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Genetics Home Reference: your guide to understanding genetic conditions
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CHRNA2

Reviewed April 2009

What is the official name of the CHRNA2 gene?

The official name of this gene is “cholinergic receptor, nicotinic, alpha 2 (neuronal).”

CHRNA2 is the gene's official symbol. The CHRNA2 gene is also known by other names, listed below.

What is the normal function of the CHRNA2 gene?

The CHRNA2 gene provides instructions for making one part (subunit) of a larger protein called a neuronal nicotinic acetylcholine receptor (nAChR). Each nAChR protein is made up of a combination of five subunits, usually two alpha (α) and three beta (β) subunits. Many different combinations are possible, and the characteristics of each nAChR protein depend on which subunits it contains. The CHRNA2 gene is responsible for producing a subunit known as α2. Little is known about the specific function of nAChR proteins made with this subunit.

In the brain, nAChR proteins are widely distributed and play an important role in chemical signaling between nerve cells (neurons). The proteins act as channels, allowing charged atoms (ions) including calcium, sodium, and potassium to cross the cell membrane. These channels open when attached to a brain chemical (neurotransmitter) called acetylcholine. The channels also open in response to nicotine, the addictive substance in tobacco.

Communication between neurons depends on neurotransmitters, which are released from one neuron and taken up by neighboring neurons. The release and uptake of these chemicals are tightly regulated to ensure that signals are passed efficiently and accurately between neurons. Researchers believe that nAChR channels play an important role in controlling the normal release and uptake of neurotransmitters.

A wide range of brain functions depend on nAChR channels, including sleep and arousal, fatigue, anxiety, attention, pain perception, and memory. The channels are also active before birth, which suggests that they are involved in early brain development. At least one drug that targets nAChR channels in the brain has been developed to help people quit smoking; other medications targeting these channels are under study for the treatment of schizophrenia, Alzheimer disease, and pain.

How are changes in the CHRNA2 gene related to health conditions?

autosomal dominant nocturnal frontal lobe epilepsy - caused by mutations in the CHRNA2 gene

At least one mutation in the CHRNA2 gene has been found to cause autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE). It appears that changes in this gene are a very rare cause of ADNFLE. Some researchers suspect that the known mutation actually causes a separate form of epilepsy with features similar to ADNFLE.

The identified CHRNA2 mutation changes a single protein building block (amino acid) in the α2 subunit of nAChR channels. Specifically, it replaces the amino acid isoleucine with the amino acid asparagine at protein position 279 (written as Ile279Asn or I279N). This mutation makes the channels more sensitive to the neurotransmitter acetylcholine, allowing them to open more easily than usual. The resulting increase in ion flow across the cell membrane alters the release of neurotransmitters, which changes signaling between neurons. Researchers believe that the overexcitement of certain neurons in the brain triggers the abnormal brain activity associated with seizures. It is unclear why the seizures seen in ADNFLE start in the frontal lobes of the brain and occur most often during sleep.

Where is the CHRNA2 gene located?

Cytogenetic Location: 8p21

Molecular Location on chromosome 8: base pairs 27,459,760 to 27,479,295

The CHRNA2 gene is located on the short (p) arm of chromosome 8 at position 21.

The CHRNA2 gene is located on the short (p) arm of chromosome 8 at position 21.

More precisely, the CHRNA2 gene is located from base pair 27,459,760 to base pair 27,479,295 on chromosome 8.

See How do geneticists indicate the location of a gene? (http://ghr.nlm.nih.gov/handbook/howgeneswork/genelocation) in the Handbook.

Where can I find additional information about CHRNA2?

You and your healthcare professional may find the following resources about CHRNA2 helpful.

You may also be interested in these resources, which are designed for genetics professionals and researchers.

What other names do people use for the CHRNA2 gene or gene products?

  • Acetylcholine receptor, neuronal nicotonic, alpha-2 subunit
  • ACHA2_HUMAN
  • Cholinergic receptor, neuronal nicotinic, alpha polypeptide 2
  • cholinergic receptor, nicotinic, alpha polypeptide 2 (neuronal)

See How are genetic conditions and genes named? (http://ghr.nlm.nih.gov/handbook/mutationsanddisorders/naming) in the Handbook.

What glossary definitions help with understanding CHRNA2?

acetylcholine ; amino acid ; anxiety ; asparagine ; autosomal ; autosomal dominant ; calcium ; cell ; cell membrane ; epilepsy ; gene ; ions ; isoleucine ; mutation ; neuron ; neurotransmitters ; nicotine ; nocturnal ; perception ; potassium ; protein ; receptor ; schizophrenia ; sodium ; subunit

You may find definitions for these and many other terms in the Genetics Home Reference Glossary (http://www.ghr.nlm.nih.gov/glossary).

References

  • Aridon P, Marini C, Di Resta C, Brilli E, De Fusco M, Politi F, Parrini E, Manfredi I, Pisano T, Pruna D, Curia G, Cianchetti C, Pasqualetti M, Becchetti A, Guerrini R, Casari G. Increased sensitivity of the neuronal nicotinic receptor alpha 2 subunit causes familial epilepsy with nocturnal wandering and ictal fear. Am J Hum Genet. 2006 Aug;79(2):342-50. Epub 2006 Jun 26. (http://www.ncbi.nlm.nih.gov/pubmed/16826524?dopt=Abstract)
  • Arneric SP, Holladay M, Williams M. Neuronal nicotinic receptors: a perspective on two decades of drug discovery research. Biochem Pharmacol. 2007 Oct 15;74(8):1092-101. Epub 2007 Jun 26. Review. (http://www.ncbi.nlm.nih.gov/pubmed/17662959?dopt=Abstract)
  • Combi R, Ferini-Strambi L, Tenchini ML. CHRNA2 mutations are rare in the NFLE population: evaluation of a large cohort of Italian patients. Sleep Med. 2009 Jan;10(1):139-42. doi: 10.1016/j.sleep.2007.11.010. Epub 2008 Jan 28. (http://www.ncbi.nlm.nih.gov/pubmed/18226955?dopt=Abstract)
  • Gu W, Bertrand D, Steinlein OK. A major role of the nicotinic acetylcholine receptor gene CHRNA2 in autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE) is unlikely. Neurosci Lett. 2007 Jul 5;422(1):74-6. Epub 2007 Jun 8. (http://www.ncbi.nlm.nih.gov/pubmed/17602836?dopt=Abstract)
  • Marini C, Guerrini R. The role of the nicotinic acetylcholine receptors in sleep-related epilepsy. Biochem Pharmacol. 2007 Oct 15;74(8):1308-14. Epub 2007 Jun 23. Review. (http://www.ncbi.nlm.nih.gov/pubmed/17662253?dopt=Abstract)
  • NCBI Gene (http://www.ncbi.nlm.nih.gov/gene/1135)

 

The resources on this site should not be used as a substitute for professional medical care or advice. Users seeking information about a personal genetic disease, syndrome, or condition should consult with a qualified healthcare professional. See How can I find a genetics professional in my area? (http://ghr.nlm.nih.gov/handbook/consult/findingprofessional) in the Handbook.

 
Reviewed: April 2009
Published: December 22, 2014