GBA gene (glucosidase, beta; acid)

http://ghr.nlm.nih.gov/gene=gba

What is the official name of the GBA gene?

The official name of this gene is “glucosidase, beta; acid (includes glucosylceramidase).”

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. 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. Tissues and organs are damaged by the abnormal accumulation and storage of these substances, causing the characteristic features of Gaucher disease.

Parkinson disease – associated with the GBA gene

Growing evidence suggests an association between GBA mutations and Parkinson disease or Parkinson-like disorders that affect movement and balance (parkinsonism). 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. Some studies suggest that people with Gaucher disease and GBA mutation carriers 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 mutations lead to these disorders. Researchers speculate that GBA mutations may contribute to the faulty breakdown of toxic substances in nerve cells by impairing the function of lysosomes, or mutations may enhance 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

Emerging research suggests an association between GBA 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 a chemical messenger called dopamine. The features of this disorder are variable, but symptoms typically include a loss of intellectual functions (dementia), visual hallucinations, and fluctuations in attention. Affected individuals may also experience changes that are characteristic of Parkinson disease such as trembling or rigidity of limbs, slow movement, and impaired balance and coordination.

People with mutations in both copies of the GBA gene in each cell develop Gaucher disease, while those with a mutation in just one copy of the gene are called carriers. Research suggests that carriers have an increased risk of developing dementia with Lewy bodies, although it remains unclear how GBA mutations increase this risk. Researchers speculate that GBA mutations can 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 153,470,866 to 153,481,111
The GBA gene is located on the long (q) arm of chromosome 1 at position 21.

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 153,470,866 to base pair 153,481,111 on chromosome 1.

See How do geneticists indicate the location of a gene? 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 (2 links)
Gene Reviews – Clinical summary
Gene Tests – DNA tests ordered by healthcare professionals

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

PubMed – Recent literature
OMIM – Genetic disorder catalog (2 links)
Research Resources – Tools for researchers (3 links)

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

Acid beta-glucosidase
Alglucerase
beta-D-glucosyl-N-acylsphingosine glucohydrolase
Beta-glucocerebrosidase
D-Glucosyl-N-acylsphingosine glucosylhydrolase
GBA1
GLCM_HUMAN
GLUC
Glucocerebrosidase
Glucocerebroside beta-Glucosidase
glucosphingosine glucosylhydrolase
Glucosylceramidase
Glucosylceramide beta-Glucosidase
Imiglucerase

See How are genetic conditions and genes named? in the Handbook.

Where can I find general information about genes?

The Handbook provides basic information about genetics in clear language.

These links provide additional genetics resources that may be useful.

What glossary definitions help with understanding GBA?

acids ; amino acid ; bacteria ; bone marrow ; carrier ; cell ; ceramides ; dementia ; digestive ; dopamine ; enzyme ; gene ; glucose ; hallucinations ; Lewy bodies ; lysosome ; macrophage ; molecule ; mutation ; nerve cell ; parkinsonism ; protein ; symptom ; tissue ; toxic ; white blood cells

You may find definitions for these and many other terms in the Genetics Home Reference Glossary.

References (14 links)

Comments

heather says:

05/08/2009 at 3:30 pm

this is amazing information. and it must be so frustrating to you, because it is to me, that they understand so much about where this disease comes from, what it does, what it makes the body NOT do, but they cannot find a way to reverse it, or find a treatment. At least not yet! I have faith!