Aliases for CHRNA4 Gene
External Ids for CHRNA4 Gene
Previous HGNC Symbols for CHRNA4 Gene
Previous GeneCards Identifiers 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.
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.