Reviewed May 2012
What is the official name of the GBA gene?
The official name of this gene is “glucosidase, beta, acid.”
GBA is the gene's official symbol. The GBA gene is also known by other names, listed below.
What is the normal function of the GBA gene?
The GBA gene provides instructions for making an enzyme called beta-glucocerebrosidase. This enzyme is active in lysosomes, which are structures inside cells that act as recycling centers. Lysosomes use digestive enzymes to break down toxic substances, digest bacteria that invade the cell, and recycle worn-out cell components. Based on these functions, enzymes in the lysosome are sometimes called housekeeping enzymes. Beta-glucocerebrosidase is a housekeeping enzyme that helps break down a large molecule called glucocerebroside into a sugar (glucose) and a simpler fat molecule (ceramide).
How are changes in the GBA gene related to health conditions?
- Gaucher disease - caused by mutations in the GBA gene
More than 200 mutations in the GBA gene have been identified in people with Gaucher disease, a disorder with varied features that affect many parts of the body. These mutations occur in both copies of the gene in each cell. Most of the GBA mutations responsible for Gaucher disease change a single protein building block (amino acid) in beta-glucocerebrosidase, altering the structure of the enzyme and preventing it from working normally. Other mutations delete or insert genetic material in the GBA gene or lead to the production of an abnormally short, nonfunctional version of the enzyme.
Mutations in the GBA gene greatly reduce or eliminate the activity of beta-glucocerebrosidase in cells. As a result, glucocerebroside is not broken down properly. This molecule and related substances can build up in white blood cells called macrophages in the spleen, liver, bone marrow, and other organs. The abnormal accumulation and storage of these substances damages tissues and organs, causing the characteristic features of Gaucher disease.
- Parkinson disease - increased risk from variations of the GBA gene
Changes in the GBA gene are also associated with Parkinson disease and parkinsonism, which are similar disorders that affect movement and balance. People with Gaucher disease have mutations in both copies of the GBA gene in each cell, while those with a mutation in just one copy of the gene are called carriers. People with Gaucher disease and people who are carriers of a GBA gene mutation have an increased risk of developing Parkinson disease or parkinsonism.
Symptoms of Parkinson disease and parkinsonism result from the loss of nerve cells that produce dopamine. Dopamine is a chemical messenger that transmits signals within the brain to produce smooth physical movements. It remains unclear how GBA gene mutations are related to these disorders. Studies suggest that changes in this gene may contribute to the faulty breakdown of toxic substances in nerve cells by impairing the function of lysosomes. Alternatively, the changes may increase the formation of abnormal protein deposits. As a result, toxic substances or protein deposits could accumulate and kill dopamine-producing nerve cells, leading to abnormal movements and balance problems.
- other disorders - associated with the GBA gene
Research suggests an association between GBA gene mutations and a disorder called dementia with Lewy bodies. Lewy bodies are abnormal deposits of the protein alpha-synuclein that form in some dead or dying nerve cells. Specifically, they occur in nerve cells that produce the chemical messenger dopamine. The features of this disorder are variable, but symptoms typically include a loss of intellectual functions (dementia), visual hallucinations, and changes in alertness and attention. Affected individuals may have features characteristic of Parkinson disease such as trembling or rigidity of limbs, slow movement, and impaired balance and coordination. Lewy bodies are also a feature of Parkinson disease, but these abnormal deposits tend to be more widespread in the brain in dementia with Lewy bodies.
Carriers of GBA gene mutations appear to have an increased risk of developing dementia with Lewy bodies, although it remains unclear how changes in this gene increase the risk. Researchers speculate that mutations in the GBA gene alter the structure of beta-glucocerebrosidase and impair the function of lysosomes. As a result, alpha-synuclein may not be processed properly, allowing the formation of Lewy bodies.
Where is the GBA gene located?
Cytogenetic Location: 1q21
Molecular Location on chromosome 1: base pairs 155,234,448 to 155,244,862
(Homo sapiens Annotation Release 107, GRCh38.p2) (NCBI (http://www.ncbi.nlm.nih.gov/gene/2629))
The GBA gene is located on the long (q) arm of chromosome 1 at position 21.
More precisely, the GBA gene is located from base pair 155,234,448 to base pair 155,244,862 on chromosome 1.
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 GBA?
You and your healthcare professional may find the following resources about GBA helpful.
