Health Topics
Official websites use .gov
A
.gov website belongs to an official government
organization in the United States.
Secure .gov websites use HTTPS
A
lock (
) or https:// means you’ve safely connected to
the .gov website. Share sensitive information only on official,
secure websites.
Normal Function
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.
Health Conditions Related to Genetic Changes
Juvenile myoclonic epilepsy
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.
More About This Health ConditionChildhood absence epilepsy
MedlinePlus Genetics provides information about Childhood absence epilepsy
More About This Health ConditionOther Names for This Gene
- ECA4
- EJM
- EJM5
- GABA(A) receptor subunit alpha-1
- GABA(A) receptor, alpha 1
- gamma-aminobutyric acid (GABA) A receptor, alpha 1
- gamma-aminobutyric acid receptor subunit alpha-1
- gamma-aminobutyric acid receptor subunit alpha-1 precursor
- GBRA1_HUMAN
Additional Information & Resources
Tests Listed in the Genetic Testing Registry
Scientific Articles on PubMed
Catalog of Genes and Diseases from OMIM
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. doi: 10.1177/1073858412438697. Epub 2012 Apr 30. Citation on PubMed
- 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. Citation on PubMed
- 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. doi: 10.1038/ng885. Epub 2002 May 6. Citation on PubMed
- 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. Citation on PubMed or Free article on PubMed Central
- 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. doi: 10.1073/pnas.0700163104. Epub 2007 Aug 1. Citation on PubMed or Free article on PubMed Central
- 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. Citation on PubMed or Free article on PubMed Central
- 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. doi: 10.1111/j.1460-9568.2005.04168.x. Citation on PubMed
The information on this site should not be used as a substitute for professional medical care or advice. Contact a health care provider if you have questions about your health.