294
nsv9825 CNV Gain 18304495
dgv4618n71 CNV Loss 21882294
nsv913165 CNV Loss 21882294
nsv913166 CNV Loss 21882294
nsv913177 CNV Loss 21882294
dgv4630n71 CNV Loss 21882294
dgv4631n71 CNV Loss 21882294
nsv913183 CNV Loss 21882294
dgv4632n71 CNV Loss 21882294
nsv913188 CNV Gain 21882294
nsv913189 CNV Loss 21882294
nsv913190 CNV Loss 21882294
dgv4633n71 CNV Loss 21882294
nsv828799 CNV Gain 20364138
nsv180574 CNV Insertion 16902084
esv1436907 CNV Insertion 17803354
esv1443132 CNV Insertion 17803354
esv1299744 CNV Insertion 17803354
esv1058695 CNV Insertion 17803354
dgv722e201 CNV Deletion 23290073
esv1955955 CNV Deletion 18987734
esv2722910 CNV Deletion 23290073
esv3964 CNV Deletion 18987735
esv2722912 CNV Deletion 23290073
esv2722913 CNV Deletion 23290073

Relevant External Links for CHRNA4 Gene

HapMap Linkage Disequilibrium report
CHRNA4
Human Gene Mutation Database (HGMD)
CHRNA4

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for CHRNA4 Gene

Disorders for CHRNA4 Gene

(2) OMIM Diseases for CHRNA4 Gene (118504)

UniProtKB/Swiss-Prot

ACHA4_HUMAN
  • 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. {ECO:0000269 PubMed:10563623, ECO:0000269 PubMed:14623738, ECO:0000269 PubMed:7550350}. Note=The disease is caused by mutations affecting the gene represented in this entry.

(19) Novoseek inferred disease relationships for CHRNA4 Gene

Disease -log(P) Hits PubMed IDs
epilepsy frontal lobe 96 38
familial benign neonatal convulsions 92.3 9
myoclonic epilepsy juvenile 81.4 5
childhood absence epilepsy 74.5 2
seizures febrile 74.3 7

Relevant External Links for CHRNA4

GeneTests
CHRNA4
GeneReviews
CHRNA4
Genetic Association Database (GAD)
CHRNA4
Human Genome Epidemiology (HuGE) Navigator
CHRNA4
genes like me logo Genes that share disorders with CHRNA4: view

Publications for CHRNA4 Gene

  1. Genetic interaction between alpha4 and beta2 subunits of high affinity nicotinic receptor: analysis in schizophrenia. (PMID: 16636791) De Luca V. … Kennedy J.L. (Exp Brain Res 2006) 3 23 25 48
  2. A missense mutation in the neuronal nicotinic acetylcholine receptor alpha-4 subunit is associated with autosomal dominant nocturnal frontal lobe epilepsy. (PMID: 7550350) Steinlein O.K. … Berkovic S.F. (Nat. Genet. 1995) 3 4 23
  3. Exon-intron structure of the human neuronal nicotinic acetylcholine receptor alpha 4 subunit (CHRNA4). (PMID: 8833159) Steinlein O.K. … Propping P. (Genomics 1996) 3 4 23
  4. A novel mutation of CHRNA4 responsible for autosomal dominant nocturnal frontal lobe epilepsy. (PMID: 10563623) Hirose S. … Mitsudome A. (Neurology 1999) 3 4 23
  5. Nicotinic acetylcholine receptor alpha4 subunit gene polymorphism and attention deficit hyperactivity disorder. (PMID: 11409698) Kent L. … Craddock N. (Psychiatr. Genet. 2001) 3 23 48

Products for CHRNA4 Gene

Sources for CHRNA4 Gene

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