Educational resources - Information pages
- HuGENet Case Study: Glucocerebrosidase Gene Mutations and Parkinson's Disease (http://www.cdc.gov/genomics/hugenet/CaseStudy/PARKINSON/PARKview.htm)
- National Institute of Neurological Disorders and Stroke: Dementia with Lewy Bodies (http://www.ninds.nih.gov/disorders/dementiawithlewybodies/dementiawithlewybodies.htm)
- NIH News Release: Researchers Uncover Genetic Clues to a Common Form of Age-Related Dementia (July 17, 2006) (https://www.genome.gov/19517231)
- Gene Reviews - Clinical summary (http://www.ncbi.nlm.nih.gov/books/NBK1269)
Genetic Testing Registry - Repository of genetic test information
- GTR: Genetic tests for GBA (http://www.ncbi.nlm.nih.gov/gtr/tests/?term=2629%5Bgeneid%5D)
You may also be interested in these resources, which are designed for genetics professionals and researchers.
- PubMed - Recent literature (http://www.ncbi.nlm.nih.gov/pubmed?term=%28%28GBA%5BTI%5D%29%20OR%20%28beta%20glucosidase%5BTIAB%5D%29%20OR%20%28glucosylceramidase%5BTIAB%5D%29%20OR%20%28Glucocerebrosidase%5BTIAB%5D%29%29%20AND%20%28%28Genes%5BMH%5D%29%20OR%20%28Genetic%20Phenomena%5BMH%5D%29%29%20AND%20english%5Bla%5D%20AND%20human%5Bmh%5D%20AND%20%22last%20720%20days%22%5Bdp%5D)
OMIM - Genetic disorder catalog
- DEMENTIA, LEWY BODY (http://omim.org/entry/127750)
- GLUCOSIDASE, BETA, ACID (http://omim.org/entry/606463)
Research Resources - Tools for researchers
- Atlas of Genetics and Cytogenetics in Oncology and Haematology (http://atlasgeneticsoncology.org/Genes/GC_GBA.html)
- HGNC Gene Symbol Report (http://www.genenames.org/cgi-bin/gene_symbol_report?q=data/hgnc_data.php&hgnc_id=4177)
- NCBI Gene (http://www.ncbi.nlm.nih.gov/gene/2629)
- PDGene (http://www.pdgene.org/view?gene=GBA)
What other names do people use for the GBA gene or gene products?
- Acid beta-glucosidase
- beta-D-glucosyl-N-acylsphingosine glucohydrolase
- D-Glucosyl-N-acylsphingosine glucosylhydrolase
- Glucocerebroside beta-Glucosidase
- glucosidase, beta; acid (includes glucosylceramidase)
- glucosphingosine glucosylhydrolase
- Glucosylceramide beta-Glucosidase
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 GBA?
amino acid ;
bone marrow ;
Lewy bodies ;
white blood cells
You may find definitions for these and many other terms in the Genetics Home Reference
- Aharon-Peretz J, Rosenbaum H, Gershoni-Baruch R. Mutations in the glucocerebrosidase gene and Parkinson's disease in Ashkenazi Jews. N Engl J Med. 2004 Nov 4;351(19):1972-7. (http://www.ncbi.nlm.nih.gov/pubmed/15525722?dopt=Abstract)
- Charrow J, Andersson HC, Kaplan P, Kolodny EH, Mistry P, Pastores G, Prakash-Cheng A, Rosenbloom BE, Scott CR, Wappner RS, Weinreb NJ. Enzyme replacement therapy and monitoring for children with type 1 Gaucher disease: consensus recommendations. J Pediatr. 2004 Jan;144(1):112-20. Review. (http://www.ncbi.nlm.nih.gov/pubmed/14722528?dopt=Abstract)
- Clark LN, Kartsaklis LA, Wolf Gilbert R, Dorado B, Ross BM, Kisselev S, Verbitsky M, Mejia-Santana H, Cote LJ, Andrews H, Vonsattel JP, Fahn S, Mayeux R, Honig LS, Marder K. Association of glucocerebrosidase mutations with dementia with lewy bodies. Arch Neurol. 2009 May;66(5):578-83. doi: 10.1001/archneurol.2009.54. (http://www.ncbi.nlm.nih.gov/pubmed/19433657?dopt=Abstract)
- Clark LN, Ross BM, Wang Y, Mejia-Santana H, Harris J, Louis ED, Cote LJ, Andrews H, Fahn S, Waters C, Ford B, Frucht S, Ottman R, Marder K. Mutations in the glucocerebrosidase gene are associated with early-onset Parkinson disease. Neurology. 2007 Sep 18;69(12):1270-7. (http://www.ncbi.nlm.nih.gov/pubmed/17875915?dopt=Abstract)
