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Genetics Home Reference: your guide to understanding genetic conditions
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GABRA1

Reviewed June 2012

What is the official name of the GABRA1 gene?

The official name of this gene is “gamma-aminobutyric acid (GABA) A receptor, alpha 1.”

GABRA1 is the gene's official symbol. The GABRA1 gene is also known by other names, listed below.

What is the normal function of the GABRA1 gene?

The GABRA1 gene provides instructions for making one piece, the alpha-1 (α1) subunit, of the GABAA receptor protein. GABAA receptors are made up of different combinations of five protein subunits, each produced from a different gene. (Nineteen different genes provide instructions for GABAA receptor subunits.) These subunits form a hole (pore) in the cell membrane through which negatively charged chlorine atoms (chloride ions) can flow.

A chemical that transmits signals in the brain (a neurotransmitter) called gamma-amino butyric acid (GABA) attaches to GABAA receptors. Once GABA attaches, the pore formed by the subunits opens, and chloride ions flow across the cell membrane. After infancy, chloride ions flow into the cell through the open pore, which creates an environment in the cell that blocks (inhibits) signaling between neurons. The primary role of GABA in children and adults is to prevent the brain from being overloaded with too many signals. In contrast, in newborns and infants, chloride ions flow out of the cell when the pore is opened, creating an environment that allows signaling between neurons.

Does the GABRA1 gene share characteristics with other genes?

The GABRA1 gene belongs to a family of genes called ligand-gated ion channels (ligand-gated ion channels).

A gene family is a group of genes that share important characteristics. Classifying individual genes into families helps researchers describe how genes are related to each other. For more information, see What are gene families? (http://ghr.nlm.nih.gov/handbook/howgeneswork/genefamilies) in the Handbook.

How are changes in the GABRA1 gene related to health conditions?

juvenile myoclonic epilepsy - caused by mutations in the GABRA1 gene

A mutation in the GABRA1 gene has been identified in at least one family with juvenile myoclonic epilepsy. This condition typically begins in childhood or adolescence and causes recurrent myoclonic seizures, which are characterized by rapid, uncontrolled muscle jerks. Affected individuals can also have other types of seizures called generalized tonic-clonic seizures (or grand mal seizures) and absence seizures. The mutation associated with this condition changes a single protein building block (amino acid) in the α1 subunit. The amino acid alanine at protein position 322 is replaced by the amino acid asparagine. This gene mutation is written as Ala322Asp or A322D.

This GABRA1 gene mutation leads to the formation of an abnormal α1 subunit that reduces GABAA receptor function. GABAA receptors containing the abnormal subunit are broken down before they reach the cell membrane. Studies show that the altered receptors can also interfere with normal receptors inside the cell, leading to the additional loss of normal receptors. Because of the reduction of GABAA receptor function, signaling between neurons is not regulated, which can lead to overstimulation of neurons. Researchers believe that the overstimulation of certain neurons in the brain triggers the abnormal brain activity associated with seizures.

Where is the GABRA1 gene located?

Cytogenetic Location: 5q34

Molecular Location on chromosome 5: base pairs 161,847,190 to 161,899,958

The GABRA1 gene is located on the long (q) arm of chromosome 5 at position 34.

The GABRA1 gene is located on the long (q) arm of chromosome 5 at position 34.

More precisely, the GABRA1 gene is located from base pair 161,847,190 to base pair 161,899,958 on chromosome 5.

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 GABRA1?

You and your healthcare professional may find the following resources about GABRA1 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 GABRA1 gene or gene products?

  • ECA4
  • EJM
  • EJM5
  • GABA(A) receptor, alpha 1
  • GABA(A) receptor subunit alpha-1
  • gamma-aminobutyric acid receptor subunit alpha-1
  • gamma-aminobutyric acid receptor subunit alpha-1 precursor
  • GBRA1_HUMAN

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 GABRA1?

alanine ; amino acid ; asparagine ; cell ; cell membrane ; chloride ; epilepsy ; GABA ; gamma-aminobutyric acid ; gene ; ions ; juvenile ; mutation ; precursor ; protein ; receptor ; 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

  • Ben-Ari Y, Khalilov I, Kahle KT, Cherubini E. The GABA excitatory/inhibitory shift in brain maturation and neurological disorders. Neuroscientist. 2012 Oct;18(5):467-86. Epub 2012 Apr 30. Review. (http://www.ncbi.nlm.nih.gov/pubmed/22547529?dopt=Abstract)
  • Bradley CA, Taghibiglou C, Collingridge GL, Wang YT. Mechanisms involved in the reduction of GABAA receptor alpha1-subunit expression caused by the epilepsy mutation A322D in the trafficking-competent receptor. J Biol Chem. 2008 Aug 8;283(32):22043-50. doi: 10.1074/jbc.M801708200. Epub 2008 Jun 5. (http://www.ncbi.nlm.nih.gov/pubmed/18534981?dopt=Abstract)
  • Cossette P, Liu L, Brisebois K, Dong H, Lortie A, Vanasse M, Saint-Hilaire JM, Carmant L, Verner A, Lu WY, Wang YT, Rouleau GA. Mutation of GABRA1 in an autosomal dominant form of juvenile myoclonic epilepsy. Nat Genet. 2002 Jun;31(2):184-9. Epub 2002 May 6. (http://www.ncbi.nlm.nih.gov/pubmed/11992121?dopt=Abstract)
  • Ding L, Feng HJ, Macdonald RL, Botzolakis EJ, Hu N, Gallagher MJ. GABA(A) receptor alpha1 subunit mutation A322D associated with autosomal dominant juvenile myoclonic epilepsy reduces the expression and alters the composition of wild type GABA(A) receptors. J Biol Chem. 2010 Aug 20;285(34):26390-405. doi: 10.1074/jbc.M110.142299. Epub 2010 Jun 15. (http://www.ncbi.nlm.nih.gov/pubmed/20551311?dopt=Abstract)
  • Gallagher MJ, Ding L, Maheshwari A, Macdonald RL. The GABAA receptor alpha1 subunit epilepsy mutation A322D inhibits transmembrane helix formation and causes proteasomal degradation. Proc Natl Acad Sci U S A. 2007 Aug 7;104(32):12999-3004. Epub 2007 Aug 1. (http://www.ncbi.nlm.nih.gov/pubmed/17670950?dopt=Abstract)
  • OMIM: GAMMA-AMINOBUTYRIC ACID RECEPTOR, ALPHA-1 (http://omim.org/entry/137160)
  • Kang JQ, Shen W, Macdonald RL. Two molecular pathways (NMD and ERAD) contribute to a genetic epilepsy associated with the GABA(A) receptor GABRA1 PTC mutation, 975delC, S326fs328X. J Neurosci. 2009 Mar 4;29(9):2833-44. doi: 10.1523/JNEUROSCI.4512-08.2009. (http://www.ncbi.nlm.nih.gov/pubmed/19261879?dopt=Abstract)
  • Krampfl K, Maljevic S, Cossette P, Ziegler E, Rouleau GA, Lerche H, Bufler J. Molecular analysis of the A322D mutation in the GABA receptor alpha-subunit causing juvenile myoclonic epilepsy. Eur J Neurosci. 2005 Jul;22(1):10-20. (http://www.ncbi.nlm.nih.gov/pubmed/16029191?dopt=Abstract)
  • NCBI Gene (http://www.ncbi.nlm.nih.gov/gene/2554)

 

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: June 2012
Published: October 20, 2014