- Cox TM. Gaucher disease: understanding the molecular pathogenesis of sphingolipidoses. J Inherit Metab Dis. 2001;24 Suppl 2:106-21; discussion 87-8. Review. (http://www.ncbi.nlm.nih.gov/pubmed/11758671?dopt=Abstract)
- Germain DP. Gaucher's disease: a paradigm for interventional genetics. Clin Genet. 2004 Feb;65(2):77-86. Review. (http://www.ncbi.nlm.nih.gov/pubmed/14984463?dopt=Abstract)
- Goker-Alpan O, Giasson BI, Eblan MJ, Nguyen J, Hurtig HI, Lee VM, Trojanowski JQ, Sidransky E. Glucocerebrosidase mutations are an important risk factor for Lewy body disorders. Neurology. 2006 Sep 12;67(5):908-10. Epub 2006 Jun 21. (http://www.ncbi.nlm.nih.gov/pubmed/16790605?dopt=Abstract)
- Jmoudiak M, Futerman AH. Gaucher disease: pathological mechanisms and modern management. Br J Haematol. 2005 Apr;129(2):178-88. Review. (http://www.ncbi.nlm.nih.gov/pubmed/15813845?dopt=Abstract)
- Mata IF, Samii A, Schneer SH, Roberts JW, Griffith A, Leis BC, Schellenberg GD, Sidransky E, Bird TD, Leverenz JB, Tsuang D, Zabetian CP. Glucocerebrosidase gene mutations: a risk factor for Lewy body disorders. Arch Neurol. 2008 Mar;65(3):379-82. doi: 10.1001/archneurol.2007.68. (http://www.ncbi.nlm.nih.gov/pubmed/18332251?dopt=Abstract)
- NCBI Gene (http://www.ncbi.nlm.nih.gov/gene/2629)
- Orvisky E, Park JK, Parker A, Walker JM, Martin BM, Stubblefield BK, Uyama E, Tayebi N, Sidransky E. The identification of eight novel glucocerebrosidase (GBA) mutations in patients with Gaucher disease. Hum Mutat. 2002 Apr;19(4):458-9. (http://www.ncbi.nlm.nih.gov/pubmed/11933202?dopt=Abstract)
- Pelled D, Trajkovic-Bodennec S, Lloyd-Evans E, Sidransky E, Schiffmann R, Futerman AH. Enhanced calcium release in the acute neuronopathic form of Gaucher disease. Neurobiol Dis. 2005 Feb;18(1):83-8. (http://www.ncbi.nlm.nih.gov/pubmed/15649698?dopt=Abstract)
- Sidransky E, Nalls MA, Aasly JO, Aharon-Peretz J, Annesi G, Barbosa ER, Bar-Shira A, Berg D, Bras J, Brice A, Chen CM, Clark LN, Condroyer C, De Marco EV, Dürr A, Eblan MJ, Fahn S, Farrer MJ, Fung HC, Gan-Or Z, Gasser T, Gershoni-Baruch R, Giladi N, Griffith A, Gurevich T, Januario C, Kropp P, Lang AE, Lee-Chen GJ, Lesage S, Marder K, Mata IF, Mirelman A, Mitsui J, Mizuta I, Nicoletti G, Oliveira C, Ottman R, Orr-Urtreger A, Pereira LV, Quattrone A, Rogaeva E, Rolfs A, Rosenbaum H, Rozenberg R, Samii A, Samaddar T, Schulte C, Sharma M, Singleton A, Spitz M, Tan EK, Tayebi N, Toda T, Troiano AR, Tsuji S, Wittstock M, Wolfsberg TG, Wu YR, Zabetian CP, Zhao Y, Ziegler SG. Multicenter analysis of glucocerebrosidase mutations in Parkinson's disease. N Engl J Med. 2009 Oct 22;361(17):1651-61. doi: 10.1056/NEJMoa0901281. (http://www.ncbi.nlm.nih.gov/pubmed/19846850?dopt=Abstract)
- Sidransky E. Gaucher disease: complexity in a "simple" disorder. Mol Genet Metab. 2004 Sep-Oct;83(1-2):6-15. Review. (http://www.ncbi.nlm.nih.gov/pubmed/15464415?dopt=Abstract)
- Sidransky E. Heterozygosity for a Mendelian disorder as a risk factor for complex disease. Clin Genet. 2006 Oct;70(4):275-82. Review. (http://www.ncbi.nlm.nih.gov/pubmed/16965318?dopt=Abstract)
- Velayati A, Yu WH, Sidransky E. The role of glucocerebrosidase mutations in Parkinson disease and Lewy body disorders. Curr Neurol Neurosci Rep. 2010 May;10(3):190-8. doi: 10.1007/s11910-010-0102-x. Review. (http://www.ncbi.nlm.nih.gov/pubmed/20425034?dopt=Abstract)
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
See How can I find a genetics professional in my area? (http://ghr.nlm.nih.gov/handbook/consult/findingprofessional) in the Handbook.